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Sample records for pth 1-84 secretion

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

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    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.

  2. 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

  3. 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...

  4. 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...

  5. 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

  6. 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...

  7. 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...

  8. Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands.

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    Huan, Jinxing; Olgaard, Klaus; Nielsen, Lars Bo; Lewin, Ewa

    2006-07-01

    Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84-treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.

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

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

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    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

  11. 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.

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    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.

  12. PTH Reloaded: A New Evolutionary Perspective

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    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.

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

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    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.

  14. 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.

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    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.

  15. AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM.

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    Lakatos, Peter; Bajnok, Laszlo; Lagast, Hjalmar; Valkusz, Zsuzsanna

    2016-05-01

    Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia. Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred. This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.

  16. Efficacy and safety of human parathyroid hormone-(1-84) in increasing bone mineral density in postmenopausal osteoporosis.

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    Hodsman, Anthony B; Hanley, David A; Ettinger, Mark P; Bolognese, Michael A; Fox, John; Metcalfe, Anna J; Lindsay, Robert

    2003-11-01

    Daily sc injections of N-terminal analogs of PTH increase bone mass and decrease fractures in osteoporotic women. We investigated the efficacy and safety of human PTH-(1-84) (full-length PTH) in the treatment of postmenopausal osteoporosis in a double-blind, placebo-controlled study. The women (n = 50-53/group) self-administered PTH (50, 75, or 100 microg) or placebo by daily sc injection for 12 months. PTH treatment induced time- and dose-related increases in lumbar spine bone mineral density (BMD). The 100-microg dose increased BMD significantly at 3 months (+2.0%) and 12 months (+7.8%). BMD underestimated the anabolic effect of PTH in lumbar spine (bone mineral content, +10.0%) because bone area increased significantly (+2.0%). A nonsignificant decrease (-0.9%) in total hip BMD occurred during the first 6 months with the 100-microg dose, but this trend reversed (+1.6%) during the second 6 months. Bone turnover markers increased during the first half of the study and were maintained at elevated levels during the second 6 months. Protocol compliance was excellent (95-98%), and treatment was generally safe and well tolerated. Dose-related incidences of transient hypercalcemia occurred, but only one patient (100-microg group) was withdrawn because of repeated hypercalcemia. Thus, full-length PTH was efficacious and safe over 12 months.

  17. PTH-analogs: comparable or different?

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    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.

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

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    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

  19. Parathyroid hormone 1-84 targets bone vascular structure and perfusion in mice: impacts of its administration regimen and of ovariectomy.

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    Roche, Bernard; Vanden-Bossche, Arnaud; Malaval, Luc; Normand, Myriam; Jannot, Martin; Chaux, Robin; Vico, Laurence; Lafage-Proust, Marie-Hélène

    2014-07-01

    Bone vessel functions during bone remodeling are poorly understood. They depend on both vessel network structure and vasomotor regulation. Parathyroid hormone (PTH) is a systemic vasodilator that may modulate microvascularization. Moreover, although intermittent PTH is anti-osteoporotic, continuous PTH administration can be catabolic for bone. Finally, ovariectomy (OVX) reduces bone perfusion and vessel density in mice. We reasoned that the effects of PTH on bone vascularization might depend on its administration regimen and be impacted by ovariectomy. A 100-µg/kg PTH 1-84 daily dose was administered for 15 days to 4-month-old female C57BL/6 mice, either as daily sc injection (iPTH) or continuously (cPTH; ALZET minipump). Blood pressure (BP) and tibia bone perfusion were measured in vivo with a laser Doppler device. Histomorphometry of bone and barium-contrasted vascular network were performed on the same tibia. Compared with untreated controls, both iPTH and cPTH increased bone formation but had opposite effects on resorption. Both iPTH and cPTH were slightly angiogenic. Intermittent PTH increased microvessel size (+48%, p < 0.001), whereas cPTH decreased it (-29%, p = 0.009). iPTH increased bone perfusion (27%, p < 0.001) with no change in BP, whereas cPTH did not. The vascular effects of a 15-day iPTH treatment were analyzed in OVX mice and compared with sham-operated and OVX untreated controls. Two other anti-osteoporotic drugs, zoledronate (one injection, 70 µg/kg) and propranolol, (5 mg/kg/d) were tested in OVX mice. Although no change in bone mass was observed, iPTH stimulated bone formation and prevented the OVX-induced reduction in bone perfusion and vessel density. Both zoledronate and propranolol strongly lowered bone turnover, but surprisingly, zoledronate prevented OVX-induced reduction in bone perfusion but propranolol did not. Our integrative approach thus demonstrates that the effects of PTH on bone vessel structure and function depend on its

  20. 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.

  1. Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis.

    Science.gov (United States)

    Antoniucci, Diana M; Sellmeyer, Deborah E; Bilezikian, John P; Palermo, Lisa; Ensrud, Kristine E; Greenspan, Susan L; Black, Dennis M

    2007-03-01

    The effect of PTH therapy on serum and urinary calcium levels and the risk of hypercalcemia or hypercalciuria has not been formally evaluated. The objective was to examine changes in serum and urinary calcium associated with PTH(1-84) therapy in the PaTH trial and the extent to which a defined algorithm resolved the elevated values. A total of 178 postmenopausal women were randomized to PTH(1-84) either alone or in combination with alendronate during the first year of the PaTH study. The main outcome measures were fasting serum calcium at baseline and 1, 3, and 12 months and 24-h urinary calcium at baseline and 3 months. In 14% of participants, serum calcium more than 10.5 mg/dl (>2.6 mmol/liter) developed. Following the defined algorithm, 58% of elevated measurements were normal on repeat testing; 38% required discontinuation of calcium and vitamin D supplementation, and one necessitated a decrease in PTH injection frequency to normalize serum calcium. One participant developed transient hypercalcemia between study visits and required hospitalization; the episode resolved with iv hydration and PTH discontinuation. Baseline characteristics associated with the development of hypercalcemia were serum calcium [relative hazards = 1.9 per 0.5 mg/dl (0.12 mmol/liter); 95% confidence interval = 1.1-3.2] and serum 1,25-dihydroxyvitamin D [relative hazard = 1.9 per 10 pg/ml (26 pmol/liter); 95% confidence interval = 1.2-3.1]. Fifteen women (8%) developed hypercalciuria [urinary calcium > 400 mg (100 mmol)/24 h or calcium/creatinine ratio > 0.4]; 80% of cases resolved after discontinuing calcium and vitamin D, 13% without intervention, and one after PTH injection frequency was decreased. Higher baseline urinary calcium excretion was associated with development of hypercalciuria [relative hazard = 1.5 per 50 mg/d (12.5 mmol/d); 95% confidence interval = 1.2-4.0]. Proportions of patients with elevated serum and urinary calcium were similar on single and combination therapy

  2. 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.

  3. Efectos de la Hormona Paratiroidea PTH (1-84) en la consolidación de las fracturas

    OpenAIRE

    2015-01-01

    1.- INTRODUCCIÓN La osteoporosis es una enfermedad sistémica crónica y progresiva que se caracteriza por una densidad ósea baja y un deterioro de la micro-arquitectura del tejido óseo, que reduce la resistencia a las fuerzas de carga, con un incremento de la fragilidad ósea y de la susceptibilidad de experimentar una fractura ante mínimos traumatismos. Por lo tanto, las fracturas por fragilidad son la consecuencia clínica de la osteoporosis. La incidencia de este tipo de fracturas es m...

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  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. 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.

  10. 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

  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. 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...

  15. 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.

  16. 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.

  17. 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

  18. 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...

  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. 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.

  1. Pharmacokinetic study of the injection of recombinant human parathyroid hormone (1-84) in osteoporotic rats%骨质疏松症大鼠注射重组人甲状旁腺素药动学研究

    Institute of Scientific and Technical Information of China (English)

    王胜军; 杨澔侠; 张晶; 姚昶

    2013-01-01

    Objective To study the pharmacokinetic characteristics of injected recombinant human parathyroid hormone rhPTH (1-84) in ovariectomized rats with osteoporosis.Methods Forty-eight rats, with an average weight of 250 ±10g, were randomly divided into control group ( small piece of adipose tissue around the ovary was removed ) and model group ( bilateral ovariectomy was performed), and each group had 8 rats.At the 4th week after the surgery, rats received a subcutaneous injection of 1μg/kg, 2μg/kg, or 4 μg/kg rhPTH ( 1-84 ) , respectively .The plasma concentration of rhPTH ( 1-84 ) at different time points was determined using radioimmunoassay method .The pharmacokinetic parameters were calculated .Results Excellent linear correlation was showed within the range of 24-1850 pg/mL.The minimum detection of rhPTH (1-84) in plasma was 10 pg/mL.The extraction efficiency in plasma was within the range of 80.2-90.6%.The AUC (0-∞), a pharmacokinetic parameter, in low, middle, and high dose model group was 24628.9 ±1281, 47059.3 ±3311, and 96652.1 ±2174 ng/L· min, respectively.The AUC (0-∞) in control group was 21974.0 ±1587, 42651.2 ±1336, and 87736.8 ±1938 ng/L· min, respectively.Conclusion After the single injection of low, middle, and high dose of rhPTH(1-84), the Cmax and ACU (0-∞) in both groups show a linear metabolic characteristics . The plasma concentration time curves show a clear bimodal in model groups , which can provide important information for the drug design and optimization of clinical research .%目的:研究注射用重组人甲状旁腺素rhPTH1-84)在去卵巢骨质疏松症大鼠的药代动力学特征。方法48只大鼠(250±10)g,分成对照组(切除卵巢周围小块脂肪组织)和模型组(双侧卵巢切除),每组8只,手术4周后皮下注射1.0、2.0、4.0 ug/kg rhPTH(1-84),采用放射免疫分析法测定rhPTH(1-84)不同时间点的血药浓度,计算药代动力学参数。结果 rhPTH

  2. 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.

  3. 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

  4. 16 CFR 1.84 - Draft environmental impact statements: Availability and comment.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Draft environmental impact statements... Environmental Policy Act of 1969 § 1.84 Draft environmental impact statements: Availability and comment. Except for proposals for legislation, environmental impact statements shall be prepared in two stages: Draft...

  5. Humoral hypercalcemia associated with gastric carcinoma secreting parathyroid hormone: a case report and review of the literature.

    Science.gov (United States)

    Nakajima, Koji; Tamai, Masataka; Okaniwa, Shinji; Nakamura, Yoshiyuki; Kobayashi, Mutsuhiro; Niwa, Tomohiro; Horigome, Naoto; Ito, Nobuo; Suzuki, Satoru; Nishio, Shinichi; Komatsu, Mitsuhisa

    2013-01-01

    Hypercalcemia with concomitant elevation of serum parathyroid hormone (PTH) and PTH-related protein (PTHrP) levels was found in a patient with advanced gastric carcinoma and multiple liver metastases. The most common features are hypercalcemia associated with hypersecretion of PTHrP and physiological suppression of PTH secretion in the syndrome of humoral hypercalcemia of malignancy (HHM). Although we initially made a diagnosis of primary hyperparathyroidism concomitant with HHM due to gastric cancer, diagnostic imaging studies, such as echography, CT, sestamibi scintigraphy, and autopsy findings, did not reveal evidence of any parathyroid tumors or ectopic parathyroid glands in the mediastinum. Both primary and metastatic tumor cells showed positive staining with PTH-specific antibody as well as PTHrP-specific antibody on immunohistochemical examination. PTH concentration in the cytosolic fraction of the metastatic tumor was elevated compared to that from a control patient with no calcium metabolic disorders in vitro. These findings indicated that PTH secreted ectopically by gastric cancer cells, not by parathyroid glands, caused hypercalcemia in this patient. To our knowledge, this is the first case report of PTH-secreting gastric carcinoma cells. We report the case and a review of the previous reported PTH-secreting non-parathyroid tumors along with the mechanisms of secretion.

  6. 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...

  7. Direct suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog.

    Science.gov (United States)

    Lopez, Ignacio; Rodriguez, Mariano; Felsenfeld, Arnold J; Estepa, Jose Carlos; Aguilera-Tejero, Escolastico

    2003-08-01

    Acute alkalosis may directly affect PTH secretion. The effect of acute metabolic and respiratory alkalosis was studied in 20 dogs. PTH values were lower in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml). Acute alkalosis is an independent factor that decreases PTH values during normocalcemia and delays the PTH response to hypocalcemia. We recently showed that acute metabolic and respiratory acidosis stimulated PTH secretion. This study was designed to evaluate whether acute metabolic and respiratory alkalosis suppressed parathyroid hormone (PTH) secretion. Three groups of 10 dogs were studied: control, acute metabolic alkalosis, and acute respiratory alkalosis. Metabolic alkalosis was induced with an infusion of sodium bicarbonate and respiratory alkalosis by hyperventilation. Calcium chloride was infused to prevent alkalosis-induced hypocalcemia during the first 60 minutes. During the next 30 minutes, disodium EDTA was infused to induce hypocalcemia and to evaluate the PTH response to hypocalcemia. Because the infusion of sodium bicarbonate resulted in hypernatremia, the effect of hypernatremia was studied in an additional group that received hypertonic saline. After 60 minutes of a normocalcemic clamp, PTH values were less (p respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml); the respective blood pH values were 7.61 +/- 0.01, 7.59 +/- 0.02, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was similar among the three groups. However, the maximal PTH response was observed after a decrease in ionized calcium of 0.20 mM in the control group but not until a decrease of 0.40 mM in the metabolic and respiratory alkalosis groups. In contrast to the metabolic alkalosis group, hypernatremia (157 +/- 2 mEq/liter) in the hypertonic saline group was associated with an increased PTH value (46 +/- 4 pg/ml). Finally, the half-life of intact PTH

  8. Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.

    Directory of Open Access Journals (Sweden)

    Hua Wang

    Full Text Available Osteoporosis is a common disorder characterized by compromised bone strength that predisposes patients to increased fracture risk. Parathyroid hormone related protein (PTHrP is one of the candidates for clinical osteoporosis treatment. In this study, GST Gene Fusion System was used to express recombinant human PTHrP (hPTHrP 1-34 and 1-84. To determine whether the recombinant hPTHrP1-34 and 1-84 can enhance renal calcium reabsorption and promote bone formation, we examined effects of recombinant hPTHrP1-34 and 1-84 on osteogenic lineage commitment in a primary bone marrow cell culture system and on osteoporosis treatment. Results revealed that both of recombinant hPTHrP1-34 and 1-84 increased colony formation and osteogenic cell differentiation and mineralization in vitro; however, the effect of recombinant hPTHrP1-84 is a little stronger than that of hPTHrP1-34. Next, ovariectomy was used to construct osteoporosis animal model (OVX to test activities of these two recombinants in vivo. HPTHrP1-84 administration elevated serum calcium by up-regulating the expression of renal calcium transporters, which resulted in stimulation of osteoblastic bone formation. These factors contributed to augmented bone mass in hPTHrP1-84 treated OVX mice but did not affect bone resorption. There was no obvious bone mass alteration in hPTHrP1-34 treated OVX mice, which may be, at least partly, associated with shorter half-life of hPTHrP1-34 compared to hPTHrP1-84 in vivo. This study implies that recombinant hPTHrP1-84 is more effective than hPTHrP1-34 to enhance renal calcium reabsorption and to stimulate bone formation in vivo.

  9. Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.

    Science.gov (United States)

    Wang, Hua; Liu, Jingning; Yin, Ying; Wu, Jun; Wang, Zilu; Miao, Dengshun; Sun, Wen

    2014-01-01

    Osteoporosis is a common disorder characterized by compromised bone strength that predisposes patients to increased fracture risk. Parathyroid hormone related protein (PTHrP) is one of the candidates for clinical osteoporosis treatment. In this study, GST Gene Fusion System was used to express recombinant human PTHrP (hPTHrP) 1-34 and 1-84. To determine whether the recombinant hPTHrP1-34 and 1-84 can enhance renal calcium reabsorption and promote bone formation, we examined effects of recombinant hPTHrP1-34 and 1-84 on osteogenic lineage commitment in a primary bone marrow cell culture system and on osteoporosis treatment. Results revealed that both of recombinant hPTHrP1-34 and 1-84 increased colony formation and osteogenic cell differentiation and mineralization in vitro; however, the effect of recombinant hPTHrP1-84 is a little stronger than that of hPTHrP1-34. Next, ovariectomy was used to construct osteoporosis animal model (OVX) to test activities of these two recombinants in vivo. HPTHrP1-84 administration elevated serum calcium by up-regulating the expression of renal calcium transporters, which resulted in stimulation of osteoblastic bone formation. These factors contributed to augmented bone mass in hPTHrP1-84 treated OVX mice but did not affect bone resorption. There was no obvious bone mass alteration in hPTHrP1-34 treated OVX mice, which may be, at least partly, associated with shorter half-life of hPTHrP1-34 compared to hPTHrP1-84 in vivo. This study implies that recombinant hPTHrP1-84 is more effective than hPTHrP1-34 to enhance renal calcium reabsorption and to stimulate bone formation in vivo.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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...

  16. 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.

  17. 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

  18. Oral phosphorus supplementation secondarily increases circulating fibroblast growth factor 23 levels at least partially via stimulation of parathyroid hormone secretion.

    Science.gov (United States)

    Takasugi, Satoshi; Akutsu, Miho; Nagata, Masashi

    2014-01-01

    Oral phosphorus supplementation stimulates fibroblast growth factor 23 (FGF23) secretion; however, the underlying mechanism remains unclear. The aim of this study was to investigate the involvement of parathyroid hormone (PTH) in increased plasma FGF23 levels after oral phosphorus supplementation in rats. Rats received single dose of phosphate with concomitant subcutaneous injection of saline or human PTH (1-34) after treatment with cinacalcet or its vehicle. Cinacalcet is a drug that acts as an allosteric activator of the calcium-sensing receptor and reduces PTH secretion. Plasma phosphorus and PTH levels significantly increased 1 h after oral phosphorus administration and returned to basal levels within 3 h, while plasma FGF23 levels did not change up to 2 h post-treatment, but rather significantly increased at 3 h after administration and maintained higher levels for at least 6 h compared with the 0 time point. Plasma PTH and FGF23 levels were significantly lower in the cinacalcet-treated rats than in the vehicle-treated rats. Plasma phosphorus levels were significantly higher in the cinacalcet-treated rats than in the vehicle-treated rats at 2, 3, 4, and 6 h after oral phosphorus administration. Furthermore, rats treated with cinacalcet+human PTH (1-34) showed transiently but significantly higher plasma FGF23 levels at 3 h after oral phosphorus administration compared with cinacalcet-treated rats. These results suggest that oral phosphorus supplementation secondarily increases circulating FGF23 levels at least partially by stimulation of PTH secretion.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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...

  5. 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.

  6. Measurement of $R$ between 1.84 and 3.05 GeV at the KEDR detector

    CERN Document Server

    Anashin, V V; Baldin, E M; Barladyan, A K; Barnyakov, A Yu; Barnyakov, M Yu; Baru, S E; Basok, I Yu; Batrakov, A M; Blinov, A E; Blinov, V E; Bobrov, A V; Bobrovnikov, V S; Bogomyagkov, A V; Bondar, A E; Buzykaev, A R; Eidelman, S I; Grigoriev, D N; Glukhovchenko, Yu M; Karnaev, S E; Karpov, G V; Karpov, S V; Kasyanenko, P V; Kharlamova, T A; Kiselev, V A; Kolmogorov, V V; Kononov, S A; Kotov, K Yu; Kravchenko, E A; Kudryavtsev, V N; Kulikov, V F; Kurkin, G Ya; Kuyanov, I A; Levichev, E B; Maksimov, D A; Malyshev, V M; Maslennikov, A L; Meshkov, O I; Mishnev, S I; Morozov, I I; Muchnoi, N Yu; Neufeld, V V; Nikitin, S A; Nikolaev, I B; Okunev, I N; Onuchin, A P; Oreshkin, S B; Osipov, A A; Ovtin, I V; Peleganchuk, S V; Pivovarov, S G; Piminov, P A; Petrov, V V; Prisekin, V G; Rezanova, O L; Ruban, A A; Sandyrev, V K; Savinov, G A; Shamov, A G; Shatilov, D N; Shwartz, B A; Simonov, E A; Sinyatkin, S V; Skrinsky, A N; Sokolov, A V; Sukharev, A M; Starostina, E V; Talyshev, A A; Tayursky, V A; Telnov, V I; Tikhonov, Yu A; Todyshev, K Yu; Tumaikin, G M; Usov, Yu V; Vorobiov, A I; Zhilich, V N; Zhulanov, V V; Zhuravlev, A N

    2016-01-01

    Using the KEDR detector at the VEPP-4M $e^+e^-$ collider, we have determined the values of $R$ at thirteen points of the center-of-mass energy between 1.84 and 3.05 GeV. The achieved accuracy is about or better than $3.9\\%$ at most of the energy points with a systematic uncertainty less than $2.4\\%$.

  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. Phases of LiMn1.84V0.06Ti0.1O4 cathode material

    Science.gov (United States)

    Zainol, N. H.; Kamarulzaman, N.; Osman, Z.; Fadzil, A. F. M.; Yahya, N. F.

    2017-09-01

    In this work, LiMn1.84V0.06Ti0.1O4 was prepared via a combustion method using citric acid as a reductant. The precursor obtained was annealed at 700 °C for 24h in a furnace. The thermal profile of the precursor was obtained by simultaneous thermogravimetric analysis (STA). The observed material was characterized by X-ray Diffraction (XRD) and found to be pure and single-phase of cubic structure. The electrochemical performance of LiMn1.84V0.06Ti0.1O4 cathode material was studied by applying a constant current of 1.0 mA at a voltage range of 4.2 to 2.5 V. The specific capacity of LiMn1.84V0.06Ti0.1O4 cathode material at the 1st cycle shows the value of 95mAh/g which is less than the specific capacity of LiMn2O4, which is 117 mAh/g.

  9. Secretion of human parathyroid hormone from rat pituitary cells infected with a recombinant retrovirus encoding preproparathyroid hormone.

    OpenAIRE

    Hellerman, J G; Cone, R C; Potts, J. T.; Rich, A; Mulligan, R C; Kronenberg, H M

    1984-01-01

    In order to study the functions of precursors to secreted proteins, we expressed cloned DNA encoding human preproparathyroid hormone (preproPTH) in rat pituitary cells. We first constructed a recombinant plasmid containing human preproPTH cDNA and retroviral control signals. This recombinant plasmid was transfected into psi-2 cells, a packaging cell line that produces Moloney murine leukemia viral particles containing no retroviral RNA. The transfected psi-2 cells generated helper-free recomb...

  10. Calcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans.

    Science.gov (United States)

    Cañadillas, Sagrario; Canalejo, Antonio; Santamaría, Rafael; Rodríguez, Maria E; Estepa, Jose C; Martín-Malo, Alejandro; Bravo, Juan; Ramos, Blanca; Aguilera-Tejero, Escolastico; Rodríguez, Mariano; Almadén, Yolanda

    2005-07-01

    In uremic patients, severe parathyroid hyperplasia is associated with reduced parathyroid calcium-sensing receptor (CaR) expression. Thus, in these patients, a high serum Ca concentration may be required to inhibit parathyroid hormone (PTH) secretion. This study compares the magnitude of reduction in CaR expression and the degree of the abnormality in Ca-regulated PTH release in vitro. A total of 50 glands from 23 hemodialysis patients with refractory hyperparathyroidism were studied. Tissue slices were incubated in vitro to evaluate (1) the PTH secretory output in a normal Ca concentration (1.25 mM) and (2) the PTH secretory response to high (1.5 mM) and low (0.6 mM) Ca concentration. Tissue aliquots were processed for determination of CaRmRNA expression. The results showed that, corrected for DNA, parathyroid tissue with lowest CaR expression secreted more PTH than that with relatively high CaR expression (146 +/- 23 versus 60 +/- 2 pg/microg DNA; P < 0.01). Furthermore, glands with low CaR expression demonstrated a blunted PTH secretory response to both the inhibitory effect of high Ca and the stimulatory effect of low Ca. The study also showed that the larger the gland, the lower the CaRmRNA expression. Thus, large parathyroid glands produce a large amount of PTH not only as a result of the increased gland size but also because the parathyroid tissue secretory output is increased. These abnormalities in PTH regulation are related to low CaR expression.

  11. 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...

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Secrets Law

    Directory of Open Access Journals (Sweden)

    Luz Helena Guamanzara Torres

    2013-01-01

    Full Text Available This paper provides a review of the book The Law of Secrets, of the author Juan Carlos Martínez-Villalba Riofrío studying the secrets and how law does protect. To this end, the author has analyzed the general theory of secrecy, secrets and methodology, its overall rating, essential elements and their different legal dimensions, the secret as a subjective right. It also establishes that professional secrecy is protected by constitutional principles such as the right to privacy.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Microwave-assisted synthesis of self-assembled BiO{sub 1.84}H{sub 0.08} hierarchical nanostructures as a new photocatalyst

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Pei; Hou, Dongfang; Shi, Hongyu; Chen, Chaoji; Huang, Yunhui; Hu, Xianluo, E-mail: huxl@mail.hust.edu.cn

    2014-11-15

    Highlights: • Hierarchical BiO{sub 1.84}H{sub 0.08} nanostructures were prepared by microwave irradiation. • The microwave-hydrothermal method is rapid, one-pot, and low-temperature. • The morphology of the BiO{sub 1.84}H{sub 0.08} nanostructures can be tailored. • The photocatalytic properties were studied upon UV–visible irradiation. • Self-assembled flower-like BiO{sub 1.84}H{sub 0.08} shows enhanced photocatalytic activity. - Abstract: Self-assembled hierarchical nanostructures of BiO{sub 1.84}H{sub 0.08} spheres have been successfully synthesized by a rapid, one-pot, low-temperature hydrothermal route under microwave irradiation. The as-prepared hierarchically nanostructured BiO{sub 1.84}H{sub 0.08} possesses a high surface area of 113 m{sup 2} g{sup −1}. By adjusting the reaction temperature and reactant concentration, the morphology of the as-formed BiO{sub 1.84}H{sub 0.08} nanostructures can be tailored. As a new photocatalyst, the flower-like spherical BiO{sub 1.84}H{sub 0.08} exhibits enhanced photocatalytic activity for degradation of Rhodamine B (RhB) under UV–visible light. The synthetic procedure is simple, efficient, and scalable for mass production. Therefore, the as-formed BiO{sub 1.84}H{sub 0.08} hierarchical nanostructures may offer great potential applications for decomposition of organic contaminants.

  4. 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

  5. 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...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  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. 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

  3. 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.

  4. 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

  5. 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...

  6. 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

  7. Google Secrets

    CERN Document Server

    Davis, Yvette

    2011-01-01

    Become a Google guru with these effective tips, tricks, and techniques Sure, you use Google. But do you really use Google-and everything it has to offer-in the most effective way possible? Wish you could just sit down with a Google expert who would show you how to take your Google savviness to the next level? With Google Secrets, you can! Tech expert Jerri Ledford reveals the ins, outs, and little-known facts about Google to show you how to sharpen your skills so you can get more done, more efficiently. You may already be familiar with Google's most popular applications, but this indispensable

  8. Effect of calcitriol on insulin secretion in uraemia.

    Science.gov (United States)

    Quesada, J M; Martín-Malo, A; Santiago, J; Hervas, F; Martinez, M E; Castillo, D; Barrio, V; Aljama, P

    1990-01-01

    To evaluate the role of calcitriol on insulin secretion in uraemia, nine patients on maintenance haemodialysis, never treated with vitamin D nor with calcium-channel blockers, were studied. Baseline glucose, insulin, C peptide, calcium, intact PTH, and calcitriol serum values were measured, and after an oral load of 75 g glucose, insulin and C peptide were also determined at 15, 30, 45, 60, and 120 min. Following 14 days of treatment with oral calcitriol (0.5 microgram/day), the same study protocol was applied. Serum calcitriol values, which were low as expected, increased after therapy, but did not reach the values observed in healthy controls. Despite no change in total serum calcium, intact PTH values decreased significantly (182 vs 88.3 ng/ml, P less than 0.003). Baseline serum insulin was significantly increased after calcitriol (7.5 vs 35 microU/ml, P less than 0.001). Similarly, an enhancement in insulin secretion following calcitriol was observed at 15 min (34 vs 70, P less than 0.01) and 30 min (57 vs 96 microU/ml, P less than 0.01). Computation of the total area under the curve confirmed these results. Changes in C peptide profile paralleled those described for insulin. These data confirm that vitamin D modulates pancreatic beta-cell secretion and suggest that calcitriol may regulate insulin release in uraemic patients.

  9. Parathyroid hormone secretion in chronic renal failure

    DEFF Research Database (Denmark)

    Madsen, J C; Rasmussen, A Q; Ladefoged, S D

    1996-01-01

    The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during....../ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...... of a standardized method we show that the calcium set-point is normal or slightly elevated, indicating normal parathyroid reactivity to calcium in chronic renal failure....

  10. 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.

  11. 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.

  12. 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.

  13. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    Science.gov (United States)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  14. 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...

  15. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

    Science.gov (United States)

    Gowen, Maxine; Stroup, George B.; Dodds, Robert A.; James, Ian E.; Votta, Bart J.; Smith, Brian R.; Bhatnagar, Pradip K.; Lago, Amparo M.; Callahan, James F.; DelMar, Eric G.; Miller, Michael A.; Nemeth, Edward F.; Fox, John

    2000-01-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a “calcilytic”) of the parathyroid cell Ca2+ receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17β-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca2+ receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  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. 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.

  8. 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.

  9. 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

  10. 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).

  11. 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

  12. PTH Test

    Science.gov (United States)

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  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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...

  4. A new measure of Δα/α at redshift z = 1.84 from very high resolution spectra of Q 1101-264

    Science.gov (United States)

    Levshakov, S. A.; Molaro, P.; Lopez, S.; D'Odorico, S.; Centurión, M.; Bonifacio, P.; Agafonova, I. I.; Reimers, D.

    2007-05-01

    Aims:We probe the evolution of the fine-structure constant α with cosmic time. Methods: Accurate positions of the Fe II lines λ1608, λ2382, and λ2600 are measured in the z_abs = 1.84 absorption system from a high-resolution (FWHM ~ 3.8 km s-1) and high signal-to-noise (S/N ⪆ 100) spectrum of the quasar Q 1101-264 (z_em = 2.15, V = 16.0), integrated for 15.4 h. The Single Ion Differential α Measurement (SIDAM) procedure and the Δ χ2 method are used to set constraints on Δα/α. Results: We have found a relative radial velocity shift between the λ1608 and λλ2382,2600 lines of Δ v = -180 ± 85 m s-1 (both random and systematic errors are included), which, if real, would correspond to Δα/α = (5.4±2.5) × 10-6 (1σ C.L.). Considering the strong implications of a such variability, additional observations with comparable accuracy at redshift z ˜ 1.8 are required to confirm this result. Based on observations performed at the VLT Kueyen telescope (ESO, Paranal, Chile), the ESO programme No. 076.A-0463.

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. 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...

  13. 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

  14. 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.

  15. Effects of 1.84 GHz Radiation-frequency Electromagnetic Radiation on Energy Metabolism and Anti-oxidative Damage of Male SD Rat Testis%1.84 GHz射频电磁辐射对SD大鼠睾丸能量代谢酶的影响及其抗氧化损伤作用

    Institute of Scientific and Technical Information of China (English)

    吴涛; 林艳云; 郭奇彦; 郎海洋; 王锐; 刘军叶; 曾丽华; 郭国祯

    2016-01-01

    为了探讨频率为1.84 GHz的射频电磁辐射对SD大鼠睾丸能量代谢酶的影响及其抗氧化损伤作用,将24只成年雄性SD大鼠按体质量随机分成了l组对照组(即假辐照组)和3组辐照组,采用频率为1.84 GHz、比吸收率(SAR)分别为0.2、0.5、1.5 W/kg的射频电磁辐射,连续辐照3周时间,每周辐照5d时间,每天辐照30 min时间;辐照后立即麻醉处死SD大鼠,取睾丸组织,左侧睾丸组织给予多聚甲醛固定,右侧睾丸组织制备组织匀浆;采用苏木精-伊红(HE)染色后用十字交叉法观察了SD大鼠生精小管直径,采用化学比色法检测了睾丸组织内乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性及丙二醛(MDA)的浓度.研究结果表明:与对照组相比,辐照组SD大鼠睾丸生精小管直径没有明显缩短,辐照组CAT活性和MDA浓度没有明显差异,但辐照组SOD的活性明显降低(概率P<0.05),且SAR为0.5 W/kg和1.5 W/kg的辐照组LDH和SDH活性明显降低(P<0.05).在此辐照条件下,频率为1.84 GHz的射频电磁辐射,没有对雄性SD大鼠睾丸组织造成明显的氧化损伤,但是降低了SD大鼠睾丸组织内能量代谢酶和部分抗氧化酶的活性.

