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Sample records for human c-peptide levels

  1. Human C-peptide. Part II: Clinical studies.

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    Beischer, W; Heinze, E; Keller, L; Raptis, S; Kerner, W; Pfeiffer, E F

    1976-08-01

    Human C-peptide is determined by radioimmunoassay. On gel filtration of serum from a healthy subject and from a patient with islet cell carcinoma, C-peptide (MW 3025) appears ahead of insulin (MW 5808) and shows much higher molar concentrations than the hormone. Human proinsulin cross-reacts with our antiserum to synthetic human C-peptide. On direct determination of immunomeasurable C-peptide (IMCP) in fasting serum of 25 healthy subjects we find an average of 1.8 (+/- 0.4) ng/ml, corresponding to 60.4 X 10(-11) Mol/l. The molar concentration is about five-fold as compared to IMI (immuno-measurable insulin). IMCP and IMI patterns are not identical on stimulation of beta-cell secretion in healthy subjects by i.v. glucose or glucose-glibenclamide. This is probably due to differences in peripheral metabolism of both compounds. We conclude from our results that C-peptide determined in peripheral venous serum is a better indicator of beta-cell secretion than is insulin. Among 26 insulin-treated juvenile diabetics 15 show not measurable and 11 subnormal IMCP levels in fasting serum. No rise in IMCP is found 1-2 h following breakfast. Four juvenile patients receiving no insulin in a phase of total diabetes remission have normal or raised fasting IMCP concentrations. Only 2 out of 24 adult diabetics (16 treated with insulin and 8 with tablets) show non-measurable fasting IMCP concentrations, in another 4 patients values are below and in the remaining 18 cases above 1 ng/ml serum. Stimulation of beta-cell secretion through glucose-glibenclamide is more or less impaired in all adult diabetics compared to the healthy subjects.

  2. C-peptide modifies leptin and visfatin secretion in human adipose tissue.

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    Garcia-Serrano, Sara; Gutiérrez-Repiso, Carolina; Gonzalo, Montserrat; Garcia-Arnes, Juan; Valdes, Sergio; Soriguer, Federico; Perez-Valero, Vidal; Alaminos-Castillo, Miguel A; Francisco Cobos-Bravo, Juan; Moreno-Ruiz, Francisco J; Rodriguez-Cañete, Alberto; Rodríguez-Pacheco, Francisca; Garcia-Escobar, Eva; García-Fuentes, Eduardo

    2015-08-01

    The effects of C-peptide on adipose tissue, an organ involved in the development of obesity and insulin resistance, are not yet well known. The aim of this study was to determine whether C-peptide could be involved in the regulation of the adipocytokine synthesis in human visceral adipose tissue. The association between C-peptide and different serum adipocytokines, with an intravenous glucose tolerance test (IVGTT), and in an in vitro study in subjects without obesity and in subjects with morbid obesity were analyzed. In different multiple regression analysis models, C-peptide and C-peptide increase above basal levels during total IVGTT and between 0 and 10 min were associated positively with leptin and negatively with visfatin. Rhodamine-labeled C-peptide binds to human adipocytes, and this binding was blocked with excess of unlabeled C-peptide. Exposure of human visceral explants and adipocytes from subjects with morbid obesity to C-peptide at 1 and 10 nM induced a significant increase in leptin and a decrease in visfatin secretion. In subjects without obesity, these C-peptide effects were found mainly at 10 nM. These effects can be inhibited by phosphatidylinositol 3-kinase (PI3K) or protein kinase B (PKB) inhibitors. C-peptide may be involved in the regulation of leptin and visfatin secretion, molecules intimately involved in energy homeostasis processes, through PI3K or PKB pathways. © 2015 The Obesity Society.

  3. Human Proinsulin C-peptide from a Precursor Overexpressed in Pichia pastoris

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    Yang-Bin HUANG; Jun REN; You-Shang ZHANG; Jiang LI; Xin GAO; Jiu-Ru SUN; Yi LU; Tao FENG; Jian FEI; Da-Fu CUI; Qi-Chang XIA

    2006-01-01

    In this article we report the production of human proinsulin C-peptide with 31 amino acid residues from a precursor overexpressed in Pichia pastoris. A C-peptide precursor expression plasmid containing nine C-peptide genes in tandem was constructed and used to transform P. pastoris. Transformants with a high copy number of the C-peptide precursor gene integrated into the chromosome of P. pastoris were selected. In high-density fermentation in a 300 liter fermentor using a simple culture medium composed mainly of salt and methanol, the C-peptide precursor was overexpressed to a level of 2.28 g per liter. A simple procedure was established to purify the expression product from the culture medium. The purified C-peptide precursor was converted into C-peptide by trypsin and carboxypeptidase B joint digestion. The yield of C-peptide with a purity of 96% was 730 mg per liter of culture. The purified C-peptide was characterized by mass spectrometry, N- and C-terminal amino acid sequencing, and sodium dodecylsulfate-polyacrylamide gel electrophoresis.

  4. Syntheses of C-peptides and human proinsulin.

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    Yanaihara, N; Yanaihara, C; Sakagami, M; Sakura, N; Hashimoto, T; Nishida, T

    1978-01-01

    Syntheses of human, dog, rat, and duck C-peptides and their analogues and preliminary results on the total synthesis of human proinsulin are described. In the syntheses of the C-peptides, chain elongation was performed exclusively by the azide-fragment condensation method in solution. The synthetic human, dog, rat, and duck C-peptides and their analogues were proved to be homogeneous by several analytic means. With these synthetic peptides, radioimmunoassay systems for dog, rat, and duck C-peptides were developed. For the total synthesis of human proinsulin, 10 protected peptide hydrazides were prepared, and the linearly protected hexaoctacontapeptide having the proposed sequence of human proinsulin was constructed by the azide-fragment condensation method in solution starting from the C-terminal undecapeptide (HP 75-86). After deblocking of the alpha-amino protection, the partially protected hexaoctacontapeptide was treated with sodium in liquid ammonia. The ensuing sulfhydryl form was converted to the S-sulfonate form, which was reduced and then air-oxidized. The oxidized material was purified by gel filtration on Sephadex G-50 (fine) followed by ion-exchange chromatography on DEAE-cellulose. The cross-reactivity in the insulin radioimmunoassay of the ensuing product was 62.5 per cent of porcine proinsulin on a weight basis at B/Bo = 60 per cent. Acid hydrolysis and amino acid analysis of this product gave the theoretically expected ratios. In addition, this peptide, as well as the S-sulfonate form of the hexaoctacontapeptide, showed displacement curves superimposable on that of synthetic human C-peptide on an equimolar basis in the human C-peptide radioimmunoassay (antiserum 527). These results confirm the synthesis of human proinsulin.

  5. Unraveling the aggregation propensity of human insulin C-peptide.

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    Tsiolaki, Paraskevi L; Louros, Nikolaos N; Zompra, Aikaterini A; Hamodrakas, Stavros J; Iconomidou, Vassiliki A

    2017-03-01

    Over the last 20 years, proinsulin C-peptide emerged as an important player in various biological events. Much time and effort has been spent in exploring all functional features of C-peptide and recording its implications in Diabetes mellitus. Only a few studies, though, have addressed C-peptide oligomerization and link this procedure with Diabetes. The aim of our work was to examine the aggregation propensity of C-peptide, utilizing Transmission Electron Microscopy, Congo Red staining, ATR-FTIR, and X-ray fiber diffraction at a 10 mg ml(-1) concentration. Our experimental work clearly shows that C-peptide self-assembles into amyloid-like fibrils and therefore, the aggregation propensity of C-peptide is a characteristic novel feature that should be related to physiological and also pathological conditions. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 108: 1-8, 2017.

  6. Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients

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    Sung-Tae Kim

    2011-02-01

    Full Text Available BackgroundRecent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM patients.MethodsData was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed.ResultsA simple correlation was found between basal C-peptide and components of metabolic syndrome (MS. Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III of the National Cholesterol Education Program's (NCEP's, World Health Organization (WHO, and the International Diabetes Federation (IDF criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029. The multiple regression analysis between intima-media thickness (IMT and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043, while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226.ConclusionBasal C-peptide is related to cardiovascular predictors (IMT of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.

  7. C-Peptide Levels Predict the Effectiveness of Dipeptidyl Peptidase-4 Inhibitor Therapy

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    Sevin Demir

    2016-01-01

    Full Text Available Background. Our aim was to define the conditions that affect therapeutic success when dipeptidyl peptidase-4 (DPP-4 inhibitor is added to metformin monotherapy. Materials and Methods. We reviewed the medical records of 56 patients who had received DPP-4 inhibitor as an add-on to metformin monotherapy and evaluated their response in the first year of therapy. Fasting blood glucose (FBG, HbA1c, C-peptide, and weight of the patients were recorded at 3-month intervals during the first year of treatment. Results. Patients who added DPP-4 inhibitor to metformin monotherapy had significant weight loss (P=0.004 and FBG and HbA1c levels were significantly lowered during the first 6 months (both P<0.001. Baseline levels of C-peptide were predictive for success of the treatment (P=0.02, even after correction for confounding factors, for example, age, gender, or BMI (P=0.03. Duration of diabetes was not a predictor of response to treatment (P=0.60. Conclusion. Our study demonstrates that in patients having inadequate glycemic control, the addition of a DPP-4 inhibitor as a second oral agent to metformin monotherapy provides better glycemic control, protects β-cell reserves, and does not cause weight gain. These effects depend on baseline C-peptide levels.

  8. C-peptide levels predict type 2 diabetes remission after bariatric surgery

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    Ana M. Ramos-Leví

    2013-10-01

    Full Text Available Background: C-peptide (Cp serves as a surrogate of pancreatic beta-cell reserve. This study evaluates the clinical significance of basal Cp as a predictor of type 2 diabetes (T2D remission after bariatric surgery (BS. Research design and methods: Retrospective study of 22 patients with BMI > 35 kg/m² and T2D who underwent BS. Evaluation of anthropometric and glucose metabolism parameters before BS and at one-year follow-up. Analysis of patients with T2D remission (HbAlc 3.75 ng/mL provided a clinically useful cut-off for prediction of T2D remission. T2D remission rates were different according to median preoperative Cp: 27.3% if Cp 3.8 ng/mL (p = 0.010. Conclusions: Patients with elevated preoperative Cp levels achieve higher rates of T2D remission one year after BS. A Cp concentration > 3.75 ng/mL seems clinically useful.

  9. [C-peptide physiological effects].

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    Shpakov, A O; Granstrem, O K

    2013-02-01

    In the recent years there were numerous evidences that C-peptide, which was previously considered as a product of insulin biosynthesis, is one of the key regulators of physiological processes. C-peptide via heterotrimeric G(i/o) protein-coupled receptors activates a wide range of intracellular effector proteins and transcription factors and, thus, controls the inflammatory and neurotrophic processes, pain sensitivity, cognitive function, macro- and microcirculation, glomerular filtration. These effects of C-peptide are mainly expressed in its absolute or relative deficiency occurred in type 1 diabetes mellitus and they are less pronounced when the level of C-peptide is close to normal. Replacement therapy with C-peptide prevents many complications of type 1 diabetes, such as atherosclerosis, diabetic peripheral neuropathy, and nephropathy. C-peptide interacts with the insulin hexamer complexes and induces their dissociation and, as a result, regulates the functional activity of the insulin signaling system. At the same time, C-peptide at the concentrations above physiological may demonstrate pro-inflammatory effects on the endothelial cells and cause atherosclerotic changes in the vessels, which should be considered in the study of pathogenic mechanisms of complications of type 2 diabetes mellitus, where the level of C peptide is increased, as well as in the development of approaches for C-peptide application in clinic. This review is devoted contemporary achievements and unsolved problems in the study of C-peptide, as an important regulator of physiological and biochemical processes.

  10. C-peptide levels predict type 2 diabetes remission after bariatric surgery

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    Ana M. Ramos-Leví; Pilar Matía; Lucio Cabrerizo; Ana Barabash; María José Torrejón; Andrés Sánchez-Pernaute; Torres, Antonio J.; Rubio, Miguel A.

    2013-01-01

    Background: C-peptide (Cp) serves as a surrogate of pancreatic beta-cell reserve. This study evaluates the clinical significance of basal Cp as a predictor of type 2 diabetes (T2D) remission after bariatric surgery (BS). Research design and methods: Retrospective study of 22 patients with BMI > 35 kg/m² and T2D who underwent BS. Evaluation of anthropometric and glucose metabolism parameters before BS and at one-year follow-up. Analysis of patients with T2D remission (HbAlc < 6%, fasting gluco...

  11. C-Peptide Test

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    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities C-peptide Share this page: Was this page helpful? Also known as: Insulin C-peptide; Connecting Peptide Insulin; Proinsulin C-peptide Formal ...

  12. No association of plasma levels of adiponectin and c-peptide with risk of aggressive prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

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    Stevens, Victoria L; Jacobs, Eric J; Sun, Juzhong; Gapstur, Susan M

    2014-05-01

    Obesity is associated with a higher risk of aggressive prostate cancer and alters circulating levels of insulin and adiponectin, two hormones that influence biologic processes implicated in carcinogenesis. Results of some studies showed associations of circulating levels of adiponectin, insulin, and c-peptide (a marker of insulin secretion) with aggressive prostate cancer, but the size of these studies was limited. A nested case-control study of 272 aggressive prostate cancer cases [Gleason score ≥ 7 (4+3) or T3-T4] and 272 age- and race-matched controls from the Cancer Prevention Study II Nutrition Cohort was conducted to determine the associations of prediagnostic plasma levels of c-peptide and adiponectin with risk of aggressive prostate cancer. Neither circulating adiponectin nor c-peptide was associated with risk of aggressive prostate cancer. In analyses of the highest-risk aggressive prostate cancer (Gleason score ≥ 8 or T3-T4), the highest quartile of c-peptide, compared with the lowest, was associated with an OR of 1.41 [95% confidence interval (CI), 0.72-2.78]. Our findings provide no support for the hypothesis that adiponectin is associated with risk of aggressive prostate cancer but a possible association of high levels of c-peptide with particularly high-risk prostate cancer cannot be ruled out. These results indicate that changes in circulating levels of adiponectin and c-peptide do not play an important role in risk of aggressive prostate cancer. ©2014 AACR.

  13. Pilot study on peptide purity—synthetic human C-peptide

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    Josephs, R. D.; Li, M.; Song, D.; Daireaux, A.; Choteau, T.; Stoppacher, N.; Westwood, S.; Wielgosz, R.; Xiao, P.; Liu, Y.; Gao, X.; Zhang, C.; Zhang, T.; Mi, W.; Quan, C.; Huang, T.; Li, H.; Melanson, J. E.; Ün, I.; Gören, A. C.; Quaglia, M.; Warren, J.

    2017-01-01

    Under the auspices of the Protein Analysis Working Group (PAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a pilot study, CCQM-P55.2, was coordinated by the Bureau International des Poids et Mesures (BIPM) and the Chinese National Institute of Metrology (NIM). Four Metrology Institutes or Designated Institutes and the BIPM participated. Participants were required to assign the mass fraction of human C-peptide (hCP) present as the main component in the comparison sample for CCQM-P55.2. The comparison samples were prepared from synthetic human hCP purchased from a commercial supplier and used as provided without further treatment or purification. hCP was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of short (up to 5 kDa), non-cross-linked synthetic peptides/proteins. It was anticipated to provide an analytical measurement challenge representative for the value-assignment of compounds of broadly similar structural characteristics. The majority of participants used a quantitative nuclear magnetic resonance spectroscopy (qNMR) corrected for peptide impurities. Other participants provided results obtained by peptide impurity corrected amino acid analysis (PICAA) or elemental analysis (PICCHN). It was decided to assign reference values based on the KCRVs of CCQM-K115 for both the hCP mass fraction and the mass fraction of the peptide related impurities as indispensable contributor regardless of the use of PICAA, mass balance or any other approach to determine the hCP purity. This allowed participants to demonstrate the efficacy of their implementation of the approaches used to determine the hCP mass fraction. In particular it allows participants to demonstrate the efficacy of their implementation of peptide related impurity identification and quantification. The assessment of the mass fraction of peptide impurities is based on the assumption that only the most exhaustive and

  14. Key comparison study on peptide purity—synthetic human C-peptide

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    Josephs, R. D.; Li, M.; Song, D.; Westwood, S.; Stoppacher, N.; Daireaux, A.; Choteau, T.; Wielgosz, R.; Xiao, P.; Liu, Y.; Gao, X.; Zhang, C.; Zhang, T.; Mi, W.; Quan, C.; Huang, T.; Li, H.; Flatschart, R.; Borges Oliveira, R.; Melanson, J. E.; Ohlendorf, R.; Henrion, A.; Kinumi, T.; Wong, L.; Liu, Q.; Oztug Senal, M.; Vatansever, B.; Ün, I.; Gören, A. C.; Akgöz, M.; Quaglia, M.; Warren, J.

    2017-01-01

    Under the auspices of the Protein Analysis Working Group (PAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a key comparison, CCQM-K115, was coordinated by the Bureau International des Poids et Mesures (BIPM) and the Chinese National Institute of Metrology (NIM). Eight Metrology Institutes or Designated Institutes and the BIPM participated. Participants were required to assign the mass fraction of human C-peptide (hCP) present as the main component in the comparison sample for CCQM-K115. The comparison samples were prepared from synthetic human hCP purchased from a commercial supplier and used as provided without further treatment or purification. hCP was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of short (up to 5 kDa), non-cross-linked synthetic peptides/proteins. It was anticipated to provide an analytical measurement challenge representative for the value-assignment of compounds of broadly similar structural characteristics. The majority of participants used a peptide impurity corrected amino acid analysis (PICAA) approach as the amount of material that has been provided to each participant (25 mg) is insufficient to perform a full mass balance based characterization of the material by a participating laboratory. The coordinators, both the BIPM and the NIM, were the laboratories to use the mass balance approach as they had more material available. It was decided to propose KCRVs for both the hCP mass fraction and the mass fraction of the peptide related impurities as indispensable contributor regardless of the use of PICAA, mass balance or any other approach to determine the hCP purity. This allowed participants to demonstrate the efficacy of their implementation of the approaches used to determine the hCP mass fraction. In particular it allows participants to demonstrate the efficacy of their implementation of peptide related impurity identification and quantification

  15. Effect of maternal lipid profile, C-peptide, insulin, and HBA1c levels during late pregnancy on large-for-gestational age newborns

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    Ruo-Lin Hou; Huan-Huan Zhou; Xiao-Yang Chen; Xiu-Min Wang; Jie Shao; Zheng-Yan Zhao

    2014-01-01

    Background: Large-for-gestational age (LGA) newborns can increase the risk of metabolic syndrome. Previous studies have shown that the levels of maternal blood lipids, connecting peptide (C-peptide), insulin and glycosylated hemoglobin (HbA1c) were significantly different between LGA and appropriate-for-gestational age (AGA) newborns. This study aimed to determine the effect of the levels of maternal lipids, C-peptide, insulin, and HbA1c during late pregnancy on LGA newborns. Methods: This study comprised 2790 non-diabetic women in late pregnancy. Among their newborns, 2236 (80.1%) newborns were AGA, and 554 (19.9%) newborns were LGA. Maternal and neonatal characteristics were obtained from questionnaires and their case records. The levels of maternal fasting serum apolipoprotein A1 (ApoA1), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-peptide, insulin and blood HbA1c were measured. The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups, respectively. Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns. Results: Maternal TG, C-peptide, insulin and HbA1c levels were signifi cantly higher in the LGA group than in the AGA group (P Conclusion: High maternal TG level during late pregnancy is signifi cantly associated with LGA newborns.

  16. Fasting C-peptide levels and death resulting from all causes and breast cancer: the health, eating, activity, and lifestyle study.

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    Irwin, Melinda L; Duggan, Catherine; Wang, Ching-Yun; Smith, Ashley Wilder; McTiernan, Anne; Baumgartner, Richard N; Baumgartner, Kathy B; Bernstein, Leslie; Ballard-Barbash, Rachel

    2011-01-01

    To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer. This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses. Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m(2), women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive. Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored.

  17. Insulin C-peptide test

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    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  18. Changes of Leptin Level in Serum, Cord Venous Blood and Placenta in Women with Gestational Diabetes Mellitus and Correlations with Insulin and C-Peptide

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    Jin-ming ZHU; Li SHI; Xiao-yuan LU; Rong-rong ZHANG; Min LI; Xiao-ning ZHANG

    2014-01-01

    ObjectiveTo investigate the changes of leptin levels in serum, cord venous blood and placenta and examine the possible relationships among them in women with gestational diabetes mellitus (GDM).Methods This case-control study was performed in 40 women with GDM and 40 normal women. The women with GDM received dietary advice, blood glucose monitoring and insulin treatment when necessary. Maternal serum and venous cord blood leptin, insulin and C-peptide levels were detected by ELISA. The expression level of leptin in placenta was measured by an immunohistochemical method. Results1. Leptin, insulin and C-peptide levels in serum of the women with GDM were significantly higher than those of the normal women (P<0.01,P<0.05, P<0.01). 2. Cord venous blood leptin and insulin in GDM group were significantly higher than in the normal group (P<0.01,P<0.05). No significant difference was found in cord venous blood C-peptide between two groups. 3. The expression of placenta leptin protein was significantly higher in GDM women than in normal women (P<0.01). There were positive correlations between placental leptin, cord venous leptin and insulin, birth weight, ponderal index in GDM women (r=0.37,P<0.05;r=0.39,P<0.05;r=0.53,P<0.01;r=0.54,P<0.01). However, there was no correlation between placental leptin and serum leptin.Conclusion The women with GDM and their fetuses suffer from hyperleptinaemia and hyperinsulinaemia. In the women with GDM, there was disorder in the interaction between leptin and insulin. The GDM women and their fetuses may be prone to insulin resistance and leptin resistance in late pregnancy.

  19. C-peptide and diabetic kidney disease.

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    Brunskill, N J

    2017-01-01

    Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney disease, there have been no new therapies for this condition in the last 20 years. Mounting evidence supports a biological role for C-peptide, and findings from multiple studies now suggest that C-peptide may beneficially affect the disturbed metabolic and pathophysiological pathways leading to the development of diabetic nephropathy. Studies of C-peptide in animal models and in humans with type 1 diabetes all suggest a renoprotective effect for this peptide. In diabetic rodents, C-peptide reduces glomerular hyperfiltration and albuminuria. Cohort studies of diabetic patients with combined islet and kidney transplants suggest that maintained C-peptide secretion is protective of renal graft function. Further, in short-term studies of patients with type 1 diabetes, administration of C-peptide is also associated with a lowered hyperfiltration rate and reduced microalbuminuria. Thus, the available information suggests that type 1 diabetes should be regarded as a dual hormone deficiency disease and that clinical trials of C-peptide in diabetic nephropathy are both justified and urgently required.

  20. Effects of Clear Kefir on Biomolecular Aspects of Glycemic Status of Type 2 Diabetes Mellitus (T2DM Patients in Bandung, West Java [Study on Human Blood Glucose, c Peptide and Insulin

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    Judiono J

    2014-08-01

    Full Text Available Background: Diabetes Mellitus (DM triggers an excessive reaction of free-radicals. It increases reactive oxygen species and reduces antioxidants status as well as the β cell damage. Clear kefir was used for DM therapies, however it limited biomolecular exploration of its bioactive roles. Research aimed to investigate the effects of clear kefir on the biomolecular nature of the glycemic status of T2DM in Bandung. Methods: The randomized pretest-posttest control group was conducted by 106 T2DM patients. Research was done in several hospitals in Bandung and Cimahi, West Java from 2012–2013. Samples were divided randomly into three groups: (1 T2DM with HbA1c 7 fed standard diet and supplemented 200 ml/day by clear kefir, (3 T2DM with HbA1c was fed a standard diet as a control group. Dose response was obtained from a preeliminary vivo study, and then converted to human dosage by year 2011. Intervention was effectively done for 30 days. HbA1c was measured by HPLC. Fasting blood glucose (FBG and Postprandial blood glucose levels (PBG were measured by enzymes levels. C Peptide and insulin were measured by Elisa. Data was analyzed by a statictics programme by significance p<0,05. Study was approved by ethic committee. Results : HbA1c was significantly reduced in delta level (p<0.01 and FBG (p<0.015 among kefir groups. PBG was not significantly reduced among groups. C-Peptide was significantly increased in delta level, except in control group (p<0.014. Insulin was reduced significantly, except in control group (p<0.003. Conclusions : Supplementation of clear kefir reduced blood glucose levels (HbA1c, FBG, PBG and increased c-peptide. Clear kefir’s biomolecular mechanisms and chemistry characterization is a challenge for future studies.

  1. [Levels of some auto-antibodies and C-peptide in insulin-treated patients with diabetes mellitus (DM) depending on gender of the patients and disease duration].

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    Likhonosov, P N; Khalangot, N D

    2007-01-01

    Determination of antibodies to thyroid peroxidase was recently proposed to single out subgroups among patients with DM1 for following clinical and genetic studies. 73 men and 64 women who are being treated with insulin and included in territorial register of patients with DM of Mariupol city, Donetsk region, Ukraine. Average age of patients at the stage of investigation was 35.17+/-1.16, the duration of the disease was 11.85+/-0.74, BMI-23.13+/-0.32 kg/m2, HBA1c9.23+/-0.25, C-peptide 0.48+/-0.09 nmol/l, glutaminic acid decarboxylase antibodies-GADAs-0.63+/-0.04 units/ml and did not depend on gender. Patients aged less then 30 years had their level of GADAbs and TPOAbs changed linearly correlated with the duration of diabetes mellitus. Obtained data can be used to assess subgroups among patients with DM1.

  2. C-peptide protects against hyperglycemic memory and vascular endothelial cell apoptosis.

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    Bhatt, Mahendra Prasad; Lee, Yeon-Ju; Jung, Se-Hui; Kim, Yong Ho; Hwang, Jong Yun; Han, Eun-Taek; Park, Won Sun; Hong, Seok-Ho; Kim, Young-Myeong; Ha, Kwon-Soo

    2016-10-01

    C-peptide exerts protective effects against diabetic complications; however, its role in inhibiting hyperglycemic memory (HGM) has not been elucidated. We investigated the beneficial effect of C-peptide on HGM-induced vascular damage in vitro and in vivo using human umbilical vein endothelial cells and diabetic mice. HGM induced apoptosis by persistent generation of intracellular ROS and sustained formation of ONOO(-) and nitrotyrosine. These HGM-induced intracellular events were normalized by treatment with C-peptide, but not insulin, in endothelial cells. C-peptide also inhibited persistent upregulation of p53 and activation of mitochondrial adaptor p66(shc) after glucose normalization. Further, C-peptide replacement therapy prevented persistent generation of ROS and ONOO(-) in the aorta of diabetic mice whose glucose levels were normalized by the administration of insulin. C-peptide, but not insulin, also prevented HGM-induced endothelial apoptosis in the murine diabetic aorta. This study highlights a promising role for C-peptide in preventing HGM-induced intracellular events and diabetic vascular damage.

  3. Modification of a traditional breakfast leads to increased satiety along with attenuated plasma increments of glucose, C-peptide, insulin, and glucose-dependent insulinotropic polypeptide in humans.

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    Ohlsson, Bodil; Höglund, Peter; Roth, Bodil; Darwiche, Gassan

    2016-04-01

    Our hypothesis was that carbohydrate, fat, and protein contents of meals affect satiety, glucose homeostasis, and hormone secretion. The objectives of this crossover trial were to examine satiety, glycemic-insulinemic response, and plasma peptide levels in response to 2 different recommended diabetes diets with equivalent energy content. One traditional reference breakfast and one test breakfast, with lower carbohydrate and higher fat and protein content, were randomly administered to healthy volunteers (8 men, 12 women). Blood samples were collected, and satiety was scored on a visual analog scale before and 3 hours after meals. Plasma glucose was measured, and levels of C-peptide, ghrelin, glucagon, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide (GIP), insulin, plasminogen activator inhibitor-1, and adipokines were analyzed by Luminex. Greater satiety, visual analog scale, and total and delta area under the curve (P satiety and attenuation of C-peptide, glucose, insulin, and GIP responses compared with the reference breakfast but does not affect adipokines, ghrelin, glucagon, glucagon-like peptide-1, and plasminogen activator inhibitor-1.

  4. Single vagus nerve stimulation reduces early postprandial C-peptide levels but not other hormones or postprandial metabolism.

    Science.gov (United States)

    Tang, M W; van Nierop, F S; Koopman, F A; Eggink, H M; Gerlag, D M; Chan, M W; Zitnik, R; Vaz, F M; Romijn, J A; Tak, P P; Soeters, M R

    2017-04-08

    A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.

  5. Influence of C-Peptide on Glucose Utilisation

    Directory of Open Access Journals (Sweden)

    B. Wilhelm

    2008-01-01

    Full Text Available During the recent years, multiple studies demonstrated that C-peptide is not an inert peptide, but exerts important physiological effects. C-peptide binds to cell membranes, stimulates the Na,K-ATPase and the endothelial nitric oxide (NO synthase. Moreover, there is evidence that C-peptide decreases glomerular hyperfiltration and increases glucose utilisation. Nevertheless, there is still limited knowledge concerning mechanisms leading to an increased glucose utilisation either in rats or in humans. The aim of this paper is to give an overview over the published studies regarding C-peptide and glucose metabolism from in vitro studies to longer lasting studies in humans.

  6. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells

    DEFF Research Database (Denmark)

    Galuska, Dana; Pirkmajer, Sergej; Barres, Romain

    2011-01-01

    Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity...

  7. Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene

    DEFF Research Database (Denmark)

    Blume, N; Petersen, J S; Andersen, L C;

    1992-01-01

    Synthetic peptides representing unique sequences in rat proinsulin C-peptide I and II were used to generate highly specific antisera, which, when applied on sections of normal rat pancreas, confirm a homogeneous coexpression of the two C-peptides in all islet beta-cells. Insulin gene expression...... is induced in the transformed heterogeneous rat islet cell clone, NHI-6F, by transient in vivo passage. During this process a transfected human insulin gene is coactivated with the endogenous nonallelic rat insulin I and II genes. Newly established cultures from NHI-6F insulinomas having a high frequency...

  8. Hemolysis Affects C-Peptide Immunoassay.

    Science.gov (United States)

    Wu, Zhi-Qi; Lu, Ju; Xu, Hua-Guo

    2016-11-01

    C-peptide is used widely as a marker of insulin secretion, and it participates in the inflammatory response and contributes to the development of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Previous studies have reported that C-peptide measurement was unaffected by hemolysis. However, we found that hemolysis negatively affected C-peptide assay in routine laboratory practice. We further established and validated an individualized hemolysis correction equation to correct and report accurate serum C-peptide results for hemolyzed samples. We studied the effects of hemolysis on C-peptide assay by adding lysed self red blood cells (self-RBCs) to serum. An individualized correction equation was derived. Further, we evaluated the performance of this individualized correction equation by artificially hemolyzed samples. C-peptide concentration decreased with increasing degree and exposure time of hemolysis. The individualized hemolysis correction equation derived: C-Pcorr = C-Pmeas /(0.969-1.5Hbserum/plasma -5.394 ×10(-5) Time), which can correct bias in C-peptide measurement caused by hemolysis. Hemolysis negatively affects C-peptide measurement. We can correct and report accurate serum C-peptide results for a wide range of degrees of sample hemolysis by individualized hemolysis correction equation for C-peptide assay. This correction would improve diagnostic accuracy and reduce inappropriate therapeutic decisions. © 2016 Wiley Periodicals, Inc.

  9. C-Peptide and Atherogenesis: C-Peptide as a Mediator of Lesion Development in Patients with Type 2 Diabetes Mellitus?

    Directory of Open Access Journals (Sweden)

    Nikolaus Marx

    2008-01-01

    Full Text Available Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. While some studies demonstrated beneficial effects of C-peptide, for example, by showing an inhibition of smooth muscle cell proliferation, others suggested proatherogenic mechanisms in patients with type 2 diabetes. Among them, C-peptide may facilitate the recruitment of inflammatory cells into early lesions and promote lesion progression by inducing smooth muscle cell proliferation. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential role of C-peptide in atherogenesis in patients with type 2 diabetes.

  10. C-PEPTIDE AMELIORATES KIDNEY INJURY FOLLOWING HEMORRHAGIC SHOCK

    Science.gov (United States)

    Chima, Ranjit S; Maltese, Giuseppe; LaMontagne, Timberly; Piraino, Giovanna; Denenberg, Alvin; O’Connor, Michael; Zingarelli, Basilia

    2013-01-01

    Reperfusion injury following hemorrhagic shock is accompanied by the development of a systemic inflammatory state that may lead to organ failure. C-peptide has been shown to exert anti-inflammatory effects in sepsis and myocardial ischemia-reperfusion injury, and to ameliorate renal dysfunction in diabetic animals. Hence, we investigated the effect of C-peptide on kidney injury following hemorrhagic shock. We hypothesized that C-peptide would exert reno-protective effects by blunting inflammation. Hemorrhagic shock was induced in male rats (3–4 months old) by withdrawing blood from the femoral artery to a mean arterial pressure of 50 mmHg. Animals were kept in shock for 3h at which time they were rapidly resuscitated by returning their shed blood. At the time of resuscitation and every hour thereafter, one group of animals received C-peptide (280 nmol/kg intravenously) while another group received vehicle. Hemorrhagic shock resulted in significant rise in plasma levels of creatinine and elevated kidney neutrophil infiltration as evaluated by myeloperoxidase (MPO) activity in vehicle-treated rats in comparison with sham rats, thus suggesting kidney injury. Treatment with C-peptide significantly attenuated the rise in creatinine and kidney MPO activity when compared to vehicle group. At a molecular level these effects of C-peptide were associated with reduced expression of the c-Fos subunit and reduced activation of the pro-inflammatory kinases, extracellular signal-regulated kinase (ERK 1/2) and c-Jun N-terminal kinase (JNK) and subsequently, reduced DNA binding of activator protein-1 (AP-1) in the kidney. Thus, our data suggest that C-peptide may exert reno-protective effects following hemorrhagic shock by modulating AP-1 signaling. PMID:21263384

  11. C-peptide promotes lesion development in a mouse model of arteriosclerosis.

    Science.gov (United States)

    Vasic, Dusica; Marx, Nikolaus; Sukhova, Galina; Bach, Helga; Durst, Renate; Grüb, Miriam; Hausauer, Angelina; Hombach, Vinzenz; Rottbauer, Wolfgang; Walcher, Daniel

    2012-04-01

    Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show elevated serum levels of the proinsulin cleavage product C-peptide and immunohistochemical data from our group revealed C-peptide deposition in early lesions of these individuals. Moreover, in vitro studies suggest that C-peptide could promote atherogenesis. This study examined whether C-peptide promotes vascular inflammation and lesion development in a mouse model of arteriosclerosis. ApoE-deficient mice on a high fat diet were treated with C-peptide or control injections for 12 weeks and the effect on lesion size and plaque composition was analysed. C-peptide treatment significantly increased C-peptide blood levels by 4.8-fold without having an effect on glucose or insulin levels, nor on the lipid profile. In these mice, C-peptide deposition in atherosclerotic plaques was significantly increased compared with controls. Moreover, lesions of C-peptide-treated mice contained significantly more macrophages (1.6 ± 0.3% versus 0.7 ± 0.2% positive area; P arteriosclerosis support the hypothesis that C-peptide may have an active role in atherogenesis in patients with diabetes and insulin resistance.

  12. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S;

    2000-01-01

    (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ...The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...... in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite...

  13. Different short-term effect of protein and carbohydrate intake on TSH, growth hormone (GH), insulin, C-peptide, and glucagon in humans

    DEFF Research Database (Denmark)

    Matzen, L E; Andersen, B B; Jensen, B G

    1990-01-01

    hormone (GH) and thyroid stimulating hormone (TSH) to protein and carbohydrate was identical, with a reduction in both GH and TSH, and nadir occurring after 45-60 min and 120 min, respectively. During the next 120 min TSH returned to starting level after carbohydrate intake but was still reduced after...... protein intake (p less than 0.04). After both diets GH increased after the initial decline, the increase was greatest after protein intake and maximum was reached at 180 min (p less than 0.02). It has been reported that the 5'-deiodination of T4 is stimulated by insulin and inhibited by glucagon......The effect of isocaloric (500 kcal) protein and carbohydrate ingestion was studied in a crossover study in nine healthy humans. Subjects were studied twice after overnight fasting, with an interval of 3 to 7 days. Blood was collected for 240 min after food ingestion. The initial reaction of growth...

  14. Development of SI-traceable C-peptide certified reference material NMIJ CRM 6901-a using isotope-dilution mass spectrometry-based amino acid analyses.

    Science.gov (United States)

    Kinumi, Tomoya; Goto, Mari; Eyama, Sakae; Kato, Megumi; Kasama, Takeshi; Takatsu, Akiko

    2012-07-01

    A certified reference material (CRM) is a higher-order calibration material used to enable a traceable analysis. This paper describes the development of a C-peptide CRM (NMIJ CRM 6901-a) by the National Metrology Institute of Japan using two independent methods for amino acid analysis based on isotope-dilution mass spectrometry. C-peptide is a 31-mer peptide that is utilized for the evaluation of β-cell function in the pancreas in clinical testing. This CRM is a lyophilized synthetic peptide having the human C-peptide sequence, and contains deamidated and pyroglutamylated forms of C-peptide. By adding water (1.00 ± 0.01) g into the vial containing the CRM, the C-peptide solution in 10 mM phosphate buffer saline (pH 6.6) is reconstituted. We assigned two certified values that represent the concentrations of total C-peptide (mixture of C-peptide, deamidated C-peptide, and pyroglutamylated C-peptide) and C-peptide. The certified concentration of total C-peptide was determined by two amino acid analyses using pre-column derivatization liquid chromatography-mass spectrometry and hydrophilic chromatography-mass spectrometry following acid hydrolysis. The certified concentration of C-peptide was determined by multiplying the concentration of total C-peptide by the ratio of the relative area of C-peptide to that of the total C-peptide measured by liquid chromatography. The certified value of C-peptide (80.7 ± 5.0) mg/L represents the concentration of the specific entity of C-peptide; on the other hand, the certified value of total C-peptide, (81.7 ± 5.1) mg/L can be used for analyses that does not differentiate deamidated and pyroglutamylated C-peptide from C-peptide itself, such as amino acid analyses and immunochemical assays.

  15. Pathological consequences of C-peptide deficiency in insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Ghorbani, Ahmad; Shafiee-Nick, Reza

    2015-02-15

    Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependent diabetes mellitus (type-1 diabetes). In this metabolic syndrome, in addition to decrease of endogenous insulin, the plasma level of connecting peptide (C-peptide) is also reduced due to beta cell destruction. Studies in the past decade have shown that C-peptide is much more than a byproduct of insulin biosynthesis and possess different biological activities. Therefore, it may be possible that C-peptide deficiency be involved, at least in part, in the development of different complications of diabetes. It has been shown that a small level of remaining C-peptide is associated with significant metabolic benefit. The purpose of this review is to describe beneficial effects of C-peptide replacement on pathological features associated with insulin-dependent diabetes. Also, experimental and clinical findings on the effects of C-peptide on whole-body glucose utilization, adipose tissue metabolism and tissues blood flow are summarized and discussed. The hypoglycemic, antilipolytic and vasodilator effects of C-peptide suggest that it may contribute to fine-tuning of the tissues metabolism under different physiologic or pathologic conditions. Therefore, C-peptide replacement together with the classic insulin therapy may prevent, retard, or ameliorate diabetic complications in patients with type-1 diabetes.

  16. A New Classification Plot for the C-Peptide Suppression Test.

    Directory of Open Access Journals (Sweden)

    Saddig C

    2002-01-01

    Full Text Available CONTEXT AND OBJECTIVE: To evaluate the C-peptide suppression test as a screening test in patients with symptoms of hypoglycemia as compared to the standard fasting test. DESIGN: Retrospective discriminant analysis of data from C-peptide suppression tests. SETTING: Clinical study. PATIENTS: Patients with insulinomas and patients without insulinomas but having symptoms compatible with hypoglycemia. INTERVENTIONS: The results from C-peptide suppression tests of 26 patients with insulinomas and 100 patients without insulinomas were compared. MAIN OUTCOME MEASURES: A classification plot which introduces two discriminant parameters for the C-peptide suppression test: the ratio of [blood glucose]/[C-peptide] at the lowest C-peptide concentration and mean glycemia during insulin infusion. RESULTS: In patients with insulinomas, minimal serum C-peptide levels were higher (1.81+/- 0.87 ng/mL; median 1.83 ng/mL; maximal suppression 37 +/- 24% of basal C-peptide levels as compared to patients without insulinoma (0.40 +/- 0.15 ng/mL; median 0.30 ng/mL; maximal suppression of 75 +/- 9%; P less than 0.001. Mean glycemia during the test was lower in patients with insulinomas (30.8 +/- 3.3 vs. 47.5 +/- 8.3 mg/dL; P less than 0.001 as was the [blood glucose]/[C-peptide] ratio (21.9 +/- 14.6 vs. 139.2 +/- 43.8; P less than 0.001. Discriminant analysis revealed a specificity of 96% to rule out the diagnosis of insulinoma at a 1% probability threshold with a sensitivity of 100%. CONCLUSIONS: We developed a new classification plot for the C-peptide suppression test in order to accurately identify those patients whose symptoms of hypoglycemia are not due to endogenous hyperinsulinemia/insulinomas. Thus, the need for fasting tests and hospitalization costs can be reduced.

  17. Different short-term effect of protein and carbohydrate intake on TSH, growth hormone (GH), insulin, C-peptide, and glucagon in humans

    DEFF Research Database (Denmark)

    Matzen, L E; Andersen, B B; Jensen, B G

    1990-01-01

    hormone (GH) and thyroid stimulating hormone (TSH) to protein and carbohydrate was identical, with a reduction in both GH and TSH, and nadir occurring after 45-60 min and 120 min, respectively. During the next 120 min TSH returned to starting level after carbohydrate intake but was still reduced after...... protein intake (p less than 0.04). After both diets GH increased after the initial decline, the increase was greatest after protein intake and maximum was reached at 180 min (p less than 0.02). It has been reported that the 5'-deiodination of T4 is stimulated by insulin and inhibited by glucagon...

  18. Association between low C-peptide and fragility fractures in postmenopausal women without diabetes.

    Science.gov (United States)

    Ferro, Y; Russo, C; Russo, D; Gazzaruso, C; Coppola, A; Gallotti, P; Zambianchi, V; Fodaro, M; Romeo, S; Galliera, E; Marazzi, M G; Romanelli, M M C; Giannini, S; Pujia, A; Montalcini, T

    2017-04-11

    C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

  19. Urinary C-peptide measurement as a marker of nutritional status in macaques.

    Directory of Open Access Journals (Sweden)

    Cédric Girard-Buttoz

    Full Text Available Studies of the nutritional status of wild animals are important in a wide range of research areas such as ecology, behavioural ecology and reproductive biology. However, they have so far been strongly limited by the indirect nature of the available non-invasive tools for the measurement of individual energetic status. The measurement of urinary C-peptide (UCP, which in humans and great apes shows a close link to individual nutritional status, may be a more direct, non-invasive tool for such studies in other primates as well and possibly even in non-primate mammals. Here, we test the suitability of UCPs as markers of nutritional status in non-hominid primates, investigating relationships between UCPs and body-mass-index (BMI, skinfold fatness, and plasma C-peptide levels in captive and free-ranging macaques. We also conducted a food reduction experiment, with daily monitoring of body weight and UCP levels. UCP levels showed significant positive correlations with BMI and skinfold fatness in both captive and free-ranging animals and with plasma C-peptide levels in captive ones. In the feeding experiment, UCP levels were positively correlated with changes in body mass and were significantly lower during food reduction than during re-feeding and the pre-experimental control condition. We conclude that UCPs may be used as reliable biomarkers of body condition and nutritional status in studies of free-ranging catarrhines. Our results open exciting opportunities for energetic studies on free-ranging primates and possibly also other mammals.

  20. C-peptide and Diabetic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Xiao-jun Cai; Hui-qin Xu; Yi Lu

    2011-01-01

    With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive fimctions.Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system,hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide defidency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients.Those Findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.

  1. Pathological consequences of C-peptide deficiency in insulin-dependent diabetes mellitus

    OpenAIRE

    2015-01-01

    Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependent diabetes mellitus (type-1 diabetes). In this metabolic syndrome, in addition to decrease of endogenous insulin, the plasma level of connecting peptide (C-peptide) is also reduced due to beta cell destruction. Studies in the past decade have shown that C-peptide is much more than a byproduc...

  2. Expression and Purification of C-Peptide Containing Insulin Using Pichia pastoris Expression System

    Directory of Open Access Journals (Sweden)

    Mohammed N. Baeshen

    2016-01-01

    Full Text Available Increase in the incidence of Insulin Dependent Diabetes Mellitus (IDDM among people from developed and developing countries has created a large global market for insulin. Moreover, exploration of new methods for insulin delivery including oral or inhalation route which require very high doses would further increase the demand of cost-effective recombinant insulin. Various bacterial and yeast strains have been optimized to overproduce important biopharmaceuticals. One of the approaches we have taken is the production of recombinant human insulin along with C-peptide in yeast Pichia pastoris. We procured a cDNA clone of insulin from Origene Inc., USA. Insulin cDNA was PCR amplified and cloned into yeast vector pPICZ-α. Cloned insulin cDNA was confirmed by restriction analysis and DNA sequencing. pPICZ-α-insulin clone was transformed into Pichia pastoris SuperMan5 strain. Several Zeocin resistant clones were obtained and integration of insulin cDNA in Pichia genome was confirmed by PCR using insulin specific primers. Expression of insulin in Pichia clones was confirmed by ELISA, SDS-PAGE, and Western blot analysis. In vivo efficacy studies in streptozotocin induced diabetic mice confirmed the activity of recombinant insulin. In conclusion, a biologically active human proinsulin along with C-peptide was expressed at high level using Pichia pastoris expression system.

  3. Pathological consequences of C-peptide deficiency ininsulin-dependent diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Ahmad Ghorbani; Reza Shafiee-Nick

    2015-01-01

    Diabetes is associated with several complicationssuch as retinopathy, nephropathy, neuropathy andcardiovascular diseases. Currently, insulin is the mainused medication for management of insulin-dependentdiabetes mellitus (type-1 diabetes). In this metabolicsyndrome, in addition to decrease of endogenous insulin,the plasma level of connecting peptide (C-peptide) is alsoreduced due to beta cell destruction. Studies in the pastdecade have shown that C-peptide is much more than abyproduct of insulin biosynthesis and possess differentbiological activities. Therefore, it may be possible thatC-peptide deficiency be involved, at least in part, in thedevelopment of different complications of diabetes. It hasbeen shown that a small level of remaining C-peptide isassociated with significant metabolic benefit. The purposeof this review is to describe beneficial effects of C-peptidereplacement on pathological features associated withinsulin-dependent diabetes. Also, experimental andclinical findings on the effects of C-peptide on wholebodyglucose utilization, adipose tissue metabolism andtissues blood flow are summarized and discussed. Thehypoglycemic, antilipolytic and vasodilator effects ofC-peptide suggest that it may contribute to fine-tuningof the tissues metabolism under different physiologic orpathologic conditions. Therefore, C-peptide replacementtogether with the classic insulin therapy may prevent,retard, or ameliorate diabetic complications in patientswith type-1 diabetes.

  4. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S

    2000-01-01

    the insulin sensitivity index, calculated from the frequently sampled iv glucose tolerance test, only decreased slightly. The clearance of C-peptide and insulin increased 100% and 60%, respectively, and the prehepatic insulin secretion was tripled during rhGH treatment; but related to the impairment...... an increase in lean body mass and a reduction of fat mass. Therefore, rhGH treatment may precipitate diabetes in some patients already susceptible to the disorder....

  5. Serum C-peptide as a key contributor to lipid-related residual cardiovascular risk in the elderly.

    Science.gov (United States)

    Li, Ying; Zhao, DuoDuo; Li, Yue; Meng, Lu; Enwer, Gulmire

    2017-11-01

    The serum levels of C-peptide, an important risk factor for cardiovascular disease (CVD), increase with age. This study aimed to investigate the association between serum C-peptide and increased risk for CVD with altered lipid metabolism in the elderly. This was a population-based cross-sectional study that included 3091 elderly participants aged ≥65 years. Serum C-peptide and lipid levels were measured according to standard protocols. Sampling weights were used to estimate the characteristics of study participants. Stratified analysis of covariance was used to evaluate the changes in the serum lipid levels according to quartiles of serum C-peptide levels, and the linear trend was assessed using a linear model. The logistic regression model was carried out to determine the association between the serum C-peptide levels and serum lipid levels. The results of the analysis of covariance stratified by sex and serum insulin level showed that the serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were significantly associated with changes in the serum C-peptide levels, independent of the serum insulin level. The logistic regression analyses indicated that the serum C-peptide levels were positively associated with the serum TG levels, and negatively associated with the serum HDL-C levels. A significant dose-response association was obtained in both men and women. Serum C-peptide levels were strongly associated with increased serum TG and reduced HDL-C levels in the elderly. Our results suggest that serum C-peptide increases the risk of CVD via a pathway that increases TG or decreases HDL-C levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 21 CFR 862.1135 - C-peptides of proinsulin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false C-peptides of proinsulin test system. 862.1135 Section 862.1135 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  7. Proinsulin C-peptide interferes with insulin fibril formation

    Energy Technology Data Exchange (ETDEWEB)

    Landreh, Michael [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden); Stukenborg, Jan-Bernd [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Willander, Hanna [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Soeder, Olle [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Johansson, Jan [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, S-751 23 Uppsala (Sweden); Joernvall, Hans, E-mail: Hans.Jornvall@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic {beta}-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  8. Evaluation of insulin and C-peptide in diabetic patients undergoing renal dialysis

    Directory of Open Access Journals (Sweden)

    P. T. Annamala

    2016-10-01

    Conclusions: There are alterations in the levels of insulin, c-peptide and the glycemic status in diabetic patients during dialysis. This significant reduction may affect glucose metabolism in diabetic patients on dialysis. Hence, glycemic status should be continuously monitored in these patients. [Int J Res Med Sci 2016; 4(10.000: 4579-4582

  9. Fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and urinary C-peptide in relation to clinical type of diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Faber, O K;

    1989-01-01

    ) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved...... islet B-cell function and were separated according to the 20%, 40%, 60% and 80% C-peptide percentiles. The two classifications of patients were compared by calculating the prevalence of clinical Type 1 and Type 2 diabetes in each of the C-peptide classes. This analysis showed that patients...... diabetic subjects. Patients were classified clinically as Type 1 (insulin-dependent) diabetic subjects in the presence of at least two of the following criteria: 1) significant ketonuria, 2) insulin treatment started within one year after diagnosis, 3) age of diagnosis less than or equal to 40 years, and 4...

  10. The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes.

    Science.gov (United States)

    Crisman, Marco; Lucchetta, Luca; Luethi, Nora; Cioccari, Luca; Lam, Que; Eastwood, Glenn M; Bellomo, Rinaldo; Mårtensson, Johan

    2017-12-01

    In critically ill patients with permissive hyperglycemia, it is uncertain whether exogenous insulin administration suppresses or enhances c-peptide secretion (a marker of pancreatic beta-cell response). We aimed to explore this effect in patients with type 2 diabetes. We prospectively enrolled a cohort of 45 critically ill patients with type 2 diabetes managed according to a liberal glucose protocol (target blood glucose 10-14 mmol/l). We recorded the administration of insulin and oral hypoglycemic agents and measured plasma c-peptide as surrogate marker of endogenous insulin secretion on the first two consecutive days in ICU. Overall, 20 (44.4%) patients required insulin to achieve target blood glucose. Insulin-treated patients had higher glycated hemoglobin A1c, more premorbid insulin-requiring type 2 diabetes, and greater blood glucose levels but lower c-peptide levels on admission. Premorbid insulin-requiring diabetes was independently associated with lower admission c-peptide, whereas greater plasma creatinine was independently associated with higher levels. Increases in c-peptide were positively correlated with an increase in blood glucose both in patients who did (r = 0.54, P = 0.01) and did not (r = 0.56, P = 0.004) receive insulin. However, insulin administration was independently associated with a greater increase in c-peptide (P = 0.04). This association was not modified by the use of oral insulin secretagogues. C-peptide, a marker of beta-cell response, responds to and is influenced by glycemia and renal function in critically ill patients with type 2 diabetes. In addition, in our cohort, exogenous insulin administration was associated with a greater increase in c-peptide in response to hyperglycemia. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN12615000216516).

  11. Role of C-peptide in Altered Lipid Profile among Apparently Healthy Adults of Vijayapura City, Karnataka

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    Chandrahas M.Kulkarni

    2016-04-01

    Full Text Available Background: C-peptide is produced in equimolar concentration during insulin production as inactive molecule by beta islet cells of Langerhans. C-peptide is most useful biomarker of endogenous insulin production. Aim and Objectives: To predict metabolic syndrome in advance by estimation of C-peptide and lipid profile in healthy adults. Material and Methods: Serum C-peptide, fasting blood glucose and lipid profile of 128 healthy individuals were estimated. Adults in the age group of 18 to 60 years of both sexes were included in study. Results: C-peptide levels were increased in 27%, Serum cholesterol in 30%, LDL Cholesterol in 55% and triglyceride levels in 21% of healthy individuals. Significant correlation was observed between C peptide, age, serum cholesterol, LDL and cholesterol LDL ratio in male subjects only. In our study group most of the subjects (both males and females fell in overweight group. Conclusion: Cpeptide level and lipid profile may be considered as useful biomarkers to predict type 2 diabetes mellitus in advance, possibly due to insulin resistance.

  12.  Pleiotropic action of proinsulin C-peptid

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    Michał Usarek

    2012-03-01

    Full Text Available  Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic β cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. However, in the last two decades research has brought a substantial amount of data indicating a crucial role of C-peptide in regulating various processes in different types of cells and organs. C-peptide acts presumably via either G-protein-coupled receptor or directly inside the cell, after being internalized. However, a receptor binding this peptide has not been identified yet. This peptide ameliorates pathological changes induced by type 1 diabetes mellitus, including glomerular hyperfiltration, vessel endothelium inflammation and neuron demyelinization. In diabetic patients and diabetic animal models, C-peptide substitution in physiological doses improves the functional and structural properties of peripheral neurons and protects against hyperglycemia-induced apoptosis, promoting neuronal development, regeneration and cell survival. Moreover, it affects glycogen synthesis in skeletal muscles. In vitro C-peptide promotes disaggregation of insulin oligomers, thus enhancing its bioavailability and effects on metabolism. There are controversies concerning the biological action of C-peptide, particularly with respect to its effect on Na /K -ATPase activity. Surprisingly, the excess of circulating peptide associated with diabetes type 2 contributes to atherosclerosis development. In view of these observations, long-term, large-scale clinical investigations using C-peptide physiological doses need to be conducted in order to determine safety and health outcomes of long-term administration of C-peptide to diabetic patients.