  16. Authentication Without Secrets

    Energy Technology Data Exchange (ETDEWEB)

    Pierson, Lyndon G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Robertson, Perry J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integrity of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.

  17. 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.

  18. 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.

  19. 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.

  20. Immunoglobins in mammary secretions

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel

    2013-01-01

    Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through inte...

  1. 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...

  2. f184sc.m77t - MGD77 data file for Geophysical data from field activity F-1-84-SC in Southern California from 04/26/1984 to 05/21/1984

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Single-beam bathymetry and magnetic data along with DGPS navigation data was collected as part of field activity F-1-84-SC in Southern California from 04/26/1984 to...

  3. l184an.m77t - MGD77 data file for Geophysical data from field activity L-1-84-AN in Antarctica from 01/04/1984 to 02/01/1984

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Single-beam bathymetry, gravity, and magnetic data along with DGPS navigation data was collected as part of field activity L-1-84-AN in Antarctica from 01/04/1984 to...

  4. l184an.m77t - MGD77 data file for Geophysical data from field activity L-1-84-AN in Antarctica from 01/04/1984 to 02/01/1984

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Single-beam bathymetry, gravity, and magnetic data along with DGPS navigation data was collected as part of field activity L-1-84-AN in Antarctica from 01/04/1984...

  5. f184sc.m77t - MGD77 data file for Geophysical data from field activity F-1-84-SC in Southern California from 04/26/1984 to 05/21/1984

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Single-beam bathymetry and magnetic data along with DGPS navigation data was collected as part of field activity F-1-84-SC in Southern California from 04/26/1984 to...

  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. Incretin secretion: direct mechanisms

    DEFF Research Database (Denmark)

    Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

    2014-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Type VI secretion system.

    Science.gov (United States)

    Salomon, Dor; Orth, Kim

    2015-03-30

    Bacteria employ a variety of tools to survive in a competitive environment. Salomon and Orth describe one such tool-the Type 6 Secretion Systems used by bacteria to deliver a variety of toxins into competing cells.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Unconventional protein secretion.

    Science.gov (United States)

    Ding, Yu; Wang, Juan; Wang, Junqi; Stierhof, York-Dieter; Robinson, David G; Jiang, Liwen

    2012-10-01

    It is generally believed that protein secretion or exocytosis is achieved via a conventional ER (endoplasmic reticulum)-Golgi-TGN (trans-Golgi network)-PM (plasma membrane) pathway in the plant endomembrane system. However, such signal peptide (SP)-dependent protein secretion cannot explain the increasing number of SP-lacking proteins which are found outside of the PM in plant cells. The process by which such leaderless secretory proteins (LSPs) gain access to the cell exterior is termed unconventional protein secretion (UPS) and has been well-studied in animal and yeast cells, but largely ignored by the plant community. Here, we review the evidence for UPS in plants especially in regard to the recently discovered EXPO (exocyst-positive-organelle).

  4. 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

  5. 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

  6. 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.

  7. Secrets of Successful Homeschooling

    Science.gov (United States)

    Rivero, Lisa

    2011-01-01

    Parents who homeschool gifted children often find the daily practice of home education very different from what they had imagined. Gifted children are complex in both personality and learning styles. Parents who say that homeschooling works well for their gifted children have learned from others or discovered on their own several secrets that make…

  8. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller

    2008-01-01

    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment,in different situations,results in the syndrome of cholestasis.The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed.Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane.This review summarizes recent data on the molecular determinants of this primary bile formation.The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bileduct epithelial cells (cholangiocytes) as bile passes through bile ducts.The mechanisms of fluid and solute transport in cholangiocytes will also be discussed.In contrast to hepatocytes where secretion is constant and poorly controlled,cholangiocyte secretion is regulated by hormones and nerves.A short section dedicated to these regulatory mechanisms of bile secretion has been included.The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

  9. Salivary Gland Secretion.

    Science.gov (United States)

    Dorman, H. L.; And Others

    1981-01-01

    Describes materials and procedures for an experiment utilizing a live dog to demonstrate: (1) physiology of the salivary gland; (2) parasympathetic control of the salivary gland; (3) influence of varying salivary flow rates on sodium and potassium ions, osmolarity and pH; and (4) salivary secretion as an active process. (DS)

  10. Almost-perfect secret sharing

    CERN Document Server

    Kaced, Tarik

    2011-01-01

    Splitting a secret s between several participants, we generate (for each value of s) shares for all participants. The goal: authorized groups of participants should be able to reconstruct the secret but forbidden ones get no information about it. In this paper we introduce several notions of non- perfect secret sharing, where some small information leak is permitted. We study its relation to the Kolmogorov complexity version of secret sharing (establishing some connection in both directions) and the effects of changing the secret size (showing that we can decrease the size of the secret and the information leak at the same time).

  11. Are Secrets Immoral? The Construction of Secrets in Everyday Conversation.

    Science.gov (United States)

    Gunthner, Susanne; Luckmann, Thomas

    1998-01-01

    Investigates the communicative treatment of secrets, presenting examples from recorded communicative interactions in a wide range of social milieus and settings in which the participants revealed knowledge of secrets, tried to dig out old secrets without appearing to be doing so, and occasionally, appeared to be hiding some items of knowledge from…

  12. 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.

  13. Manipulation of calciumhomeostatic mechanisms in man: what are the possibilities?

    DEFF Research Database (Denmark)

    Schwarz, Peter

    2003-01-01

    The aim of our studies on parathyroid hormone dynamics were to establish standardized methods for induction of hypocalcaemia, sequential hypercalcaemia and normocalcaemia and sequential hypocalcaemia and hypercalcaemia suitable for careful and detailed evaluation of the PTH(1-84) secretion in viv...

  14. Extracellular secretion of recombinant proteins

    Science.gov (United States)

    Linger, Jeffrey G.; Darzins, Aldis

    2014-07-22

    Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

  15. 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.

  16. 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.

  17. Telling stories: keeping secrets.

    Science.gov (United States)

    Jensen, Joan M

    2009-01-01

    This article addresses the reticence of some farm women to share their experiences with historians and how that desire to keep secrets collides with the desire by scholars to tell the stories of these women. It argues that scholars must continue to struggle with the issue of which stories to tell publicly and which to keep private. The author discusses her own experience telling stories about rural women in the 1970s and the need to give voice to the heritage of rural women, especially of groups that have feared revealing their experiences. She offers examples of historians of rural women who have successfully worked with formerly silenced populations and urges historians to continue to tell stories about these lives, to reevaluate what has been already learned, to ask new questions, and to discuss which secrets need to be shared.

  18. Bucarest, Strictement Secret

    Directory of Open Access Journals (Sweden)

    Ionela Mihai

    2010-07-01

    Full Text Available L’émission Bucarest, strictement secret représente un documentaire organisésous la forme d’une série télé, qui dépeint le Bucarest à partir de deux perspectives: de l’histoire, de la conte et du lieu. La valeur d’une cité réside dans l’existence d’une mystique, d’un romantisme abscons, à part et des caractères empruntés de drames de Shakespeare, mystérieux, serrés d’angoisse et des secrets qui assombrissent leur existence. Par conséquence, le rôle du metteur en scène est de dévoiler leur vraie identité et de remettre en place, autant que possible, la vérité.

  19. Secret Key Crypto Implementations

    Science.gov (United States)

    Bertoni, Guido Marco; Melzani, Filippo

    This chapter presents the algorithm selected in 2001 as the Advanced Encryption Standard. This algorithm is the base for implementing security and privacy based on symmetric key solutions in almost all new applications. Secret key algorithms are used in combination with modes of operation to provide different security properties. The most used modes of operation are presented in this chapter. Finally an overview of the different techniques of software and hardware implementations is given.

  20. 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

  1. 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

  2. Dynamic secrets in communication security

    CERN Document Server

    Xiao, Sheng; Towsley, Donald

    2013-01-01

    Dynamic secrets are constantly generated and updated from messages exchanged between two communication users. When dynamic secrets are used as a complement to existing secure communication systems, a stolen key or password can be quickly and automatically reverted to its secret status without disrupting communication. 'Dynamic Secrets in Communication Security' presents unique security properties and application studies for this technology. Password theft and key theft no longer pose serious security threats when parties frequently use dynamic secrets. This book also illustrates that a dynamic

  3. Autotransporter protein secretion.

    Science.gov (United States)

    Tame, Jeremy R H

    2011-12-01

    Autotransporter proteins are a large family of virulence factors secreted from Gram-negative bacteria by a unique mechanism. First described in the 1980s, these proteins have a C-terminal region that folds into a β-barrel in the bacterial outer membrane. The so-called passenger domain attached to this barrel projects away from the cell surface and may be liberated from the cell by self-cleavage or surface proteases. Although the majority of passenger domains have a similar β-helical structure, they carry a variety of sub-domains, allowing them to carry out widely differing functions related to pathogenesis. Considerable biochemical and structural characterisation of the barrel domain has shown that 'autotransporters' in fact require a conserved and essential protein complex in the outer membrane for correct folding. Although the globular domains of this complex projecting into the periplasmic space have also been structurally characterised, the overall secretion pathway of the autotransporters remains highly puzzling. It was presumed for many years that the passenger domain passed through the centre of the barrel domain to reach the cell surface, driven at least in part by folding. This picture is complicated by conflicting data, and there is currently little hard information on the true nature of the secretion intermediates. As well as their medical importance therefore, autotransporters are proving to be an excellent system to study the folding and membrane insertion of outer membrane proteins in general. This review focuses on structural aspects of autotransporters; their many functions in pathogenesis are beyond its scope.

  4. 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

  5. Windows 8 secrets

    CERN Document Server

    Thurrott, Paul

    2012-01-01

    Tips, tricks, treats, and secrets revealed on Windows 8 Microsoft is introducing a major new release of its Windows operating system, Windows 8, and what better way to learn all its ins and outs than from two internationally recognized Windows experts and Microsoft insiders, authors Paul Thurrott and Rafael Rivera? They cut through the hype to get at useful information you'll not find anywhere else, including what role this new OS plays in a mobile and tablet world. Regardless of your level of knowledge, you'll discover little-known facts about how things work, what's new and different, and h

  6. 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.

  7. 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...

  8. Ghrelin and gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Koji Yakabi; Junichi Kawashima; Shingo Kato

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric add secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  9. Ghrelin and gastric acid secretion.

    Science.gov (United States)

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-11-07

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-induced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  10. 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

  11. On Converting Secret Sharing Scheme to Visual Secret Sharing Scheme

    Directory of Open Access Journals (Sweden)

    Wang Daoshun

    2010-01-01

    Full Text Available Abstract Traditional Secret Sharing (SS schemes reconstruct secret exactly the same as the original one but involve complex computation. Visual Secret Sharing (VSS schemes decode the secret without computation, but each share is m times as big as the original and the quality of the reconstructed secret image is reduced. Probabilistic visual secret sharing (Prob.VSS schemes for a binary image use only one subpixel to share the secret image; however the probability of white pixels in a white area is higher than that in a black area in the reconstructed secret image. SS schemes, VSS schemes, and Prob. VSS schemes have various construction methods and advantages. This paper first presents an approach to convert (transform a -SS scheme to a -VSS scheme for greyscale images. The generation of the shadow images (shares is based on Boolean XOR operation. The secret image can be reconstructed directly by performing Boolean OR operation, as in most conventional VSS schemes. Its pixel expansion is significantly smaller than that of VSS schemes. The quality of the reconstructed images, measured by average contrast, is the same as VSS schemes. Then a novel matrix-concatenation approach is used to extend the greyscale -SS scheme to a more general case of greyscale -VSS scheme.

  12. 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

  13. Positive Correlation of PTH-Related Peptide with Glucose in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Ioannis Legakis

    2009-01-01

    Full Text Available Type 2 diabetes is characterized by hyperglycemia resulting from insulin resistance in the setting of inadequate beta-cell compensation. Recent studies indicate that for attaining a well-functioning ß-cell mass, parathyroid hormone-related protein (PTHrP is a very promising candidate among several insulinotropic peptides. In order to elucidate its role, we determine the levels of PTHrP, insulin and c-peptide in type 2 diabetics and in normal subjects in the fasting state. We enrolled 28 patients (16 men and 12 postmenopausal women with type 2 diabetes and twenty eight aged-matched healthy individuals as control subjects (15 men and 13 women. PTHrP was statistically significant correlated with glucose in type 2 diabetes and in normal subjects in the fasting state. Additionally, PTHrP serum levels exhibited a significant increase in type 2 diabetes compared to control subjects. Interestingly, PTHrP showed a positive correlation with insulin levels only among healthy individuals presumably due to defective glucose stimulated insulin secretion known to occur in type 2 diabetics. In conclusion ,the strong positive relation of PTHrP with glucose in the fasting state in patients with type 2 diabetes mellitus raises several questions for further experimentation concerning its exact role and physiological significance.

  14. RIC-7 promotes neuropeptide secretion.

    Directory of Open Access Journals (Sweden)

    Yingsong Hao

    2012-01-01

    Full Text Available Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs and dense core vesicles (DCVs respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV-mediated secretion.

  15. Salmonella-secreted Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

    2011-05-01

    In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

  16. Circular threshold quantum secret sharing

    Institute of Scientific and Technical Information of China (English)

    Yang Yu-Guang; Wen Qiao-Yan

    2008-01-01

    This paper proposes a circular threshold quantum secret sharing (TQSS) scheme with polarized single photons.A polarized single photon sequence runs circularly among any t or more of n parties and any t or more of n parties can reconstruct the secret key when they collaborate.It shows that entanglement is not necessary for quantum secret sharing.Moreover,the theoretic efficiency is improved to approach 100% as the single photons carrying the secret key are deterministically forwarded among any t or more of n parties,and each photon can carry one bit of information without quantum storage.This protocol is feasible with current technology.

  17. JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.

    Science.gov (United States)

    Kimura, Shuichi; Nakagawa, Takashi; Matsuo, Yushi; Ishida, Yuji; Okamoto, Yoshihisa; Hayashi, Mikio

    2011-10-01

    Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 μg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.

  18. A Public Secret

    DEFF Research Database (Denmark)

    Bregnbæk, Susanne

    2011-01-01

    This article is based on anthropological fieldwork undertaken at two elite universities in Beijing. It addresses the paradoxical situation of the many instances of suicide among Chinese elite university students in Beijing, which constitute a public secret. The pressure of education weighs heavily...... on the shoulders of China’s only child in each family, known as the generation of little emperors and little empresses. Since the 1980s, the suzhi jiaoyu reforms (education for quality) have involved various attempts to reduce the pressure of education. However, simultaneously the aim is to increase...... the competitiveness of individuals. Drawing on existential and phenomenological thought, I suggest that the discourse seems to objectify and quantify a concern for well-being, rather than recognising its intersubjective character. Finally, I argue that the suicides are controversial since they are seen as a form...

  19. Yohimbine increases human salivary secretion.

    Science.gov (United States)

    Chatelut, E; Rispail, Y; Berlan, M; Montastruc, J L

    1989-01-01

    The effect of oral yohimbine (14 mg) on salivary secretion was evaluated in healthy volunteers. Yohimbine significantly increased salivary secretion when compared with placebo. This effect was significant from 60 min until 180 min after administration under our experimental conditions. Yohimbine (or alpha 2-adrenoceptor blocking agents) could have a potential interest in the treatment of dry mouths. PMID:2789932

  20. The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis.

    Science.gov (United States)

    Ori, Yaacov; Zingerman, Boris; Bergman, Michael; Bessler, Hanna; Salman, Hertzel

    2015-04-01

    The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4-5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134±10-116±8 mg/dl, P=0.002), potassium decreased (5.1±0.4-4.8±0.1 mequiv./l, P=0.064), pH increased (7.29±0.01-7.33±0.01, P=0.008), and serum bicarbonate increased (18.6±0.4 mequiv./l to 21.3±0.3 mequiv./l, P=0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75±0.25 ng/ml to 2.29±0.21 ng/ml, P=0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1β, IL-2, IL-6, TNFα, IFNγ, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated.

  1. 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

  2. Multiparty Quantum Secret Report

    Institute of Scientific and Technical Information of China (English)

    DENG Fu-Guo; LI Xi-Han; LI Chun-Yan; ZHOU Ping; LIANG Yu-Jie; ZHOU Hong-Yu

    2006-01-01

    @@ A multiparty quantum secret report scheme is proposed with quantum encryption. The boss Alice and her M agents first share a sequence of (M + 1)-particle Greenberger-Horne-Zeilinger (GHZ) states that only Alice knows which state each (M + 1)-particle quantum system is in. Each agent exploits a controlled-not (CNot) gate to encrypt the travelling particle by using the particle in the GHZ state as the control qubit. The boss Alice decrypts the travelling particle with a CNot gate after performing a σx operation on her particle in the GHZ state or not.After the GHZ states (the quantum key) are used up, the parties check whether there is a vicious eavesdropper,say Eve, monitoring the quantum line, by picking out some samples from the GHZ states shared and measuring them with two measuring bases. After confirming the security of the quantum key, they use the remaining GHZ states repeatedly for the next round of quantum communication. This scheme has the advantage of high intrinsic efficiency for the qubits and total efficiency.

  3. Pheochromocytomas and secreting paragangliomas

    Directory of Open Access Journals (Sweden)

    Gimenez-Roqueplo Anne-Paule

    2006-12-01

    Full Text Available Abstract Catecholamine-producing tumors may arise in the adrenal medulla (pheochromocytomas or in extraadrenal chromaffin cells (secreting paragangliomas. Their prevalence is about 0.1% in patients with hypertension and 4% in patients with a fortuitously discovered adrenal mass. An increase in the production of catecholamines causes symptoms (mainly headaches, palpitations and excess sweating and signs (mainly hypertension, weight loss and diabetes reflecting the effects of epinephrine and norepinephrine on α- and β-adrenergic receptors. Catecholamine-producing tumors mimic paroxysmal conditions with hypertension and/or cardiac rhythm disorders, including panic attacks, in which sympathetic activation linked to anxiety reproduces the same signs and symptoms. These tumors may be sporadic or part of any of several genetic diseases: familial pheochromocytoma-paraganglioma syndromes, multiple endocrine neoplasia type 2, neurofibromatosis 1 and von Hippel-Lindau disease. Familial cases are diagnosed earlier and are more frequently bilateral and recurring than sporadic cases. The most specific and sensitive diagnostic test for the tumor is the determination of plasma or urinary metanephrines. The tumor can be located by computed tomography, magnetic resonance imaging and metaiodobenzylguanidine scintigraphy. Treatment requires resection of the tumor, generally by laparoscopic surgery. About 10% of tumors are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. Recurrences and malignancy are more frequent in cases with large or extraadrenal tumors. Patients, especially those with familial or extraadrenal tumors, should be followed-up indefinitely.

  4. Ergodic Secret Alignment

    CERN Document Server

    Bassily, Raef

    2010-01-01

    In this paper, we introduce two new achievable schemes for the fading multiple access wiretap channel (MAC-WT). In the model that we consider, we assume that perfect knowledge of the state of all channels is available at all the nodes in a causal fashion. Our schemes use this knowledge together with the time varying nature of the channel model to align the interference from different users at the eavesdropper perfectly in a one-dimensional space while creating a higher dimensionality space for the interfering signals at the legitimate receiver hence allowing for better chance of recovery. While we achieve this alignment through signal scaling at the transmitters in our first scheme (scaling based alignment (SBA)), we let nature provide this alignment through the ergodicity of the channel coefficients in the second scheme (ergodic secret alignment (ESA)). For each scheme, we obtain the resulting achievable secrecy rate region. We show that the secrecy rates achieved by both schemes scale with SNR as 1/2log(SNR...

  5. Helicobacter pylori in lacrimal secretions.

    Science.gov (United States)

    Batioglu-Karaaltin, Aysegul; Saatci, Ozlem; Akpinar, Meltem; Celik, Melih Ozgür; Develioglu, Omer; Yigit, Ozgur; Külekçi, Mehmet; Akarsubaşı, Alper Tunga

    2016-03-01

    The aim of this study was to investigate the presence of Helicobacter pylori in human lacrimal and nasal secretions. Eighty patients with complaints of dyspepsia who had undergone endoscopies and gastric antrum biopsies were included in the study. A total of five specimens, including 2 lacrimal secretion samples, 2 nasal mucosal swab samples, and 1 gastric antrum biopsy, were collected from each patient and investigated with polymerase chain reaction (PCR) methods consisting of the urease enzyme coding gene GlmM (UreC) and the H pylori-specific 16S rRNA coding gene. The Reflux Symptom Index and ophthalmologic complaints of the patients were recorded. The detected positivity rates of the H pylori 16S rRNA coding gene in gastric biopsies and nasal mucous and lacrimal secretions were 55, 11.2, and 20%, respectively. The patients were grouped as gastric-antrum-biopsy-negative (Group I [n = 36]) and -positive (Group II [n = 44). In Group II, H pylori positivity in the lacrimal and nasal mucous secretions was 36.3 and 18%, respectively. A comparison between the groups in terms of H pylori presence in nasal mucous and lacrimal secretions yielded statistically significant differences (p = 0.0001, p = 0.003). The simultaneous presence of H pylori in nasal mucous and lacrimal secretions was 13.6% in Group II. H pylori positivity in nasal mucous and lacrimal secretions had a positive moderate correlation (r = 0.40; p = 0.0003). The present study is the first report on the presence of H pylori in lacrimal secretions through nested PCR, which suggested the presence of a number of mechanisms for H pylori transmission to lacrimal secretions.

  6. Secret key generation via a modified quantum secret sharing protocol

    Science.gov (United States)

    Smith, A. M.; Evans, P. G.; Lawrie, B.; Legré, M.; Lougovski, P.; Ray, W.; Williams, B. P.; Qi, B.; Grice, W. P.

    2015-05-01

    We present and experimentally show a novel protocol for distributing secret information between two and only two parties in a N-party single-qubit Quantum Secret Sharing (QSS) system. We demonstrate this new algorithm with N = 3 active parties over ~6km of telecom. fiber. Our experimental device is based on the Clavis2 Quantum Key Distribution (QKD) system built by ID Quantique but is generalizable to any implementation. We show that any two out of the N parties can build secret keys based on partial information from each other and with collaboration from the remaining N - 2 parties. This algorithm allows for the creation of two-party secret keys were standard QSS does not and significantly reduces the number of resources needed to implement QKD on a highly connected network such as the electrical grid.

  7. Secret Key Generation via a Modified Quantum Secret Sharing Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Smith IV, Amos M [ORNL; Evans, Philip G [ORNL; Lawrie, Benjamin J [ORNL; Legre, Matthieu [ID Quantique, Inc.; Lougovski, Pavel [ORNL; Ray, William R [ORNL; Williams, Brian P [ORNL; Qi, Bing [ORNL; Grice, Warren P [ORNL

    2015-01-01

    We present and experimentally show a novel protocol for distributing secret information between two and only two parties in a N-party single-qubit Quantum Secret Sharing (QSS) system. We demonstrate this new algorithm with N = 3 active parties over 6km of telecom. ber. Our experimental device is based on the Clavis2 Quantum Key Distribution (QKD) system built by ID Quantique but is generalizable to any implementation. We show that any two out of the N parties can build secret keys based on partial information from each other and with collaboration from the remaining N > 2 parties. This algorithm allows for the creation of two-party secret keys were standard QSS does not and signicantly reduces the number of resources needed to implement QKD on a highly connected network such as the electrical grid.

  8. Characterization of a secreted Chlamydia protease

    DEFF Research Database (Denmark)

    Shaw, Allan C; Vandahl, Brian; Larsen, Martin Røssel

    2002-01-01

    Chlamydiae are obligate intracellular bacteria that are important human pathogens. The Chlamydia genomes contain orthologues to secretion apparatus proteins from other intracellular bacteria, but only a few secreted proteins have been identified. Most likely, effector proteins are secreted in ord...

  9. Ghrelin and gastric acid secretion

    OpenAIRE

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In t...

  10. 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...

  11. 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.

  12. 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....

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Star-forming blue ETGs in two newly discovered galaxy overdensities in the HUDF at z=1.84 and 1.9: unveiling the progenitors of passive ETGs in cluster cores

    CERN Document Server

    Mei, Simona; Pentericci, Laura; Newman, Jeffrey A; Weiner, Benjamin J; Ashby, Matthew L N; Castellano, Marco; Conselice, Chistopher J; Filkelstein, Steven L; Galametz, Audrey; Grogin, Norman A; Koekemoer, Anton M; Huertas-Company, Marc; Lani, Caterina; Lucas, Ray A; Papovich, Casey; Rafelski, Marc; Tepliz, Harry I

    2014-01-01

    We present the discovery of two galaxy overdensities in the HST UDF: a proto-cluster, HUDFJ0332.4-2746.6 at $z = 1.84 \\pm 0.01$, and a group, HUDFJ0332.5-2747.3 at $z =1.90 \\pm 0.01$. The velocity dispersion of HUDFJ0332.4-2746.6 implies a mass of $M_{200}= (2.2 \\pm 1.8) \\times 10^{14} M_{\\odot}$, consistent with the lack of extended X-ray emission. Neither overdensity shows evidence of a red sequence. About $50\\%$ of their members show interactions and/or disturbed morphologies, which are a signature of merger remnants. Most of their morphologically classified ETGs have blue colors and show recent star-formation. These observations reveal for the first time large fractions of spectroscopically confirmed star-forming blue ETGs in proto-clusters at $z\\approx 2$. These star-forming ETGs are most likely among the progenitors of the quiescent population in clusters at more recent epochs. Their mass-size relation is consistent with that of passive ETGs in clusters at $z\\sim0.7-1.5$. If these galaxies are the proge...

  19. Preparation and characterization of Ag-added Bi1.84Pb0.4Sr2Ca2.2Cu3O10+ bulk tube conductors for cryogen free superconducting magnet

    Indian Academy of Sciences (India)

    S N Ekbote; G K Padam; M Sharma; N K Arora; B S Khurana; R C Goel; D K Suri; N Mehra; B K Das

    2001-12-01

    Bulk tube conductors of Bi1.84Pb0.4Sr2Ca2.2Cu3O10+ with addition of silver varying from 0 to 25 wt% (not reported earlier) were systematically studied using X-ray diffraction (XRD), scanning electron microscopy (SEM), electrical transport and a.c. susceptibility techniques. The tube conductors formed by cold isostatic pressing (CIP) of the powders obtained from spray drying method have been made successfully. It was found that Ag addition has not only affected the formation of the desired Bi-2223 phase and the microstructure of these large bulk tube samples thereby influencing on the critical current (c), it also reduces the contact resistance to minimize the cryogen losses. These variations have been found to be Ag content dependent. An optimized value of 10 wt% Ag has been found to produce the best quality tubes showing reproducible c value > 120 Amp at 77 K which is in general a requirement to energies of the cryogen free conventional/HTSC superconducting magnets below 20 K.

  20. Observation of a structure at 1.84 GeV/c$^2$ in the $3(\\pi^+\\pi^-)$ mass spectrum in $J/\\psi\\rightarrow \\gamma 3(\\pi^+\\pi^-)$ decays

    CERN Document Server

    Ablikim, M; Albayrak, O; Ambrose, D J; An, F F; An, Q; Bai, J Z; Ferroli, R Baldini; Ban, Y; Becker, J; Bennett, J V; Bertani, M; Bian, J M; Boger, E; Bondarenko, O; Boyko, I; Briere, R A; Bytev, V; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, J C; Chen, M L; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, Y P; Cronin-Hennessy, D; Dai, H L; Dai, J P; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; Ding, W M; Ding, Y; Dong, L Y; Dong, M Y; Du, S X; Fang, J; Fang, S S; Fava, L; Feng, C Q; Friedel, P; Fu, C D; Fu, J L; Fuks, O; Gao, Y; Geng, C; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, T; Guo, Y P; Han, Y L; Harris, F A; He, K L; He, M; He, Z Y; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Huang, G M; Huang, G S; Huang, J S; Huang, L; Huang, X T; Huang, Y; Hussain, T; Ji, C S; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L L; Jiang, X S; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Jing, F F; Kalantar-Nayestanaki, N; Kavatsyuk, M; Kopf, B; Kornicer, M; Kuehn, W; Lai, W; Lange, J S; Lara, M; Larin, P; Leyhe, M; Li, C H; Li, Cheng; Li, Cui; Li, D M; Li, F; Li, G; Li, H B; Li, J C; Li, K; Li, Lei; Li, Q J; Li, S L; Li, W D; Li, W G; Li, X L; Li, X N; Li, X Q; Li, X R; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Liao, X T; Lin, D; Liu, B J; Liu, C L; Liu, C X; Liu, F H; Liu, Fang; Liu, Feng; Liu, H; Liu, H B; Liu, H H; Liu, H M; Liu, H W; Liu, J P; Liu, K; Liu, K Y; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, Y B; Liu, Z A; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, G R; Lu, H J; Lu, J G; Lu, Q W; Lu, X R; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lv, M; Ma, C L; Ma, F C; Ma, H L; Ma, Q M; Ma, S; Ma, T; Ma, X Y; Maas, F E; Maggiora, M; Malik, Q A; Mao, Y J; Mao, Z P; Messchendorp, J G; Min, J; Min, T J; Mitchell, R E; Mo, X H; Moeini, H; Morales, C Morales; Moriya, K; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nicholson, C; Nikolaev, I B; Ning, Z; Olsen, S L; Ouyang, Q; Pacetti, S; Park, J W; Pelizaeus, M; Peng, H P; Peters, K; Ping, J L; Ping, R G; Poling, R; Prencipe, E; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, X S; Qin, Y; Qin, Z H; Qiu, J F; Rashid, K H; Rong, G; Ruan, X D; Sarantsev, A; Shao, M; Shen, C P; Shen, X Y; Sheng, H Y; Shepherd, M R; Song, W M; Song, X Y; Spataro, S; Spruck, B; Sun, D H; Sun, G X; Sun, J F; Sun, S S; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Toth, D; Ullrich, M; Uman, I; Varner, G S; Wang, B; Wang, B Q; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, Q J; Wang, S G; Wang, X F; Wang, X L; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z Y; Wei, D H; Wei, J B; Weidenkaff, P; Wen, Q G; Wen, S P; Werner, M; Wiedner, U; Wu, L H; Wu, N; Wu, S X; Wu, W; Wu, Z; Xia, L G; Xia, Y X; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, G M; Xu, Q J; Xu, Q N; Xu, X P; Xu, Z R; Xue, Z; Yan, L; Yan, W B; Yan, Y H; Yang, H X; Yang, Y; Yang, Y X; Ye, H; Ye, M; Ye, M H; Yu, B X; Yu, C X; Yu, H W; Yu, J S; Yu, S P; Yuan, C Z; Yuan, Y; Zafar, A A; Zallo, A; Zang, S L; Zeng, Y; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, LiLi; Zhang, R; Zhang, S H; Zhang, X J; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Z P; Zhang, Z Y; Zhang, Zhenghao; Zhao, G; Zhao, H S; Zhao, J W; Zhao, K X; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, S J; Zhao, T C; Zhao, X H; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, Y H; Zhong, B; Zhou, L; Zhou, X; Zhou, X K; Zhou, X R; Zhu, C; Zhu, K; Zhu, K J; Zhu, S H; Zhu, X L; Zhu, Y C; Zhu, Y M; Zhu, Y S; Zhu, Z A; Zhuang, J; Zou, B S; Zou, J H

    2013-01-01

    With a sample of 225.3 million $J/\\psi$ events taken with the BESIII detector, the decay $J/\\psi\\rightarrow \\gamma 3(\\pi^+\\pi^-)$ is analyzed. A structure at 1.84 GeV/c$^2$ is observed in the $3(\\pi^+\\pi^-)$ invariant mass spectrum with a statistical significance of 7.6$\\sigma$ . The mass and width are measured to be $M=1842.2\\pm 4.2^{+7.1}_{-2.6}$ MeV/c$^2$ and $\\Gamma=83\\pm 14 \\pm 11$ MeV. The product branching fraction is determined to be $B(J/\\psi\\rightarrow\\gamma X(1840))\\times B(X(1840)\\rightarrow 3(\\pi^+\\pi^-))=(2.44\\pm0.36^{+0.60}_{-0.74})\\times 10^{-5}$. No $\\eta^\\prime$ signals are observed in the $3(\\pi^+\\pi^-)$ invariant mass spectrum, and the upper limit of the branching fraction for the decay $\\eta^\\prime\\rightarrow 3(\\pi^+\\pi^-)$ is set to be $3.1\\times10^{-5}$ at a 90% confidence level.