  13. C peptides as entry inhibitors for gene therapy.

    Science.gov (United States)

    Egerer, Lisa; Kiem, Hans-Peter; von Laer, Dorothee

    2015-01-01

    Peptides derived from the C-terminal heptad repeat 2 region of the HIV-1 gp41 envelope glycoprotein, so-called C peptides, are very potent HIV-1 fusion inhibitors. Antiviral genes encoding either membrane-anchored (ma) or secreted (iSAVE) C peptides have been engineered and allow direct in vivo production of the therapeutic peptides by genetically modified host cells. Membrane-anchored C peptides expressed in the HIV-1 target cells by T-cell or hematopoietic stem cell gene therapy efficiently prevent virus entry into the modified cells. Such gene-protection confers a selective survival advantage and allows accumulation of the genetically modified cells. Membrane-anchored C peptides have been successfully tested in a nonhuman primate model of AIDS and were found to be safe in a phase I clinical trial in AIDS patients transplanted with autologous gene-modified T-cells. Secreted C peptides have the crucial advantage of not only protecting genetically modified cells from HIV-1 infection, but also neighboring cells, thus suppressing virus replication even if only a small fraction of cells is genetically modified. Accordingly, various cell types can be considered as potential in vivo producer cells for iSAVE-based gene therapeutics, which could even be modified by direct in vivo gene delivery in future. In conclusion, C peptide gene therapeutics may provide a strong benefit to AIDS patients and could present an effective alternative to current antiretroviral drug regimens.

  14. EDTA improves stability of whole blood C-peptide and insulin to over 24 hours at room temperature.

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    Timothy J McDonald

    Full Text Available INTRODUCTION: C-peptide and insulin measurements in blood provide useful information regarding endogenous insulin secretion. Conflicting evidence on sample stability and handling procedures continue to limit the widespread clinical use of these tests. We assessed the factors that altered the stability of insulin and C-peptide in blood. METHODS: We investigated the impact of preservative type, time to centrifugation, storage conditions and duration of storage on the stability of C-peptide and insulin on three different analytical platforms. RESULTS: C-peptide was stable for at least 24 hours at room temperature in both centrifuged and whole blood collected in K(+-EDTA and serum gel tubes, with the exception of whole blood serum gel, which decreased to 78% of baseline at 24 hours, (p = 0.008. Insulin was stable at room temperature for 24 hours in both centrifuged and whole blood collected in K(+-EDTA tubes. In contrast insulin levels decreased in serum gel tubes both centrifuged and whole blood (66% of baseline, p = 0.01 and 76% of baseline p = 0.01, by 24 hours respectively. C-peptide and insulin remained stable after 6 freeze-thaw cycles. CONCLUSIONS: The stability of C-peptide and insulin in whole blood K(+-EDTA tubes negates the need to conform to strict sample handling procedures for these assays, greatly increasing their clinical utility.

  15. History and Diagnostic Significance of C-Peptide

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    Dietrich Brandenburg

    2008-01-01

    Today, C-peptide continues to serve as a special diagnostic tool in Diabetology and related fields. Thus, its passive role is well established. Evidence for its active role in physiology and pathophysiology is more recent and is subject of the following contributions.

  16. Endocrine pancreatic control of the release of gastric inhibitory polypeptide. A possible physiological role for C-peptide.

    Science.gov (United States)

    Dryburgh, J R; Hampton, S M; Marks, V

    1980-10-01

    Intravenous infusion in anaesthetized rats of rat II C-peptide at a dose which produced circulating levels of 22.8 +/- 1.8 nmol/l after 30 min, resulted in a significant reduction (141 +/- 7 to 50 +/- 4 pmol/l, p < 0.001, mean +/- SEM) in the immunoreactive gastric inhibitory polypeptide response to an intestinal perfusion with a fat emulsion. Immunoreactive insulin levels were unchanged from basal in this study. It is suggested that C-peptide must be considered as a candidate for the endocrine pancreatic factor which exerts a negative feedback upon gastric inhibitory polypeptide release.

  17. Metal-activated C-peptide Facilitates Glucose Clearance and the Release of a Nitric Oxide Stimulus via the GLUT1 Transporter

    Science.gov (United States)

    Meyer, Jennifer A.; Froelich, Jennifer M.; Reid, Gavin E.; Karunarathne, Welivitya K.A.; Spence, Dana M.

    2008-01-01

    Objective: Proinsulin C-peptide has been implicated in reducing complications associated with diabetes and improving blood flow. We hypothesized that incubation of erythrocytes with C-peptide would improve the ability of these cells to release ATP, a stimulus of nitric oxide production. Research Design and Methods: Erythrocytes obtained from rabbits (n=11) and humans (healthy and those with type 2 diabetes, n=7) were incubated with C-peptide (in the absence and presence of Fe (II) and Cr (III)) and the resulting ATP release was measured via chemiluminescence. This release was also measured in the presence and absence of phloretin, an inhibitor of the glucose transporter GLUT1, and mannose, a glycolysis inhibitor. To determine glucose transport, 14C-labelled glucose was added to erythrocytes in the presence and absence of the C- peptide/metal complex and the aforementioned inhibitors. Results: The release of ATP from the erythrocytes of patients with diabetes increased from 64 nmol/l (± 13 nmol/l) to 260 nmol/l (± 39 nmol/l) upon incubation of the cells in C-peptide. The C-peptide activity was dependent upon binding to Fe (II), which was extended upon binding to Cr (III). The increase in ATP release from the erythrocytes is due to metal-activated C-peptide stimulation of glucose transfer into the erythrocytes via the GLUT1 transporter. In the presence of C-peptide complexed to Cr (III), the amount of glucose transferred into the erythrocyte increased by 31%. Conclusions: When complexed to Fe (II) or Cr (III), C-peptide has the ability to promote ATP release from erythrocytes. This release is due to an increase in glucose transport through the GLUT1 transporter. PMID:17965850

  18. Correlations between fasting plasma C-peptide, glucagon-stimulated plasma C-peptide, and urinary C-peptide in insulin-treated diabetics

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Frøland, A

    1987-01-01

    This study correlated fasting plasma C-peptide (CP), plasma CP 6 min after stimulation with 1 mg glucagon i.v., and the mean of three 24-h urinary excretions of C-peptide (UCP)/creatinine in 132 insulin-treated diabetics. Patients were divided into three groups: group 1, stimulated CP less than 0.......06 nM (n = 51); group 2, stimulated CP 0.06-0.60 nM (n = 48); and group 3, stimulated CP greater than 0.60 nM (n = 33). In all patients fasting CP was closely correlated to stimulated CP (r = .988, P less than .001), whereas the correlations between UCP and both fasting CP (r = .904, P less than .001......) and stimulated CP r = .902, P less than .001) were slightly less pronounced. The associations between UCP and both fasting CP (r = .716, P less than .001) and stimulated CP (r = .731, P less than .001) were modest in group 2, and even more so in group 3 (r = .557, P less than .001 and r = .641, P less than .001...

  19. C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a modelistic study.

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    Francesco Di Nardo

    Full Text Available A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT was performed in seven Zucker fatty rats (ZFR, 7-to-9 week-old, and seven age-matched Zucker lean rats (ZLR. The minimal model of C-peptide (CPMM, originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM. Our results showed that the present CPMM-based interpretation of data is able to: 1 provide a suitable fit of C-Peptide data; 2 achieve a satisfactory estimation of parameters of interest 3 quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t, and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф(1, second-phase, Ф(2, and steady-state, Ф(ss, never assessed in Zucker rats before; 4 detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation.

  20. The Association between Newborn Regional Body Composition and Cord Blood Concentrations of C-Peptide and Insulin-Like Growth Factor I.

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    Emma M Carlsen

    Full Text Available Third trimester fetal growth is partially regulated by C-peptide and insulin-like growth factor I (IGF-I. Prenatal exposures including maternal obesity and high gestational weight gain as well as high birth weight have been linked to subsequent metabolic disease. We evaluated the associations between newborn regional body composition and cord blood levels of C-peptide and IGF-I.We prospectively included obese and normal-weight mothers and their newborns; cord blood was collected and frozen. Analyses of C-peptide and IGF-I were performed simultaneously, after recruitment was completed. Newborn regional body composition was assessed with dual-energy X-ray absorptiometry scanning (DXA within 48 hours of birth.Three hundred thirty-six term infants were eligible to participate in the study; of whom 174 (52% infants had cord blood taken. Total, abdominal and arm and leg fat mass were positively associated with C-peptide (p < 0.001. Arm and leg fat mass was associated with IGF-I concentration: 28 g [95% confidence interval: 4, 53] per doubling of IGF-I. There was no association between total or abdominal fat mass and IGF-I. Fat-free mass was positively associated with both C-peptide (p < 0.001 and IGF-I (p = 0.004.Peripheral fat tissue accumulation was associated with cord blood C-peptide and IGF-I. Total and abdominal fat masses were related to C-peptide but not to IGF-I. Thus, newborn adiposity is partially mediated through C-peptide and early linear growth is associated with IGF-I.

  1. Effect of GLP-1 and GIP on C-peptide secretion after glucagon or mixed meal tests: Significance in assessing B-cell function in diabetes.

    Science.gov (United States)

    Guglielmi, C; Del Toro, R; Lauria, A; Maurizi, A R; Fallucca, S; Cappelli, A; Angeletti, S; Lachin, J M; Pozzilli, P

    2017-09-01

    The aim of the study was to investigate the different B-cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT). We conducted GST and MMTT in 10 healthy people (aged 25-40 years) and measured C-peptide, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) at different time points after the administration of 1 mg i.v. glucagon for GST or a liquid mixed meal for MMTT. The GST stimulated C-peptide showed a mean increase of 147.1%, whereas the mean increase of MMTT stimulated C-peptide was 99.82% (Δincrease = 47.2%). Maximum C-peptide level reached with the MMTT was greater than that obtained with the GST (C-pept max MMTT = 2.35 nmol/L vs C-pep max GST = 1.9 nmol/L). A positive and linear correlation was found between the GST incremental area under the curve C-peptide and the MMTT incremental area under the curve C-peptide (r = 0.618, P = .05). After GST, there was no increment of GIP and glucagon like peptide-1 levels compared to baseline levels. A positive and linear correlation between GIP and C-peptide levels was observed only for the MMTT (r = 0.922, P = .008) indicating that in the GST, the C-peptide response is independent of the incretin axis response. Although the 2 stimulation tests may elicit a similar response in C-peptide secretion, B-cell response to MMTT depends on a functionally normal incretin axis. These results may have implications when investigating the B-cell response in people with diabetes and for studies in which stimulated C-peptide secretion is used as primary or secondary outcome for response to therapy. Copyright © 2017 John Wiley & Sons, Ltd.

  2. C-peptide and zinc delivery to erythrocytes requires the presence of albumin: implications in diabetes explored with a 3D-printed fluidic device.

    Science.gov (United States)

    Liu, Yueli; Chen, Chengpeng; Summers, Suzanne; Medawala, Wathsala; Spence, Dana M

    2015-05-01

    People with type 1 diabetes (T1D) must administer insulin exogenously due to the destruction of their pancreatic β-cells. Endogenous insulin is stored in β-cell granules along with C-peptide, a 31 amino acid peptide that is secreted from these granules in amounts equal to insulin. Exogenous co-administration of C-peptide with insulin has proven to reduce diabetes-associated complications in animals and humans. The exact mechanism of C-peptide's beneficial effects after secretion from the β-cell granules is not completely understood, thus hindering its development as an exogenously administered hormone. Monitoring tissue-to-tissue communication using a 3D-printed microfluidic device revealed that zinc and C-peptide are being delivered to erythrocytes by albumin. Upon delivery, erythrocyte-derived ATP increased by >50%, as did endothelium-derived NO, which was measured downstream in the 3D-printed device. Our results suggest that hormone replacement therapy in diabetes may be improved by exogenous administration of a C-peptide ensemble that includes zinc and albumin.

  3. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans;

    1990-01-01

    Mice and rats have two functional non-allelic insulin genes. By using a synthetic peptide representing a common sequence in mouse and rat C-peptide 2 as antigen, we have produced rabbit antisera specific for an epitope which is not present in mouse or rat C-peptide 1. Long-term immunization did n...

  4. Plasmid-encoded proinsulin preserves C-peptide while specifically reducing proinsulin-specific CD8⁺ T cells in type 1 diabetes.

    Science.gov (United States)

    Roep, Bart O; Solvason, Nanette; Gottlieb, Peter A; Abreu, Joana R F; Harrison, Leonard C; Eisenbarth, George S; Yu, Liping; Leviten, Michael; Hagopian, William A; Buse, John B; von Herrath, Matthias; Quan, Joanne; King, Robert S; Robinson, William H; Utz, Paul J; Garren, Hideki; Steinman, Lawrence

    2013-06-26

    In type 1 diabetes (T1D), there is an intense inflammatory response that destroys the β cells in the pancreatic islets of Langerhans, the site where insulin is produced and released. A therapy for T1D that targets the specific autoimmune response in this disease while leaving the remainder of the immune system intact, has long been sought. Proinsulin is a major target of the adaptive immune response in T1D. We hypothesized that an engineered DNA plasmid encoding proinsulin (BHT-3021) would preserve β cell function in T1D patients through reduction of insulin-specific CD8⁺ T cells. We studied 80 subjects over 18 years of age who were diagnosed with T1D within the past 5 years. Subjects were randomized 2:1 to receive intramuscular injections of BHT-3021 or BHT-placebo, weekly for 12 weeks, and then monitored for safety and immune responses in a blinded fashion. Four dose levels of BHT-3021 were evaluated: 0.3, 1.0, 3.0, and 6.0 mg. C-peptide was used both as an exploratory efficacy measure and as a safety measure. Islet-specific CD8⁺ T cell frequencies were assessed with multimers of monomeric human leukocyte antigen class I molecules loaded with peptides from pancreatic and unrelated antigens. No serious adverse events related to BHT-3021 were observed. C-peptide levels improved relative to placebo at all doses, at 1 mg at the 15-week time point (+19.5% BHT-3021 versus -8.8% BHT-placebo, P BHT-3021 arm (P < 0.006). No significant changes were noted in interferon-γ, interleukin-4 (IL-4), or IL-10 production in CD4 T cells. Thus, we demonstrate that a plasmid encoding proinsulin reduces the frequency of CD8⁺ T cells reactive to proinsulin while preserving C-peptide over the course of dosing.

  5. Estimation of serum insulin, Homeostasis model assessment-insulin resistance and C-peptide can help identify possible cardiovascular disease risk in thyroid disorder patients

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    Purvi Purohit

    2012-01-01

    Full Text Available Aim: We aimed at evaluating the cardiovascular disease (CVD risk of thyroid disorder patients at diagnosis, using the traditional lipid profile, apo-B and apo-A1 in correlation with serum insulin and insulin resistance (IR and C-peptide. Background: With an ever increasing incidence of CVD in most urban populations, there has been a demand for newer techniques that could help in the early detection of the risk of this disease complex. Materials and Methods: The present study was conducted on 100 healthy controls and 150 hypothyroid and 70 hyperthyroid patients, coming for the first time to our OPDs. The patients were selected on the basis of symptomatology and serum T3, T4, thyroid stimulating hormone (TSH evaluations. They were then analyzed for body mass index (BMI, blood pressure (BP, serum insulin, homeostasis model assessment-insulin resistance (HOMA-IR, C-peptide, lipid profile and apo-B and -A1. Statistical analysis was done using Student′s "t" test and Spearman′s coefficient of correlation. Results: The hypothyroid patients presented with high BMI, diastolic hypertension, dyslipidemia, hyperinsulinemia, IR and raised serum C-peptide. There was highly significant correlation of serum insulin, HOMA-IR and C-peptide with lipid fractions and CVD risk ratios, T. chol/HDLc and apo-B/apo-A1, in hypothyroid patients. The hyperthyroid patients presented with systolic hypertension and a significant correlation of T. chol/HDLc with HOMA-IR. Hyperthyroid patients also had hyperinsulinemia, but reduced serum C-peptide levels. Conclusion: We conclude that the estimation of traditional lipid profile along with serum insulin, IR, C-peptide, apo-A1 and apo-B would not only help assess the thyroid status, but can also help in the early evaluation of a possible risk of CVD.

  6. Reference intervals for C-peptide and insulin derived from a general adult Danish population

    DEFF Research Database (Denmark)

    Larsen, Pia Bükmann; Linneberg, Allan; Hansen, Torben

    2016-01-01

    BACKGROUND: Despite international efforts to standardize C-peptide and insulin calibrators and immunoassays, platform dependent differences still exist, and platform specific reference intervals are hence needed for correct interpretation. We therefore wanted to establish traceable reference...... intervals for C-peptide and insulin. METHODS: In 623 consecutively recruited participants, insulin and C-peptide were measured using the Cobas e411 (Roche Diagnostics, Switzerland). Participants with diabetes were excluded (fasting Glucose ≥7.0mmol/L or HbA1c≥6.5%/≥48mmol/L) and reference intervals were...

  7. Pengaruh Transplantasi Allograf Pancreatic Stem Cell terhadap Kadar Insulin dan C-Peptide Tikus Putih Penderita Diabetes Melitus Tipe I

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    Boedi Setiawan

    2016-09-01

    Full Text Available Diabetes mellitus is one of the degenerative diseases in which the therapy still remains unresolved and is still a serious threat to the global health, including to the health of Indonesian people. The aim of this study was to describe the level of insulin and C-peptide in diabetes mellitus type I white rats treated with pancreatic stem cell allograft through intrapancreatic laparotomy. This study was conducted at the Institute of Tropical Diseases, Universitas Airlangga, Surabaya in a 6 month period (July–December 2014. Twelve male white rats Rattus novergicus Wistar strain, were randomly divided into two groups. The first group (P0 was injected by alloxan, 150 mg/kg body weight, without stem cell therapy. Another group was injected by alloxan, 150 mg/kg body weight, and was treated with 1x106/kg body weight pancreatic stem cell throughintrapancreatic laparotomy (P1. The experiment was finalized on the 31th day of the experiment. The results showed that the blood glucose levels at the end of experiment were highly significantly different p<0.01 between the treatment group that received stem cell therapy (P1 and P0 positive control, although the average value of blood glucose levels was not as normal as on the first day. C-peptide and insulin levels of P0 and P1 group differed significantly (p<0.01. It can be concluded that stem cell therapy through intrapancreatic laparotomy can reduce blood glucose levels and increase the levels of C-peptide and insulin.

  8. C-Peptides for diagnostics and therapy: a veterinary medicine point of view

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    Derek A. Rosenfield

    Full Text Available ABSTRACT: Empirical studies proved that C-peptides are performing numerous intrinsic biological roles, and serve as a marker for pancreatic performance analysis. Since the last decade, C-peptide assays for differential diagnosis in veterinary diabetic patients are becoming more available, but still only for a very limited number of species. Studies on C-peptide as a diagnostic tool, therapy for associated complications, or as replacement therapies for C-peptide deficiency still showed not to be a common practice in veterinary medicine. This review was conducted to determine the potential importance of C-peptide in Veterinary Medicine, relevant in the diagnosis of diabetes and for other metabolic processes, as well as its proposed therapeutic benefits. Numerous articles were identified that reported positive results in their experimental studies, whether C-peptide as a biomarker for pancreatic performance in dogs, cats, and horses, as a non-invasive method to monitor nutritional status in primates, or to investigate its potential therapeutic benefits for diabetes-related illnesses.

  9. Effect of C-Peptide on Diabetic Neuropathy in Patients with Type 1 Diabetes

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    Karin Ekberg

    2008-01-01

    Full Text Available Recent results indicate that proinsulin C-peptide, contrary to previous views, exerts important physiological effects and shows the characteristics of a bioactive peptide. Studies in type 1 diabetes, involving animal models as well as patients, demonstrate that C-peptide in replacement doses has the ability to improve peripheral nerve function and prevent or reverse the development of nerve structural abnormalities. Peripheral nerve function, as evaluated by determination of sensory nerve conduction velocity and quantitative sensory testing, is improved by C-peptide replacement in diabetes type 1 patients with early stage neuropathy. Similarly, autonomic nerve dysfunction is ameliorated following administration of C peptide for up to 3 months. As evaluated in animal models of type 1 diabetes, the improved nerve function is accompanied by reversal or prevention of nerve structural changes, and the mechanisms of action are related to the ability of C-peptide to correct diabetes-induced reductions in endoneurial blood flow and in Na+,K+-ATPase activity and modulation of neurotrophic factors. Combining the results demonstrates that C-peptide may be a possible new treatment of neuropathy in type 1 diabetes.

  10. Glutathione Levels in Human Tumors

    Science.gov (United States)

    Gamcsik, Michael P.; Kasibhatla, Mohit S.; Teeter, Stephanie D.; Colvin, O. Michael

    2013-01-01

    This review summarizes clinical studies in which glutathione was measured in tumor tissue from patients with brain, breast, gastrointestinal, gynecological, head and neck and lung cancer. Glutathione tends to be elevated in breast, ovarian, head and neck and lung cancer and lower in brain and liver tumors compared to disease-free tissue. Cervical, colorectal, gastric and esophageal cancers show both higher and lower levels of tumor glutathione. Some studies show an inverse relationship between patient survival and tumor glutathione. Based on this survey, we recommend approaches that may improve the clinical value of glutathione as a biomarker. PMID:22900535

  11. C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study.

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    Lingshu Wang

    Full Text Available C-peptide has been reported to be a marker of subclinical atherosclerosis in type 2 diabetes mellitus (T2DM patients, whereas its role in coronary artery disease (CAD has not been clarified, especially in diabetics with differing body mass indices (BMIs.This cross-sectional study included 501 patients with T2DM. First, all subjects were divided into the following two groups: CAD and non-CAD. Then, binary logistic regression was used to determine the risk factors for CAD for all patients. To clarify the role of obesity, we re-divided all subjects into two additional groups (obese and non-obese based on BMI. Finally, binary logistic regression was used to determine the risk factors for CAD for each weight group.The patients with CAD showed a higher BMI and fasting C-peptide level in addition to an increased prevalence of traditional risk factors for CAD, such as hypertension, insulin resistance, higher cholesterol, cysteine-C (Cys-C and lower estimated glomerular filtration rate (eGFR. Logistic regression analysis showed that fasting C-peptide (OR=1.513, p=0.005, insulin treatment (OR=1.832, p=0.027 hypertension (OR=1.987, p=0.016 and hyperlipidemia (OR=4.159, p<0.001 significantly increased the risk of clinical CAD in the T2DM patients independent of age, gender, diabetes duration, smoking and alcohol statuses, fasting insulin and glucose, hypoglycemic episodes, UA and eGFR. Additionally, in both of the obese (OR=1.488, p=0.049 and non-obese (OR=1.686, p=0.037 DM groups, C-peptide was associated with an increased risk of CAD after multiple adjustments.C-peptide is associated with an increased CAD risk in T2DM patients, no matter whether they are obese or not.

  12. Reference intervals for C-peptide and insulin derived from a general adult Danish population.

    Science.gov (United States)

    Larsen, Pia Bükmann; Linneberg, Allan; Hansen, Torben; Friis-Hansen, Lennart

    2017-05-01

    Despite international efforts to standardize C-peptide and insulin calibrators and immunoassays, platform dependent differences still exist, and platform specific reference intervals are hence needed for correct interpretation. We therefore wanted to establish traceable reference intervals for C-peptide and insulin. In 623 consecutively recruited participants, insulin and C-peptide were measured using the Cobas e411 (Roche Diagnostics, Switzerland). Participants with diabetes were excluded (fasting Glucose ≥7.0mmol/L or HbA1c≥6.5%/≥48mmol/L) and reference intervals were calculated with and without the inclusion of persons who were prediabetic, according to two definitions (The World Health Organization (WHO) and American Diabetes Association (ADA)). To ensure the correctness of calibration, the control pools were analyzed by a reference laboratory. The reference intervals were calculated according to the IFCC guidelines, using the RefVal software (Solberg, Oslo, Norway). Comparison of our results with those from the reference laboratory revealed equivalence for C-peptide results whereas the insulin determined on the Cobas e411 assay were 15-20% higher. The difference is attributed to an incorrect conversion factor for converting from activity to metric units. The Cobas e411 assay uses the factor 6.945 for converting from U/mL to pmol/L. This is in disagreement with the biological activity of insulin which is 166.8×10(6)IU/mol or 6.00nmol/IU. We successfully established reference intervals for C-peptide and insulin for non-diabetic and prediabetic participants. The reference intervals for fasting C-peptide and fasting insulin are ready for implementation. A recertification of the insulin standards is needed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Physiological effects of proinsulin-connecting peptide in human subcutaneous adipose tissue.

    Science.gov (United States)

    Ghorbani, A; Shafiee-Nick, R; Zojaji, S A; Rajabi-Mashhadi, M T

    2017-06-01

    Recent studies suggest that proinsulin-connecting peptide (C-peptide) may exhibit characteristics of a hormone and show physiological functions in various tissues. This study was aimed to determine whether C-peptide could be involved in the regulation of lipolysis, adiponectin release, and function of mesenchymal stem cells (MSCs) in adipose tissue. Human subcutaneous adipose tissue was cultured in the presence of C-peptide. The level of lipolysis was determined by glycerol measurement in the conditioned media. Effect of C-peptide on adiponectin secretion was evaluated in differentiated adipocytes. The adipogenic and osteogenic abilities of adipose MSCs were evaluated using oil red and alizarin red staining, respectively. The tetrazolium bromide test was conducted for evaluating the effect of C-peptide on MSCs proliferation. C-peptide induced a significant decrease in basal lipolysis at concentrations of 8 and 16 nM (p effects on isoproterenol-stimulated lipolysis, adiponectin secretion, and adipogenic or osteogenic differentiation of MSCs. At a concentration of 4 nM, this peptide significantly increased the proliferative capability of MSCs (p effects in human subcutaneous adipose tissue and contributes to the regulation of basal lipolysis and pool of MSCs.

  14. Iodine Treatment in Children with Subclinical Hypothyroidism Due to Chronic Iodine Deficiency Decreases Thyrotropin and C-Peptide Concentrations and Improves the Lipid Profile

    OpenAIRE

    M.B. Zimmermann; Aeberli, I; Boonstra, A.; Grimci, L.; Bridson, J; Chaouki, N.; Mbhenyane, X.; Jooste, P L

    2009-01-01

    Background: Chronic iodine deficiency (ID) increases thyrotropin (TSH) concentrations and produces a thyroid hormone pattern consistent with subclinical hypothyroidism (ScH). ScH may be associated with cardiovascular disease risk factors. Thus, the study aim was to determine if iodine treatment of children with elevated TSH concentrations due to ID would affect their lipid profile, insulin (C-peptide) levels, and/or subclinical inflammation. Methods: In controlled intervention trials of oral ...

  15. Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man

    DEFF Research Database (Denmark)

    Henriksen, J H; Tronier, B; Bülow, J B

    1987-01-01

    Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular...

  16. Discrepancy between plasma C-peptide and insulin response to oral and intravenous glucose

    DEFF Research Database (Denmark)

    Madsbad, S; Kehlet, H; Hilsted, J;

    1983-01-01

    Plasma insulin, proinsulin, and C-peptide responses to 25 g glucose orally and intravenously administered were measured in 10 healthy males. Plasma insulin response was higher during the oral load in accordance with the "incretin" concept. However, the actual amount of insulin secreted, as measur...... partially to a lower hepatic extraction of insulin....

  17. Bisphenol A levels in human urine.

    OpenAIRE

    Matsumoto, Akiko; Kunugita, Naoki; Kitagawa, Kyoko; Isse, Toyohi; Oyama, Tsunehiro; Foureman, Gary L; Morita, Masatoshi; Kawamoto, Toshihiro

    2003-01-01

    The estrogenic effects of bisphenol A (BPA) have been reported in human cells (E-screen assays) and in (italic)in vivo(/italic) studies of rodents, although the latter reports remain controversial, as do the exposure levels and adverse health effects of BPA in humans. In this study we report on an analytical high-performance liquid chromatography/fluorescence method for BPA and its conjugate in human urine and on the application of this method in two student cohorts. Urine, along with informa...

  18. Employment growth, human capital and educational levels

    DEFF Research Database (Denmark)

    Hansen, Høgni Kalsø; Winther, Lars

    2015-01-01

    human capital in understanding regional growth. We examine to what extent different labour competences and capabilities relate to municipal employment growth using nine stratified, educational categories as proxies for different levels of human capital. Dividing municipalities into four spatial...... categories ranging from the urban to the peripheral, we conclude that there is a strong spatial distinction of educational structures with an urban bias, and that educational categories other than academic human capital can make an important contribution to our understanding of what drives employment growth...

  19. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  20. Oxygen tension level and human viral infections.

    Science.gov (United States)

    Morinet, Frédéric; Casetti, Luana; François, Jean-Hugues; Capron, Claude; Pillet, Sylvie

    2013-09-01

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Unordered structured of proinsulin C-peptide in aqueous solution and in the presence of lipid vesicles.

    Science.gov (United States)

    Henriksson, M; Shafqat, J; Liepinsh, E; Tally, M; Wahren, J; Jörnvall, H; Johansson, J

    2000-02-01

    Proinsulin C-peptide ameliorates renal and autonomic nerve function and increases skeletal muscle blood flow, oxygen uptake and glucose transport in patients with insulin-dependent diabetes mellitus. These effects have in part been ascribed to the stimulatory influence of C-peptide on Na+,K+-ATPase and endothelial nitric oxide synthase. To evaluate the capacity of C-peptide to insert into lipid bilayers and form ion channels, C-peptide secondary structure and membrane interactions were studied with circular dichroism spectroscopy and size exclusion chromatography. C-peptide is shown to lack a stable secondary structure, both when part of proinsulin and when free in aqueous solution, although the N-terminal third of the peptide exhibits an alpha-helical conformation in trifluoroethanol. Moreover, C-peptide remains disordered in the aqueous solvent in the presence of lipid vesicles, regardless of vesicle composition. In conclusion, C-peptide is unlikely to elicit physiological effects through stable conformation-dependent interactions with lipid membranes.

  2. Bisphenol A levels in human urine.

    Science.gov (United States)

    Matsumoto, Akiko; Kunugita, Naoki; Kitagawa, Kyoko; Isse, Toyohi; Oyama, Tsunehiro; Foureman, Gary L; Morita, Masatoshi; Kawamoto, Toshihiro

    2003-01-01

    The estrogenic effects of bisphenol A (BPA) have been reported in human cells (E-screen assays) and in (italic)in vivo(/italic) studies of rodents, although the latter reports remain controversial, as do the exposure levels and adverse health effects of BPA in humans. In this study we report on an analytical high-performance liquid chromatography/fluorescence method for BPA and its conjugate in human urine and on the application of this method in two student cohorts. Urine, along with information on smoking, alcohol intake, and coffee/tea consumption, was collected in two different years from two different groups of university students, 50 in 1992 and 56 in 1999. Overall, the urinary BPA levels in the students in 1992 were significantly higher than were those in 1999. The BPA levels were also positively correlated with coffee and tea consumption in the 1992 cohort but not in the 1999 cohort. We speculate that recent changes made in Japan regarding the interior coating of cans used to package these beverages may partly explain these findings.

  3. [Correlation analysis of the pre-pregnant body mass index, the gestational weight gain and umbilical cord blood C peptide].

    Science.gov (United States)

    Chen, X L; Han, Y; Zhao, X M; Liu, Y; Lü, J J

    2017-01-03

    Objective: To explore the correlation among the pre-pregnant body mass index (BMI), gestational weight gain (GWG) and umbilical cord blood C peptide, and to investigate the influence of maternal weight management on the incidence of baby long-term metabolic syndrome. Methods: During May to Aug.2015, 485 pregnant women in Zhejiang Taizhou first people's hospital and Taizhou Huangyan maternal &child care service centre were selected in random and divided into four groups according to pre-pregnant BMI: low body mass, normal body mass, over body mass and obese group, and also divided into two groups for getting gestational diabetes mellitus (GDM) or not. According to the gestational weight gain (GWG), all the cases were divided into two groups: above the Institute Of Medicine (IMO) 2009 recommendations or not. According to the outcome, the GDM group which had received weight control treatment, was divided into successful treat group or not. At last, we tested the umbilical cord blood C peptide and birth weight of each newborn and compared the difference in all subgroups. The correlation between the umbilical cord blood C peptide and birth weight were analysed. Results: (1) In the pre-pregnant BMI groups, there were significant differences of incidence of GDM (P0.05). (2) Newborn birth weight and the umbilical cord blood C peptide were positively correlated (r=0.673, PUmbilical cord blood C peptide showed the correlation in all subgroups for different pre-pregnant BMI, GDM or not, overweight or not (Pumbilical cord blood C peptide, the GDM mostly (β=0.58), pre-pregnant BMI secondly (β: 0.36, 0.38) , and GWG weakly (β=0.17). (5) By stratification analysis, in GDM group, low body mass was negatively correlated with umbilical cord blood C peptide (Pumbilical cord blood C peptide (Pumbilical cord blood C peptide. Suitable maternal weight control especially pre-pregnant body mass index control will lower the baby long-term metabolic syndrome incidence.

  4. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C; Kaas, A; Hansen, L

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated...... progression of the disease. Likewise, CCL3 was negatively related to C-peptide and positively associated with the beta-cell stress marker proinsulin but increased in remitters. CCL4 associated with decreased beta-cell stress shown by negative association with proinsulin. Blockage of chemokines or antagonism...

  5. Sensitivity and reproducibility of urinary C-peptide as estimate of islet B-cell function in insulin-treated diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Faber, O K;

    1989-01-01

    The aims of the present study were to evaluate the ability of urinary C-peptide determination to demonstrate presence of residual insulin secretion, and to evaluate the reproducibility of urinary C-peptide excretion in 125 insulin-treated diabetic patients. C-peptide was determined in two consecu...

  6. The Effects of C-peptide on Type 1 Diabetic Polyneuropathies and Encephalopathy in the BB/Wor-rat

    Directory of Open Access Journals (Sweden)

    Anders A. F. Sima

    2008-01-01

    Here the effects of C-peptide replenishment will be extensively described as they pertain to DPN and diabetic encephalopathy, underpinning its beneficial effects on neurological complications in type 1 diabetes.

  7. Interdependencies among Selected Pro-Inflammatory Markers of Endothelial Dysfunction, C-Peptide, Anti-Inflammatory Interleukin-10 and Glucose Metabolism Disturbance in Obese Women.

    Science.gov (United States)

    Janowska, Joanna; Chudek, Jerzy; Olszanecka-Glinianowicz, Magdalena; Semik-Grabarczyk, Elżbieta; Zahorska-Markiewicz, Barbara

    2016-01-01

    Currently increasing importance is attributed to the inflammatory process as a crucial factor responsible for the progressive damage to vascular walls and progression of atherosclerosis in obese people. We have studied the relationship between clinical and biochemical parameters and C-peptide and anti-inflammatory IL-10, as well as selected markers of inflammation and endothelial dysfunction such as: CCL2, CRP, sICAM-1, sVCAM-1 and E-selectin in obese women with various degree of glucose metabolism disturbance. The studied group consisted of 61 obese women, and 20 normal weight, healthy volunteers. Obese patients were spited in subgroups based on the degree of glucose metabolism disorder. Serum samples were analyzed using ELISA kits. Increased concentrations of sICAM-1, sVCAM-1, E-selectin, CCL2 and CRP were found in all obese groups compared to the normal weight subjects. In patients with Type 2 diabetes mellitus (T2DM) parameters characterizing the degree of obesity significantly positively correlated with levels of CRP and CCL2. Significant relationships were found between levels of glucose and sICAM-1and also E-selectin and HOMA-IR. C-peptide levels are positively associated with CCL2, E-selectin, triglycerides levels, and inversely with IL-10 levels in newly diagnosed T2DM group (p<0.05). Concentrations of IL-10 correlated negatively with E-selectin, CCL2, C-peptide levels, and HOMA-IR in T2DM group (p<0.05). Disturbed lipid and carbohydrate metabolism are manifested by enhanced inflammation and endothelial dysfunction in patients with simply obesity. These disturbances are associates with an increase of adhesion molecules. The results suggest the probable active participation of higher concentrations of C-peptide in the intensification of inflammatory and atherogenic processes in obese patients with type 2 diabetes. In patients with obesity and type 2 diabetes, altered serum concentrations of Il-10 seems to be dependent on the degree of insulin resistance and

  8. C-peptide levels predict type 2 diabetes remission after bariatric surgery.

    Science.gov (United States)

    Ramos-Leví, Ana M; Matía, Pilar; Cabrerizo, Lucio; Barabash, Ana; Torrejón, María José; Sánchez-Pernaute, Andrés; Torres, Antonio J; Rubio, Miguel A

    2013-01-01

    Introducción: La determinación del péptido C (pC) suele emplearse como un indicador de la reserva betapancreática. El objetivo de este estudio es evaluar si el pC basal, es un parámetro predictor de remisión de diabetes mellitus tipo 2 (DM2) tras cirugía bariátrica (CB). Material y métodos: Estudio retrospectivo de 22 pacientes con DM2 e IMC > 35 kg/m2, intervenidos mediante CB. Recogida de datos clínicos, antropométricos y analíticos relativos al metabolismo de la glucosa, antes de la CB y al año. Análisis de pacientes en remisión completa de DM2 al año de la CB (glucosa basal [GB] 3,75 ng/ml supuso una sensibilidad y especificidad para remisión de DM2 de 75% y 80%, respectivamente. La tasa de remisión de DM2 fue de 27,3% si el pC basal pre-CB 3,8 ng/ml (p = 0,010). Conclusiones: Los pacientes con pC basal preoperatorio elevado son los que mayores tasas de remisión alcanzan al año de la CB. Una concentración de pC basal > 3,75 ng/dL parece un buen predictor de remisión completa de DM2 al año de la CB.

  9. C-peptide attenuates acute lung inflammation in a murine model of hemorrhagic shock and resuscitation by reducing gut injury.

    Science.gov (United States)

    Kao, Raymond L C; Xu, Xuemei; Xenocostas, Anargyros; Parry, Neil; Mele, Tina; Martin, Claudio M; Rui, Tao

    2017-08-01

    The study aims to evaluate whether C-peptide can reduce gut injury during hemorrhagic shock (HS) and resuscitation (R) therefore attenuate shock-induced inflammation and subsequent acute lung injury. Twelve-week-old male mice (C57/BL6) were hemorrhaged (mean arterial blood pressure maintained at 35 mm Hg for 60 minutes) and then resuscitated with Ringer's lactate, followed by red blood cell transfusion with (HS/R) or without C-peptide (HS/R + C-peptide). Mouse gut permeability, bacterial translocation into the circulatory system and intestinal pathology, circulating HMGB1, and acute lung injury were assessed at different times after R. The mice in the control group underwent sham procedures without HS. Compared to the sham group, the mice in the HS/R group showed increased gut permeability (6.07 ± 3.41 μg of FD4/mL) and bacterial translocation into the circulatory system (10.05 ± 4.92, lipopolysaccharide [LPS] of pg/mL), and increased gut damage; conversely, mice in the HS/R + C-peptide group showed significantly reduced gut permeability (1.59 ± 1.39 μg of FD4/mL; p C-peptide group showed decreased HMGB1 (7.27 ± 1.93 ng/mL; p C-peptide exerts beneficial effects to attenuate gut injury and dysfunction, therefore diminishing lung inflammation and subsequent injury in mice with HS and R.

  10. Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

    DEFF Research Database (Denmark)

    Kaas, A; Pfleger, Claudia Christina; Kharagjitsingh, A V;

    2012-01-01

    Aims: The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFN¿) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes. Methods: Two hundred and twenty-seven patients from the Hvidoere Study Group were...... classified in four different progression groups as assessed by change in stimulated C-peptide from 1 to 6 months. CA repeat variants of the IL-10 and IFN¿ gene were genotyped and serum levels of IL-10 and IFN¿ were measured at 1, 6 and 12 months. Results: IL-10 decreased (P...

  11. Iodine treatment in children with subclinical hypothyroidism due to chronic iodine deficiency decreases thyrotropin and C-peptide concentrations and improves the lipid profile.

    Science.gov (United States)

    Zimmermann, Michael B; Aeberli, Isabelle; Melse-Boonstra, Alida; Grimci, Lindita; Bridson, John; Chaouki, Noureddine; Mbhenyane, Xikombiso; Jooste, Pieter L

    2009-10-01

    Chronic iodine deficiency (ID) increases thyrotropin (TSH) concentrations and produces a thyroid hormone pattern consistent with subclinical hypothyroidism (ScH). ScH may be associated with cardiovascular disease risk factors. Thus, the study aim was to determine if iodine treatment of children with elevated TSH concentrations due to ID would affect their lipid profile, insulin (C-peptide) levels, and/or subclinical inflammation. In controlled intervention trials of oral iodized oil or iodized salt, 5-14-year-old children from Morocco, Albania, and South Africa with TSH concentrations > or = 2.5 mU/L (n = 262) received 400 mg iodine as oral iodized oil or household distribution of iodized salt containing 25 microg iodine/g salt. At baseline and after 5 or 6 months, urinary iodine (UI) and blood concentrations of total thyroxine, TSH, C-reactive protein (CRP), C-peptide, and lipids were measured. Median (range) UI at baseline was 46 (2-601) microg/L. Compared to the control group, iodine treatment significantly increased UI and total thyroxine and decreased TSH, C-peptide, and total and low-density lipoprotein cholesterol. The mean low-density lipoprotein/high-density lipoprotein cholesterol ratio fell from 3.3 to 2.4 after iodine treatment (p Iodine treatment had no significant effect on concentrations of high-density lipoprotein cholesterol, triglycerides, or C-reactive protein. Correction of ID-associated ScH improves the insulin and lipid profile and may thereby reduce risk for cardiovascular disease. This previously unrecognized benefit of iodine prophylaxis may be important because ID remains common in rapidly developing countries with increasing rates of obesity and cardiovascular disease.

  12. Human placental lactogen levels in multiple pregnancies.

    Science.gov (United States)

    Spellacy, W N; Buhi, W C; Birk, S A

    1978-08-01

    Serum human placental lactogen (hPL) levels were measured in duplicate with a radioimmunoassay in 206 serum samples at 30 and 36 weeks' gestation from women with normal singleton pregnancies (75) or pregnancies with twins (37). One triplet pregnancy was also studied. The results show a significant elevation of hPL in the women with twin pregnancies at both the 30th (7.0 vs 6.0 microgram/ml) and the 36th (9.2 vs 7.4 microgram/ml) weeks. One-third of the twin pregnancies had values of hPL in excess of 8.0 microgram/ml at 30 weeks and more than half had values in excess of 9.0 microgram/ml at 36 weeks. The triplet pregnancy had an hPL value of 11.0 microgram/ml at 36 weeks' gestation. These data support the potential usefulness of serum hPL measurements in the screening profile for the detection of high-risk pregnancies.

  13. Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice.

    Science.gov (United States)

    Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Abou-El-Mahasen, Mona A; Ashamallah, Sylvia A; Khater, Sherry M; El-Halawani, Sawsan M; Ibrahim, Rana Y; Uin, Gan Shu; Kloc, Malgorzata; Calne, Roy Y; Ghoneim, Mohamed A

    2013-01-01

    Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in vitro by flow cytometry, immunolabeling, RT-PCR, and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ∼5-10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin, and c-peptide were coexpressed. Nanogold immunolabeling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPC-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and nondiabetic human subjects could be differentiated without genetic manipulation to form IPCs that, when transplanted, could maintain euglycemia in diabetic mice for 3 months

  14. Human factors in healthcare level one

    CERN Document Server

    Rosenorn-Lanng, Debbie

    2014-01-01

    The majority of errors, litigation, and complaints in the health service are due to 'human factors', yet the term is still not widely understood and is sometimes used interchangeably to refer to team training or communication skills. Although including these, the subject of 'human factors' goes far beyond this to look at systems, environmental influences, and interactions with equipment, in addition to self-awareness and human interaction. All of these aspects are captured inHuman Factors in Healthcare and are built into a new framework: the SHEEP model, which breaks down into five key areas:

  15. Finasteride modifies the relation between serum C-peptide and prostate cancer risk: results from the Prostate Cancer Prevention Trial

    Science.gov (United States)

    Neuhouser, Marian L.; Till, Cathee; Kristal, Alan; Goodman, Phyllis; Hoque, Ashraful; Platz, Elizabeth A.; Hsing, Ann W.; Albanes, Demetrius; Parnes, Howard L.; Pollak, Michael

    2013-01-01

    BACKGROUND Hyperinsulinemia and obesity-related metabolic disturbances are common and have been associated with increased cancer risk and poor prognosis. METHODS Data are from a case-control study within the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial testing finasteride vs. placebo for primary prevention of prostate cancer. Cases (n=1803) and controls (n= 1797) were matched on age, PCPT treatment arm, and family history of prostate cancer; controls included all eligible non-whites. Outcomes were biopsy-determined. Baseline bloods were assayed for serum C-peptide (marker of insulin secretion) and leptin (an adipokine) using ELISA. Logistic regression calculated odds ratios for total prostate cancer and polytomous logistic regression calculated odds ratios for low-grade (Gleason prostate cancer (Gleason ≥ 7) (multivariate-adjusted OR= 1.88, 95%CI 1.19-2.97, p trend = 0.004). When C-peptide was modeled as a continuous variable, every unit increase in [log(C-peptide)], resulted in a 39% increased risk of high-grade disease (p=0.01). In contrast, there was no significant relationship between C-peptide and high-grade prostate cancer among men receiving finasteride. Leptin was not independently associated with high-grade prostate cancer. CONCLUSIONS These results support findings from other observational studies that high serum C-peptide and insulin-resistance, but not leptin, are associated with increased risk of high-grade prostate cancer. Our novel finding is that the C-peptide-associated risk was attenuated by use of finasteride. PMID:20179296

  16. Recombinant Human Leptin Does Not Alter Gut Hormone Levels after Gastric Bypass but May Attenuate Sweet Cravings

    Directory of Open Access Journals (Sweden)

    Rushika Conroy

    2014-01-01

    Full Text Available Bariatric surgery improves glucose homeostasis and alters gut hormones partly independent of weight loss. Leptin plays a role in these processes; levels are decreased following bariatric surgery, creating a relative leptin insufficiency. We previously showed that leptin administration in a weight-reduced state after Roux-en-Y gastric bypass (RYGB caused no further weight loss. Here, we discuss the impact of leptin administration on gut hormones, glucostasis, and appetite. Weight stable women after RYGB were randomized to receive placebo or recombinant human metreleptin (0.05 mg/kg twice daily. At weeks 0 and 16, a liquid meal challenge was performed. Glucose, insulin, C-peptide, GLP-1, PYY, glucagon, and ghrelin (total, acyl, and desacyl were measured fasting and postprandially. Appetite was assessed using a visual analog scale. Mean post-op period was 53±2.3 months; mean BMI was 34.6±0.2 kg/m2. At 16 weeks, there was no significant change in weight within or between groups. Fasting PYY was significantly different between groups and the leptin group had lower sweets craving at week 16 than the placebo group (P<0.05. No other differences were observed. Leptin replacement does not alter gut hormones or glucostasis but may diminish sweet cravings compared to placebo in this population of post-RYGB women.

  17. Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis

    Science.gov (United States)

    The objective of this study was to test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features. We analyzed 607 children aged <19 yr consecutively diagnosed with diabetes after ex...

  18. Changes in Bone Alkaline Phosphatase and Procollagen Type-1 C-Peptide after Static and Dynamic Exercises

    Science.gov (United States)

    Kubo, Keitaro; Yuki, Kazuhito; Ikebukuro, Toshihiro

    2012-01-01

    We investigated the effects of two types of nonweight-bearing exercise on changes in bone-specific alkaline phosphatase (BAP) and pro-collagen type 1 C-peptide (P1P). BAP is a specific marker of bone synthesis, whereas P1P reflects synthesis of type 1 collagen in other organs as well as bone. Eight participants performed static and dynamic…

  19. Investigation of relationship between serum C-peptide and diabetic retinopathy in type 2 diabetes mellitusF%探究血清C肽与2型糖尿病视网膜病变的关系

    Institute of Scientific and Technical Information of China (English)

    范进绵; 高俊泽

    2015-01-01

    目的:对血清C肽与2型糖尿病视网膜病变(DR)的关系进行分析与探讨。方法120例2型糖尿病患者,根据患者病情将其分为三组,即:无糖尿病视网膜病变(NDR)组40例,非增殖性糖尿病视网膜病变(NPDR)组42例,增殖性糖尿病视网膜病变(PDR)组38例。以电化学发光法对所有患者空腹血清C肽进行测定。结果三组患者空腹血清C肽水平均呈现下降趋势,三组比较,差异具有统计学意义(P<0.05)。血清C肽与2型糖尿病视网膜病变程度呈负相关。结论研究表明,在2型糖尿病视网膜病变中,血清C肽含量会由于病变程度的加深而逐渐降低,血清C肽水平是2型糖尿病视网膜病变进展的重要标志。%ObjectiveTo analyze and investigate the relationship between serum C-peptide and diabetic retinopathy (DR) in type 2 diabetes mellitus.MethodsA total of 120 type 2 diabetes mellitus patients were divided by their illness condition into three groups, as non diabetic retinopathy (NDR) group with 40 cases, non proliferative diabetic retinopathy (NPDR) group with 42 cases, and proliferative diabetic retinopathy (PDR) group with 38 cases. Electrochemiluminescence method was applied for detection of serum C-peptide in all patients.ResultsAll the three groups had decreased levels of fasting serum C-peptide, and the difference had statistical significance across the three groups (P<0.05). There was a negative correlation between serum C-peptide and diabetic retinopathy in type 2 diabetes mellitus.ConclusionThis study shows the content of serum C-peptide will decrease along with the development of diabetic retinopathy in type 2 diabetes mellitus, therefore, serum C-peptide acts as an important indicator for progression of diabetic retinopathy in type 2 diabetes mellitus.

  20. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C.; Kaas, A.; Hansen, L.

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated...... longitudinally circulating concentrations of CCR5 ligands of 256 newly diagnosed patients with type 1 diabetes. CCR5 ligands were differentially associated with beta-cell function and clinical remission. CCL5 was decreased in remitters and positively associated with HbA1c suggestive of a Th1 associated...... progression of the disease. Likewise, CCL3 was negatively related to C-peptide and positively associated with the beta-cell stress marker proinsulin but increased in remitters. CCL4 associated with decreased beta-cell stress shown by negative association with proinsulin. Blockage of chemokines or antagonism...

  1. Level of copper in human split ejaculate.

    Science.gov (United States)

    Skandhan, Kalanghot; Valsa, James; Sumangala, Balakrishnan; Jaya, Vasudevan

    2017-02-03

    The purpose of this study was to understand the details of splits of an ejaculate and to locate the origin of release of copper into semen. Laboratory methods routinely followed for semen analysis were carried out. Copper was estimated by employing atomic absorption spectrophotometry. First split of ejaculate showed the highest number of motile sperm, the quality of which decreased from first to third. Copper level in splits 1, 2 and 3 was 29, 23 and 22 µg%, respectively. This study concluded that copper was released from throughout the genital tract.

  2. Nutritional Factors and Preservation of C-Peptide in Youth With Recently Diagnosed Type 1 Diabetes

    Science.gov (United States)

    Mayer-Davis, Elizabeth J.; Dabelea, Dana; Crandell, Jamie L.; Crume, Tessa; D’Agostino, Ralph B.; Dolan, Lawrence; King, Irena B.; Lawrence, Jean M.; Norris, Jill M.; Pihoker, Catherine; The, Natalie

    2013-01-01

    OBJECTIVE To test the novel hypothesis that nutritional factors previously associated with type 1 diabetes etiology or with insulin secretion are prospectively associated with fasting C-peptide (FCP) concentration among youth recently diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS Included were 1,316 youth with autoantibody-positive type 1 diabetes who participated in the SEARCH for Diabetes in Youth study (baseline disease duration, 9.9 months; SD, 6.3). Nutritional exposures included breastfeeding and age at introduction of complementary foods, baseline plasma long-chain omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin D, vitamin E, and, from a baseline food frequency questionnaire, estimated intake of the branched-chain amino acid leucine and total carbohydrate. Multiple linear regression models were conducted to relate each nutritional factor to baseline FCP adjusted for demographics, disease-related factors, and other confounders. Prospective analyses included the subset of participants with preserved β-cell function at baseline (baseline FCP ≥0.23 ng/mL) with additional adjustment for baseline FCP and time (mean follow-up, 24.3 months; SD, 8.2; n = 656). FCP concentration was analyzed as log(FCP). RESULTS In adjusted prospective analyses, baseline EPA (P = 0.02), EPA plus DHA (P = 0.03), and leucine (P = 0.03) were each associated positively and significantly with FCP at follow-up. Vitamin D was unexpectedly inversely associated with FCP (P = 0.002). CONCLUSIONS Increased intake of branched-chain amino acids and long-chain omega-3 fatty acids may support preservation of β-cell function. This represents a new direction for research to improve prognosis for type 1 diabetes. PMID:23801797

  3. Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C.; Hansen, L.; Herder, C.

    2008-01-01

    OBJECTIVE: We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin, proinflammatory cytokines IL-1 beta, IL-6, and CCL2, and tumor necrosis factor-alpha with beta-cell function, metabolic status, and clinical remission in patients...... with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide, blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months...... after diagnosis. Analyses were adjusted for sex, age, and BMI percentile. RESULTS: Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 (P = 0.0009) and 12 (P = 0.009) months. The beneficial association of IL-1ra on beta-cell function was complemented by the negative association...

  4. C-peptide of preproinsulin-like peptide 7: localization in the rat brain and activity in vitro.

    Science.gov (United States)

    Brailoiu, E; Dun, S L; Gao, X; Brailoiu, G C; Li, J-G; Luo, J J; Yang, J; Chang, J K; Liu-Chen, L-Y; Dun, N J

    2009-03-17

    With the use of a rabbit polyclonal antiserum against a conserved region (54-118) of C-peptide of human preproinsulin-like peptide 7, referred to herein as C-INSL7, neurons expressing C-INSL7-immunoreactivity (irC-INSL7) were detected in the pontine nucleus incertus, the lateral or ventrolateral periaqueductal gray, dorsal raphe nuclei and dorsal substantia nigra. Immunoreactive fibers were present in numerous forebrain areas, with a high density in the septum, hypothalamus and thalamus. Pre-absorption of C-INSL7 antiserum with the peptide C-INSL7 (1 microg/ml), but not the insulin-like peptide 7 (INSL7; 1 microg/ml), also known as relaxin 3, abolished the immunoreactivity. Optical imaging with a voltage-sensitive dye bis-[1,3-dibutylbarbituric acid] trimethineoxonol (DiSBAC4(3)) showed that C-INSL7 (100 nM) depolarized or hyperpolarized a small population of cultured rat hypothalamic neurons studied. Ratiometric imaging studies with calcium-sensitive dye fura-2 showed that C-INSL7 (10-1000 nM) produced a dose-dependent increase in cytosolic calcium concentrations [Ca2+]i in cultured hypothalamic neurons with two distinct patterns: (1) a sustained elevation lasting for minutes; and (2) a fast, transitory rise followed by oscillations. In a Ca2+-free Hanks' solution, C-INSL7 again elicited two types of calcium transients: (1) a fast, transitory increase not followed by a plateau phase, and (2) a transitory rise followed by oscillations. INSL7 (100 nM) elicited a depolarization or hyperpolarization in a small population of hypothalamic neurons, and an increase of [Ca2+]i with two patterns that were dissimilar from that of C-INSL7. [125I]C-INSL7 bindings to rat brain membranes were inhibited by C-INSL7 in a dose-dependent manner; the Kd and Bmax. values were 17.7 +/- 8.2 nM and 45.4 +/- 20.5 fmol/mg protein. INSL7 did not inhibit [125I]C-INSL7 binding to rat brain membranes, indicating that C-INSL7 and INSL7 bind to distinct binding sites. Collectively, our result

  5. Urinary C peptide creatinine ratio in pregnant women with normal glucose tolerance and type 1 diabetes: evidence for insulin secretion

    Science.gov (United States)

    Markoska, Ankica; Valaiyapathi, Rajalakshmi; Thorn, Chloe; Dornhorst, Anne

    2017-01-01

    Hypothesis In pregnancy, urinary C peptide creatinine ratio (UCPCR) reflects endogenous insulin secretion in women with normal glucose tolerance and type 1 diabetes. Research design and methods UCPCR and serum C peptide were measured in 90 glucose-tolerant women at 0 and 120 min during a 75 g oral glucose tolerance test (OGTT) at 28 weeks of gestation. UCPCR was measured in 2 samples obtained over 10 weeks apart in 7 pregnant women with longstanding type 1 diabetes. Results UCPCROGTT and serum C peptideOGTT of glucose-tolerant women were significantly correlated at 0 and 120 min (rs0.675, 0.541 respectively, p<0.0001). All 7 pregnant women with type 1 diabetes had detectable first sample UCPCR (median (range) 49 (6–1038) pmol/mmol) that rose in 6 women by 477 (29–1491) pmol/mmol. Conclusions Detectable UCPCR in pregnant women with normal glucose tolerance and type 1 diabetes is likely to reflect endogenous insulin secretion and hence β-cell activity. PMID:28090333

  6. Different level of population differentiation among human genes

    Directory of Open Access Journals (Sweden)

    Zhang Ya-Ping

    2011-01-01

    Full Text Available Abstract Background During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations. Results Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher FST SNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection. Conclusion Our analysis demonstrates different level of population differentiation among human populations for different gene groups.

  7. Performance of individually-measured vs population-based C-peptide kinetics to assess β-cell function in presence and absence of acute insulin resistance.

    Science.gov (United States)

    Varghese, Ron T; Dalla Man, Chiara; Laurenti, Marcello C; Piccinini, Francesca; Sharma, Anu; Shah, Meera; Bailey, Kent R; Rizza, Robert A; Cobelli, Claudio; Vella, Adrian

    2017-09-01

    Standardized, population-based kinetics of C-peptide distribution and clearance are used to estimate insulin secretion from plasma C-peptide concentrations without direct measurement of C-peptide kinetics. We then compared the performance of population-based kinetics to directly measured C-peptide kinetics when used to calculate β-cell responsivity indices. To ensure that population-based kinetics apply to all conditions where β-cell function is measured, subjects were studied in the presence and absence of acute insulin resistance. Somatostatin was used to inhibit endogenous insulin secretion in 56 nondiabetic subjects. Subsequently, a C-peptide bolus was administered and the changing concentrations used to calculate individual kinetic parameters of C-peptide clearance. In addition, they were studied on 2 occasions in random order using an oral glucose tolerance test (OGTT). On one occasion, free fatty acid (FFA) elevation to cause insulin resistance, was achieved by infusion of intralipid + heparin. Disposition Index (DI) was then estimated by the oral minimal model using either population-based or individual C-peptide kinetics. There were marked differences in the exchange parameters (k12 and k21 ) of the model describing C-peptide kinetics, but smaller differences in the fractional clearance, i.e. the irreversible loss from the accessible compartment (k01 ), obtained from population-based estimates compared to experimental measurement. Since it is predominantly influenced by k01 , DI estimated using individual kinetics correlated well with those estimated using population-based kinetics. These data support the use of population-based measures of C-peptide kinetics to estimate β-cell function during OGTT. This article is protected by copyright. All rights reserved.

  8. Isolation, Culture, and Imaging of Human Fetal Pancreatic Cell Clusters

    Science.gov (United States)

    Lopez, Ana D.; Kayali, Ayse G.; Hayek, Alberto; King, Charles C.

    2014-01-01

    For almost 30 years, scientists have demonstrated that human fetal ICCs transplanted under the kidney capsule of nude mice matured into functioning endocrine cells, as evidenced by a significant increase in circulating human C-peptide following glucose stimulation1-9. However in vitro, genesis of insulin producing cells from human fetal ICCs is low10; results reminiscent of recent experiments performed with human embryonic stem cells (hESC), a renewable source of cells that hold great promise as a potential therapeutic treatment for type 1 diabetes. Like ICCs, transplantation of partially differentiated hESC generate glucose responsive, insulin producing cells, but in vitro genesis of insulin producing cells from hESC is much less robust11-17. A complete understanding of the factors that influence the growth and differentiation of endocrine precursor cells will likely require data generated from both ICCs and hESC. While a number of protocols exist to generate insulin producing cells from hESC in vitro11-22, far fewer exist for ICCs10,23,24. Part of that discrepancy likely comes from the difficulty of working with human fetal pancreas. Towards that end, we have continued to build upon existing methods to isolate fetal islets from human pancreases with gestational ages ranging from 12 to 23 weeks, grow the cells as a monolayer or in suspension, and image for cell proliferation, pancreatic markers and human hormones including glucagon and C-peptide. ICCs generated by the protocol described below result in C-peptide release after transplantation under the kidney capsule of nude mice that are similar to C-peptide levels obtained by transplantation of fresh tissue6. Although the examples presented here focus upon the pancreatic endoderm proliferation and β cell genesis, the protocol can be employed to study other aspects of pancreatic development, including exocrine, ductal, and other hormone producing cells. PMID:24895054

  9. Isolation, culture, and imaging of human fetal pancreatic cell clusters.

    Science.gov (United States)

    Lopez, Ana D; Kayali, Ayse G; Hayek, Alberto; King, Charles C

    2014-05-18

    For almost 30 years, scientists have demonstrated that human fetal ICCs transplanted under the kidney capsule of nude mice matured into functioning endocrine cells, as evidenced by a significant increase in circulating human C-peptide following glucose stimulation(1-9). However in vitro, genesis of insulin producing cells from human fetal ICCs is low(10); results reminiscent of recent experiments performed with human embryonic stem cells (hESC), a renewable source of cells that hold great promise as a potential therapeutic treatment for type 1 diabetes. Like ICCs, transplantation of partially differentiated hESC generate glucose responsive, insulin producing cells, but in vitro genesis of insulin producing cells from hESC is much less robust(11-17). A complete understanding of the factors that influence the growth and differentiation of endocrine precursor cells will likely require data generated from both ICCs and hESC. While a number of protocols exist to generate insulin producing cells from hESC in vitro(11-22), far fewer exist for ICCs(10,23,24). Part of that discrepancy likely comes from the difficulty of working with human fetal pancreas. Towards that end, we have continued to build upon existing methods to isolate fetal islets from human pancreases with gestational ages ranging from 12 to 23 weeks, grow the cells as a monolayer or in suspension, and image for cell proliferation, pancreatic markers and human hormones including glucagon and C-peptide. ICCs generated by the protocol described below result in C-peptide release after transplantation under the kidney capsule of nude mice that are similar to C-peptide levels obtained by transplantation of fresh tissue(6). Although the examples presented here focus upon the pancreatic endoderm proliferation and β cell genesis, the protocol can be employed to study other aspects of pancreatic development, including exocrine, ductal, and other hormone producing cells.

  10. Carotenoid levels in human lymphocytes, measured by Raman microspectroscopy

    NARCIS (Netherlands)

    Ramanauskaite, R B; SegersNolten, IGMJ; DeGrauw, K J; Sijtsema, N M; VanderMaas, L; Greve, J; Otto, C; Figdor, C G

    1997-01-01

    Carotenoid levels in lymphocytes obtained from peripheral blood of healthy people have been investigated by Raman microspectroscopy. We observed that carotenoids are concentrated in so-called ''Gall bodies''. The level of carotenoids in living human lymphocytes was found to be age-dependent and to d

  11. Genome-wide search for susceptibility genes to type 2 diabetes in West Africans: potential role of C-peptide.

    Science.gov (United States)

    Chen, Guanjie; Adeyemo, Adebowale; Zhou, Jie; Chen, Yuanxiu; Huang, Hanxia; Doumatey, Ayo; Lashley, Kerrie; Agyenim-Boateng, Kofi; Eghan, Benjamin A; Acheampong, Joseph; Fasanmade, Olufemi; Johnson, Thomas; Okafor, Godfrey; Oli, Johnnie; Amoah, Albert; Rotimi, Charles

    2007-12-01

    C-peptide is a substance that the pancreas releases into the circulation in equimolar amounts to insulin and has demonstrated important physiological effects which relate to the vascular field, in particular the microcirculation. For this analysis, we included 321 full and 36 half sibling pairs affected with type 2 diabetes (T2D) from West Africa. A genome-wide panel of 390 tri-nucleotide and tetra-nucleotide repeats with an average distance of 8.9 cM was performed on a total of 691 persons. Variance components based on multipoint linkage approach as implemented in SOLAR were performed for log C-peptide. Significant linkage evidences were observed on 10q23 at D10S2327 with a LOD score of 4.04 (nominal p-value=0.000008, empirical p-value=0.0004); and on 4p15 at D4S2632 with a LOD score of 3.48 (nominal p-value=0.000031, empirical p-value=0.0013). Other suggestive evidence of linkage were observed on 15q14 at D15S659 with a LOD score 2.41 (nominal p-value=0.000435, empirical p-value=0.0068), and on 18p11 near D18S976 with a LOD score 2.18 (nominal p-value=0.000771 and empirical p-value=0.0094). Interestingly, five positional candidate genes for diabetes and related complications are located in our linkage region (the pituitary adenylate cyclase activating polypeptide (PACAP in 18p11); the peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1 in 4p15); PTEN, PPP1R5, and IDE located in 10q23. In conclusion, we identified four major genetic loci (10q23, 4p15, 15q14, and 18p11) influencing C-peptide concentration in West Africans with T2D.

  12. EFFECT OF ACUPUNCTURE ON PLASMA GLUCOSE LEVEL IN HUMAN VOLUNTEERS

    Institute of Scientific and Technical Information of China (English)

    Amit Kumar Chakraborty; Mrigendranath Gantait; Biswapati Mukherjee

    2006-01-01

    Objective To observe the changes of plasma glucose level (PGL) in human volunteers after acupuncture. Methods Seventy-seven human volunteers were taken up from the acupuncture clinic. All of pletion of acupuncture. All cases were at four hours abstinence from food before doing acupuncture. Results Plasma glucose level varied 5 mg% or more in 62 cases (80.51%) and only those were considered for computation. PGL increased in cases who had generally plasma glucose level below 90 mg% before acupuncture;and PGL decreased in cases who had plasma glucose 90 mg% or above. In 10 control cases there was no variation of the considerable level of 5 mg% in any case. Conclusion Bi-directional variation of PGL after acupuncture indicates that acupuncture can be used to maintain optimum PGL through endogenous mechanism,suggesting that it is applicable in controlling hyperglycemia in diabetes mellitus patients.

  13. Cadmium levels in Europe: implications for human health.

    Science.gov (United States)

    Pan, Jilang; Plant, Jane A; Voulvoulis, Nikolaos; Oates, Christopher J; Ihlenfeld, Christian

    2010-02-01

    In this study we used the Forum of European Geological Surveys geochemical baseline data to examine the distribution of cadmium (Cd) in Europe, with a particular reference to the international soil and water guideline values. The highest cadmium levels were found to occur in topsoil and to follow closely the distribution of P(2)O(5), suggesting that the contamination was from the use of rock phosphate fertilizer in intensive arable agriculture. In terms of human health impacts, food (up to several hundred microg/day) was found as the only major route of exposure to Cd for the non-smoking general population. It appeared that low levels of chronic exposure to Cd resulted in completely different human health impacts than those high levels that had caused the 'itai-itai' disease. Some correlations were suggested between cadmium levels and the age-adjusted prostate or breast cancer rates distributed in the European countries under study.

  14. Global analysis of overweight prevalence by level of human development

    Directory of Open Access Journals (Sweden)

    Carmen D Ng

    2016-02-01

    Full Text Available Less developed countries are increasingly afflicted with over–nutrition, and the escalating overweight prevalence has become a global problem. However, a problem as global as this may not be amenable to a general set of remedial interventions applicable to all countries. I use data from various sources, including the World Health Organization and the World Bank, to test the association of overweight prevalence with economic, social, and demographic indicators. I then split the countries up by human development index to investigate to what extent these associations vary between development levels. On a global scale, overweight prevalence is most associated with gross domestic product (GDP per capita, the proportion of a country that is rural, the proportion of elderly in a country's population, and the average years of schooling. At what magnitude, and even in which direction, these relationships go vary with a country's level of development. Generally, GDP per capita has a positive association with overweight prevalence, with the magnitude of such association for countries of very high human development more than twice of that for countries of low human development. However, proportion rural has a negative association with overweight prevalence, with the magnitude of such association for countries of low human development nearly twice of that for countries of very high human development. All four of these variables have statistically significant association with overweight prevalence in countries with low human development. I make policy suggestions to combat increasing overweight prevalence, based on the models that are developed, paying special attention to the differences in magnitude and direction of the regressors between human development levels.

  15. Global analysis of overweight prevalence by level of human development.

    Science.gov (United States)

    Ng, Carmen D

    2015-12-01

    Less developed countries are increasingly afflicted with over-nutrition, and the escalating overweight prevalence has become a global problem. However, a problem as global as this may not be amenable to a general set of remedial interventions applicable to all countries. I use data from various sources, including the World Health Organization and the World Bank, to test the association of overweight prevalence with economic, social, and demographic indicators. I then split the countries up by human development index to investigate to what extent these associations vary between development levels. On a global scale, overweight prevalence is most associated with gross domestic product (GDP) per capita, the proportion of a country that is rural, the proportion of elderly in a country's population, and the average years of schooling. At what magnitude, and even in which direction, these relationships go vary with a country's level of development. Generally, GDP per capita has a positive association with overweight prevalence, with the magnitude of such association for countries of very high human development more than twice of that for countries of low human development. However, proportion rural has a negative association with overweight prevalence, with the magnitude of such association for countries of low human development nearly twice of that for countries of very high human development. All four of these variables have statistically significant association with overweight prevalence in countries with low human development. I make policy suggestions to combat increasing overweight prevalence, based on the models that are developed, paying special attention to the differences in magnitude and direction of the regressors between human development levels.

  16. Positioning the human resource business using service level agreements.

    Science.gov (United States)

    Tonks, P; Flanagan, H

    1994-01-01

    Explores the introduction and development of Service Level Agreements (SLAs) in relation to Human Resource Departments. Considers approaches to SLAs and highlights four dimensions necessary for the completion of an SLA. Stresses that Human Resource Specialists should have a thorough understanding of how directorates and other departments relate to one another to provide added value in terms of contribution to the organizational outcomes. Suggests the idea of adding value is an integral part of the SLA process which ensures that it operates as a means to an end and does not become an end in itself. Examines the degree of devolved freedom given to a department to seek work or sell its products outside its Trust/Unit. Scrutinizes the format of SLAs and concludes that the benefits of SLAs for users of Human Resource Departments and the benefits to the Human Resource Departments are similar.

  17. Consciousness, Mind, and Spirit: Three Levels of Human Cognition

    Directory of Open Access Journals (Sweden)

    Andrej Ule

    2015-10-01

    Full Text Available The article elucidates three important concepts and realities that refer to cognitive phenomena and are often (mistakenly used as synonyms: consciousness (slo. zavest, mind (slo. um, and spirit (slo. duh. They present three levels of human cognition: individual-experiential, individual-mental, and trans-individual-mental. Simply put: the concept of consciousness pertains to the waking mental life of a human being, while the concept of mind pertains to the ability and activity to consciously comprehend and understand contents and objects of human activity. I delineate three “types” of spirit: personal spirit, objective spirit, and the objectification of spirit in productions of human culture; I have doubts, however, about the existence of cosmic or super-cosmic dimensions of spirit, although some interpretations of quantum physics and modern cosmology suggest that such dimensions are possible.

  18. Sequence-level mechanisms of human epigenome evolution.

    Science.gov (United States)

    Prendergast, James G D; Chambers, Emily V; Semple, Colin A M

    2014-06-24

    DNA methylation and chromatin states play key roles in development and disease. However, the extent of recent evolutionary divergence in the human epigenome and the influential factors that have shaped it are poorly understood. To determine the links between genome sequence and human epigenome evolution, we examined the divergence of DNA methylation and chromatin states following segmental duplication events in the human lineage. Chromatin and DNA methylation states were found to have been generally well conserved following a duplication event, with the evolution of the epigenome largely uncoupled from the total number of genetic changes in the surrounding DNA sequence. However, the epigenome at tissue-specific, distal regulatory regions was observed to be unusually prone to diverge following duplication, with particular sequence differences, altering known sequence motifs, found to be associated with divergence in patterns of DNA methylation and chromatin. Alu elements were found to have played a particularly prominent role in shaping human epigenome evolution, and we show that human-specific AluY insertion events are strongly linked to the evolution of the DNA methylation landscape and gene expression levels, including at key neurological genes in the human brain. Studying paralogous regions within the same sample enables the study of the links between genome and epigenome evolution while controlling for biological and technical variation. We show DNA methylation and chromatin divergence between duplicated regions are linked to the divergence of particular genetic motifs, with Alu elements having played a disproportionate role in the evolution of the epigenome in the human lineage.

  19. Mesenchymal Stem Cell Levels of Human Spinal Tissues.

    Science.gov (United States)

    Harris, Liam; Vangsness, C Thomas

    2017-09-06

    .: Systematic Review. .: The aim of this study was to investigate, quantify, compare and compile the various mesenchymal stem cell tissue sources within human spinal tissues to act as a compendium for clinical and research application. .: Recent years have seen a dramatic increase in academic and clinical understanding of human mesenchymal stem cells (MSCs). Previously limited to cells isolated from bone marrow, the past decade has illicited the characterization and isolation of human MSCs from adipose, bone marrow, synovium, muscle, periosteum, peripheral blood, umbilical cord, placenta and numerous other tissues. As researchers explore practical applications of cells in these tissues, the absolute levels of MSCs in specific spinal tissue will be critical to guide future research. .: The PubMED, MEDLINE, EMBASE and Cochrane databases were searched for articles relating to the harvest, characterization, isolation and quantification of human mesenchymal stem cells from spinal tissues. Selected articles were examined for relevant data, categorized according to type of spinal tissue, and when possible, standardized to facilitate comparisons between sites. .: Human mesenchymal stem cell levels varied widely between spinal tissues. Yields for Intervertebral disc demonstrated roughly 5% of viable cells to be positive for MSC surface markers. Cartilage endplate cells yielded 18,500- 61,875 cells/ 0.8 mm thick sample of cartilage end plate. Ligamentum flavum yielded 250,000- 500,000 cells per gram of tissue. Annulus fibrosus FACS treatment found 29% of cells positive for MSC marker Stro-1. Nucleus pulposus yielded mean tissue samples of 40,584-234,137 MSCs/gram of tissue. .: Numerous tissues within and surrounding the spine represent a consistent and reliable source for the harvest and isolation of human mesenchymal stem cells. Among the tissues of the spine, the annulus fibrosus and ligamentum flavum each offer considerable levels of mesenchymal stem cells, and may

  20. Determinants of C-peptide levels and acute insulin resistance/sensitivity in nondiabetic STEMI role of Killip class

    Directory of Open Access Journals (Sweden)

    Chiara Lazzeri

    2014-03-01

    According to our data, the development of acute insulin resistance in the early phase of STEMI can be viewed as an adaptive mechanism to stress (represented by acute myocardial ischemia, similar to other acute critical conditions, related to the severity of stress (that is to the hemodynamic impairment.

  1. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Human-level concept learning through probabilistic program induction.

    Science.gov (United States)

    Lake, Brenden M; Salakhutdinov, Ruslan; Tenenbaum, Joshua B

    2015-12-11

    People learning new concepts can often generalize successfully from just a single example, yet machine learning algorithms typically require tens or hundreds of examples to perform with similar accuracy. People can also use learned concepts in richer ways than conventional algorithms-for action, imagination, and explanation. We present a computational model that captures these human learning abilities for a large class of simple visual concepts: handwritten characters from the world's alphabets. The model represents concepts as simple programs that best explain observed examples under a Bayesian criterion. On a challenging one-shot classification task, the model achieves human-level performance while outperforming recent deep learning approaches. We also present several "visual Turing tests" probing the model's creative generalization abilities, which in many cases are indistinguishable from human behavior.

  3. Human plasma DNP level after severe brain injury

    Institute of Scientific and Technical Information of China (English)

    GAO Yi-lu; XIN Hui-ning; FENG Yi; FAN Ji-wei

    2006-01-01

    Objective: To determine the relationship between DNP level after human severe brain injury and hyponatremia as well as isorrhea.Methods: The peripheral venous plasma as control was collected from 8 volunteers. The peripheral venous plasma from 14 severe brain injury patients were collected in the 1, 3, 7 days after injury. Radioimmunoassay was used to detect the DNP concentration. Meanwhile, daily plasma and urine electrolytes, osmotic pressure as well as 24 h liquid intake and output volume were detected.Results: The normal adult human plasma DNP level was 62. 46 pg/ml ± 27. 56 pg/ml. In the experimental group, the plasma DNP levels were higher from day 1 today 3 in 8 of the 14 patients than those in the control group (P1 =0.05, P3 =0.03). Negative fluid balance occurred in 8 patients and hyponatremia in 7 patients. The increase of plasma DNP level was significantly correlated with the development of a negative fluid balance (r=-0.69,P<0.01) and hyponatremia (x2 =4.38, P<0.05).Conclusions: The increase of plasma DNP level is accompanied by the enhancement of natriuretic and diuretic responses in severe brain-injured patients, which is associated with the development of a negative fluid balance and hyponatremia after brain injury.

  4. Amyloid β levels in human red blood cells.

    Directory of Open Access Journals (Sweden)

    Takehiro Kiko

    Full Text Available UNLABELLED: Amyloid β-peptide (Aβ is hypothesized to play a key role by oxidatively impairing the capacity of red blood cells (RBCs to deliver oxygen to the brain. These processes are implicated in the pathogenesis of Alzheimer's disease (AD. Although plasma Aβ has been investigated thoroughly, the presence and distribution of Aβ in human RBCs are still unclear. In this study, we quantitated Aβ40 and Aβ42 in human RBCs with ELISA assays, and provided evidence that significant amounts of Aβ could be detected in RBCs and that the RBC Aβ levels increased with aging. The RBC Aβ levels increased with aging. On the other hand, providing an antioxidant supplement (astaxanthin, a polar carotenoid to humans was found to decrease RBC Aβ as well as oxidative stress marker levels. These results suggest that plasma Aβ40 and Aβ42 bind to RBCs (possibly with aging, implying a pathogenic role of RBC Aβ. Moreover, the data indicate that RBC Aβ40 and Aβ42 may constitute biomarkers of AD. As a preventive strategy, therapeutic application of astaxanthin as an Aβ-lowering agent in RBCs could be considered as a possible anti-dementia agent. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN42483402.

  5. Lactoferrin Levels in Human Milk after Preterm and Term Delivery.

    Science.gov (United States)

    Albenzio, Marzia; Santillo, Antonella; Stolfi, Ilaria; Manzoni, Paolo; Iliceto, Alice; Rinaldi, Matteo; Magaldi, Rosario

    2016-09-01

    Background Lactoferrin (LF) is a highly represented, functional glycoprotein in human milk, exerting a wide range of anti-infective, immunomodulatory, and prebiotic actions in the neonate. Limited data are available assessing the concentrations and levels of LF in maternal milk over time during lactation in mothers who delivered infants at different GAs. Our aim with the present study was to determine the levels of LF in human milk from mothers of preterm and term infants and to evaluate the variations at a different time from delivery, in colostrum and mature milk. Methods Mothers of preterm and term infants from the Neonatology Unit in Foggia, Italy, were approached and enrolled in this study. From each mother, milk samples were collected within the first 3 days after birth (group A, 0-72 hours), between the 5th and 7th day after delivery (group B, 120-168 hours), and after the 10th day (group C, > 240 hours). All milk samples were divided into five groups, according to the GA of the infants: 24 to 27.6 weeks of GA (I), 28 to 31.6 weeks of GA (II), 32 to 34.6 weeks of GA (III), 35 to 37.6 weeks of GA (IV), and > 38 weeks of GA (V). Milk samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the content of LF. Results A total of 84 milk samples were collected from 28 mothers. We found that infant's GA, as well as the time of sampling, affected the levels of LF in milk. On one hand, LF showed higher content in human milk from group I (GA: 24-27.6 weeks) compared with the other groups (p milk had a significant decreasing trend over time. Overall, the highest values of LF were detected in preterm infants' maternal milk with a baby birth weight, lower than 1,400 g. Approximately 350 µg/mL was identified as the mean, physiological LF content in human mature milk in our population. Conclusions Levels of LF in human milk vary significantly over time during lactation and according to GA. This variability in the

  6. Outer Surface Protein C Peptide Derived from Borrelia burgdorferi Sensu Stricto as a Target for Serodiagnosis of Early Lyme Disease

    Science.gov (United States)

    Arnaboldi, Paul M.; Seedarnee, Rudra; Sambir, Mariya; Callister, Steven M.; Imparato, Josephine A.

    2013-01-01

    Current serodiagnostic assays for Lyme disease are inadequate at detecting early infection due to poor sensitivity and nonspecificity that arise from the use of whole bacteria or bacterial proteins as assay targets; both targets contain epitopes that are cross-reactive with epitopes found in antigens of other bacterial species. Tests utilizing peptides that contain individual epitopes highly specific for Borrelia burgdorferi as diagnostic targets are an attractive alternative to current assays. Using an overlapping peptide library, we mapped linear epitopes in OspC, a critical virulence factor of B. burgdorferi required for mammalian infection, and confirmed the results by enzyme-linked immunosorbent assay (ELISA). We identified a highly conserved 20-amino-acid peptide epitope, OspC1. Via ELISA, OspC1 detected specific IgM and/or IgG in 60 of 98 serum samples (62.1%) obtained from patients with erythema migrans (early Lyme disease) at the time of their initial presentation. By comparison, the commercially available OspC peptide PepC10 detected antibody in only 48 of 98 serum samples (49.0%). In addition, OspC1 generated fewer false-positive results among negative healthy and diseased (rheumatoid arthritis and positive Rapid Plasma Reagin [RPR+] test result) control populations than did PepC10. Both highly specific and more sensitive than currently available OspC peptides, OspC1 could have value as a component of a multipeptide Lyme disease serological assay with significantly improved capabilities for the diagnosis of early infection. PMID:23365204

  7. Improvement of C peptide zero BMI 24-34 diabetic patients after tailored one anastomosis gastric bypass (BAGUA

    Directory of Open Access Journals (Sweden)

    M. Garcia-Caballero

    2013-01-01

    Full Text Available Background: Although bariatric surgery proved to be a very effective method in the treatment of patients in whose pancreas still produce insulin (type 2 diabetes, the accompanied metabolic syndrome and their diabetes complications, there is no information on the effect of this type of surgery in BMI24-34 patients when pancreas do not produce insulin at all (type 1, LADA and long term evolution type 2 diabetes among others. Patients and methods: We report preliminary data of a serie of 11 patients all with a C-peptide values below 0.0 ng/ml. They were followed for 6 to 60 months (mean 19 months after surgery. We studied the changes in glycemic control, evolution of the metabolic syndrome and diabetes complications after one anastomosis gastric bypass (BAGUA. Results: All values relative to glycemic control were improved HbA1c (from 8.9 ± 0.6 to 6.7 ± 0.2%, FPG (Fasting Plasma Glucose [from 222.36 ± 16.87 to 94 ± 5 (mg/dl] as well as the daily insulin requirement of rapid (from 40.6 ± 12.8 to 0 (U/d and long-lasting insulin (from 41.27 ± 7.3 U/day to 15.2 ± 3.3 U/day. It resolved 100% of the metabolic syndrome diseases as well as severe hypoglycaemia episodes present before surgery and improved some serious complications from diabetes like retinopathy, nephropathy, neuropathy, peripheral vasculopathy and cardiopathy. Conclusions: Tailored one anastomosis gastric bypass in BMI 24-34 C peptide zero diabetic patients eliminated the use of rapid insulin, reduced to only one injection per day long-lasting insulin and improved the glycemic control. After surgery disappear metabolic syndrome and severe hypoglycaemia episodes and improves significantly retinopathy, neuropathy, nephropathy, peripheral vasculopathy and cardiopathy.

  8. NAD kinase levels control the NADPH concentration in human cells.

    Science.gov (United States)

    Pollak, Nadine; Niere, Marc; Ziegler, Mathias

    2007-11-16

    NAD kinases (NADKs) are vital, as they generate the cellular NADP pool. As opposed to three compartment-specific isoforms in plants and yeast, only a single NADK has been identified in mammals whose cytoplasmic localization we established by immunocytochemistry. To understand the physiological roles of the human enzyme, we generated and analyzed cell lines stably deficient in or overexpressing NADK. Short hairpin RNA-mediated down-regulation led to similar (about 70%) decrease of both NADK expression, activity, and the NADPH concentration and was accompanied by increased sensitivity toward H(2)O(2). Overexpression of NADK resulted in a 4-5-fold increase in the NADPH, but not NADP(+), concentration, although the recombinant enzyme phosphorylated preferentially NAD(+). Surprisingly, NADK overexpression and the ensuing increase of the NADPH level only moderately enhanced protection against oxidant treatment. Apparently, to maintain the NADPH level for the regeneration of oxidative defense systems human cells depend primarily on NADP-dependent dehydrogenases (which re-reduce NADP(+)), rather than on a net increase of NADP. The stable shifts of the NADPH level in the generated cell lines were also accompanied by alterations in the expression of peroxiredoxin 5 and Nrf2. Because the basal oxygen radical level in the cell lines was only slightly changed, the redox state of NADP may be a major transmitter of oxidative stress.

  9. Vision Influence on Whole-Body Human Vibration Comfort Levels

    Directory of Open Access Journals (Sweden)

    Maria Lúcia Machado Duarte

    2006-01-01

    Full Text Available The well being of people needs to be a priority in the modern world. In that respect, vibration cannot be one more cause of stress. Besides that, vibration comfort is very important, since high levels may cause health or even tasks' accomplishment problems. Several parameters may influence the levels of vibration a human being supports. Among them, one can mention the influence of gender, age, corporeal mass index (CMI, temperature, humor, anxiety, hearing, posture, vision, etc. The first three parameters mentioned were already investigated in previous studies undertaken by GRAVI (Group of Acoustics and Vibration researchers. In this paper, the influence of vision is evaluated. The main objective with this series of tests performed is to try to quantify in a future the influence of each parameter in a global vibration comfort level. Conclusions are presented for the parameter investigated.

  10. Diurnal variation of blood ketone bodies in insulin-dependent diabetes mellitus and noninsulin-dependent diabetes mellitus patients: the relationship to serum C-peptide immunoreactivity and free insulin.

    Science.gov (United States)

    Ubukata, E

    1990-01-01

    We examined whether the rise in ketone body concentration around midnight and in the early morning was due to the lack of free insulin (IRI) or excess of insulin counterregulatory hormones such as human growth hormone (hGH), cortisol and glucagon in noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) patients and whether the monitoring of blood ketone body concentration was clinically useful as an index of metabolic control for deciding to increase or decrease the insulin dose in the treatment of diabetes mellitus. Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects. Mirror image diurnal changes were found between serum concentrations of 3-OHBA and serum C-peptide or free IRI in normal subjects and NIDDM patients treated with diet alone or sulfonylurea during the 24-hour daily profiles. However, there were no correlations between 3-OHBA and free IRI in the NIDDM patients treated with insulin and IDDM patients who had a much larger increase in the mean concentration of serum 3-OHBA at 6 a.m. caused by a low concentration of free IRI. Counterregulatory hormones were not increased in IDDM patients compared to normal subjects in the early morning. Cortisol/free IRI and hGH/free IRI molar ratios were significantly increased in NIDDM and IDDM patients compared to normal subjects in the early morning, but glucagon/free IRI molar ratio was not changed between IDDM and normal subjects. In conclusion, the early morning rising of ketone body concentration in insulin-treated diabetic patients, particularly IDDM patients, is due to the absolute lack of free IRI and/or the relative lack of free IRI to the levels of hGH or cortisol, and the monitoring of 3-OHBA is clinically useful as a more sensitive index of metabolic

  11. Multi-level human evolution: ecological patterns in hominin phylogeny.

    Science.gov (United States)

    Parravicini, Andrea; Pievani, Telmo

    2016-06-20

    Evolution is a process that occurs at many different levels, from genes to ecosystems. Genetic variations and ecological pressures are hence two sides of the same coin; but due both to fragmentary evidence and to the influence of a gene-centered and gradualistic approach to evolutionary phenomena, the field of paleoanthropology has been slow to take the role of macro-evolutionary patterns (i.e. ecological and biogeographical at large scale) seriously. However, several very recent findings in paleoanthropology stress both climate instability and ecological disturbance as key factors affecting the highly branching hominin phylogeny, from the earliest hominins to the appearance of cognitively modern humans. Allopatric speciation due to geographic displacement, turnover-pulses of species, adaptive radiation, mosaic evolution of traits in several coeval species, bursts of behavioral innovation, serial dispersals out of Africa, are just some of the macro-evolutionary patterns emerging from the field. The multilevel approach to evolution proposed by paleontologist Niles Eldredge is adopted here as interpretative tool, and has yielded a larger picture of human evolution that integrates different levels of evolutionary change, from local adaptations in limited ecological niches to dispersal phenotypes able to colonize an unprecedented range of ecosystems. Changes in global climate and Earth's surface most greatly affected human evolution. Precisely because it is cognitively hard for us to appreciate the long-term common destiny we share with the whole biosphere, it is particularly valuable to highlight the accumulating evidence that human evolution has been deeply affected by global ecological changes that transformed our African continent of origin.

  12. Next Level of Data Fusion for Human Face Recognition

    CERN Document Server

    Bhowmik, Mrinal Kanti; Bhattacharjee, Debotosh; Basu, Dipak Kumar; Nasipuri, Mita

    2011-01-01

    This paper demonstrates two different fusion techniques at two different levels of a human face recognition process. The first one is called data fusion at lower level and the second one is the decision fusion towards the end of the recognition process. At first a data fusion is applied on visual and corresponding thermal images to generate fused image. Data fusion is implemented in the wavelet domain after decomposing the images through Daubechies wavelet coefficients (db2). During the data fusion maximum of approximate and other three details coefficients are merged together. After that Principle Component Analysis (PCA) is applied over the fused coefficients and finally two different artificial neural networks namely Multilayer Perceptron(MLP) and Radial Basis Function(RBF) networks have been used separately to classify the images. After that, for decision fusion based decisions from both the classifiers are combined together using Bayesian formulation. For experiments, IRIS thermal/visible Face Database h...

  13. Human placental lactogen levels during and after labor.

    Science.gov (United States)

    Ylikorkala, O; Kauppila, A; Pennanen, S

    1975-08-01

    In order to estimate the human placental lactogen (HPL) level and its value as an indicator of fetoplacental function during labor, we determined HPL levels (N equals 225) before, during, and after labor in normal (N equals 16) and preeclamptic (N equals 14) subjects or in patients with benign intrahepatic cholestasis of pregnancy (N equals 5). During labor, greater decreases in this value were found in preeclamptic than in normal subjects and similarly in mothers with fetoplacental dysfunction than with normal fetoplacental function. The rupture of the membranes had no effect on the level of HPL, which was not related to parity, oxytocin infusion, time interval from rupture of the membranes to delivery, nor to relative placental weight. The half-life of HPL varied in the range of 20-23 minutes immediately after delivery and in the range of 30-39 minutes some time later. During labor, greater decreases in HPL level in cases of preeclampsia or fetoplacental dysfunction may be caused by relative uteroplacental ischemia during uterine contractions, but from this finding it is hard to expect any advantage of HPL as a monitor of fetoplacental function during labor.

  14. Human Development Index and Efficiency level of Social Security Hospitals

    Directory of Open Access Journals (Sweden)

    H. Sepehrdost

    2012-04-01

    Full Text Available Introduction & Objective: Hospitals as one of the main institutions providing health care services play an important role in the health system and allocate a high percentage of health sector's budget to them. This study aimed to answer whether social security hospitals efficiency levels are the same for all provinces in Iran? And whether any relationship exists between the human development indexes (HDI of the provinces and technical efficiency levels of the hospitals?Materials & Methods: Data envelopment analysis model has been used to measure technical efficiency of 65 social security hospitals, including small hospitals (working with lower than one hundred active beds and large hospitals (working with over one hundred active beds during the years 2007 to 2009. Further, the relationship between human development index and technical efficiency of hospitals in the provinces has been analyzed.Results: Results show that the average technical efficiency of small and large hospitals working in low and medium HDI provinces (0.912 and 0.937 are more than the average technical efficiency of hospitals in higher HDI provinces (0.870 and 0.887.Conclusion: It is recommended that social security organization concentrated distribute its hospital services in provinces with lower HDI and higher density of population living under the coverage of organization’s insurance. This will eventually puts its positive effects on per capita income of people, as well as more equitable distribution of income. (Sci J Hamadan Univ Med Sci 2012;19(1:32-38

  15. Quantifying human response capabilities towards tsunami threats at community level

    Science.gov (United States)

    Post, J.; Mück, M.; Zosseder, K.; Wegscheider, S.; Taubenböck, H.; Strunz, G.; Muhari, A.; Anwar, H. Z.; Birkmann, J.; Gebert, N.

    2009-04-01

    Decision makers at the community level need detailed information on tsunami risks in their area. Knowledge on potential hazard impact, exposed elements such as people, critical facilities and lifelines, people's coping capacity and recovery potential are crucial to plan precautionary measures for adaptation and to mitigate potential impacts of tsunamis on society and the environment. A crucial point within a people-centred tsunami risk assessment is to quantify the human response capabilities towards tsunami threats. Based on this quantification and spatial representation in maps tsunami affected and safe areas, difficult-to-evacuate areas, evacuation target points and evacuation routes can be assigned and used as an important contribution to e.g. community level evacuation planning. Major component in the quantification of human response capabilities towards tsunami impacts is the factor time. The human response capabilities depend on the estimated time of arrival (ETA) of a tsunami, the time until technical or natural warning signs (ToNW) can be received, the reaction time (RT) of the population (human understanding of a tsunami warning and the decision to take appropriate action), the evacuation time (ET, time people need to reach a safe area) and the actual available response time (RsT = ETA - ToNW - RT). If RsT is larger than ET, people in the respective areas are able to reach a safe area and rescue themselves. Critical areas possess RsT values equal or even smaller ET and hence people whin these areas will be directly affected by a tsunami. Quantifying the factor time is challenging and an attempt to this is presented here. The ETA can be derived by analyzing pre-computed tsunami scenarios for a respective area. For ToNW we assume that the early warning center is able to fulfil the Indonesian presidential decree to issue a warning within 5 minutes. RT is difficult as here human intrinsic factors as educational level, believe, tsunami knowledge and experience

  16. Beyond HLA-A*0201: new HLA-transgenic nonobese diabetic mouse models of type 1 diabetes identify the insulin C-peptide as a rich source of CD8+ T cell epitopes.

    Science.gov (United States)

    Antal, Zoltan; Baker, Jason C; Smith, Carla; Jarchum, Irene; Babad, Jeffrey; Mukherjee, Gayatri; Yang, Yang; Sidney, John; Sette, Alessandro; Santamaria, Pere; DiLorenzo, Teresa P

    2012-06-01

    Type 1 diabetes is an autoimmune disease characterized by T cell responses to β cell Ags, including insulin. Investigations employing the NOD mouse model of the disease have revealed an essential role for β cell-specific CD8(+) T cells in the pathogenic process. As CD8(+) T cells specific for β cell Ags are also present in patients, these reactivities have the potential to serve as therapeutic targets or markers for autoimmune activity. NOD mice transgenic for human class I MHC molecules have previously been employed to identify T cell epitopes having important relevance to the human disease. However, most studies have focused exclusively on HLA-A*0201. To broaden the reach of epitope-based monitoring and therapeutic strategies, we have looked beyond this allele and developed NOD mice expressing human β(2)-microglobulin and HLA-A*1101 or HLA-B*0702, which are representative members of the A3 and B7 HLA supertypes, respectively. We have used islet-infiltrating T cells spontaneously arising in these strains to identify β cell peptides recognized in the context of the transgenic HLA molecules. This work has identified the insulin C-peptide as an abundant source of CD8(+) T cell epitopes. Responses to these epitopes should be of considerable utility for immune monitoring, as they cannot reflect an immune reaction to exogenously administered insulin, which lacks the C-peptide. Because the peptides bound by one supertype member were found to bind certain other members also, the epitopes identified in this study have the potential to result in therapeutic and monitoring tools applicable to large numbers of patients and at-risk individuals.

  17. Effect of Technological Treatments on Human-Like Leptin Level in Bovine Milk for Human Consumption

    Directory of Open Access Journals (Sweden)

    Damiano Magistrelli

    2014-07-01

    Full Text Available In this experiment, raw milk and commercially available full-cream UHT milk, semi-skimmed UHT milk, skimmed UHT milk, full-cream pasteurized milk, semi-skimmed pasteurized milk and infant formulas for babies between 6 and 12 months of age were analyzed by RIA, with a method using an antibody directed against human leptin and human leptin as reference standard. Raw milk and full-cream UHT milk did not differ for human-like leptin. Leptin content of full-cream pasteurized milk was not different to that of full-cream UHT milk, but it was 14% lower (p < 0.05 than that observed in raw milk. Human-like leptin level of semi-skimmed UHT milk was not different to that of semi-skimmed pasteurized milk, but it was 30% lower (p < 0.0001 than those of full-cream UHT and full-cream pasteurized milks. In skimmed UHT milk, leptin was 40% lower (p < 0.0001 than in full-cream UHT milk. Leptin was correlated (p < 0.001 with lipid content. Leptin level of infant formulas was not different to that of skimmed milks. Results suggest that the heat treatment (pasteurization or UHT is not a modifier of human-like leptin content of edible commercial bovine milks, whereas the skimming process significantly reduces milk leptin level.

  18. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices

    NARCIS (Netherlands)

    S. Jainandunsing (Sjaam); J.L.D. Wattimena (Josias); T. Rietveld (Trinet); J.N.I. van Miert (Joram); E.J.G. Sijbrands (Eric); F.W.M. de Rooij (Felix)

    2016-01-01

    textabstractThe purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January

  19. Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans

    DEFF Research Database (Denmark)

    Meier, J J; Gethmann, A; Götze, O;

    2006-01-01

    . Venous blood was drawn frequently for measurement of glucose, insulin, C-peptide, glucagon, GLP-1, triglycerides and NEFA. RESULTS: GLP-1 administration lowered fasting and postprandial glycaemia (p... administration, insulin secretory responses were higher in the fasting state but lower after meal ingestion. After meal ingestion, triglyceride plasma levels increased by 0.33+/-0.14 mmol/l in the placebo experiments (ptriglyceride levels was completely...... abolished by GLP-1 (change in triglycerides, -0.023+/-0.045 mmol/l; p

  20. Elevated C-Peptides, Abdominal Obesity, and Abnormal Adipokine Profile are Associated With Higher Gleason Scores in Prostate Cancer.

    Science.gov (United States)

    Di Sebastiano, Katie M; Pinthus, Jehonathan H; Duivenvoorden, Wilhelmina C M; Patterson, Laurel; Dubin, Joel A; Mourtzakis, Marina

    2017-02-01

    Prostate cancer development is associated with numerous lifestyle factors (i.e., physical activity, nutrition intake) and metabolic perturbations. These factors have been studied independently; here, we used an integrative approach to characterize these lifestyle and metabolic parameters in men undergoing diagnostic prostate biopsies. We prospectively evaluated 51 consecutive men for body composition, metabolic factors including glucose- and lipid-related measures, as well as lifestyle factors prior to prostate biopsy. Evaluations were performed in a blinded manner and were subsequently related to biopsy outcomes for: (i) presence or absence of cancer; and (ii) where cancer was present, Gleason score. Serum C-peptide concentrations were significantly greater in participants with Gleason scores ≥4 + 3 (2.8 ± 1.1 ng/ml) compared to those with Gleason 3 + 3 (1.4 ± 0.6 ng/ml) or Gleason 3 + 4 (1.3 ± 0.8 ng/ml, P = 0.002), suggesting greater insulin secretion despite lack of differences in fasting glucose concentrations. Central adiposity, measured by waist circumference, was significantly greater in participants with Gleason ≥4 + 3 (110.1 ± 7.4 cm) compared to those with Gleason 3 + 4 (102.0 ± 9.5 cm, P = 0.028). Men with Gleason ≥4 + 3 also had significantly greater leptin concentrations than those with lower Gleason scores (Gleason ≥4 + 3: 15.6 ± 3.3 ng/ml vs. Gleason 3 + 4: 8.1 ± 8.1 ng/ml, P obesity-related metabolic perturbations (C-peptide, central adiposity, leptin, and leptin:adiponectin ratios) which may associate with more aggressive prostate cancer histology. Prostate 77:211-221, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    Science.gov (United States)

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P oral (Cau r = -0.61, P indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C-peptide and glucose in urine collected during OGTT might be used as non-invasive measures for endogenous insulin secretion and glucose tolerance state.

  2. The effect of smoking on serum human placental lactogen levels.

    Science.gov (United States)

    Spellacy, W N; Buhi, W C; Birk, S A

    1977-02-01

    Serial serum samples (162) were drawn weekly from normal pregnant women (53) during the last month of gestation and measurements were made of the human placental lactogen (HPL) content. The women were interviewed as to their smoking habits and divided into nonsmokers (32) and smokers of from one to two packages of cigarettes per day (21). The infant birth weight and placental weights were not significantly different. The HPL levels were elevated in the women who smoked and the differences were significant at the thirty-sixth and thirty-eighth weeks. The importance of this in interpreting HPL as a placental function test and in terms of the biology of placental function and the control of protein hormone synthesis is emphasized.

  3. Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.

    Science.gov (United States)

    Matveyenko, Aleksey V; Georgia, Senta; Bhushan, Anil; Butler, Peter C

    2010-11-01

    Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.

  4. Vitamin K plasma levels determination in human health.

    Science.gov (United States)

    Fusaro, Maria; Gallieni, Maurizio; Rizzo, Maria Antonietta; Stucchi, Andrea; Delanaye, Pierre; Cavalier, Etienne; Moysés, Rosa M A; Jorgetti, Vanda; Iervasi, Giorgio; Giannini, Sandro; Fabris, Fabrizio; Aghi, Andrea; Sella, Stefania; Galli, Francesco; Viola, Valentina; Plebani, Mario

    2017-05-01

    Vitamin K (phylloquinone or vitamin K1 and menaquinones or vitamin K2) plays an important role as a cofactor in the synthesis of hepatic blood coagulation proteins, but recently has also aroused an increasing interest for its action in extra-hepatic tissues, in particular in the regulation of bone and vascular metabolism. The accurate measurement of vitamin K status in humans is still a critical issue. Along with indirect assays, such as the undercarboxylated fractions of vitamin K-dependent proteins [prothrombin, osteocalcin (OC), and matrix gla protein], the direct analysis of blood levels of phylloquinone and menaquinones forms might be considered a more informative and direct method for assessing vitamin K status. Different methods for direct quantification of vitamin K serum levels are available. High-performance liquid chromatography (HPLC) methods coupled with post-column reduction procedures and fluorimetric or electrochemical detection are commonly used for food and blood analysis of phylloquinone, but they show some limitations when applied to the analysis of serum menaquinones because of interferences from triglycerides. Recent advancements include liquid chromatography tandem mass spectrometry (LCMS/MS) detection, which assures higher specificity. The optimization and standardization of these methods requires specialized laboratories. The variability of results observed in the available studies suggests the need for further investigations to obtain more accurate analytical results.

  5. Low level CO2 effects on pulmonary function in humans

    Science.gov (United States)

    Sexton, J.; Mueller, K.; Elliott, A.; Gerzer, D.; Strohl, K. P.; West, J. B. (Principal Investigator)

    1998-01-01

    The purpose of the study was to determine whether chamber exposure to low levels of CO2 results in functional alterations in gas mixing and closing volume in humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2. Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for carbon monoxide (DLCO) by two methods, and cardiac output were measured in triplicate. Values were obtained over two non-consecutive days during the training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to each CO2 level. Measurements were made during the same time of day. There was one day of testing after exposure, while still in the chamber but off carbon dioxide. The order of testing, up until measurements of DLCO and cardiac output, were randomized to avoid presentation effects. The consistent findings were a reduction in diffusing capacity for carbon monoxide and a fall in cardiac output, occurring to a similar degree with both exposures. For the group as a whole, there was no indication of major effects on spirometry, lung volumes, gas mixing or dead space. We conclude that small changes may occur in the function of distal gas exchanging units; however, these effects were not associated with any adverse health effects. The likelihood of pathophysiologic changes in lung function or structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore, low.

  6. 血清C肽与2型糖尿病下肢动脉硬化的关系%Relationship between C-peptide and artherosclerosis in lower extremity in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    崔琦; 杨春杰; 曹贵文; 周虹

    2015-01-01

    Objective To investigate the relationship between C-peptide and artherosclerosis in lower ex-tremity in patients with type 2 diabetes. Methods Two hundred and fourteen type 2 diabetic patients were included in this retrospective study. They were divided into two groups:type 2 diabetes with artherosclerosis in lower extremi-ty in 123 cases and type 2 diabetes without artherosclerosis in lower extremity in 91 cases. Their medical history and the laboratory data were collected such as fasting serum C-peptide levels and postprandial serum C-peptide levels of 1 hour, 2 hours and 3 hours, glycated hemoglobin (HbA1c) and so on. Results Compared with artherosclerosis group in lower extremity, the age, duration of diabetes, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), glycated hemoglobin and smoking rate were significantly higher in type 2 diabetes without artherosclero-sis in lower extremity (P 0.05). Logistic regression analysis showed that fasting and postprandial (1 hour, 2 hours and 3 hours)serum C-pep-tide levels were all negatively related to artherosclerosis in lower extremity (OR 0.524,P = 0; OR 0.440, P = 0;OR 0.688, P=0;OR 0.795, P=0). Conclusions Serum C-peptide level may be an independent associated fac-tor with artherosclerosis in lower extremity in type 2 diabetes.%目的:探讨血清C肽与2型糖尿病下肢动脉硬化的关系. 方法:选取214例2型糖尿病患者,分为非下肢动脉硬化组(91 例)和下肢动脉硬化组(123 例). 检测患者空腹C肽(CP0),馒头餐后1 h(CP1)、2 h(CP2)、3 h(CP3)C肽,糖化血红蛋白(HbA1c)等指标. 结果:下肢动脉硬化组的年龄、糖尿病病程、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、HbA1c、吸烟率高于非动脉硬化组(P 0.05). 经Logistic 回归分析,空腹与餐后(1、2、3 h)C 肽与下肢动脉硬化呈负相关,经其他相关因素校正后仍显著相关(OR 0.524, P = 0; OR 0.440, P = 0;OR 0.688,P = 0; OR 0.795, P = 0). 结论: 血清C肽为2

  7. Human-level control through deep reinforcement learning

    Science.gov (United States)

    Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A.; Veness, Joel; Bellemare, Marc G.; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K.; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

    2015-02-01

    The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

  8. Human-level control through deep reinforcement learning.

    Science.gov (United States)

    Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A; Veness, Joel; Bellemare, Marc G; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

    2015-02-26

    The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

  9. Groundwater: Quality Levels and Human Exposure, SW Nigeria

    Directory of Open Access Journals (Sweden)

    Olusola Adeyemi

    2017-04-01

    Full Text Available Groundwater serves as a source of freshwater for agricultural, industrial and domestic purposes and it accounts for about 42%, 27% and 36% respectively. As it remains the only source of all-year-round supply of freshwater globally, it is of vital importance as regards water security, human survival and sustainable agriculture. The main goal of this study is to identify the main cause-effect relationship between human activities and the state of groundwater quality using a communication tool (the DPSIR Model; Drivers, Pressures, State, Impact and Response. A total of twenty-one samples were collected from ten peri-urban communities scattered across three conterminous Local Government Areas in Southwestern Nigeria. Each of the groundwater samples was tested for twelve parameters - total dissolved solids, pH, bicarbonate, chloride, lead, electrical conductivity, dissolved oxygen, nitrate, sulphate, magnesium and total suspended solids. The study revealed that the concentrations of DO and Pb were above threshold limits, while pH and N were just below the threshold and others elements were within acceptable limits based on Guidelines for Drinking Water Quality and Nigeria Standard for Drinking Water Quality. The study revealed that groundwater quality levels from the sampled wells are under pressure leading to reduction in the amount of freshwater availability. This is a first-order setback in achieving access to freshwater as a sustainable development goal across Less Developed Communities (LDCs globally. To combat this threat, there is the need for an integrated approach in response towards groundwater conservation and sustainability by all stakeholders.