  1. 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.

  2. Secret Key Generation From Mobility

    CERN Document Server

    Gungor, Onur; Koksal, C Emre

    2011-01-01

    We consider secret key generation from relative localization information of a pair of nodes in a mobile wireless network in the presence of a mobile eavesdropper. Our scheme consists of two phases: in the first phase, legitimate node pair exchanges beacon signals to establish localization information based on noisy observations of these beacons; in the second phase, nodes generate secret key bits via a public discussion. Our problem can be categorized under the source models of information theoretic secrecy, where the distance between the legitimate nodes acts as the observed common randomness. We characterize the achievable secret key bit rate in terms of the observation noise variance at the legitimate nodes and the eavesdropper. This work provides a framework that combines information theoretic secrecy and wireless localization, and proves that the localization information provides a significant additional resource for secret key generation in mobile wireless networks.

  3. An Image Secret Sharing Method

    Science.gov (United States)

    2006-07-01

    M. E. Hellman, “On secret sharing systems,” vol. IT-29, no. 1, pp. 35–41, Jan. 1983. [10] K. Kurosawa , K. Okada, K. Sakano, W. Ogata, and S. Tsujii...Ed., Berlin, Germany, 1994, pp. 1–12. [14] W. Ogata and K. Kurosawa , “Some ba- sic properties of general nonperfect secret sharing schemes,” J.UCS

  4. 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

  5. Exposure assessment of arc welders to extremely low frequency magnetic field: its relationship with the secretion of paratormone hormone and mood states

    Directory of Open Access Journals (Sweden)

    Roohalah Hajizadeh

    2016-09-01

    Full Text Available Introduction: Nowadays, exposure to extremely low frequency (ELF magnetic field has been interested in many studies due to possible effects on human physical-mental health. Therefore, this study aimed to assess arc welders’ exposure to extremely low frequency magnetic field and to determine its relationship with the secretion of paratormone (PTH hormone and mood states. Material and Method: The present study has been conducted among 35 healthy production workers (as exposed group and 35 healthy administrative personnel (as unexposed group. After checking the work activities of participants according to the guide recommended by the National Institute for Occupational Safety and Health (NIOSH, ELF magnetic fields were measured using an ELF measurement device in the regions including trunk, head, and neck. The plasma levels of PTH hormone of both groups were evaluated by the Electrochemiluminescence method. Stress-Arousal Checklist (SACL was used to assess the mode states of subjects in both groups. The collected data were analyzed by SPSS software version 16. Result: There was a significant difference between the exposed and unexposed groups with respect to the exposure level to ELF magnetic fields (P-value<0.0001. Mean PTH hormone level in exposed group (34.54 pg/ml was lower than unexposed ones (37 pg/ml, however these mean values weren’t significantly different (P-value=0.67. Score of “stress” subscale related to the “pleasure” and score of “arousal” subscale  related to the “activities and alertness” in the unexposed group were significantly higher than those in exposed group (p<0.0001. Regarding the relationship between exposure level to ELF electromagnetic field and scores of  stress, arousal, and PTH hormone level in the two groups, it should be stated that only a significant and positive association was found between the average exposure to ELF magnetic fields and PTH levels in the exposed group (P-value<0.009, r=0

  6. Secret sharing using biometric traits

    Science.gov (United States)

    Kholmatov, Alisher; Yanikoglu, Berrin; Savas, Erkay; Levi, Albert

    2006-04-01

    In biometric based authentication, biometric traits of a person are matched against his/her stored biometric profile and access is granted if there is sufficient match. However, there are other access scenarios, which require participation of multiple previously registered users for a successful authentication or to get an access grant for a certain entity. For instance, there are cryptographic constructs generally known as secret sharing schemes, where a secret is split into shares and distributed amongst participants in such a way that it is reconstructed/revealed only when the necessary number of share holders come together. The revealed secret can then be used for encryption or authentication (if the revealed key is verified against the previously registered value). In this work we propose a method for the biometric based secret sharing. Instead of splitting a secret amongst participants, as is done in cryptography, a single biometric construct is created using the biometric traits of the participants. During authentication, a valid cryptographic key is released out of the construct when the required number of genuine participants present their biometric traits.

  7. Thyroid hormones and renin secretion.

    Science.gov (United States)

    Ganong, W F

    Circulating angiotensin is produced by the action of renin from the kidneys on circulating angiotensinogen. There are other renin-angiotensin systems in various organs in the body, and recent observations raise the intriguing possibility that angiotensin II is produced by a totally intracellular pathway in the juxtaglomerular cells, the gonadotrops of the anterior pituitary, neurons, in the brain, salivary duct cells, and neuroblastoma cells. Circulating angiotensin II levels depend in large part on the plasma concentration of angiotensinogen, which is hormonally regulated, and on the rate of renin secretion. Renin secretion is regulated by an intrarenal baroreceptor mechanism, a macula densa mechanism, angiotensin II, vasopressin, and the sympathetic nervous system. The increase in renin secretion produced by sympathetic discharge is mediated for the most part by beta-adrenergic receptors, which are probably located on the juxtaglomerular cells. Hyperthyroidism would be expected to be associated with increased renin secretion in view of the increased beta-adrenergic activity in this condition, and hypothyroidism would be associated with decreased plasma renin activity due to decreased beta-adrenergic activity. Our recent research on serotonin-mediated increases in renin secretion that depend on the integrity of the dorsal raphe nucleus and the mediobasal hypothalamus has led us to investigate the effect of the pituitary on the renin response to p-chloroamphetamine. The response is potentiated immediately after hypophysectomy, but 22 days after the operation, it is abolished. This slowly developing decrease in responsiveness may be due to decreased thyroid function.

  8. On family secrets and -K.

    Science.gov (United States)

    Orgad, Yariv

    2014-08-01

    In this paper I present a novel interpretation of family secrets. Leaning on Bion's concept of -K, the constitution of secrecy is interpreted in terms of family dynamics that actively prevent knowledge formation and mental growth. Family secrets are interpreted as a destructive process that attacks the family's truth-generating-space - the shared semiotic space within which meanings are constituted through family relationships. The paper explores the microstructure interpersonal process of -K through the analysis of Mike Leigh's movie, Secrets and Lies. Two scenes in the movie are used to demonstrate how -K is worked out in the form of a specific intersubjective semiotic endeavor that unconsciously blocks the process of meaning-making.

  9. Of Plants, and Other Secrets

    Directory of Open Access Journals (Sweden)

    Michael Marder

    2012-12-01

    Full Text Available In this article, I inquire into the reasons for the all-too-frequent association of plants and secrets. Among various hypotheses explaining this connection from the standpoint of plant morphology and physiology, the one that stands out is the idea that plants are not only objects in the natural environment, but also subjects with a peculiar mode of accessing the world. The core of the “plant enigma” is, therefore, onto-phenomenological. Positively understood, the secret of their subjectivity leaves just enough space for the self-expression and the self-interpretation of vegetal life.

  10. 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.

  11. 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

  12. Raspberry Pi for secret agents

    CERN Document Server

    Sjogelid, Stefan

    2015-01-01

    This book is an easy-to-follow guide with practical examples in each chapter. Suitable for the novice and expert alike, each topic provides a fast and easy way to get started with exciting applications and also guides you through setting up the Raspberry Pi as a secret agent toolbox.

  13. Histaminergic regulation of prolactin secretion

    DEFF Research Database (Denmark)

    Knigge, U P

    1990-01-01

    of DA synthesis and of DA or serotonin (5-HT) receptors inhibit or prevent the PRL stimulatory action of HA infused centrally or systemically. However, other factors regulating PRL secretion (e.g. beta-endorphin, vasoactive intestinal peptide, vasopressin or TRH) may be involved in the mediation...

  14. Wnt Secretion and Gradient Formation

    Directory of Open Access Journals (Sweden)

    Vladimir L. Katanaev

    2013-03-01

    Full Text Available Concentration gradients formed by the lipid-modified morphogens of the Wnt family are known for their pivotal roles during embryogenesis and adult tissue homeostasis. Wnt morphogens are also implicated in a variety of human diseases, especially cancer. Therefore, the signaling cascades triggered by Wnts have received considerable attention during recent decades. However, how Wnts are secreted and how concentration gradients are formed remains poorly understood. The use of model organisms such as Drosophila melanogaster has provided important advances in this area. For instance, we have previously shown that the lipid raft-associated reggie/flotillin proteins influence Wnt secretion and spreading in Drosophila. Our work supports the notion that producing cells secrete Wnt molecules in at least two pools: a poorly diffusible one and a reggie/flotillin-dependent highly diffusible pool which allows morphogen spreading over long distances away from its source of production. Here we revise the current views of Wnt secretion and spreading, and propose two models for the role of the reggie/flotillin proteins in these processes: (i reggies/flotillins regulate the basolateral endocytosis of the poorly diffusible, membrane-bound Wnt pool, which is then sorted and secreted to apical compartments for long-range diffusion, and (ii lipid rafts organized by reggies/flotillins serve as “dating points” where extracellular Wnt transiently interacts with lipoprotein receptors to allow its capture and further spreading via lipoprotein particles. We further discuss these processes in the context of human breast cancer. A better understanding of these phenomena may be relevant for identification of novel drug targets and therapeutic strategies.

  15. Incretin hormone secretion over the day

    DEFF Research Database (Denmark)

    Ahren, B; Carr, RD; Deacon, Carolyn F.

    2010-01-01

    . Regulation of incretin hormone secretion is less well characterized. The main stimulus for incretin hormone secretion is presence of nutrients in the intestinal lumen, and carbohydrate, fat as well as protein all have the capacity to stimulate GIP and GLP-1 secretion. More recently, it has been established...

  16. Pancreatic bicarbonate secretion involves two proton pumps

    DEFF Research Database (Denmark)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium expres...

  17. Keeping Secrets : Quantity, Quality and Consequences

    NARCIS (Netherlands)

    Frijns, T.

    2005-01-01

    Keeping Secrets deals with the consequences of an elusive yet everyday phenomenon. It addresses both the quantity and quality of secret-keeping. With respect to quantity, it presents research on the intra- and interpersonal consequences of keeping secrets from parents in adolescence. With respect t

  18. Electronic enhancement of tear secretion

    Science.gov (United States)

    Brinton, Mark; Lim Chung, Jae; Kossler, Andrea; Kook, Koung Hoon; Loudin, Jim; Franke, Manfred; Palanker, Daniel

    2016-02-01

    Objective. To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion. Approach. We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz). Main results. Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm-2 with 170-680 μs pulses) than the damage threshold (3.5 μC mm-2 with 1 ms pulses). Significance. Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and

  19. A dopamine-secreting pheochromocytoma.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Minami, M; Kano, H; Ohhira, M; Nakamura, K; Yoshikawa, J

    2000-01-01

    We describe a patient with pheochromocytoma, which secretes dopamine. He was admitted to hospital because of chronic diarrhea. After surgical resection of the tumor, dramatic cessation of the diarrhea and blood pressure elevation were observed. Decreased expression of dopamine beta-hydroxylase in the tumor was considered a possible mechanism of producing a pathophysiological concentration of dopamine. This case shows that excessive excretion of dopamine, a vasodilative hormone, may affect blood pressure.

  20. Multiscale modelling of saliva secretion.

    Science.gov (United States)

    Sneyd, James; Crampin, Edmund; Yule, David

    2014-11-01

    We review a multiscale model of saliva secretion, describing in brief how the model is constructed and what we have so far learned from it. The model begins at the level of inositol trisphosphate receptors (IPR), and proceeds through the cellular level (with a model of acinar cell calcium dynamics) to the multicellular level (with a model of the acinus), finally to a model of a saliva production unit that includes an acinus and associated duct. The model at the level of the entire salivary gland is not yet completed. Particular results from the model so far include (i) the importance of modal behaviour of IPR, (ii) the relative unimportance of Ca(2+) oscillation frequency as a controller of saliva secretion, (iii) the need for the periodic Ca(2+) waves to be as fast as possible in order to maximise water transport, (iv) the presence of functional K(+) channels in the apical membrane increases saliva secretion, (v) the relative unimportance of acinar spatial structure for isotonic water transport, (vi) the prediction that duct cells are highly depolarised, (vii) the prediction that the secondary saliva takes at least 1mm (from the acinus) to reach ionic equilibrium. We end with a brief discussion of future directions for the model, both in construction and in the study of scientific questions.

  1. Transporter-mediated biofuel secretion.

    Science.gov (United States)

    Doshi, Rupak; Nguyen, Tuan; Chang, Geoffrey

    2013-05-07

    Engineering microorganisms to produce biofuels is currently among the most promising strategies in renewable energy. However, harvesting these organisms for extracting biofuels is energy- and cost-intensive, limiting the commercial feasibility of large-scale production. Here, we demonstrate the use of a class of transport proteins of pharmacological interest to circumvent the need to harvest biomass during biofuel production. We show that membrane-embedded transporters, better known to efflux lipids and drugs, can be used to mediate the secretion of intracellularly synthesized model isoprenoid biofuel compounds to the extracellular milieu. Transporter-mediated biofuel secretion sustainably maintained an approximate three- to fivefold boost in biofuel production in our Escherichia coli test system. Because the transporters used in this study belong to the ubiquitous ATP-binding cassette protein family, we propose their use as "plug-and-play" biofuel-secreting systems in a variety of bacteria, cyanobacteria, diatoms, yeast, and algae used for biofuel production. This investigation showcases the potential of expressing desired membrane transport proteins in cell factories to achieve the export or import of substances of economic, environmental, or therapeutic importance.

  2. Unconventional Pathways of Secretion Contribute to Inflammation

    Science.gov (United States)

    Daniels, Michael J. D.; Brough, David

    2017-01-01

    In the conventional pathway of protein secretion, leader sequence-containing proteins leave the cell following processing through the endoplasmic reticulum (ER) and Golgi body. However, leaderless proteins also enter the extracellular space through mechanisms collectively known as unconventional secretion. Unconventionally secreted proteins often have vital roles in cell and organism function such as inflammation. Amongst the best-studied inflammatory unconventionally secreted proteins are interleukin (IL)-1β, IL-1α, IL-33 and high-mobility group box 1 (HMGB1). In this review we discuss the current understanding of the unconventional secretion of these proteins and highlight future areas of research such as the role of nuclear localisation. PMID:28067797

  3. Cheater identifiable visual secret sharing scheme

    Institute of Scientific and Technical Information of China (English)

    Gan Zhi; Chen Kefei

    2005-01-01

    The visual secret sharing scheme proposed by Naor and Shamir provides a way to encrypt a secret black-white image into shares. A qualified group of participants can recover the secret message without using any cryptographic computation. But the original scheme can easily be corrupted by malicious participant. We propose an extension of VSS(visual secret sharing) to identify cheaters before the secret is recovered. Without the need for any additional information and cryptographic computation, every participant can verify the validity of shares of other participants, thus the security of VSS is enhanced.

  4. Secret sharing scheme with inherited characteristic

    Institute of Scientific and Technical Information of China (English)

    Ye Zhenjun; Meng Fanzhen

    2006-01-01

    To assure the shareholders can look for their "legal" attorneys to renew the secret, once the secret sharing scheme is initialized, a secret sharing scheme with inherited characteristic is constructed. In this scheme, each shareholder can produce a new share by his algorithm, which is equivalent to the primary one. Together with other shares, the primary secret can be renewed. Since this scheme is constructed not by replacing the primary share with a new share produced by the dealer in his primitive secret sharing scheme, so no matter how much shares the shareholder produces, these shares can not be gathered together to renew the secret in this scheme. Compared with the existing secret sharing schemes, this scheme provides more agility for the shareholders by investing each of them a function but not affect its security.

  5. LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Matson Jyl S

    2008-02-01

    Full Text Available Abstract Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

  6. Weegee’s City Secrets

    Directory of Open Access Journals (Sweden)

    Alan TRACHTENBERG

    2010-03-01

    Full Text Available En tant que photographe indépendant de meurtres, d’accidents, d’incendies, mais aussi de moments de loisirs dans la ville — de scènes de violence et de plaisir — Weegee travaillait essentiellement la nuit et utilisait un flash puissant associé à son appareil-photo de presse. Ses « secrets pour réaliser des photographies avec un flash » consistent à donner des conseils pratiques et techniques pour débutants. Mais au cœur de la rhétorique de ses « secrets » se trouvent des réflexions subtiles et convaincantes révélant la relation entre la lumière et l’obscurité, et plus particulièrement la manière dont la lumière du flash permet de rendre visible l’obscurité. Dans le récit de Weegee, le flash confère à la photographie le pouvoir d’écrire — d’écrire avec la lumière, un mode de représentation singulièrement approprié pour enregistrer des instants de vie dans les rues nocturnes de la ville.As a freelance photographer of crime, accidents, fires, and also of the recreational life of the city—scenes of violence and of pleasure—Weegee worked mainly at night and employed a powerful photoflash attachment to his press camera. His "secrets of shooting with photoflash" consist of practical technical advice for beginners. But within the rhetoric of his "secrets" there lie cogent and subtle reflections on the relation of light to darkness, especially on the way the flash of light makes darkness visible. In Weegee’s account, the photoflash gives photography the power of writing—writing with light, a mode of picturing uniquely suited to recording instants of life on city streets at night.

  7. 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.

  8. The evidence for secretion clearance techniques.

    Science.gov (United States)

    Hess, D R

    2001-11-01

    Many acute and chronic respiratory diseases are associated with increased respiratory secretions in the airways. Narrative reviews and a few systematic reviews of secretion clearance techniques have been published. These reviews raise concerns regarding the lack of evidence to support the various secretion clearance techniques. I conducted a comprehensive MEDLINE search of the following subjects: chest physical therapy, chest physiotherapy, postural drainage, forced expiratory technique, autogenic drainage, high-frequency chest wall compression, flutter device and secretions, positive expiratory pressure and secretions, intrapulmonary percussion, mechanical in-exsufflation and secretions. This was followed by a comprehensive search of cross-references to identify additional studies. The results of this review are reported herein. There are a number of methodological limitations of the literature reporting studies of the use of secretion clearance techniques. Most of the studies were small, most used crossover designs, and few used sham therapy. Many studies were limited to short-term outcomes such as sputum clearance with a single treatment session. Despite the clinical observation that retained secretions are detrimental to respiratory function and despite anecdotal associations between secretion clearance and improvements in respiratory function, there is a dearth of high-level evidence to support any secretion clearance technique.

  9. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems.

    Directory of Open Access Journals (Sweden)

    Ram Samudrala

    2009-04-01

    Full Text Available The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates--effector proteins--are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating protein sequence-based features, including evolutionary measures such as the pattern of homologs in a range of other organisms, G+C content, amino acid composition, and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from the plant pathogen Pseudomonas syringae and validated on a set of effectors from the animal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium after eliminating effectors with detectable sequence similarity. We show that this approach can predict known secreted effectors with high specificity and sensitivity. Furthermore, by considering a large set of effectors from multiple organisms, we computationally identify a common putative secretion signal in the N-terminal 20 residues of secreted effectors. This signal can be used to discriminate 46 out of 68 total known effectors from both organisms, suggesting that it is a real, shared signal applicable to many type III secreted effectors. We use the method to make novel predictions of secreted effectors in S. Typhimurium, some of which have been experimentally validated. We also apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis, identifying the majority of known secreted proteins in addition to providing a number of novel predictions. This approach provides a new way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  10. Metabolic regulation of insulin secretion.

    Science.gov (United States)

    Keane, Kevin; Newsholme, Philip

    2014-01-01

    Regulation of metabolic fuel homeostasis is a critical function of β-cells, which are located in the islets of Langerhans of the animal pancreas. Impairment of this β-cell function is a hallmark of pancreatic β-cell failure and may lead to development of type 2 diabetes mellitus. β-Cells are essentially "fuel sensors" that monitor and react to elevated nutrient load by releasing insulin. This response involves metabolic activation and generation of metabolic coupling factors (MCFs) that relay the nutrient signal throughout the cell and induce insulin biosynthesis and secretion. Glucose is the most important insulin secretagogue as it is the primary fuel source in food. Glucose metabolism is central to generation of MCFs that lead to insulin release, most notably ATP. In addition, other classes of nutrients are able to augment insulin secretion and these include members of the lipid and amino acid family of nutrients. Therefore, it is important to investigate the interplay between glucose, lipid, and amino acid metabolism, as it is this mixed nutrient sensing that generate the MCFs required for insulin exocytosis. The mechanisms by which these nutrients are metabolized to generate MCFs, and how they impact on β-cell insulin release and function, are discussed in detail in this article.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Quantum secret sharing with minimized quantum communication

    Science.gov (United States)

    Fortescue, Ben; Gour, Gilad

    2013-03-01

    Standard techniques for sharing a quantum secret among multiple players (such that certain subsets of the players can recover the secret while others are denied all knowledge of the secret) require a large amount of quantum communication to distribute the secret, which is likely to be the most costly resource in any practical scheme. Two known methods for reducing this cost are the use of imperfect ``ramp'' secret sharing (in which security is sacrificed for efficiency) and classical encryption (in which certain elements of the players' shares consist of classical information only). We demonstrate how one may combine these methods to reduce the required quantum communication below what has been previously achieved, in some cases to a provable minimum, without any loss of security. The techniques involved are closely-related to the properties of stabilizer codes, and thus have strong potential for being adapted to a wide range of quantum secret sharing schemes.

  16. Secretion by numbers: protein traffic in prokaryotes

    Science.gov (United States)

    Economou, Anastasias; Christie, Peter J.; Fernandez, Rachel C.; Palmer, Tracy; Plano, Greg V.; Pugsley, Anthony P.

    2013-01-01

    Summary Almost all aspects of protein traffic in bacteria were covered at the ASM-FEMS meeting on the topic in Iraklio, Crete in May 2006. The studies presented ranged from mechanistic analysis of specific events leading proteins to their final destinations to the physiological roles of the targeted proteins. Among the highlights from the meeting that are reviewed here are the molecular dynamics of SecA protein, membrane protein insertion, type III secretion needles and chaperones, type IV secretion, the two partner and autosecretion systems, the ‘secretion competent state’, and the recently discovered type VI secretion system. PMID:17020575

  17. Random Secretion of Growth Hormone in Humans

    Science.gov (United States)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

    1996-08-01

    In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

  18. Noninvasive clearance of airway secretions.

    Science.gov (United States)

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  19. Metabolic control of renin secretion.

    Science.gov (United States)

    Peti-Peterdi, János; Gevorgyan, Haykanush; Lam, Lisa; Riquier-Brison, Anne

    2013-01-01

    One emerging topic in renin-angiotensin system (RAS) research is the direct local control of renin synthesis and release by endogenous metabolic intermediates. During the past few years, our laboratory has characterized the localization and signaling of the novel metabolic receptor GPR91 in the normal and diabetic kidney and established GPR91 as a new, direct link between high glucose and RAS activation in diabetes. GPR91 (also called SUCNR1) binds tricarboxylic acid (TCA) cycle intermediate succinate which can rapidly accumulate in the local tissue environment when energy supply and demand are out of balance. In a variety of physiological and pathological conditions associated with metabolic stress, succinate signaling via GPR91 appears to be an important mediator or modulator of renin secretion. This review summarizes our current knowledge on the control of renin release by molecules of endogenous metabolic pathways with the main focus on succinate/GPR91.

  20. [Functional morphology of stomach secretions].

    Science.gov (United States)

    Liebich, H G

    1985-01-01

    The stimulation of gastric secretion is regulated by neurovagal, endocrine and immunological reactions. During the gastric phase of digestion, especially acetylcholin, gastrin and histamin react as main transmitters, activated by mediators (prostaglandines, leucotrienes, lipoxygenases). The dominant role of nervus vagus has to be seen in the transactions of vago-vagal reflexes, the stimulation of gastrin liberation by an non-cholinergic mechanism and the regulation of the gastric microcirculation. The antrum pylori can be seen as an immunological area of reception, where immunological active cells (macrophages, NK-lymphocytes and T-lymphocytes) are recognizing antigens (e.g. food antigens). These immunocytes induce a cascade of endocrine and exocrine mechanisms of digestion. Mastcells, located intra-and extraepithelial, take a regulatory influence in producing histamins, leucotrienes and also prostaglandines.

  1. [Mucoprotein secretion in calculous gallbladder].

    Science.gov (United States)

    Fernández Lobato, R; Ortega, L; Balibrea, J L; Torres, A J; García-Calvo, M; Alvarez Sánchez, J A

    1994-05-01

    Secretion of mucoproteins or mucine (MP) have been studied as possible markers in several pathological conditions of the digestive tract, such us colonic polyposis or gastric dysplasia. In the gallbladder (VB) it has been established that form the core of crystalization for the calculi. A study in 100 gallbladders have been made based on the utility of the analysis of the qualitative and quantitative modifications of MP in lithogenesis. It was been determined by histochemical techniques the three main types of MP (neutral, low and high sulphated acid) to evaluate the alterations in the process of lithiasis. Results show a high production of the MP in VB with lithiasis, presenting in 97% a mixed composition of MP (48.9% of 2 types, and 3 types in 46%), without a predominating type in this pathology.

  2. Elastase secretion in Acanthamoeba polyphaga.

    Science.gov (United States)

    Ferreira, Gabriela A; Magliano, Ana C M; Pral, Elizabeth M F; Alfieri, Silvia C

    2009-11-01

    Acanthamoeba species are frequently isolated from soil and water collections. In the environment, the organisms multiply as phagotrophic trophozoites and encyst under adverse conditions. Several species are known to infect man, causing keratitis and opportunistic diseases. The mechanisms underlying tissue damage and invasion by the amoebae are being elucidated and the involvement of secreted peptidases, particularly serine peptidases, has been demonstrated. Here, elastase activity was examined in Acanthamoeba-conditioned medium (ACM), making use of elastin-Congo red (ECR) and synthetic peptide p-nitroanilide substrates. ACM hydrolysed ECR over a broad pH range and optimally at a pH of 7.5 and above. Indicating the activity of serine and metallopeptidases, Congo red release was potently inhibited by PMSF, antipain, chymostatin and 1,10-phenanthroline, partially reduced by elastatinal and EDTA, and unaffected by 1,7-phenanthroline and E-64. Screening with synthetic substrates mainly showed the activity of serine peptidases. ACM efficiently hydrolysed Suc-Ala(2)-Pro-Leu-pNA and Suc-Ala(2)-Pro-Phe-pNA over a broad pH range (7.0-9.5) and was weakly active against Suc-Ala(3)-pNA, a substrate found to be optimally hydrolysed at a pH around 7.0. Following ammonium sulfate precipitation of ACM proteins and FPLC analysis, the majority of the ECR-splitting activity, characterised as serine peptidases, bound to CM-sepharose and co-eluted with part of the Suc-Ala(2)-Pro-Phe-pNA-hydrolysing activity in a gradient of 0-0.6M NaCl. In the corresponding FPLC fractions, serine peptidases resolving in the region of 70-130kDa were detected in gelatin gels. Overall, the results demonstrate that trophozoites secrete elastases, and additionally suggest the high molecular weight serine peptidases as possible elastase candidates.

  3. DYNAMIC AND VERIFIABLE SECRET SHARING AMONG WEIGHTED PARTICIPANTS

    Institute of Scientific and Technical Information of China (English)

    Yanshuo ZHANG; Zhuojun LIU

    2007-01-01

    A secret sharing scheme permits a secret to be shared among participants in such a way that only qualified subsets of participants can recover the secret. Secret sharing is useful in management of cryptographic keys. Based on identity, we analyze the secret sharing scheme among weighted participants. Then we present a dynamic scheme about secret sharing among weighted participants. At last, we analyze the secret sharing scheme among weighted participants, which can make all weighted participants verifiable and dynamic.

  4. On Secret Sharing with Nonlinear Product Reconstruction

    DEFF Research Database (Denmark)

    Cascudo Pueyo, Ignacio; Cramer, Ronald; Mirandola, Diego

    2015-01-01

    Multiplicative linear secret sharing is a fundamental notion in the area of secure multiparty computation and, since recently, in the area of two-party cryptography as well. In a nutshell, this notion guarantees that the product of two secrets is obtained as a linear function of the vector consis...

  5. Secret-involved Information System Security Audit

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Ya-lan

    2015-01-01

    Secret-involved information system security audit is a network security technology developing rapidly in recent years.It uses various technical to detect the problem of secret-involved information system,and uses certain audit methods to analyze all kinds of suspicious behavior and irregularities.

  6. "The Secret Garden": A Literary Journey.

    Science.gov (United States)

    Jordan, Anne Devereaux

    1998-01-01

    Outlines the life of Frances Hodgson Burnett, author of "The Secret Garden." Argues that it not only tells an enthralling tale, but takes readers on a journey through the history of English literature. Discusses the gothic tradition and romanticism of "The Secret Garden." Lists classic elements in the book and offers five ideas…

  7. On Secret Sharing with Nonlinear Product Reconstruction

    DEFF Research Database (Denmark)

    Cascudo Pueyo, Ignacio; Cramer, Ronald; Mirandola, Diego

    2015-01-01

    Multiplicative linear secret sharing is a fundamental notion in the area of secure multiparty computation and, since recently, in the area of two-party cryptography as well. In a nutshell, this notion guarantees that the product of two secrets is obtained as a linear function of the vector consis...

  8. Family Secrets: The Bioethics of Genetic Testing

    Science.gov (United States)

    Markowitz, Dina G.; DuPre, Michael J.; Holt, Susan; Chen, Shaw-Ree; Wischnowski, Michael

    2006-01-01

    This article discusses "Family Secrets," a problem-based learning (PBL) curriculum module that focuses on the bioethical implications of genetic testing. In high school biology classrooms throughout New York State, students are using "Family Secrets" to learn about DNA testing; Huntington's disease (HD); and the ethical, legal,…

  9. Toxins and Secretion Systems of Photorhabdus luminescens

    Directory of Open Access Journals (Sweden)

    Athina Rodou

    2010-06-01

    Full Text Available Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae.Recent studies show the importance of this bacterium as an alternative source of insecticides, as well as an emerging human pathogen. Various toxins have been identified and characterized in this bacterium. These toxins are classified into four major groups: the toxin complexes (Tcs, the Photorhabdus insect related (Pir proteins, the “makes caterpillars floppy” (Mcf toxins and the Photorhabdus virulence cassettes (PVC; the mechanisms however of toxin secretion are not fully elucidated. Using bioinformatics analysis and comparison against the components of known secretion systems, multiple copies of components of all known secretion systems, except the ones composing a type IV secretion system, were identified throughout the entire genome of the bacterium. This indicates that Photorhabdus luminescens has all the necessary means for the secretion of virulence factors, thus it is capable of establishing a microbial infection.

  10. Toxins and secretion systems of Photorhabdus luminescens.

    Science.gov (United States)

    Rodou, Athina; Ankrah, Dennis O; Stathopoulos, Christos

    2010-06-01

    Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae. Recent studies show the importance of this bacterium as an alternative source of insecticides, as well as an emerging human pathogen. Various toxins have been identified and characterized in this bacterium. These toxins are classified into four major groups: the toxin complexes (Tcs), the Photorhabdus insect related (Pir) proteins, the "makes caterpillars floppy" (Mcf) toxins and the Photorhabdus virulence cassettes (PVC); the mechanisms however of toxin secretion are not fully elucidated. Using bioinformatics analysis and comparison against the components of known secretion systems, multiple copies of components of all known secretion systems, except the ones composing a type IV secretion system, were identified throughout the entire genome of the bacterium. This indicates that Photorhabdus luminescens has all the necessary means for the secretion of virulence factors, thus it is capable of establishing a microbial infection.

  11. Regulation of glucagon secretion by incretins

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Christensen, M; Lund, A;

    2011-01-01

    Glucagon secretion plays an essential role in the regulation of hepatic glucose production, and elevated fasting and postprandial plasma glucagon concentrations in patients with type 2 diabetes (T2DM) contribute to their hyperglycaemia. The reason for the hyperglucagonaemia is unclear, but recent...... that endogenous GLP-1 plays an important role in regulation of glucagon secretion during fasting as well as postprandially. The mechanisms whereby GLP-1 regulates glucagon secretion are debated, but studies in isolated perfused rat pancreas point to an important role for a paracrine regulation by somatostatin...... studies have shown lack of suppression after oral but preserved suppression after isoglycaemic intravenous glucose, pointing to factors from the gut. Gastrointestinal hormones that are secreted in response to oral glucose include glucagon-like peptide-1 (GLP-1) that strongly inhibits glucagon secretion...

  12. Non-classical protein secretion in bacteria

    Directory of Open Access Journals (Sweden)

    Fausbøll Anders

    2005-10-01

    Full Text Available Abstract Background We present an overview of bacterial non-classical secretion and a prediction method for identification of proteins following signal peptide independent secretion pathways. We have compiled a list of proteins found extracellularly despite the absence of a signal peptide. Some of these proteins also have known roles in the cytoplasm, which means they could be so-called "moon-lightning" proteins having more than one function. Results A thorough literature search was conducted to compile a list of currently known bacterial non-classically secreted proteins. Pattern finding methods were applied to the sequences in order to identify putative signal sequences or motifs responsible for their secretion. We have found no signal or motif characteristic to any majority of the proteins in the compiled list of non-classically secreted proteins, and conclude that these proteins, indeed, seem to be secreted in a novel fashion. However, we also show that the apparently non-classically secreted proteins are still distinguished from cellular proteins by properties such as amino acid composition, secondary structure and disordered regions. Specifically, prediction of disorder reveals that bacterial secretory proteins are more structurally disordered than their cytoplasmic counterparts. Finally, artificial neural networks were used to construct protein feature based methods for identification of non-classically secreted proteins in both Gram-positive and Gram-negative bacteria. Conclusion We present a publicly available prediction method capable of discriminating between this group of proteins and other proteins, thus allowing for the identification of novel non-classically secreted proteins. We suggest candidates for non-classically secreted proteins in Escherichia coli and Bacillus subtilis. The prediction method is available online.

  13. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems

    Energy Technology Data Exchange (ETDEWEB)

    Samudrala, Ram; Heffron, Fred; McDermott, Jason E.

    2009-04-24

    The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, after eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  14. 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.

  15. Identification of protein secretion systems and novel secreted proteins in Rhizobium leguminosarum bv. viciae

    Directory of Open Access Journals (Sweden)

    Krehenbrink Martin

    2008-01-01

    Full Text Available Abstract Background Proteins secreted by bacteria play an important role in infection of eukaryotic hosts. Rhizobia infect the roots of leguminous plants and establish a mutually beneficial symbiosis. Proteins secreted during the infection process by some rhizobial strains can influence infection and modify the plant defence signalling pathways. The aim of this study was to systematically analyse protein secretion in the recently sequenced strain Rhizobium leguminosarum bv. viciae 3841. Results Similarity searches using defined protein secretion systems from other Gram-negative bacteria as query sequences revealed that R. l. bv. viciae 3841 has ten putative protein secretion systems. These are the general export pathway (GEP, a twin-arginine translocase (TAT secretion system, four separate Type I systems, one putative Type IV system and three Type V autotransporters. Mutations in genes encoding each of these (except the GEP were generated, but only mutations affecting the PrsDE (Type I and TAT systems were observed to affect the growth phenotype and the profile of proteins in the culture supernatant. Bioinformatic analysis and mass fingerprinting of tryptic fragments of culture supernatant proteins identified 14 putative Type I substrates, 12 of which are secreted via the PrsDE, secretion system. The TAT mutant was defective for the symbiosis, forming nodules incapable of nitrogen fixation. Conclusion None of the R. l. bv. viciae 3841 protein secretion systems putatively involved in the secretion of proteins to the extracellular space (Type I, Type IV, Type V is required for establishing the symbiosis with legumes. The PrsDE (Type I system was shown to be the major route of protein secretion in non-symbiotic cells and to secrete proteins of widely varied size and predicted function. This is in contrast to many Type I systems from other bacteria, which typically secrete specific substrates encoded by genes often localised in close proximity to

  16. Lycaenid Caterpillar Secretions Manipulate Attendant Ant Behavior.

    Science.gov (United States)

    Hojo, Masaru K; Pierce, Naomi E; Tsuji, Kazuki

    2015-08-31

    Mutualistic interactions typically involve the exchange of different commodities between species. Nutritious secretions are produced by a number of insects and plants in exchange for services such as defense. These rewards are valuable metabolically and can be used to reinforce the behavior of symbiotic partners that can learn and remember them effectively. We show here novel effects of insect exocrine secretions produced by caterpillars in modulating the behavior of attendant ants in the food-for-defense interaction between lycaenid butterflies and ants. Reward secretions from the dorsal nectary organ (DNO) of Narathura japonica caterpillars function to reduce the locomotory activities of their attendant ants, Pristomyrmex punctatus workers. Moreover, workers that feed from caterpillar secretions are significantly more likely to show aggressive responses to eversion of the tentacle organs of the caterpillars. Analysis of the neurogenic amines in the brains of workers that consumed caterpillar secretions showed a significant decrease in levels of dopamine compared with controls. Experimental treatments in which reserpine, a known inhibitor of dopamine in Drosophila, was fed to workers similarly reduced their locomotory activity. We conclude that DNO secretions of lycaenid caterpillars can manipulate attendant ant behavior by altering dopaminergic regulation and increasing partner fidelity. Unless manipulated ants also receive a net nutritional benefit from DNO secretions, this suggests that similar reward-for-defense interactions that have been traditionally considered to be mutualisms may in fact be parasitic in nature. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

    Directory of Open Access Journals (Sweden)

    Dusik eKim

    2014-06-01

    Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

  18. Digestive Secretion of Dionaea muscipula (Venus's Flytrap).

    Science.gov (United States)

    Scala, J; Iott, K; Schwab, D W; Semersky, F E

    1969-03-01

    The digestive fluid of Dionaea muscipula has been studied with respect to its protein content as a function of time after entrapment of protein material and some enzymes of the secretion. Maximum secretion of enzyme occurs within the first 3 days of the digestive cycle and protein reaches its maximum at 4 days. Phosphatase, proteinase, nuclease and amylase have been observed in the secretion. The enzymes have acid pH optima and the proteinase has a molecular weight of about 40,000.

  19. Digestive Secretion of Dionaea muscipula (Venus's Flytrap)

    Science.gov (United States)

    Scala, J.; Iott, K.; Schwab, D. W.; Semersky, F. E.

    1969-01-01

    The digestive fluid of Dionaea muscipula has been studied with respect to its protein content as a function of time after entrapment of protein material and some enzymes of the secretion. Maximum secretion of enzyme occurs within the first 3 days of the digestive cycle and protein reaches its maximum at 4 days. Phosphatase, proteinase, nuclease and amylase have been observed in the secretion. The enzymes have acid pH optima and the proteinase has a molecular weight of about 40,000. PMID:16657071

  20. Secreted HSP Vaccine for Malaria Prophylaxis

    Science.gov (United States)

    2016-10-26

    AWARD NUMBER: W81XWH-13-2-0098 TITLE: Secreted HSP Vaccine for Malaria Prophylaxis PRINCIPAL INVESTIGATOR: Dr. Natasa Strbo CONTRACTING ORGANIZATION...Secreted HSP Vaccine for Malaria Prophylaxis 4. TITLE AND SUBTITLE NATASA STRBO, M.D., D.SC NAME(S) AND E-M tzA UNIVERS]TY OF MTAMI 1600 NW 1OTH AVENUE ROOM...Here we developed malaria vaccine that relies on secreted gp96-lg chaperon-ing Plasmodium falciparum antigenic sporozoite proteins CSP and AMA1. The

  1. Hash function based secret sharing scheme designs

    CERN Document Server

    Chum, Chi Sing

    2011-01-01

    Secret sharing schemes create an effective method to safeguard a secret by dividing it among several participants. By using hash functions and the herding hashes technique, we first set up a (t+1, n) threshold scheme which is perfect and ideal, and then extend it to schemes for any general access structure. The schemes can be further set up as proactive or verifiable if necessary. The setup and recovery of the secret is efficient due to the fast calculation of the hash function. The proposed scheme is flexible because of the use of existing hash functions.

  2. 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.

  3. 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.

  4. Mild hyperparathyroidism: a novel surgically correctable feature of primary aldosteronism.

    Science.gov (United States)

    Maniero, Carmela; Fassina, Ambrogio; Seccia, Teresa M; Toniato, Antonio; Iacobone, Maurizio; Plebani, Mario; De Caro, Raffaele; Calò, Lorenzo A; Pessina, Achille C; Rossi, Gian P

    2012-02-01

    The parathyroid hormone (PTH) stimulates aldosterone secretion and cell proliferation in human adrenocortical cells; moreover, in rats hyperaldosteronism was associated with hyperparathyroidism. Hence, PTH could drive aldosterone excess in human primary aldosteronism. To test this hypothesis, we recruited 105 consecutive hypertensive patients, of whom 44 had primary aldosteronism due to an aldosterone-producing adenoma (APA) and 61 had primary (essential) hypertension. We measured the plasma levels of (1-84)-PTH, 25(OH)D, 1,25(OH)2D, and serum Ca (total and ionized), inorganic P, Mg, K, and the 24-h urinary excretion of Ca, P, and deoxypyridinoline. In primary aldosteronism patients, these measurements were repeated after adrenalectomy or mineralocorticoid receptor blockade. We also sought for PTH receptor (PTHR-1) mRNA and protein in APA tissue. Compared with primary (essential) hypertension patients, those with primary aldosteronism showed significantly higher plasma PTH (+31%), despite comparable urinary Ca excretion and similarly deficient 25(OH) vitamin D levels. In APA patients, who showed the PTHR-1 transcript and protein in tumor tissue, adrenalectomy normalized PTH levels (from 118 ± 13 to 76 ± 12 ng/l; P = 0.002) and increased ionized Ca(from 1.17 ± 0.04 to 1.22 ± 0.03 mmol/l; P PTHR-1 in APA might contribute to maintaining hyperaldosteronism despite suppression of angiotensin II formation.

  5. Information Flow in Secret Sharing Protocols

    CERN Document Server

    Kashefi, Elham; Mhalla, Mehdi; Perdrix, Simon

    2009-01-01

    The entangled graph states have emerged as an elegant and powerful quantum resource, indeed almost all multiparty protocols can be written in terms of graph states including measurement based quantum computation (MBQC), error correction and secret sharing amongst others. In addition they are at the forefront in terms of implementations. As such they represent an excellent opportunity to move towards integrated protocols involving many of these elements. In this paper we look at expressing and extending graph state secret sharing and MBQC in a common framework and graphical language related to flow. We do so with two main contributions. First we express in entirely graphical terms which set of players can access which information in graph state secret sharing protocols. These succinct graphical descriptions of access allow us to take known results from graph theory to make statements on the generalisation of the previous schemes to present new secret sharing protocols. Second, we give a set of necessary condit...

  6. Secretion management in the mechanically ventilated patient

    Directory of Open Access Journals (Sweden)

    Mantellini E.

    2012-01-01

    Full Text Available Purpose: the aim of this work is to highlight the importance of a correct management of the secretions in the patient submitted to mechanical ventilation (MV. Methods: analysis of the current bibliography related to respiratory infections and secretion in patients with mechanically ventilation. We focus on the use of in-ex suflator achine (cough machine associated with High Frequency Chest Wall Oscillation (HFCWO.Results: we observe a reduction of pulmonary infection and a better management of bronchial secretion in patient undergone to the use of in-ex suflator machine (cough machine associated with High Frequency Chest Wall Oscillation (HFCWO.Conclusions: the correct approach to patients submitted to mechanical ventilation (MV expect the use of High Frequency Chest Wall Oscillation (HFCWO (VEST and in-ex suflator machine (cough machine to decrease pulmonary infection thank to a reduction of permanence of bronchial secretions in the lungs .

  7. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

    2015-01-01

    +/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...

  8. Acetylcholine regulates ghrelin secretion in humans

    NARCIS (Netherlands)

    F. Broglio (Fabio); E. Ghigo (Ezio); C. Gottero; F. Prodam (Flavia); S. Destefanis; A. Benso; C. Gauna (Carlotta); L.J. Hofland (Leo); E. Arvat; A-J. van der Lely (Aart-Jan); P.M. van Koetsveld (Peter)

    2004-01-01

    textabstractGhrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g.

  9. Microbial cell surfaces and secretion systems

    NARCIS (Netherlands)

    Tommassen, J.P.M.; Wosten, H.A.B.

    2015-01-01

    Microbial cell surfaces, surface-exposed organelles, and secreted proteins are important for the interaction with the environment, including adhesion to hosts, protection against host defense mechanisms, nutrient acquisition, and intermicrobial competition. Here, we describe the structures of the ce

  10. Cell Secretion: Current Structural and Biochemical Insights

    Directory of Open Access Journals (Sweden)

    Saurabh Trikha

    2010-01-01

    Full Text Available Essential physiological functions in eukaryotic cells, such as release of hormones and digestive enzymes, neurotransmission, and intercellular signaling, are all achieved by cell secretion. In regulated (calcium-dependent secretion, membrane-bound secretory vesicles dock and transiently fuse with specialized, permanent, plasma membrane structures, called porosomes or fusion pores. Porosomes are supramolecular, cup-shaped lipoprotein structures at the cell plasma membrane that mediate and control the release of vesicle cargo to the outside of the cell. The sizes of porosomes range from 150nm in diameter in acinar cells of the exocrine pancreas to 12nm in neurons. In recent years, significant progress has been made in our understanding of the porosome and the cellular activities required for cell secretion, such as membrane fusion and swelling of secretory vesicles. The discovery of the porosome complex and the molecular mechanism of cell secretion are summarized in this article.

  11. 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.

  12. Linear multi-secret sharing schemes

    Institute of Scientific and Technical Information of China (English)

    XIAO Liangliang; LIU Mulan

    2005-01-01

    In this paper the linear multi-secret sharing schemes are studied by using monotone span programs. A relation between computing monotone Boolean functions by using monotone span programs and realizing multi-access structures by using linear multisecret sharing schemes is shown. Furthermore, the concept of optimal linear multi-secret sharing scheme is presented and the several schemes are proved to be optimal.

  13. Secretion management in the mechanically ventilated patient

    OpenAIRE

    Mantellini E.; Perrero L.; Provenzano G.; Petrozzino S.

    2012-01-01

    Purpose: the aim of this work is to highlight the importance of a correct management of the secretions in the patient submitted to mechanical ventilation (MV). Methods: analysis of the current bibliography related to respiratory infections and secretion in patients with mechanically ventilation. We focus on the use of in-ex suflator achine (cough machine) associated with High Frequency Chest Wall Oscillation (HFCWO).Results: we observe a reduction of pulmonary infection and a better managemen...

  14. Secretion of invertase in mitotic yeast cells.

    OpenAIRE

    Makarow, M

    1988-01-01

    In mammalian cells intracellular transport is inhibited during mitosis. Here we show that in the yeast Saccharomyces cerevisiae secretion continues uninterrupted during mitosis. S. cerevisiae cells were arrested in mitosis by treating wild-type cells with the microtubule-inhibitor nocodazole, or by incubating a temperature-sensitive cell division cycle mutant (cdc16) at the restrictive temperature. Secretion of invertase into the periplasmic space was equally efficient in mitotic and in unsyn...

  15. Peptides and neurotransmitters that affect renin secretion

    Science.gov (United States)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  16. Percolation of secret in a network

    CERN Document Server

    Leverrier, Anthony

    2011-01-01

    In this work, we explore the analogy between entanglement and secret classical correlations in the context of large networks, more precisely the question of percolation of secret correlations in a network. It is known that entanglement percolation in quantum networks can display a highly nontrivial behavior depending on the topology of the network and on the presence of entanglement between the nodes. Here we show that this behavior, thought to be of a genuine quantum nature, also occurs in a classical context.

  17. Peptides and neurotransmitters that affect renin secretion

    Science.gov (United States)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  18. Spinal astrocytes produce and secrete dynorphin neuropeptides.

    Science.gov (United States)

    Wahlert, Andrew; Funkelstein, Lydiane; Fitzsimmons, Bethany; Yaksh, Tony; Hook, Vivian

    2013-04-01

    Dynorphin peptide neurotransmitters (neuropeptides) have been implicated in spinal pain processing based on the observations that intrathecal delivery of dynorphin results in proalgesic effects and disruption of extracellular dynorphin activity (by antisera) prevents injury evoked hyperalgesia. However, the cellular source of secreted spinal dynorphin has been unknown. For this reason, this study investigated the expression and secretion of dynorphin-related neuropeptides from spinal astrocytes (rat) in primary culture. Dynorphin A (1-17), dynorphin B, and α-neoendorphin were found to be present in the astrocytes, illustrated by immunofluorescence confocal microscopy, in a discrete punctate pattern of cellular localization. Measurement of astrocyte cellular levels of these dynorphins by radioimmunoassays confirmed the expression of these three dynorphin-related neuropeptides. Notably, BzATP (3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate) and KLA (di[3-deoxy-D-manno-octulosonyl]-lipid A) activation of purinergic and toll-like receptors, respectively, resulted in stimulated secretion of dynorphins A and B. However, α-neoendorphin secretion was not affected by BzATP or KLA. These findings suggest that dynorphins A and B undergo regulated secretion from spinal astrocytes. These findings also suggest that spinal astrocytes may provide secreted dynorphins that participate in spinal pain processing.

  19. An unexpected knock on Corrigan's secret door.

    Science.gov (United States)

    Woywodt, Alexander

    2010-10-01

    Corrigan's secret door describes a metaphorical escape route for busy physicians. The term was derived from the successful and exceptionally busy professional life of Irish physician Dominic John Corrigan (1802-80). It is claimed that Corrigan's outpatient clinic was so busy that he required a secret door in his consulting rooms to escape from the ever-growing queue of eager patients. The origins of this charming story are unknown, and the door may have never existed. However, at present, Corrigan's secret door is often quoted when busy physicians have their own little ways in surviving a stressful professional life. Generations of British-trained doctors have grown up with Corrigan's secret door, as it was featured in the introduction of the Oxford Handbook of Clinical Medicine. Accordingly, trainees as well as more senior doctors are often reminded that having a 'secret door' is vital in surviving in the medical profession. My own escape is through classical music and the violoncello, in particular. As the name implies, my own secret door is normally invisible to colleagues and patients. This little article is about a patient who found me out, and a reflection on the role of classical music and the cello in my professional life.

  20. 37 CFR 1.84 - Standards for drawings.

    Science.gov (United States)

    2010-07-01

    ... (stained and unstained), histological tissue cross sections (stained and unstained), animals, plants, in... illustration by a drawing, the examiner may require a drawing in place of the photograph. The photographs must... should be provided, and if provided, should include the title of the invention, inventor's name, and...

  1. Intestinal Bicarbonate Secretion in Cystic Fibrosis Mice

    Directory of Open Access Journals (Sweden)

    Clarke LL

    2001-07-01

    Full Text Available Gene-targeted disruption of the cystic fibrosis transmembrane conductance regulator (CFTR in mice results in an intestinal disease phenotype that is remarkably similar to bowel disease in cystic fibrosis patients. In the intestinal segment downstream from the stomach (i.e., the duodenum, CFTR plays an important role in bicarbonate secretion that protects the epithelium from acidic gastric effluent. In this report, we examine the role of CFTR in cAMP-stimulated bicarbonate secretion in the murine duodenum and the mechanisms of acid-base transport that are revealed in CFTR knockout (CF mice. Ion substitution, channel blocker and pH stat studies comparing duodena from wild-type and CF mice indicate that CFTR mediates a HCO(3(- conductance across the apical membrane of the epithelium. In the presence of a favorable cell-to-lumen HCO(3(- gradient, the CFTR-mediated HCO(3(- current accounts for about 80% of stimulated HCO(3(- secretion. Exposure of the duodenal mucosa to acidic pH reveals another role of CFTR in facilitating HCO(3(- secretion via an electroneutral, 4,4'-diisothiocyanato-stilbene-2,2' disulfonic acid (DIDS sensitive Cl(-/HCO(3(- exchange process. In CF duodenum, other apical membrane acid-base transporters retain function, thereby affording limited control of transepithelial pH. Activity of a Cl(--dependent anion exchanger provides near-constant HCO(3(- secretion in CF intestine, but under basal conditions the magnitude of secretion is lessened by simultaneous activity of a Na(+/H(+ exchanger (NHE. During cAMP stimulation of CF duodenum, a small increase in net base secretion is measured but the change results from cAMP inhibition of NHE activity rather than increased HCO(3(- secretion. Interestingly, a small inward current that is sensitive to the anion channel blocker, 5-nitro-2(3-phenylpropyl amino-benzoate (NPPB, is also activated during cAMP stimulation of the CFTR-null intestine but the identity of the current is yet to be

  2. Effects of endothelin family on ANP secretion.

    Science.gov (United States)

    Yuan, Kuichang; Park, Byung Mun; Choi, Young Tae; Kim, Jong Hun; Cho, Kyung Woo; Kim, Suhn Hee

    2016-08-01

    The endothelins (ET) peptide family consists of ET-1, ET-2, ET-3, and sarafotoxin (s6C, a snake venom) and their actions appears to be different among isoforms. The aim of this study was to compare the secretagogue effect of ET-1 on atrial natriuretic peptide (ANP) secretion with ET-3 and evaluate its physiological meaning. Isolated nonbeating atria from male Sprague-Dawley rats were used to evaluate stretch-activated ANP secretion in response to ET-1, ET-2, ET-3, and s6C. Changes in mean blood pressure (MAP) were measured during acute injection of ET-1 and ET-3 with and without natriuretic peptide receptor-A antagonist (A71915) in anesthetized rats. Changes in atrial volume induced by increased atrial pressure from o to 1, 2, 4, or 6cm H2O caused proportional increases in mechanically-stimulated extracellular fluid (ECF) translocation and stretch-activated ANP secretion. ET-1 (10nM) augmented basal and stretch-activated ANP secretion in terms of ECF translocation, which was blocked by the pretreatment with ETA receptor antagonist (BQ123, 1μM) but not by ETB receptor antagonist (BQ788, 1μM). ETA receptor antagonist itself suppressed stretch-activated ANP secretion. As compared to ET-1- induced ANP secretion (3.2-fold by 10nM), the secretagogue effects of ANP secretion by ET-2 was similar (2.8-fold by 10nM) and ET-3 and s6C were less potent (1.7-fold and 1.5-fold by 100nM, respectively). Acute injection of ET-1 or ET-3 increased mean blood pressure (MAP), which was augmented in the presence of natriuretic peptide receptor-A antagonist. Therefore, we suggest that the order of secretagogue effect of ET family on ANP secretion was ET-1≥ET-2>ET-3>s6C and ET-1-induced ANP secretion negatively regulates the pressor effect of ET-1. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Role of adipose secreted factors and kisspeptin in the metabolic control of gonadotropin secretion and puberty

    Science.gov (United States)

    Factors secreted by adipose tissue continue to be discovered. Evidence indicates a strong link between neural influences and adipocyte expression and secretion of a wide array of cytokines, neurotrophic factors, growth factors, binding proteins, and neuropeptides. These “adipokines” are linked to im...

  4. Secrets and the Sociological Imagination: Using PostSecret.com to Illustrate Sociological Concepts

    Science.gov (United States)

    Noy, Shiri

    2014-01-01

    Introductory sociology classes afford instructors an opportunity to expose students, often from a variety of backgrounds and majors, to the sociological imagination. In this article, I describe how the use of secrets from a popular website, PostSecret.com, can help teach students about the sociological imagination and incorporate biographical…

  5. Meaningful Share Generation for Increased Number of Secrets in Visual Secret-Sharing Scheme

    Directory of Open Access Journals (Sweden)

    Mustafa Ulutas

    2010-01-01

    Full Text Available This paper presents a new scheme for hiding two halftone secret images into two meaningful shares created from halftone cover images. Meaningful shares are more desirable than noise-like (meaningless shares in Visual Secret Sharing because they look natural and do not attract eavesdroppers' attention. Previous works in the field focus on either increasing number of secrets or creating meaningful shares for one secret image. The method outlined in this paper both increases the number of secrets and creates meaningful shares at the same time. While the contrast ratio of shares is equal to that of Extended Visual Cryptography, two secrets are encoded into two shares as opposed to one secret in the Extended Visual Cryptography. Any two natural-looking images can be used as cover unlike the Halftone Visual Cryptography method where one cover should be the negative of the other cover image and can only encode one secret. Effectiveness of the proposed method is verified by an experiment.

  6. Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

    Science.gov (United States)

    Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

    2013-01-01

    It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

  7. Hiding secret data into a carrier image

    Directory of Open Access Journals (Sweden)

    Ovidiu COSMA

    2012-06-01

    Full Text Available The object of steganography is embedding hidden information in an appropriate multimedia carrier, e.g., image, audio, or video. There are several known methods of solving this problem, which operate either in the space domain or in the frequency domain, and are distinguished by the following characteristics: payload, robustness and strength. The payload is the amount of secret data that can be embedded in the carrier without inducing suspicious artefacts, robustness indicates the degree in which the secret data is affected by the normal processing of the carrier e.g., compression, and the strength indicate how easy the presence of hidden data can be detected by steganalysis techniques. This paper presents a new method of hiding secret data into a digital image compressed by a technique based on the Discrete Wavelet Transform (DWT [2] and the Set Partitioning In Hierarchical Trees (SPIHT subband coding algorithm [6]. The proposed method admits huge payloads and has considerable strength.

  8. Standpoints and protection of business secrets

    Directory of Open Access Journals (Sweden)

    Brane Bertoncelj

    2001-06-01

    Full Text Available The human impact on an information system where data bases, containing business secretes, are stored is one of the most unreliable and unforeseeable factors. For this reason, it must not be underestimated. The results of this study indicate a correlation between behavioural intention and protection of business secretes. There is a statistically significant correlation between behavioural intention and behavioural supervision. This means that an increased level of perceived supervision over one's own behaviour is related to behavioural intention. A great majority of participants would not divulge a business secret due to internal moral factors, i.e., they possess the appropriate capabilities to determine the advantages of social moral values over personal values.

  9. The 'Secret' of success part 1.

    Science.gov (United States)

    Busby, Mike

    2011-03-01

    Practice success is defined across the four'dimensions' of oral health, patient satisfaction, job satisfaction and financial profit. It is suggested that the 'secret' of success in dental practice is to make patient (customer) satisfaction the primary focus. Not a very earth shattering or surprising'secret' perhaps! This is hardly a new idea, and not a concept restricted to dental practice. This principle applies to all businesses. This series of articles reviews evidence from across a broad spectrum of publications: from populist business publications through to refereed scientific papers, this'secret' seems to be confirmed. The evidence for which aspects of our service are most important in achieving patient satisfaction (and therefore success) is explored. Good oral health outcomes for patients are defined as the primary purpose of dental practice and, therefore, an essential dimension of success. The link between positive patient perceptions of general care and their own oral health to practice success is explored.

  10. Melatonin Secretion Pattern in Critically Ill Patients

    DEFF Research Database (Denmark)

    Boyko, Yuliya; Holst, René; Jennum, Poul

    2017-01-01

    Critically ill patients have abnormal circadian and sleep homeostasis. This may be associated with higher morbidity and mortality. The aims of this pilot study were (1) to describe melatonin secretion in conscious critically ill mechanically ventilated patients and (2) to describe whether melatonin...... secretion and sleep patterns differed in these patients with and without remifentanil infusion. Eight patients were included. Blood-melatonin was taken every 4th hour, and polysomnography was carried out continually during a 48-hour period. American Academy of Sleep Medicine criteria were used for sleep...... scoring if sleep patterns were identified; otherwise, Watson's classification was applied. As remifentanil was periodically administered during the study, its effect on melatonin and sleep was assessed. Melatonin secretion in these patients followed a phase-delayed diurnal curve. We did not observe any...

  11. Lubiprostone Stimulates Duodenal Bicarbonate Secretion in Rats

    OpenAIRE

    Mizumori, Misa; Akiba, Yasutada; Kaunitz, Jonathan D.

    2009-01-01

    Background Lubiprostone, a bicyclic fatty acid, is used for the treatment of chronic constipation. No published study has addressed the effect of lubiprostone on intestinal ion secretion in vivo. Aim The aim of this study was to test the hypothesis that lubiprostone augments duodenal HCO3 − secretion (DBS). Methods Rat proximal duodenal loops were perfused with pH 7.0 Krebs, control vehicle (medium-chain triglycerides), or lubiprostone (0.1–10 μM). We measured DBS with flow-through pH and CO2...

  12. Quantum Secret Sharing by applying Analytic Geometry

    OpenAIRE

    Liu, Ruilong

    2010-01-01

    In this paper, we investigate a novel $(2,2)$-threshold scheme and then generalize this to a $(n,n)$-threshold scheme for quantum secret sharing (QSS) which makes use of the fundamentals of Analytic Geometry. The dealer aptly selects GHZ states related to the coefficients which determine straight lines on a two-dimension plane. Then by computing each two of the lines intercept or not, we obtain a judging matrix whose rank can be used to determine the secret stored in entangled bits. Based on ...

  13. Pancreatic enzyme secretion during intravenous fat infusion.

    Science.gov (United States)

    Burns, G P; Stein, T A

    1987-01-01

    The nutritional support of patients with pancreatic and high gastrointestinal fistulas and severe pancreatitis frequently involves intravenous fat infusion. There are conflicting reports on the effect of intravenous fat on pancreatic exocrine secretion. In 10 dogs with chronic pancreatic fistulas, pancreatic juice was collected during secretin (n = 10) or secretin + cholecystokinin (n = 4) stimulation, with and without intravenous fat infusion (5 g/hr). The hormonal-stimulated secretion of lipase, amylase, trypsin, total protein, bicarbonate, and water was unchanged during fat infusion. This study supports the use of intravenous fat as a nutritional source when it is desirable to avoid stimulation of the pancreas.

  14. Unique substrates secreted by the type VI secretion system of Francisella tularensis during intramacrophage infection.

    Directory of Open Access Journals (Sweden)

    Jeanette E Bröms

    Full Text Available Gram-negative bacteria have evolved sophisticated secretion machineries specialized for the secretion of macromolecules important for their life cycles. The Type VI secretion system (T6SS is the most widely spread bacterial secretion machinery and is encoded by large, variable gene clusters, often found to be essential for virulence. The latter is true for the atypical T6SS encoded by the Francisella pathogenicity island (FPI of the highly pathogenic, intracellular bacterium Francisella tularensis. We here undertook a comprehensive analysis of the intramacrophage secretion of the 17 FPI proteins of the live vaccine strain, LVS, of F. tularensis. All were expressed as fusions to the TEM β-lactamase and cleavage of the fluorescent substrate CCF2-AM, a direct consequence of the delivery of the proteins into the macrophage cytosol, was followed over time. The FPI proteins IglE, IglC, VgrG, IglI, PdpE, PdpA, IglJ and IglF were all secreted, which was dependent on the core components DotU, VgrG, and IglC, as well as IglG. In contrast, the method was not directly applicable on F. novicida U112, since it showed very intense native β-lactamase secretion due to FTN_1072. Its role was proven by ectopic expression in trans in LVS. We did not observe secretion of any of the LVS substrates VgrG, IglJ, IglF or IglI, when tested in a FTN_1072 deficient strain of F. novicida, whereas IglE, IglC, PdpA and even more so PdpE were all secreted. This suggests that there may be fundamental differences in the T6S mechanism among the Francisella subspecies. The findings further corroborate the unusual nature of the T6SS of F. tularensis since almost all of the identified substrates are unique to the species.

  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. Effect of 15% Alcohol Dependence on Alveolar Bone Loss and TNF-α Secretion in Wistar Rats.