  10. Somatostatin signaling system as an ancestral mechanism: Myoregulatory activity of an Allatostatin-C peptide in Hydra.

    Science.gov (United States)

    Alzugaray, María Eugenia; Hernández-Martínez, Salvador; Ronderos, Jorge Rafael

    2016-08-01

    The coordination of physiological processes requires precise communication between cells. Cellular interactions allow cells to be functionally related, facilitating the maintaining of homeostasis. Neuropeptides functioning as intercellular signals are widely distributed in Metazoa. It is assumed that neuropeptides were the first intercellular transmitters, appearing early during the evolution. In Cnidarians, neuropeptides are mainly involved in neurotransmission, acting directly or indirectly on epithelial muscle cells, and thereby controlling coordinated movements. Allatostatins are a group of chemically unrelated neuropeptides that were originally characterized based on their ability to inhibit juvenil hormone synthesis in insects. Allatostatin-C has pleiotropic functions, acting as myoregulator in several insects. In these studies, we analyzed the myoregulatory effect of Aedes aegypti Allatostatin-C in Hydra sp., a member of the phylum Cnidaria. Allatostatin-C peptide conjugated with Qdots revealed specifically distributed cell populations that respond to the peptide in different regions of hydroids. In vivo physiological assays using Allatostatin-C showed that the peptide induced changes in shape and length in tentacles, peduncle and gastrovascular cavity. The observed changes were dose and time dependent suggesting the physiological nature of the response. Furthermore, at highest doses, Allatostatin-C induced peristaltic movements of the gastrovascular cavity resembling those that occur during feeding. In silico search of putative Allatostatin-C receptors in Cnidaria showed that genomes predict the existence of proteins of the somatostatin/Allatostatin-C receptors family. Altogether, these results suggest that Allatostatin-C has myoregulatory activity in Hydra sp, playing a role in the control of coordinated movements during feeding, indicating that Allatostatin-C/Somatostatin based signaling might be an ancestral mechanism.

  11. Study of the Levels of Human-Human and Human-Animal Empathy in Veterinary Medical Students from Chile.

    Science.gov (United States)

    Calderón-Amor, Javiera; Luna-Fernández, Daniela; Tadich, Tamara

    Social relationships are based on our ability to put ourselves in the place of others, and from there to react appropriately and logically. This empathic ability can be extended to other species, based on the human ability to develop techniques to understand and communicate with animals. In education, the benefits of training professionals with ethical and empathic tools are known. Gender, diet, past experiences, and other factors can modify a person's levels of empathy toward humans and animals, and a relationship exists between both types of empathy. The aims of this study were to investigate some determinants of the level of empathy and to gain insight into the possible correlation between human-animal and human-human empathy. For this, the Animal Empathy Scale and the Interpersonal Reactivity Index by Davis were applied through an electronic survey system to freshmen and final-year students (n=452) from five schools of veterinary medicine in Chile. The correlation between the empathy scores of both instruments and their association with individual factors were studied using Spearman's correlation, the Wilcoxon signed-rank test, and the Kruskal-Wallis test. The results suggest that both instruments correlate significantly, and that gender, year of study, diet, and area of interest have a significant association with the score for empathy toward animals. This research shows that individual characteristics and changes that occur during veterinary training can affect students' attitudes toward animals.

  12. Skim Milk, Whey, and Casein Increase Body Weight and Whey and Casein Increase the Plasma C-Peptide Concentration in Overweight Adolescents12

    DEFF Research Database (Denmark)

    Arnberg, Karina; Mølgaard, Christian; Michaelsen, Kim Fleischer

    2012-01-01

    insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12–15 y with a BMI of 25.4 ± 2.3 kg/m2 (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein...... and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P ... that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated....

  13. Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3

    Energy Technology Data Exchange (ETDEWEB)

    Springer, Timothy A.; Zhu, Jianghai; Xiao, Tsan (Harvard-Med)

    2009-01-12

    Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin {alpha}{sub IIb}{beta}{sub 3} on platelets, resulting in platelet aggregation. {alpha}{sub v}{beta}{sub 3} binding fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's {alpha} subunit. {alpha}{sub IIb}{beta}{sub 3} also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the {gamma} subunit ({gamma}C peptide). These distinct modes of fibrinogen binding enable {alpha}{sub IIb}{beta}{sub 3} and {alpha}{sub v}{beta}{sub 3} to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin {alpha}{sub IIb}{beta}{sub 3}-{gamma}C peptide interface, and, for comparison, integrin {alpha}{sub IIb}{beta}{sub 3} bound to a lamprey {gamma}C primordial RGD motif. Compared with RGD, the GAKQAGDV motif in {gamma}C adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg{sup 2+} ion binds the {gamma}C Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca{sup 2+} ion binds the {gamma}C C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered {gamma}C peptide enhances our understanding of the involvement of {gamma}C peptide and integrin {alpha}{sub IIb}{beta}{sub 3} in hemostasis and thrombosis.

  14. Short reaction of C-peptide, glucagon-like peptide-1, ghrelin and endomorphin-1 for different style diet in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi; WANG Xin; ZHANG Mei-fang; LI Yan-xiang; LI Ying; GU Ting; XIA Fang-zhen; YU Jiao; LU Ying-li

    2011-01-01

    Background Food composition and style is changing dramatically now,which causes inappropriate secretion of hormones from brain,gastrointestinal and endo-pancreas,may be related to unbalance of glucose in blood.The aim of this study was to explore the fast response of C-peptide,glucagon-like peptide-1 (GLP-1),ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus.Methods The study enrolled 57 patients with type 2 diabetes (20 men and 37 women,mean age (67.05±8.26) years).Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect.C-peptide,GLP-1,ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet.Results The delta (2h-0h) of C- peptide in meal A was significantly lower than that in meal B (P=0.0004).C-peptide,GLP-1,ghrelin and EM-1 were obviously higher before meal B than those before meal A (P <0.0001,<0.0001,=0.001,=0.0004 respectively).Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P=-0.0005,0.0079 respectively).Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (rA0h=0.7836,rB0h=0.9368,rAsh=0.7615,rB2h=0.9409,rA(2h_0h)=0.7531,rB(2h-0h)=0.9980,respectively,P <0.0001).Conclusion Western style meal (high fat and protein food) could make more response of C-peptide than eastern style meal,and could stimulate more gut hormones (GLP-1,ghrelin) and brain peptide (EM-1) at the first phase of digestion.

  15. Fructose ingestion acutely stimulates circulating FGF21 levels in humans

    OpenAIRE

    Dushay, Jody R.; Toschi, Elena; Mitten, Emilie K.; Fisher, ffolliott M.; Herman, Mark A.; Maratos-Flier, Eleftheria

    2014-01-01

    Objective Fibroblast growth factor 21 (FGF21) is a hormone with pleiotropic metabolic activities which, in rodents, is robustly regulated by fasting and ketogenic diets. In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no intervention or dietary challenge has been shown to acutely stimulate circulating FGF21 in either humans or animals. Recent animal data suggest that the transcription factor Carbohydrate Responsive-Element...

  16. Human insulin production from a novel mini-proinsulin which has high receptor-binding activity.

    Science.gov (United States)

    Chang, S G; Kim, D Y; Choi, K D; Shin, J M; Shin, H C

    1998-02-01

    To increase the folding efficiency of the insulin precursor and the production yield of insulin, we have designed a mini-proinsulin (M2PI) having the central C-peptide region replaced with a sequence forming a reverse turn. The mini-proinsulin was fused at the N-terminus to a 21-residue fusion partner containing a His10 tag for affinity purification. The gene for the fusion protein was inserted downstream of the T7 promoter of the expression plasmid pET-3a, and the fusion proteins were produced as inclusion bodies in the Escherichia coli cytoplasm at levels up to 25% of the total cell protein. The protein was sulphonated, cleaved by CNBr and the M2PI mini-proinsulin was purified using ion-exchange chromatography. The refolding yield of M2PI was 20-40% better than that of proinsulin studied at the same molar concentrations, indicating that the short turn-forming sequence is more effective in the refolding process than the much longer C-peptide. Native human insulin was successfully generated by subsequent enzymic conversion of mini-proinsulin. The mini-proinsulin exhibited high receptor-binding activity, about 50% as potent as insulin, suggesting that this single-chained mini-proinsulin may provide a foundation in understanding the receptor-bound structure of insulin as well as the role of C-peptide in the folding and activity of proinsulin.

  17. Validation of methods for measurement of insulin secretion in humans in vivo

    DEFF Research Database (Denmark)

    Kjems, L L; Christiansen, E; Vølund, A

    2000-01-01

    ). These results indicate that both approaches provide accurate assessment of prehepatic ISRs in type 2 diabetic patients and control subjects. A simplified version of the deconvolution method based on standard kinetic parameters for C-peptide (Van Cauter et al.) was compared with the 2-day deconvolution method......, and a close agreement was found for the results of an oral glucose tolerance test. We also studied whether C-peptide kinetics are influenced by somatostatin infusion. The decay curves after bolus injection of exogenous biosynthetic human C-peptide, the kinetic parameters, and the metabolic clearance rate were...... similar whether measured during constant peripheral somatostatin infusion or without somatostatin infusion. Assessment of C-peptide kinetics can be performed without infusion of somatostatin, because the endogenous insulin concentration remains constant. Assessment of C-peptide kinetics with and without...

  18. Human identification & forensic analyses of degraded or low level DNA

    NARCIS (Netherlands)

    Westen, Antoinette-Andrea

    2013-01-01

    DNA-based human identification is employed in varying situations, such as disaster victim identification, relationship testing and forensic analyses. When DNA is of low quality and/or quantity, standard methods for DNA profiling may not suffice. The research described in this thesis is aimed at the

  19. Polymorphic GGC repeat differentially regulates human reelin gene expression levels.

    Science.gov (United States)

    Persico, A M; Levitt, P; Pimenta, A F

    2006-10-01

    The human gene encoding Reelin (RELN), a pivotal protein in neurodevelopment, includes a polymorphic GGC repeat in its 5' untranslated region (UTR). CHO cells transfected with constructs encompassing the RELN 5'UTR with 4-to-13 GGC repeats upstream of the luciferase reporter gene show declining luciferase activity with increasing GGC repeat number (P autism.

  20. Human identification & forensic analyses of degraded or low level DNA

    NARCIS (Netherlands)

    Westen, Antoinette-Andrea

    2013-01-01

    DNA-based human identification is employed in varying situations, such as disaster victim identification, relationship testing and forensic analyses. When DNA is of low quality and/or quantity, standard methods for DNA profiling may not suffice. The research described in this thesis is aimed at the

  1. Levels of organochlorine pesticides in Brazilian human milk

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, T. [INCQS/FIOCRUZ, RJ (Brazil); Braga, A.M.C.B.; Rosa, J.M. [CESTEH/ENSP/FIOCRUZ, RJ (Brazil); Kypke, K.; Malisch, R. [State Inst. for Chemical and Veterinary Analysis of Food, Freiburg (Germany)

    2004-09-15

    Breastfeeding has been intensively encouraged, especially in developing countries, due to its beneficial properties, i.e., increase infant immune factors and resistance to chronic diseases such as asthma, diabetes or allergies. In addition, human exposure to environmental pollution has led the scientific community to study the pathways of these contaminants and the possible risks they pose to human health. Exposure to organochlorine pesticides (OCs), in special, has been the subject of great interest during recent years given their potential toxicity, resistance to degradation and bioaccumulation through the food chain. The major source of OC has been agriculture and public health campaigns to vector control. General population exposure occur mainly through the diet and human milk can be an indicator of exposure since OCs are lipophilic xenobiotics that accumulate in adipose tissue and breastfeeding is the main pathway of elimination through the fatty fraction of milk. In this study pooled samples of mothers living in the capitals of two different states of Brazil were evaluated in order to assess the trends of human exposure to persistent pollutants.

  2. Perinatal Oxidative Stress May Affect Fetal Ghrelin Levels in Humans

    OpenAIRE

    Zhong-Cheng Luo; Jean-François Bilodeau; Anne Monique Nuyt; Fraser, William D; Pierre Julien; Francois Audibert; Lin Xiao; Carole Garofalo; Emile Levy

    2015-01-01

    In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), p...

  3. Adopting level set theory based algorithms to segment human ear

    OpenAIRE

    2013-01-01

    Human identification has always been a topic that interested researchers around the world. Biometric methods are found to be more effective and much easier for the users than the traditional identification methods like keys, smart cards and passwords. Unlike with the traditional methods, with biometric methods the data acquisition is most of the times passive, which means the users do not take active part in data acquisition. Data acquisition can be performed using cameras, scanners or sensor...

  4. Human more complex than mouse at cellular level.

    Directory of Open Access Journals (Sweden)

    Alexander E Vinogradov

    Full Text Available The family of transcription factors with the C2H2 zinc finger domain is expanding in the evolution of vertebrates, reaching its highest numbers in the mammals. The question arises: whether an increased amount of these transcription factors is related to embryogenesis, nervous system, pathology or more of them are expressed in individual cells? Among mammals, the primates have a more complex anatomical structure than the rodents (e.g., brain. In this work, I show that a greater number of C2H2-ZF genes are expressed in the human cells than in the mouse cells. The effect is especially pronounced for C2H2-ZF genes accompanied with the KRAB domain. The relative difference between the numbers of C2H2-ZF(-KRAB genes in the human and mouse cellular transcriptomes even exceeds their difference in the genomes (i.e. a greater subset of existing in the genome genes is expressed in the human cellular transcriptomes compared to the mouse transcriptomes. The evolutionary turnover of C2H2-ZF(-KRAB genes acts in the direction of the revealed phenomenon, i.e. gene duplication and loss enhances the difference in the relative number of C2H2-ZF(-KRAB genes between human and mouse cellular transcriptomes. A higher amount of these genes is expressed in the brain and embryonic cells (compared with other tissues, whereas a lower amount--in the cancer cells. It is specifically the C2H2-ZF transcription factors whose repertoire is poorer in the cancer and richer in the brain (other transcription factors taken together do not show this trend. These facts suggest that increase of anatomical complexity is accompanied by a more complex intracellular regulation involving these transcription factors. Malignization is associated with simplification of this regulation. These results agree with the known fact that human cells are more resistant to oncogenic transformation than mouse cells. The list of C2H2-ZF genes whose suppression might be involved in malignization is provided.

  5. Skim milk, whey, and casein increase body weight and whey and casein increase the plasma C-peptide concentration in overweight adolescents.

    Science.gov (United States)

    Arnberg, Karina; Mølgaard, Christian; Michaelsen, Kim Fleischer; Jensen, Signe Marie; Trolle, Ellen; Larnkjær, Anni

    2012-12-01

    In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.

  6. Serum C peptide and glycosylated hemoglobin the significance of combined detection of diabetes diagnosis%血清C肽与糖化血红蛋白联合检测对糖尿病诊断的意义

    Institute of Scientific and Technical Information of China (English)

    闫东; 王霞

    2015-01-01

    目的:总结血清C肽与糖化血红蛋白联合检测对糖尿病诊断的意义,重点研究能够提升糖尿病病人诊断效率的重要方案。方法该研究资料选取2013年11月-2014年11月期间在我院接受诊治的糖尿病病人45例,视作实验组。同期选取45名来院体检的健康者为对照组,均予以血清C肽与糖化血红蛋白联合检测,同时对两组研究对象糖化血红蛋白、餐后两小时血糖值、空腹血糖值等指标进行对比。结果研究结果发现,对照组病患血清C肽值是(1.42±0.41)μg/l,实验组是(1.02±0.08)μg/l;实验组糖化血红蛋白是(10.05±2.19)%,对照组是(5.08±0.41)%;实验组空腹血糖值是(8.91±2.62)mmol/l,对照组是(4.19±0.62)mmol/l;实验组餐后两小时血糖值是(12.05±2.04)mmol/l,对照组是(4.79±1.52)mmol/l,两组研究对象在糖化血红蛋白、餐后两小时血糖值、空腹血糖值等指标方面的对比差异十分显著(P<0.05)。结论血清C肽与糖化血红蛋白联合检测对糖尿病诊断的意义十分突出,这是由于糖尿病病人血清C肽与糖化血红蛋白均会出现异常,因此检测结果可用作判断机体疾病严重性的重要指标。%Objective to summarize the serum C peptide and glycosylated hemoglobin significance of combined detection of diabetes diagnosis, key research important scheme can improve diabetes patients diagnosis efficiency.Methods this study data selection in November 2013 - November 2014 to accept the diagnosis and treatment in our hospital during the period of 45 cases of diabetes patients, as the experimental group. Selection in the same period of 45 to hospital medical healthy subjects as control group, both to serum C peptide and glycated hemoglobin joint detection, at the same time on two groups of research object glycosylated hemoglobin, two hours after the meal, fasting blood sugar levels in blood sugar levels such as index were compared.Results the results of the study

  7. Human placental lactogen levels in amniotic fluid in normal and toxemic pregnancies.

    Science.gov (United States)

    Lolis, D; Kaskarelis, D

    1978-01-01

    Amniotic fluid human placental lactogen (HPL) levels were measured by radioimmunoassay in 162 cases of women with normal pregnancy and 43 with toxemic pregnancy, in the last trimester of pregnancy. A significant differences in levels was observed.

  8. Plasma levels of oestriol-17 beta, oestriol and human placental lactogen during bed rest.

    Science.gov (United States)

    Chew, P C; Mok, H; Ratnam, S S

    1976-11-01

    Plasma unconjugated oestradiol-17 beta, total oestriol and human placental lactogen levels were measured in twelve healthy volunteers admitted for bed rest in the last trimester of pregnancy. No significant alteration in levels was observed.

  9. Two-step ion-exchange chromatographic purification combined with reversed-phase chromatography to isolate C-peptide for mass spectrometric analysis.

    Science.gov (United States)

    Kabytaev, Kuanysh; Durairaj, Anita; Shin, Dmitriy; Rohlfing, Curt L; Connolly, Shawn; Little, Randie R; Stoyanov, Alexander V

    2016-02-01

    A liquid chromatography with mass spectrometry on-line platform that includes the orthogonal techniques of ion exchange and reversed phase chromatography is applied for C-peptide analysis. Additional improvement is achieved by the subsequent application of cation- and anion-exchange purification steps that allow for isolating components that have their isoelectric points in a narrow pH range before final reversed-phase mass spectrometry analysis. The utility of this approach for isolating fractions in the desired "pI window" for profiling complex mixtures is discussed.

  10. Piracy on the molecular level: human herpesviruses manipulate cellular chemotaxis.

    Science.gov (United States)

    Cornaby, Caleb; Tanner, Anne; Stutz, Eric W; Poole, Brian D; Berges, Bradford K

    2016-03-01

    Cellular chemotaxis is important to tissue homeostasis and proper development. Human herpesvirus species influence cellular chemotaxis by regulating cellular chemokines and chemokine receptors. Herpesviruses also express various viral chemokines and chemokine receptors during infection. These changes to chemokine concentrations and receptor availability assist in the pathogenesis of herpesviruses and contribute to a variety of diseases and malignancies. By interfering with the positioning of host cells during herpesvirus infection, viral spread is assisted, latency can be established and the immune system is prevented from eradicating viral infection.

  11. From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Gabr

    2017-01-01

    Full Text Available The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs and adipose tissue-derived mesenchymal stem cells (AT-MSCs, for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs, was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine. Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.

  12. Human brain mercury levels related to exposure to amalgam fillings.

    Science.gov (United States)

    Ertaş, E; Aksoy, A; Turla, A; Karaarslan, E S; Karaarslan, B; Aydın, A; Eken, A

    2014-08-01

    The safety of dental amalgam as the primary material in dental restoration treatments has been debated since its introduction. It is widely accepted that amalgam restorations continuously release elemental mercury (Hg) vapor, which is inhaled and absorbed by the body and distributed to tissues, including the brain. The aim of the present study was to investigate whether the presence of amalgam fillings is correlated with brain Hg level. The Hg levels in the parietal lobes of the brains of 32 cadavers were analyzed with an atomic absorption spectrometer with the mercury hydride system. A total of 32 brain samples were tested; of these, 10 were from cadavers with amalgam fillings, while 22 of them were amalgam free. Hg was detected in 60.0% (6 of 10) of the samples in the amalgam group and in 36.3% (8 of 22) in the amalgam-free group. The average Hg level of the amalgam group was 0.97 ± 0.83 µg/g (minimum: 0.3 µg/g and maximum: 2.34 µg/g), and in the amalgam-free group, it was 1.06 ± 0.57 µg/g (minimum: 0.17 µg/g and maximum: 1.76 µg/g). The results of the present study showed no correlation between the presence of amalgam fillings and brain Hg level.

  13. MMP-1 serum levels predict coronary atherosclerosis in humans

    Directory of Open Access Journals (Sweden)

    Reiser Maximilian

    2009-09-01

    Full Text Available Background Myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Lipid enriched non-calcified lesions are considered more instable and rupture prone than calcified lesions. Matrix metalloproteinases (MMPs are extracellular matrix degrading enzymes with plaque destabilisating characteristics which have been implicated in atherogenesis. We therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non-calcified lesions as determined by CT-angiography in patients with coronary artery disease. Methods 260 patients with typical or atypical chest pain underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms gantry rotation time to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. Results In multivariable regession analysis, MMP-1 serum levels were associated with total plaque burden (OR: 1.37 (CI: 1.02-1.85; p Conclusion MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.

  14. Salivary arecoline levels during areca nut chewing in human volunteers.

    Science.gov (United States)

    Cox, Stephen; Vickers, Edward R; Ghu, Sonia; Zoellner, Hans

    2010-07-01

    Arecoline stimulates cultured cells above 0.1 microg/ml and is cytotoxic above 10 microg/ml. Although this alkaloid seems important for areca nut induced oral carcinogenesis, little is known of the levels achieved during chewing. Saliva was collected in 3- to 5-min intervals over 50 min in 32 habitual chewers: before, for 25 min during, and for 20 min after chewing areca nut (0.5 g) without any other additives. Salivary arecoline was quantitated by HPLC-MS. Controls comprised six subjects who denied areca nut use, and who were given rubber-base material to chew during experiments instead. Arecoline was detected before chewing in 22 subjects, exceeding the 0.1 microg/ml threshold in 20 cases. Salivary arecoline exceeded either the 0.1 or 10 microg/ml thresholds in all participants during chewing (P arecoline in at least 85% of time points studied (P Arecoline concentrations varied greatly over time between individuals, and levels were much lower when peak concentrations were reached before 3 min, than in cases where arecoline peaked later (P arecoline was found in control saliva. Areca nut users have persistent background salivary arecoline levels long after chewing, whereas concentrations achieved are highly variable and consistent with a role in oral pre-malignancy and malignancy.

  15. A two-layered approach to recognize high-level human activities

    NARCIS (Netherlands)

    N. Hu; G. Englebienne; B. Kröse

    2014-01-01

    Automated human activity recognition is an essential task for Human Robot Interaction (HRI). A successful activity recognition system enables an assistant robot to provide precise services. In this paper, we present a two-layered approach that can recognize sub-level activities and high-level activi

  16. Natural levels of {sup 210}Po in human urine

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Frances, I.; Manjon, G.; Mantero, J.; Diaz, J. [Departament of Applied Phisic II, University of Seville, P.O. Box 41012 Seville (Spain); Garcia-Tenorio, R. [Departament of Applied Phisic II, University of Seville, P.O. Box 41012 Seville (Spain); National Accelerator Centre, P.O. Box 41092 Seville (Spain)

    2014-07-01

    Since the secret agent Alexander Litvinenko was murdered in 2006 by a {sup 210}Po lethal dose, presumably ingested, there is renovated interest on the toxicity of this radionuclide in humans. {sup 210}Po is a radioactive isotope naturally found in nature, mainly incorporated by humans via food and water ingestion, as well as inhaled through its progenitor, the {sup 222}Rn. The total amount of natural {sup 210}Po in the human body can vary from person to person depending on their lifestyle: dietary habits, drinking water source, place of residence (associated with exposure to {sup 222}Rn), etc- and therefore in the concentrations of this element to be found in urine. To analyze the influence of dietary habits on the amount of {sup 210}Po excreted in urine, two volunteers in Seville had a well-defined and time-varying diet for a month, following a daily collection of their urine and determination of the concentrations therein of this radionuclide. The results obtained and the conclusions derived from them form the core of this communication. {sup 210}Po determinations were performed daily in 200 ml aliquots of urine using the technique of high resolution alpha spectrometry. This has involved the application of a single radiochemical method for the concentration and isolation {sup 210}Po, followed by its auto-deposition on copper planchets for proper measure. Daily {sup 210}Po activity concentrations in voluntary urine analyzed during the month of study show high variability with a difference of up to an order of magnitude between maximum and minimum values obtained, and a clear dependence on the diet type followed in the various stages of the experiment. The lowest concentrations obtained are associated with a diet rich in carbohydrates and proteins 'terrestrial' (pork, beef,...), while the highest concentrations were obtained in the final phase of the experiment when the diet was enriched with presence of marine products in fair correspondence with the

  17. Human and great ape red blood cells differ in plasmalogen levels and composition

    Directory of Open Access Journals (Sweden)

    Ely John J

    2011-06-01

    Full Text Available Abstract Background Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease. Results In a human and great ape cohort, we measured the red blood cell (RBC levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the sn-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the sn-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues. Conclusion We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and

  18. C肽灌注对Wistar大鼠胰岛微循环的影响%Effect of C peptide on pancreatic islet microcirculation in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    吴琳; 黄镇; (A)ke Sj(o)holm; 高鑫

    2009-01-01

    目的 测定生理剂量重组人C肽静脉注射对雄性Wistar大鼠胰岛微循环、血糖和胰岛素分泌的影响.方法 成年雄性Wistar大鼠分为C肽组和对照组,分别给予C肽(75 nmol/kg体重)和相同容积生理盐水静脉注射;每组再分为葡萄糖组和生理盐水组两个亚组.血流测定采用微球技术.结果 C肽显著增高Wistar大鼠基础胰岛血流[C肽组vs对照组:(0.156±0.018 vs 0.050±0.003)ml·min-1·g-1胰腺,P<0.01]和胰岛/胰腺血流比值[C肽组vs对照组:(14.33±0.53vs9.16±0.64)%,P<0.01],胰腺血流向胰岛内重分布.C肽对糖负荷后胰岛微循环无显著影响.C肽降低大鼠腹腔糖耐量试验30 min血糖[C肽组vs对照组:(7.9±0.7 vs 11.5±0.6)mmol/L,P<0.01];增加胰岛素分泌(AUC胰岛素(0-120),C肽组vs对照组:141.36±15.00 vs 49.78±5.60,P<0.01).结论 C肽静脉注射改善Wistar大鼠基础胰岛微循环,调节糖负荷后胰岛素分泌.%Objective To evaluate the effects of physiological doses of C-peptide on islet microcirculation,blood glucose,and insulin concentrations.Methods Adult male Wistar rats were divided into two groups i.v either with C-peptide (75nmoL/kg body wt)or saline (control).Each group was further divided into 2 subgroups using 1 ml saline or 30% glucose.A microsphere technique was adopted to measure the pancreatic islet microcirculation.Results Intravenous injection of C-peptide markedly increased basal islet blood flow[(0.156±flow[(14.33±0.53 vs 9.16±0.64) %,P<0.01],but did not affect islet microcircuJation after intravenous glucose administration.In IPGT,C-peptide decreased blood glucose at 30 min[(7.9±0.7 vs 11.5±0.6) mmol/L,P<0.01]after glucose challenge and stimulated insulin secretion(for AUCins(0.120),141.36±15.00 vs 49.78±5.60,P < 0.01).Conclusion C-peptide induces redistribution of pancreatic blood flow in favour of islet in normoglycemic rats,and modulates insulin release in hyperglycaemic rats.

  19. Impact of infusion method on amikacin serum levels in humans.

    Science.gov (United States)

    Simon, N; Décaudin, B; Lannoy, D; Odou, M F; De Broucker, M; Barthélémy, C; Poret, E; Dubreuil, L; Odou, P

    2010-08-01

    Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact. Twenty-four patients hospitalised for community-acquired pulmonary infections received amikacin by IV route over 1 h with a targeted peak concentration of 35 mg/L. They were randomly distributed into two groups, one receiving infusion through a pump system, the other by gravity. Amikacin serum levels were determined at the end of infusion and 24 h later. C(max) values were significantly lower with gravity than pump (40.2 +/- 12.3 vs. 50.6 +/- 17.6 mg/L, respectively; p = 0.04). Elimination half-life time, volume of distribution and clearance did not differ significantly from one group to the other. The percentage of patients who failed to achieve the targeted peak concentration was significantly higher with gravity than pump (41.7% vs. 16.7%, respectively; p infusion flow-rate provides better control over amikacin C(max). This study underlines the fact that infusion device characteristics should be added to the physiopathological information of a patient if we are to make a better estimation of pharmacokinetic parameters.

  20. BMI对血压、血糖、糖化血红蛋白及C肽的影响%Influence of BMI on blood pressure, blood glucose, glycosylated hemoglobin and C-peptide

    Institute of Scientific and Technical Information of China (English)

    张惠新; 姜博仁; 李影; 李艳香; 夏芳珍

    2011-01-01

    目的:探讨年龄32~56岁的健康者体质指数(body mass index,BMI)增高对血压、血糖、糖化血红蛋白及C肽的影响.方法:79名健康者按BMI分为标准组(18.5≤BMI<24,n=44)、超重组(24≤BMI<28,n=27)及肥胖组(BMI≥28,n=8)三组,比较三组之间血压、血糖、糖化血红蛋白及C肽的变化.结果:随着BMI的增高,收缩压(SBP)[(115.8±15.24) mm Hg vs(121.1±18.38)mm Hg vs(133.4±18.36)mm Hg](1 mm Hg=0.133 kPa)、餐后2 h血糖(PBG)[(5.76±0.73)mmol/L vs(5.86±0.76)mmol/L vs(6.61±1.85)mmol/L],及糖化血红蛋白(HbA1C)[(5.20±0.29)% vs(5.29±0.28)% vs(5.64±0.53)%]显著增高,差异有统计学意义(P=0.033,P=0.048,P=0.004);而舒张压(DBP)[(72.57±11.14)mm Hg vs(75.81±10.04)mm Hg vs(80.71±11.31)mm Hg]、空腹血糖(FBG)[(5.73±0.52)mmol/L vs(5.48±0.54)mmol/L vs(5.85±0.61)mmol/L]、空腹C肽[(1.37±0.81)pmol/L vs(1.26±0.43)pmol/L vs(1.98±0.75)pmol/L]及餐后2 h C肽[(2.70±1.14)pmol/L vs(2.99±1.49)pmol/L vs(3.25±1.53)pmol/L]也有增高趋势,但差异无统计学意义(P=0.137,P=0.107,P=0.110,P=0.530).结论:肥胖使血压、血糖水平增加,从而增加高血压以及糖尿病的患病风险.%Objective: To investigate the influence of body mass index (BMI) increasing on levels of blood pressure, blood glucose, glycosylated hemoglobin and C-peptide in the healthy people aged from 32 to 56. Methods: 79 healthy subjects were divided by BMI to three groups, standard group (18.5 ≤SBMI<24, n=44), overweight group (24 ≤S BMI<28, n=21) and obese group (BMI ≥28, n=8), the levels of blood pressure, blood glucose, glycated hemoglobin and C-peptide among the three groups were compared. Results: With the increasing of BMI, the levels of systolic blood pressure (SBP) [(115.8 ± 15.24)mm Hg vs (121.1±18.38)mm Hg vs (133.4±18.36)mm Hg] (1 mm Hg=0.133 kPa), 2-hour postprandial blood glucose (PBG) [(5.76±0.73)mmol/L vs (5.86±0.76)mmol/L vs (6.61±1.85)mmol/L] and glycated hemoglobin (HbA1c) [(5.20±0.29)% vs

  1. Taking it to another level: do personality-based human capital resources matter to firm performance?

    Science.gov (United States)

    Oh, In-Sue; Kim, Seongsu; Van Iddekinge, Chad H

    2015-05-01

    Drawing on the attraction-selection-attrition perspective, strategic human resource management (SHRM) scholarship, and recent human capital research, this study explores organization-level emergence of personality (i.e., personality-based human capital resources) and its direct, interactive, and (conditional) indirect effects on organization-level outcomes based on data from 6,709 managers across 71 firms. Results indicate that organization-level mean emotional stability, extraversion, and conscientiousness are positively related to organization-level managerial job satisfaction and labor productivity but not to financial performance. Furthermore, organization-level mean and variance in emotional stability interact to predict all three organization-level outcomes, and organization-level mean and variance in extraversion interact to predict firm financial performance. Specifically, the positive effects of organization-level mean emotional stability and extraversion are stronger when organization-level variance in these traits is lower. Finally, organization-level mean emotional stability, extraversion, and conscientiousness are all positively related to firm financial performance indirectly via labor productivity, and the indirect effects are more positive when organization-level variance in those personality traits is lower. Overall, the findings suggest that personality-based human capital resources demonstrate tangible effects on organization-level outcomes. Theoretical and practical implications of these findings are discussed along with study limitations and future research directions.

  2. Gene-specific correlation of RNA and protein levels in human cells and tissues

    DEFF Research Database (Denmark)

    Edfors, Fredrik; Danielsson, Frida; Hallström, Björn M.

    2016-01-01

    to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP...

  3. The Changes of the Human Development on Micro-Regional and Settlement Levels

    Directory of Open Access Journals (Sweden)

    Katalin Lipták

    2015-10-01

    Full Text Available The purpose of this paper is to define and estimate the human potential of the settlements in South-Cserehát,, Hungary. The human development index in the classical view can be estimated atmicroregional level with only hard distortions, to which the list of starting indicators differ from the usual indicators, such as GDP and GNI, the life expectancy at birth and the portion of taking part in education. However, the estimating calculations made for defining the human potential in a settlement level should be handled with hard restrictions , at the same time it perfectly shows the formation of the human factor in the region. As a research question the following was defined: In what range has the human potential changed on the basis of the census data and what kind of configuration changes have happened in the South-Cserehát? The aim of the study to attempt to estimate the HDI on settlement level.

  4. Human factors programs for high-level radioactive waste handling systems

    Energy Technology Data Exchange (ETDEWEB)

    Pond, D.J.

    1992-04-01

    Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples from other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process.

  5. Designing a Top-Level Ontology of Human Beings: A Multi-Perspective Approach

    Institute of Scientific and Technical Information of China (English)

    田雯; 顾芳; 曹存根

    2002-01-01

    Knowledge about human beings is an integral part of any intelligent agent ofconsiderable significance. Delimiting, modeling and acquiring such knowledge are the centraltopics of this paper. Because of the tremendous complexity in knowledge of human beings, weintroduce a top-level ontology of human beings from the perspectives of psychology, sociology,physiology and pathology. This ontology is not only an explicit conceptualization of humanbeings, but also an efficient way of acquiring and organizing relevant knowledge.

  6. Improved methodology for the affinity isolation of human protein complexes expressed at near endogenous levels

    DEFF Research Database (Denmark)

    Domanski, Michal; Molloy, Kelly; Jiang, Hua;

    2012-01-01

    An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous......-level tagged proteins. Isolations of triple-FLAG and GFP-tagged fusion proteins involved in RNA metabolism are presented.......An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous...

  7. Index of Human Development: Measurement Problems at the National and World Levels

    Directory of Open Access Journals (Sweden)

    Sarychev Volodymyr I.

    2014-02-01

    Full Text Available The article analyses main modern approaches to measurement of the index of human development at the world level by the UN Development Programme and at the national level in Ukraine. It identifies main components and stages of formation of national methods of measurement of the index of regional human development and also advantages of its renovated modern variant against the background of fighting poverty, analyses key directions of human development, which reflect main possibilities in ensuring the process of life, generalises the “living standard” category definition by works of domestic and foreign scientists, analyses dynamics of indicators of the index of human development of Ukraine for the period 2007 – 2012 and explains main reasons of drop of ratings of Ukraine in the world and conducts comparative analysis of tendencies of changes of the index of human development of Ukrainian regions in recent years.

  8. A model for assessing the risk of human trafficking on a local level

    Science.gov (United States)

    Colegrove, Amanda

    Human trafficking is a human rights violation that is difficult to quantify. Models for estimating the number of victims of trafficking presented by previous researchers depend on inconsistent, poor quality data. As an intermediate step to help current efforts by nonprofits to combat human trafficking, this project presents a model that is not dependent on quantitative data specific to human trafficking, but rather profiles the risk of human trafficking at the local level through causative factors. Businesses, indicated by the literature, were weighted based on the presence of characteristics that increase the likelihood of trafficking in persons. The mean risk was calculated by census tract to reveal the multiplicity of risk levels in both rural and urban settings. Results indicate that labor trafficking may be a more diffuse problem in Missouri than sex trafficking. Additionally, spatial patterns of risk remained largely the same regardless of adjustments made to the model.

  9. Human-Level Natural Language Understanding: False Progress and Real Challenges

    Science.gov (United States)

    Bignoli, Perrin G.

    2013-01-01

    The field of Natural Language Processing (NLP) focuses on the study of how utterances composed of human-level languages can be understood and generated. Typically, there are considered to be three intertwined levels of structure that interact to create meaning in language: syntax, semantics, and pragmatics. Not only is a large amount of…

  10. High taxonomic level fingerprint of the human intestinal microbiota by Ligase Detection Reaction - Universal Array approach

    Directory of Open Access Journals (Sweden)

    Vitali Beatrice

    2010-04-01

    Full Text Available Abstract Background Affecting the core functional microbiome, peculiar high level taxonomic unbalances of the human intestinal microbiota have been recently associated with specific diseases, such as obesity, inflammatory bowel diseases, and intestinal inflammation. Results In order to specifically monitor microbiota unbalances that impact human physiology, here we develop and validate an original DNA-microarray (HTF-Microbi.Array for the high taxonomic level fingerprint of the human intestinal microbiota. Based on the Ligase Detection Reaction-Universal Array (LDR-UA approach, the HTF-Microbi.Array enables specific detection and approximate relative quantification of 16S rRNAs from 30 phylogenetically related groups of the human intestinal microbiota. The HTF-Microbi.Array was used in a pilot study of the faecal microbiota of eight young adults. Cluster analysis revealed the good reproducibility of the high level taxonomic microbiota fingerprint obtained for each of the subject. Conclusion The HTF-Microbi.Array is a fast and sensitive tool for the high taxonomic level fingerprint of the human intestinal microbiota in terms of presence/absence of the principal groups. Moreover, analysis of the relative fluorescence intensity for each probe pair of our LDR-UA platform can provide estimation of the relative abundance of the microbial target groups within each samples. Focusing the phylogenetic resolution at division, order and cluster levels, the HTF-Microbi.Array is blind with respect to the inter-individual variability at the species level.

  11. Peanut consumption increases levels of plasma very long chain fatty acids in humans.

    Science.gov (United States)

    Lam, Christina; Wong, Derek; Cederbaum, Stephen; Lim, Bennie; Qu, Yong

    2012-11-01

    Peanut consumption has been suspected of raising plasma very long chain fatty acid (VLCFA) levels in humans. The effect of peanut consumption on VLCFAs was studied in six human subjects. After 3 to 4h of peanut butter ingestion, plasma C26:0 and C26:0/C22:0 were found to be significantly elevated to levels seen in patients with peroxisomal disorders. These levels returned to normal within 12h. Peanut consumption needs to be accounted for when interpreting VLCFAs.

  12. Serum human placental lactogen levels in intra-uterine fetal growth retardation.

    Science.gov (United States)

    Zail, S S; Safro, I L

    1975-11-12

    Serum human placental lactogen (HPL) levels were measured in the last trimester of pregnancy in 16 mothers who delivered small-for-gestational-age babies. Only 3 patients had levels which were below the normal range, while 4 others had levels close to the lower limit of the normal range. The finding of a normal serum HPL level therefore does not exclude the possibility of intra-uterine fetal growth retardation. No correlation was found between serum HPL levels at 37-39 weeks and infant or placental weights in full-term normal deliveries.

  13. PBDE levels in human milk: the situation in Germany and potential influencing factors - a controlled study

    Energy Technology Data Exchange (ETDEWEB)

    Vieth, B.; Mielke, H.; Ostermann, B.; Ruediger, T. [Federal Inst. for Risk Assessment, Berlin (Germany); Herrmann, T.; Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany)

    2004-09-15

    An exponential increase of PBDE levels in breast milk from Sweden between 1972 and 1997 has been reported, which is in contrast to the continuous decline of other chlorinated POPs in breast milk. Also in blood samples from Germany, an increasing trend has been observed during the period from 1985 to 1999. The knowledge about human exposure pathways, which contribute to the PBDE body burden, is very limited. Consumption of food of animal origin, inhalation or ingestion of dust and further factors possibly influencing the PBDE levels in human matrices, like age, breast-feeding or smoking are under discussion. Only a few data on PBDE levels in breast milk from Germany have been published. To fill the data gaps, a controlled study was started in 2001 to characterise the PBDE levels in human milk from Germany with special efforts to identify and quantify deca-BDE-209. Furthermore, it was intended to verify potential factors possibly influencing PBDE levels. Two main hypotheses were proposed: (1) Are PBDE levels in breast milk from mothers consuming traditional food (omnivores) higher than those found in breast milk from mothers consuming vegetarian or vegan food? and (2) Are the PBDE levels found in human milk after a three-months period of breast-feeding lower than those detected at the beginning or does breast feeding result in a lower body burden, respectively? This paper summarises preliminary results. Further analytical data and results of data evaluation will be presented at the conference.

  14. Human arsenic exposure and risk assessment at the landscape level: a review.

    Science.gov (United States)

    Khan, Nasreen Islam; Owens, Gary; Bruce, David; Naidu, Ravi

    2009-04-01

    Groundwater contaminated with arsenic (As), when extensively used for irrigation, causes potentially long term detrimental effects to the landscape. Such contamination can also directly affect human health when irrigated crops are primarily used for human consumption. Therefore, a large number of humans are potentially at risk worldwide due to daily As exposure. Numerous previous studies have been severely limited by small sample sizes which are not reliably extrapolated to large populations or landscapes. Human As exposure and risk assessment are no longer simple assessments limited to a few food samples from a small area. The focus of more recent studies has been to perform risk assessment at the landscape level involving the use of biomarkers to identify and quantify appropriate health problems and large surveys of human dietary patterns, supported by analytical testing of food, to quantify exposure. This approach generates large amounts of data from a wide variety of sources and geographic information system (GIS) techniques have been used widely to integrate the various spatial, demographic, social, field, and laboratory measured datasets. With the current worldwide shift in emphasis from qualitative to quantitative risk assessment, it is likely that future research efforts will be directed towards the integration of GIS, statistics, chemistry, and other dynamic models within a common platform to quantify human health risk at the landscape level. In this paper we review the present and likely future trends of human As exposure and GIS application in risk assessment at the landscape level.

  15. Dosagem do peptídeo C sérico ao acaso em adultos com diagnóstico clínico de diabetes mellitus tipo 1 Random C peptide measurement in adults with clinical diagnosis of type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Melanie Rodacki

    2008-06-01

    Full Text Available OBJETIVO: A dosagem de peptídeo C (PC pode ser útil para a classificação do Diabetes mellitus (DM. O objetivo deste estudo foi investigar a associação entre o diagnóstico clínico de DM tipo 1 e os níveis séricos de PC randômico. MÉTODOS: Foi feita dosagem de PC ao acaso em pacientes de origem multiétnica com diagnóstico clínico de DM tipo 1 na idade adulta ( > 18 anos. RESULTADOS: Estudamos 51 pacientes, sendo 28 mulheres (54,9% e 23 homens (45,1%, 36 brancos (70,6% e 15 não-brancos (29,4% com idade média ao diagnóstico de 27,9 (±7,5 anos e duração média da doença de 9,9 (±7,2 anos. Oito pacientes (15,7% apresentaram PC > 1,5 ng/ml indicativo de função pancreática preservada. Neste grupo, foi detectado índice de massa corporal mais elevado (26,05 vs 23,05 kg/m²; p=0,006 e maior proporção de não-brancos (62,5% vs 23,3%; p=0,039 do que naqueles com PC baixo. CONCLUSÃO: A maioria dos pacientes com diagnóstico clínico de DM tipo 1 apresenta PC baixo. Entretanto, a secreção pancreática de insulina parece preservada em uma quantidade significativa de pacientes com quadro clínico indicativo de DM tipo 1. É possível que estes pacientes apresentem alguma forma atípica de DM, ainda não completamente compreendida, com características de DM tipo 1 e tipo 2 superpostas.OBJECTIVE: C peptide measurement can be helpful for classification of diabetes mellitus (DM. The aim of this study was to investigate the association between clinical diagnosis of type 1 diabetes (T1D and levels of random C peptide. METHODS: Random C peptide was measured in adults of multi-ethnic background who had been classified as having T1D according to their clinical presentation. All individuals were > 18 years old at onset. RESULTS: The study included 51 adults, 28 (54.9% females and 23 (45.1% males, 36 (70.6% Caucasian and 15 (29.4% non-Caucasian. Their mean age at onset and duration of DM mean age were 27.9 (± 7.5 years and 9.9 (±7.2 years

  16. Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Thomas J. van 't Erve

    2017-08-01

    In conclusion, we have established a quantitative classification for the level of 8-iso-PGF2α generation in different human pathologies and exposures based on a comprehensive meta-analysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation.

  17. Contamination status of persistent organochlorines in human breast milk from Japan: recent levels and temporal trend.

    Science.gov (United States)

    Kunisue, Tatsuya; Muraoka, Masayoshi; Ohtake, Masako; Sudaryanto, Agus; Minh, Nguyen Hung; Ueno, Daisuke; Higaki, Yumi; Ochi, Miyuki; Tsydenova, Oyuna; Kamikawa, Satoko; Tonegi, Tomoyuki; Nakamura, Yumi; Shimomura, Hiroshi; Nagayama, Junya; Tanabe, Shinsuke

    2006-08-01

    Contamination levels of persistent organochlorines (OCs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), and chlordane compounds (CHLs) was examined in human breast milk collected during 2001-2004 from Fukuoka prefecture in Japan. The concentrations of OCs such as dioxins and related compounds, DDTs, CHLs and HCB in human breast milk from primiparae were comparable to or slightly higher than the data obtained during 1998, indicating that the levels of these contaminants in Japanese human breast milk have not decreased since 1998 and Japanese are continuously exposed to these chemicals, presumably via fish intake. In addition, OC levels in human breast milk from primiparae were significantly higher than those from multiparae, implying elimination of OCs via lactation. Furthermore, significant positive correlations were observed between levels of OCs in human breast milk and the age of primiparae. These results indicate that the mothers with higher age may transfer higher amounts of OCs to the first infant than to the infants born afterwards through breast-feeding, and hence the first born children might be at higher risk by OCs.

  18. INFLUENCE OF WELFARE ON THE LEVEL OF DEVELOPMENT OF THE HUMAN CAPITAL OF RUSSIAN REGIONS

    Directory of Open Access Journals (Sweden)

    И. А. Гурбан

    2014-01-01

    Full Text Available The paper provides a methodological approach for mea-suring the level of human capital development in the regions of Russian Federation. The approach suggested enables to determine the qualitative state of human capital in each region, to find out the reasons underpinning the current situation, to asses regions’ contribution to the overall national human ca-pital, to develop some individual approach to forming another quality human capital and its managing for each territory. The methodology afforded the instrument ware based on the qualimetric analysis which uses the natural estimates (indi-cators of an object. A system of indicators simulating the human capital state puts forward the following modules: demographic, educational, labor, research and sociocultural. The tool offered allows differentiation of the Russian regions into the levels of human capital state. 2000 and 2011 rating of Russian regions according to the human capital state and his dynamics over 2000-2011 is given.Purchase on Elibrary.ru > Buy now

  19. Enhanced memory for emotional material following stress-level cortisol treatment in humans.

    Science.gov (United States)

    Buchanan, T W; Lovallo, W R

    2001-04-01

    Memory tends to be better for emotionally arousing information than for neutral information. Evidence from animal studies indicates that corticosteroids may be necessary for this memory enhancement to occur. We extend these findings to human memory performance. Following administration of cortisol (20 mg) or placebo, participants were exposed to pictures varying in emotional arousal. Incidental memory for the pictures was assessed one week later. We show that elevated cortisol levels during memory encoding enhances the long-term recall performance of emotionally arousing pictures relative to neutral pictures. These results extend previous work on corticosteroid enhancement of memory and suggest that high cortisol levels during arousing events result in enhanced memory in humans.

  20. Higher-level goals in the processing of human action events

    OpenAIRE

    Eisenberg, M.L.; Zacks, J.M.; Flores, S.; Howard, L.H.; Woodward, A.L.; Loucks, J.; Meltzoff, A N; Cooper, Richard

    2016-01-01

    The concept of a goal critically separates dynamic events involving humans from other events. Human behaviours are motivated by goals, which are known to the actor but typically inferred on the part of the observer. Goals can be hierarchical in nature, such that a collection of sub-goals (e.g., getting a mug, boiling water) can be nested under a higher-level goal (e.g., making tea), which can be further nested under an even higher-level goal (e.g., making breakfast).\\ud The diverse set of tal...

  1. Incidence of high-level evernimicin resistance in Enterococcus faecium among food animals and humans

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; McNicholas, P. M.

    2002-01-01

    to a susceptible E. faecium strain. The resulting transconjugants all tested positive for the presence of emtA, a gene encoding a methyltransferase previously linked with high-level evernimicin resistance. The four transconjugants derived from animal isolates all carried the same plasmid, while a differently sized...... plasmid was found in the isolate from humans. This study demonstrated a low incidence of high-level evernimicin resistance mediated by the emtA gene in different E. faecium isolates of animal and human origin....

  2. Review (laws for compliance and human rights multi-level protection in Inter-American Human Rights System

    Directory of Open Access Journals (Sweden)

    Natalia Torres Zúñiga

    2013-12-01

    Full Text Available This article addresses diverse perspectives concerning relationship between reviewing (laws for compliance and the process of putting international law of human rights on a constitutional footing. Therefore, a parallel is established between reviewing (laws for compliance and constitutional review (laws in order to outline features and application impact of this research. The design of a multi-level protection system for fundamental rights in Latin America is also discussed in this article.

  3. Effect of cholesterol and triglycerides levels on the rheological behavior of human blood

    Science.gov (United States)

    Moreno, Leonardo; Calderas, Fausto; Sanchez-Olivares, Guadalupe; Medina-Torres, Luis; Sanchez-Solis, Antonio; Manero, Octavio

    2015-02-01

    Important public health problems worldwide such as obesity, diabetes, hyperlipidemia and coronary diseases are quite common. These problems arise from numerous factors, such as hyper-caloric diets, sedentary habits and other epigenetic factors. With respect to Mexico, the population reference values of total cholesterol in plasma are around 200 mg/dL. However, a large proportion has higher levels than this reference value. In this work, we analyze the rheological properties of human blood obtained from 20 donors, as a function of cholesterol and triglyceride levels, upon a protocol previously approved by the health authorities. Samples with high and low cholesterol and triglyceride levels were selected and analyzed by simple-continuous and linear-oscillatory shear flow. Rheometric properties were measured and related to the structure and composition of human blood. In addition, rheometric data were modeled by using several constitutive equations: Bautista-Manero-Puig (BMP) and the multimodal Maxwell equations to predict the flow behavior of human blood. Finally, a comparison was made among various models, namely, the BMP, Carreau and Quemada equations for simple shear rate flow. An important relationship was found between cholesterol, triglycerides and the structure of human blood. Results show that blood with high cholesterol levels (400 mg/dL) has flow properties fully different (higher viscosity and a more pseudo-plastic behavior) than blood with lower levels of cholesterol (tendency to Newtonian behavior or viscosity plateau at low shear rates).

  4. Four basic levels of the interactions between humanity and the imbalanced Nature

    Science.gov (United States)

    Kontar, V. A.

    2013-12-01

    There are the clearly distinguishable four basic levels of interaction the humanity with the imbalanced Nature: 1 Level - Naivety: Self-healing Nature in defiance of the humanity activities. 2 Level - Collaboration: Restoration of Nature in cooperation with humanity. 3 Level - Conflict: The resistance of Nature against the humanity's interference. 4 Level - Disappearance: Nature destroys humanity as the trouble maker. On the first level the people were afraid and respected Nature and are taking from Nature only what Nature gave willingly. Therefore Nature could easy regenerate itself. So it was thousands of years and people become under the false impression that it will be forever. The first signs the end of this period was visible in the era of industrialization. It turned out that resources are not infinite, and the waste of humanity grows much faster than Nature can utilize or dispose it. But in the world still had plenty of the untouched places and industrialization continued to develop rapidly. Thus problems with Nature were dislocated into the colonies rather far off from the prosperous metropolitan countries. The false impression about the man's victory over Nature has increased. Very soon the main untouched place was used, and the global circulations bring the pollutions from colonies to the metropolis. The second level was started as processes to creating the national parks, natural reservations, etc. It was some beginning of the cooperation humanity with Nature. The invasion into the Nature of the colonies was intensified. In addition start increasing the pollution in the metropolis from the waste of resources which have been imported from the colonies. The third level was started and Nature began to resist and revenge to the self-confident man. But man didn't stop and continued create more and more aggressive processes which provoked some avalanches-looks reactions of Nature. Now people can start these avalanches, but cannot stop it. One of these man

  5. Insulin Plays a Permissive Role for the Vasoactive Effect of GIP Regulating Adipose Tissue Metabolism in Humans.

    Science.gov (United States)

    Asmar, Meena; Simonsen, Lene; Asmar, Ali; Holst, Jens Juul; Dela, Flemming; Bülow, Jens

    2016-08-01

    Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increases blood flow and triglyceride (TAG) clearance in subcutaneous (sc) abdominal adipose tissue in lean humans. The present experiments were performed to further investigate the role of insulin for the vasoactive effect of GIP in adipose tissue metabolism and whether the vasodilatory effect of GIP is dependent on C-peptide. Six lean healthy subjects were studied. The sc abdominal adipose tissue metabolism was assessed by Fick's principle during GIP infusion (1.5 pmol/kg/min) in combination with 1) euglycemic-high insulinemic clamp (Eugluc-Hiinsu), raising plasma insulin concentrations to postprandial levels, 2) hyperglycemic-euinsulinemic clamp (Hygluc-Euinsu), and 3) hyperglycemic-hyperinsulinemic clamp, raising plasma insulin concentrations to supraphysiological levels. During the hyperglycemic clamps, endogenous insulin and C-peptide secretion were inhibited by infusion of the somatostatin analogue octreotide. During GIP infusion, Eugluc-Hiinsu, and hyperglycemic-hyperinsulinemic clamps, sc abdominal adipose tissue blood flow (ATBF) was similar and increased from 2.1 ± 0.2 and 2.2 ± 0.4 ml min(-1) (100 g tissue)(-1) to 7.1 ± 0.6 and 7.6 ± 0.1 ml min(-1) (100 g tissue)(-1), respectively (P tissue](-1)) during Hygluc-Euinsu and GIP infusion. In addition, adipose tissue TAG clearance increased significantly (P = .03), whereas free fatty acid output (P = .01), glycerol output (P = .02) and free fatty acid/glycerol release ratio (P = .04) decreased during the Eugluc-Hiinsu clamp compared to Hygluc-Euinsu clamp with GIP. In healthy lean humans, insulin is permissive for GIP to induce an increase in blood flow and TAG clearance in sc abdominal adipose tissue. This effect is independent of C-peptide.