    Science.gov (United States)

    Wagner, Marcius Comparsi; Rocha, José Mariano da; Gaio, Eduardo José; Cavagni, Juliano; Carrard, Vinícius Coelho; Rösing, Cassiano Kuchenbecker

    2016-01-01

    The aim of the present study was to evaluate the effect of 15% alcohol dependence on ligature-induced alveolar bone loss and TNF-α secretion in Wistar rats. Thirty-three male Wistar rats aged 45-60 days (mean weight=253 g) were randomly allocated test or control groups. Test group (n=18) received 15% alcohol as liquid intake and control group (n=15) received water during the experimental period. TNF-α was analyzed by ELISA assay in 11 animals per group. After 14 days of alcohol/water intake, alcohol dependency was assessed and silk ligatures were placed around the left second upper molars. Ligature presence and body weight were checked weekly. After 40 days, animals were sacrificed and the maxillae were defleshed for morphometric analysis using standardized images. All animals in the test group displayed signs of alcohol dependency at day 14. No statistically significant differences in final body weight (334.83±21.38 vs. 322.48±30.65 g, p=0.20) were observed between groups. In relation to alveolar bone loss, no statistically significant difference was observed among test and control groups both for ligated teeth (0.76±0.06 vs. 0.74±0.10 mm, p=0.60) and unligated teeth (0.41±0.16 vs. 0.35±0.05 mm, p=0.22). The TNF-α secretion also did not display statistically significant differences between test and control groups (10.78±1.84 vs. 12.13±2.11 pg/mL, p=0.12). It may be concluded that 15% alcohol dependency was not capable to alter alveolar bone loss and TNF-α secretion in Wistar rats.

  19. Scalable Mechanisms for Rational Secret Sharing

    CERN Document Server

    Dani, Varsha; Saia, Jared

    2012-01-01

    We consider the classical secret sharing problem in the case where all agents are selfish but rational. In recent work, Kol and Naor show that, when there are two players, in the non-simultaneous communication model, i.e. when rushing is possible, there is no Nash equilibrium that ensures both players learn the secret. However, they describe a mechanism for this problem, for any number of players, that is an epsilon-Nash equilibrium, in that no player can gain more than epsilon utility by deviating from it. Unfortunately, the Kol and Naor mechanism, and, to the best of our knowledge, all previous mechanisms for this problem require each agent to send O(n) messages in expectation, where n is the number of agents. This may be problematic for some applications of rational secret sharing such as secure multi-party computation and simulation of a mediator. We address this issue by describing mechanisms for rational secret sharing that are designed for large n. Both of our results hold for n > 2, and are Nash equil...

  20. Secret Shopping as User Experience Assessment Tool

    Science.gov (United States)

    Boyce, Crystal M.

    2015-01-01

    Secret shopping is a form of unobtrusive evaluation that can be accomplished with minimal effort, but still produce rich results. With as few as 11 shoppers, the author was able to identify trends in user satisfaction with services provided across two entry-level desks at Illinois Wesleyan University's The Ames Library. The focus of this secret…

  1. A mathematical model of insulin secretion.

    Science.gov (United States)

    Shannon, A G; Hogg, J M; Ollerton, R L; Luzio, S; Owens, D R

    1994-01-01

    Diabetes mellitus is a chronic state of excessive blood glucose levels (hyperglycaemia), which may result from many environmental and genetic factors, often acting jointly. The major regulator of glucose concentration in the blood is insulin. It is known that about 50% of the insulin is taken up by the liver on passing through it after secretion from the pancreas. The precise value of this fractional uptake is not known, so the prehepatic insulin secretion rates cannot be readily estimated from the plasma insulin concentration levels. By utilizing the equimolar secretion of insulin and connecting peptide (C-peptide) from the pancreas, a noninvasive method has been formulated. This was based on a compartmental model which involved the pancreas, liver, and plasma. The resulting differential equation yielded a gamma variate solution which could be readily linearized. The model was then tested on 56 normal (51 nonobese and 5 obese) subjects, and three groups of subjects with diabetes who could be labelled as mild, moderate, and severe (based on the fasting plasma glucose concentration) with 83, 88, and 64 subjects respectively. We have focused on the human patient environment of the clinician to produce a distinct model which gave a consistent pattern within all four groups with good fits between observed and theoretical values of the plasma insulin levels. The consequent rates for insulin secretion were consistent across the groups and were clinically meaningful.

  2. Secret Sharing Schemes and Advanced Encryption Standard

    Science.gov (United States)

    2015-09-01

    Professor Bard xv Mansager, my academic advisor in the Department of Applied Mathematics. Bard was the one who reassured me that the Math Department...are obtained by an eavesdropper, and the eavesdropper decomposes the public shares into the generalized formula yi = (xi+α)k−b0 for secret recovery

  3. Secret Codes, Remainder Arithmetic, and Matrices.

    Science.gov (United States)

    Peck, Lyman C.

    This pamphlet is designed for use as enrichment material for able junior and senior high school students who are interested in mathematics. No more than a clear understanding of basic arithmetic is expected. Students are introduced to ideas from number theory and modern algebra by learning mathematical ways of coding and decoding secret messages.…

  4. An Approach to Hide Secret Speech Information

    Institute of Scientific and Technical Information of China (English)

    WU Zhi-jun; DUAN Hai-xin; LI Xing

    2006-01-01

    This paper presented an approach to hide secret speech information in code excited linear prediction(CELP)-based speech coding scheme by adopting the analysis-by-synthesis (ABS)-based algorithm of speech information hiding and extracting for the purpose of secure speech communication. The secret speech is coded in 2.4Kb/s mixed excitation linear prediction (MELP), which is embedded in CELP type public speech. The ABS algorithm adopts speech synthesizer in speech coder. Speech embedding and coding are synchronous, i.e. a fusion of speech information data of public and secret. The experiment of embedding 2.4 Kb/s MELP secret speech in G.728 scheme coded public speech transmitted via public switched telephone network (PSTN) shows that the proposed approach satisfies the requirements of information hiding, meets the secure communication speech quality constraints, and achieves high hiding capacity of average 3.2 Kb/s with an excellent speech quality and complicating speakers' recognition.

  5. Acetylcholine regulates ghrelin secretion in humans

    NARCIS (Netherlands)

    F. Broglio (Fabio); E. Ghigo (Ezio); C. Gottero; F. Prodam (Flavia); S. Destefanis; A. Benso; C. Gauna (Carlotta); L.J. Hofland (Leo); E. Arvat; A-J. van der Lely (Aart-Jan); P.M. van Koetsveld (Peter)

    2004-01-01

    textabstractGhrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g. stimulatio

  6. Secret Shopping as User Experience Assessment Tool

    Science.gov (United States)

    Boyce, Crystal M.

    2015-01-01

    Secret shopping is a form of unobtrusive evaluation that can be accomplished with minimal effort, but still produce rich results. With as few as 11 shoppers, the author was able to identify trends in user satisfaction with services provided across two entry-level desks at Illinois Wesleyan University's The Ames Library. The focus of this secret…

  7. Kinins as mediators of intestinal secretion.

    Science.gov (United States)

    Gaginella, T S; Kachur, J F

    1989-01-01

    Kinins are small peptides that have diverse biological actions. Concentrations of kinins in the nanomolar or subnanomolar range induce intestinal smooth muscle contraction and evoke mucosal electrolyte secretion. Hyperkininemia is associated with effects on gastrointestinal motility and intestinal mucosal inflammation. Bradykinin and kallidin are the predominant kinins with effects on the gastrointestinal tract of mammals. Bradykinin stimulates chloride ion secretion by the guinea pig and rabbit ileum, rabbit colon, rat colon and monolayers of human HCA-7 cells. Kinins directly or indirectly stimulate phospholipase A2 and phospholipase C. Cells in the lamina propria of the mucosa (e.g., fibroblasts, mast cells, leukocytes), by liberating cyclooxygenase and lipoxygenase metabolites of arachidonic acid, are involved in the kinin response; direct effects on epithelial cells cannot be ruled out, however. Antagonists now exist for kinin receptors. Based on studies with these antagonists in smooth muscle preparations, two subgroups of kinin receptor have been identified. The B2-type receptor appears to be responsible for both the contraction of ileal muscle and ileal secretion. Kinins are probably more important as pathophysiological rather than as physiological mediators. They may amplify the effect of inflammatory products that induce intestinal secretion. The precise involvement of kinins in clinical mucosal secretory states and diarrhea will require quantitative assessment of their levels during each phase of mucosal inflammation. Additional studies on the mechanism of action of kinins will be essential in designing therapy to mitigate the symptoms associated with mucosal inflammation.

  8. Secret Symmetries in AdS/CFT

    CERN Document Server

    de Leeuw, Marius; Moriyama, Sanefumi; Regelskis, Vidas; Torrielli, Alessandro

    2012-01-01

    We discuss special quantum group (secret) symmetries of the integrable system associated to the AdS/CFT correspondence. These symmetries have by now been observed in a variety of forms, including the spectral problem, the boundary scattering problem, n-point amplitudes, the pure-spinor formulation and quantum affine deformations.

  9. Metabolic priming by a secreted fungal effector.

    Science.gov (United States)

    Djamei, Armin; Schipper, Kerstin; Rabe, Franziska; Ghosh, Anupama; Vincon, Volker; Kahnt, Jörg; Osorio, Sonia; Tohge, Takayuki; Fernie, Alisdair R; Feussner, Ivo; Feussner, Kirstin; Meinicke, Peter; Stierhof, York-Dieter; Schwarz, Heinz; Macek, Boris; Mann, Matthias; Kahmann, Regine

    2011-10-05

    Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation.

  10. Insulin: pancreatic secretion and adipocyte regulation.

    Science.gov (United States)

    Baumgard, L H; Hausman, G J; Sanz Fernandez, M V

    2016-01-01

    Insulin is the primary acute anabolic coordinator of nutrient partitioning. Hyperglycemia is the main stimulant of insulin secretion, but other nutrients such as specific amino acids, fatty acids, and ketoacids can potentiate pancreatic insulin release. Incretins are intestinal hormones with insulinotropic activity and are secreted in response to food ingestion, thus integrating diet chemical composition with the regulation of insulin release. In addition, prolactin is required for proper islet development, and it stimulates β-cell proliferation. Counterintuitively, bacterial components appear to signal insulin secretion. In vivo lipopolysaccharide infusion acutely increases circulating insulin, which is paradoxical as endotoxemia is a potent catabolic condition. Insulin is a potent anabolic orchestrator of nutrient partitioning, and this is particularly true in adipocytes. Insulin dictates lipid accretion in a dose-dependent manner during preadipocyte development in adipose tissue-derived stromal vascular cell culture. However, in vivo studies focused on insulin's role in regulating adipose tissue metabolism from growing, and market weight pigs are sometimes inconsistent, and this variability appears to be animal, age and depot dependent. Additionally, porcine adipose tissue synthesizes and secretes a number of adipokines (leptin, adiponectin, and so forth) that directly or indirectly influence insulin action. Therefore, because insulin has an enormous impact on agriculturally important phenotypes, it is critical to have a better understanding of how insulin homeostasis is governed.

  11. 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.

  12. 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.

  13. 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.

  14. Parathyroid hormone induces adipocyte lipolysis via PKA-mediated phosphorylation of hormone-sensitive lipase.

    Science.gov (United States)

    Larsson, Sara; Jones, Helena A; Göransson, Olga; Degerman, Eva; Holm, Cecilia

    2016-03-01

    Parathyroid hormone (PTH) is secreted from the parathyroid glands in response to low plasma calcium levels. Besides its classical actions on bone and kidney, PTH may have other important effects, including metabolic effects, as suggested for instance by increased prevalence of insulin resistance and type 2 diabetes in patients with primary hyperparathyroidism. Moreover, secondary hyperparathyroidism may contribute to the metabolic derangements that characterize states of vitamin D deficiency. PTH has been shown to induce adipose tissue lipolysis, but the details of the lipolytic action of PTH have not been described. Here we used primary mouse adipocytes to show that intact PTH (1-84) as well as the N-terminal fragment (1-37) acutely stimulated lipolysis in a dose-dependent manner, whereas the C-terminal fragment (38-84) was without lipolytic effect. The lipolytic action of PTH was paralleled by phosphorylation of known protein kinase A (PKA) substrates, i.e. hormone-sensitive lipase (HSL) and perilipin. The phosphorylation of HSL in response to PTH occurred at the known PKA sites S563 and S660, but not at the non-PKA site S565. PTH-induced lipolysis, as well as phosphorylation of HSL at S563 and S660, was blocked by both the PKA-inhibitor H89 and the adenylate cyclase inhibitor MDL-12330A, whereas inhibitors of extracellular-regulated kinase (ERK), protein kinase B (PKB), AMP-activated protein kinase (AMPK) and Ca(2+)/calmodulin-dependent protein kinase (CaMK) had little or no effect. Inhibition of phosphodiesterase 4 (PDE4) strongly potentiated the lipolytic action of PTH, whereas inhibition of PDE3 had no effect. Our results show that the lipolytic action of PTH is mediated by the PKA signaling pathway with no or minor contribution of other signaling pathways and, furthermore, that the lipolytic action of PTH is limited by simultaneous activation of PDE4. Knowledge of the signaling pathways involved in the lipolytic action of PTH is important for our

  15. Ubiquitination-deubiquitination balance dictates ligand-stimulated PTHR sorting.

    Science.gov (United States)

    Alonso, Verónica; Magyar, Clara E; Wang, Bin; Bisello, Alessandro; Friedman, Peter A

    2011-12-01

    Parathyroid hormone receptors (PTHR) are promptly internalized upon stimulation by activating (PTH[1-84], PTH[1-34]) and non-activating (PTH[7-84], PTH[7-34]) ligands. Here, we characterized the mechanism regulating the sorting of internalized receptors between recycling and degradative pathways. PTHR recycles faster after challenge with PTH(1-34) than with PTH(7-34). PTHR recycling is complete by 2 h after PTH(1-34) stimulation, but incomplete at this time in cells treated with PTH(7-34). The slower and incomplete recycling induced by PTH(7-34) is due to proteasomal degradation. Both PTH(1-34) and PTH(7-34) induced PTHR polyubiquitination. Ubiquitination by PTH(1-34) was transient, whereas receptor ubiquitination after PTH(7-34) was sustained. PTH(1-34), but not PTH(7-34), induced expression of the PTHR-specific deubiquitinating enzyme USP2. Overexpression of USP2 prevented PTH(7-34)-induced PTHR degradation. We conclude that PTH(1-34) promotes coupled PTHR ubiquitination and deubiquitination, whereas PTH(7-34) activates only ubiquitination, thereby leading to PTHR downregulation. These findings may explain PTH resistance in diseases associated with elevated PTH(7-84) levels. Copyright © 2011 American Society for Bone and Mineral Research.

  16. Properties of Duvernoy's secretions from opisthoglyphous and aglyphous colubrid snakes.

    Science.gov (United States)

    Weinstein, S A; Kardong, K V

    1994-10-01

    Relatively little attention has been given to the biological properties of Duvernoy's secretions produced by opisthoglyphous and some aglyphous colubrid snakes. A review is presented of literature pertaining to these secretions. Most detailed analyses of Duvernoy's secretions and their biological properties have been performed since the late 1970s. The dispholidines, Dispholidus typus and Thelotornis sp., and the natricines, Rhabdophis tigrinus and R. subminiata, have received the most attention due to the high toxicity of their secretions and their medical importance. These species produce secretions with variably strong prothrombin-activating activity, defibrinating activity, and hemorrhagic potential. Boigines, and natricines other than Rhabdophis, produce secretions of low to moderate toxicity and are variably hemorrhagic and proteolytic. Xenodontines and homalopsines similarly show hemorrhagic potential with low to moderate toxicity. Neurotoxic activity has been reported only from secretions of the boigines, Boiga blandingi and B. irregularis and the xenodontine, Heterodon platyrhinos. These species produce secretions containing postsynaptically acting components. Analyses of some of these secretions have shown that enzymes common to many ophidian venoms such as phospholipases A and L-amino acid oxidase are uncommon in the colubrid secretions studied. This may be due to few studies assaying for multiple enzyme activities and/or the unavailability of many secretion samples for study. Methods of secretion extraction, storage, and assay are discussed. Projected future research and the adaptive implications of Duvernoy's secretions are considered.

  17. Somatomammotrophic cells in GH-secreting and PRL-secreting human pituitary adenomas.

    Science.gov (United States)

    Bassetti, M; Brina, M; Spada, A; Giannattasio, G

    1989-11-01

    A morphological study has been carried out on 20 GH-secreting adenomas removed from acromegalic normoprolactinemic patients, on 29 PRL-secreting adenomas removed from hyperprolactinemic patients without signs of acromegaly and on one normal human anterior pituitary gland collected at autopsy. The protein A-gold immunoelectron microscopic technique has been utilized in order to verify the presence of mixed cells producing both GH and PRL (somatomammotrophs) in these pituitary tissues. In the normal pituitary a considerable number of somatomammotrophs (15-20%) was found, thus supporting the idea that these cells are normal components of the human anterior pituitary gland. In 10 GH-secreting adenomas and in 10 PRL-secreting adenomas somatomammotrophs were present in a variable number (from 4 to 20% of the whole cell population in GH adenomas and from 1 to 47% in PRL tumors). It can be concluded therefore that these cells, largely present in all GH/PRL-secreting adenomas, can also be found in GH-secreting and PRL-secreting tumors without clinical evidence of a mixed secretion. Adenomatous somatomammotrophs displayed ultrastructural features of adenomatous somatotrophs and mammotrophs (prominent Golgi complexes, abundant rough endoplasmic reticulum, irregular nuclei). The size and the number of granules were variable. In some cells GH and PRL were stored in distinct secretory granules, in others in mixed granules or both in mixed and distinct granules, thus suggesting that in adenomatous somatomammotrophs the efficiency of the mechanisms of sorting of the two hormones varies from one cell to another.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Hasselbalch, Hans C; Nielsen, Claus H

    2013-01-01

    Activated platelets are known to modulate immune responses by secreting or shedding a range of immunomodulatory substances. We examined the influence of activated platelets on cytokine production by normal human mononuclear cells, induced by tetanus toxoid (TT), human thyroglobulin (TG), Escheric......Activated platelets are known to modulate immune responses by secreting or shedding a range of immunomodulatory substances. We examined the influence of activated platelets on cytokine production by normal human mononuclear cells, induced by tetanus toxoid (TT), human thyroglobulin (TG...

  19. Involvement of type VI secretion system in secretion of iron chelator pyoverdine in Pseudomonas taiwanensis

    Science.gov (United States)

    Chen, Wen-Jen; Kuo, Tzu-Yen; Hsieh, Feng-Chia; Chen, Pi-Yu; Wang, Chang-Sheng; Shih, Yu-Ling; Lai, Ying-Mi; Liu, Je-Ruei; Yang, Yu-Liang; Shih, Ming-Che

    2016-01-01

    Rice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive rice diseases worldwide. Therefore, in addition to breeding disease-resistant rice cultivars, it is desirable to develop effective biocontrol agents against Xoo. Here, we report that a soil bacterium Pseudomonas taiwanensis displayed strong antagonistic activity against Xoo. Using matrix-assisted laser desorption/ionization imaging mass spectrometry, we identified an iron chelator, pyoverdine, secreted by P. taiwanensis that could inhibit the growth of Xoo. Through Tn5 mutagenesis of P. taiwanensis, we showed that mutations in genes that encode components of the type VI secretion system (T6SS) as well as biosynthesis and maturation of pyoverdine resulted in reduced toxicity against Xoo. Our results indicated that T6SS is involved in the secretion of endogenous pyoverdine. Mutations in T6SS component genes affected the secretion of mature pyoverdine from the periplasmic space into the extracellular medium after pyoverdine precursor is transferred to the periplasm by the inner membrane transporter PvdE. In addition, we also showed that other export systems, i.e., the PvdRT-OpmQ and MexAB-OprM efflux systems (for which there have been previous suggestions of involvement) and the type II secretion system (T2SS), are not involved in pyoverdine secretion. PMID:27605490

  20. Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2016-06-15

    To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma.

  1. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol originat

  2. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol

  3. Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Je Min, E-mail: jemin@knu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of); Department of Horticultural Science, Kyungpook National University, Daegu (Korea, Republic of); Lee, Sang-Jik [Biotechnology Institute, Nongwoo Bio Co, Ltd, Yeoju (Korea, Republic of); Department of Plant Biology, Cornell University, Ithaca, NY (United States); Rose, Jocelyn K.C. [Department of Plant Biology, Cornell University, Ithaca, NY (United States); Yeam, Inhwa [Department of Horticulture and Breeding, Andong National University, Andong (Korea, Republic of); Kim, Byung-Dong [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of)

    2014-04-18

    Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.

  4. Quantum Secret Sharing Based on Chinese Remainder Theorem

    Institute of Scientific and Technical Information of China (English)

    SHI Rong-Hua; SU Qian; GUO Ying; LEE Moon Ho

    2011-01-01

    A novel quantum secret sharing (QSS) scheme is proposed on the basis of Chinese Remainder Theorem (CRT).In the scheme, the classical messages are mapped to secret sequences according to CRT equations, and distributed to different receivers by different dimensional superdense-coding respectively.CRT's secret sharing function, together with high-dimensional superdense-coding, provide convenience, security, and large capability quantum channel for secret distribution and recovering.Analysis shows the security of the scheme.

  5. Measurement of secretion in nasal lavage

    DEFF Research Database (Denmark)

    Bisgaard, H; Krogsgaard, O W; Mygind, N

    1987-01-01

    secretion to be carried out on the whole sample of lavage fluid, thereby avoiding the necessity of complete admixture between marker and lavage fluid which would be pertinent to marker molecules measured chemically. The radiation from a nasal lavage is minimal and the procedure is fully acceptable...... for repeated use in humans. 4. The nasal lavage technique adopted allowed the return of 99.2% (median value) of the instilled volume. The area irrigated was visualized on a gamma-camera, and was demonstrated to cover an area larger than the area reached by challenge from a pumpspray, i.e. a large part...... of the nose, yet not the oropharynx. 5. A dose related increase in nasal secretion harvested by the nasal lavage in 10 persons challenged with histamine chloride could be demonstrated by this technique. 6. It is concluded that the use of 99mTc-albumin in a nasal washing provides a safe, simple and quick...

  6. Secrets of over-indebted people

    Directory of Open Access Journals (Sweden)

    Valérie BILLAUDEAU

    2013-12-01

    Full Text Available Today, the economic and financial crisis is brought to light and it is now clear that many people are directly impacted by this phenomenon. However, a lot of situations are obviously hidden and in particular those concerning over-indebted people. These people often find that it is difficult to express the hardship they are going through and keep silent because is more comfortable for them. The media also does not tackle this burning issue because the complexity of some situations complicates the message. Therefore, a giant gap has appeared leaving over-indebted people entrapped in their secret. Starting from this hypothesis, this article will examine the results of a research conducted on the over-indebted people (survey on written press, analysis of TV broadcasts, analysis of records related to person in debts and responses of people in debts and the secrets that this phenomenon involves.

  7. Quantum Secret Sharing with Error Correction

    Institute of Scientific and Technical Information of China (English)

    Aziz Mouzali; Fatiha Merazka; Damian Markham

    2012-01-01

    We investigate in this work a quantum error correction on a five-qubits graph state used for secret sharing through five noisy channels. We describe the procedure for the five, seven and nine qubits codes. It is known that the three codes always allow error recovery if only one among the sent qubits is disturbed in the transmitting channel. However, if two qubits and more are disturbed, then the correction will depend on the used code. We compare in this paper the three codes by computing the average fidelity between the sent secret and that measured by the receivers. We will treat the case where, at most, two qubits are affected in each one of five depolarizing channels.

  8. Apical secretion of apolipoproteins from enterocytes

    DEFF Research Database (Denmark)

    Danielsen, E M; Hansen, Gert Helge; Poulsen, Mona Dam

    1993-01-01

    Synthesis and secretion of apolipoproteins in pig small intestine was studied by pulse-chase labeling of jejunal segments, kept in organ culture. Apo A-1 and apo B-48 were the two major proteins released, constituting 25 and 10%, respectively, of the total amount of labeled protein in the mucosal...... that enterocytes release most of their newly made free apo A-1 and a significant portion of apo B-48 by exocytosis via the brush border membrane into the intestinal lumen. Fat absorption reduced apolipoprotein secretion to the medium and induced the formation of chylomicrons, containing apo A-1 at their surface......-side medium where they appeared with a t1/2 of 50-60 min. Using tissue from fasting animals, > 85% of newly synthesized apo A-1 and about one third of apo B-48 was released to the mucosal-side medium. Newly synthesized apolipoprotein that remained associated with the intestinal segment accumulated...

  9. Visual Secret Sharing Based Digital Image Watermarking

    Directory of Open Access Journals (Sweden)

    B. Surekha

    2012-05-01

    Full Text Available In this paper, a spatial domain image watermarking technique based on Visual Secret Sharing (VSS and unique statistical properties is proposed. A random looking image is generated during watermark hiding process and is secretly registered with an arbitrator for verification during conflicts. Another random looking image is generated during watermark revelation stage and is combined with the existing one, to recover the watermark. This whole process is done without altering the image to be protected and hence the quality of the cover image is high. When compared with similar existing techniques, the proposed technique has three main advantages: Provides greater convenience in carrying and storing the intermediate images called shares; Provides high security; Reduce tradeoff between spatial and frequency domain techniques in terms of robustness

  10. The SNARE machinery in mast cell secretion

    Directory of Open Access Journals (Sweden)

    Axel eLorentz

    2012-06-01

    Full Text Available Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators – stored in granules – as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-Sensitive Factor (NSF Attachment Protein (SNAP Receptors (SNARE proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, SCAMPs, complexins or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

  11. Charting Secrets Stop Reading Start Practicing

    CERN Document Server

    Bedford, Louise

    2012-01-01

    It is a common myth that the sharemarket is a fast ticket to the easy life. Buy a few shares and watch them go up. Call your broker for up-to-the-minute price information as you drive the Porsche to the golf club. Yell 'Sell! Sell! Sell' into your mobile as you ski through the Swiss Alps. Nothing could be further from the truth. Louise Bedford believes that the only way to be successful in the market is to spend time studying and putting in the hard work, just like any other job. With this in mind, she has written Charting Secrets. Not just another trading book, Charting Secrets is a workbook

  12. [The symbolic power of bodily secretions].

    Science.gov (United States)

    Isaksen, Lise Widding

    2002-01-10

    Are ethical and political questions discussed more in aesthetic than in social terms? Political debates in contemporary art are often expressed through the use of symbolic power structures that are related to bodily secretions and products. By visualizing the less delicate parts of the organic body, contemporary artists focus on the vulnerability of the human body and its illness and pain. If human suffering is aestheticized: is this a question of form or a question of creating a cultural cover-up? Bodily secretions are associated with a range of complex social and cultural meanings and symbols. Metaphors related to body products may function as markers of ethnic, religious, social and sexual differences. In postmodern cultural criticism, the symbolic power of body metaphors is of great importance.

  13. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2015-12-01

    Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

  14. Information Theoretic Secret Key Generation: Structured Codes and Tree Packing

    Science.gov (United States)

    Nitinawarat, Sirin

    2010-01-01

    This dissertation deals with a multiterminal source model for secret key generation by multiple network terminals with prior and privileged access to a set of correlated signals complemented by public discussion among themselves. Emphasis is placed on a characterization of secret key capacity, i.e., the largest rate of an achievable secret key,…

  15. Hoopoes color their eggs with antimicrobial uropygial secretions

    Science.gov (United States)

    Soler, Juan J.; Martín-Vivaldi, M.; Peralta-Sánchez, J. M.; Arco, L.; Juárez-García-Pelayo, N.

    2014-09-01

    Uropygial gland secretions are used as cosmetics by some species of birds to color and enhance properties of feathers and teguments, which may signal individual quality. Uropygial secretions also reach eggshells during incubation and, therefore, may influence the coloration of birds' eggs, a trait that has attracted the attention of evolutionary biologists for more than one century. The color of hoopoe eggs typically changes along incubation, from bluish-gray to greenish-brown. Here, we test experimentally the hypothesis that dark uropygial secretion of females is responsible for such drastic color change. Moreover, since uropygial secretion of hoopoes has antimicrobial properties, we also explore the association between color and antimicrobial activity of the uropygial secretion of females. We found that eggs stayed bluish-gray in nests where female access to the uropygial secretion was experimentally blocked. Furthermore, experimental eggs that were maintained in incubators and manually smeared with uropygial secretion experienced similar color changes that naturally incubated eggs did, while control eggs that were not in contact with the secretions did not experience such color changes. All these results strongly support the hypothesis that female hoopoes use their uropygial gland secretion to color the eggs. Moreover, saturation of the uropygial secretion was associated with antimicrobial activity against Bacillus licheniformis. Given the known antimicrobial potential of uropygial secretions of birds, this finding opens the possibility that in scenarios of sexual selection, hoopoes in particular and birds in general signal antimicrobial properties of their uropygial secretion by mean of changes in egg coloration along incubation.

  16. 10 CFR 1016.34 - Accountability for Secret Restricted Data.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall...

  17. Gastric Lipase Secretion in Children with Gastritis

    OpenAIRE

    Krystyna Sztefko; Krzysztof Fyderek; Andrzej Zając; Andrzej Wędrychowicz; Iwona Rogatko; Tomasik, Przemyslaw J

    2013-01-01

    Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), ...

  18. Mucin secretion induced by titanium dioxide nanoparticles.

    Directory of Open Access Journals (Sweden)

    Eric Y T Chen

    Full Text Available Nanoparticle (NP exposure has been closely associated with the exacerbation and pathophysiology of many respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD and asthma. Mucus hypersecretion and accumulation in the airway are major clinical manifestations commonly found in these diseases. Among a broad spectrum of NPs, titanium dioxide (TiO(2, one of the PM10 components, is widely utilized in the nanoindustry for manufacturing and processing of various commercial products. Although TiO(2 NPs have been shown to induce cellular nanotoxicity and emphysema-like symptoms, whether TiO(2 NPs can directly induce mucus secretion from airway cells is currently unknown. Herein, we showed that TiO(2 NPs (<75 nm can directly stimulate mucin secretion from human bronchial ChaGo-K1 epithelial cells via a Ca(2+ signaling mediated pathway. The amount of mucin secreted was quantified with enzyme-linked lectin assay (ELLA. The corresponding changes in cytosolic Ca(2+ concentration were monitored with Rhod-2, a fluorescent Ca(2+ dye. We found that TiO(2 NP-evoked mucin secretion was a function of increasing intracellular Ca(2+ concentration resulting from an extracellular Ca(2+ influx via membrane Ca(2+ channels and cytosolic ER Ca(2+ release. The calcium-induced calcium release (CICR mechanism played a major role in further amplifying the intracellular Ca(2+ signal and in sustaining a cytosolic Ca(2+ increase. This study provides a potential mechanistic link between airborne NPs and the pathoetiology of pulmonary diseases involving mucus hypersecretion.

  19. Eosinophil secretion of granule-derived cytokines

    Directory of Open Access Journals (Sweden)

    Lisa A Spencer

    2014-10-01

    Full Text Available Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include: classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines.

  20. A new scheme for quantum secret sharing

    CERN Document Server

    Bagherinezhad, S; Bagherinezhad, Saber; Karimipour, Vahid

    2002-01-01

    We introduce a protocol for quantum secret sharing based on reusable entangled states. The entangled state between the sender and the receiver acts only as a carrier and no measurement is performed on this shared state. Half of the sequence of bits can be retrieved independently and for the other half the receivers need each other's assistance. We also show that the protocol is completely safe against eavesdropping.

  1. ACTH-Secreting Pheochromocytoma. Case report

    Directory of Open Access Journals (Sweden)

    N S Kuznetsov

    2012-12-01

    Full Text Available Ectopic hormone-secreting pheochromocytomas are rare. Only case reports exist in the literature. Despite the large number of guides on diagnosis and treatment of pheochromocytoma, and Cushing syndrome, the extreme rarity of ectopic ACTH-syndrome caused by pheochromocytoma, and complexity of clinical cause numerous diagnostic errors leading to treatment failure. Therefore, we belive it appropriate to share our experience of this group of patients.

  2. Hiding secret data into a carrier image

    OpenAIRE

    Ovidiu COSMA

    2012-01-01

    The object of steganography is embedding hidden information in an appropriate multimedia carrier, e.g., image, audio, or video. There are several known methods of solving this problem, which operate either in the space domain or in the frequency domain, and are distinguished by the following characteristics: payload, robustness and strength. The payload is the amount of secret data that can be embedded in the carrier without inducing suspicious artefacts, robustness indicates the degree in wh...

  3. George's secret key to the universe

    CERN Document Server

    Hawking, Lucy; Galfard, Christophe; Parsons, Gary

    2007-01-01

    In their bestselling book for young readers, noted physicist Stephen Hawking and his daughter, Lucy, provide a grand and funny adventure that explains fascinating information about our universe, including Dr. Hawking's latest ideas about black holes. It's the story of George, who's taken through the vastness of space by a scientist, his daughter, and their super-computer named Cosmos. George's Secret Key to the Universe was a New York Times bestseller and a selection of Al's Book Club on the Today show.

  4. Activated microglia enhance neurogenesis via trypsinogen secretion.

    Science.gov (United States)

    Nikolakopoulou, Angeliki M; Dutta, Ranjan; Chen, Zhihong; Miller, Robert H; Trapp, Bruce D

    2013-05-21

    White matter neurons in multiple sclerosis brains are destroyed during demyelination and then replaced in some chronic multiple sclerosis lesions that exhibit a morphologically distinct population of activated microglia [Chang A, et al. (2008) Brain 131(Pt 9):2366-2375]. Here we investigated whether activated microglia secrete factors that promote the generation of neurons from white matter cells. Adult rat brain microglia (resting or activated with lipopolysaccharide) were isolated by flow cytometry and cocultured with neonatal rat optic nerve cells in separate but media-connected chambers. Optic nerve cells cocultured with activated microglia showed a significant increase in the number of cells of neuronal phenotype, identified by neuron-specific class III beta-tubulin (TUJ-1) labeling, compared with cultures with resting microglia. To investigate the possible source of the TUJ-1-positive cells, A2B5-positive oligodendrocyte progenitor cells and A2B5-negative cells were isolated and cocultured with resting and activated microglia. Significantly more TUJ-1-positive cells were generated from A2B5-negative cells (∼70%) than from A2B5-positive cells (~30%). Mass spectrometry analysis of microglia culture media identified protease serine 2 (PRSS2) as a factor secreted by activated, but not resting, microglia. When added to optic nerve cultures, PRSS2 significantly increased neurogenesis, whereas the serine protease inhibitor, secretory leukocyte protease inhibitor, decreased activated microglia-induced neurogenesis. Collectively our data provide evidence that activated microglia increase neurogenesis through secretion of PRSS2.

  5. Secret Sharing of a Quantum State.

    Science.gov (United States)

    Lu, He; Zhang, Zhen; Chen, Luo-Kan; Li, Zheng-Da; Liu, Chang; Li, Li; Liu, Nai-Le; Ma, Xiongfeng; Chen, Yu-Ao; Pan, Jian-Wei

    2016-07-15

    Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

  6. Dragon's blood secretion and its ecological significance.

    Science.gov (United States)

    Jura-Morawiec, Joanna; Tulik, Mirela

    Dragon's blood is the name given to a red exudate produced by some plant species belonging to the genera Daemonorops, Dracaena, Croton and Pterocarpus. These are endemic to various parts of the globe. It is classified as a resin or latex depending on its mode of secretion and its chemical composition, which is species specific. This red substance functions in defence and is produced (a) constitutively and stored in preformed anatomical structures, or (b) by induction in response to traumatic events, such as mechanical injury, pathogen attack or invasion by insects. Apart from its defensive role in plants, dragon's blood is also a valuable natural resource renowned since antiquity for its diverse medicinal properties and uses in art. Despite the great importance of dragon's blood, our knowledge of the biological basis for its secretion is still incomplete. This review summarizes recent advances in the study of the anatomical basis for its secretion, and discusses its classification and ecological function. Bringing some clarity to these issues may also help in the commercial sourcing of dragon's blood.

  7. Effects of ZnO addition on mechanical properties of Bi{sub 1.84}Pb{sub 0.34}Sr{sub 1.91}Ca{sub 2.03}Cu{sub 3.06}O{sub 10} prepared by a wet technique

    Energy Technology Data Exchange (ETDEWEB)

    Karaca, I. [Department of Physics, Faculty of Science and Arts, Nigde University, 51200 Nigde (Turkey)], E-mail: ikaraca38@hotmail.com; Uzun, O.; Koelemen, U.; Yilmaz, F. [Department of Physics, Faculty of Science and Arts, Gaziosmanpasa University, 60240 Tokat (Turkey); Sahin, O. [Department of Physics, Faculty of Science and Arts, Mustafa Kemal University, 31034 Hatay (Turkey)

    2009-05-12

    In this study, ZnO molar wt% 0, 5, 10, 20, 30, and 50 added Bi{sub 1.84}Pb{sub 0.34}Sr{sub 1.91}Ca{sub 2.03}Cu{sub 3.06}O{sub 10} superconductors were prepared by wet technique. The experimental works consist of powder X-ray diffraction (XRD) for phase analyses and c-axes parameters, scanning electron microscopy (SEM) for microstructure examination, and microhardness measurements for mechanical properties. These measurements showed that Zn-added material, in comparison with the pure sample, had increased c-axes parameters and decreased grain size. In addition, the experimental results of microhardness measurements were analyzed using Oliver-Pharr model. It was observed that the change of indentation hardness (H{sub IT}) and reduced elastic modulus (E{sub r}) values showed an increasing trend with ZnO addition and exhibited peak load dependence (i.e., indentation size effect (ISE))

  8. 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)

  9. Advanced Steganography Algorithm using Encrypted secret message

    Directory of Open Access Journals (Sweden)

    Joyshree Nath

    2011-03-01

    Full Text Available In the present work the authors have introduced a new method for hiding any encrypted secret message inside a cover file. For encrypting secret message the authors have used new algorithm proposed by Nath et al(1. For hiding secret message we have used a method proposed by Nath et al(2. In MSA(1 method we have modified the idea of Play fair method into a new platform where we can encrypt or decrypt any file. We have introduced a new randomization method for generating the randomized key matrix to encrypt plain text file and to decrypt cipher text file. We have also introduced a new algorithm for encrypting the plain text multiple times. Our method is totally dependent on the random text_key which is to be supplied by the user. The maximum length of the text_key can be of 16 characters long and it may contain any character(ASCII code 0 to 255. We have developed an algorithm to calculate the randomization number and the encryption number from the given text_key. The size of the encryption key matrix is 16x16 and the total number of matrices can be formed from 16 x 16 is 256! which is quite large and hence if someone applies the brute force method then he/she has to give trail for 256! times which is quite absurd. Moreover the multiple encryption method makes the system further secured. For hiding secret message in the cover file we have inserted the 8 bits of each character of encrypted message file in 8 consecutive bytes of the cover file. We have introduced password for hiding data in the cover file. We propose that our new method could be most appropriate for hiding any file in any standard cover file such as image, audio, video files. Because the hidden message is encrypted hence it will be almost impossible for the intruder to unhide the actual secret message from the embedded cover file. This method may be the most secured method in digital water marking.

  10. Adopting Frank Warren's PostSecret Art Project to Illustrate the Role of Secrets in Interpersonal Communication

    Science.gov (United States)

    Paxman, Christina G.

    2013-01-01

    The exploration of secrets summons the adage that ''what someone doesn't know won't hurt them.'' While this phrase implies that keeping secrets can be advantageous, it also foreshadows another consideration: secrets have the propensity to hurt others (Caughlin, Scott, Miller, & Hefner, 2009). Despite this, the act…

  11. EFFECTS OF SECRETABLE PLACENTAL FACTORS UPON SECRETION OF CYTOKINES BY THP-1 MONOCYTE-LIKE CELLS

    Directory of Open Access Journals (Sweden)

    Ya. S. Onokhina

    2013-01-01

    Full Text Available Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.The work is supported by grants ГК № 02.740.11.0711 from Ministry of Education and Science, and НШ-3594.2010.7 grant from the President of Russian Federation.

  12. Constructions for Anonymous Secret Sharing Schemes Using Combinatorial Designs

    Institute of Scientific and Technical Information of China (English)

    Ying-pu Deng; Li-feng Guo; Mu-lan Liu

    2007-01-01

    In an anonymous secret sharing scheme the secret can be reconstructed without knowledge of which participants hold which shares. In this paper some constructions of anonymous secret sharing schemes with 2 thresholds by using combinatorial designs are given. Let υ(t, ω, q) denote the minimum size of the set of shares of a perfect anonymous (t, ω) threshold secret sharing scheme with q secrets. In this paper we prove that υ(t, ω, q) = Θ(q) if t and ω are fixed and that the lower bound of the size of the set of shares in [4] is not optimal under certain condition.

  13. Shift visual cryptography scheme of two secret images

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A new visual cryptography scheme of two secret images, which is named the shift visual cryptography of two secret images, is given. The compound function family of a general construction model is also introduced. The uniqueness and validity of this model are proved, and the minimum rows and columns for realizing the scheme are obtained. Compared with visual cryptography of one secret image, the shift visual cryptography scheme can share two secret images with the same size of pixels expansion without losing the contrast. It has randomness and various forms, and furthermore, we can also visually recover two secret images even if the two shares are different in form and color.

  14. Verifiable Quantum ( k, n)-threshold Secret Key Sharing

    Science.gov (United States)

    Yang, Yu-Guang; Teng, Yi-Wei; Chai, Hai-Ping; Wen, Qiao-Yan

    2011-03-01

    Based on Lagrange interpolation formula and the post-verification mechanism, we show how to construct a verifiable quantum ( k, n) threshold secret key sharing scheme. Compared with the previous secret sharing protocols, ours has the merits: (i) it can resist the fraud of the dealer who generates and distributes fake shares among the participants during the secret distribution phase; Most importantly, (ii) It can check the cheating of the dishonest participant who provides a false share during the secret reconstruction phase such that the authorized group cannot recover the correct secret.

  15. The role of jasmonates in floral nectar secretion.

    Directory of Open Access Journals (Sweden)

    Venkatesan Radhika

    Full Text Available Plants produce nectar in their flowers as a reward for their pollinators and most of our crops depend on insect pollination, but little is known on the physiological control of nectar secretion. Jasmonates are well-known for their effects on senescence, the development and opening of flowers and on plant defences such as extrafloral nectar. Their role in floral nectar secretion has, however, not been explored so far. We investigated whether jasmonates have an influence on floral nectar secretion in oil-seed rape, Brassica napus. The floral tissues of this plant produced jasmonic acid (JA endogenously, and JA concentrations peaked shortly before nectar secretion was highest. Exogenous application of JA to flowers induced nectar secretion, which was suppressed by treatment with phenidone, an inhibitor of JA synthesis. This effect could be reversed by additional application of JA. Jasmonoyl-isoleucine and its structural mimic coronalon also increased nectar secretion. Herbivory or addition of JA to the leaves did not have an effect on floral nectar secretion, demonstrating a functional separation of systemic defence signalling from reproductive nectar secretion. Jasmonates, which have been intensively studied in the context of herbivore defences and flower development, have a profound effect on floral nectar secretion and, thus, pollination efficiency in B. napus. Our results link floral nectar secretion to jasmonate signalling and thereby integrate the floral nectar secretion into the complex network of oxylipid-mediated developmental processes of plants.

  16. Reelin secreted by GABAergic neurons regulates glutamate receptor homeostasis.

    Directory of Open Access Journals (Sweden)

    Cecilia Gonzalez Campo

    Full Text Available BACKGROUND: Reelin is a large secreted protein of the extracellular matrix that has been proposed to participate to the etiology of schizophrenia. During development, reelin is crucial for the correct cytoarchitecture of laminated brain structures and is produced by a subset of neurons named Cajal-Retzius. After birth, most of these cells degenerate and reelin expression persists in postnatal and adult brain. The phenotype of neurons that bind secreted reelin and whether the continuous secretion of reelin is required for physiological functions at postnatal stages remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Combining immunocytochemical and pharmacological approaches, we first report that two distinct patterns of reelin expression are present in cultured hippocampal neurons. We show that in hippocampal cultures, reelin is secreted by GABAergic neurons displaying an intense reelin immunoreactivity (IR. We demonstrate that secreted reelin binds to receptors of the lipoprotein family on neurons with a punctate reelin IR. Secondly, using calcium imaging techniques, we examined the physiological consequences of reelin secretion blockade. Blocking protein secretion rapidly and reversibly changes the subunit composition of N-methyl-D-aspartate glutamate receptors (NMDARs to a predominance of NR2B-containing NMDARs. Addition of recombinant or endogenously secreted reelin rescues the effects of protein secretion blockade and reverts the fraction of NR2B-containing NMDARs to control levels. Therefore, the continuous secretion of reelin is necessary to control the subunit composition of NMDARs in hippocampal neurons. CONCLUSIONS/SIGNIFICANCE: Our data show that the heterogeneity of reelin immunoreactivity correlates with distinct functional populations: neurons synthesizing and secreting reelin and/or neurons binding reelin. Furthermore, we show that continuous reelin secretion is a strict requirement to maintain the composition of NMDARs. We propose

  17. Secret Objective Standoff: International Safeguards Educational Exercise

    Energy Technology Data Exchange (ETDEWEB)

    Okowita, Samantha L [ORNL

    2014-01-01

    The International Safeguards Regime, being so multi-faceted, can be overwhelming to those first introduced to its many components. The organizers and lecturers of workshops and courses on nonproliferation often provide a series of independent lectures and must somehow demonstrate the cohesive and effective nature of the system. An exercise titled The Secret Objective Standoff was developed to complement lectures with hands-on learning to assist participants in bringing all the many components (IAEA agreements, export controls, treaty obligations, international diplomacy, etc.) of the International Safeguards Regime together. This exercise divides participants into teams that are assigned the role of either a country or the IAEA and asks that they fully immerse themselves in their roles. The teams are then randomly assigned three unique and secret objectives that are intended to represent realistic and current geopolitical scenarios. Through construction, trading, or hoarding of four resources (experts, technology, money, and uranium), the teams have a finite number of turns to accomplish their objectives. Each turn has three phases random dispersal of resources, a timed discussion where teams can coordinate and strategize with others, and an action phase. During the action phase, teams inform the moderator individually and secretly what they will be doing that turn. The exercise has been tested twice with Oak Ridge National Laboratory personnel, and has been conducted with outside participants twice, in each case the experience was well received by both participants and instructors. This exercise provides instructors the ability to modify the exercise before or during game play to best fit their educational goals. By offering a range of experiences, from an in-depth look at specific components to a generalized overview, this exercise is an effective tool in helping participants achieve a full understanding the International Safeguards Regime.

  18. 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

  19. 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

  20. Secret neutrino interactions: a pseudoscalar model

    Science.gov (United States)

    Archidiacono, Maria; Hannestad, Steen; Sloth Hansen, Rasmus; Tram, Thomas

    2016-05-01

    Neutrino oscillation experiments point towards the existence of additional mostly sterile neutrino mass eigenstates in the eV mass range. At the same time, such sterile neutrinos are disfavoured by cosmology (Big Bang Nucleosynthesis, Cosmic Microwave Background and Large Scale Structure), unless they can be prevented from being thermalised in the early Universe. To this aim, we introduce a model of sterile neutrino secret interactions mediated by a new light pseudoscalar: The new interactions can accomodate sterile neutrinos in the early Universe, providing a good fit to all the up to date cosmological data.

  1. Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

    Science.gov (United States)

    Komaba, Hirotaka; Nakanishi, Shohei; Fujimori, Akira; Tanaka, Motoko; Shin, Jeongsoo; Shibuya, Koji; Nishioka, Masato; Hasegawa, Hirohito; Kurosawa, Takeshi

    2010-01-01

    Background and objectives: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume. Design, setting, participants, & measurements: This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH 30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n = 87) where parathyroid gland volume progressively increased with traditional therapy alone. Conclusions: Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia. PMID:20798251

  2. Testosterone and dihydrotestosterone concentrations in elephant serum and temporal gland secretions.

    Science.gov (United States)

    Rasmussen, L E; Buss, I O; Hess, D L; Schmidt, M J

    1984-03-01

    Serum and temporal gland secretions (TGS) were obtained from mature wild African (Loxodonta africana) and captive Asian elephants (Elephas maximus). Samples were obtained from five cows and eight bulls culled for management purposes in Kruger National Park, South Africa, and from four females and two males residing at the Washington Park Zoo, Portland, Oregon. Our purpose was to describe the levels of the androgens, testosterone (T), and dihydrotestosterone (DHT), and to correlate these observations with sex, species and behavioral status. Male-female differences in serum T were pronounced in the Asian species, whereas male and female concentrations overlapped in the African elephant serum. Serum T concentrations in African females were greater than in Asian females. Serum DHT reflected T levels, except that the striking elevation of testosterone in Asian bulls during musth was not paralleled by equal increases in DHT levels. A species difference observed among males was higher serum T levels in nonmusth Asian bulls (1.84-5.35 ng/ml) compared to the levels in African bulls (0.38-0.68 ng/ml), except for one dominant African bull (6.64 ng/ml). This single African value was still considerably lower than the serum T values of the Asian males during musth. These musth values were the highest serum androgen concentrations: T was between 19 and 40 ng/ml (average 26.10 ng/ml). The TSG values of T and DHT were much higher than serum levels except in the Asian female. T/DHT ratios in TGS were more similar than in serum. One dominant African bull had a T TGS value of 78 ng/ml, which was much higher than the rest of the African males or females, but considerably lower than as Asian bull in musth (547 ng/ml). It seems apparent that a change in androgen status as reflected in serum and TGS levels of T and DHT precedes or is concomitant with overt alteration in behavior in the Asian male. The temporal gland appears to actively concentrate androgens in both African males and

  3. Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Werb, Z.; Aggeler, J.

    1978-04-01

    We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 6/ cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continued presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, ..cap alpha../sub 1/-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.

  4. Gastric Lipase Secretion in Children with Gastritis

    Directory of Open Access Journals (Sweden)

    Krystyna Sztefko

    2013-07-01

    Full Text Available Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10, the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14 and the control group including healthy adolescents (n = 14. Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK, glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic peptide (GIP were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005 and the control group (p < 0.005. Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003 and the HPG group (p < 0.01. We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

  5. Dopamine-Secreting Paraganglioma in the Retroperitoneum.

    Science.gov (United States)

    Matsuda, Yusuke; Kimura, Noriko; Yoshimoto, Takanobu; Sekiguchi, Yoshihiro; Tomoishi, Junzo; Kasahara, Ichiro; Hara, Yoshihito; Ogawa, Yoshihiro

    2017-03-01

    Pheochromocytomas and paragangliomas, which exclusively produce dopamine, are very rare. Herein, we report for the first time a Japanese case of an exclusively dopamine-producing paraganglioma accompanied by detailed immunohistochemical analyses. A 70-year-old Japanese woman was referred to our hospital for functional examination of her left retroperitoneal mass. Her adrenal functions were normal, except for excessive dopamine secretion. After the tumorectomy, her dopamine level normalized. The histopathological diagnosis of the tumor was paraganglioma; this was confirmed by positive immunostaining of chromogranin A (CgA), tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), and succinate dehydrogenase gene subunit B (SDHB). However, the immunostaining of CgA in the tumor cells showed peculiar dot-like staining located corresponding to Golgi complex in the perinuclear area, rather than the diffuse cytoplasmic staining usually observed in epinephrine- or norepinephrine-producing functional pheochromocytomas and paragangliomas. The immunohistochemical results suggested that the tumor cells had sparse neuroendocrine granules in the cytoplasm, resulting in inhibition of catecholamine synthesis from dopamine to norepinephrine in neurosecretory granules. This may be the mechanism responsible for exclusive dopamine secretion in the present case.

  6. Role of potassium in acid secretion

    Institute of Scientific and Technical Information of China (English)

    John P Geibel

    2005-01-01

    Potassium (K+) ions are critical for the activation and catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of hydrochloric acid into the parietal cell canaliculus. As both symptom, severity and esophageal mucosal damage in gastro-esophageal reflux disease (GERD) are related to the degree of acid exposure, K+ is a logical target for approaches to inhibit acid production.The probable K+ binding site on the gastric H+,K+-ATPase has recently been described and studies are elucidating how K+ activates the enzyme. K+ channels in the apical membrane of the parietal cell are implicated in the recycling of K+ and, to date, three potential K+ channels (KCNQ1, Kir2.1 and Kir4.1) have been identified. The channels represent theoretical sites for agents to control acid secretion but it will be difficult to develop selective blockers. An alternative strategy is to prevent K+ from activating gastric H+,K+-ATPase; the potassiumcompetitive acid blocker (P-CAB) class inhibits acidsecretion by binding at or near the K+ binding site.Ongoing research is further defining the role of K+ in the functioning of the gastric H+,K+-ATPase, as well as determining the clinical utility of agents directed toward this important cation.

  7. Secrets Pages in DR’s Playbook

    DEFF Research Database (Denmark)

    Nielsen, Jakob Isak

    According to former Head of Drama at DR, Ingolf Gabold, one of the “great” and “strange” secrets subtending the success of DR’s TV series is the extremely deliberate work with audiovisual style (Gabold in Nielsen 2012). Here - as elsewhere - Gabold highlights the so-called “paramount-meeting” and......According to former Head of Drama at DR, Ingolf Gabold, one of the “great” and “strange” secrets subtending the success of DR’s TV series is the extremely deliberate work with audiovisual style (Gabold in Nielsen 2012). Here - as elsewhere - Gabold highlights the so-called “paramount...... aspect of DR’s productions by interviewing both management and creative personnel) this paper will discuss the causal mechanisms that subtend the development of audiovisual style in DR series from Gøngehøvdingen to 1864 and will conclude with reflections on the role of DR-series’ style in the age...

  8. Weapons of Mass Secretion : The Type III Secretion System of Shigella flexneri

    NARCIS (Netherlands)

    Sani, Musa

    2007-01-01

    In bacteria that are pathogenic for animals, type III secretion systems allow extracellular bacteria adhering to the surface of a host cell to inject specialized proteins across the plasma membrane. The injected proteins subvert the functioning of the aggressed cell or destroy its communications, fa

  9. Trade Secret Law and Information Systems: Can Your Students Keep a Secret?

    Science.gov (United States)

    Willey, Lorrie; Ford, Janet C.; White, Barbara Jo; Clapper, Danial L.

    2011-01-01

    The impact of intellectual property (IP) law on information systems (IS) professionals in business cannot be overstated. The IS 2010 model curriculum guidelines for undergraduate IS programs stress the importance of information security and knowledge about IP. While copyright and patents are the most well-known types of IP, another, trade secrets,…

  10. Weapons of Mass Secretion : The Type III Secretion System of Shigella flexneri

    NARCIS (Netherlands)

    Sani, Musa

    2007-01-01

    In bacteria that are pathogenic for animals, type III secretion systems allow extracellular bacteria adhering to the surface of a host cell to inject specialized proteins across the plasma membrane. The injected proteins subvert the functioning of the aggressed cell or destroy its communications,

  11. Trade Secret Law and Information Systems: Can Your Students Keep a Secret?

    Science.gov (United States)

    Willey, Lorrie; Ford, Janet C.; White, Barbara Jo; Clapper, Danial L.

    2011-01-01

    The impact of intellectual property (IP) law on information systems (IS) professionals in business cannot be overstated. The IS 2010 model curriculum guidelines for undergraduate IS programs stress the importance of information security and knowledge about IP. While copyright and patents are the most well-known types of IP, another, trade secrets,…

  12. Inhibition of gastric secretion by omeprazole and efficiency of calcium carbonate on the control of hyperphosphatemia in patients on chronic hemodialysis.

    Science.gov (United States)

    Hardy, P; Sechet, A; Hottelart, C; Oprisiu, R; Abighanem, O; Said, S; Rasombololona, M; Brazier, M; Moriniere, P; Achard, J M; Pruna, A; Fournier, A

    1998-07-01

    Contradictions exist in the literature regarding the effect of gastric secretion inhibition on phosphate absorption. In healthy controls, omeprazole would decrease the hyperphosphatemia or the hyperphosphaturia induced by an acute phosphate load, suggesting an inhibition of phosphate absorption. In chronic hemodialysis patients, gastric hypersecretion is associated with hyperphosphatemia, but inhibition of gastric hypersecretion by ranitidine in those receiving calcium carbonate (CaCO3) as a phosphate binder would paradoxically exacerbate their hyperphosphatemia. Because of these conflicting observations, we performed an open crossover study on 16 chronic stable hemodialyzed patients with a daily mean intake of 9.4+/-4 g of CaCO3, and we compared the plasmatic predialysis levels of phosphate, calcium, protides, bicarbonates, intact parathyroid hormone (PTH), urea, and creatininemia during 2 successive periods of 2 months, the first one without omeprazole and the second one with 20 mg omeprazole intake in the morning. Phosphatemia increased with omeprazole but not significantly from 1.80+/-0.38 to 1.89+/-0.42 mM whereas corrected calcemia decreased significantly (p = 0.04) from 2.41+/-0.18 to 2.36+/-0.16 mM as did bicarbonatemia from 26.7+/-3.5 to 25.7+/-3.1 mM (p omeprazole increases the plasmatic phosphate predialytic level but in a nonsignificant way. This increase may be explained by a slight but significant concomitant decrease of calcemia and bicarbonatemia. These results do not support the phosphate binding efficiency of CaCO3 being decreased by the inhibition of gastric acid secretion.

  13. 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.

  14. 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.

  15. Secret Key Generation for a Pairwise Independent Network Model

    CERN Document Server

    Nitinawarat, Sirin; Barg, Alexander; Narayan, Prakash; Reznik, Alex

    2010-01-01

    We consider secret key generation for a "pairwise independent network" model in which every pair of terminals observes correlated sources that are independent of sources observed by all other pairs of terminals. The terminals are then allowed to communicate publicly with all such communication being observed by all the terminals. The objective is to generate a secret key shared by a given subset of terminals at the largest rate possible, with the cooperation of any remaining terminals. Secrecy is required from an eavesdropper that has access to the public interterminal communication. A (single-letter) formula for secret key capacity brings out a natural connection between the problem of secret key generation and a combinatorial problem of maximal packing of Steiner trees in an associated multigraph. An explicit algorithm is proposed for secret key generation based on a maximal packing of Steiner trees in a multigraph; the corresponding maximum rate of Steiner tree packing is thus a lower bound for the secret ...

  16. Evaluation of the effects of quercetin on damaged salivary secretion.

    Directory of Open Access Journals (Sweden)

    Ayako Takahashi

    Full Text Available With the aim of discovering an effective method to treat dry mouth, we analyzed the effects of quercetin on salivary secretion and its mechanism of action. We created a mouse model with impaired salivary secretion by exposure to radiation and found that impaired secretion is suppressed by quercetin intake. Moreover, secretion levels were enhanced in quercetin-fed normal mice. To elucidate the mechanisms of these effects on salivary secretion, we conducted an analysis using mouse submandibular gland tissues, a human salivary gland epithelial cell line (HSY, and mouse aortic endothelial cells (MAECs. The results showed that quercetin augments aquaporin 5 (AQP5 expression and calcium uptake, and suppresses oxidative stress and inflammatory responses induced by radiation exposure, suggesting that quercetin intake may be an effective method to treat impaired salivary secretion.

  17. Threshold Quantum Secret Sharing of Secure Direct Communication

    Institute of Scientific and Technical Information of China (English)

    LI Bao-Kui; YANG Yu-Guang; WEN Qiao-Yan

    2009-01-01

    We propose a (t, n)-threshold quantum secret sharing protocol of secure direct communication following some ideas of Zhang's protocol [Phys. Lett. A 342 (2005) 60] and Tokunaga et al.'s protocol [Phys. Rev. A 71 (2005) 012314]. The sender distributes the classical secret shares to his or her n agents and each agent owns a secret share in advance. The sender's secure direct communication message can be extracted by an agent subset by collaboration in such a way that at least t or more agents can obtain the secret message with the mutual assistances but any t - 1 or fewer agents cannot. In contrast to the previous multiparty quantum secret sharing protocols in which the sender's secret message can be recovered only if all the agents collaborate, our protocol is more practical and more flexible.

  18. Special secret sharing scheme with the function of assignment

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A concept of secret sharing scheme with the function of assignment is proposed. It provides great capabilities for many practical applications. In this scheme, the dealer can randomly assign one or more than one participant to get the secret at any time, but these participants can get nothing about the secret before that moment. At the same time, the other participants cannot get any-thing about the secret by stealing the secret value when it is transferred. However, if the dealer is lost, a certain number or more participants of them can reconstruct the secret by cooperating. In order to clear this concept, an illustrating scheme with geometry method and a practical scheme with algebra method is given.

  19. Short-term regulation of adiponectin secretion in rat adipocytes.

    Science.gov (United States)

    Szkudelski, T; Nogowski, L; Szkudelska, K

    2011-01-01

    Adiponectin belongs to the group of biologically active substances secreted by adipocytes and referred to as adipokines. Disturbances in its secretion and/or action are thought to be involved in the pathogenesis of some metabolic diseases. However, regulation of adiponectin secretion is poorly elucidated. In the present study, short-term regulation of adiponectin secretion in primary rat adipocytes was investigated. Isolated rat adipocytes were incubated in Krebs-Ringer buffer containing 5 mM glucose and insulin alone or in the combination with epinephrine, dibutyryl-cAMP, adenosine A(1) receptor antagonist (DPCPX), palmitate, 2-bromopalmitate or inhibitor of mitochondrial electron transport (rotenone). Adipocyte exposure for 2 h to insulin (1-100 nM) significantly increased secretion of adiponectin compared with secretion observed without insulin. Furthermore, secretion of adiponectin from adipocytes incubated with glucose and insulin was reduced by 1 and 2 microM epinephrine, but not by 0.25 and 0.5 microM epinephrine. Under similar conditions, 1 and 2 mM dibutyryl-cAMP substantially diminished secretion of adiponectin, whereas 0.5 mM dibutyryl-cAMP was ineffective. Secretion of adiponectin was found to be effectively decreased by DPCPX. Moreover, adipocyte exposure to rotenone also resulted in a substantial diminution of secretory response of adipocytes incubated for 2 h with glucose and insulin. It was also demonstrated that palmitate and 2-bromopalmitate (0.06-0.5 mM) failed to affect secretion of leptin. The obtained results indicated that in short-term regulation of adiponectin secretion, insulin and epinephrine exert the opposite effects. These effects appeared as early as after 2 h of exposure. Moreover, deprivation of energy or blockade of adenosine action substantially decreased secretion of adiponectin.

  20. Continuous-variable quantum secret sharing by optical interferometry

    CERN Document Server

    Tyc, T; Tyc, Tomas; Sanders, Barry C.

    2001-01-01

    We develop the theory of continuous-variable quantum secret sharing and propose its interferometric realization using passive and active optical elements. In the ideal case of infinite squeezing, a fidelity ${\\cal F}$ of unity can be achieved with respect to reconstructing the quantum secret. We quantify the reduction in fidelity for the (2,3) threshold scheme due to finite squeezing and establish the condition for verifying that genuine quantum secret sharing has occurred.

  1. How to secretly share the treasure map of the captain?

    Science.gov (United States)

    Islam, N.; Puech, W.; Brouzet, R.

    2010-01-01

    In this paper we present a new approach for sharing a secret image between l users exploiting additive homomorphic property of Paillier algorithm. With a traditional approach, when a dealer wants to share an image between l players, the secret image must be sequentially encrypted l + 1 times using l + 1 keys (secret or public keys). When the dealer and the l players want to extract the secret image, they must decrypt sequentially, keeping the same order of the encryption step, by using l + 1 keys (secret or private). With the proposed approach, during the encryption step, each player encrypts his own secret image using the same public key given by the dealer, the dealer encrypts the secret image to be shared with the same key and then the l secret encrypted images plus the encrypted image to be shared are multiplied between them to get a scrambled image. After this step, the dealer can securely use the private key to decrypt this scrambled image to get a new scrambled image which corresponds to the addition of the l + 1 original images because of the additive homomorphic property of Paillier algorithm. When the l players want to extract the secret image, they do not need the dealer and to use keys. Indeed, with our approach, to extract the secret image, the l players need only to subtract their own secret image from the scrambled image. In this paper we illustrate our approach with an example of a captain who wants to share a secret treasure map between l pirates. Experimental results and security analysis show the effectiveness of the proposed scheme.

  2. Reappraisal of bicarbonate secretion by the human oesophagus.

    OpenAIRE

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1997-01-01

    BACKGROUND AND AIMS: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosal bicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophageal bicarbonate secretion and thus contribute to the therapeutic efficacy of the drug in gastro-oesophageal reflux disease. SUBJECTS AND METHODS: In nine healthy volunteers, oesophageal "steady state" perfusion of a 10 cm open segm...