  6. Proteins differentially expressed in human beta-cells-enriched pancreatic islet cultures and human insulinomas

    DEFF Research Database (Denmark)

    Terra, Letícia F; Teixeira, Priscila C; Wailemann, Rosangela A M

    2013-01-01

    In view of the great demand for human beta-cells for physiological and medical studies, we generated cell lines derived from human insulinomas which secrete insulin, C-peptide and express neuroendocrine and islet markers. In this study, we set out to characterize their proteomes, comparing them t...

  7. An evaluation of human placental lactogen levels in hypertension of pregnancy.

    Science.gov (United States)

    Kelly, A M; England, P; Lorimer, J D; Ferguson, J C; Govan, A D

    1975-04-01

    Maternal plasma levels of human placental lactogen (HPL) are decreased in hypertensive pregnancies and the concentration is related to the severity of the condition. Of infants who had HPL concentrations in the fetal danger zone (more than 2 SD's below normal mean) 75 per cent developed fetal distress, neonatal asphyxia or were light for dates. Patients who are identified in this way have lighter infants and placentae than their unidentified counterparts with normal HPL levels.

  8. Population-level impact and herd effects following human papillomavirus vaccination programmes

    DEFF Research Database (Denmark)

    Drolet, Mélanie; Bénard, Élodie; Boily, Marie-Claude

    2015-01-01

    BACKGROUND: Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether...... results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING: The Canadian Institutes of Health Research....

  9. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta

    OpenAIRE

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L.; Perdomo, Germán

    2013-01-01

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase...

  10. Pleistocene sea-level fluctuations and human evolution on the southern coastal plain of South Africa

    Science.gov (United States)

    Compton, John S.

    2011-03-01

    Humans evolved in Africa, but where and how remain unclear. Here it is proposed that the southern coastal plain (SCP) of South Africa may have served as a geographical point of origin through periodic expansion and contraction (isolation) in response to glacial/interglacial changes in sea level and climate. During Pleistocene interglacial highstands when sea level was above -75 m human populations were isolated for periods of 360-3400 25-yr generations on the SCP by the rugged mountains of the Cape Fold Belt, climate and vegetation barriers. The SCP expands five-fold as sea level falls from -75 to -120 m during glacial maxima to form a continuous, unobstructed coastal plain accessible to the interior. An expanded and wet glacial SCP may have served as a refuge to humans and large migratory herds and resulted in the mixing of previously isolated groups. The expansive glacial SCP habitat abruptly contracts, by as much as one-third in 300 yr, during the rapid rise in sea level associated with glacial terminations. Rapid flooding may have increased population density and competition on the SCP to select for humans who expanded their diet to include marine resources or hunted large animals. Successful adaptations developed on an isolated SCP are predicted to widely disperse during glacial terminations when the SCP rapidly contracts or during the initial opening of the SCP in the transition to glacial maxima. The hypothesis that periodic expansion and contraction of the SCP, as well as the coastal plain of North Africa, contributed to the stepwise origin of our species over the last 800 thousand years (kyr) is evaluated by comparing the archeological, DNA and sea-level records. These records generally support the hypothesis, but more complete and well dated records are required to resolve the extent to which sea-level fluctuations influenced the complex history of human evolution.

  11. [Management of fetuses in the late pregnancy by serial determinations of serum human placental lactogen levels].

    Science.gov (United States)

    Kaibara, M; Marumoto, Y; Taniguchi, I; Kobayashi, T

    1982-10-01

    Serum human placental lactogen levels (HPL) were measured serially during the last three weeks before full term deliveries of 69 normal and 60 high risk pregnant women with the method of latex agglutination (Gestefollow 'Eiken'). Except pregnancies complicated with diabetes mellitus, no fetal distress were observed when deliveries were made while HPL levels were increasing. The incidence of fetal distress was only 3.7 per cent when the range of variation of HPL levels was within 20 per cent for 3 weeks before delivery. On the contrary, the incidence of fetal distress increased to 29.4 per cent when infants were delivered after decreasing of HPL levels to less than 80 per cent of the highest HPL levels. It was also demonstrated that single determinations of HPL levels were not clinically useful in predicting fetal distress or fetal growth retardation.

  12. Providing the Scientific Backbone for Positive Psychology: A Multi-Level Conception of Human Thriving

    Directory of Open Access Journals (Sweden)

    Kennon M. Sheldon

    2009-12-01

    Full Text Available This article begins with a consideration of what is missing in positive psychology – namely, an integrative framework within which to view the entire person, especially as nested within more-or-less supportive social contexts and cultures. Thus, I presented a multi-level hierarchical framework for considering and explaining human behavior, arguing that all levels of the framework are necessary for complete exposition. From this point of view, personality processes cannot be reduced to "mere" cognitive processes; there are trans-cognitive rules and laws operating at this higher level. I also considered a four level sub-framework within the personality level of analysis, consisting of organismic needs/characteristics, traits/dispositions, goals/intentions, and self/self-narratives. I contended that each of these spheres of the person operates via unique rules and regularities, processes that cannot be reduced to lower levels of analysis (such as biological, neurological, and cognitive levels of analysis. Finally, I described some recent research that simultaneously examines factors at multiple levels of the SLOPIC model, showing that each has influence for predicting SWB, and moreover, that all of these effects are mediated by basic need satisfaction. Hopefully this line of research will prove useful for other positive psychologists seeking "the big picture" on human flourishing.

  13. Availability verification of information for human system interface in automatic SG level control using activity diagram

    Energy Technology Data Exchange (ETDEWEB)

    Nuraslinda, Anuar; Kim, Dong Young; Kim, Jong Hyun [KEPCO International Nuclear Graduate School, Uljugun (Korea, Republic of)

    2012-10-15

    Steam Generator (SG) level control system in OPR 1000 is one of representative automatic systems that falls under the Supervisory Control level in Endsley's taxonomy. Supervisory control of automated systems is classified as a form of out of the loop (OOTL) performance due to passive involvement in the systems operation, which could lead to loss of situation awareness (SA). There was a reported event, which was caused by inadequate human automation communication that contributed to an unexpected reactor trip in July 2005. A high SG level trip occurred in Yeonggwang (YGN) Unit 6 Nuclear Power Plant (NPP) due to human operator failure to recognize the need to change the control mode of the economizer valve controller (EVC) to manual mode during swap over (the transition from low power mode to high power mode) after the loss of offsite power (LOOP) event was recovered. This paper models the human system interaction in NPP SG level control system using Unified Modeling Language (UML) Activity Diagram. Then, it identifies the missing information for operators in the OPR1000 Main Control Room (MCR) and suggests some means of improving the human system interaction.

  14. Is There a Relationship between Improving Human Relation Skills and Levels of Academic Performance?

    Science.gov (United States)

    Burns, Jolene; Byrne, Susan; Kiedaisch, Jan; Thiele, Nancy; Weber, Gwyn

    This Action Research Project implemented a program for improving human relation skills intended to raise the academic performance level of students. The target population consists of kindergarten, seventh grade (regular/at-risk), and high school (regular/behavior disordered) students. Analysis of both research literature and problem evidence…

  15. Human perception of the conservation and biodiversity state of forest remnants under different levels of urbanization

    Directory of Open Access Journals (Sweden)

    Thallita Oliveira de Grande

    2016-07-01

    Full Text Available Human perception of local environmental biodiversity and conservation may provide another dimension to understanding the ecology of urban ecosystems. This perception can vary according to the environmental urbanization level and may contribute towards its conservation. We investigated the relationship between the human perception of the conservation and state of animal richness in urban remnants and level of landscape urbanization, and between the human perception of animal richness and the remnants’ area. In addition, we tested the effectiveness of interviews as the means for evaluating animal richness. The subjects' perception of the conservation of remnants did not correlate with the level of urbanization. Richness was reported as high and varied with the remnant’s area - indicating maintenance of a possible species-area relationship in the studied landscape - but did not correlate with the level of urbanization. Urbanization can standardize the popular knowledge about conservation. Interviews with local residents proved to bring efficient insights into urban animal richness, especially for primates, and can be supplemented by camera-trapping. Human perception, obtained through interviews, is relevant and useful for the description of ecological aspects of urban regions and supports environmental awareness, actions, research projects, and management for conservation purposes.

  16. Water distribution and related morphology in human stratum corneum at different hydration levels

    NARCIS (Netherlands)

    Bouwstra, J.A.; Graaff, de A.; Gooris, G.S.; Nijsse, J.; Wiechers, J.W.; Aelst, van A.C.

    2003-01-01

    This study focused on the water distribution in human stratum corneum and on the swelling of the corneocytes. For this purpose stratum corneum was hydrated to various levels and used either for Fourier transform infrared spectroscopy or for cryo-scanning electron microscopy. The images were analyzed

  17. Vitamin D status is not associated with inflammatory cytokine levels during experimental human endotoxaemia

    NARCIS (Netherlands)

    Kox, M.; Berg, M.J. van den; Hoeven, J.G. van der; Wielders, J.P.; Ven, A.J.A.M. van der; Pickkers, P.

    2013-01-01

    Vitamin D has been shown to modulate innate immune responses in vitro and ex vivo; however, human in-vivo data are lacking. At high latitudes, seasonal vitamin D deficiency is common due to alternating ultraviolet (UV)-B radiation exposure. In the present study, we investigated whether levels of 25

  18. GALNT2 effect on HDL-cholesterol and triglycerides levels in humans: Evidence of pleiotropy?

    Science.gov (United States)

    Di Paola, R; Marucci, A; Trischitta, V

    2017-04-01

    A wide range of studies both in humans and animal models point GALNT2 as a shaper of serum HDL-C and TG levels. Available data in humans indicate that, while under conditions of extreme GALNT2 loss-of-function HDL-C is the main target, a fine-tuning of GALNT2 changes is mostly associated with TG levels. Understanding whether different degrees of GALNT2 change do modulate different serum lipid fractions and, if so, addressing the mechanisms underlying such pleiotropic effects has the potential not only to improve our understanding of HDL-C and TG metabolism, but also to make GALNT2 becoming a target for treating atherogenic dyslipidemia and related clinical events. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  19. Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans

    DEFF Research Database (Denmark)

    Snyder, Eric M; Carr, Richard D; Deacon, Carolyn F

    2008-01-01

    Altitude exposure has been associated with loss of appetite and weight loss in healthy humans; however, the endocrine factors that contribute to these changes remain unclear. Leptin and glucagon-like peptide-1 (GLP-1) are peptide hormones that contribute to the regulation of appetite. Leptin...... increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure...... to normobaric hypoxia (fraction of inspired oxygen of 12.5%, simulating approximately 4100 m). Plasma leptin was assessed before the meal, and GLP-1 was assessed premeal, at 20 min postmeal, and at 40 min postmeal. We found that hypoxia caused a significant elevation in plasma leptin levels (normoxia, 4.9 +/- 0...

  20. Increased levels of IgG antibodies against human HSP60 in patients with spondyloarthritis.

    Directory of Open Access Journals (Sweden)

    Astrid Hjelholt

    Full Text Available Spondyloarthritis (SpA comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA-B27. A triggering bacterial infection has been considered as the cause of SpA, and bacterial heat shock protein (HSP seems to be a strong T cell antigen. Since bacterial and human HSP60, also named HSPD1, are highly homologous, cross-reactivity has been suggested in disease initiation. In this study, levels of antibodies against bacterial and human HSP60 were analysed in SpA patients and healthy controls, and the association between such antibodies and disease severity in relation to HLA-B27 was evaluated.Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA for immunoglobulin (IgG1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from Chlamydia trachomatis, Salmonella enteritidis and Campylobacter jejuni. Disease severity was assessed by the clinical scorings Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI and Bath Ankylosing Spondylitis Metrology Index (BASMI. Levels of IgG1 and IgG3 antibodies against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27⁺ patients. Only weak correlation between antibodies against bacterial and human HSP60 was seen, and there was no indication of cross-reaction. These results suggest that antibodies against human HSP60 is associated with SpA, however, the theory that antibodies against human HSP60 is a specific part of the aetiology, through cross-reaction to bacterial HSP60, cannot be supported by results from this study. We suggest that the association between elevated levels of antibodies against human HSP60 and disease may reflect a general activation of the immune system and an increased

  1. Human cognitive and perceptual factors in JDL level 4 hard/soft data fusion

    Science.gov (United States)

    Rimland, Jeffrey C.; Hall, David L.; Graham, Jacob L.

    2012-06-01

    Utilization of human participants as "soft sensors" is becoming increasingly important for gathering information related to a wide range of phenomena including natural and man-made disasters, environmental changes over time, crime prevention, and other roles of the "citizen scientist." The ubiquity of advanced mobile devices is facilitating the role of humans as "hybrid sensor platforms", allowing them to gather data (e.g. video, still images, GPS coordinates), annotate it based on their intuitive human understanding, and upload it using existing infrastructure and social networks. However, this new paradigm presents many challenges related to source characterization, effective tasking, and utilization of massive quantities of physical sensor, human-based, and hybrid hard/soft data in a manner that facilitates decision making instead of simply amplifying information overload. In the Joint Directors of Laboratories (JDL) data fusion process model, "level 4" fusion is a meta-process that attempts to improve performance of the entire fusion system through effective source utilization. While there are well-defined approaches for tasking and categorizing physical sensors, these methods fall short when attempting to effectively utilize a hybrid group of physical sensors and human observers. While physical sensor characterization can rely on statistical models of performance (e.g. accuracy, reliability, specificity, etc.) under given conditions, "soft" sensors add the additional challenges of characterizing human performance, tasking without inducing bias, and effectively balancing strengths and weaknesses of both human and physical sensors. This paper addresses the challenges of the evolving human-centric fusion paradigm and presents cognitive, perceptual, and other human factors that help to understand, categorize, and augment the roles and capabilities of humans as observers in hybrid systems.

  2. Human cytomegalovirus infection leads to elevated levels of transplant arteriosclerosis in a humanized mouse aortic xenograft model.

    Science.gov (United States)

    Abele-Ohl, S; Leis, M; Wollin, M; Mahmoudian, S; Hoffmann, J; Müller, R; Heim, C; Spriewald, B M; Weyand, M; Stamminger, T; Ensminger, S M

    2012-07-01

    Recent findings emphasized an important role of human cytomegalovirus (HCMV) infection in the development of transplant arteriosclerosis. Therefore, the aim of this study was to develop a human peripheral blood lymphocyte (hu-PBL)/Rag-2(-/-) γc(-/-) mouse-xenograft-model to investigate both immunological as well as viral effector mechanisms in the progression of transplant arteriosclerosis. For this, sidebranches from the internal mammary artery were recovered during coronary artery bypass graft surgery, tissue-typed and infected with HCMV. Then, size-matched sidebranches were implanted into the infrarenal aorta of Rag-2(-/-) γc(-/-) mice. The animals were reconstituted with human peripheral blood mononuclear cells (PBMCs) 7 days after transplantation. HCMV-infection was confirmed by Taqman-PCR and immunofluorescence analyses. Arterial grafts were analyzed by histology on day 40 after transplantation. PBMC-reconstituted Rag-2(-/-) γc(-/-) animals showed splenic chimerism levels ranging from 1-16% human cells. After reconstitution, Rag-2(-/-) γc(-/-) mice developed human leukocyte infiltrates in their grafts and vascular lesions that were significantly elevated after infection. Cellular infiltration revealed significantly increased ICAM-1 and PDGF-R-β expression after HCMV-infection of the graft. Arterial grafts from unreconstituted Rag-2(-/-) γc(-/-) recipients showed no vascular lesions. These data demonstrate a causative relationship between HCMV-infection as an isolated risk factor and the development of transplant-arteriosclerosis in a humanized mouse arterial-transplant-model possibly by elevated ICAM-1 and PDGF-R-β expression.

  3. A Comparison of Artificial Subtle Expressions with Human-like Expressions on Expressing Confidence Level

    Science.gov (United States)

    Komatsu, Takanori; Kobayashi, Kazuki; Yamada, Seiji; Funakoshi, Kotaro; Nakano, Mikio

    Expressing the confidence level of a system's suggestions by using speech sounds is an important cue to users of the system for perceiving how likely it is for the suggestions to be correct. We assume that expressing confidence levels by using human-like expressions would cause users to have a poorer impression of the systems than if artificial subtle expressions (ASEs) were used when the quality of the presented information does not match the expressed confidence level. We confirmed that this assumption was correct by conducting a psychological experiment.

  4. A global view on cancer incidence and national levels of the human development index.

    Science.gov (United States)

    Fidler, Miranda M; Soerjomataram, Isabelle; Bray, Freddie

    2016-12-01

    Socioeconomic factors are associated with cancer incidence through complex and variable pathways. We assessed cancer incidence for all cancers combined and 27 major types according to national human development levels. Using GLOBOCAN data for 184 countries, age-standardized incidence rates (ASRs) were assessed by four levels (low, medium, high, very high) of the Human Development Index (HDI), a composite index of life expectancy, education, and gross national income. A strong positive relationship between overall cancer incidence and HDI level was observed. When comparing the ASR in very high HDI regions with that in low HDI regions, we observed a positive association ranging from 2 to 14 and 2 to 11 times higher in males and females, respectively, depending on the cancer type. Positive dose-response relationships between the ASR and HDI level were observed in both sexes for the following cancer types: lung, pancreas, leukemia, gallbladder, colorectum, brain/nervous system, kidney, multiple myeloma, and thyroid. Positive associations were also observed for testicular, bladder, lip/oral cavity, and other pharyngeal cancers, Hodgkin lymphoma, and melanoma of the skin in males, and corpus uteri, breast, and ovarian cancers and non-Hodgkin lymphoma in females. A negative dose-response relationship was observed for cervical and other pharyngeal cancers and Kaposi sarcoma in females. Although the relationship between incidence and the HDI remained when assessed at the country-specific level, variations in risk within HDI levels were also observed. We highlight positive and negative associations between incidence and human development for most cancers, which will aid the planning of cancer control priorities among countries undergoing human development transitions. © 2016 UICC.

  5. Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets.

    Science.gov (United States)

    Kanatsuna, Norio; Taneera, Jalal; Vaziri-Sani, Fariba; Wierup, Nils; Larsson, Helena Elding; Delli, Ahmed; Skärstrand, Hanna; Balhuizen, Alexander; Bennet, Hedvig; Steiner, Donald F; Törn, Carina; Fex, Malin; Lernmark, Åke

    2013-10-04

    Insulin is a major autoantigen in islet autoimmunity and progression to type 1 diabetes. It has been suggested that the insulin B-chain may be critical to insulin autoimmunity in type 1 diabetes. INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain, and eight amino acids of the C-peptide in addition to 138 amino acids from the IGF2 gene. We aimed to determine the expression of INS-IGF2 in human pancreatic islets and autoantibodies in newly diagnosed children with type 1 diabetes and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared with donors with either type 2 diabetes (p = 0.006) or high HbA1c levels (p INS-IGF2 autoantibody levels were increased in newly diagnosed patients with type 1 diabetes (n = 304) compared with healthy controls (n = 355; p INS-IGF2 revealed that more patients than controls had doubly reactive insulin-INS-IGF2 autoantibodies. These data suggest that INS-IGF2, which contains the preproinsulin signal peptide, the B-chain, and eight amino acids of the C-peptide may be an autoantigen in type 1 diabetes. INS-IGF2 and insulin may share autoantibody-binding sites, thus complicating the notion that insulin is the primary autoantigen in type 1 diabetes.

  6. Correlation between human placental lactogen levels and glucose metabolism in pregnant women with intrauterine growth retardation.

    Science.gov (United States)

    Bagga, R; Vasishta, K; Majumdar, S; Garg, S K

    1990-11-01

    Twenty pregnant women with fetal growth retardation and 20 pregnant women with appropriate for gestational age fetuses (controls) were recruited after the 28th week of gestation. Samples were collected for estimation of serum insulin and human placental lactogen (HPL) levels in the fasting state and a glucose tolerance test was carried out on all the subjects. The results showed the glucose and HPL levels to be significantly lower in the fetal growth retardation group compared to controls. There were no differences in the fasting serum insulin levels in the 2 groups. Fetal growth retardation appears to be linked with the absence of development of the physiological 'diabetogenic' state in the second half of pregnancy. This maternal hypoglycaemic state is associated with low HPL levels and not with raised maternal insulin levels as measured in the fasting state.

  7. Energy-Efficient Crowdsensing of Human Mobility and Signal Levels in Cellular Networks.

    Science.gov (United States)

    Foremski, Paweł; Gorawski, Michał; Grochla, Krzysztof; Polys, Konrad

    2015-09-02

    The paper presents a practical application of the crowdsensing idea to measure human mobility and signal coverage in cellular networks. Currently, virtually everyone is carrying a mobile phone, which may be used as a sensor to gather research data by measuring, e.g., human mobility and radio signal levels. However, many users are unwilling to participate in crowdsensing experiments. This work begins with the analysis of the barriers for engaging people in crowdsensing. A survey showed that people who agree to participate in crowdsensing expect a minimum impact on their battery lifetime and phone usage habits. To address these requirements, this paper proposes an application for measuring the location and signal strength data based on energy-efficient GPS tracking, which allows one to perform the measurements of human mobility and radio signal levels with minimum energy utilization and without any engagement of the user. The method described combines measurements from the accelerometer with effective management of the GPS to monitor the user mobility with the decrease in battery lifetime by approximately 20%. To show the applicability of the proposed platform, the sample results of signal level distribution and coverage maps gathered for an LTE network and representing human mobility are shown.

  8. Behaviors of extreme water level in the Pearl River Delta and possible impacts from human activities

    Directory of Open Access Journals (Sweden)

    Y. D. Chen

    2007-12-01

    Full Text Available Trends and variations of the extreme water levels defined as exceeding/falling below certain thresholds (mean ± std across the Pearl River Delta (PRD are systematically explored using the linear regression method. Research results indicate that: 1 The upper PRD is dominated by the significant decreasing low water level, and significant increasing low water level can be identified in the lower PRD. The variations of the relative frequency of the high water level are characterized by the decreasing variability in the middle PRD. However more stations show significant changes of the relative frequency of the low water level across the PRD. No confirmative changing patterns of the relative frequency of the low water level can be detected in the middle PRD; 2 When it comes to the seasonal variations of the high/low water level in JJA (high flow periods in the PRD, stations located closer to the estuary tend to exhibit increasing high/low water level. However stations located closer to the upper PRD tend to show decreasing high/low water level. Similar patterns can be identified in the high/low water level in DJF (low flow periods in the PRD; 3 The changes of the water level in the PRD are heavily affected by human interferences, e.g. in-channel dredging, sand mining and the construction of levees. The stations dominated by decreasing water level are mostly located along the river channels featured by highly-intensive dredging. The stations along the coastal regions show significant increasing extreme high/low water level. The coastal regions are not influenced by in-channel dredging, and furthermore, sediment loads from upper and middle PRD are deposited in the river mouths and which will tend to raise the water level in the estuary of the PRD. The findings of this paper may be helpful for local water resource management.

  9. Determination of phthalic acid diesters in human milk at low ppb levels.

    Science.gov (United States)

    Zimmermann, Simone; Gruber, Ludwig; Schlummer, Martin; Smolic, Sonja; Fromme, Hermann

    2012-01-01

    Phthalic acid diesters (PAE) are omnipresent in the human environment and food is a major contributor to the overall human exposure towards these chemicals. Due to developmental effects, PAE infants' exposure via human milk has been subjected to a number of analytical studies. These previous studies, however, revealed that normal laboratory blank values are in the range of or even higher than human milk levels due to the presence of PAE in laboratory environments. In order to provide more reliable data on PAE exposure via human milk, the aim of this study was to develop and validate a robust and sensitive analytical method. This should be capable of removing matrix components efficiently and guarantee limits of quantification in the low ppb range. The method development took into account liquid-liquid extraction and selective pressurised fluid extraction (sPFE) as well as chromatography-based clean-up steps. The final method consisted of a liquid-liquid extraction followed by an automated chromatographic clean-up by an sPFE device. After volume reduction the cleaned extracts were analysed by quadrupole GC/MS. Quantification was based on internal standards. An extensive quality assurance and method test programme demonstrated conservatively determined limits of detection and quantification from 0.3 to 10 ng g⁻¹ in human milk, with recoveries of internal standards from 50% to 101%. Thus, the method allowed the quality-assured detection of di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), di-allyl phthalate (DAP), benzylbutyl phthalate (BBP) and di-cyclohexyl phthalate (DcHP) in 30 human milk samples provided by 30 volunteers from southern Germany. DiBP, DBP and DEHP were the most commonly detected PAE, with median levels of 1.0, 0.6 and 2.3 ng g⁻¹, respectively.

  10. Production of Cloned Miniature Pigs Expressing High Levels of Human Apolipoprotein(a in Plasma.

    Directory of Open Access Journals (Sweden)

    Masayuki Ozawa

    Full Text Available High lipoprotein(a [Lp(a] levels are a major risk factor for the development of atherosclerosis. However, because apolipoprotein(a [apo(a], the unique component of Lp(a, is found only in primates and humans, the study of human Lp(a has been hampered due to the lack of appropriate animal models. Using somatic cell nuclear transfer (SCNT techniques, we produced transgenic miniature pigs expressing human apo(a in the plasma. First, we placed the hemagglutinin (HA-tagged cDNA of human apo(a under the control of the β-actin promoter and cytomegalovirus enhancer, and then introduced this construct into kidney epithelial cells. Immunostaining of cells with anti-HA antibody allowed identification of cells stably expressing apo(a; one of the positive clones was used to provide donor cells for SCNT, yielding blastocysts that expressed apo(a. Immunohistochemical analysis of tissue sections and RT-PCR analysis of total RNA from organs of cloned piglet revealed that apo(a is expressed in various tissues/organs including heart, liver, kidney, and intestine. More importantly, a transgenic line exhibited a high level (>400 mg/dL of Lp(a in plasma, and the transgenic apo(a gene was transmitted to the offspring. Thus, we generated a human apo(a-transgenic miniature pig that can be used as a model system to study advanced atherosclerosis related to human disease. The anatomical and physiological similarities between the swine and human cardiovascular systems will make this pig model a valuable source of information on the role of apo(a in the formation of atherosclerosis, as well as the mechanisms underlying vascular health and disease.

  11. Dynamic Landscapes and Sea Level Change in Human Evolution and Dispersal

    Science.gov (United States)

    King, G. C.; Devès, M. H.; Bailey, G.; Inglis, R.; Williams, M.

    2012-12-01

    Archaeological studies of human settlement in its wider landscape setting usually focus on climate change as the principal environmental driver of change in the physical features of the landscape, even on the long time scales of early human evolution. We emphasize that landscapes evolve dynamically due to an interplay of processes occurring over different timescales. Tectonic deformation, volcanism, sea level changes, by acting on the topography, the lithology and on the patterns of erosion-deposition in a given area, can moderate or amplify the influence of climate at the regional and local scale. These processes impose or alleviate physical barriers to movement, and modify the distribution and accessibility of plant and animal resources in ways critical to human ecological and evolutionary success (King and Bailey, JHE 2006; Bailey and King, Antiquity 2011). The DISPERSE project, an ERC-funded collaboration between the University of York and the Institut de Physique du Globe de Paris,are developing systematic methods for reconstructing landscapes associated with active tectonics, volcanism and sea level change at a variety of scales in order to study their potential impact on patterns of human evolution and dispersal. These approaches use remote sensing techniques combined with archaeological and tectonic field surveys on land and underwater. Examples are shown from Europe, the Middle East and Africa to illustrate the ways in which changes of significance to human settlement can occur at a range of geographical scales and on time scales that range from lifetimes to tens of millennia, creating and sustaining attractive conditions for human settlement and exercising powerful selective pressures on human development.

  12. Increased Levels of IgG Antibodies against Human HSP60 in Patients with Spondyloarthritis

    DEFF Research Database (Denmark)

    Nielsen, Astrid Hjelholt; Carlsen, Thomas; Deleuran, Bent

    2013-01-01

    severity in relation to HLA-B27 was evaluated.Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from Chlamydia trachomatis, Salmonella enteritidis...... and Campylobacter jejuni. Disease severity was assessed by the clinical scorings Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI). Levels of IgG1 and IgG3 antibodies against human HSP60...

  13. 血清C肽与糖化血红蛋白联合检测在糖尿病诊断中的临床价值%Clinical Value of Combined Detection of Serum C-peptide and Glycosylated Hemoglobin in the Diagnosis of Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    陈思

    2015-01-01

    目的:探讨血清C肽与糖化血红蛋白联合(HbAlc)检测在糖尿病诊断中的临床价值。方法选取该院2012年3月-2013年8月60例糖尿病患者,其中糖尿病组为单纯2型糖尿病患者(40例),糖尿病肾病组为糖尿病肾病患者(20例),并选取同时期健康体检者15例为对照组,检测各组HbA1c、空腹血糖(FBG)、餐后2 h血糖、血清C肽等指标变化。结果糖尿病组、糖尿病肾病组患者血清HbA1c、FBG、餐后2 h血糖对比对照组均明显上升,血清C肽水平明显降低,差异有统计学意义(P0.05);糖尿病肾病组HbA1C水平显著高于糖尿病组,血清C肽水平显著低于对照组(P0.05); the level of HbA1C of the diabetic nephropathy group was much higher than that of the diabetes group, while that of serum C-peptide was significantly lower than that of the control group (P<0.05). HbAlc was positively correlated with FBG, but was negatively correlated with C-peptide. Conclusion The combined detection of serum C-peptide and glycosylated hemoglobin has an important value in the diagnosis of diabetic patients, therefore it is worthy of clinical application.

  14. Human impacts on tides overwhelm the effect of sea level rise on extreme water levels in the Rhine–Meuse delta

    NARCIS (Netherlands)

    Vellinga, N.E.; Hoitink, A.J.F.; Vegt, van der M.; Zhang, W.; Hoekstra, P.

    2014-01-01

    With the aim to link tidal and subtidal water level changes to human interventions, 70 years of water level data for the Rhine–Meuse tidal river network is analysed using a variety of statistical methods. Using a novel parameterization of probability density functions, mean high and low water levels

  15. Human impacts on tides overwhelm the effect of sea level rise on extreme water levels in the Rhine-Meuse delta

    NARCIS (Netherlands)

    Vellinga, N. E.; Hoitink, A. J F; van der Vegt, M.; Zhang, W.; Hoekstra, P.

    2014-01-01

    With the aim to link tidal and subtidal water level changes to human interventions, 70. years of water level data for the Rhine-Meuse tidal river network is analysed using a variety of statistical methods. Using a novel parameterization of probability density functions, mean high and low water level

  16. [Levels of carcinogenic, polycyclic aromatic hydrocarbons in human and animal tissues. IIIrd communication (author's transl)].

    Science.gov (United States)

    Gräf, W; Eff, H; Schormair, S

    1975-10-01

    (1) The mean content in benzypyrene (bp) of human pulmonary tissue amounts to 0.2 mug./100 g. of dry substance. As in all other organ tissues, however, the content differs with the age of the individual: in infants, we find maximum concentrations, in the medium age groups the levels decline and rise once more with increasing age. (2) No increase in the 3,4-benzpyrene levels (average: 0.2 mug./100 g. of dry substance) will be found in tissues with high cellular proliferative activity, such as exocrine and endocrine glands (pancreas, testicles, thyroid gland, adrenals, mammary glands, as well as bone marrow). (3) In human adipose tissue, as well as in that of pork and beef, the 3,4-benzpyrene levels are found to be exceedingly low. With values of 0.1 mug./100 g, the average concentrations lie markedly below the organ tissue levels. Hence, this class of noxious substances in not stored in the adipose tissue. (4) Both in man and in animals (pig, fowl), the 3,4-benzyprene concentrations consistently exceed the average values during early postnatal life. (5) This relatively high concentration of bp in early infancy is due to exogenous factors and is not the expression of biogenous synthesis, as has been demonstrated in examinations of the environmentally influenced embryonic development of the chick. Throughout the entire development of the embryo within the hen's egg, the benzpyrene levels remain constant. Only when the chickens have been hatched out do the benzyprene levels rise significantly. Thus, the low 3,4-benzpyrene levels detected in all human and animal organ tissues prove to be the result of the interplay of exogenous environmental loading and individual capability of eliminating this substance.

  17. Traffic signatures in suspended dust at pedestrian levels in semiarid zones: Implications for human exposure

    Science.gov (United States)

    Meza-Figueroa, Diana; González-Grijalva, Belem; Del Río-Salas, Rafael; Coimbra, Rute; Ochoa-Landin, Lucas; Moreno-Rodríguez, Verónica

    2016-08-01

    Deeper knowledge on dust suspension processes along semiarid zones is critical for understanding potential impacts on human health. Hermosillo city, located in the heart of the Sonoran Desert was chosen to evaluate such impacts. A one-year survey of Total Suspended Particulate Matter (TSPM) was conducted at two different heights (pedestrian and rooftop level). The minimum values of TSPM were reported during monsoon season and winter. Maximum values showed a bimodal distribution, with major peaks associated with increase and decrease of temperature, as well as decreasing humidity. Concentrations of TSPM were significantly exceeded at pedestrian level (∼44% of analyzed days) when compared to roof level (∼18% of analyzed days). Metal concentrations of As, Pb, Cu, Sb, Be, Mg, Ni, and Co were higher at pedestrian level than at roof level. Pixel counting and interpretations based on scanning electron microscopy of dust filters showed a higher percentage of fine particulate fractions at pedestrian level. These fractions occur mainly as metal-enriched agglomerates resembling coarser particles. According to worldwide guidelines, particulate matter sampling should be conducted by monitoring particle sizes equal and inferior to PM10. However, this work suggests that such procedures may compromise risk assessment in semiarid environments, where coarse particles act as main carriers for emergent contaminants related to traffic. This effect is especially concerning at pedestrian level, leading to an underestimation of potential impacts of human exposure. This study brings forward novel aspects that are of relevance for those concerned with dust suspension processes across semiarid regions and related impact on human health.

  18. [Influence of human body target's spectral characteristics on visual range of low light level image intensifiers].

    Science.gov (United States)

    Zhang, Jun-Ju; Yang, Wen-Bin; Xu, Hui; Liu, Lei; Tao, Yuan-Yaun

    2013-11-01

    To study the effect of different human target's spectral reflective characteristic on low light level (LLL) image intensifier's distance, based on the spectral characteristics of the night-sky radiation and the spectral reflective coefficients of common clothes, we established a equation of human body target's spectral reflective distribution, and analyzed the spectral reflective characteristics of different human targets wearing the clothes of different color and different material, and from the actual detection equation of LLL image intensifier distance, discussed the detection capability of LLL image intensifier for different human target. The study shows that the effect of different human target's spectral reflective characteristic on LLL image intensifier distance is mainly reflected in the average reflectivity rho(-) and the initial contrast of the target and the background C0. Reflective coefficient and spectral reflection intensity of cotton clothes are higher than polyester clothes, and detection capability of LLL image intensifier is stronger for the human target wearing cotton clothes. Experimental results show that the LLL image intensifiers have longer visual ranges for targets who wear cotton clothes than targets who wear same color but polyester clothes, and have longer visual ranges for targets who wear light-colored clothes than targets who wear dark-colored clothes. And in the full moon illumination conditions, LLL image intensifiers are more sensitive to the clothes' material.

  19. Ontology-Based High-Level Context Inference for Human Behavior Identification

    Directory of Open Access Journals (Sweden)

    Claudia Villalonga

    2016-09-01

    Full Text Available Recent years have witnessed a huge progress in the automatic identification of individual primitives of human behavior, such as activities or locations. However, the complex nature of human behavior demands more abstract contextual information for its analysis. This work presents an ontology-based method that combines low-level primitives of behavior, namely activity, locations and emotions, unprecedented to date, to intelligently derive more meaningful high-level context information. The paper contributes with a new open ontology describing both low-level and high-level context information, as well as their relationships. Furthermore, a framework building on the developed ontology and reasoning models is presented and evaluated. The proposed method proves to be robust while identifying high-level contexts even in the event of erroneously-detected low-level contexts. Despite reasonable inference times being obtained for a relevant set of users and instances, additional work is required to scale to long-term scenarios with a large number of users.

  20. Gene-specific correlation of RNA and protein levels in human cells and tissues.

    Science.gov (United States)

    Edfors, Fredrik; Danielsson, Frida; Hallström, Björn M; Käll, Lukas; Lundberg, Emma; Pontén, Fredrik; Forsström, Björn; Uhlén, Mathias

    2016-10-20

    An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP) conversion factor independent of the tissue type is introduced, thus significantly enhancing the predictability of protein copy numbers from RNA levels. The results show that the RTP ratio varies significantly with a few hundred copies per mRNA molecule for some genes to several hundred thousands of protein copies per mRNA molecule for others. In conclusion, our data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell, thus forming an attractive link between the field of genomics and proteomics.

  1. Basal HIF-1a expression levels are not predictive for radiosensitivity of human cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Schilling, D.; Multhoff, G. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Helmholtz Center Munich, CCG - Innate Immunity in Tumor Biology, Munich (Germany). German Research Center for Environmental Health - Inst. of Pathology; Bayer, C.; Emmerich, K.; Molls, M.; Vaupel, P. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Huber, R.M. [Klinikum der Univ. Muenchen (Germany). Dept. of Pneumology

    2012-04-15

    High levels of hypoxia inducible factor (HIF)-1a in tumors are reported to be associated with tumor progression and resistance to therapy. To examine the impact of HIF-1a on radioresistance under normoxia, the sensitivity towards irradiation was measured in human tumor cell lines that differ significantly in their basal HIF-1a levels. HIF-1a levels were quantified in lysates of H1339, EPLC-272H, A549, SAS, XF354, FaDu, BHY, and CX- tumor cell lines by ELISA. Protein levels of HIF-1a, HIF-2a, carbonic anhydrase IX (CA IX), and GAPDH were assessed by Western blot analysis. Knock-down experiments were performed using HIF-1a siRNA. Clonogenic survival after irradiation was determined by the colony forming assay. According to their basal HIF-1a status, the tumor cell lines were divided into low (SAS, XF354, FaDu, A549, CX-), intermediate (EPLC-272H, BHY), and high (H1339) HIF-1a expressors. The functionality of the high basal HIF-1a expression in H1339 cells was proven by reduced CA IX expression after knocking-down HIF-1a. Linear regression analysis revealed no correlation between basal HIF-1a levels and the survival fraction at either 2 or 4 Gy in all tumor cell lines investigated. Our data suggest that basal HIF-1a levels in human tumor cell lines do not predict their radiosensitivity under normoxia. (orig.)

  2. Accumulation levels and characteristics of some pesticides in human adipose tissue samples from Southeast China.

    Science.gov (United States)

    Wang, Na; Shi, Lili; Kong, Deyang; Cai, Daoji; Cao, Yanzhong; Liu, Yongming; Pang, Guofang; Yu, Rongbin

    2011-08-01

    This paper presents a comprehensive study of pesticide levels and bio-accumulation characteristics in human adipose tissues among residents of Southeast China. A large number of adipose samples (n=633) were selected for 58 pesticides and were analyzed by high sensitive Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS). The results showed that POPs pesticides were frequently detected, including 2,4'-DDD, 2,4'-DDE, 2,4'-DDT, 4,4'-DDD, 4,4'-DDE, 4,4'-DDT, α-HCH, β-HCH, γ-HCH, δ-HCH, hexachlorobenzene (HCB), and mirex. Other detected pesticide species were dicofol, methamidophos and chlordimeform, which have rarely been reported. Comparing to different countries, the concentrations of total DDT and HCH in these three Chinese southeastern sites were in the middle range, whereas the HCB and mirex were in the lower end. A significant correlation was observed between region as well as age and POPs pesticide levels. Some pesticide residue levels were also found significantly correlated to occupation. However, there was no significant correlation between gender and pesticides. Meanwhile, it is interesting to find that mortality of malignant tumors tends to associate with the pesticides levels in human adipose tissue. More importantly, the measured data presented in this study provide realistic information which is useful for assessing human exposure to pesticides in the general population of Southeast China. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Inverse relation between FASN expression in human adipose tissue and the insulin resistance level

    Directory of Open Access Journals (Sweden)

    Bernal Rosa

    2010-01-01

    Full Text Available Abstract Background Adipose tissue is a key regulator of energy balance playing an active role in lipid storage and may be a dynamic buffer to control fatty acid flux. Just like PPARγ, fatty acid synthesis enzymes such as FASN have been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance or dyslipemia. The aim of this work is to investigate how FASN and PPARγ expression in human adipose tissue is related to carbohydrate metabolism dysfunction and obesity. Methods The study included eighty-seven patients which were classified according to their BMI and to their glycaemia levels in order to study FASN and PPARγ gene expression levels, anthropometric and biochemical variables. Results The main result of this work is the close relation between FASN expression level and the factors that lead to hyperglycemic state (increased values of glucose levels, HOMA-IR, HbA1c, BMI and triglycerides. The correlation of the enzyme with these parameters is inversely proportional. On the other hand, PPARγ is not related to carbohydrate metabolism. Conclusions We can demonstrate that FASN expression is a good candidate to study the pathophysiology of type II diabetes and obesity in humans.

  4. Human fetal islet transplantation in type 1 diabetic patients: comparison of metabolic effects between single and multiple implantation regimens.

    Science.gov (United States)

    Djordjevic, P B; Lalic, N M; Jotic, A; Paunovic, I; Lalic, K; Raketic, N; Nikolic, D; Zamaklar, M; Rajkovic, N; Lukic, L; Dimitrijevic-Sreckovic, V; Dragasevic, M; Nikolic, D; Markovic, I

    2004-11-01

    Previous studies suggest that multiple transplantations might be equally efficient to a single regimen for human adult islets. The aim of this study was to compare metabolic parameters after each of the two regimens of human fetal islet (HFI) transplantation in type 1 diabetics. In group A (single transplant, n = 9), 180 +/- 20 x 1000 HFI equivalents (IEQs) were implanted by a single IM injection; in group B (multiple transplants, n = 8) islets were implanted as three consecutive injections (60 +/- 10 x 1000 IEQs) at 7-day intervals. We analyzed the metabolic parameters on days -1, 30, 60, 90, 120, 150, and 180 after the procedure. Among the metabolic parameters, we evaluated insulin secretion capacity-ISC (C peptide, RIA), metabolic control (HbA1c, chromatography), and insulin daily dose IDD. We found that C peptide levels increased, peaking on day 90 (A: 0.38 +/- 0.15; B: 0.34 +/- 0.19 nmol/L, P = NS) and then rapidly decreasing without differences, the HbA1c levels and IDD decreased in the same manner without differences between the groups. Our results demonstrate that multiple and single islet transplant regimens are equally efficient to temporarily restore a significant ISC with improvement of metabolic and clinical parameters. The results imply that the two regimens have an equal clinical value.

  5. Increasing ascorbate levels in crops to enhance human nutrition and plant abiotic stress tolerance.

    Science.gov (United States)

    Macknight, Richard C; Laing, William A; Bulley, Sean M; Broad, Ronan C; Johnson, Alexander At; Hellens, Roger P

    2017-02-20

    Ascorbate (or vitamin C) is an essential human micronutrient predominantly obtained from plants. In addition to preventing scurvy, it is now known to have broader roles in human health, for example as a cofactor for enzymes involved in epigenetic programming and as regulator of cellular iron uptake. Furthermore, ascorbate is the major antioxidant in plants and underpins many environmentally induced abiotic stress responses. Biotechnological approaches to enhance the ascorbate content of crops therefore have potential to improve both human health and abiotic stress tolerance of crops. Identifying the genetic basis of ascorbate variation between plant varieties and discovering how some 'super fruits' accumulate extremely high levels of ascorbate should reveal new ways to more effectively manipulate the production of ascorbate in crops.

  6. Human internal and external exposure to PBDEs - A review of levels and sources

    DEFF Research Database (Denmark)

    Frederiksen, Marie; Vorkamp, Katrin; Thomsen, Marianne

    2009-01-01

    ingest more dust than adults. Infants are also exposed to PBDEs via breast milk. Internal human exposure has generally been found to be one order of magnitude larger in North America than in Europe and Asia. These differences cannot solely be explained by the dietary intake as meat products are the only......This paper reviews the existing literature on human exposure to polybrominated diphenyl ethers (PBDEs), with particular focus on external exposure routes (e.g. dust, diet, and air) and the resulting internal exposure to PBDEs (e.g. breast milk and blood). Being lipophilic and persistent organic...... compounds, PBDEs accumulate in lipid-rich tissues. Consequently, food items like fish from high trophic levels or lipid-rich oils have been found to contain relatively high concentrations of PBDEs, thus presenting an important exposure pathway to humans. The presence of PBDEs in various products of everyday...

  7. Impact assessment of climate change and human activities on annual highest water level of Taihu Lake

    Institute of Scientific and Technical Information of China (English)

    Qing-fang HU; Yin-tang WANG

    2009-01-01

    The annual highest water level of Taihu Lake (Zm) is very significant for flood management in the Taihu Basin. This paper first describes the inter-annual and intra-annual traits of Zm from 1956 to 2000. Then, using the Mann-Kenall (MK) and Spearman (SP) nonparametric tests, the long-term change trends of area precipitation and pan evaporation in the Taihu Basin are determined. Meanwhile, using the Morlet wavelet transformation, the fluctuation patterns and change points of precipitation and pan evaporation are analyzed. Also, human activities in the Taihu Basin are described, including land use change and hydraulic project construction. Finally, the relationship between Zm, the water level of Taihu Lake 30 days prior to the day of Zm (Z0), and the 30-day total precipitation and pan evaporation prior to the day of Zm (P and E0, respectively) is described based on multi-linear regression equations. The relative influence of climate change and human activities on the change of Zm is quantitatively ascertained. The results demonstrate that: (1) Zm was distinctly higher during the 1980-2000 period than during the 1956-1979 period, and the 30 days prior to the day of Zm are the key phase influencing Zm every year; (2) P increased significantly at a confidence level of 95% during the 1956-2000 period, while the reverse was true for E0; (3) The relationship between Zm, P and E0 distinctly changed after 1980; (4) Climate change and human activities together caused frequent occurrences of high Zm after 1980; (5) Climate change caused a substantially greater Zm difference between the 1956-1979 and 1980-2000 periods than human activities. Climate change, as represented by P and E0, was the dominant factor raising Zm, with a relative influence ratio of 83.6%, while human activities had a smaller influence ratio of 16.4%.

  8. Using the Pyramid of Neurological Levels in the Human Resources Motivation Management

    Directory of Open Access Journals (Sweden)

    Antonio SANDU

    2016-12-01

    Full Text Available Staff motivation is a great responsibility of the managers, most of the times making the difference between the performant, and the less performant ones. The article aims to present a possible theoretical model of using the Pyramid of Neurological Levels formulated by Dilts in the construction of the intrinsic motivation of human resource in the postmodern organisations. The Pyramid of Neurological Levels is an extension to the pyramid of needs, being structured by Dilts on the following levels: environment, behaviour and language, abilities, competences and talent, beliefs and values, identity, belonging and spirituality, mission and supreme goal. Each of these levels was attached to a series of motivational practices, more or less used in postmodern organizations.

  9. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Science.gov (United States)

    Sano, Akiko; Matsushita, Hiroaki; Wu, Hua; Jiao, Jin-An; Kasinathan, Poothappillai; Sullivan, Eddie J; Wang, Zhongde; Kuroiwa, Yoshimi

    2013-01-01

    Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.

  10. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  11. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of Justice, Shanghai 200063 (China); Liu, Siwen [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Bode, Liv [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Liu, Chengyu [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Zhang, Liang [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Wang, Xiao [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Li, Dan [Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing 400016 (China); Lei, Yang [Department of Internal Medicine, University-Town Hospital of Chongqing Medical University, Chongqing 400016 (China); Peng, Xiaojun [Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou 310018 (China); Cheng, Zhongyi [Advanced Institute of Translational Medicine, Tongji University, Shanghai 200092 (China); and others

    2015-11-15

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  12. Influence of ritodrine on plasma steroids and human placental lactogen levels in third-trimester pregnancies.

    Science.gov (United States)

    Schreyer, P; Zer, Y; Ariely, S; Herman, A; Caspi, E

    1989-01-01

    The effects of ritodrine, administered by intravenous, intramuscular or per os routes, upon plasma levels of unconjugated estriol, estradiol, progesterone and human placental lactogen (HPL) were investigated in 24 third-trimester pregnancies. Ritodrine administered at a constant rate of 200 micrograms/min for 3 h, injected intramuscularly 8 x 10 mg/day for 5 days or given orally in doses of 6 x 20 mg/day for 10 days resulted in a significant decrease in the steroid hormone concentration and a significant elevation of HPL levels.

  13. Population-level impact, herd immunity, and elimination after human papillomavirus vaccination

    DEFF Research Database (Denmark)

    Brisson, Marc; Bénard, Élodie; Drolet, Mélanie

    2016-01-01

    BackgroundModelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta......-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination....

  14. The relationship between levels of PCBs and pesticides in human hair and blood: preliminary result.

    Science.gov (United States)

    Altshul, Larisa; Covaci, Adrian; Hauser, Russ

    2004-08-01

    Human hair as a biologic measure of exposure to persistent organic pollutants (POPs) has some advantages over the more commonly used blood and adipose tissue samples. However, one of the primary limitations is the difficulty in distinguishing between exogenous and endogenous contamination. In addition, there are currently no standardized methods for hair sample collection, washing, and chemical analysis. There is also very limited information describing the correlation between levels of organic contaminants in hair and other body compartments. To explore levels of POPs in blood and hair, samples from 10 volunteers were collected and analyzed for select organochlorine pesticides and 57 individual polychlorinated biphenyl (PCB) congeners. We demonstrated that the method for analyzing organic contaminants in human hair was reliable and reproducible. Washing hair with shampoo decreased levels of PCBs, pesticides, and lipids by 25-33% on average and up to 62% for low-chlorinated congeners. The percentage of lipids and the levels of organochlorines in hair were higher than in serum. We found strong correlation (r = 0.8) between p,p -DDE (dichlorodiphenyldichloroethylene) levels in hair and blood and moderate correlations for the more persistent PCB congeners, but no correlations or weak correlations for other organochlorines. The present study provides preliminary evidence on the utility of hair analysis for POPs; however, further larger studies are recommended before hair analysis can be successfully applied in epidemiologic studies on POPs.

  15. Interevent time distributions of human multi-level activity in a virtual world

    Science.gov (United States)

    Mryglod, O.; Fuchs, B.; Szell, M.; Holovatch, Yu.; Thurner, S.

    2015-02-01

    Studying human behavior in virtual environments provides extraordinary opportunities for a quantitative analysis of social phenomena with levels of accuracy that approach those of the natural sciences. In this paper we use records of player activities in the massive multiplayer online game Pardus over 1238 consecutive days, and analyze dynamical features of sequences of actions of players. We build on previous work where temporal structures of human actions of the same type were quantified, and provide an empirical understanding of human actions of different types. This study of multi-level human activity can be seen as a dynamic counterpart of static multiplex network analysis. We show that the interevent time distributions of actions in the Pardus universe follow highly non-trivial distribution functions, from which we extract action-type specific characteristic 'decay constants'. We discuss characteristic features of interevent time distributions, including periodic patterns on different time scales, bursty dynamics, and various functional forms on different time scales. We comment on gender differences of players in emotional actions, and find that while males and females act similarly when performing some positive actions, females are slightly faster for negative actions. We also observe effects on the age of players: more experienced players are generally faster in making decisions about engaging in and terminating enmity and friendship, respectively.

  16. Levels of PCDDs and PCDFs in human milk from populations in Madrid and Paris

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, M.J.; Hernandez, L.M.; Jimenez, B. [Institute of Organic Chemistry, Madrid (Spain)] [and others

    1996-02-01

    Human breast milk represents a good substrate to examine the polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) background contamination of a population and also supplies important information about the exposure risk for nursing infants. Although adipose tissue and blood samples are commonly studied in the literature milk Dioxin levels are more specifically of concern because of the facility of sampling and also the potential health damage which may be caused to the breastfed babies by those highly toxic synthetic chemicals. The occurrence of dioxins in mother milk among the general population in all countries studied until now, has confirmed a widespread pollution and intake of those compounds. Dietary and other sources such as contaminated chemicals, industrial activity, waste combustion and leaded car gasoline may be responsible for such a contamination, and also for the differences among levels found in different countries. Human contamination by PCDDs and PCDFs from the environment is clearly a multisource problem. Human milk as well as other human fluids studies up to know have only found the presence of 2,3,7,8 substituted PCDD or PCDF congeners present. The reason for this congener specific retention is usually explained by the metabolic conversion on the 2,3,7, and 8 lateral positions in combination with high binding affinities for the cytosolic receptor proteins.

  17. Depth of penetration of an 850nm wavelength low level laser in human skin.

    Science.gov (United States)

    Esnouf, Alan; Wright, Philip A; Moore, Joan C; Ahmed, Salim

    2007-01-01

    Low Level Laser Therapy is used for a wide variety of conditions including superficial skin sores, musculoskeletal and joint problems, and dentistry. Knowledge of the penetration depth of laser radiation in human skin is an essential prerequisite to identifying its method of action. Mathematical simulations and estimates from the literature suggest that the depth of penetration of laser radiation using wavelengths from 630nm up to 1100nm may be up to 50mm. The aim of this study is to directly measure the penetration depth of a Low Level Laser in human tissue. Human abdominal skin samples up to 0.784mm thickness were harvested by dermatome following abdominoplasty procedures. These samples were irradiated by a Gallium Aluminium Arsenide Laser (Wavelength 850nm near infra-red invisible light, 100mW, 24kHz, 0.28mm diameter probe) and the transmitted radiation measured with an Ophir Optronics 'Nova' external energy meter. The intensity of laser radiation reduced by 66% after being transmitted through a 0.784mm sample of human abdominal tissue. In this study most laser radiation was absorbed within the first 1mm of skin.