  3. Information-Theoretic Secure Verifiable Secret Sharing over RSA Modulus

    Institute of Scientific and Technical Information of China (English)

    QIU Gang; WANG Hong; WEI Shimin; XIAO Guozhen

    2006-01-01

    The well-known non-interactive and information-theoretic secure verifiable secret sharing scheme presented by Pedersen is over a large prime. In this paper, we construct a novel non-interactive and information-theoretic verifiable secret sharing over RSA (Rivest,Shamir,Adleman) modulus and give the rigorous security proof. It is shown how to distribute a secret among a group such that any set of k parties get no information about the secret. The presented scheme is generally applied to constructions of secure distributed multiplication and threshold or forward-secure signature protocols.

  4. Hyperphosphorylation and cleavage at D421 enhance tau secretion.

    Directory of Open Access Journals (Sweden)

    Vanessa Plouffe

    Full Text Available It is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD. Moreover, tau accumulates in the cerebrospinal fluid (CSF of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF.

  5. Efficient sharing of a continuous-variable quantum secret

    CERN Document Server

    Tyc, T; Sanders, B C; Tyc, Tomas; Rowe, David J.; Sanders, Barry C.

    2003-01-01

    We propose an efficient scheme for sharing a continuous variable quantum secret using passive optical interferometry and squeezers: this efficiency is achieved by showing that a maximum of two squeezers is required to replicate the secret state, and we obtain the cheapest configuration in terms of total squeezing cost. Squeezing is a cost for the dealer of the secret as well as for the receivers, and we quantify limitations to the fidelity of the replicated secret state in terms of the squeezing employed by the dealer.

  6. Continuous Variables (2,3) Threshold Quantum Secret Sharing Schemes

    CERN Document Server

    Lance, A M; Bowen, W P; Tyc, T; Sanders, B C; Lam, P K

    2003-01-01

    We present two experimental schemes to perform continuous variable (2,3) threshold quantum secret sharing on the quadratures amplitudes of bright light beams. Both schemes require a pair of entangled light beams. The first scheme utilizes two phase sensitive optical amplifiers, whilst the second uses an electro-optic feedforward loop for the reconstruction of the secret. We examine the efficacy of quantum secret sharing in terms of fidelity, as well as the signal transfer coefficients and the conditional variances of the reconstructed output state. We show that both schemes in the ideal case yield perfect secret reconstruction.

  7. Multiparty Quantum Secret Sharing of Quantum States with Quantum Registers

    Institute of Scientific and Technical Information of China (English)

    GUO Ying; ZENG Gui-Hua; CHEN Zhi-Gang

    2007-01-01

    A quantum secret sharing scheme is proposed by making use of quantum registers.In the proposed scheme,secret message state is encoded into multipartite entangled states.Several identical multi-particle entanglement states are generated and each particle of the entanglement state is filled in different quantum registers which act as shares of the secret message.Two modes,j.e.the detecting mode and the message mode,are employed so that the eavesdropping can be detected easily and the secret message may be recovered.The seeurity analysis shows that the proposed scheme is secure against eavesdropping of eavesdropper and cheating of participants.

  8. The ESX system in Bacillus subtilis mediates protein secretion.

    Directory of Open Access Journals (Sweden)

    Laura A Huppert

    Full Text Available Esat-6 protein secretion systems (ESX or Ess are required for the virulence of several human pathogens, most notably Mycobacterium tuberculosis and Staphylococcus aureus. These secretion systems are defined by a conserved FtsK/SpoIIIE family ATPase and one or more WXG100 family secreted substrates. Gene clusters coding for ESX systems have been identified amongst many organisms including the highly tractable model system, Bacillus subtilis. In this study, we demonstrate that the B. subtilis yuk/yue locus codes for a nonessential ESX secretion system. We develop a functional secretion assay to demonstrate that each of the locus gene products is specifically required for secretion of the WXG100 virulence factor homolog, YukE. We then employ an unbiased approach to search for additional secreted substrates. By quantitative profiling of culture supernatants, we find that YukE may be the sole substrate that depends on the FtsK/SpoIIIE family ATPase for secretion. We discuss potential functional implications for secretion of a unique substrate.

  9. Security of the AES with a Secret S-Box

    DEFF Research Database (Denmark)

    Tiessen, Tyge; Knudsen, Lars Ramkilde; Kölbl, Stefan

    2015-01-01

    How does the security of the AES change when the S-box is replaced by a secret S-box, about which the adversary has no knowledge? Would it be safe to reduce the number of encryption rounds? In this paper, we demonstrate attacks based on integral cryptanalysis which allow to recover both the secret...... key and the secret S-box for respectively four, five, and six rounds of the AES. Despite the significantly larger amount of secret information which an adversary needs to recover, the attacks are very efficient with time/data complexities of 217/216, 238/240 and 290/264, respectively. Another...

  10. Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

    Science.gov (United States)

    Guttu, K; Røsok, B; Gislason, H; Fändriks, L; Svanes, K; Grønbech, J E

    1991-04-01

    In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.

  11. A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins.

    Science.gov (United States)

    Tejeda-Dominguez, Farid; Huerta-Cantillo, Jazmin; Chavez-Dueñas, Lucia; Navarro-Garcia, Fernando

    2017-03-28

    The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic Escherichia coli (EPEC) autotransporter, and YopH, a protein detected on the surface of Yersinia, require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore. Interestingly, this novel mechanism does not exclude the injection model (i.e., EspF) operating through the T3SS conduit; therefore, T3SS can be functioning as an internal conduit or as an external railway, which can be used to reach the translocator pore, and this mechanism appears to be conserved among different T3SS-dependent pathogens.IMPORTANCE The type 3 secretion system is essential for injection of virulence factors, which are delivered directly into the cytosol of the host cells for usurping and subverting host processes. Recent studies have shown that these effectors proteins indeed travel inside an "injectisome" conduit through a single step of translocation by connecting the bacterium and host cell cytoplasms. However, all findings are not compatible with this model. For example, both YopH, a protein detected on the surface of Yersinia, and EspC, an autotransporter protein secreted by enteropathogenic E. coli, require a functional T3

  12. Kinetic regulation of coated vesicle secretion

    CERN Document Server

    Foret, Lionel

    2008-01-01

    The secretion of vesicles for intracellular transport often rely on the aggregation of specialized membrane-bound proteins into a coat able to curve cell membranes. The nucleation and growth of a protein coat is a kinetic process that competes with the energy-consuming turnover of coat components between the membrane and the cytosol. We propose a generic kinetic description of coat assembly and the formation of coated vesicles, and discuss its implication to the dynamics of COP vesicles that traffic within the Golgi and with the Endoplasmic Reticulum. We show that stationary coats of fixed area emerge from the competition between coat growth and the recycling of coat components, in a fashion resembling the treadmilling of cytoskeletal filaments. We further show that the turnover of coat components allows for a highly sensitive switching mechanism between a quiescent and a vesicle producing membrane, upon a slowing down of the exchange kinetics. We claim that the existence of this switching behaviour, also tri...

  13. Multiple Ca2+ sensors in secretion

    DEFF Research Database (Denmark)

    Walter, Alexander M; Groffen, Alexander J; Sørensen, Jakob Balslev;

    2011-01-01

    Regulated neurotransmitter secretion depends on Ca(2+) sensors, C2 domain proteins that associate with phospholipids and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complexes to trigger release upon Ca(2+) binding. Ca(2+) sensors are thought to prevent spontaneous...... fusion at rest (clamping) and to promote fusion upon Ca(2+) activation. At least eight, often coexpressed, Ca(2+) sensors have been identified in mammals. Accumulating evidence suggests that multiple Ca(2+) sensors interact, rather than work autonomously, to produce the complex secretory response...... observed in neurons and secretory cells. In this review, we present several working models to describe how different sensors might be arranged to mediate synchronous, asynchronous and spontaneous neurotransmitter release. We discuss the scenario that different Ca(2+) sensors typically act on one shared...

  14. Secrets of mlearning failures: confronting reality

    Directory of Open Access Journals (Sweden)

    Thomas Cochrane

    2012-08-01

    Full Text Available Having implemented and evaluated over 35 mlearning projects in a variety of contexts in higher education over the past 6 years the researcher is ready to share the untold secret: not all mlearning projects succeed! This article critiques three of the researcher's mlearning projects that can be classed as “failures” and compares them to successful projects to draw out critical implications for mlearning project design and implementation to avoid common pitfalls leading to potential project failure. This article uses the researcher's six critical success factors identified across the 35 mlearning projects to evaluate these three projects, and concludes that projects resulting in “no significant difference” in pedagogical outcomes are the result of attempts to shoehorn old pedagogies into new technologies. Lecturer professional development and sustained collaborative support are critical to fostering new pedagogies utilising the unique affordances of mobile devices.

  15. Secreted fungal aspartic proteases: A review.

    Science.gov (United States)

    Mandujano-González, Virginia; Villa-Tanaca, Lourdes; Anducho-Reyes, Miguel Angel; Mercado-Flores, Yuridia

    2016-01-01

    The aspartic proteases, also called aspartyl and aspartate proteases or acid proteases (E.C.3.4.23), belong to the endopeptidase family and are characterized by the conserved sequence Asp-Gly-Thr at the active site. These enzymes are found in a wide variety of microorganisms in which they perform important functions related to nutrition and pathogenesis. In addition, their high activity and stability at acid pH make them attractive for industrial application in the food industry; specifically, they are used as milk-coagulating agents in cheese production or serve to improve the taste of some foods. This review presents an analysis of the characteristics and properties of secreted microbial aspartic proteases and their potential for commercial application. Copyright © 2016 Asociación Española de Micología. Published by Elsevier Espana. All rights reserved.

  16. Droog纽约首展Secret natures

    Institute of Scientific and Technical Information of China (English)

    Ron Lam; Galerie Kreo

    2009-01-01

    <正>荷兰品牌Droog今年二月在纽约开设分店,店里除了售卖自家出品的家具外,还设有展览场地,以举办不定期的产品或艺术展览,首个展览于五月中开始举行。这场名叫Secret Natures的展览共展出四件来自不同设计师的作品,当中包括西班牙设计师Nacho Carbonell的家具系列Skin。Skin被由弹力物料制成的外衣包裹着,

  17. ARQ-Based Secret Key Sharing

    CERN Document Server

    Ghany, Mohamed Abdel; Gamal, Hesham El

    2008-01-01

    This paper develops a novel framework for sharing secret keys using existing Automatic Repeat reQuest (ARQ) protocols. Our approach exploits the multi-path nature of the wireless environment to hide the key from passive eavesdroppers. The proposed framework does not assume the availability of any prior channel state information (CSI) and exploits only the one bit ACK/NACK feedback from the legitimate receiver. Compared with earlier approaches, the main innovation lies in the distribution of key bits among multiple ARQ frames. Interestingly, this idea allows for achieving a positive secrecy rate even when the eavesdropper experiences more favorable channel conditions, on average, than the legitimate receiver. In the sequel, we characterize the information theoretic limits of the proposed schemes, develop low complexity explicit implementations, and conclude with numerical results that validate our theoretical claims.

  18. An engineered yeast efficiently secreting penicillin.

    Directory of Open Access Journals (Sweden)

    Loknath Gidijala

    Full Text Available This study aimed at developing an alternative host for the production of penicillin (PEN. As yet, the industrial production of this beta-lactam antibiotic is confined to the filamentous fungus Penicillium chrysogenum. As such, the yeast Hansenula polymorpha, a recognized producer of pharmaceuticals, represents an attractive alternative. Introduction of the P. chrysogenum gene encoding the non-ribosomal peptide synthetase (NRPS delta-(L-alpha-aminoadipyl-L-cysteinyl-D-valine synthetase (ACVS in H. polymorpha, resulted in the production of active ACVS enzyme, when co-expressed with the Bacillus subtilis sfp gene encoding a phosphopantetheinyl transferase that activated ACVS. This represents the first example of the functional expression of a non-ribosomal peptide synthetase in yeast. Co-expression with the P. chrysogenum genes encoding the cytosolic enzyme isopenicillin N synthase as well as the two peroxisomal enzymes isopenicillin N acyl transferase (IAT and phenylacetyl CoA ligase (PCL resulted in production of biologically active PEN, which was efficiently secreted. The amount of secreted PEN was similar to that produced by the original P. chrysogenum NRRL1951 strain (approx. 1 mg/L. PEN production was decreased over two-fold in a yeast strain lacking peroxisomes, indicating that the peroxisomal localization of IAT and PCL is important for efficient PEN production. The breakthroughs of this work enable exploration of new yeast-based cell factories for the production of (novel beta-lactam antibiotics as well as other natural and semi-synthetic peptides (e.g. immunosuppressive and cytostatic agents, whose production involves NRPS's.

  19. An engineered yeast efficiently secreting penicillin.

    Science.gov (United States)

    Gidijala, Loknath; Kiel, Jan A K W; Douma, Rutger D; Seifar, Reza M; van Gulik, Walter M; Bovenberg, Roel A L; Veenhuis, Marten; van der Klei, Ida J

    2009-12-15

    This study aimed at developing an alternative host for the production of penicillin (PEN). As yet, the industrial production of this beta-lactam antibiotic is confined to the filamentous fungus Penicillium chrysogenum. As such, the yeast Hansenula polymorpha, a recognized producer of pharmaceuticals, represents an attractive alternative. Introduction of the P. chrysogenum gene encoding the non-ribosomal peptide synthetase (NRPS) delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) in H. polymorpha, resulted in the production of active ACVS enzyme, when co-expressed with the Bacillus subtilis sfp gene encoding a phosphopantetheinyl transferase that activated ACVS. This represents the first example of the functional expression of a non-ribosomal peptide synthetase in yeast. Co-expression with the P. chrysogenum genes encoding the cytosolic enzyme isopenicillin N synthase as well as the two peroxisomal enzymes isopenicillin N acyl transferase (IAT) and phenylacetyl CoA ligase (PCL) resulted in production of biologically active PEN, which was efficiently secreted. The amount of secreted PEN was similar to that produced by the original P. chrysogenum NRRL1951 strain (approx. 1 mg/L). PEN production was decreased over two-fold in a yeast strain lacking peroxisomes, indicating that the peroxisomal localization of IAT and PCL is important for efficient PEN production. The breakthroughs of this work enable exploration of new yeast-based cell factories for the production of (novel) beta-lactam antibiotics as well as other natural and semi-synthetic peptides (e.g. immunosuppressive and cytostatic agents), whose production involves NRPS's.

  20. Pyrilamine inhibits nicotine-induced catecholamine secretion.

    Science.gov (United States)

    Kim, Dong-Chan; Yun, So Jeong; Park, Yong-Soo; Jun, Dong-Jae; Kim, Dongjin; Jiten Singh, N; Kim, Sanguk; Kim, Kyong-Tai

    2014-07-01

    Function of nicotine, which induces activation of all parts of the body including our brain, has been receiving much attention for a long period of time and also been actively studied by researchers for its pharmacological actions in the central nervous system. The modulation of nicotine concentration and the inhibition of nicotine binding on target receptors in the brain are the key factors for smoking addiction therapy. In previous studies showed that influx of nicotine at the blood-brain barrier was through the pyrilamine-sensitive organic cation transporters. But the direct interacting mechanism of pyrilamine on the nicotine binding target receptors has not yet been clarified. The aim of the present study is to investigate the direct binding mechanisms of a pyrilamine on the nicotinic acetylcholine receptors (nAChRs). We found that pyrilamine shares the same ligand binding pocket of nicotine (NCT) on nAChRs but interacts with more amino acid residues than NCT does. The extended part of pyrilamine interacts with additional residues in the ligand binding pocket of nAChRs which are located nearby the entrance of the binding pocket. The catecholamine (CA) secretion induced by nAChR agonist (NCT') was significantly inhibited by the pyrilamine pretreatment. Real time carbon-fiber amperometry confirmed the inhibition of the NCT'-induced exocytosis by pyrilamine in a single cell level. We also found that pyrilamine inhibited the NCT'-induced [Ca(2+)]i. In contrast, pyrilamine did not affect the increase in calcium induced by high K(+). Overall, these data suggest that pyrilamine directly docks into the ligand binding site of nAChRs and specifically inhibits the nAChR-mediated effects thereby causing inhibition of CA secretion. Therefore, pyrilamine may play an important role to explore new treatments to aid smoking cessation.

  1. The secretion of lecithinase of Pseudomonas alcaligenes S2 was via type II secretion pathway

    Institute of Scientific and Technical Information of China (English)

    L(U) Jing; LI Fan; CHEN Sanfeng; LI Jilun

    2005-01-01

    Strain S2 is a lecithin (or phosphatidylcholine)- solubilizing bacterium, which was isolated from the rice rhizosphere in rural areas of Beijing, China. On the basis of a polyphasic study involving phenotypic tests, physiological and biochemical tests, 16S rDNA sequence analysis, G+C content determination and DNA-DNA hybridizations analysis, strain S2 was identified as Pseudomonas alcaligenes. P. alcaligenes S2 was mutagenized with Tn5 and four mutants showing decreased or increased solubilizing ability of lecithin were isolated based on the halo size around colonies on the solid plate supplemented with egg yolk. To characterize the genes of P. alcaligenes S2 involved in solubilization of lecithin, the EcoR I fragments of the chromosomes from the four mutant strains carrying a single transposon were cloned, and the DNA sequences flanking the Tn5 were determined. The Tn5 insertion sites in the mutants M808, M1329 and M1400, showing decreased solubilizing ability of lecithin, were found to be located in the xcpS, xcpX and xcpW , respectively, whose products XcpS, XcpX and XcpW were the components of type II secretion pathway. Complementation of xcpS, xcpX and xcpW could restore the corresponding mutants M808, M1329 and M1400 to solubilize lecithin. The data suggested that mutation in one of these xcp genes would lead to the absence of mature lecithinase secretion into the extracellular medium. The data also indicated that the secretion of lecithin-hydrolyzing enzyme of P. alcaligenes was via type II secretion pathway. In the mutant M20 showing increasing lecithin-hydrolyzing activity, the interrupted gene showed 86% identity with chpA of Pseudomonas aeruginosa PAO1, whose product plays an important role in controlling twitching motility of the bacterial cells.

  2. Secretion of salivary statherin is compromised in uncontrolled diabetic patients

    Directory of Open Access Journals (Sweden)

    Masahiro Izumi

    2015-06-01

    Conclusions and general significance: The results show that synthesis and secretion of statherin is reduced in diabetics and this reduction is salivary gland specific. As compromised salivary statherin secretion leads to increased oral health risk, this study indicates that routine oral health assessment of these patients is warranted.

  3. Pathogenesis of canine cortisol-secreting adrenocortical tumors

    NARCIS (Netherlands)

    Kool, Miriam

    2015-01-01

    In dogs, hypercortisolism is one of the most frequently observed endocrine disorders, with an estimated incidence of about 1-2 cases per 1000 dogs per year. Approximately 15% of these cases is due to a cortisol-secreting adrenocortical tumor (AT). Cortisol-secreting ATs are characterized by uncontro

  4. A catalogue of human secreted proteins and its implications

    Directory of Open Access Journals (Sweden)

    Shivakumar Keerthikumar

    2016-11-01

    Full Text Available Under both normal and pathological conditions, cells secrete variety of proteins through classical and non-classical secretory pathways into the extracellular space. Majority of these proteins represent pathophysiology of the cell from which it is secreted. Recently, though more than 92% of the protein coding genes has been mapped by human proteome map project, but number of those proteins that constitutes secretome of the cell still remains elusive. Secreted proteins or the secretome can be accessible in bodily fluids and hence are considered as potential biomarkers to discriminate between healthy and diseased individuals. In order to facilitate the biomarker discovery and to further aid clinicians and scientists working in these arenas, we have compiled and catalogued secreted proteins from the human proteome using integrated bioinformatics approach. In this study, nearly 14% of the human proteome is likely to be secreted through classical and non-classical secretory pathways. Out of which, ~38% of these secreted proteins were found in extracellular vesicles including exosomes and shedding microvesicles. Among these secreted proteins, 94% were detected in human bodily fluids including blood, plasma, serum, saliva, semen, tear and urine. We anticipate that this high confidence list of secreted proteins could serve as a compendium of candidate biomarkers. In addition, the catalogue may provide functional insights in understanding the molecular mechanisms involved in various physiological and pathophysiological conditions of the cell.

  5. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    Science.gov (United States)

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.

  6. Type VII Secretion Systems in Gram-Positive Bacteria

    NARCIS (Netherlands)

    Bottai, Daria; Gröschel, Matthias I.; Brosch, Roland; Bagnoli, Fabio; Rappuoli, Rino

    2017-01-01

    Bacterial secretion systems are sophisticated molecular machines that fulfil a wide range of important functions, which reach from export/secretion of essential proteins or virulence factors to the implication in conjugation processes. In contrast to the widely distributed Sec and Twin Arginine

  7. Inhibition of secretion by asexual reproduction in Aspergillus niger

    NARCIS (Netherlands)

    Wang, Fengfeng

    2014-01-01

    The aim of this Thesis was to study mechanism involved in zonal secretion in colonies of A. niger with emphasis on sporulation inhibited secretion. These mechanisms may be targets to improve A. nigeras a cell factory. I focused in particular on A. niger homologues of fluG and veA that are known spor

  8. PACAP stimulates insulin secretion but inhibits insulin sensitivity in mice

    NARCIS (Netherlands)

    Filipsson, K; Pacini, G; Scheurink, AJW; Ahren, B

    Although pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin secretion, its net influence on glucose homeostasis in vivo has not been established. We therefore examined the action of PACAP-27 and PACAP-38 on insulin secretion, insulin sensitivity, and glucose disposal as

  9. Lipid-independent secretion of a Drosophila Wnt protein.

    Science.gov (United States)

    Ching, Wendy; Hang, Howard C; Nusse, Roel

    2008-06-20

    Wnt proteins comprise a large class of secreted signaling molecules with key roles during embryonic development and throughout adult life. Recently, much effort has been focused on understanding the factors that regulate Wnt signal production. For example, Porcupine and Wntless/Evi/Sprinter have been identified as being required in Wnt-producing cells for the processing and secretion of many Wnt proteins. Interestingly, in this study we find that WntD, a recently characterized Drosophila Wnt family member, does not require Porcupine or Wntless/Evi/Sprinter for its secretion or signaling activity. Because Porcupine is involved in post-translational lipid modification of Wnt proteins, we used a novel labeling method and mass spectrometry to ask whether WntD undergoes lipid modification and found that it does not. Although lipid modification is also hypothesized to be required for Wnt secretion, we find that WntD is secreted very efficiently. WntD secretion does, however, maintain a requirement for the secretory pathway component Rab1. Our results show that not all Wnt family members require lipid modification, Porcupine, or Wntless/Evi/Sprinter for secretion and suggest that different modes of secretion may exist for different Wnt proteins.

  10. Dynamic Vector Space Secret Sharing Based on Certificates

    Institute of Scientific and Technical Information of China (English)

    XU Chunxiang; LI Jiajia; LIU Dongsu

    2006-01-01

    A vector space secret sharing scheme based on certificates is proposed in this paper. The difficulties of solving discrete logarithm assure confidential information's security, and the use of each participant's certificate makes the dealer have no need to transfer secret information to the participants. The proposed scheme is dynamic. It can effectively check cheaters and does not have secure channel requirements.

  11. Sur les usages publics du secret : les archives du Service Secret Communiste Roumain

    Directory of Open Access Journals (Sweden)

    Andi Mihalache

    2009-10-01

    Full Text Available L’étude s’occupe des dossiers de l’ancienne police politique du régime communiste de Roumanie, la Securitate. Il a comme point de départ le fait que la mémoire sociale, le contexte politique et les débats publics actuels influencent la recherche historique, modifiant les perceptions sur le document d’archive. Ce dernier n’est plus vu seulement comme source principale de la recherche historique, devenant outil redoutable dans les disputes électorales, car, en base des informations extraites d’un dossier de la Securitate, l’on peut évincer un adversaire incommode. Se montrant utile à dénoncer la collaboration de quelqu’un sous le régime communiste, le document d’archive a acquis des mises symboliques imprévues, étant caché, protégé, volé, racheté, truqué, perdu et redécouvert à commande. Toutes ces pratiques compromettent de plus en plus les chances des historiens de reconstituer de manière crédible l’histoire récente des Roumains. On obtient difficilement l’accès aux dossiers de la Securitate, la patrimonialisation excessive des documents - en vérité leur trésorisation - étant conséquence directe du prestige idéologique et social que le secret détenait au temps communiste.This article focuses on the Securitate files as a political stake, but also as first rank sources for academic research, not from the current perspective of recent history, but from that of cultural history. In post-communist Romania, silence is the secret’s poor relative and confidentiality its respectable form. Ironically or not, we could state that in our country the secrets of communist repression are literally protected by law. The secret is an unbidden, illegitimate competence. In its ethics it does not matter what is good and what is bad, what is true and what is false. The main interest is what is said and what isn’t. The secret being a convention, a pact, the gesture of not saying seems to be more important than

  12. Regulation of gut hormone secretion. Studies using isolated perfused intestines

    DEFF Research Database (Denmark)

    Svendsen, Berit; Holst, Jens Juul.

    2016-01-01

    hormones is highly increased after gastric bypass operations, which have turned out to be an effective therapy of not only obesity but also type 2 diabetes. These effects are likely to be due, at least in part, to increases in the secretion of these gut hormones (except GIP). Therefore, stimulation......A review. The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from enteroendocrine cells in the intestine along with other gut hormones (PYY, CCK and neurotensin) shown to affect metab. and/or appetite. The secretion of many gut...... detailed mapping of the expression profiles of these cells, whereas they are less suitable for physiol. studies of secretion. Isolated perfused prepns. of mouse and rat intestines have proven to be reliable models for dynamic hormone secretion and should be able to bridge the gap between the mol. details...

  13. Cropping and noise resilient steganography algorithm using secret image sharing

    Science.gov (United States)

    Juarez-Sandoval, Oswaldo; Fierro-Radilla, Atoany; Espejel-Trujillo, Angelina; Nakano-Miyatake, Mariko; Perez-Meana, Hector

    2015-03-01

    This paper proposes an image steganography scheme, in which a secret image is hidden into a cover image using a secret image sharing (SIS) scheme. Taking advantage of the fault tolerant property of the (k,n)-threshold SIS, where using any k of n shares (k≤n), the secret data can be recovered without any ambiguity, the proposed steganography algorithm becomes resilient to cropping and impulsive noise contamination. Among many SIS schemes proposed until now, Lin and Chan's scheme is selected as SIS, due to its lossless recovery capability of a large amount of secret data. The proposed scheme is evaluated from several points of view, such as imperceptibility of the stegoimage respect to its original cover image, robustness of hidden data to cropping operation and impulsive noise contamination. The evaluation results show a high quality of the extracted secret image from the stegoimage when it suffered more than 20% cropping or high density noise contamination.

  14. Enhanced secretion of natto phytase by Bacillus subtilis.

    Science.gov (United States)

    Tsuji, Shogo; Tanaka, Kosei; Takenaka, Shinji; Yoshida, Ken-ichi

    2015-01-01

    Phytases comprise a group of phosphatases that trim inorganic phosphates from phytic acid (IP6). In this study, we aimed to achieve the efficient secretion of phytase by Bacillus subtilis. B. subtilis laboratory standard strain 168 and its derivatives exhibit no phytase activity, whereas a natto starter secretes phytase actively. The natto phytase gene was cloned into strain RIK1285, a protease-defective derivative of 168, to construct a random library of its N-terminal fusions with 173 different signal peptides (SPs) identified in the 168 genome. The library was screened to assess the efficiency of phytase secretion based on clear zones around colonies on plates, which appeared when IP6 was hydrolyzed. The pbp SP enhanced the secretion of the natto phytase most efficiently, i.e. twice that of the original SP. Thus, the secreted natto phytase was purified and found to remove up to 3 phosphates from IP6.

  15. Secret Sharing and Proactive Renewal of Shares in Hierarchical Groups

    CERN Document Server

    Naskar, Ruchira; 10.5121/ijcsit.2010.2312

    2010-01-01

    Secret sharing in user hierarchy represents a challenging area for research. Although a lot of work has already been done in this direc- tion, this paper presents a novel approach to share a secret among a hierarchy of users while overcoming the limitations of the already exist- ing mechanisms. Our work is based on traditional (k +1; n)-threshold secret sharing, which is secure as long as an adversary can compromise not more than k secret shares. But in real life it is often feasible for an adversary to obtain more than k shares over a long period of time. So, in our work we also present a way to overcome this vulnerability, while implementing our hierarchical secret sharing scheme. The use of Elliptic Curve Cryptography makes the computations easier and faster in our work.

  16. J774 macrophages secrete antibiotics via organic anion transporters.

    Science.gov (United States)

    Cao, C X; Silverstein, S C; Neu, H C; Steinberg, T H

    1992-02-01

    Mouse macrophages and J774 macrophage-like cells express probenecid-inhibitable organic anion transporters that remove anionic dyes from the cells' cytoplasmic matrix and secrete these dyes into the extracellular medium. The present studies show that these transporters also secrete antibiotics from J774 macrophages. Penicillin G permeates J774 cells poorly, but after it was introduced into the cell cytoplasm, it was secreted in a probenecid-inhibitable fashion. The quinolone norfloxacin enters macrophages readily. Probenecid retarded the secretion of intracellular norfloxacin by J774 cells and enhanced norfloxacin accumulation three- to fourfold. Thus the intracellular accumulation of norfloxacin is regulated in part by organic anion transporters that secrete norfloxacin (and penicillin G) from J774 cells. This transport process may have clinical significance, as fluoroquinolones inhibit growth of intracellular pathogens such as mycobacteria and Brucella organisms in vitro but fail to arrest infections with these organisms in vivo.

  17. A Bayesian approach to estimating the prehepatic insulin secretion rate

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Højbjerre, Malene

    the time courses of insulin and C-peptide subsequently are used as known forcing functions. In this work we adopt a Bayesian graphical model to describe the unied model simultaneously. We develop a model that also accounts for both measurement error and process variability. The parameters are estimated......The prehepatic insulin secretion rate of the pancreatic $beta$-cells is not directly measurable, since part of the secreted insulin is absorbed by the liver prior to entering the blood stream. However, C-peptide is co-secreted equimolarly and is not absorbed by the liver, allowing...... for the estimation of the prehepatic insulin secretion rate. We consider a stochastic differential equation model that combines both insulin and C-peptide concentrations in plasma to estimate the prehepatic insulin secretion rate. Previously this model has been analysed in an iterative deterministic set-up, where...

  18. Multiparty Quantum Secret Sharing of Quantum States Using Entanglement States

    Institute of Scientific and Technical Information of China (English)

    GUO Ying; HUANG Da-Zu; ZENG Gui-Hua; LEE Moon Ho

    2008-01-01

    A multi-partite-controlled quantum secret sharing scheme using several non-orthogonal entanglement states is presented with unconditional security.In this scheme,the participants share the secret quantum state by exchanging the secret polarization angles of the disordered travel particles.The security of the secret quantum state is also guaranteed by the non-orthogonal multi-partite-controlled entanglement states,the participants'secret polarizations,and the disorder of the travelling particles.Moreover,the present scheme is secure against the particle-number splitting attack and the intercept-and-resend attack.It may be still secure even if the distributed quantum state is embedded in a not-so-weak coherent-state pulse.

  19. Regulation of mucous acinar exocrine secretion with age.

    Science.gov (United States)

    Culp, D J; Richardson, L A

    1996-01-01

    Denny and co-workers (Navazesh et al., 1992) recently reported decreased concentrations of MG1 and MG2 mucins in resting and stimulated whole human saliva with age. The current study was therefore conducted to examine whether there is a corresponding attenuation with age in stimulus secretion coupling regulating mucous cell exocrine secretion. We utilized an in vitro model system, isolated rat sublingual acini, to evaluate the regulation of mucous cell exocrine secretion. Rat sublingual glands are similar to human sublingual and minor mucous glands, both histologically and in terms of their pattern of innervation, which is predominantly parasympathetic. Mucin secretion is thus activated primarily by muscarinic cholinergic agonist and to a lesser extent by vasoactive intestinal peptide (VIP), which is co-localized with acetylcholine in parasympathetic nerve terminals. We isolated sublingual mucous acini from five-month-old and 24-month-old rats and compared the concentration responses for mucin secretion induced by VIP and the muscarinic agonist, arecaidine propargyl ester (APE). Concentration-response curves for VIP were nearly identical for mucous acini from the five-month-old and 24-month-old animals. Values for basal secretion, maximal secretion, and EC50 (approximately equal to 200 nmol/L VIP) were statistically equivalent between both age groups. Concentration-response curves for APE were also very similar between age groups, with no statistically significant difference in basal secretion or EC50 values (approximately equal to 50 nmol/L APE). Maximal secretion was slightly less but statistically different for 24-month-old vs. five-month-old animals, 158% vs. 169% above basal secretion, respectively. Collectively, we found no substantial age-related changes in the secretory responsiveness of salivary mucous cells.

  20. Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST).

    Science.gov (United States)

    Lee, Je Min; Lee, Sang-Jik; Rose, Jocelyn K C; Yeam, Inhwa; Kim, Byung-Dong

    2014-04-18

    Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.

  1. Identification of genes encoding the type IX secretion system and secreted proteins in Flavobacterium columnare IA-S-4

    Science.gov (United States)

    Flavobacterium columnare, a member of the phylum Bacteroidetes, causes columnaris disease in wild and aquaculture-reared freshwater fish. The mechanisms responsible for columnaris disease are not known. Many members of the phylum Bacteroidetes use type IX secretion systems (T9SSs) to secrete enzymes...

  2. Undocumented secrets of MATLAB-Java programming

    CERN Document Server

    Altman, Yair

    2012-01-01

    For a variety of reasons, the MATLAB®-Java interface was never fully documented. This is really quite unfortunate: Java is one of the most widely used programming languages, having many times the number of programmers and programming resources as MATLAB. Also unfortunate is the popular claim that while MATLAB is a fine programming platform for prototyping, it is not suitable for real-world, modern-looking applications. Undocumented Secrets of MATLAB®-Java Programming aims to correct this misconception. This book shows how using Java can significantly improve MATLAB program appearance and functionality, and that this can be done easily and even without any prior Java knowledge. Readers are led step-by-step from simple to complex customizations. Code snippets, screenshots, and numerous online references are provided to enable the utilization of this book as both a sequential tutorial and as a random-access reference suited for immediate use. Java-savvy readers will find it easy to tailor code samples for th...

  3. Gastric lipase secretion in children with gastritis.

    Science.gov (United States)

    Tomasik, Przemyslaw J; Wędrychowicz, Andrzej; Rogatko, Iwona; Zając, Andrzej; Fyderek, Krzysztof; Sztefko, Krystyna

    2013-07-29

    Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14) and the control group including healthy adolescents (n = 14). Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

  4. "ON-AIR SECRETS": TEN YEARS LATER

    Directory of Open Access Journals (Sweden)

    Bysko Maxim V.

    2013-12-01

    Full Text Available The article is a scientific review on the training manual On-air secret by Andrey Bubukin, published in 2003. This guide has been written by a man who never had anything to do with radio, but by the will of fate suddenly became at once the program director of Russia's first non-state radio station Europa Plus Moscow, the commercial music radio. Then came to the fore not the questions of art qualities of broadcast, but technical-mathematical details of the automated programming of song material. Therefore, at the end of the Soviet broadcasting, it became possible appearance some people obviously alien to the electronic mass media. They are, however, strongly influenced the further "format" broadcasting in new Russia, so as the principles of songs rotation and playlist making on the radio still can’t do without recourse to the Bubukin's textbook. There are serious concerns about the fact that the book is intended not only for program directors, but for the music editors also. Extremely dubious assertions and recommendations related to the problems of arts, journalism, radio-presenter's skill, history of radio.

  5. Choice of measurement as the secret

    Science.gov (United States)

    Liu, Bin; Gao, Fei; Qin, Su-Juan; Huang, Wei; Liu, Feng; Wen, Qiao-Yan

    2014-04-01

    Recently, Kalev et al. [A. Kalev, A. Mann, and M. Revzen, Phys. Rev. Lett. 110, 260502 (2013)., 10.1103/PhysRevLett.110.260502] proposed a quantum (public) communication protocol with an interesting encoding style, where the signal is encoded in the choice of the measurement basis of one of the communicating parties (Bob) and Bob's measurement results are irrelevant for the communication. As we know, one of the main advantages of quantum technique in communication over the classical one is the higher security. Therefore, as Kalev et al. have mentioned in their paper, an interesting open question is whether one could and how to utilize this new encoding style to design a secure communication protocol, i.e., translate the choice of measurement into the secret. Here we propose a quantum key distribution protocol, which is a secure communication protocol, with this encoding style, where Bob's measurement results are still irrelevant. Furthermore, the security of the proposed protocol in the zero-error case has been proved.

  6. Gamma knife radiosurgery for secreting pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Noren, G. [Brown Univ., Providence, RI (United States). Rhode Island Hospital; Jackson, I.M.D.; Chougule, P.; Zheng, Z.; Epstein, M.H.

    1998-09-01

    Transsphenoidal surgery usually represents first line treatment for pituitary adenomas with the aim of removing the tumor, decompressing the optic apparatus and, in secreting tumors, eliminating the hypersecretion. Gamma Knife radiosurgery is indicated for tumor remnants or recurrences in or above the sella including those invading the cavernous sinus and also as initial treatment in patients who are unable to tolerate an open surgical procedure and where medication has failed. In this study, the target definition was retrospectively studied and when necessary corrected in 10 acromegalic patients, 8 with Cushing`s disease, and 12 with prolactinomas undergoing Gamma Knife radiosurgery. The dose plan was analyzed and the volume of the target covered by a minimum of 15, 20, 25, 30 and 35 Gy was estimated. A dose/volume profile for each treatment was created and correlated to the endocrinological and clinical outcome. Cure, according to strict endocrinological criteria, was seen in 6 of the acromegalic patients, in 2 of the patients with ACTH hypersecretion, and in 2 of the patients with prolactinomas. Analysis of these profiles, also for the patients with partial effect, show that a minimum radiation dose of 20 Gy may be adequate to eliminate the hypersecretion in acromegalic patients whereas a dose of at least 25 Gy may be required in patients with Cushing`s disease and prolactinoma. (author)

  7. 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

  8. Leakproof secret sharing protocols with applications to group identification scheme

    Institute of Scientific and Technical Information of China (English)

    TANG ChunMing; GAO ShuHong

    2012-01-01

    In a traditional (t,n)-threshold secret sharing scheme,t or more honest participants can reconstruct the secret K.In the reconstruction process,the individual shares and the secret key K are revealed,hence K is shared once only. In this paper,we firstly give the definition of leakproof secret sharing scheme which is composed of a distribution protocol and a proof protocol,then propose two leakproof secret sharing protocols,a computationally secure protocol and an information-theoretically secure protocol.In our protocols,t or more participants can jointly prove that they hold the secret K by using a multi-prover zero-knowledge argument of knowledge.As a result,the secret K will be shared for as many times as desired.Furthermore,each participant can detect the dealer in the distribution protocol from cheating,and any verifier can prevent non-qualified set of participants in proof protocol from cheating.As an example of the practical impact of our work we use our techniques to construct group identification schemes with zero-knowledge.

  9. The behavior of pollination drop secretion in Ginkgo biloba L.

    Science.gov (United States)

    Jin, Biao; Jiang, Xiaoxue; Wang, Di; Zhang, Lei; Wan, Yinglang; Wang, Li

    2012-01-01

    Pollination drop (PD) secretion plays a critical role in wind pollination in many gymnosperms. We conducted detailed investigations on PD secretion in Ginkgo biloba, and found that PDs could not form when the micropyle was removed, but were able to form after removal of the shoot, leaves, ovular stalk, or ovular collar. The duration and volume of the PD increased under high relative humidity, but addition of salt or sugar did not affect PD secretion, its size, or its duration. Morphological and anatomical observations showed that many secretion cells at the nucellus tip contributed to secreting the PD after the formation of pollen chamber. Under laboratory conditions, the PD persisted for approximately 10 d if not pollinated, and re-formed five times after it was removed, with the total volume of PDs reaching approximately 0.4 μL. These results suggested that PDs can be continuously secreted by the tip of the nucellus cells during the pollination stage to increase the chance of capturing pollen from the air. Importantly, PD secretion is an independent behavior of the ovule and PDs were produced apoplastically. PMID:22899081

  10. Exosome secretion affects social motility in Trypanosoma brucei

    Science.gov (United States)

    Shaked, Hadassa; Arvatz, Gil; Tkacz, Itai Dov; Binder, Lior; Waldman Ben-Asher, Hiba; Okalang, Uthman; Chikne, Vaibhav; Cohen-Chalamish, Smadar; Michaeli, Shulamit

    2017-01-01

    Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites. PMID:28257521

  11. SSDLP: Sharing Secret Data between Leader and Participant

    Directory of Open Access Journals (Sweden)

    Hazem Al-Najjar

    2014-01-01

    Full Text Available This paper investigates the problem of sharing the secret document containing a secret data between leader and participant(s depending on specific conditions and rules. The participant(s can retrieve part of the secret document but will not be able to retrieve any secret data without the leader. At the same time, the leader may have a little information about the secret document but cannot retrieve the secret data and the secret document without cooperating with participant(s. To evaluate the proposed model and the system efficiency, four tests are suggested, which are concatenation and sharing data test, leader visual test, information entropy analysis, and correlation analysis. Results show that the proposed model is efficient in sharing the data between the leader and participant(s and the model can achieve our concept of the data sharing between leader and participant(s. However, by analyzing the proposed model using numerical tests and visual tests, the results show that the visual tests will not give attackers useful information about the original data, while the numerical tests show that the entropy attacks are not possible and the correlation between the adjacent pixels will not give useful information. Finally, the results show that the proposed model is strong against different types of attacks.

  12. Salt-gland secretion and blood flow in the goose.

    Science.gov (United States)

    Hanwell, A; Linzell, J L; Peaker, M

    1971-03-01

    1. Salt-gland blood flow in the domestic goose has been measured using a combination of Sapirstein's indicator fractionation technique for organ blood flow and Fegler's thermodilution method for cardiac output.2. Nasal salt secretion was induced by giving 0.5 M-NaCl or 0.154 M-NaCl I.V. or by giving artificial sea water by stomach tube into the proventriculus.3. During secretion, salt-gland blood flow increased from 82.7 +/- 21.9 ml./100 g tissue. min to as high as 2179 ml./100 g. min (mean 1209 +/- 140).4. The rate of secretion in response to salt loading was very variable and was not correlated with the rate of blood flow.5. From the data obtained, it could be calculated that the median values for the percentage extraction of ions from the arterial plasma were Na 15%, K 35%, Cl 21% and water 5.8%.6. Atropine abolished secretion but not the increase in blood flow produced by salt loading.7. Unilateral complete denervation abolished secretion from and the increase in blood flow through the operated but not the control gland.8. Anaesthesia, induced by pentobarbitone sodium, almost completely blocked secretion and the increase in blood flow in the salt-gland in response to salt loading.9. In geese given 0.5 or 0.154 M-NaCl I.V. a positive, significant correlation was found between the total amount of nasal secretion collected over 30 min and the concentrations of Na and Cl in the nasal fluid. However, when the time course of secretion was followed in any one bird, the rate of secretion was inversely related to the concentrations of Na and Cl.10. Harderian gland blood flow was not affected by salt loading.

  13. Identification of new secreted effectors in Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Geddes, Kaoru; Worley, Micah; Niemann, George; Heffron, Fred

    2005-10-01

    A common theme in bacterial pathogenesis is the secretion of bacterial products that modify cellular functions to overcome host defenses. Gram-negative bacterial pathogens use type III secretion systems (TTSSs) to inject effector proteins into host cells. The genes encoding the structural components of the type III secretion apparatus are conserved among bacterial species and can be identified by sequence homology. In contrast, the sequences of secreted effector proteins are less conserved and are therefore difficult to identify. A strategy was developed to identify virulence factors secreted by Salmonella enterica serovar Typhimurium into the host cell cytoplasm. We constructed a transposon, which we refer to as mini-Tn5-cycler, to generate translational fusions between Salmonella chromosomal genes and a fragment of the calmodulin-dependent adenylate cyclase gene derived from Bordetella pertussis (cyaA'). In-frame fusions to bacterial proteins that are secreted into the eukaryotic cell cytoplasm were identified by high levels of cyclic AMP in infected cells. The assay was sufficiently sensitive that a single secreted fusion could be identified among several hundred that were not secreted. This approach identified three new effectors as well as seven that have been previously characterized. A deletion of one of the new effectors, steA (Salmonella translocated effector A), attenuated virulence. In addition, SteA localizes to the trans-Golgi network in both transfected and infected cells. This approach has identified new secreted effector proteins in Salmonella and will likely be useful for other organisms, even those in which genetic manipulation is more difficult.

  14. The secret of neuroscience boom: Are there secret human experiments in Latin América?

    Directory of Open Access Journals (Sweden)

    David Salinas Flores

    2016-01-01

    Full Text Available About 6 years ago there sparked a phenomenon in science called the neuroscientific boom. Neurologists underpin this phenomenon to cost reduction techniques such as electroencephalograms and to improved noninvasive technology such as functional MRI. But the human brain, the most complex organ in the universe, has not yet been fully investigated with the existing noninvasive technologies. Thus, there is a suspicion that the real reason for this boom is a secret, forced, and illicit human experimentation in Latin America. Physicians should investigate, be alert, and report these potential unethical human experiments to prevent any further damage to the public health of the citizens of Latin societies.

  15. Regulation of interleukin-6 secretion in murine pituicytes

    DEFF Research Database (Denmark)

    Thorn, Anders; Tuxen, Mikkel; Moesby, Lise;

    2005-01-01

    Pituicytes, the astrocytic glial cells of the neural lobe, are known to secrete interleukin-6 and nitric oxide upon stimulation with various inflammatory mediators, i.e. interleukin-1beta. Nitric oxide is described to modulate the secretion of interleukin-6 in various cell types. The aim...... dependently but did not induce any detectable nitric oxide release. Co-stimulation with interferon-gamma and interleukin-1beta induced a significant nitric oxide release. In addition interferon-gamma inhibits interleukin-1beta induced interleukin-6 secretion dose dependently. The observed effect of interferon...

  16. The type II secretion system: biogenesis, molecular architecture and mechanism.

    Science.gov (United States)

    Korotkov, Konstantin V; Sandkvist, Maria; Hol, Wim G J

    2012-04-02

    Many gram-negative bacteria use the sophisticated type II secretion system (T2SS) to translocate a wide range of proteins from the periplasm across the outer membrane. The inner-membrane platform of the T2SS is the nexus of the system and orchestrates the secretion process through its interactions with the periplasmic filamentous pseudopilus, the dodecameric outer-membrane complex and a cytoplasmic secretion ATPase. Here, recent structural and biochemical information is reviewed to describe our current knowledge of the biogenesis and architecture of the T2SS and its mechanism of action.

  17. Insulin secretion and action in North Indian women during pregnancy

    DEFF Research Database (Denmark)

    Arora, G P; Almgren, P; Thaman, R G

    2017-01-01

    with normal glucose tolerance, and furthermore displayed lower insulin secretion than GDM1999 women. Urban habitat, illiteracy, high age and low BMI were independently associated with reduced insulin secretion, whereas Sikh religion, increasing age and BMI, as well as a family history of diabetes were....... RESULTS: Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women...

  18. Quantum secret sharing using the d-dimensional GHZ state

    Science.gov (United States)

    Bai, Chen-Ming; Li, Zhi-Hui; Xu, Ting-Ting; Li, Yong-Ming

    2017-03-01

    We propose a quantum secret sharing scheme that uses an orthogonal pair of n-qudit GHZ states and local distinguishability. In the proposed protocol, the participants use an X-basis measurement and classical communication to distinguish between the two orthogonal states and reconstruct the original secret. We also present (2, n)-threshold and generalized restricted (2, n)-threshold schemes that enable any two cooperating players from two disjoint groups to always reconstruct the secret. Compared to the existing scheme by Rahaman and Parker (Phys Rev A 91:022330, 2015), the proposed scheme is more general and the access structure contains more authorized sets.

  19. Nanoparticles secreted from ivy rootlets for surface climbing.

    Science.gov (United States)

    Zhang, Mingjun; Liu, Maozi; Prest, Harry; Fischer, Steve

    2008-05-01

    Using atomic force microscopy, we observed ivy secretes nanoparticles through adhering disks of the ivy aerial rootlets which allow the plant to affix to a surface. We analyzed the organic composition of the secretions using high-performance liquid chromatography/mass spectrometry and were able to determine the formula of 19 compounds. This study suggests that the nanoparticles play a direct and important role for ivy surface "climbing". Weak adhesion and hydrogen bonding seem to be the forces for the climbing mechanism. This ivy secretion mechanism may inspire new methods for synthesizing nanoparticles biologically or new approaches to adhesion mechanisms for engineering applications.

  20. Competitively coupled maps for hiding secret visual information

    Science.gov (United States)

    Vaidelys, M.; Ziaukas, P.; Ragulskis, M.

    2016-02-01

    A novel digital image hiding scheme based on competitively coupled maps is presented in this paper. Self-organizing patterns produced by an array of non-diffusively coupled nonlinear maps are exploited to conceal the secret. The secret image is represented in the form of a dot-skeleton representation and is embedded into a spatially homogeneous initial state far below the noise level. Self-organizing patterns leak the secret image at a predefined set of system parameters. Computational experiments are used to demonstrate the effectiveness and the security of the proposed image hiding scheme.

  1. Quantum Secret Sharing with Two-Particle Entangled States

    Institute of Scientific and Technical Information of China (English)

    LIU Wei-Tao; LIANG Lin-Mei; LI Cheng-Zu; YUAN Jian-Min

    2006-01-01

    We present a new protocol for the quantum secret sharing (QSS) task among multiparties with two-particle entangled states. In our scheme, the secret is split among a number of participating partners and the reconstruction requires collaboration of all the authorized partners. Instead of multiparticle Greenberger-Horne-Zeilinger states,only two-particle entangled states are employed in this scheme. By local operations and individual measurements on either of the two entangled particles, each authorized partner obtains a sequence of secret bits shared with other authorized partners. This protocol can be experimentally realized using only linear optical elements and simple entanglement source. It is scalable in practice.

  2. [Glutamate neurotransmission, stress and hormone secretion].

    Science.gov (United States)

    Jezová, D; Juránková, E; Vigas, M

    1995-11-01

    Glutamate neurotransmission has been investigated in relation to several physiological processes (learning, memory) as well as to neurodegenerative and other disorders. Little attention has been paid to its involvement in neuroendocrine response during stress. Penetration of excitatory amino acids from blood to the brain is limited by the blood-brain barrier. As a consequence, several toxic effects but also bioavailability for therapeutic purposes are reduced. A free access to circulating glutamate is possible only in brain structures lacking the blood-brain barrier or under conditions of its increased permeability. Excitatory amino acids were shown to stimulate the pituitary hormone release, though the mechanism of their action is still not fully understood. Stress exposure in experimental animals induced specific changes in mRNA levels coding the glutamate receptor subunits in the hippocampus and hypothalamus. The results obtained with the use of glutamate receptor antagonists indicate that a number of specific receptor subtypes contribute to the stimulation of ACTH release during stress. The authors provided also data on the role of NMDA receptors in the control of catecholamine release, particularly in stress-induced secretion of epinephrine. These results were the first piece of evidence on the involvement of endogenous excitatory amino acids in neuroendocrine activation during stress. Neurotoxic effects of glutamate in animals are well described, especially after its administration in the neonatal period. In men, glutamate toxicity and its use as a food additive are a continuous subject of discussions. The authors found an increase in plasma cortisol and norepinephrine, but not epinephrine and prolactin, in response to the administration of a high dose of glutamate. It cannot be excluded that these effects might be induced even by lower doses in situations with increased vulnerability to glutamate action (age, individual variability). (Tab. 1, Fig. 6, Ref. 44.).

  3. Secret letters cast light on Copenhagen

    Energy Technology Data Exchange (ETDEWEB)

    Durrani, Matin

    2001-11-01

    Letters by Niels Bohr that have been kept secret since his death could explain the mystery of why Werner Heisenberg visited him in Copenhagen in 1941. When the author Michael Frayn spent two years writing Copenhagen, he had no idea how successful the play would become. He doubted that audiences would sit through a historical drama about a war-time meeting between Werner Heisenberg - head of Germany's nuclear programme - and his old mentor Niels Bohr in the Nazi-occupied Danish capital in 1941. But Frayn's efforts paid off. Audiences and critics alike have thrilled at the way the award-winning play probes the historical uncertainty that surrounds the encounter. Was Heisenberg fishing for information about the Allies' atomic plans - or was he trying to recruit Bohr for Germany's bomb programme? Did Heisenberg want to suggest that the Germans were close to finishing a bomb so that the Allies would make peace with Hitler? Maybe he was simply seeking approval from Bohr for his own atomic work. There is also a moral debate: did Heisenberg know how to build a bomb, but decided not to - or did he want to build one, but got his calculations wrong? Unfortunately, no-one was there to record or observe the encounter and we cannot know for sure what was said or implied between the two men. All we do know is that the pair dined together and took a short walk - and that the incident damaged Bohr and Heisenberg's friendship forever. To piece together what happened, historians of science have had to rely on Heisenberg's post-war recollections - which have been ambiguous and contradictory - along with scraps of evidence from secondary sources. (U.K.)

  4. A Bespoke Technique for Secret Messaging

    Directory of Open Access Journals (Sweden)

    Mahimn Pandya

    2013-04-01

    Full Text Available The communication of digital assets on the internet infrastructure is increasing in its volume with threats on its security with regard to active and passive attacks of eavesdroppers. This concern has opened up the research channel to improve the techniques of secure and reliable communication protecting intellectual property rights and message security. Constant efforts of researchers in this area to achieve communication at faster rate maintaining security of digital assets, is giving improved techniques to achieve the goal. The efforts made here in this work are in the direction to enhance level of security in making faster reliable and secure communication. In spite of continued efforts, still as on today, it is challenging to hide the communication from eavesdropper. The disciplines of Cryptography, Steganography and Digital Watermarking are still popular areas of research. They are continuously digging to find robust and effective algorithms to protect digital communications and digital assets. It is very true that if the complexity in algorithm is increased, higher security level can be achieved. In the reviewed work, Researchers have developed algorithms for text encryption and embedment in digital watermarking using LSB at cost of time. The proposed work is targeted to maintain the tradeoff between the complexity level of algorithm and security level of message considering the time factor. The proposed work has evolved with two algorithms: AMEADT (ASCII Message Encryption and Decryption Technique to protect secret message and AMEAET (ASCII Message Embedment and Extraction Technique to embed encrypted text to digital image. The implementation of these algorithms has resulted in justifying higher level of security with comparatively lower level of complexity of algorithm.

  5. Burkholderia cenocepacia type VI secretion system mediates escape of type II secreted proteins into the cytoplasm of infected macrophages.

    Directory of Open Access Journals (Sweden)

    Roberto Rosales-Reyes

    Full Text Available Burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. We have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (BcCVs resembling arrested autophagosomes. Intracellular bacteria stimulate IL-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion system (T6SS is required for these phenotypes but surprisingly it is not required for the maturation arrest of the BcCV. Here, we show that macrophages infected with B. cenocepacia employ the NLRP3 inflammasome to induce IL-1β secretion and pyroptosis. Moreover, IL-1β secretion by B. cenocepacia-infected macrophages is suppressed in deletion mutants unable to produce functional Type VI, Type IV, and Type 2 secretion systems (SS. We provide evidence that the T6SS mediates the disruption of the BcCV membrane, which allows the escape of proteins secreted by the T2SS into the macrophage cytoplasm. This was demonstrated by the activity of fusion derivatives of the T2SS-secreted metalloproteases ZmpA and ZmpB with adenylcyclase. Supporting this notion, ZmpA and ZmpB are required for efficient IL-1β secretion in a T6SS dependent manner. ZmpA and ZmpB are also required for the maturation arrest of the BcCVs and bacterial intra-macrophage survival in a T6SS-independent fashion. Our results uncover a novel mechanism for inflammasome activation that involves cooperation between two bacterial secretory pathways, and an unanticipated role for T2SS-secreted proteins in intracellular bacterial survival.

  6. 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.

  7. Cosmic microwave background constraints on secret interactions among sterile neutrinos

    Science.gov (United States)

    Forastieri, Francesco; Lattanzi, Massimiliano; Mangano, Gianpiero; Mirizzi, Alessandro; Natoli, Paolo; Saviano, Ninetta

    2017-07-01

    Secret contact interactions among eV sterile neutrinos, mediated by a massive gauge boson X (with MX ll MW), and characterized by a gauge coupling gX, have been proposed as a mean to reconcile cosmological observations and short-baseline laboratory anomalies. We constrain this scenario using the latest Planck data on Cosmic Microwave Background anisotropies, and measurements of baryon acoustic oscillations (BAO). We consistently include the effect of secret interactions on cosmological perturbations, namely the increased density and pressure fluctuations in the neutrino fluid, and still find a severe tension between the secret interaction framework and cosmology. In fact, taking into account neutrino scattering via secret interactions, we derive our own mass bound on sterile neutrinos and find (at 95 % CL) ms relatively large coupling gX~ 10-1, previously indicated as a possible solution to the small scale dark matter problem.

  8. Secrets of universe eyed as collider core installed

    CERN Multimedia

    Evans, Robert

    2007-01-01

    "The world's leading centre for research into the origins of matter on Wedneday took a giant step towards completion of 1 15-year project which scientists hope will unlock many secrets of the universe."(1 page)

  9. Secrets of universe eyed as collider core installed

    CERN Multimedia

    Evans, Robert

    2007-01-01

    "The world's leading centre for researach into the origins of matter on Wednesday took a giant step towards completion of a 15-year project which scientists hope will unlock many secrets of the universe." (1/2 page)

  10. Machine set to probe secrets of the universe

    CERN Multimedia

    Lovell, Jeremy

    2006-01-01

    "Deep underground on the Franco-Swiss border someonw will throw a switch next year to start one of the most ambitious experiments in history, probing the secrets of the universe and possibly finding new dimensions."

  11. ROCKing cytokine secretion balance in human T cells.

    Science.gov (United States)

    Zanin-Zhorov, Alexandra; Waksal, Samuel D

    2015-04-01

    Balanced regulation of cytokine secretion in T cells is critical for maintenance of immune homeostasis and prevention of autoimmunity. The Rho-associated kinase (ROCK) 2 signaling pathway was previously shown to be involved in controlling of cellular movement and shape. However, recent work from our group and others has demonstrated a new and important role of ROCK2 in regulating cytokine secretion in T cells. We found that ROCK2 promotes pro-inflammatory cytokines such as IL-17 and IL-21, whereas IL-2 and IL-10 secretion are negatively regulated by ROCK2 under Th17-skewing activation. Also, in disease, but not in steady state conditions, ROCK2 contributes to regulation of IFN-γ secretion in T cells from rheumatoid arthritis patients. Thus, ROCK2 signaling is a key pathway in modulation of T-cell mediated immune responses underscoring the therapeutic potential of targeted inhibition of ROCK2 in autoimmunity.

  12. Issue of Franchising Operational Resources:IP and Business Secret

    Institute of Scientific and Technical Information of China (English)

    萧仁杰

    2015-01-01

    Franchising is a business model which uses business resources(trade mark, patent or business secret etc) to contract others to use for profit.In the franchise operation, business resources are the core value, business resources can make the franchisee to establish strong competitiveness or edges within the market, which also made a franchisor to develop and growth.Business resources are usually makes the franchise operation to have sufficient market advantages, the content of intellectual property or trade secrets which usually other industry competitors do not have, which made this kind of business resources for the franchisor more attractive to investors in the business world. Although, intellectual property and trade secrets there are a lot of different in the field of franchising sector, but there are sometimes have some overlap in content, it is a decision for franchisor to use intellectual property rights, or to use the trade secret to franchising as the core resource for protection.

  13. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... genes were expressed in placenta and microsomal extracts from human placenta contained triglyceride transfer activity, indicating expression of bioactive MTP. To detect lipoprotein secretion, biopsies from term placentas were placed in medium with [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  14. Ghrelin drives GH secretion during fasting in man

    NARCIS (Netherlands)

    A.F. Muller (Alex); S.W.J. Lamberts (Steven); L.J. Hofland (Leo); M. Bidlingmaier (Martin); C.J. Strasburger; E. Ghigo (Ezio); A-J. van der Lely (Aart-Jan); J.A.M.J.L. Janssen (Joseph); P.M. van Koetsveld (Peter)

    2002-01-01

    textabstractOBJECTIVES: In humans, fasting leads to elevated serum GH concentrations. Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin release are considered as the main mechanisms that induce this elevated GH secretion during fasting. Ghrelin is an

  15. A secreted tyrosine kinase acts in the extracellular environment.

    Science.gov (United States)

    Bordoli, Mattia R; Yum, Jina; Breitkopf, Susanne B; Thon, Jonathan N; Italiano, Joseph E; Xiao, Junyu; Worby, Carolyn; Wong, Swee-Kee; Lin, Grace; Edenius, Maja; Keller, Tracy L; Asara, John M; Dixon, Jack E; Yeo, Chang-Yeol; Whitman, Malcolm

    2014-08-28

    Although tyrosine phosphorylation of extracellular proteins has been reported to occur extensively in vivo, no secreted protein tyrosine kinase has been identified. As a result, investigation of the potential role of extracellular tyrosine phosphorylation in physiological and pathological tissue regulation has not been possible. Here, we show that VLK, a putative protein kinase previously shown to be essential in embryonic development, is a secreted protein kinase, with preference for tyrosine, that phosphorylates a broad range of secreted and ER-resident substrate proteins. We find that VLK is rapidly and quantitatively secreted from platelets in response to stimuli and can tyrosine phosphorylate coreleased proteins utilizing endogenous as well as exogenous ATP sources. We propose that discovery of VLK activity provides an explanation for the extensive and conserved pattern of extracellular tyrosine phosphophorylation seen in vivo, and extends the importance of regulated tyrosine phosphorylation into the extracellular environment.

  16. Giant machine set to probe secrets of the universe

    CERN Multimedia

    2006-01-01

    "Deep underground on the Franco-Swiss border someone will throw a switch next year to start one of the most ambitious experiments in history, probing the secrets of the universe and possibly finding new dimensions." (2/3 page)

  17. Giant machine set to probe secrets of the universe

    CERN Multimedia

    2006-01-01

    "Deep underground on the Franco-Swiss border someone will throw a switch next year to start one of the most ambitious experiments in history, probing the secrets of the universe and possibly finding new dimensions." (1 page)

  18. The secretory synapse: the secrets of a serial killer.

    Science.gov (United States)

    Bossi, Giovanna; Trambas, Christina; Booth, Sarah; Clark, Richard; Stinchcombe, Jane; Griffiths, Gillian M

    2002-11-01

    Cytotoxic T lymphocytes (CTLs) destroy their targets by a process involving secretion of specialized granules. The interactions between CTLs and target can be very brief; nevertheless, adhesion and signaling proteins segregate into an immunological synapse. Secretion occurs in a specialized secretory domain. Use of live and fixed cell microscopy allows this secretory synapse to be visualized both temporally and spatially. The combined use of confocal and electron microscopy has produced some surprising findings, which suggest that the secretory synapse may be important both in delivering the lethal hit and in facilitating membrane transfer from target to CTL. Studies on the secretory synapse in wild-type and mutant CTLs have been used to identify proteins involved in secretion. Further clues as to the signals required for secretion are emerging from comparisons of inhibitory and activating synapses formed by natural killer cells.

  19. ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge.

    LENUS (Irish Health Repository)

    McDermott, J H

    2008-09-01

    We describe a case of Cushing\\'s syndrome due to ectopic ACTH secretion, where the only potential source on conventional imaging was a tiny benign-appearing lung nodule, which failed to take up radiolabelled octreotide.

  20. Reappraisal of bicarbonate secretion by the human oesophagus

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, Klaus

    1997-01-01

    BACKGROUND AND AIMS: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosalbicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophagealbicarbonate secretion and thus....../day omeprazole for three days and 80 mg intravenous omeprazole before perfusionor 600 mg/day ranitidine for three days and 50 mg/h intravenously during the perfusion. Saliva and samples of aspirate from the perfusedoesophagus and stomach were collected and bicarbonate concentrations were measured. RESULTS......: The median rates (95% confidence intervals)of intrinsic oesophageal bicarbonate secretion, corrected for contaminating salivary and gastric bicarbonate, were 89 (33-150) and 121 (63-203)mumol/h/10 cm (p > 0.5) in omeprazole and ranitidine treated subjects respectively. Salivary and gastric bicarbonate...