  18. The Relationship between Levels of PCBs and Pesticides in Human Hair and Blood: Preliminary Results

    OpenAIRE

    Covaci, Adrian; Altshul, Larisa M.; Hauser, Russ B.

    2004-01-01

    Human hair as a biologic measure of exposure to persistent organic pollutants (POPs) has some advantages over the more commonly used blood and adipose tissue samples. However, one of the primary limitations is the difficulty in distinguishing between exogenous and endogenous contamination. In addition, there are currently no standardized methods for hair sample collection, washing, and chemical analysis. There is also very limited information describing the correlation between levels of organ...

  19. Does Postevacuation β -Human Chorionic Gonadotropin Level Predict the Persistent Gestational Trophoblastic Neoplasia?

    OpenAIRE

    2014-01-01

    β -human chorionic gonadotropin (HCG) level is not a reliable marker for early identification of persistent gestational trophoblastic neoplasia (GTN) after evacuation of hydatidiform mole. Thus, this study was conducted to evaluate β -HCG regression after evacuation as a predictive factor of malignant GTN in complete molar pregnancy. Methods. In this cross-sectional study, we evaluated a total of 260 patients with complete molar pregnancy. Sixteen of the 260 patients were excluded. Serum leve...

  20. Levels of contamination for various pollutants present in Belgian human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Wouwe, N. Van; Goeyens, L. [Scientific Inst. of Public Health, Brussels (Belgium); Covaci, A. [Toxicological Center, Univ. of Antwerp, Wilrijk (Belgium); Kannan, K. [Wadsworth Center, New York State Dept. of Health, Albany, NY (United States); Gordon, J.; Chu, A. [Xenobiotic Detection System Inc., Durham, NC (United States); Eppe, G.; Pauw, E. De [Center of Analysis of residues in Traces (CART), Univ. of Liege (Belgium)

    2004-09-15

    During the last century, numerous compounds, such as polychlorinated biphenyls (PCBs) or organochlorine pesticides (OCPs), were banned because of their bioaccumulative and toxic properties, while other compounds, such as polybrominated diphenyl ethers (PBDEs), appeared on the market and consequently in the environment. The experiences gained from accidents involving PBBs, PCBs or PCDD/Fs are useful to conduct scientific investigations focused on preventing similar catastrophies with the newly introduced compounds. Several studies have reported potential increase in the concentration of PBDEs in food and wildlife. Monitoring the levels of toxic chemicals is therefore useful to understand the exposure pathways, sources and trends. The aim of the paper is to present actual contamination's levels of various pollutants in human plasma from Belgium. Several classes of pollutants, such PCDD/Fs, PCBs and OCPs were determined in 20 human plasmas. In addition, perfluorooctanesulfonate (PFOS) and related fluorochemicals, which are of current concern, were measured. Although anticipated, concentrations of PBDEs in the same samples were not yet determined. Through this study, a good approximation of the contamination level in Belgian human is given, allowing thus comparison with concentrations observed in other countries.

  1. Analyses of the rate of decline in stimulated c-peptide 12 months after diagnosis in children with newly diag-nosed type 1 diabetes. results from the Hvidoere study group on childhood diabetes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise Max; Porksen, S.; Nielsen, L.B.

    2010-01-01

    Objectives: Direct measurement of C-peptide has been recommended to provide the most appropriate primary outcome in trials evaluating the efficacy of therapies to preserve beta-cell function. The aim of the present study was to quantitatively characterize the natural history of disease progression...... as assessed by stimulated C-peptide the first 12 months after diagnosis in children with new onset T1D in two independent cohorts collected over a time interval of 6 years. Furthermore the purpose was to assess whether the natural history of disease has changed over time. Materials and methods...... for both cohorts was calculated to 8.0 ± 0.7%/ month.This is in the same range as the value reported of 0.019 nmol/l/month (1982-1985) by Wallensteen corresponding to a relative change of 9.5%/month. Conclusion: Thus, the natural history of disease progression during the first 12 months after diagnosis has...

  2. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mazière, Cécile, E-mail: maziere.cecile@chu-amiens.fr [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France); Salle, Valéry [Internal Medicine, North Hospital University, Place Victor Pauchet, Amiens 80000 (France); INSERM U1088 (EA 4292), SFR CAP-Santé (FED 4231), University of Picardie – Jules Verne (France); Gomila, Cathy; Mazière, Jean-Claude [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France)

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  3. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  4. Response of the Gypsy Moth, Lymantria dispar to Transgenic Poplar, Populus simonii x P. nigra, Expressing Fusion Protein Gene of the Spider Insecticidal Peptide and Bt-toxin C-peptide

    OpenAIRE

    Cao, Chuan-Wang; Liu, Gui-Feng; Wang, Zhi-Ying; Yan, Shan-Chun; Ma, Ling; Yang, Chuan-Ping

    2010-01-01

    The response of the Asian gypsy moth Lymantria dispar (L.) (Lepidoptera: Lymantriidae) to a fusion gene consisting of the spider, Atrax robustus Simon (Araneae: Hexanthelidae) ω?-ACTX-Ar1 sequence coding for an ω?-atracotoxin and a sequence coding for the Bt-toxin C-peptide, expressed in transgenic poplar Populus simonii x P. nigra L. (Malphigiales: Salicaceae) was investigated. Individual performance, feeding selection, midgut proteinase activity and nutrition utilization were monitored. The...

  5. Increased FGF21 plasma levels in humans with sepsis and SIRS.

    Science.gov (United States)

    Gariani, Karim; Drifte, Geneviève; Dunn-Siegrist, Irène; Pugin, Jérôme; Jornayvaz, François R

    2013-01-01

    Fibroblast growth factor 21 (FGF21) is a key regulator in glucose and lipid metabolism and its plasma levels have been shown to be increased not only in humans in different situations such as type 2 diabetes, obesity, and nonalcoholic fatty liver disease but also in animal models of sepsis and pancreatitis. FGF21 is considered as a pharmacological candidate in conditions associated with insulin resistance. The aim of this study was to compare FGF21 plasma levels in patients with sepsis, in patients with systemic inflammatory response syndrome (SIRS), and in healthy controls. We measured FGF21 plasma concentrations in 22 patients with established sepsis, in 11 with SIRS, and in 12 healthy volunteers. Here, we show that FGF21 levels were significantly higher in plasma obtained from patients with sepsis and SIRS in comparison with healthy controls. Also, FGF21 levels were significantly higher in patients with sepsis than in those with noninfectious SIRS. FGF21 plasma levels measured at study entry correlated positively with the APACHE II score, but not with procalcitonin levels, nor with C-reactive protein, classical markers of sepsis. Plasma concentrations of FGF21 peaked near the onset of shock and rapidly decreased with clinical improvement. Taken together, these results indicate that circulating levels of FGF21 are increased in patients presenting with sepsis and SIRS, and suggest a role for FGF21 in inflammation. Further studies are needed to explore the potential role of FGF21 in sepsis as a potential therapeutic target.

  6. Multi-level model for 2D human motion analysis and description

    Science.gov (United States)

    Foures, Thomas; Joly, Philippe

    2003-01-01

    This paper deals with the proposition of a model for human motion analysis in a video. Its main caracteristic is to adapt itself automatically to the current resolution, the actual quality of the picture, or the level of precision required by a given application, due to its possible decomposition into several hierarchical levels. The model is region-based to address some analysis processing needs. The top level of the model is only defined with 5 ribbons, which can be cut into sub-ribbons regarding to a given (or an expected) level of details. Matching process between model and current picture consists in the comparison of extracted subject shape with a graphical rendering of the model built on the base of some computed parameters. The comparison is processed by using a chamfer matching algorithm. In our developments, we intend to realize a platform of interaction between a dancer and tools synthetizing abstract motion pictures and music in the conditions of a real-time dialogue between a human and a computer. In consequence, we use this model in a perspective of motion description instead of motion recognition: no a priori gestures are supposed to be recognized as far as no a priori application is specially targeted. The resulting description will be made following a Description Scheme compliant with the movement notation called "Labanotation".

  7. Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans

    Energy Technology Data Exchange (ETDEWEB)

    Studer-Rohr, I. [Inst. of Toxicology, Swiss Federal Inst. of Tech. and Univ. of Zurich, Schwerzenbach (Switzerland); Dept. of Food Science, Swiss Federal Inst. of Tech., Zurich (Switzerland); Schlatter, J. [Toxicology Section, Div. of Food Science, Swiss Federal Office of Public Health, Zurich (Switzerland); Dietrich, D.R. [Dept. of Environmental Toxicology, Univ. of Konstanz, Konstanz (Germany); Inst. of Toxicology, Swiss Federal Inst. of Tech. and Univ. of Zurich, Schwerzenbach (Switzerland)

    2000-11-01

    The mycotoxin ochratoxin A (OTA) is a rodent carcinogen produced by species of the ubiquitous fungal genera Aspergillus and Penicillium. OTA is found in a variety of food items and as a consequence is also found in human plasma (average concentrations found in this study: 0.1-1 ng OTA/ml plasma). To improve the scientific basis for cancer risk assessment the toxicokinetic profile of OTA was studied in one human volunteer following ingestion of 395 ng {sup 3}H-labeled OTA (3.8 {mu}Ci). A two-compartment open model consisting of a central compartment was found to best describe the in vivo data. This two-compartment model consisted of a fast elimination and distribution phase (T{sub 1/2} about 20 h) followed by a slow elimination phase (renal clearance about 0.11 ml/min.) and a calculated plasma half-life of 35.55 days. This half-life was approximately eight times longer than that determined previously in rats. In addition, the intraindividual fluctuation of OTA plasma levels was investigated in eight individuals over a period of 2 months. The concentrations determined ranged between 0.2 and 0.9 ng OTA/ml plasma. The plasma levels in some individuals remained nearly constant over time, while others varied considerably (e.g. increase of 0.4 ng/ml within 3 days, decrease of 0.3 ng/ml within 5 days) during the observation period. This intraindividual fluctuation in OTA plasma levels, which may represent differences in OTA exposure and/or metabolism, as well as the large difference in plasma half-life in humans compared to rats must be taken into consideration when the results of rat cancer study data are extrapolated to humans for risk assessment purposes. (orig.)

  8. Dexamethasone reduces cell surface levels of CD11b on human eosinophils

    Directory of Open Access Journals (Sweden)

    A. M. Das

    1997-01-01

    Full Text Available Overnight incubation of human eosinophils (Eøs with the glucocorticoid hormone dexamethasone (DEX; 0.1 μM resulted in lower expression of the CD11b, but not CD49d, antigen on their plasma membrane, as assessed by flow cytometry. DEX produced a consistent inhibitory effect (ranging from 16% to 20% when tested at a concentration of 0.1 μM. Eø stimulation with 100 ng/ml eotaxin produced an increase in CD11b (+26%, but not CD11c, levels and concomitantly a reduction (–25% on CD62L expression. The inhibition exerted by DEX upon CD11b levels was also evident following eotaxin upregulation, with a degree of inhibition similar to that seen on basal levels. These data highlight a novel mechanism of action by which glucocorticoid hormones may be effective in reducing Eø accumulation during allergic inflammation in man.

  9. [Asymmetry of the bioelectrical activity of the human brain at different levels of consciousness].

    Science.gov (United States)

    Rusalova, M N

    2006-12-01

    Asymmetry of different human EEG indices was studied at different levels of consciousness. Subjects' self-reported changes in the content of consciousness: the intensity and quality of involuntary mental processes served as indicator of the level of consciousness. It was shown that a certain profile of EEG asymmetry corresponded to each the observed level of consciousness. In active state of consciousness, the connections in the high-frequency bands: beta-2 and gamma, were more pronounced in the left hemisphere of the brain. At the same time, transition of the focus of coherent connections to the right hemisphere was characteristic of the state of inhibition of "internal speech". The interhemisphere dynamics of autospectra amplitude and foci of coherent connections supports the notion that the character of interhemisphere asymmetry of the brain bioelectrical activity depends on its functional state.

  10. Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci.

    Science.gov (United States)

    Buxton, Jessica L; Suderman, Matthew; Pappas, Jane J; Borghol, Nada; McArdle, Wendy; Blakemore, Alexandra I F; Hertzman, Clyde; Power, Christine; Szyf, Moshe; Pembrey, Marcus

    2014-05-14

    In humans, leukocyte telomere length (LTL) is positively correlated with lifespan, and shorter LTL is associated with increased risk of age-related disease. In this study we tested for association between telomere length and methylated cytosine levels. Measurements of mean telomere length and DNA methylation at >450,000 CpG sites were obtained for both blood (N = 24) and EBV-transformed cell-line (N = 36) DNA samples from men aged 44-45 years. We identified 65 gene promoters enriched for CpG sites at which methylation levels are associated with leukocyte telomere length, and 36 gene promoters enriched for CpG sites at which methylation levels are associated with telomere length in DNA from EBV-transformed cell-lines. We observed significant enrichment of positively associated methylated CpG sites in subtelomeric loci (within 4 Mb of the telomere) (P telomere length, DNA methylation and gene expression in health and disease.

  11. A survey of human brain transcriptome diversity at the single cell level.

    Science.gov (United States)

    Darmanis, Spyros; Sloan, Steven A; Zhang, Ye; Enge, Martin; Caneda, Christine; Shuer, Lawrence M; Hayden Gephart, Melanie G; Barres, Ben A; Quake, Stephen R

    2015-06-09

    The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.

  12. Mercury contamination in human hair and fish from Cambodia: levels, specific accumulation and risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Agusa, Tetsuro [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kunito, Takashi [Department of Environmental Sciences, Faculty of Science, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Iwata, Hisato [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Monirith, In [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Tana, Touch Seang [Social and Cultural Observation Unit (OBSES) of the Cabinet of the Council of Ministers, Phnom Penh (Cambodia); Subramanian, Annamalai [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)]. E-mail: shinsuke@agr.ehime-u.ac.jp

    2005-03-01

    Mercury (Hg) concentrations in human hair and fish samples from Phnom Penh, Kien Svay, Tomnup Rolork and Batrong, Cambodia, collected in November 1999 and December 2000 were determined to understand the status of contamination, and age- and sex-dependent accumulation in humans and to assess the intake of mercury via fish consumption. Mercury concentrations in human hair ranged from 0.54 to 190 {mu}g/g dry wt. About 3% of the samples contained Hg levels exceeding the no observed adverse effects level (NOAEL) of WHO (50 {mu}g/g) and the levels in some hair samples of women also exceeded the NOAEL (10 {mu}g/g) associated with fetus neurotoxicity. A weak but significant positive correlation was observed between age and Hg levels in hair of residents. Mercury concentrations in muscle of marine and freshwater fish from Cambodia ranged from <0.01 to 0.96 {mu}g/g wet wt. Mercury intake rates were estimated on the basis of the Hg content in fish and daily fish consumption. Three samples of marine fish including sharp-tooth snapper and obtuse barracuda, and one sample of sharp-tooth snapper exceeded the guidelines by US EPA and by Joint FAO/WHO Expert Committee on Food Additives (JECFA), respectively, which indicates that some fish specimens examined (9% and 3% for US EPA and JECFA guidelines, respectively) were hazardous for consumption at the ingestion rate of Cambodian people (32.6 g/day). It is suggested that fish is probably the main source of Hg for Cambodian people. However, extremely high Hg concentrations were observed in some individuals and could not be explained by Hg intake from fish consumption, indicating some other contamination sources of Hg in Cambodia. - A source other than fish may be responsible for high Hg in some Cambodians.

  13. Freezing adversely affects measurement of vascular endothelial growth factor levels in human aqueous samples

    Directory of Open Access Journals (Sweden)

    Sankarathi Balaiya

    2011-01-01

    Full Text Available Sankarathi Balaiya Sandeep Grover Ravi K Murthy Kakarla V ChalamDepartment of Ophthalmology, University of Florida College of Medicine, Jacksonville, FL, USAPurpose: Aqueous levels of vascular endothelial growth factor (VEGF can be a surrogate marker of intraocular VEGF activity and a measure of efficacy of anti-VEGF treatment in a variety of vasoproliferative retinal disorders, including diabetic retinopathy, age-related macular degeneration, and central retinal vein occlusion. Measurement of the VEGF level may be adversely affected by premeasurement variables, such as freezing and delay, in sample analysis. We aim to evaluate the effect of storage and delayed measurement of human aqueous VEGF levels in these conditions.Methods: Aqueous samples collected from patients receiving intravitreal injection of bevacizumab for various retinal diseases were divided into two groups. In Group 1, the VEGF levels were analyzed on the same day; in Group 2, the VEGF levels were analyzed after 21 days of freezer storage (-80°C using immunobead assay. Statistical comparison using a paired t-test was performed between the two groups.Results: Thirty-one aqueous humor samples were collected, and the VEGF concentration for fresh samples was 7.8 ± 5.9 pg/mL (mean ± SD compared to 6.5 ± 6.0 pg/mL in frozen samples, resulting in a statistically significant difference (P = 0.03.Conclusions: Accurate measurement of the VEGF level is a vital component of clinical decision-making. Delayed analysis of VEGF levels in aqueous samples may result in significant sample degradation and lower levels of measured VEGF.Keywords: VEGF level, aqueous humor, immunobead assay, VEGF storage

  14. Protein levels of heme oxygenase-1 during reperfusion in human kidney transplants with delayed graft function.

    Science.gov (United States)

    Ollinger, Robert; Kogler, Pamela; Biebl, Matthias; Sieb, Michael; Sucher, Robert; Bösmüller, Claudia; Troppmair, Jakob; Mark, Walter; Weiss, Helmut; Margreiter, Raimund

    2008-01-01

    Delayed graft function (DGF) as a consequence of ischemia reperfusion injury (IRI) is associated with a decrease in long-term allograft survival. Heme oxygenase-1 (HO-1) is a stress responsive gene that is highly expressed in multiple pathological processes. The aim of our study was to analyze whether HO-1 protein levels in human kidney transplants during IRI correlate with the incidence of DGF. Kidney biopsies were obtained from 27 kidney allografts at two time points: at the end of cold storage and shortly after reperfusion. Samples were analyzed for HO-1 protein levels by Western blot. Heme oxygenase-1 protein levels were significantly higher in post-reperfusion biopsies (39.4 vs. 13.7 arbitrary units, p = 0.001). In pre-reperfusion biopsies no association was observed between HO-1 protein levels and DGF. In post-reperfusion biopsies, higher levels of HO-1 protein were measured in kidneys with DGF (53.7 vs. 36.2 arbitrary units, p = 0.064). DGF kidneys showed a significantly higher increase from pre- to post-reperfusion in HO-1 protein (42.0 vs. 18.7 arbitrary units, p = 0.025). Heme oxygenase-1 protein levels shortly after allograft reperfusion are closely related with initial graft function. Assessment thereof may be considered a valuable tool to predict DGF.

  15. Entropy Generation and Human Aging: Lifespan Entropy and Effect of Physical Activity Level

    Science.gov (United States)

    Silva, Carlos; Annamalai, Kalyan

    2008-06-01

    The first and second laws of thermodynamics were applied to biochemical reactions typical of human metabolism. An open-system model was used for a human body. Energy conservation, availability and entropy balances were performed to obtain the entropy generated for the main food components. Quantitative results for entropy generation were obtained as a function of age using the databases from the U.S. Food and Nutrition Board (FNB) and Centers for Disease Control and Prevention (CDC), which provide energy requirements and food intake composition as a function of age, weight and stature. Numerical integration was performed through human lifespan for different levels of physical activity. Results were presented and analyzed. Entropy generated over the lifespan of average individuals (natural death) was found to be 11,404 kJ/ºK per kg of body mass with a rate of generation three times higher on infants than on the elderly. The entropy generated predicts a life span of 73.78 and 81.61 years for the average U.S. male and female individuals respectively, which are values that closely match the average lifespan from statistics (74.63 and 80.36 years). From the analysis of the effect of different activity levels, it is shown that entropy generated increases with physical activity, suggesting that exercise should be kept to a “healthy minimum” if entropy generation is to be minimized.

  16. Serum Phosphorus Levels in Premature Infants Receiving a Donor Human Milk Derived Fortifier

    Directory of Open Access Journals (Sweden)

    Katherine E. Chetta

    2015-04-01

    Full Text Available An elevated serum phosphorus (P has been anecdotally described in premature infants receiving human milk fortified with donor human milk-derived fortifier (HMDF. No studies have prospectively investigated serum P in premature infants receiving this fortification strategy. In this single center prospective observational cohort study, extremely premature infants ≤1250 grams (g birth weight (BW were fed an exclusive human milk-based diet receiving HMDF and serum P levels were obtained. We evaluated 93 infants with a mean gestational age of 27.5 ± 2.0 weeks (Mean ± SD and BW of 904 ± 178 g. Seventeen infants (18.3% had at least one high serum P level with a mean serum P of 9.2 ± 1.1 mg/dL occurring at 19 ± 11 days of life. For all infants, the highest serum P was inversely correlated to the day of life of the infant (p < 0.001, R2 = 0.175 and positively correlated with energy density of HMDF (p = 0.035. Serum P was not significantly related to gender, BW, gestational age, or days to full feeds. We conclude that the incidence of hyperphosphatemia was mild and transient in this population. The risk decreased with infant age and was unrelated to gender, BW, or ethnicity.

  17. Optimizing conditions for production of high levels of soluble recombinant human growth hormone using Taguchi method.

    Science.gov (United States)

    Savari, Marzieh; Zarkesh Esfahani, Sayyed Hamid; Edalati, Masoud; Biria, Davoud

    2015-10-01

    Human growth hormone (hGH) is synthesized and stored by somatotroph cells of the anterior pituitary gland and can effect on body metabolism. This protein can be used to treat hGH deficiency, Prader-Willi syndrome and Turner syndrome. The limitations in current technology for soluble recombinant protein production, such as inclusion body formation, decrease its usage for therapeutic purposes. To achieve high levels of soluble form of recombinant human growth hormone (rhGH) we used suitable host strain, appropriate induction temperature, induction time and culture media composition. For this purpose, 32 experiments were designed using Taguchi method and the levels of produced proteins in all 32 experiments were evaluated primarily by ELISA and dot blotting and finally the purified rhGH protein products assessed by SDS-PAGE and Western blotting techniques. Our results indicate that media, bacterial strains, temperature and induction time have significant effects on the production of rhGH. The low cultivation temperature of 25°C, TB media (with 3% ethanol and 0.6M glycerol), Origami strain and a 10-h induction time increased the solubility of human growth hormone.

  18. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    Energy Technology Data Exchange (ETDEWEB)

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  19. Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Rubin, Edward M.

    2002-09-15

    Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies have provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.

  20. Provincial human development index, a guide for efficiency level analysis: the case of iran.

    Science.gov (United States)

    Sabermahani, Asma; Barouni, Mohsen; Seyedin, Hesam; Aryankhesal, Aidin

    2013-01-01

    Human Development Index (HDI) is a composite indicator that can show the impact of economic strategies on human life standards. The index is calculated by three main factors of income, education and health. This research studies the status of HDI across the Iranian provinces, its changes over time and the efficiency of provinces in using resources. The data for 2001 and 2009 was obtained from the Iranian Center of Statistics. Data envelopment analysis technique was used to analyze the data. To calculate the efficiency, Banker, Charnes and Cooper's model was used. The national mean for the HDI in 2001 was 0.717 while it grew to 0.747 in 2009. Except for one province, all others had an improved human development index. Low ranked provinces such as Sistan & Baluchistan and Kurdistan stayed at the bottom in 2009 as well. Some provinces such as Bushehr with developing oil industries, or those purposively benefited from national oil income showed good growth. In some provinces, such as Hormozgan, out-migration of manpower to its neighboring province, Bushehr, was associated with decrease of the provincial income level. The number of efficient provinces increased from 5 to 13 in 2009. Iran falls among countries with high human development index based on the 2009 data. However, the distribution of HDI status across provinces was highly varied and the difference between high- and low-developed provinces increased in 2009. The government needs to revise policies concerning distribution of resources among the provinces.

  1. Low-level lasers on microRNA and uncoupling protein 2 mRNA levels in human breast cancer cells

    Science.gov (United States)

    Canuto, K. S.; Teixeira, A. F.; Rodrigues, J. A.; Paoli, F.; Nogueira, E. M.; Mencalha, A. L.; Fonseca, A. S.

    2017-06-01

    MicroRNA is short non-coding RNA and is a mediator of post-transcriptional regulation of gene expression. In addition, uncoupling proteins (UCPs) regulate thermogenesis, metabolic and energy balance, and decrease reactive oxygen species production. Both microRNA and UCP2 expression can be altered in cancer cells. At low power, laser wavelength, frequency, fluence and emission mode deternube photobiological responses, which are the basis of low-level laser therapy. There are few studies on miRNA and UCP mRNA levels after low-level laser exposure on cancer cells. In this work, we evaluate the micrRNA (mir-106b and mir-15a) and UCP2 mRNA levels in human breast cancer cells exposed to low-level lasers. MDA-MB-231 human breast cancer cells were exposed to low-level red and infrared lasers, total RNA was extracted for cDNA synthesis and mRNA levels by real time quantitative polymerase chain reaction were evaluated. Data show that mir-106b and mir-15a relative levels are not altered, but UCP2 mRNA relative levels are increased in MDA-MB-231 human breast cancer cells exposed to low-level red and infrared lasers at fluences used in therapeutic protocols.

  2. Applicability of the CALUX bioassay for screening of dioxin levels in human milk samples

    DEFF Research Database (Denmark)

    Laier, P.; Cederberg, Tommy Licht; Larsen, John Christian;

    2003-01-01

    . The results obtained with the bioassay when testing milk extracts fractionated into dioxins/furans, non-ortho PCB and mono/di-ortho PCB fractions indicated that the correlation between the bioassay and the chemical analyses depends primarily on the A receptor activity observed in the mono/di-ortho PCB......The CALUX (chemically activated luciferase expression) bioassay based on rat hepatoma (H4IIE) cells is a sensitive assay for the detection of Ah receptor agonists like 2,3,7,8-substituted chlorinated dibenzo-p-dioxins and dibenzofurans and related PCBs. In this paper, the assay was optimized...... and applied for monitoring levels of dioxins in human milk samples. Combination effects of dioxin-like compounds were evaluated by testing potential mechanisms of interaction between seven of the major dioxin-like compounds in human milk using the isobole method. Results showed that the compounds acted...

  3. Mechanical properties of human patellar tendon at the hierarchical levels of tendon and fibril

    DEFF Research Database (Denmark)

    Svensson, René B; Hansen, Philip; Hassenkam, Tue

    2012-01-01

    Tendons are strong hierarchical structures, but how tensile forces are transmitted between different levels remains incompletely understood. Collagen fibrils are thought to be primary determinants of whole tendon properties, and therefore we hypothesized that the whole human patellar tendon and its...... distinct collagen fibrils would display similar mechanical properties. Human patellar tendons (n = 5) were mechanically tested in vivo by ultrasonography. Biopsies were obtained from each tendon, and individual collagen fibrils were dissected and tested mechanically by atomic force microscopy. The Young......'s modulus was 2.0 ± 0.5 GPa, and the toe region reached 3.3 ± 1.9% strain in whole patellar tendons. Based on dry cross-sectional area, the Young's modulus of isolated collagen fibrils was 2.8 ± 0.3 GPa, and the toe region reached 0.86 ± 0.08% strain. The measured fibril modulus was insufficient to account...

  4. The F7 gene and clotting factor VII levels: dissection of a human quantitative trait locus.

    Science.gov (United States)

    Soria, Jose Manuel; Almasy, Laura; Souto, Juan Carlos; Sabater-Lleal, Maria; Fontcuberta, Jordi; Blangero, John

    2005-10-01

    Localization of human quantitative trait loci (QTLs) is now routine. However, identifying their functional DNA variants is still a formidable challenge. We present a complete dissection of a human QTL using novel statistical techniques to infer the most likely functional polymorphisms of a QTL that influence plasma levels of clotting factor VII (FVII), a risk factor for cardiovascular disease. Resequencing of 15 kb in and around the F7 gene identified 49 polymorphisms, which were then genotyped in 398 people. Using a Bayesian quantitative trait nucleotide (BQTN) method, we identified four to seven functional variants that completely account for this QTL. These variants include both rare coding variants and more common, potentially regulatory polymorphisms in intronic and promoter regions.

  5. Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene.

    Science.gov (United States)

    Gan, Shu Uin; Notaridou, Maria; Fu, Zhen Ying; Lee, Kok Onn; Sia, Kian Chuan; Nathwani, Amit Chunilal; Della Peruta, Marco; Calne, Roy Yorke

    2016-01-01

    We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter. In vivo dose titration experiments were carried out and we identified an optimal range that achieved maintenance of euglycaemia or a mild diabetic condition for at least 9 months and ongoing to beyond 1 year for some animals, accompanied by human C-peptide secretion and weight gain. Further DNA codon optimization of the insulin gene construct resulted in approximately 3-10 times more human C-peptide secreted in the blood of codon optimized treated animals thereby reducing the number of vector particles required to achieve the same extent of reduction in blood glucose levels as the non-codon optimized vector. The constitutive secretion of insulin achieved with a single administration of the vector could be of therapeutic value for some diabetic patients.

  6. Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-12-01

    Full Text Available Pluripotent human embryonic stem cells (hESCs are a potential source of transplantable cells for treating patients with diabetes. To investigate the impact of the host recipient on hESC-derived pancreatic progenitor cell maturation, cells were transplanted into immunodeficient SCID-beige mice or nude rats. Following the transplant, basal human C-peptide levels were consistently higher in mice compared with rats, but only rats showed robust meal- and glucose-responsive human C-peptide secretion by 19–21 weeks. Grafts from rats contained a higher proportion of insulin:glucagon immunoreactivity, fewer exocrine cells, and improved expression of mature β cell markers compared with mice. Moreover, ECM-related genes were enriched, the collagen network was denser, and blood vessels were more intricately integrated into the engrafted endocrine tissue in rats relative to mice. Overall, hESC-derived pancreatic progenitor cells matured faster in nude rats compared with SCID-beige mice, indicating that the host recipient can greatly influence the fate of immature pancreatic progenitor cells post-transplantation.

  7. The human BDNF gene: peripheral gene expression and protein levels as biomarkers for psychiatric disorders

    Science.gov (United States)

    Cattaneo, A; Cattane, N; Begni, V; Pariante, C M; Riva, M A

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders. We will discuss several mechanisms as possibly underlying BDNF modulation, including epigenetic mechanisms. We will also discuss the potential use of peripheral BDNF as a biomarker for psychiatric disorders, focusing on the factors that can influence BDNF gene expression and protein levels. Within this context, we have also characterized, for we believe the first time, the expression of BDNF transcripts in the blood, with the aim to provide novel insights into the molecular mechanisms and signaling that may regulate peripheral BDNF gene expression levels. PMID:27874848

  8. Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis.

    Science.gov (United States)

    Endo, Nobuhide; Tsuboi, Naotake; Furuhashi, Kazuhiro; Shi, Yiqin; Du, Qiuna; Abe, Tomoko; Hori, Mayuko; Imaizumi, Takahiro; Kim, Hangsoo; Katsuno, Takayuki; Ozaki, Takenori; Kosugi, Tomoki; Matsuo, Seiichi; Maruyama, Shoichi

    2016-12-01

    In addition to classically activated macrophages that have effector roles in tissue injury, alternatively activated M2 macrophages are involved in the resolution of inflammation in animal models of kidney disease. To clarify the clinical relevance of macrophage phenotypes in human glomerular diseases, we evaluated the renal accumulation of macrophages and plasma and urine levels of CD163, an M2 marker, in lupus nephritis (LN) patients. Kidney biopsies and plasma and urine samples were obtained from LN patients who underwent renal biopsy between 2008 and 2012. CD163(+), CD68(+) and CD204(+) cells were counted in paraffin-embedded and frozen sections. LN histological activity was evaluated semiquantitatively using the biopsy activity index. Plasma and urinary soluble CD163 (sCD163) concentrations were also measured and evaluated for their significance as potential LN biomarkers. Immunohistological analysis of glomeruli from LN patients revealed that >60% of CD68(+) macrophages had merged with CD163(+) cells. The increased number of glomerular CD163(+) macrophages was correlated with LN severity, as determined by the biopsy active index (r = 0.635). Urinary (u-) sCD163 level was strongly correlated with glomerular CD163(+) cell counts and histological disease score as well as urinary monocyte chemoattractant protein 1 levels (r = 0.638 and 0.592, respectively). Furthermore, the u-sCD163 level was higher in patients with active LN than in those with other diseases. Glomerular CD163(+) macrophages are the predominant phenotype in the kidneys of lupus patients. These findings indicate that the u-sCD163 level can serve as a biomarker for macrophage-dependent glomerular inflammation in human LN. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  9. Analysis of adequacy levels for human resources improvement within primary health care framework in Africa

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    Piette Danielle

    2005-12-01

    Full Text Available Abstract Human resources in health care system in sub-Saharan Africa are generally picturing a lack of adequacy between expected skills from the professionals and health care needs expressed by the populations. It is, however, possible to analyse these various lacks of adequacy related to human resource management and their determinants to enhance the effectiveness of the health care system. From two projects focused on nurse professionals within the health care system in Central Africa, we present an analytic grid for adequacy levels looking into the following aspects: - adequacy between skills-based profiles for health system professionals, quality of care and service delivery (health care system /medical standards, needs and expectations from the populations, - adequacy between allocation of health system professionals, quality of care and services delivered (health care system /medical standards, needs and expectations from the populations, - adequacy between human resource management within health care system and medical standards, - adequacy between human resource management within education/teaching/training and needs from health care system and education sectors, - adequacy between basic and on-going education and realities of tasks expected and implemented by different categories of professionals within the health care system body, - adequacy between intentions for initial and on-going trainings and teaching programs in health sciences for trainers (teachers/supervisors/health care system professionals/ directors (teaching managers of schools.... This tool is necessary for decision-makers as well as for health care system professionals who share common objectives for changes at each level of intervention within the health system. Setting this adequacy implies interdisciplinary and participative approaches for concerned actors in order to provide an overall vision of a more broaden system than health district, small island with self

  10. Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes.

    Science.gov (United States)

    Ramos, Patrícia; Santos, Agostinho; Pinto, Edgar; Pinto, Nair Rosas; Mendes, Ricardo; Magalhães, Teresa; Almeida, Agostinho

    2016-12-01

    The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder. Potassium was found as the most abundant alkali metal, followed by Na, Rb, Cs and Li. Lithium, K and Cs distribution showed to be quite heterogeneous. On the contrary, Rb and Na appeared quite homogeneously distributed within the human brain tissue. The lowest levels of Na, K, Rb and Li were found in the brainstem (midbrain, medulla and pons) and cerebellum, while the lowest levels of Cs were found in the frontal cortex. The highest levels of K (mean±sd; range 15.5±2.5; 8.9-21.8mg/g) Rb (17.2±6.1; 3.9-32.4μg/g and Cs (83.4±48.6; 17.3-220.5ng/g) were found in putamen. The highest levels of Na and Li were found in the frontal cortex (11.6±2.4; 6.6-17.1mg/g) and caudate nucleus (7.6±4.6 2.2-21.3ng/g), respectively. Although K, Cs and Li levels appear to remain largely unchanged with age, some age-related changes were observed for Na and Rb levels in particular brain regions (namely in the hippocampus). Copyright © 2016 Elsevier GmbH. All

  11. Effects of low levels of ciprofloxacin on a chemostat model of the human colonic microflora.

    Science.gov (United States)

    Carman, R J; Woodburn, M A

    2001-06-01

    To study the utility of an in vitro model system for assessing the effect of low concentrations of a fluoroquinolone (FQ) drug on the ecology of the human intestinal microflora, chemostats containing human fecal flora were exposed to 0.43, 4.3, and 43microg of ciprofloxacin (CI) per milliliter. Prior to and during drug exposure, we assayed short-chain fatty acids (SCFA), bacterial populations, and the relative levels of susceptibility of these populations to CI and trovafloxacin (TV), a newer related FQ with increased activity against anaerobes. The degree to which CI affected the chemostat ecology was measured statistically by comparing observed data with the corresponding predicted "no effect" level. No changes in total SCFA were observed; only butyrate was significantly higher at the intermediate and high-dose levels. Enterococci counts and the levels of susceptibility to CI among enterococci were also unaffected. Escherichia coli counts decreased in a dose-dependent manner. Susceptibility levels in E. coli followed no interpretable pattern. Bacteroides fragilis group (BfG) counts decreased significantly following exposure to 43 and 4.3microg/mL CI. Ciprofloxacin susceptibility among the BfG in these chemostats was not determined because the BfG counts were too low (less than 30 colonies per plate) when undiluted chemostat samples were plated. However, within 2 days of exposure to 0.43microg/mL CI, the percentage of BfG resistant to 4microg/mL CI increased to over 95%. Before exposure, all BfG were susceptible to both CI (2microg/mL) and TV (0.25microg/mL). All BfG isolated during exposure were resistant to both CI (4microg/mL) and TV (2microg/mL). Resistance selection in the BfG was unexpected as the MIC(90) of CI for B. fragilis is 8microg/mL. Since the average colon flora is about 20% B. fragilis and other bacteroides, CI may impact the human gut flora even at subtherapeutic levels.

  12. The alteration and investigation of c-peptide, glycosylated hemoglobin and sensitive C-reactive protein test of gestational diabetes mellitus%妊娠糖尿病患者C-P、HbAlc和hs-CRP的改变及意义

    Institute of Scientific and Technical Information of China (English)

    谢则金; 王厚照; 黄璐; 黄幼芳

    2011-01-01

    目的 探讨C肽(C-P)、糖化血红蛋白(HbAlc)和超敏C反应蛋白(hs-CRP)在妊娠糖尿病诊断中的临床意义.方法 对正常对照组36例、正常妊娠组50例及妊娠糖尿病组56例采用生化和化学发光免疫方法进行hs-CRP、HbAlc、C-P的测定.结果 妊娠糖尿病组hs-CRP、HbAlc和C-P结果与正常妊娠组相比均明显增高(P<0.01);C-P对妊娠糖尿病诊断的特异性高于HbAlc(P<0.05);阳性预测值为91.42%,也明显高于HbAlc(P<0.05);两者联合检测的结果中,联合检测的特异性和阳性预测值分别为98.84%和96.77%,明显高于两者单独检测的结果(Pc -peptide, glycosylated hemoglobin and sensitive C -reactive protein test in diagnosis of gestational diabetes mellitns.Methods: 36 cases health control, 56 cases of gestational diabetes mellitus and 50 cases of normal pregnant women were selected.C - peptide, glycosylated hemoglobin and sensitive C - reactive protein test were measured by biochemical and chemiluminescence immunoassay methods.Results: Compared with the control and the normal pregnant group,the values of glycosylated hemoglobin, C - peptide and sensitive C - reactive protein were higher apparently in the gestational diabetes mellitus group ( P <0.01 ).The specificity of c -peptide were significantly higher than glycosylated hemoglobin in the gestational diabetes mellitus; The specificity and the positive (98.84%and 96.77% ) predictive value of combined detection of aglycosylated hemoglobin and c - peptide were significantly higher than Single detection ( P <0.05 ).Conclusions: There were high value of c - peptide, glycosylated hemoglobin and sensitive C -reactive protein test in diagnosis of gestational diabetes mellitus; Combined detection of C - peptide, glycosylated

  13. Glutathione Levels and Susceptibility to Chemically Induced Injury in Two Human Prostate Cancer Cell Lines

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    Lawrence H. Lash

    2015-06-01

    Full Text Available More aggressive prostate cancer cells (PCCs are often resistant to chemotherapy. Differences exist in redox status and mitochondrial metabolism that may help explain this phenomenon. Two human PCC lines, PC-3 cells (more aggressive and LNCaP cells (less aggressive, were compared with regard to cellular glutathione (GSH levels, susceptibility to either oxidants or GSH depletors, and expression of several proteins involved in apoptosis and stress response to test the hypothesis that more aggressive PCCs exhibit higher GSH concentrations and are relatively resistant to cytotoxicity. PC-3 cells exhibited 4.2-fold higher GSH concentration than LNCaP cells but only modest differences in acute cytotoxicity were observed at certain time points. However, only LNCaP cells underwent diamide-induced apoptosis. PC-3 cells exhibited higher levels of Bax and caspase-8 cleavage product but lower levels of Bcl-2 than LNCaP cells. However, LNCaP cells exhibited higher expression of Fas receptor (FasR but also higher levels of several stress response and antioxidant proteins than PC-3 cells. LNCaP cells also exhibited higher levels of several mitochondrial antioxidant systems, suggesting a compensatory response. Thus, significant differences in redox status and expression of proteins involved in apoptosis and stress response may contribute to PCC aggressiveness.

  14. MYOCILIN LEVELS IN PRIMARY OPEN-ANGLE GLAUCOMA AND PSEUDOEXFOLIATION GLAUCOMA HUMAN AQUEOUS HUMOR

    Science.gov (United States)

    Howell, Kyle G.; Vrabel, Anne M.; Chowdhury, Uttio Roy; Stamer, W. Daniel; Fautsch, Michael P.

    2010-01-01

    Purpose To determine the concentration of myocilin in primary open-angle and pseudoexfoliation glaucoma aqueous humor. Methods Aqueous humor was collected during surgery from patients with primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEXG), and elective cataract removal (control). Volume-equivalent aqueous samples were separated on SDS-PAGE gradient gels. Quantification of myocilin levels was performed using Western blots probed with two independent N-terminal polyclonal anti-myocilin antibodies (AB1 and AB2) followed by densitometry. Myocilin levels in aqueous humor were quantified by plotting the densitometry readings of the aqueous samples against a recombinant myocilin standard curve. Total protein concentration was determined by Bradford protein assay. Transforming growth factor beta 2 (TGFβ2) levels were assessed by ELISA. Results Myocilin levels are significantly elevated in human POAG aqueous humor when compared to control aqueous humor (AB1: 0.66 ± 0.53 ng/μl vs. 0.23 ± 0.20 ng/μl, phumor compared to control aqueous (AB1: 0.26 ± 0.20% vs. 0.10 ± 0.20%, phumor when compared to control aqueous humor. No correlation between myocilin and TGFβ2 levels was observed. Conclusions Myocilin is elevated in POAG, but not PEXG aqueous humor. PMID:20179615

  15. Post-transcriptional regulation of neurofibromin level in cultured human melanocytes in response to growth factors.

    Science.gov (United States)

    Griesser, J; Kaufmann, D; Maier, B; Mailhammer, R; Kuehl, P; Krone, W

    1997-03-01

    Among the symptoms that characterize neurofibromatosis type 1 (NF1) are pigmentation anomalies such as cafe au lait spots. It has been suggested that the reduction of the neurofibromin level in the epidermis of NF1 patients is responsible for the observed signs such as altered melanogenesis and altered density of melanocytes. Our studies show that in cultured normal human melanocytes, the neurofibromin level can be varied in vitro over a wide range by using different culture conditions. The influence of factors that control differentiation and proliferation of melanocytes on neurofibromin levels was studied. Immunoprecipitation followed by western blotting showed a 3- to 4-fold increase of neurofibromin after stimulation by PMA or bFGF, respectively, and a 1.5-fold increase in cells stimulated with steel factor. The increase of neurofibromin was not paralleled by a higher NF1 mRNA level as proved by northern blotting. Pulse-chase experiments with 35S-labeled melanocytes revealed an approximately 3-fold increase in the half-life of neurofibromin in bFGF- or PMA-stimulated cells compared to controls. These results indicate that the neurofibromin level of cultured melanocytes can be regulated by a mechanism independent of NF1 gene transcription and translation, which might influence the degradation rate of the protein.

  16. Antibody and cytokine levels in humans fed on by the common bedbug, Cimex lectularius L.

    Science.gov (United States)

    Sheele, J M; Ridge, G E; Coppolino, K; Bonfield, T; Young, A B; Gaines, S L; McCormick, T S

    2017-03-01

    Little is known about cimicosis, the resultant dermal reaction from feeding activity by the common bedbug, Cimex lectularius L. We fed C. lectularius on human study subjects four times over four weeks and measured serum cytokine and antibody levels, and subjects recorded any cimicosis. The average time for subjects to develop cimicosis decreased with each feeding from 8.4, to 2.1, 1.5 and 1.3 days, respectively. There were no significant changes in total IgG, IgG1, IgG2, IgG4 or IgE levels between the first and fourth bedbug feedings, but there was a significant decrease in total IgG3 levels (Plectularius feeding. Lower post-C. lectularius feeding IL-6 levels were associated with increased pruritis (P=.001) and the time to maximum pruritis (P=.04), respectively. Higher post-C. lectularius feeding IL-5 levels were associated with a longer duration of pruritis (P=.05).

  17. Can Population-Level Laterality Stem from Social Pressures? Evidence from Cheek Kissing in Humans.

    Science.gov (United States)

    Chapelain, Amandine; Pimbert, Pauline; Aube, Lydiane; Perrocheau, Océane; Debunne, Gilles; Bellido, Alain; Blois-Heulin, Catherine

    2015-01-01

    Despite extensive research, the origins and functions of behavioural laterality remain largely unclear. One of the most striking unresolved issues is the fact that laterality generally occurs at the population-level. Why would the majority of the individuals of a population exhibit the same laterality, while individual-level laterality would yet provide the advantages in terms of improving behavioural efficiency? Are social pressures the key factor? Can social pressures induce alignment of laterality between the individuals of a population? Can the effect of social pressures overpass the effect of other possible determining factors (e.g. genes)? We tested this important new hypothesis in humans, for the first time. We asked whether population-level laterality could stem from social pressures. Namely, we assessed social pressures on laterality in an interactive social behaviour: kissing on the cheek as a greeting. We performed observations in 10 cities of France. The observations took place in spots where people of the city meet and greet each other. We showed that: a) there is a population-level laterality for cheek kissing, with the majority of individuals being aligned in each city, and b) there is a variation between populations, with a laterality that depends on the city. These results were confirmed by our complementary data from questionnaires and internet surveys. These findings show that social pressures are involved in determining laterality. They demonstrate that population-level laterality can stem from social pressures.

  18. Oxylipins, endocannabinoids, and related compounds in human milk: Levels and effects of storage conditions.

    Science.gov (United States)

    Wu, Junfang; Gouveia-Figueira, Sandra; Domellöf, Magnus; Zivkovic, Angela M; Nording, Malin L

    2016-01-01

    The presence of fatty acid derived oxylipins, endocannabinoids and related compounds in human milk may be of importance to the infant. Presently, clinically relevant protocols for storing and handling human milk that minimize error and variability in oxylipin and endocannabinoid concentrations are lacking. In this study, we compared the individual and combined effects of the following storage conditions on the stability of these fatty acid metabolites in human milk: state (fresh or frozen), storage temperature (4 °C, -20 °C or -80 °C), and duration (1 day, 1 week or 3 months). Thirteen endocannabinoids and related compounds, as well as 37 oxylipins were analyzed simultaneously by liquid chromatography coupled to tandem mass spectrometry. Twelve endocannabinoids and related compounds (2-111 nM) and 31 oxylipins (1.2 pM-1242 nM) were detected, with highest levels being found for 2-arachidonoylglycerol and 17(R)hydroxydocosahexaenoic acid, respectively. The concentrations of most endocannabinoid-related compounds and oxylipins were dependent on storage condition, and especially storage at 4 °C introduced significant variability. Our findings suggest that human milk samples should be analyzed immediately after, or within one day of collection (if stored at 4 °C). Storage at -80 °C is required for long-term preservation, and storage at -20 °C is acceptable for no more than one week. These findings provide a protocol for investigating the oxylipin and endocannabinoid metabolome in human milk, useful for future milk-related clinical studies.

  19. STUDY ON NOISE LEVEL GENERATED BY HUMAN ACTIVITIES IN SIBIU CITY, ROMANIA

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    Cristina STANCA-MOISE

    2014-10-01

    Full Text Available In this paper I have proposed an analysis and monitoring of the noise sources in the open spaces of air traffic, rail and car in Sibiu. From centralizing data obtained from the analysis of the measurements performed with equipment noise levels, we concluded that the noise and vibration produced by means of Transportation (air, road, rail can affect human health if they exceed limits. Noise is present and part of our lives and always a source of pollution as any of modern man is not conscious.

  20. Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

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    Xian-E Peng

    Full Text Available Liver fatty acid-binding protein (L-FABP, also known as fatty acid-binding protein 1 (FABP1, is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182 from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032.Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05. The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01. In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003, while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014. Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans.

  1. Durations of extended mental rehearsals are remarkably reproducible in higher level human performances.

    Science.gov (United States)

    Brothers, L; Shaw, G L; Wright, E L

    1993-12-01

    It has been extremely difficult to quantify temporal aspects of higher level human brain function. We have found that mental rehearsals of musical performance of several minutes duration provide such a measure in that they can be highly reproducible, varying to less than 1%. These remarkable results pose fundamental neurophysiological problems. It is necessary to understand the underlying neuronal bases for this accuracy in the spatial-temporal activity of billions of neurons over minutes without sensory input. Further, they present a powerful constraint on neuronal models of brain function. Such highly reproducible (in duration) mental rehearsals might be used in conjunction with multielectrode EEG recordings to look for reproducible spatial-temporal patterns. Further, we suggest that our results may provide an extremely useful behavioural correlate for high level performance.

  2. Human resource in tourism and hospitality industry: Relation between level of education and job satisfaction

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    Kovačević Bojana

    2012-01-01

    Full Text Available The paper offers a concise summary of current problems including the impact of education on (dissatisfaction of human resources in tourism and hospitality industry. In recent years, many researches have been focused on the phenomena of the relation between level of education and job satisfaction of the employees in tourism organizations as it is well known that employee satisfaction enhance competitiveness and efficiency in business. A current issue was set as the fundamental goal in designing this paper, and the basic parameter of the research is employee satisfaction with business operations and working conditions, or to be more precise, examining the extent of (dissatisfaction with the given segments depending on the employees' educational level. This paper represents a synthesis of the electronic research, the analysis of available references, as well as the use of descriptive, analytical and synthetic methods, and it will result in a critical analysis and confirmation (denial of certain hypotheses.

  3. Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level

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    Juan E. Losa García

    1999-01-01

    Full Text Available In addition to its well-established effect on T cells, cyclosporin A (CsA also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO. Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a inhibition of the synthesis of an early common regulatory protein, (b inhibition of cytokine gene transcription, or (c modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.

  4. Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bayer, Christine, E-mail: christine.bayer@yahoo.com [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Kielow, Achim [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Schilling, Daniela [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany); Maftei, Constantin-Alin [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Zips, Daniel; Yaromina, Ala; Baumann, Michael [OncoRay Center for Radiation Research, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany); Molls, Michael [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Multhoff, Gabriele [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany)

    2012-11-01

    Purpose: Previous studies have shown that the plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are regulated by hypoxia and irradiation and are involved in neoangiogenesis. The aim of this study was to determine in vivo whether changes in PAI-1 and VEGF during fractionated irradiation could predict for radiation resistance. Methods and Materials: Six xenografted tumor lines from human squamous cell carcinomas (HSCC) of the head and neck were irradiated with 0, 3, 5, 10, and 15 daily fractions of 2 Gy. The PAI-1 and VEGF antigen levels in tumor lysates were determined by enzyme-linked immunosorbent assay kits. The amounts of PAI-1 and VEGF were compared with the dose to cure 50% of tumors (TCD{sub 50}). Colocalization of PAI-1, pimonidazole (hypoxia), CD31 (endothelium), and Hoechst 33342 (perfusion) was examined by immunofluorescence. Results: Human PAI-1 and VEGF (hVEGF) expression levels were induced by fractionated irradiation in UT-SCC-15, UT-SCC-14, and UT-SCC-5 tumors, and mouse VEGF (msVEGF) was induced only in UT-SCC-5 tumors. High hVEGF levels were significantly associated with radiation sensitivity after 5 fractions (P=.021), and high msVEGF levels were significantly associated with radiation resistance after 10 fractions (P=.007). PAI-1 staining was observed in the extracellular matrix, the cytoplasm of fibroblast-like stroma cells, and individual tumor cells at all doses of irradiation. Colocalization studies showed PAI-1 staining close to microvessels. Conclusions: These results indicate that the concentration of tumor-specific and host-specific VEGF during fractionated irradiation could provide considerably divergent information for the outcome of radiation therapy.

  5. Economic growth and marine biodiversity: influence of human social structure on decline of marine trophic levels.

    Science.gov (United States)

    Clausen, Rebecca; York, Richard

    2008-04-01

    We assessed the effects of economic growth, urbanization, and human population size on marine biodiversity. We used the mean trophic level (MTL) of marine catch as an indicator of marine biodiversity and conducted cross-national time-series analyses (1960-2003) of 102 nations to investigate human social influences on fish catch and trends in MTL. We constructed path models to examine direct and indirect effects relating to marine catch and MTL. Nations' MTLs declined with increased economic growth, increased urbanization, and increased population size, in part because of associated increased catch. These findings contradict the environmental Kuznets curve hypothesis, which claims that economic modernization will reduce human impact on the environment. To make informed decisions on issues of marine resource management, policy makers, nonprofit entities, and professional societies must recognize the need to include social analyses in overall conservation-research strategies. The challenge is to utilize the socioeconomic and ecological research in the service of a comprehensive marine-conservation movement.

  6. Human embryonic stem cells express elevated levels of multiple pro-apoptotic BCL-2 family members.

    Directory of Open Access Journals (Sweden)

    David T Madden

    Full Text Available Two of the greatest challenges in regenerative medicine today remain (1 the ability to culture human embryonic stem cells (hESCs at a scale sufficient to satisfy clinical demand and (2 the ability to eliminate teratoma-forming cells from preparations of cells with clinically desirable phenotypes. Understanding the pathways governing apoptosis in hESCs may provide a means to address these issues. Limiting apoptosis could aid scaling efforts, whereas triggering selective apoptosis in hESCs could eliminate unwanted teratoma-forming cells. We focus here on the BCL-2 family of proteins, which regulate mitochondrial-dependent apoptosis. We used quantitative PCR to compare the steady-state expression profile of all human BCL-2 family members in hESCs with that of human primary cells from various origins and two cancer lines. Our findings indicate that hESCs express elevated levels of the pro-apoptotic BH3-only BCL-2 family members NOXA, BIK, BIM, BMF and PUMA when compared with differentiated cells and cancer cells. However, compensatory expression of pro-survival BCL-2 family members in hESCs was not observed, suggesting a possible explanation for the elevated rates of apoptosis observed in proliferating hESC cultures, as well as a mechanism that could be exploited to limit hESC-derived neoplasms.

  7. Regulation of cAMP Intracellular Levels in Human Platelets Stimulated by 2-Arachidonoylglycerol.

    Science.gov (United States)

    Signorello, Maria Grazia; Leoncini, Giuliana

    2016-05-01

    We demonstrated that in human platelets the endocannabinoid 2-arachidonoylglycerol (2-AG) decreased dose- and time-dependently cAMP intracellular levels. No effect on cAMP decrease induced by 2-AG was observed in the presence of the adenylate cyclase inhibitor SQ22536 as well in platelets pretreated with the thromboxane A2 receptor antagonist, SQ29548 or with aspirin, inhibitor of arachidonic acid metabolism through the cyclooxygenase pathway. An almost complete recovering of cAMP level was measured in platelets pretreated with the specific inhibitor of phosphodiesterase (PDE) 3A, milrinone. In platelets pretreated with LY294002 or MK2206, inhibitors of PI3K/AKT pathway, and with U73122, inhibitor of phospholipase C pathway, only a partial prevention was shown. cAMP intracellular level depends on synthesis by adenylate cyclase and hydrolysis by PDEs. In 2-AG-stimulated platelets adenylate cyclase activity seems to be unchanged. In contrast PDEs appear to be involved. In particular PDE3A was specifically activated, as milrinone reversed cAMP reduction by 2-AG. 2-AG enhanced PDE3A activity through its phosphorylation. The PI3K/AKT pathway and PKC participate to this PDE3A phosphorylation/activation mechanism as it was greatly inhibited by platelet pretreatment with LY294002, MK2206, U73122, or the PKC specific inhibitor GF109203X. Taken together these data suggest that 2-AG potentiates its power of platelet agonist reducing cAMP intracellular level.

  8. BUILDING HUMAN CAPITAL: THE IMPACT OF PARENTS´ INITIAL EDUCATIONAL LEVEL AND LIFELONG LEARNING ON THEIR CHILDREN

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    FISCHER, Jakub

    2013-12-01

    Full Text Available The aim of this paper is to examine the impact of parents´ educational level on lifelong learning of children and relationship between parents´ and student´ lifelong learning including language skills and computer literacy. This intergenerational transmission, if proven, could influence the investments into the human capital in the long run. We used data from Adult Education Survey 2011 (AES to test the hypothesis that the parental attained level of education has a significant impact on the initial educational level of their children as well as on their lifelong learning participation. Furthermore, using data from AES, we tested the association between parental educational level and children´s language skills and reading activity and between parental non-formal as well as informal education and students´ lifelong learning. We have found that the parental effect on lifelong learning participation is slightly weaker than the effect of initial adult´s education. Nevertheless, the intergenerational transmission mechanism obviously works. The relationship between parental and students computer literacy is statistically significant, nevertheless weak. As for the nominal and ordinal character of the data, we used mainly the standard statistical methods including nonparametric tests, logit model and correspondence analysis.

  9. Increase of {sup 210}Po levels in human semen fluid after mussel ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Kelecom, Alphonse, E-mail: lararapls@hotmail.co [Laboratory of Radiobiology and Radiometry-LARARA-PLS, Universidade Federal Fluminense, P.O.Box 100.436, 24001-970 Niteroi, RJ (Brazil); Programs in Environmental Science and Marine Biology, Universidade Federal Fluminense, Niteroi, RJ (Brazil); Gouvea, Rita de Cassia dos Santos [Laboratory of Radiobiology and Radiometry-LARARA-PLS, Universidade Federal Fluminense, P.O.Box 100.436, 24001-970 Niteroi, RJ (Brazil)

    2011-05-15

    Polonium-210 ({sup 210}Po) radioactive concentrations were determined in human semen fluid of vasectomized non-smoker volunteers. The {sup 210}Po levels ranged from 0.10 to 0.39 mBq g{sup -1} (mean: 0.23 {+-} 0.08 mBq g{sup -1}). This value decreased to 0.10 {+-} 0.02 mBq g{sup -1} (range from 0.07 to 0.13 mBq g{sup -1}) after two weeks of a controlled diet, excluding fish and seafood. Then, volunteers ate during a single meal 200 g of the cooked mussel Perna perna L., and {sup 210}Po levels were determined again, during ten days, in semen fluid samples collected every morning. Volunteers continued with the controlled diet and maintained sexual abstinence through the period of the experiment. A 300% increase of {sup 210}Po level was observed the day following mussel consumption, with a later reduction, such that the level returned to near baseline by day 4.

  10. Increase of 210Po levels in human semen fluid after mussel ingestion.

    Science.gov (United States)

    Kelecom, Alphonse; Gouvea, Rita de Cássia dos Santos

    2011-05-01

    Polonium-210 ((210)Po) radioactive concentrations were determined in human semen fluid of vasectomized non-smoker volunteers. The (210)Po levels ranged from 0.10 to 0.39 mBq g(-1) (mean: 0.23 ± 0.08 mBq g(-1)). This value decreased to 0.10 ± 0.02 mBq g(-1) (range from 0.07 to 0.13 mBq g(-1)) after two weeks of a controlled diet, excluding fish and seafood. Then, volunteers ate during a single meal 200 g of the cooked mussel Perna perna L., and (210)Po levels were determined again, during ten days, in semen fluid samples collected every morning. Volunteers continued with the controlled diet and maintained sexual abstinence through the period of the experiment. A 300% increase of (210)Po level was observed the day following mussel consumption, with a later reduction, such that the level returned to near baseline by day 4.

  11. Effect of Cyclosporin A and Angiotensin II on cytosolic calcium levels in primary human gingival fibroblasts

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    Ajitkumar Supraja

    2016-01-01

    Full Text Available Background: To evaluate the effect of Cyclosporin A (CsA and angiotensin II (Ang II on cytosolic calcium levels in cultured human gingival fibroblasts (HGFs. Materials and Methods: Healthy gingival samples from six volunteers were obtained, and primary HGFs were cultured. Cell viability and proliferation assay were performed to identify the ideal concentrations of CsA and Ang II. Cytosolic calcium levels in cultured gingival fibroblasts treated with CsA and Ang II were studied using colorimetric assay, confocal and fluorescence imaging. Statistical analyses were done using SPSS software and GraphPad Prism. Results: Higher levels of cytosolic levels were evident in cells treated with CsA and Ang II when compared to control group and was statistically significant (P < 0.05 in both colorimetric assay and confocal imaging. Fluorescent images of the cultured HGFs revealed the same. Conclusion: Thus calcium being a key player in major cellular functions, plays a major role in the pathogenesis of drug-induced gingival overgrowth.

  12. Levels of PCDDs, PCDFs, and dioxin-like PCBs in human milk among Hong Kong mothers.

    Science.gov (United States)

    Wong, Tze Wai; Wong, Andromeda H S; Nelson, E Anthony S; Qiu, Hong; Ku, Susanna Y K

    2013-10-01

    Dioxins are a family of persistent organic pollutants (POPs) listed under the Stockholm Convention, and include PCDDs, PCDFs, and dioxin-like PCBs. These toxic chemicals are carcinogenic, widely dispersed, and have long half-lives. They have contaminated the food web and, being fat-soluble, accumulate in adipose tissues and milk in the human body. To assess human exposure, we collected breast milk samples from 137 first-time mothers recruited from around Hong Kong. Samples were analysed by HRGC-HRMS in four pools, according to the subject's age and length of residency. Exposure was related to age, duration of stay, and possibly diet. Generally, older mothers, and mothers with a longer stay in Hong Kong, had higher levels of dioxins in their milk. This pattern was clearest for the PCBs, although deviations were observed for some of the PCDD/Fs. Mean concentrations, measured per gram of lipid weight in terms of WHO toxic equivalents (WHO-TEQs), were 7.48 pg/g for PCDD/Fs and 3.79 pg/g for PCBs, giving a total of 11.27 pg/g for PCDD/Fs and PCBs combined. Compared to an earlier Hong Kong study we conducted in 2002, the mean WHO-TEQ values in our latest findings were about 9% lower overall for PCDD/Fs and 19% lower for PCBs, with the mean total WHO-TEQ for PCDD/Fs and PCBs being around 13% lower in this study. This indicates a general declining trend in the levels of POPs in Hong Kong. However, our levels were still high when compared to those in some other Asian-Pacific countries. More stringent policies on reducing and eliminating POPs should help to lower these. Continued surveillance for POPs in human milk, as well as in common foodstuffs, will provide us with important information on human exposures that will be necessary for tracking our progress, and making future health risk assessments. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Outdoor and indoor ozone level: A potential impact on human health

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    Valuntaitė Vaida

    2015-01-01

    Full Text Available Background/Aim. Air pollution outside and inside is still one of the most sensitive issues. The aim of this study was to assess the ozone level in ambient air and working premises in terms of its possible influence on human health. Methods. The study was based on the results obtained in Lithuanian conditions. Continuous ozone measurement data from the rural monitoring station in Preila over the period 1995-2011 were analyzed. More than 180,000 hourly values were examined according to the requirements in the Directive 2008/50/EC. The World Health Organization (WHO and European Union indicators the Sum of Ozone Means Over 35 ppb (SOMO 35, the maximum daily 8-hour mean concentration of ozone higher than 100 and 120 μg/m3 were estimated. Indoor ozone concentrations in copying and welding rooms were evaluated. The ozone concentration was measured with the ozone analyzer O341M. Results. The frequency distribution of ozone hourly concentrations at the Preila station showed that less than 1% of the data were higher than 120 μg/m3 and 6% of them higher than 100 μg/m3, that could have the adverse effect on human health, during 1995-2011. The investigations made in working premises showed that near a copying machine the ozone concentration can reach 330 μg/m3, however in the room, i.e. 0.5 m from the machine, the average ozone concentration during automatic copying was 165 μg/m³ and during manual copying it was 50 μg/m³. Measurements in a welding room showed that the ozone concentration was in the range of 380-1,850 μg/m3 at the distance of 25 cm from the electrode and at the distance of 1 m from the source the ozone concentration decreased 2.5 times. Conclusion. The danger of the ambient ozone level to human health practically was not observed in Lithuanian conditions. However, almost 6% of the data exceed the new WHO guideline of 100 μg/m3 during the measurement time. Indoor ozone during welding reached a higher level than during copying that

  14. Human resources for health at the district level in Indonesia: the smoke and mirrors of decentralization.

    Science.gov (United States)

    Heywood, Peter F; Harahap, Nida P

    2009-02-03

    In 2001 Indonesia embarked on a rapid decentralization of government finances and functions to district governments. One of the results is that government has less information about its most valuable resource, the people who provide the services. The objective of the work reported here is to determine the stock of human resources for health in 15 districts, their service status and primary place of work. It also assesses the effect of decentralization on management of human resources and the implications for the future. We enumerated all health care providers (doctors, nurses and midwives), including information on their employment status and primary place of work, in each of 15 districts in Java. Data were collected by three teams, one for each province. Provider density (number of doctors, nurses and midwives/1000 population) was low by international standards--11 out of 15 districts had provider densities less than 1.0. Approximately half of all three professional groups were permanent public servants. Contractual employment was also important for both nurses and midwives. The private sector as the primary source of employment is most important for doctors (37% overall) and increasingly so for midwives (10%). For those employed in the public sector, two-thirds of doctors and nurses work in health centres, while most midwives are located at village-level health facilities. In the health system established after Independence, the facilities established were staffed through a period of obligatory service for all new graduates in medicine, nursing and midwifery. The last elements of that staffing system ended in 2007 and the government has not been able to replace it. The private sector is expanding and, despite the fact that it will be of increasing importance in the coming decades, government information about providers in private practice is decreasing. Despite the promise of decentralization to increase sectoral "decision space" at the district level, the

  15. Human resources for health at the district level in Indonesia: the smoke and mirrors of decentralization

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    Harahap Nida P

    2009-02-01

    Full Text Available Abstract Background In 2001 Indonesia embarked on a rapid decentralization of government finances and functions to district governments. One of the results is that government has less information about its most valuable resource, the people who provide the services. The objective of the work reported here is to determine the stock of human resources for health in 15 districts, their service status and primary place of work. It also assesses the effect of decentralization on management of human resources and the implications for the future. Methods We enumerated all health care providers (doctors, nurses and midwives, including information on their employment status and primary place of work, in each of 15 districts in Java. Data were collected by three teams, one for each province. Results Provider density (number of doctors, nurses and midwives/1000 population was low by international standards – 11 out of 15 districts had provider densities less than 1.0. Approximately half of all three professional groups were permanent public servants. Contractual employment was also important for both nurses and midwives. The private sector as the primary source of employment is most important for doctors (37% overall and increasingly so for midwives (10%. For those employed in the public sector, two-thirds of doctors and nurses work in health centres, while most midwives are located at village-level health facilities. Conclusion In the health system established after Independence, the facilities established were staffed through a period of obligatory service for all new graduates in medicine, nursing and midwifery. The last elements of that staffing system ended in 2007 and the government has not been able to replace it. The private sector is expanding and, despite the fact that it will be of increasing importance in the coming decades, government information about providers in private practice is decreasing. Despite the promise of decentralization to

  16. Effects of consumption of probiotics and prebiotics on serum lipid levels in humans.

    Science.gov (United States)

    Pereira, Dora I A; Gibson, Glenn R

    2002-01-01

    The objective of this article is to review existing studies concerning the effects of probiotics and prebiotics on serum cholesterol concentrations, with particular attention on the possible mechanisms of their action. Although not without exception, results from animal and human studies suggest a moderate cholesterol-lowering action of dairy products fermented with appropriate strain(s) of lactic acid bacteria and bifidobacteria. Mechanistically, probiotic bacteria ferment food-derived indigestible carbohydrates to produce short-chain fatty acids in the gut, which can then cause a decrease in the systemic levels of blood lipids by inhibiting hepatic cholesterol synthesis and/or redistributing cholesterol from plasma to the liver. Furthermore, some bacteria may interfere with cholesterol absorption from the gut by deconjugating bile salts and therefore affecting the metabolism of cholesterol, or by directly assimilating cholesterol. For prebiotic substances, the majority of studies have been done with the fructooligosaccharides inulin and oligofructose, and although convincing lipid-lowering effects have been observed in animals, high dose levels had to be used. Reports in humans are few in number. In studies conducted in normal-lipidemic subjects, two reported no effect of inulin or oligofructose on serum lipids, whereas two others reported a significant reduction in serum triglycerides (19 and 27%, respectively) with more modest changes in serum total and LDL cholesterol. At present, data suggest that in hyperlipidemic subjects, any effects that do occur result primarily in reductions in cholesterol, whereas in normal lipidemic subjects, effects on serum triglycerides are the dominant feature.

  17. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    Science.gov (United States)

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (penzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  18. Towards a predictive systems-level model of the human microbiome: progress, challenges, and opportunities.

    Science.gov (United States)

    Greenblum, Sharon; Chiu, Hsuan-Chao; Levy, Roie; Carr, Rogan; Borenstein, Elhanan

    2013-08-01

    The human microbiome represents a vastly complex ecosystem that is tightly linked to our development, physiology, and health. Our increased capacity to generate multiple channels of omic data from this system, brought about by recent advances in high throughput molecular technologies, calls for the development of systems-level methods and models that take into account not only the composition of genes and species in a microbiome but also the interactions between these components. Such models should aim to study the microbiome as a community of species whose metabolisms are tightly intertwined with each other and with that of the host, and should be developed with a view towards an integrated, comprehensive, and predictive modeling framework. Here, we review recent work specifically in metabolic modeling of the human microbiome, highlighting both novel methodologies and pressing challenges. We discuss various modeling approaches that lay the foundation for a full-scale predictive model, focusing on models of interactions between microbial species, metagenome-scale models of community-level metabolism, and models of the interaction between the microbiome and the host. Continued development of such models and of their integration into a multi-scale model of the microbiome will lead to a deeper mechanistic understanding of how variation in the microbiome impacts the host, and will promote the discovery of clinically relevant and ecologically relevant insights from the rich trove of data now available. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Alterations in interferon-gamma and nitric oxide levels in human echinococcosis.

    Science.gov (United States)

    Ait Aissa, S; Amri, M; Bouteldja, R; Wietzerbin, J; Touil-Boukoffa, C

    2006-05-15

    Human cystic hydatid disease is characterized by the long-term coexistence of Echinococcus granulosus and its host without effective rejection of the parasite. This parasitic helminth infection currently constitutes a major health problem in Algeria. We investigated interferon-gamma (IFN-gamma) and nitrite (NO2-) production in PBMC culture 2 supernatants from Algerian patients (n = 35), stimulated by a major antigen (antigen 5). Nitrite was also observed in 74 sera and 28 cyst fluids of patients carrying cysts in different locations. In addition, we report the detection of Nitric Oxide Synthase-2 (NOS2) in liver biopsies of patients (n = 8) by an immunochemical method using human NOS2 antibody. In vivo nitrite levels in host sera and cyst biological fluid point to a tight relation between host response and macro-parasite effects. Our in vitro results indicate a correlation between nitrite and IFN-gamma production in PBMC culture supernatants. Furthermore, by immunohistochemistry NOS2 expression was observed in hepatocytes and Küpffer cells from hydatid patients. Collectively, our data imply NO production in host defense against the extracellular parasite, probably in response to an IFN-gamma activating signal. Concomitant enhanced levels of IFN-gamma and nitrite represent useful indicators of the clinical aggressiveness of hydatidosis.

  20. Expression of DMP-1 in the human pulp tissue using low level laser therapy

    Science.gov (United States)

    Lourenço Neto, Natalino; Teixeira Marques, Nádia Carolina; Fernandes, Ana Paula; Oliveira Rodini, Camila; Cruvinel Silva, Thiago; Moreira Machado, Maria Aparecida Andrade; Marchini Oliveira, Thais

    2015-09-01

    This study aimed to evaluate the effects of low-level laser therapy (LLLT) on DMP-1 expression in pulp tissue repair of human primary teeth. Twenty mandibular primary molars were randomly assigned into the following groups: Group I—Buckley’s Formocresol (FC); Group II—Calcium Hydroxide (CH); Group III—LLLT + CH and Group IV—LLLT + Zinc oxide/Eugenol. The teeth at the regular exfoliation period were extracted for histological analysis and immunolocalization of DMP-1. Descriptive analysis was performed on the dentin pulp complex. Histopathological assessment showed internal resorption in group FC. Groups CH and LLLT + CH provided better pulpal repair due to the absence of inflammation and the formation of hard tissue barrier. These two groups presented odontoblastic layer expressing DMP-1. According to this study, low level laser therapy preceding the use of calcium hydroxide exhibited satisfactory bio-inductive activity on pulp tissue repair of human primary teeth. However, other histological and cellular studies are needed to confirm the laser tissue action and efficacy.

  1. DETERMINING THE MOTIVATION LEVEL OF THE 25TH WINTER UNIVERSIADE HUMAN RESOURCES

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    Alparslan Muharrem KURUDİREK

    2012-12-01

    Full Text Available The aim of this research is to determine the motivation level of the personnel Working for the human resources in the 25th Winter Universiade Coordination Center and to comprehend whether there is any reaction against some demographic factors such like gender, marital status, administrative status and education level. Motivation scale which is of quinary Likert developed by Incir (1990 was implemented on 79 women (%35,4 and 144 men (%64,6 ,223 in total to acquire some data about the motivation of these personnel. When considered the distributions related to marital status %19.7 of them is married with the number of 44 people, %80.3 of them is single with the number of 179 people; when considered the distributions related to status, %19,3 of them is administrator with the number of 43 people, %80,7 of them is personnel with the number of 180 people.Frequency analysis in determining the demographic factors of the participants , t-test within independent groups in determining their motivation according to gender,status and marital status and single sided variance analysis (Anova in determining their motivation according to education levels were used. In this research, great difference was revealed in the comparison of motivation levels according to gender. According to this, male employees ( =4.47±375 have more average compared to female ones ( =3.13±217. This can be a result of that male employees are less effected from increasing workload, the concept of extra overtime which is not subject to any additional charge, and sometimes working even at the weekends. Additionally there was no great difference in the motivation level according to education level.

  2. Levels of matrix metalloproteinase-7 and osteopontin in human gingival crevicular fluid during initial tooth movement

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    Dhaval Oswal

    2015-01-01

    Full Text Available Purpose: During orthodontic treatment, the early response of periodontal tissues to mechanical stress involves several metabolic changes that allow tooth movement. The purpose of this investigation was to evaluate osteopontin (OPN and matrix metalloproteinase (MMP-7 in the gingival crevicular fluid (GCF of human teeth exposed to orthodontic force. Materials and Methods: GCF samples were obtained from 15 healthy orthodontic patients (age, 12-22 years. In each patient, the left maxillary canine having the fixed orthodontic appliance was used as the test tooth, and its antagonist, with no appliance, was the control. Orthodontic force, 75 g was applied using a 16 × 22 beta titanium closing loop. The GCF sampling on the disto-buccal aspects of experimental and control tooth was performed at specific time interval with sterilized absorbent paper point. Processing was carried out with enzyme-linked immunosorbent assay to detect OPN and MMP-7 levels. Results: The peak level of OPN was seen after 1 h application of orthodontic force which was 1280.36 pg/ml ± 185.02. The peak level of MMP-7 was seen at 0 h which was 598.3 pg/ml ± 107.5. The levels of OPN after 1 h increased to 1280.36 pg/ml ± 185.02, and they decreased at 24 h to 1012.86 pg/ml ± 168.47 (P = 0.001. The levels of MMP-7 after 1 h decreased to 478 pg/ml ± 99.7 which increased at 24 h to 526.9 pg/ml ± 99.2. Conclusions: Orthodontic forces affect both OPN and MMP-7 protein levels on the compression side in a time-dependent fashion.

  3. Tissue-specific variation in DNA methylation levels along human chromosome 1

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    De Bustos Cecilia

    2009-06-01

    Full Text Available Abstract Background DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Most methods to scan the genome in different tissues for differentially methylated sites have focused on the methylation of CpGs in CpG islands, which are concentrations of CpGs often associated with gene promoters. Results Here, we use a methylation profiling strategy that is predominantly responsive to methylation differences outside of CpG islands. The method compares the yield from two samples of size-selected fragments generated by a methylation-sensitive restriction enzyme. We then profile nine different normal tissues from two human donors relative to spleen using a custom array of genomic clones covering the euchromatic portion of human chromosome 1 and representing 8% of the human genome. We observe gross regional differences in methylation states across chromosome 1 between tissues from the same individual, with the most striking differences detected in the comparison of cerebellum and spleen. Profiles of the same tissue from different donors are strikingly similar, as are the profiles of different lobes of the brain. Comparing our results with published gene expression levels, we find that clones exhibiting extreme ratios reflecting low relative methylation are statistically enriched for genes with high expression ratios, and vice versa, in most pairs of tissues examined. Conclusion The varied patterns of methylation differences detected between tissues by our methylation profiling method reinforce the potential functional significance of regional differences in methylation levels outside of CpG islands.

  4. Comparison of organochlorine pesticide levels in human adipose tissue of inhabitants from Veracruz and Puebla, Mexico.

    Science.gov (United States)

    Waliszewski, Stefan M; Valencia Quintana, R; Corona, C A; Herrero, M; Sánchez, K; Aguirre, H; Aldave, I A; Gomez Arroyo, S; Villalobos Pietrini, R

    2010-01-01

    Since the discovery of insecticide properties of DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) and HCH (hexachlorocyclohexane), they have provided great benefits to humans in sanitary actions to combat the spread of infection-borne disease vectors. Public Health Programs in Mexico used DDT and HCH until 1999 as the insecticides of choice to control disease-transmitting organisms. Because of their persistence and accumulative properties, organochlorine pesticides bioconcentrate in lipids of the human body, reflecting the rate of environmental exposure. Eighty human abdominal adipose tissue samples from Veracruz and 80 samples from Puebla were analyzed and the obtained results were compared among both populations. The results from Veracruz showed higher contamination levels (mg/kg on lipid base) compared to Puebla: beta-HCH, 0.072 vs. 0.029; pp'DDE (Dichlorodiphenyldichloroethylene), 2.364 vs. 0.726; op'DDT, 0.022 vs. 0.025; pp'DDT, 0.192 vs. 0.061; and Sigma-DDT, 2.589 vs. 0.806. The population from Veracruz and from Puebla divided by sex, origin, and cause of death presented no statistical differences. The comparison between sexes (women and men groups) at Veracruz and Puebla indicated significantly higher levels in Veracruz and statistical significant differences. Calculating possible risks (odds ratios, OR), pp'DDE (OR = 5.04) and op'DDT (OR = 2.93) revealed significantly higher risk for the Veracruz population. The study indicated prolonged DDT exposure of Mexicans caused by the past sanitary use and persistence of its residues in soils and air.

  5. Provincial Human Development Index, a Guide for Efficiency Level Analysis: The Case of Iran

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    Asma Sabermahani

    2013-02-01

    Full Text Available Background: Human Development Index (HDI is a composite indicator that can show the impact of economic strategies on human life standards. The index is calculated by three main factors of income, education and health. This research studies the status of HDI across the Iranian provinces, its changes over time and the efficiency of provinces in using resources.Methods: The data for 2001 and 2009 was obtained from the Iranian Center of Statistics. Data envelopment analysis technique was used to analyze the data. To calculate the efficiency, Banker, Charnes and Cooper's model was used.Results: The national mean for the HDI in 2001 was 0.717 while it grew to 0.747 in 2009. Except for one province, all others had an improved human development index. Low ranked provinces such as Sistan & Baluchistan and Kurdistan stayed at the bottom in 2009 as well. Some provinces such as Bushehr with developing oil industries, or those purposively benefited from national oil income showed good growth. In some provinces, such as Hormozgan, out-migration of manpower to its neighboring province, Bushehr, was associated with decrease of the provincial income level. The number of efficient provinces increased from 5 to 13 in 2009.Conclusion: Iran falls among countries with high human development index based on the 2009 data. However, the distribution of HDI status across provinces was highly varied and the difference between high- and low-developed provinces increased in 2009. The government needs to revise policies concerning distribution of resources among the provinces.

  6. The impact of low level radioactive waste on humans and environment the next 100 thousands years

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, E.; Saetre, P.; Lindborg, T.; Norden, S.; Kautsky, U. [Svensk Kaernbraenslehantering AB - SKB (Sweden); Loefgren, A. [Ecoanalytica, Stockholm (Sweden)

    2014-07-01

    A safety assessment for the extension of the low level repository of operational waste (SFR) has been performed (SR-PSU). The repository (both existing and planned extension) is situated c 60 - 120 m below the surface in archaean granitoid rock. SR-PSU evaluates the risk to humans and the environment for the next 100 000 years. During this time period considerable changes are expected in the surface environment due climate change and its effects on shore line displacement, terrestrialisation of lakes and expansion of forest and agricultural land. In this paper specific approaches and results for the surface ecosystems (i.e. biosphere) are presented. The transport and accumulation of radionuclides in marine, lake, and terrestrial ecosystems are modelled and expose of future human populations during present conditions, greenhouse warming, and peri-glacial climate conditions are estimated taking into account different habits and diets of future humans. A new radionuclide transport model was developed to improve the representation of C-14 in the ecosystem modelling. In SR-PSU it is shown that the primary release from the repository via the geosphere to the biosphere is focused to a small area that will be a mire in about 1000 year. The radionuclides can thereafter be transported to downstream lakes and sea ecosystems. The aquatic systems can be utilised for fish and water whereas the mire can either be utilised directly by e.g. collecting, mushroom berries, hay, or hunting, or the mire can be transformed to a small agricultural area and utilised for crops. Important dose contributing radionuclides from SFR are Cl-36, Mo-93, C-14, Ni-59 and I-129 and in some of the scenarios the dose is close to the regulatory limit of 14 μSv/y (i.e. the risk 10{sup -6}). For Non-human biota (NHB) doses are estimated with a novel implementation of the ERICA tool in Ecolego. Generally the same radionuclides contributes to dose to NHB (reference organisms and site -specific organisms) as

  7. High-level expression of nonglycosylated human pancreatic lipase-related protein 2 in Pichia pastoris.

    Science.gov (United States)

    Sebban-Kreuzer, Corinne; Deprez-Beauclair, Paule; Berton, Amelie; Crenon, Isabelle

    2006-10-01

    The human pancreatic lipase-related protein 2 (HPLRP2) was produced in the methylotrophic yeast Pichia pastoris. The HPLRP2 cDNA corresponding to the protein coding sequence including the native signal sequence, was cloned into the pPIC9K vector and integrated into the genome of P. pastoris. P. pastoris transformants secreting high-level rHPLRP2 were obtained and the expression level into the liquid culture medium reached about 40mg/L after 4 days of culture. rHPLRP2 was purified by a single anion-exchange step after an overnight dialysis. N-terminal sequence analysis showed that the purified rHPLRP2 mature protein possessed a correct N-terminal amino acid sequence indicating that its signal peptide was properly processed. Mass spectrometry analysis showed that the recombinant HPLRP2 molecular weight was 52,532Da which was 2451Da greater than the mass calculated from the sequence of the protein (50,081Da) and 1536Da greater than the mass of the native human protein (50,996Da). In vitro deglycosylation experiments by peptide:N-glycosidase F (PNGase F) indicated that rHPLRP2 secreted from P. pastoris was N-glycosylated. Specific conditions were setup in order to obtain a recombinant protein free of glycan chain. We observed that blocking glycosylation in vivo by addition of tunicamycin in the culture medium during the production resulted in a correct processing of the rHPLRP2 mature protein. The lipase activity of glycosylated or nonglycosylated rHPLRP2, which was about 800U/mg on tributyrin, was inhibited by the presence of bile salts and not restored by adding colipase. In conclusion, the experimental procedure which we have developed will allow us to get a high-level production in P. pastoris of glycosylated and nonglycosylated rHPLRP2, suitable for subsequent biophysical and structural studies.

  8. Validation of a standardised method for determining beryllium in human urine at nanogram level.

    Science.gov (United States)

    Devoy, Jérôme; Melczer, Mathieu; Antoine, Guillaume; Remy, Aurélie; Heilier, Jean-François

    2013-10-01

    The potential toxicity of beryllium at low levels of exposure means that a biological and/or air monitoring strategy may be required to monitor the exposure of subjects. The main objective of the work presented in this manuscript was to develop and validate a sensitive and reproducible method for determining levels of beryllium in human urine and to establish reference values in workers and in non-occupationally exposed people. A chelate of beryllium acetylacetonate formed from beryllium(II) in human urine was pre-concentrated on a SPE C18 cartridge and eluted with methanol. After drying the eluate, the residue was solubilised in nitric acid and analysed by atomic absorption spectrometry and/or inductively coupled plasma mass spectrometry. The proposed method is 4 to 100 times more sensitive than other methods currently in routine use. The new method was validated with the concordance correlation coefficient test for beryllium concentrations ranging from 10 to 100 ng/L. Creatinine concentration, urine pH, interfering compounds and freeze-thaw cycles were found to have only slight effects on the performance of the method (less than 6%). The effectiveness of the two analytical techniques was compared statistically with each other and to direct analysis techniques. Even with a detection limit of 0.6 ng/L (obtained with inductively coupled plasma mass spectrometry), the method is not sensitive enough to detect levels in non-occupationally exposed persons. The method performance does however appear to be suitable for monitoring worker exposure in some industrial settings and it could therefore be of use in biological monitoring strategies.

  9. Fractalkine and TGF-β1 levels reflect the severity of chronic pancreatitis in humans

    Institute of Scientific and Technical Information of China (English)

    Mikihiko Yasuda; Tetsuhide Ito; Takamasa Oono; Ken Kawabe; Toyoma Kaku; Hisato Igarashi; Taichi Nakzmura; Ryoichi Takayanagi

    2008-01-01

    AIM: To darify whether serum chemoldne and cytokine levels can become useful biological and functional markers to assess the severity of chronic pancreatitis (CP). This study aimed at darifying whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of CP. METHODS: Serum monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta-1 (TGF-β1), and soluble type fractalkine (s-fractalkine) concentrations were examined in patients with CP (n = 109) and healthy controls (n = 116). Severity of disease was classified in patients with CP by a staging system. Relationships between stage-specific various clinical factors and serum MCP-1, TGF-β1, and s-fractalkine levels were investigated. Furthermore, 57 patients with non-alcoholic CP were similarly evaluated in order to exclude influence of alcohol intake. RESULTS: Patients with CP showed significant higher levels of serum TGF-β1 and s-fractalkine, but not MCP-1, compared to the controls. Serum TGF-β1 in the severe stage and s-fractalkine in the mild and the severe stage of CP significantly increased compared to those of controls. However, it was observed that both TGF-β1 and s-fractalkine levels were affected by alcohol intake. In patients with non-alcoholic CP, serum TGF-β1 showed significant increase in the moderate stage of CP, and serum s-fractalkine revealed significant increase in the early stage of CP. CONCLUSION: It is suggested that the measurement of serum F-fractalkine is useful to diagnose early-stage CP. Moreover, the combined determination of both, s-fractalkine and TGF-β1, in human sera may be helpful in evaluating the severity status of CP.

  10. Calcium and magnesium concentrations in mature human milk: influence of calcium intake, age and socioeconomic level.

    Science.gov (United States)

    Vítolo, M R; Valente Soares, L M; Carvalho, E B; Cardoso, C B

    2004-03-01

    Concentrations of calcium and magnesium were measured in mature milk, collected between 30 and 90 days after childbirth, from a group of 90 mothers between 14 and 39 years of age, exclusively breastfeeding. The group was divided into three sub-groups: low socioeconomic-level adolescents (LSAd), low socioeconomic-level adults (LSA), and high socioeconomic-level adults (HSA). Each mother's nutritional status was determined using the body-mass index (BMI) and her eating habits, obtained on the basis of a 24-h dietary recall. Adolescent and adult mothers in the low socioeconomic-level group had lower average calcium intake (LSAd = 618.4 +/- 555.2 mg and LSA = 679.4 +/- 411.4 mg) than adult mothers in the higher socioeconomic-level group (853.6 +/- 415.5 mg). The average concentration of calcium in the adolescent mothers' milk (LSAd) was significantly lower (5.30 +/- 1.42 mmol Ca/L, P = 0.01) than that of the two adult groups (LSA = 5.82 +/- 1.55 mmol Ca/L and HSA = 6.40 mmol Ca/L). The average magnesium concentrations for all groups did not show significant differences (LSAd = 1.06 +/- 0.18, LSA = 1.16 +/- 0.23 and HSA = 1.11 +/- 0.23 mmol Mg/L, for P= 0.16). These results indicate that magnesium concentrations in mature human milk do not seem to depend on maternal nutritional status. The condition of adolescence, however, associated with lower calcium intake by the mother, resulted in lower calcium concentrations in the milk secreted when compared to that of adult mothers.

  11. Heavy Metal Level in Human Semen with Different Fertility: a Meta-Analysis.

    Science.gov (United States)

    Sun, Jiantao; Yu, Guangxia; Zhang, Yucheng; Liu, Xi; Du, Chuang; Wang, Lu; Li, Zhen; Wang, Chunhong

    2017-03-01

    There are conflicting reports on the heavy metal levels in human semen with different fertilities. The purpose of this analysis is to merge and analyze the differences of heavy metal lead (Pb), cadmium (Cd), zinc (Zn), and copper (Cu) levels in male semen with normal and low fertilities. All documents in both Chinese and English were collected from the PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) database from inception date to February 19, 2016. We have used RevMan software (version 5.2) for the meta-analysis and Stata software (version 12.0) for the meta-regression and sensitivity analyses. A total of 20 literatures were included in the study. The results of the meta-analysis indicate a significant difference between fertility with three metal ions (Pb, Cd, Zn) while no significant difference with copper, detailed as follows: (i) 10 studies on the lead concentrations with a standardized mean difference (SMD) = 2.07, 95 %CI (0.97, 3.17), P < 0.01; (ii) 13 studies on the cadmium concentrations with an SMD = 0.75, 95 %CI (0.44, 1.07), P < 0.01; (iii) 8 studies on the concentrations of zinc with an SMD = -0.61, 95 %CI (-1.08, -0.14), P < 0.01; and (iv) 9 studies on the copper concentrations with an SMD = 0.42, 95 %CI (-0.29, 1.13), P = 0.247. The results indicate that the men with low fertility have higher semen Pb and Cd levels and lower semen Zn levels; more studies are needed to indicate the association of the semen copper level with fertility.

  12. The impact of climate change and emissions control on future ozone levels: Implications for human health.

    Science.gov (United States)

    Stowell, Jennifer D; Kim, Young-Min; Gao, Yang; Fu, Joshua S; Chang, Howard H; Liu, Yang

    2017-11-01

    Overwhelming evidence has shown that, from the Industrial Revolution to the present, human activities influence ground-level ozone (O3) concentrations. Past studies demonstrate links between O3 exposure and health. However, knowledge gaps remain in our understanding concerning the impacts of climate change mitigation policies on O3 concentrations and health. Using a hybrid downscaling approach, we evaluated the separate impact of climate change and emission control policies on O3 levels and associated excess mortality in the US in the 2050s under two Representative Concentration Pathways (RCPs). We show that, by the 2050s, under RCP4.5, increased O3 levels due to combined climate change and emission control policies, could contribute to an increase of approximately 50 premature deaths annually nationwide in the US. The biggest impact, however, is seen under RCP8.5, where rises in O3 concentrations are expected to result in over 2,200 additional premature deaths annually. The largest increases in O3 are seen in RCP8.5 in the Northeast, the Southeast, the Central, and the West regions of the US. Additionally, when O3 increases are examined by climate change and emissions contributions separately, the benefits of emissions mitigation efforts may significantly outweigh the effects of climate change mitigation policies on O3-related mortality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Modulation of Apolipoprotein D levels in human pregnancy and association with gestational weight gain

    Directory of Open Access Journals (Sweden)

    Lafond Julie

    2009-09-01

    Full Text Available Abstract Background Apolipoprotein D (ApoD is a lipocalin involved in several processes including lipid transport, but its modulation during human pregnancy was never examined. Methods We investigated the changes in the levels of ApoD in the plasma of pregnant women at the two first trimesters of gestation and at delivery as well as in the placenta and in venous cord blood. These changes were studied in 151 women classified into 9 groups in relation to their prepregnancy body mass index (BMI and gestational weight gain (GWG. Results Plasma ApoD levels decrease significantly during normal uncomplicated pregnancy. ApoD is further decreased in women with excessive GWG and their newborns. In these women, the ApoD concentration was tightly associated with the lipid parameters. However, the similar ApoD levels in low cholesterol (LC and high cholesterol (HC women suggest that the plasma ApoD variation is not cholesterol dependant. A tight regulation of both placental ApoD transcription and protein content is most probably at the basis of the low circulating ApoD concentrations in women with excessive GWG. After delivery, the plasma ApoD concentrations depended on whether the mother was breast-feeding or not, lactation favoring a faster return to baseline values. Conclusion It is speculated that the decrease in plasma ApoD concentration during pregnancy is an adaptive response aimed at maintaining fetal lipid homeostasis. The exact mechanism of this adaptation is not known.

  14. [Heart rhythm in humans with different processing levels of acoustic information].

    Science.gov (United States)

    Makarenko, M V; Lyzohub, V S; Iukhymenko, L I; Khomenko, S M

    2011-01-01

    The peculiarities of the heart rhythm regulation were investigated in humans during the processing of acoustic information. Statistically significant differences were found in individuals with different levels of auditory-motor reactions according to the heart rhythm characteristics. Individuals with the high level of reactions were characterized by significantly lower total power spectrum (TP=1276.2 ms2), by the power spectrum of high (HL=280.1 ms12) and very low frequencies (VLF-469.8 ms2), as well as by low indexes of standard deviation of R-R intervals (SDNN=37.4 ms), when compared with the persons with the low level of reactions (5248.8; 866.7; 1937.0; 69.8 ms2). The correlation analysis confirmed the dif- ferences between the groups ol persons with adtierent number of processed information and variable (r=0.41, P<0.05) and spectral characteristics of heart rate (r=-0.49--0.56, P<0.05). Different strategies of activation of non-specific brain systems in formation of psycho-physiological reactions and participation of heart rhythm regulatory mechanisms in vegetative support of auditory information processing are discussed.

  15. Examination of blood clobazam levels and several pupillary measures in humans.

    Science.gov (United States)

    Kotzan, J A; Needham, T E; Honigberg, I L; Vallner, J J; Stewart, J T; Brown, W J; Jun, H W

    1979-08-01

    The State-Trait Anxiety Inventory was administered to 15 subjects before initiation of the experiment. Three subgroups of five subjects were defined by computing the unweighted sum of the state and trait anxiety scores. A 40-mg dose of clobazam, a 1.5-benzodiazepine, was administered to each subject and repeated with two additional dosage forms following a 2-week washout period. Blood samples were withdrawn, and blood levels were determined by fluorometric analysis. Additionally, pupillary measures of critical flicker fusion, constriction, and dilation in response to a cognitive task were obtained at 0, 2, 4, and 6 hr. A repeated measures analysis of variance revealed that blood levels were, as expected, statistically different over time and dosage form. The pupillary constriction mirrored the blood levels in statistical patterns. The pupillary measure of cognition related to the anxiety state after the performance effects of the cognitive task were statistically removed. The results suggest that clobazam has less immediate human effect than does diazepam.

  16. Influence of Breastfeeding Time on Levels of Organochlorine Pesticides in Human Milk of a Mexican Population.

    Science.gov (United States)

    Chávez-Almazán, Luis A; Diaz-Ortiz, Jesús; Alarcón-Romero, Mario; Davila-Vazquez, Gustavo; Saldarriaga-Noreña, Hugo; Sampedro-Rosas, Laura; López-Silva, Saúl; Santiago-Moreno, Agustín; Rosas-Acevedo, José L; Waliszewski, Stefan M

    2016-02-01

    This study was conducted with the objective of determining whether there is a depuration of organochlorine pesticides in breast milk according to breastfeeding time. In total, 171 samples from mothers that lived in the State of Guerrero, Mexico were analyzed. There was a weak negative relationship between pp'DDE (r = -0.216) and Σ-DDT (r = -0.222) concentrations with the days of lactation. In a comparison analysis, a statistically significant decrease of pp'DDT and pp'DDE levels was observed, as well as the Σ-DDT from the first to the fifth week of lactation. A reduction of 0.188 mg/kg lipid of pp'DDE and 0.181 mg/kg lipid of Σ-DDT per week was obtained. HCB, β-HCH and op'DDT concentrations were low and had no major fluctuations between subgroups. The low levels found and the observed reduction in time involve less exposure to the infant to these pollutants. Through this methodology changes in levels of certain organochlorine pesticides in various stages of human milk production may be shown.

  17. A study on the levels of a polybrominated biphenyl in Chinese human milk samples collected in 2007 and 2011.

    Science.gov (United States)

    Liu, Xiao; Wen, Sheng; Li, Jingguang; Zhang, Lei; Zhao, Yunfeng; Wu, Yongning

    2016-09-01

    The levels of a 2,2',4,4',5,5'-hexabromobiphenyl (BB-153) were measured in human milk samples collected in 2007 and 2011 from residents in China by high-resolution gas chromatography-high-resolution mass chromatography (HRGC-HRMS) with isotope dilution. The median concentrations of BB-153 from the samples collected in 2007 and 2011 were 8.3 and 7.2 pg/g lipid weight, respectively. The levels of BB-153 in the human milk collected from rural areas were not significantly different to those collected from the urban areas in China. Meanwhile, significant positive correlations were found between the levels of BB-153 in human milk and the consumption of animal-origin foods. In the present study, the mean levels of BB-153 in human milk from Chinese mothers were found to be lower than those from European and American mothers.

  18. Levels of fecal corticosterone in sandhill cranes during a human-led migration

    Science.gov (United States)

    Hartup, B.K.; Olsen, G.H.; Czekala, Nancy M.; Paul-Murphy, J.; Langenberg, J.A.

    2004-01-01

    Fourteen captive-reared greater sandhill cranes (Grus canadensis tabida) were conditioned to follow ultralight aircraft to promote migration between Wisconsin and Florida (U SA) after release. Fecal samples were collected throughout the training period in Wisconsin and during a 1,977-km human-led migration to Florida to determine fecal corticosterone (FC) concentrations by radioimmunoassay. The mean (?SE) FC concentration during the training period was 1O9.5?7.5 ng/g and was representative of baseline levels recorded previously from sandhill cranes. Fecal corticosterone concentrations increased in early migration compared to concentrations 1 mo prior to departure (Pmigration period. The variability of FC concentrations in individual samples was greater throughout the migration than the training period. Increases in FC during migration were modest and generally consistent with normal corticosterone elevations observed in migrating birds.

  19. [Human placental lactogen levels in normal pregnancy monitored by serial ultrasound].

    Science.gov (United States)

    Sulović, V; Marinac, D; Stanković, A; Nikolić, Lj; Savić, M

    1991-01-01

    Parallel to the great use of ultrasound in diagnostical purposes the interest for biological effects of ultrasound is growing every day. The present studies of the biological action of ultrasound concerned the cytogenetic investigations as well as those of animals and men. Taking into account that the extrapolation of results from animals to men is uncertain all data obtained in human population are of utmost importance. We tried to define the possible biological action of routine diagnostical ultrasound on foetoplacental unit. Women with physiological pregnancy were exposed to ultrasound during regular antenatal control-examinations in the 20th, 30th and 38th week of gestation. The follow-up concerned HPL levels in the serum 1 hour before and 1 hour after exposure to ultrasound. There was no significant difference in concentrations of the examined hormone in both blood samples.

  20. Vitamin B12 levels in human milk during the first nine months of lactation.

    Science.gov (United States)

    Ford, C; Rendle, M; Tracy, M; Richardson, V; Ford, H

    1996-01-01

    Vitamin B12 concentration was measured by competitive binding radioassay in 48 samples of human milk from healthy mothers eating unrestricted diets. Specimens were collected 1-35 weeks after full-term delivery and were subjected to proteolytic digestion before radioassay in order to destroy binding proteins. The distribution of the results was skewed, but the distribution of the logged values was not significantly different from normal. The geometric mean vitamin B12 level remained almost unchanged during the first 12 weeks postpartum (261-297 pmol/l) and then declined to a low of 139 pmol/l at 27-35 weeks. A significant (P = 0.033) decline in vitamin B12 concentration between 6-12 weeks and 19-25 weeks postpartum was observed.

  1. Functional specificity for high-level linguistic processing in the human brain.

    Science.gov (United States)

    Fedorenko, Evelina; Behr, Michael K; Kanwisher, Nancy

    2011-09-27

    Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.

  2. Lead levels in human teeth from the inhabitants of Mexico City from three different historical periods

    Energy Technology Data Exchange (ETDEWEB)

    Mansilla, J.; Solis, C.; Chavez, M.E. [Instituto Nacional de Antropologia e Historia, Direccion de Antropologia Fisica, Mexico D.F. (Mexico)

    1999-07-01

    Human teeth from pre-Columbian, colonial and contemporary population groups were analyzed by PIXE in order to evaluate the lead contents in the inhabitants of Mexico City through different historical periods. Lead contents showed significant differences among the three groups, in Pre-Columbian teeth no lead was found, colonial teeth showed higher lead levels than contemporary ones. This results suggest that the native americans had no exposure to this toxic metal. The lead-glaze pottery introduced by the Spaniards, utilized in pottery and lead pipes, was the main source of lead in the colonial period. In recent teeth the deposited lead is mainly due to the absorption from the contaminated atmosphere. (Author)

  3. Future climate change driven sea-level rise: secondary consequences from human displacement for island biodiversity.

    Science.gov (United States)

    Wetzel, Florian T; Kissling, W Daniel; Beissmann, Helmut; Penn, Dustin J

    2012-09-01

    Sea-level rise (SLR) due to global warming will result in the loss of many coastal areas. The direct or primary effects due to inundation and erosion from SLR are currently being assessed; however, the indirect or secondary ecological effects, such as changes caused by the displacement of human populations, have not been previously evaluated. We examined the potential ecological consequences of future SLR on >1,200 islands in the Southeast Asian and the Pacific region. Using three SLR scenarios (1, 3, and 6 m elevation, where 1 m approximates most predictions by the end of this century), we assessed the consequences of primary and secondary SLR effects from human displacement on habitat availability and distributions of selected mammal species. We estimate that between 3-32% of the coastal zone of these islands could be lost from primary effects, and consequently 8-52 million people would become SLR refugees. Assuming that inundated urban and intensive agricultural areas will be relocated with an equal area of habitat loss in the hinterland, we project that secondary SLR effects can lead to an equal or even higher percent range loss than primary effects for at least 10-18% of the sample mammals in a moderate range loss scenario and for 22-46% in a maximum range loss scenario. In addition, we found some species to be more vulnerable to secondary than primary effects. Finally, we found high spatial variation in vulnerability: species on islands in Oceania are more vulnerable to primary SLR effects, whereas species on islands in Indo-Malaysia, with potentially 7-48 million SLR refugees, are more vulnerable to secondary effects. Our findings show that primary and secondary SLR effects can have enormous consequences for human inhabitants and island biodiversity, and that both need to be incorporated into ecological risk assessment, conservation, and regional planning. © 2012 Blackwell Publishing Ltd.

  4. Characterization of the tissue-level Ca2+ signals in spontaneously contracting human myometrium.

    Science.gov (United States)

    Bru-Mercier, Gilles; Gullam, Joanna E; Thornton, Steven; Blanks, Andrew M; Shmygol, Anatoly

    2012-12-01

    In the labouring uterus, millions of myocytes forming the complex geometrical structure of myometrium contract in synchrony to increase intrauterine pressure, dilate the cervix and eventually expel the foetus through the birth canal. The mechanisms underlying the precise coordination of contractions in human myometrium are not completely understood. In the present study, we have characterized the spatio-temporal properties of tissue-level [Ca(2+)](i) transients in thin slices of intact human myometrium. We found that the waveform of [Ca(2+)](i) transients and isotonic contractions recorded from thin slices was similar to the waveform of isometric contractions recorded from the larger strips in traditional organ bath experiments, suggesting that the spatio-temporal information obtained from thin slices is representative of the whole tissue. By comparing the time course of [Ca(2+)](i) transients in individual cells to that recorded from the bundles of myocytes we found that the majority of myocytes produce rapidly propagating long-lasting [Ca(2+)](i) transients accompanied by contractions. We also found a small number of cells showing desynchronized [Ca(2+)](i) oscillations that did not trigger contractions. The [Ca(2+)](i) oscillations in these cells were insensitive to nifedipine, but readily inhibited by the T-type Ca(2+) channel inhibitor NNC55-0396. In conclusion, our data suggest that the spread of [Ca(2+)](i) signals in human myometrium is achieved via propagation of long-lasting action potentials. The propagation was fast when action potentials propagated along bundles of myocytes and slower when propagating between the bundles of uterine myocytes. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  5. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    Science.gov (United States)

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.

  6. CBFA1 and topoisomerase I mRNA levels decline during cellular aging of human trabecular osteoblasts

    DEFF Research Database (Denmark)

    Christiansen, M; Kveiborg, Marie; Kassem, M

    2000-01-01

    reverse transcriptase-polymerase chain reaction (RT-PCR). There is a progressive and significant reduction of the CBFA1 steady-state mRNA level down to 50% during cellular aging of human osteoblasts. In comparison to the normal cells, human osteosarcoma cell lines SaOS-2 and KHOS/NP, and the SV40...

  7. Strain-level dissection of the contribution of the gut microbiome to human metabolic disease.

    Science.gov (United States)

    Zhang, Chenhong; Zhao, Liping

    2016-04-20

    The gut microbiota has been linked with metabolic diseases in humans, but demonstration of causality remains a challenge. The gut microbiota, as a complex microbial ecosystem, consists of hundreds of individual bacterial species, each of which contains many strains with high genetic diversity. Recent advances in genomic and metabolomic technologies are facilitating strain-level dissection of the contribution of the gut microbiome to metabolic diseases. Interventional studies and correlation analysis between variations in the microbiome and metabolome, captured by longitudinal sampling, can lead to the identification of specific bacterial strains that may contribute to human metabolic diseases via the production of bioactive metabolites. For example, high-quality draft genomes of prevalent gut bacterial strains can be assembled directly from metagenomic datasets using a canopy-based algorithm. Specific metabolites associated with a disease phenotype can be identified by nuclear magnetic resonance-based metabolomics of urine and other samples. Such multi-omics approaches can be employed to identify specific gut bacterial genomes that are not only correlated with detected metabolites but also encode the genes required for producing the precursors of those metabolites in the gut. Here, we argue that if a causative role can be demonstrated in follow-up mechanistic studies--for example, using gnotobiotic models--such functional strains have the potential to become biomarkers for diagnostics and targets for therapeutics.

  8. High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation.

    Directory of Open Access Journals (Sweden)

    Mirzokhid Rakhmanov

    Full Text Available Currently very little is known about the differential expression and function of the transcription factor SOX5 during B cell maturation. We identified two new splice variants of SOX5 in human B cells, encoding the known L-SOX5B isoform and a new shorter isoform L-SOX5F. The SOX5 transcripts are highly expressed during late stages of B-cell differentiation, including atypical memory B cells, activated CD21low B cells and germinal center B cells of tonsils. In tonsillar sections SOX5 expression was predominantly polarized to centrocytes within the light zone. After in vitro stimulation, SOX5 expression was down-regulated during proliferation while high expression levels were permissible for plasmablast differentiation. Overexpression of L-SOX5F in human primary B lymphocytes resulted in reduced proliferation, less survival of CD138neg B cells, but comparable numbers of CD138+CD38hi plasmablasts compared to control cells. Thus, our findings describe for the first time a functional role of SOX5 during late B cell development reducing the proliferative capacity and thus potentially affecting the differentiation of B cells during the germinal center response.

  9. Levels of perfluorooctanesulfonate and related fluorochemicals in human blood from the general population of Korea

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jae-Ho; Kim, Sun-Young; Shin, Im-Hee [Catholic Univ. of Daegu, School of Medicine, Dept. of Pharmacology/Toxicology, Daegu (Korea); Kannan, K. [Wardsworth Center, New York State Dept. of Health and Dept. of Env. Health and Tox., SUNY, Albany, NY (United States)

    2004-09-15

    Perfluorooctanesulfonate (PFOS) was found to be widespread in human populations and wildlife Major applications of these POSF-based products have included surfactants in: specialty paper and packaging products, carpet, upholstery, and textile products and in certain insecticide formulation. Depending on the specific functional derivatization or the degree of polymerization, such POSF based products may degrade or metabolize to PFOS, a stable and persistent end product that has the potential to bioaccumulate in the food chain. The mechanisms and pathways leading to the presence of PFOS in human blood are not well characterized but likely involve environmental and dietary exposure to PFOS or to precursor molecules of PFOS. PFOS and related perfluorinated compounds have recently been detected at low parts per billion (nanogram per milliliter) concentrations in the general population from 10 different countries including Korea. In the present report, the levels of perfluoroalkylated compounds in the general population from Korea were analyzed with respect to occupation, smoking status, sex, age and socio-economic status. The degree of association between the four target fluorochemicals measured in this study (PFOS, PFHxS, PFOA, and PFOSA) were also analyzed by linear regression to determine the potential association between their sources of exposure.

  10. Frequency-specific modulation of population-level frequency tuning in human auditory cortex

    Directory of Open Access Journals (Sweden)

    Roberts Larry E

    2009-01-01

    Full Text Available Abstract Background Under natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random under auditory focused attention by means of magnetoencephalography (MEG. Results In total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands. Conclusion The present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

  11. A Novel Human Radixin Peptide Inhibits Hepatitis C Virus Infection at the Level of Cell Entry.

    Science.gov (United States)

    Bukong, Terence N; Kodys, Karen; Szabo, Gyongyi

    2014-09-01

    Hepatitis C virus infection of hepatocytes is a multistep process involving the interaction between viral and host cell molecules. Recently, we identified ezrin-moesin-radixin proteins and spleen tyrosine kinase (SYK) as important host therapeutic targets for HCV treatment development. Previously, an ezrin hinge region peptide (Hep1) has been shown to exert anti-HCV properties in vivo, though its mechanism of action remains limited. In search of potential novel inhibitors of HCV infection and their functional mechanism we analyzed the anti-HCV properties of different human derived radixin peptides. Sixteen different radixin peptides were derived, synthesized and tested. Real-time quantitative PCR, cell toxicity assay, immuno-precipitation/western blot analysis and computational resource for drug discovery software were used for experimental analysis. We found that a human radixin hinge region peptide (Peptide1) can specifically block HCV J6/JFH-1 infection of Huh7.5 cells. Peptide 1 had no cell toxicity or intracellular uptake into Huh7.5 cells. Mechanistically, the anti-HCV activity of Peptide 1 extended to disruption of HCV engagement of CD81 thereby blocking downstream SYK activation, which we have recently demonstrated to be important for effective HCV infection of target hepatocytes. Our findings highlight a novel functional class of anti-HCV agents that can inhibit HCV infection, most likely by disrupting vital viral-host signaling interactions at the level of virus entry.

  12. Satisfaction Levels of Students and Professors with the Integration Workshop on Human Morphophysiology III

    Directory of Open Access Journals (Sweden)

    Luis Alberto Mass Sosa

    2012-12-01

    Full Text Available Background: Integration is a skill that is acquired and developed through exercises and learning activities designed for this purpose.Objective: To determine the level of satisfaction of students and professors with the integration workshop on the subject of Human Morphophysiology III in medicine studies from 2010 to 2011.Methods: A descriptive study was conducted at the Faculty of Medical Sciences of Cienfuegos, in the 2010-2011 academic years, with all students and professors who attended the workshop on the subject of Integration of Human Morphophysiology III, of medicine studies, (91 students and 16 teachers. A questionnaire was administered to students and professors who addressed the organizational and methodological considerations for the development of these activities.Results: Students were satisfied with the usefulness of the study guide (Iadov 0.68 and the activities for the consolidation of the contents (Iadov 0.60. Professors showed satisfaction with quality of the guide, usefulness of tasks and organization of the workshop (Iadov 0.81. Students reported the following as positive aspects of the workshop: basic clinical linking (36.46%, usefulness of the activity for the consolidation of content (32.97% and the participation of professors in the clinical area (26.37 %. Coincidentally, professors also considered as positive the latter two aspects. There were contradictions with the participation of students and professors.Conclusions: There was satisfaction in student and professors with organizational aspects and methodological considerations taken into account.

  13. Motivation of human resources for health: a case study at rural district level in Tanzania.

    Science.gov (United States)

    Zinnen, Véronique; Paul, Elisabeth; Mwisongo, Aziza; Nyato, Daniel; Robert, Annie

    2012-01-01

    An increasing number of studies explore the association between financial and non-financial incentives and the retention of health workers in developing countries. This study aims to contribute to empirical evidence on human resource for health motivation factors to assist policy makers in promoting effective and realistic interventions. A cross-sectional survey was conducted in four rural Tanzanian districts to explore staff stability and health workers' motivation. Data were collected using qualitative and quantitative techniques, covering all levels and types of health facilities. Stability of staff was found to be quite high. Public institutions remained very attractive with better job security, salary and retirement benefits. Satisfaction over working conditions was very low owing to inadequate working equipment, work overload, lack of services, difficult environment, favouritism and 'empty promotions'. Positive incentives mentioned were support for career development and supportive supervision. Attracting new staff in rural areas appeared to be more difficult than retaining staff in place. The study concluded that strategies to better motivate health personnel should focus on adequate remuneration, positive working and living environment and supportive management. However, by multiplying health facilities, the latest Tanzanian human resource for health plan could jeopardize current positive results.

  14. OAHG: an integrated resource for annotating human genes with multi-level ontologies

    Science.gov (United States)

    Cheng, Liang; Sun, Jie; Xu, Wanying; Dong, Lixiang; Hu, Yang; Zhou, Meng

    2016-01-01

    OAHG, an integrated resource, aims to establish a comprehensive functional annotation resource for human protein-coding genes (PCGs), miRNAs, and lncRNAs by multi-level ontologies involving Gene Ontology (GO), Disease Ontology (DO), and Human Phenotype Ontology (HPO). Many previous studies have focused on inferring putative properties and biological functions of PCGs and non-coding RNA genes from different perspectives. During the past several decades, a few of databases have been designed to annotate the functions of PCGs, miRNAs, and lncRNAs, respectively. A part of functional descriptions in these databases were mapped to standardize terminologies, such as GO, which could be helpful to do further analysis. Despite these developments, there is no comprehensive resource recording the function of these three important types of genes. The current version of OAHG, release 1.0 (Jun 2016), integrates three ontologies involving GO, DO, and HPO, six gene functional databases and two interaction databases. Currently, OAHG contains 1,434,694 entries involving 16,929 PCGs, 637 miRNAs, 193 lncRNAs, and 24,894 terms of ontologies. During the performance evaluation, OAHG shows the consistencies with existing gene interactions and the structure of ontology. For example, terms with more similar structure could be associated with more associated genes (Pearson correlation γ2 = 0.2428, p < 2.2e–16). PMID:27703231

  15. Circulating levels of human salusin-β, a potent hemodynamic and atherogenesis regulator.

    Directory of Open Access Journals (Sweden)

    Kazumi Fujimoto

    Full Text Available Using bioinformatics analysis, we previously identified salusin-β, an endogenous bioactive peptide with diverse physiological activities. Salusin-β is abundantly expressed in the neuroendocrine system and in systemic endocrine cells/macrophages. Salusin-β acutely regulates hemodynamics and chronically induces atherosclerosis, but its unique physicochemical characteristics to tightly adhere to all types of plastic and glassware have prevented elucidation of its precise pathophysiological role. To quantitate plasma total salusin-β concentrations, we produced rabbit and chicken polyclonal antibodies against the C- and N-terminal end sequences, circumvented its sticky nature, and successfully established a sandwich enzyme-linked immunosorbent assay (ELISA. Salusin-β was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to 6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed that a single immunoreactive salusin-β peak coincided with synthetic authentic salusin-β. Plasma salusin-β concentrations were unaffected by postural changes and by potent vasopressin release stimuli, such as hypertonic saline infusion or smoking. However, salusin-β concentrations showed significant circadian variation; concentrations were high during the daytime and reached the lowest concentrations in the early morning. Plasma salusin-β levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls. Patients with panhypopituitarism combined with complete central diabetes insipidus also showed significantly higher plasma salusin-β levels. Therefore, the ELISA system developed in this study will be useful for evaluating circulating total salusin-β levels and for confirming the presence of authentic salusin-β in human plasma. The obtained results suggest a limited contribution of the neuroendocrine system to peripheral total salusin

  16. Circulating interleukin-8 levels explain breast cancer osteolysis in mice and humans.

    Science.gov (United States)

    Kamalakar, Archana; Bendre, Manali S; Washam, Charity L; Fowler, Tristan W; Carver, Adam; Dilley, Joshua D; Bracey, John W; Akel, Nisreen S; Margulies, Aaron G; Skinner, Robert A; Swain, Frances L; Hogue, William R; Montgomery, Corey O; Lahiji, Parshawn; Maher, Jacqueline J; Leitzel, Kim E; Ali, Suhail M; Lipton, Alan; Nicholas, Richard W; Gaddy, Dana; Suva, Larry J

    2014-04-01

    Skeletal metastases of breast cancer and subsequent osteolysis connote a dramatic change in the prognosis for the patient and significantly increase the morbidity associated with disease. The cytokine interleukin 8 (IL-8/CXCL8) is able to directly stimulate osteoclastogenesis and bone resorption in mouse models of breast cancer bone metastasis. In this study, we determined whether circulating levels of IL-8 were associated with increased bone resorption and breast cancer bone metastasis in patients and investigated IL-8 action in vitro and in vivo in mice. Using breast cancer patient plasma (36 patients), we identified significantly elevated IL-8 levels in bone metastasis patients compared with patients lacking bone metastasis (pIL-8 and increased bone resorption (pIL-8 expression. In vitro, human MDA-MB-231 and MDA-MET breast cancer cell lines secrete two distinct IL-8 isoforms, both of which were found to stimulate osteoclastogenesis. However, the more osteolytic MDA-MET-derived full length IL-8(1-77) had significantly higher potency than the non-osteolytic MDA-MB-231-derived IL-8(6-77), via the CXCR1 receptor. MDA-MET breast cancer cells were injected into the tibia of nude mice and 7days later treated daily with a neutralizing IL-8 monoclonal antibody. All tumor-injected mice receiving no antibody developed large osteolytic bone tumors, whereas 83% of the IL-8 antibody-treated mice had no evidence of tumor at the end of 28days and had significantly increased survival. The pro-osteoclastogenic activity of IL-8 in vivo was confirmed when transgenic mice expressing human IL-8 were examined and found to have a profound osteopenic phenotype, with elevated bone resorption and inherently low bone mass. Collectively, these data suggest that IL-8 plays an important role in breast cancer osteolysis and that anti-IL-8 therapy may be useful in the treatment of the skeletal related events associated with breast cancer.

  17. Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration

    Directory of Open Access Journals (Sweden)

    Goffinet Christine

    2008-07-01

    Full Text Available Abstract Background The development of an immunocompetent, genetically modified mouse model to study HIV-1 pathogenesis and to test antiviral strategies has been hampered by the fact that cells from native mice do not or only inefficiently support several steps of the HIV-1 replication cycle. Upon HIV-1 infection, mouse T-cell lines fail to express viral proteins, but the underlying replication barrier has thus far not been unambiguously identified. Here, we performed a kinetic and quantitative assessment of consecutive steps in the early phase of the HIV-1 replication cycle in T-cells from mice and humans. Results Both T-cell lines and primary T-cells from mice harbor a severe post-entry defect that is independent of potential species-specTR transactivation. Reverse transcription occurred efficiently following VSV-G-mediated entry of virions into mouse T-cells, and abundant levels of 2-LTR circles indicated successful nuclear import of the pre-integration complex. To probe the next step in the retroviral replication cycle, i.e. the integration of HIV-1 into the host cell genome, we established and validated a nested real-time PCR to specifically quantify HIV-1 integrants exploiting highly repetitive mouse B1 elements. Importantly, we demonstrate that the frequency of integrant formation is diminished 18- to > 305-fold in mouse T-cell lines compared to a human counterpart, resulting in a largely abortive infection. Moreover, differences in transgene expression from residual vector integrants, the transcription off which is cyclin T1-independent, provided evidence for an additional, peri-integrational deficit in certain mouse T-cell lines. Conclusion In contrast to earlier reports, we find that mouse T-cells efficiently support early replication steps up to and including nuclear import, but restrict HIV-1 at the level of chromosomal integration.

  18. High-level, erythroid specific, expression of the human α-globin gene in transgenic mice and the production of human haemoglobin in murine erythrocytes.

    NARCIS (Netherlands)

    O. Hanscombe (Olivia); M. Vidal; J. Kaeda; L. Luzzatto; D.R. Greaves (David); F.G. Grosveld (Frank)

    1989-01-01

    textabstractUsing the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver and blood is copy number dependent and at levels comparable to that of

  19. Modulation of the human gut microbiota by dietary fibres occurs at the species level.

    Science.gov (United States)

    Chung, Wing Sun Faith; Walker, Alan W; Louis, Petra; Parkhill, Julian; Vermeiren, Joan; Bosscher, Douwina; Duncan, Sylvia H; Flint, Harry J

    2016-01-11

    Dietary intake of specific non-digestible carbohydrates (including prebiotics) is increasingly seen as a highly effective approach for manipulating the composition and activities of the human gut microbiota to benefit health. Nevertheless, surprisingly little is known about the global response of the microbial community to particular carbohydrates. Recent in vivo dietary studies have demonstrated that the species composition of the human faecal microbiota is influenced by dietary intake. There is now potential to gain insights into the mechanisms involved by using in vitro systems that produce highly controlled conditions of pH and substrate supply. We supplied two alternative non-digestible polysaccharides as energy sources to three different human gut microbial communities in anaerobic, pH-controlled continuous-flow fermentors. Community analysis showed that supply of apple pectin or inulin resulted in the highly specific enrichment of particular bacterial operational taxonomic units (OTUs; based on 16S rRNA gene sequences). Of the eight most abundant Bacteroides OTUs detected, two were promoted specifically by inulin and six by pectin. Among the Firmicutes, Eubacterium eligens in particular was strongly promoted by pectin, while several species were stimulated by inulin. Responses were influenced by pH, which was stepped up, and down, between 5.5, 6.0, 6.4 and 6.9 in parallel vessels within each experiment. In particular, several experiments involving downshifts to pH 5.5 resulted in Faecalibacterium prausnitzii replacing Bacteroides spp. as the dominant sequences observed. Community diversity was greater in the pectin-fed than in the inulin-fed fermentors, presumably reflecting the differing complexity of the two substrates. We have shown that particular non-digestible dietary carbohydrates have enormous potential for modifying the gut microbiota, but these modifications occur at the level of individual strains and species and are not easily predicted a priori

  20. Haemodynamic changes in human masseter and temporalis muscles induced by different levels of isometric contraction.

    Science.gov (United States)

    Kim, Y J; Kuboki, T; Tsukiyama, Y; Koyano, K; Clark, G T

    1999-08-01

    This study evaluated the influence of low contraction forces on intramuscular haemodynamics in human masseter and temporalis using near-infrared tissue spectroscopy. This method allowed the intramuscular haemoglobin (Hb) to be assessed dynamically before, during and after a 5, 15, 25 and 100% maximum voluntary contraction (MVC). Twenty volunteers, 10 males and 10 females, without pain or dysfunction in the masticatory system were included in this study. Data were recorded for 30 s before, 30 s during and 5 min after the four sustained contraction tasks. The results showed that all four levels of voluntary contraction produced a clear haemodynamic response (during and after contraction) in both muscles. For analytical purposes, the maximum Hb achieved after 100% MVC was set equal to 1.00. In the masseter the mean peak Hb during the 5, 15, 25 and 100% MVC was 0.49, 0.92, 1.30 and 1.73 while after the contractions it was 0.50, 0.65, 0.78 and 1.00, respectively. In the temporalis the peak Hb during the contractions was 0.23, 0.36, 0.48 and 0.66 and after the contractions 0.32, 0.45, 0.56 and 1.00, respectively. Repeated-measures analysis of variance revealed a significant main effect for the different contraction levels both in the masseter (during contraction, p = 0.001; after contraction, parchitecture between the two muscles contributes to these differences in blood flow.

  1. Lesion Size Correlates with Leishmania Antigen-Stimulated TNF-Levels in Human Cutaneous Leishmaniasis

    Science.gov (United States)

    Oliveira, Fabiano; Bafica, Andre; Rosato, Andrea B.; Favali, Cecilia B. F.; Costa, Jackson M.; Cafe, Virginia; Barral-Netto, Manoel; Barral, Aldina

    2011-01-01

    Cutaneous leishmaniasis (CL) is a worldwide disease endemic in several regions of the globe. The hallmark of CL is skin ulcers likely driven by efforts of the immune system to control Leishmania growth. Cytokines, such as tumor necrosis factor (TNF) and interferon-gamma can control disease progression in animal models. Nevertheless, the impact of these cytokines in CL ulcer outcome is not well established in humans. In this study, 96 CL patients from an endemic area of Leishmania braziliensis were enrolled for a follow-up study that consisted of clinical and immunological evaluations in a 2-year period. Statistical analysis revealed that healing time (P = 0.029), age (P = 0.002), and TNF levels (P = 0.0002) positively correlate with ulcer size at the time of the first clinical evaluation. Our findings suggest that ulcer size correlates with healing time and TNF levels support the use of TNF inhibitors combined with standard therapy to improve healing in CL patients with severe lesions. PMID:21734128

  2. Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans.

    Science.gov (United States)

    Djurhuus, C B; Gravholt, C H; Nielsen, S; Mengel, A; Christiansen, J S; Schmitz, O E; Møller, N

    2002-07-01

    Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.

  3. Physiological level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle

    OpenAIRE

    Akiko Sano; Hiroaki Matsushita; Hua Wu; Jin-An Jiao; Poothappillai Kasinathan; Eddie J. Sullivan; Zhongde Wang; Yoshimi Kuroiwa

    2013-01-01

    Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human...

  4. Levels and complexity of IgA antibody against oral bacteria in samples of human colostrum.

    Science.gov (United States)

    Petrechen, L N; Zago, F H; Sesso, M L T; Bertoldo, B B; Silva, C B; Azevedo, K P; de Lima Pereira, S A; Geraldo-Martins, V R; Ferriani, V P L; Nogueira, R D

    2015-01-01

    Streptococcus mutans (SM) have three main virulence antigens: glucan binding protein B (gbpB), glucosyltransferase (Gtf) and antigens I/II (Ag I/II) envolved in the capacity of those bacteria to adhere and accumulate in the dental biofilm. Also, the glycosyltransferases 153 kDa of Streptococcus gordonii (SGO) and 170kDa of Streptococcus sanguinis (SSA) were important antigens associated with the accumulation of those bacterias. Streptococcus mitis (SMI) present IgA1 protease of 202 kDa. We investigated the specificity and levels IgA against those antigens of virulence in samples of human colostrum. This study involved 77 samples of colostrum that were analyzed for levels of immunoglobulian A, M and G by Elisa. The specificity of IgA against extracts of SM and initials colonizators (SSA, SMI, SGO) were analyzed by the Western blot. The mean concentration of IgA was 2850.2 (±2567.2) mg/100 mL followed by IgM and IgG (respectively 321.8±90.3 and 88.3±51.5), statistically different (pbacteria antigens and theirs virulence antigens. To SM, the GbpB was significantly lower detected than others antigens of SM (p0.4). So, the breast milk from first hours after birth presented significant levels of IgA specific against important virulence of antigens those oral streptococci, which can disrupt the installation and accumulation process of these microorganisms in the oral cavity. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. Real-time Quantitative RT-PCR for CT9 Level in Human Cancer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    CT9 is a recently cloned cancer-testis antigen, which is a member of the bromodomain and extraterminal family.Each member of this protein family contains two N-terminal bromodomain motifs. We investigated the distribution of CT9 in different tissues and the possibility for it to be used as a potential therapeutic target in cancer treament. By using the real-time RT-PCR method and 18SrRNA as an internal standard, we analyzed the CT9 expression in several normal human tissues and in the tissues of patients suffering from cancer. The result of this study shows that the highest level of mRNA is only present in testis tissue because the CT9 expression has not been detected in other normal tissues. In 6 of 10 cases of gastric adenocarcinoma, in 3 of 10 cases of esophageal squamous cell carcinoma, in 2 of 9 cases of endometrial carcinoma and only in 1 of 12 cases of brain cancer, the low level expression of CT9 was detected. In none of the 12 cases of cervical squamous cell carcinoma, the expression of CT9 was detected. Since the high level expression of CT9 is only found in the normal testis tissue, but the low expression in cancer tissues, for example tissues of cervical squamous cell carcinoma, brain cancer, endometrial adenocarcinoma, esophageal squamous cell carcinoma, we conclude that CT9 cannot be used as a cancer therapeutic target molecule for cervical squamous cell carcinoma, brain cancer, endometrial adenocarcinoma, esophageal squamous cell carcinoma.

  6. Broadened population-level frequency tuning in human auditory cortex of portable music player users.

    Directory of Open Access Journals (Sweden)

    Hidehiko Okamoto

    Full Text Available Nowadays, many people use portable players to enrich their daily life with enjoyable music. However, in noisy environments, the player volume is often set to extremely high levels in order to drown out the intense ambient noise and satisfy the appetite for music. Extensive and inappropriate usage of portable music players might cause subtle damages in the auditory system, which are not behaviorally detectable in an early stage of the hearing impairment progress. Here, by means of magnetoencephalography, we objectively examined detrimental effects of portable music player misusage on the population-level frequency tuning in the human auditory cortex. We compared two groups of young people: one group had listened to music with portable music players intensively for a long period of time, while the other group had not. Both groups performed equally and normally in standard audiological examinations (pure tone audiogram, speech test, and hearing-in-noise test. However, the objective magnetoencephalographic data demonstrated that the population-level frequency tuning in the auditory cortex of the portable music player users was significantly broadened compared to the non-users, when attention was distracted from the auditory modality; this group difference vanished when attention was directed to the auditory modality. Our conclusion is that extensive and inadequate usage of portable music players could cause subtle damages, which standard behavioral audiometric measures fail to detect in an early stage. However, these damages could lead to future irreversible hearing disorders, which would have a huge negative impact on the quality of life of those affected, and the society as a whole.

  7. Late Post-glacial Sea Level Rise and Its Effects On Human Activity In Asia

    Science.gov (United States)

    Oppenheimer, S. J.

    Three rapid post-glacial sea-level rises flooded coastlines with large continental shelves. The last of these, shortly before the interglacial optimum c.7,500BP, not only changed coastal Neolithic societies, but may also have stimulated maritime skills. Two Asian examples explore these aspects. First, during the Mid-Holocene, the Arabian Gulf transgressed as far inland as Ur probably laying down Woolley's famous Ur Flood silt layer between 7,000-5,500 BP. Stratigraphy and dating suggests the phase of rapid sea level rise immediately preceded the start of the 'Ubaid pottery period. Red-slipped Uruk pottery and copper items then appear from about 6,000BP, but above Woolley's silt layer. The Sumerian King Lists also record a major upheaval and dynastic change after 'the Flood'. Second, the final flooding of the Sunda shelf in Southeast Asia was followed by a maritime extension of human occupation from Northern Melanesia south into the Solomon Islands 6,000 years ago. Simultaneously, further west on the north coast of New Guinea, new archaeological assemblages ap- pear beneath a silt layer left by a pro-grading 6,000 year-old inland sea. The presence of arboriculture items such as betel nuts and the contemporary arrival of dogs and pigs in the same region suggests intrusion from Southeast Asia. This supports Solheim's suggestion that rapid sea-level rise on the eastern edge of the Sunda Shelf stimulated maritime skills and invention in Southeast Asia. This may have provided the initial stimulus to the first maritime expansion that was later to colonise the whole Pacific.

  8. Cardiac lipid levels show diurnal changes and long-term variations in healthy human subjects.

    Science.gov (United States)

    Ith, Michael; Stettler, Christoph; Xu, Jian; Boesch, Chris; Kreis, Roland

    2014-11-01

    (1) H-MRS is regularly applied to determine lipid content in ectopic tissue - mostly skeletal muscle and liver - to investigate physiological and/or pathologic conditions, e.g. insulin resistance. Technical developments also allow non-invasive in vivo assessment of cardiac lipids; however, basic data about methodological reliability (repeatability) and physiological variations are scarce. The aim of the presented work was to determine potential diurnal changes of cardiac lipid stores in humans, and to put the results in relation to methodological repeatability and normal physiological day-to-day variations. Optimized cardiac- and respiratory-gated (1) H-MRS was used for non-invasive quantification of intracardiomyocellular lipids (ICCL), creatine, trimethyl-ammonium compounds (TMA), and taurine in nine healthy young men at three time points per day on two days separated by one week. This design allowed determination of (a) diurnal changes, (b) physiological variation over one week and (c) methodological repeatability of the ICCL levels. Comparison of fasted morning to post-absorptive evening measurements revealed a significant 37 ± 19% decrease of ICCL during the day (p = 0.0001). There was a significant linear correlation between ICCL levels in the morning and their decrease during the day (p = 0.015). Methodological repeatability for the ICCL/creatine ratio was excellent, with a coefficient of variance of ~5%, whereas physiological variation was found to be considerably higher (22%) in spite of a standardized physiological preparation protocol. In contrast, TMA levels remained stable over this time period. The proposed (1) H-MRS technique provides a robust way to investigate relevant physiological changes in cardiac metabolites, in particular ICCL. The present results suggest that ICCL reveal a diurnal course, with higher levels in the morning as compared to evening. In addition, a considerable long-term variation of ICCL levels, in both the morning and evening

  9. The Human Brain Does Not Need High Levels of Motivation to Learn a Foreign Language: Motivation Has Had Its Day

    Science.gov (United States)

    Green, Kieran

    2016-01-01

    Language is nature in action and something humans do. This literature review presents evidence from the literature that suggests that learning a foreign language in a classroom situation does not require high levels of student motivation. It is instead suggested that high levels of motivation are needed to make progress when a teacher is using…

  10. Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels

    DEFF Research Database (Denmark)

    Bøtkjær, Jane Alrø; Jeppesen, Janni Vikkelsø; Wissing, Marie Louise

    2015-01-01

    To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological ...

  11. Dietary whey protein lowers serum C-peptide concentration and duodenal SREBP-1c mRNA abundance, and reduces occurrence of duodenal tumors and colon aberrant crypt foci in azoxymethane-treated male rats.

    Science.gov (United States)

    Xiao, Rijin; Carter, Julie A; Linz, Amanda L; Ferguson, Matthew; Badger, Thomas M; Simmen, Frank A

    2006-09-01

    We evaluated partially hydrolyzed whey protein (WPH) for inhibitory effects on the development of colon aberrant crypt foci (ACF) and intestinal tumors in azoxymethane (AOM)-treated rats. Pregnant Sprague-Dawley rats and their progeny were fed AIN-93G diets containing casein (CAS, control diet) or WPH as the sole protein source. Colons and small intestines from the male progeny were obtained at 6, 12, 20 and 23 weeks after AOM treatment. At 6 and 23 weeks, post-AOM, WPH-fed rats had fewer ACF than did CAS-fed rats. Intestinal tumors were most frequent at 23 weeks, post-AOM. At this time point, differences in colon tumor incidence with diet were not observed; however, WPH-fed rats had fewer tumors in the small intestine (7.6% vs. 26% incidence, P=.004). Partially hydrolized whey protein suppressed circulating C-peptide concentration (a stable indicator of steady-state insulin secretion) at all four time points relative to the corresponding CAS-fed animals. The relative mRNA abundance for the insulin-responsive, transcription factor gene, SREBP-1c, was reduced by WPH in the duodenum but not colon. Results indicate potential physiological linkages of dietary protein type with circulating C-peptide (and by inference insulin), local expression of SREBP-1c gene and propensity for small intestine tumorigenesis.

  12. Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines.

    Science.gov (United States)

    Taylor, C W; Kim, Y S; Childress-Fields, K E; Yeoman, L C

    1992-02-29

    Six human colon tumor cell lines were analyzed for their constitutive levels of the c-myc protein. The nuclear proto-oncogene, c-myc, was detected as an expressed product in all of the human colon tumor cell lines analyzed. The poorly differentiated cell lines HCT116, RKO and C showed c-myc levels that averaged 2-fold greater than their well-differentiated counterparts, i.e., GEO, CBS and FET. When c-myc levels and responses to serum induction were analyzed in the presence of inducers of differentiation, i.e., dimethylformamide, retinoic acid, sodium butyrate and TGF-beta, distinct patterns of sensitivity and resistance emerged. Nuclear c-myc levels were reduced in all the colon cell phenotypes treated with dimethylformamide or sodium butyrate. Only the well-differentiated human colon tumor cell lines were responsive to transforming growth factor-beta. Only one of the human colon tumor cell lines (GEO) responded to retinoic acid. Increased levels of c-myc protein were found to correlate well with greater growth rates and with poor differentiation class. Similarly, a parallel sensitivity to down-regulation of c-myc levels and attenuation of c-myc induction curves for inducers of differentiation were observed in growth sensitive human colon tumor cell lines.

  13. High taxonomic level fingerprint of the human intestinal microbiota by ligase detection reaction--universal array approach.

    Science.gov (United States)

    Candela, Marco; Consolandi, Clarissa; Severgnini, Marco; Biagi, Elena; Castiglioni, Bianca; Vitali, Beatrice; De Bellis, Gianluca; Brigidi, Patrizia

    2010-04-19

    Affecting the core functional microbiome, peculiar high level taxonomic unbalances of the human intestinal microbiota have been recently associated with specific diseases, such as obesity, inflammatory bowel diseases, and intestinal inflammation. In order to specifically monitor microbiota unbalances that impact human physiology, here we develop and validate an original DNA-microarray (HTF-Microbi.Array) for the high taxonomic level fingerprint of the human intestinal microbiota. Based on the Ligase Detection Reaction-Universal Array (LDR-UA) approach, the HTF-Microbi.Array enables specific detection and approximate relative quantification of 16S rRNAs from 30 phylogenetically related groups of the human intestinal microbiota. The HTF-Microbi.Array was used in a pilot study of the faecal microbiota of eight young adults. Cluster analysis revealed the good reproducibility of the high level taxonomic microbiota fingerprint obtained for each of the subject. The HTF-Microbi.Array is a fast and sensitive tool for the high taxonomic level fingerprint of the human intestinal microbiota in terms of presence/absence of the principal groups. Moreover, analysis of the relative fluorescence intensity for each probe pair of our LDR-UA platform can provide estimation of the relative abundance of the microbial target groups within each samples. Focusing the phylogenetic resolution at division, order and cluster levels, the HTF-Microbi.Array is blind with respect to the inter-individual variability at the species level.

  14. Morphine Produces Immunosuppressive Effects in Non-human Primates at the Proteomic and Cellular Levels

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Joseph N.; Ortiz, Gabriel M.; Angel, Thomas E.; Jacobs, Jon M.; Gritsenko, Marina A.; Chan, Eric Y.; Purdy, David E.; Murnane, Robert D.; Larsen, Kay; Palermo, Robert E.; Shukla, Anil K.; Clauss, Therese RW; Katze, Michael G.; McCune, Joseph M.; Smith, Richard D.

    2012-05-11

    Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. As a prelude to understanding how these changes might interact with lentiviral infection in vivo, animals from two non-human primate (NHP) species [African green monkey (AGMs) and pigtailed macaque (PTs)] were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g., lymph node, colon, cerebrospinal fluid (CSF), and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an inter-organ, inter-individual, and inter-species basis. In both species, morphine was associated with decreased levels of (Ki-67+) T cell activation but with only minimal changes in overall T cell counts, neutrophil counts, and NK cells counts. While changes in T cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in the lymph node, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the interplay between opioid abuse and the response to infection with agents such as the human immunodeficiency virus, type 1 (HIV).

  15. HLA-G expression levels influence the tolerogenic activity of human DC-10

    Science.gov (United States)

    Amodio, Giada; Comi, Michela; Tomasoni, Daniela; Gianolini, Monica Emma; Rizzo, Roberta; LeMaoult, Joël; Roncarolo, Maria-Grazia; Gregori, Silvia

    2015-01-01

    Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions. Our group identified a subset of human dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 pathway. In this study we aimed at defining the role of HLA-G in DC-10-mediated Tr1 cell differentiation. We analyzed phenotype, functions, and genetic variations in the 3′ untranslated region of the HLA-G locus of in vitro-differentiated DC-10 from 67 healthy donors. We showed that HLA-G expression on DC-10 is donor-dependent. Functional studies demonstrated that DC-10, independently of HLA-G expression, secrete interleukin-10 and negligible levels of interleukin-12. Interestingly, DC-10 with high HLA-G promote allo-specific anergic T cells that contain a significantly higher frequency of Tr1 cells, defined as interleukin-10-producing (P=0.0121) or CD49b+LAG-3+ (P=0.0031) T cells, compared to DC-10 with low HLA-G. We found that the HLA-G expression on DC-10 is genetically imprinted, being associated with specific variations in the 3′ untranslated region of the gene, and it may be finely tuned by microRNA-mediated post-transcriptional regulation. These data highlight the important role of HLA-G in boosting DC-10 tolerogenic activity and confirm that interleukin-10 production by DC-10 is necessary but not sufficient to promote Tr1 cells at high frequency. These new insights into the role of HLA-G in DC-10-mediated induction of Tr1 cells provide additional information for clinical use in Tr1- or DC-10-based cell therapy approaches. PMID:25661445

  16. Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Samandari, Nasim; Mirza, Aashiq H; Nielsen, Lotte B

    2017-01-01

    from the Danish Remission Phase Cohort, and profiled for miRNAs. At the same time points, meal-stimulated C-peptide and HbA1c levels were measured and insulin-dose adjusted HbA1c (IDAA1c) calculated. miRNAs that at 3 months after diagnosis predicted residual beta cell function and glycaemic control......, hsa-miR-197-3p, hsa-miR-301a-3p and hsa-miR-375) at 3 months correlated with residual beta cell function 6-12 months after diagnosis. Stimulated C-peptide at 12 months was predicted by hsa-miR-197-3p at 3 months (p = 0.034). A doubling of this miRNA level corresponded to a sixfold higher stimulated C-peptide...

  17. Pineal melatonin level disruption in humans due to electromagnetic fields and ICNIRP limits.

    Science.gov (United States)

    Halgamuge, Malka N

    2013-05-01

    The International Agency for Research on Cancer (IARC) classifies electromagnetic fields (EMFs) as 'possibly carcinogenic' to humans that might transform normal cells into cancer cells. Owing to high utilisation of electricity in day-to-day life, exposure to power-frequency (50 or 60 Hz) EMFs is unavoidable. Melatonin is a natural hormone produced by pineal gland activity in the brain that regulates the body's sleep-wake cycle. How man-made EMFs may influence the pineal gland is still unsolved. The pineal gland is likely to sense EMFs as light but, as a consequence, may decrease the melatonin production. In this study, more than one hundred experimental data of human and animal studies of changes in melatonin levels due to power-frequency electric and magnetic fields exposure were analysed. Then, the results of this study were compared with the International Committee of Non-Ionizing Radiation Protection (ICNIRP) limit and also with the existing experimental results in the literature for the biological effect of magnetic fields, in order to quantify the effects. The results show that this comparison does not seem to be consistent despite the fact that it offers an advantage of drawing attention to the importance of the exposure limits to weak EMFs. In addition to those inconsistent results, the following were also observedfrom this work: (i) the ICNIRP recommendations are meant for the well-known acute effects, because effects of the exposure duration cannot be considered and (ii) the significance of not replicating the existing experimental studies is another limitation in the power-frequency EMFs. Regardless of these issues, the above observation agrees with our earlier study in which it was confirmed that it is not a reliable method to characterise biological effects by observing only the ratio of AC magnetic field strength to frequency. This is because exposure duration does not include the ICNIRP limit. Furthermore, the results show the significance of

  18. The Prosecution of State-Level Human Trafficking Cases in the United States

    Directory of Open Access Journals (Sweden)

    Amy Farrell

    2016-05-01

    Full Text Available In an effort to combat human trafficking, the United States federal government and all fifty states passed new laws that criminalise human trafficking and support the identification and prosecution of human trafficking perpetrators. Despite the passage of these laws, only a small number of human trafficking cases have been prosecuted in the last fifteen years. Guided by the notion that prosecutors seek to avoid uncertainty when making decisions to pursue criminal prosecution, we explore how human trafficking crimes are indicted under these newly defined state laws. Using a sample of cases from twelve US counties and interviews with police, prosecutors and court personnel, we examine the factors that influence the decision to prosecute crimes investigated as human trafficking in state court. This research informs our understanding of why so few human trafficking cases are prosecuted and why human trafficking suspects are rarely convicted of trafficking offenses.

  19. Productive human immunodeficiency virus infection levels correlate with AIDS-related manifestations in the patient

    Energy Technology Data Exchange (ETDEWEB)

    Mathez, D.; Paul, D.; de Belilovsky, C.; Sultan, Y.; Deleuze, J.; Gorin, I.; Saurin, W.; Decker, R.; Leibowitch, J. (Univ. Rene-Descartes Paris-Ouest, Garches (France))

    1990-10-01

    Mononuclear cells were obtained from 71 human immunodeficiency virus type 1 (HIV-1) seropositive subjects presenting and first visit either as asymptomatic or with minor symptoms and with CD4 lymphocytes greater than 550 per mm3 (group A, 35 patients) or as patients with AIDS, AIDS-related illnesses, or CD4 lymphocytes less than 400 per mm3 (group B, 36 patients). After 1-5 years of follow-up, 13 patients of group A had essentially retained their initial status (asymptomatics); the 22 others had suffered clinical or immunological deterioration (progressors). Frozen cells were thawed and submitted to lethal gamma-irradiation in vitro (4500 rads; 1 rad = 0.01 Gy) before they were cultured with normal phytohemagglutinin-stimulated lymphocytes to determine radiation-resistant HIV expression ex vivo (R-HEV). HIV antigenemia correlated with R-HEV values in 142 samples (r = 0.92, P less than 0.001) but was a less sensitive predictor of disease than R-HEV. R-HEV was detected in all specimens from patients with major AIDS-related illnesses or HIV-associated CD4 lymphopenia. In 77% of the progressors from group A, R-HEV detection preceded the onset of AIDS-associated disease or CD4 lymphopenia by 1 year (average). Conversely, R-HEV was low or was not detected in 36 sequential specimens from the 13 patients who remained asymptomatic over the following 2-5 years. Thus, persistently low HIV expression in vivo predicted a nondiseased state, whereas higher HIV expression levels seemed necessary for disease to occur. These data indicate that R-HEV is related to productive HIV infection in vivo, the latter acting as a determinant of AIDS-related illnesses. In view of this, measurement of HIV expression levels in the patient should be useful in antiviral efficacy trials.

  20. The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene.

    Directory of Open Access Journals (Sweden)

    Hiroki Isomura

    Full Text Available BACKGROUND: Human cytomegalovirus (HCMV can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5' mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth. CONCLUSIONS/SIGNIFICANCE: While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV- infected cells.

  1. The Prosecution of State-Level Human Trafficking Cases in the United States

    OpenAIRE

    Amy Farrell; Monica J DeLateur; Colleen Owens; Stephanie Fahy

    2016-01-01

    In an effort to combat human trafficking, the United States federal government and all fifty states passed new laws that criminalise human trafficking and support the identification and prosecution of human trafficking perpetrators. Despite the passage of these laws, only a small number of human trafficking cases have been prosecuted in the last fifteen years. Guided by the notion that prosecutors seek to avoid uncertainty when making decisions to pursue criminal prosecution, we explore how h...

  2. The Effect of Low Level Laser Irradiation on Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Hossein Baharvand

    2005-01-01

    Full Text Available Introduction: Different effects of low level laser irradiation (LLLI on various cell types have already been demonstrated. However, its effects on embryonic stem cells have not yet been shown. The present study evaluates the morphological and immunocytochemical effects of LLLI on human embryonic stem cell (hESC colonies. Material and Methods: Equal-sized pieces of hESC line (Royan H1 were irradiated with a single dose of 830-nm Ga-Al-As diode laser (3, 5, and 8 jcm-2, 30mW and cultured on mouse embryonic fibroblasts. The morphology of the colonies was evaluated qualitatively by observation under an inverted microscope (grades A, B, C, and D exhibited 0-30%, 30-50%, 50-80%, and 80-100% differentiation, respectively. The stemness area was assessed by expression of surface antigens using anti-Tra-1-60 and anti-Tra-1-81. Results: Our data demonstrated a dose-dependent stimulatory effect of LLLI on hESC differentiation. Two doses of 5 and 8jcm-2 induced statistically significant differentiation (grades C and D. Conclusions: These data showed that LLLI influenced hESC differentiation, which might be used for cell therapy after transplantation

  3. [Hyaluronic acid (hyaluronan) levels in pathological human saphenous veins. Effects of procyanidol oligomers].

    Science.gov (United States)

    Drubaix, I; Maraval, M; Robert, L; Robert, A M

    1997-01-01

    We investigated the hyaluronan content in the pathologic human venous wall using an ELSA assay with hyaluronectin according to the method of Delpech et al. The mean hyaluronan content in the 74 fragments from 12 venous walls studied was 596 +/- 528 ng/mg dry weight. These 12 venous walls could be separated in 3 distinct groups according to their hyaluronan content, low (277 +/- 141 ng/mg dry weight), moderate (552 +/- 361 ng/m dry weight) or high (1299 +/- 568 ng/mg dry weight). The differences between these groups are significant (p < 0.001). The presence of a veino-lymphatic oedema was generally associated with a high hyaluronan level (in 65% of cases). The 3H-glucosamine incorporation in cultured venous wall explants showed a 35% increase (p < 0.002) in varicosis as compared with the non or less modified segments of the vein and a 29% (p < 0.001) increase in presence of a veino-lymphatic oedema. The addition of 1 mg/ml of PCO (Procyanidolic Oligomers) to the culture media induced near to 20% decrease of the 3H-glucosamine incorporation and a 34% decrease of the hyaluronan content. Our results confirm the role of local overproduction of hyaluronan in the establishment of oedema and the potential effect of PCO to counteract it.

  4. Lead levels in human milk and children's health risk: a systematic review.

    Science.gov (United States)

    Koyashiki, Gina Ayumi Kobayashi; Paoliello, Monica Maria Bastos; Tchounwou, Paul B

    2010-01-01

    Lead (Pb), a naturally-occurring element and industrially-produced metal, is highly toxic to children, causing intellectual and behavioral deficits, hyperactivity, fine motor function deficits, decreased intelligence quotient, alteration of hand-eye coordination, and problems in reaction time. Children's exposure to Pb occurs mainly through ingestion of contaminated food, water and soil. Few discussions have been held on the magnitude and potential risk associated with exposure from the consumption of breast milk. Hence, this research was designed to systematically review the scientific literature on published epidemiologic studies, with an emphasis on the study designs and analytical procedures used for Pb assessment in breast milk. From a total of 112 selected articles published since the 1980s, 11 met the inclusion criteria. A review of the data indicated that Pb levels varied from 0.15 to 6.1 microg L(-1) in mature milk samples, from 0.48 to 14.6 microg L(-1) in colostrum samples, and were non-detectable in some samples. The milk/blood ratio, which estimates the mean efficiency transfer of lead from blood to milk, varied between 0.01 and 0.48. The heterogeneity of methods revealed by our assessment of published studies underscores the need for harmonization of study designs and sample collection and analysis protocols to reflect specific exposure scenarios. Human milk seems to be one of the relevant biological matrices for use as a biomarker for assessing children's health risk to Pb poisoning.

  5. Normal human epidermal keratinocytes treated with 7-dehydrocholesterol express increased levels of heat shock protein.

    Science.gov (United States)

    Mammone, Thomas; Muizzuddin, Neelam; Goyarts, Earl; Gan, David; Giacomoni, Paolo; Marenus, Ken; Maes, Daniel

    2004-01-01

    Human skin, and its isolated cells, respond to insults with a variety of repair and protective mechanisms. One such mechanism is the production of heat shock proteins (HSPs). Heat shock proteins help the other cellular proteins fold correctly into their active three-dimensional structures. Therefore, they can enhance the survival of cells under harsh, denaturing conditions. In order to develop a means of promoting the heat shock response to prepare the skin to withstand insult, we are investigating materials that appear to protect the skin biologically. One such material is vitamin D3 and its precursors. We have observed that keratinocytes treated with 7-dehydrocholesterol (7-DHC), a precursor of vitamin D3, have increased levels of protein and mRNA for heat shock proteins. In addition, we observed that topically applied 7-DHC increases the minimal dose of UVB required to induce erythema. These data suggest that 7-DHC can induce heat shock proteins in skin keratinocytes and that they will be more resistant to UVB insult.

  6. Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

    Science.gov (United States)

    Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

    2015-09-01

    Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

  7. Occurrence of Organochlorines Contaminants in Coastal Fish from Sepetiba Bay: Levels and Human Health Repercussions

    Directory of Open Access Journals (Sweden)

    A. Pacheco Ferreira

    2013-11-01

    Full Text Available The aim of this study was to survey levels of polychlorinated biphenyls (PCBs, polychlorinateddibenzofurans (PCDFs, and polychlorinated dibenzo-p-dioxins (PCDDs in white mullet (Mugil curema,common snook (Centropomus undecimalis, and acoupa weakfish (Cynoscion acoupa, collected at Sepetibabay, Rio de Janeiro, Brazil, March-August 2013. PCBs and PCDD/Fs were determined by High Resolution GasChromatography/High Resolution Mass Spectrometry (HRGC/HRMS as stated by the US EPA 1613B, 1668B,and 8290A methods. The concentration of total PCBs ranged from 0.589688 ~ 0.6981629 pg-WHO-TEQ/g wwand PCDDs/PCDFs ranged from 0.134037 ~ 0.242573 pg-WHO-TEQ/g ww. The concentrations of thesecontaminants on fish species currently appear to fall below critical values, and the dietary consumption of thesespecies did not represent a risk for human health. However, seeking to avoid future problems, systematicmonitoring can prevent complications to the environment, marine wildlife and public health impacts.

  8. Pursuit tracking and higher levels of skill development in the human pilot

    Science.gov (United States)

    Hess, R. A.

    1981-01-01

    A model of the human pilot is offered for pursuit tracking tasks; the model encompasses an existing model for compensatory tracking. The central hypothesis in the development of this model states that those primary structural elements in the compensatory model responsible for the pilot's equalization capabilities remain intact in the pursuit model. In this latter case, effective low-frequency inversion of the controlled-element dynamics occurs by feeding-forward derived input rate through the equalization dynamics, with low-frequency phase droop minimized. The sharp reduction in low-frequency phase lag beyond that associated with the disappearance of phase droop is seen to accompany relatively low-gain feedback of vehicle output. The results of some recent motion cue research are discussed and interpreted in terms of the compensatory-pursuit display dichotomy. Tracking with input preview is discussed in a qualitative way. In terms of the model, preview is shown to demand no fundamental changes in structure or equalization and to allow the pilot to eliminate the effective time delays that accrue in the inversion of the controlled-element dynamics. Precognitive behavior is discussed, and a model that encompasses all the levels of skill development outlined in the successive organizations of perception theory is finally proposed.

  9. Detection of Human Papillomavirus Infections at the Single-Cell level

    Science.gov (United States)

    Hulbert, Ayaka; Koutsky, Laura A.; Kiviat, Nancy B.; Xi, Long Fu

    2016-01-01

    Objective To explore a possibility of single-cell analysis of human papillomavirus (HPV) infection. Methods Two hundred and twenty cells were isolated by laser-capture microdissection from formalin-fixed and paraffin-embedded cervical tissue blocks from 8 women who had HPV DNA detected in their cervical swab samples. The number of type-specific HPV copies in individual cells was measured by quantitative polymerase chain reaction with and without a prior reverse transcription. Cells were assayed and counted for more than once if the corresponding swab sample was positive for ≥2 HPV types. Results Infection with HPV16, HPV39, HPV51, HPV52, HPV58, HPV59, and HPV73 was detected in 12 (5.5%) of 220, 3 (9.4%) of 32, 3 (5.8%) of 52, 11 (22.9%) of 48, 9 (18.8%) of 48, 3 (9.4%) of 32 and none of 20 cells, respectively. Numbers of HPV genome copies varied widely from cell to cell. Coexistence of multiple HPV types was detected in 6 (31.6%) of 19 positive cells from one of the 6 women who had 2 or 3 HPV types detected in their swab samples. Conclusion Given the heterogeneity of HPV status in individual cells, further clarification of HPV infection at the single-cell level may refine our understanding of HPV-related carcinogenesis. PMID:26820741

  10. Hudson River Paleoclimate, Sea Level, and Human Impact: A Record From Piermont Marsh, NY

    Science.gov (United States)

    Kurdyla; Peteet, Dorothy; Liberman, Louisa; Sugar; Wong; Hansen, James E. (Technical Monitor)

    2001-01-01

    A 13.77 meter sediment core from Piermont Marsh, NY (40 00 N, 73 55W) records the local and regional vegetational and foraminiferal history of the Hudson Estuary. The sediments were sampled every 4 cm, which represents a decadal to centuryscale resolution. Basal sediment dating is in progress, and the 11-m depth represents about 4000 years. Changes in plant macrofossils and charcoal appear to indicate differences in salinIty and drought, suggesting changes in climate. Scirpus, Salicornia, and high levels of charcoal seem to indicate drier/more saline conditions, while lack of these macrofossils and increases in Chara/Nitella, aquatic leaves, and very little charcoal suggests wetter conditions. Other macrofossils include Carex, Juncus, Polygonum, Zanichellia, Ruppia. High resolution AMS dating of plant macrofossils is in progress, and will be compared with changes in Hudson River sediment cores offshore. Foraminiferal assemblages from key intervals of the core will be presented. Human impact in the upper sediments is visible from the influx of grass seeds, primarily Phragmites, and the ragweed pollen rise.

  11. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution

    Directory of Open Access Journals (Sweden)

    Sambavi Kugananthan

    2016-11-01

    Full Text Available Human milk (HM contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p < 0.0001, n = 287. No association was found between whole HM leptin and fat content (p = 0.17, n = 287, supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89. These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding.

  12. Screening-level human health risk assessment of toluene and dibutyl phthalate in nail lacquers.

    Science.gov (United States)

    Kopelovich, Luda; Perez, Angela L; Jacobs, Neva; Mendelsohn, Emma; Keenan, James J

    2015-07-01

    Toluene and dibutyl phthalate (DBP) are found in many consumer products, including cosmetics, synthetic fragrances, and nail polish. In 2012, the California Environmental Protection Agency evaluated 25 nail products and found that 83% of the products that claimed to be toluene-free contained toluene at concentrations ranging up to 190,000 ppm, and 14% of the products that claimed to be DBP-free contained DBP at concentrations ranging up to 88,000 ppm. We conducted a preliminary, screening-level analysis of the potential toluene and DBP-related health risks to consumers and professionals based on the medium and maximum concentrations of toluene and DBP presented in the 2012 report and evaluated dermal and inhalation exposure to a salon patron, nail technician, and home user. We concluded that the maximum toluene concentration for the technician and home user scenarios exceeded the California MADL, but the estimated air concentrations did not exceed the Federal or Cal OSHA PEL. The MADL for DBP was exceeded for all user scenarios at both the median and maximum concentrations. Using these highly conservative assumptions, exposures above regulatory limits could possibly occur during routine use of nail products; further research is needed in order to evaluate potential human health risks. Published by Elsevier Ltd.

  13. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution.

    Science.gov (United States)

    Kugananthan, Sambavi; Lai, Ching Tat; Gridneva, Zoya; Mark, Peter J; Geddes, Donna T; Kakulas, Foteini

    2016-11-08

    Human milk (HM) contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p leptin and fat content (p = 0.17, n = 287), supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89). These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding.

  14. Human Walk Modeled by PCPG to Control a Lower Limb Neuroprosthesis by High-Level Commands

    Directory of Open Access Journals (Sweden)

    Matthieu Duvinage

    2012-06-01

    Full Text Available Current active leg prostheses do not integrate the most recent advances in Brain-Computer Interfaces (BCI and bipedal robotics. Moreover, their actuators are seldom driven by the subject’s intention. This paper aims at showing a summary of our current results in the field of human gait rehabilitation. In a first prototype, the main focus was on people suffering from foot drop problems, i.e. people who are unable to lift their feet. However, current work is focusing on a full active ankle orthosis. The approach is threefold: a BCI system, a gait model and an orthosis. Thanks to the BCI system, patients are able to generate high-level commands. Typically, a command could represent a speed modification. Then, a gait model based on a programmable central pattern generator is used to generate the adequate kinematics. Finally, the orthosis is tracking this kinematics when the foot is in the air, whereas, the orthosis is mimicking a spring when the foot is on the ground.

  15. Repeat use of human recombinant bone morphogenetic protein-2 for second level lumbar arthrodesis.

    Science.gov (United States)

    Singh, Kern; Dumonski, Mark; Stanley, Tom; Ponnappan, Ravi; Phillips, Frank M

    2011-02-01

    Prospective randomized controlled animal model. The purpose of this study is to determine whether the readministration of human recombinant bone morphogenetic protein-2 (rhBMP-2) induces an immune response and inhibits successful fusion in repeat posterolateral spinal surgery. Little research has been performed on the effectiveness or immunoreactivity of rhBMP-2 (Infuse, Medtronic, Memphis, TN) in the context of its reuse in posterolateral fusion spinal surgery at adjacent levels. A total of 34 New Zealand White rabbits underwent posterior intertransverse process fusion with the use of rhBMP-2 delivered on an absorbable collagen sponge (rhBMP-2/ACS). Two rabbits were killed early leaving 32 total rabbits. Serologic studies (Type I bovine collagen and rhBMP-2 antibodies) were obtained at 2-week intervals throughout the experiment. At 10 weeks, posteroanterior radiographs confirmed solid fusion masses in all rabbits. The 32 rabbits were randomly separated into 2 groups of 16, and each group underwent an adjacent level, bilateral intertransverse process fusion with either rhBMP-2/ACS or iliac crest. There was no statistical difference in fusion rates with repeat use of rhBMP-2 (n = 15/16, 94%) or iliac crest (n = 11/16, 69%) (P = 0.17) at the adjacent level. Four rabbits (n = 4/32, 13%) developed rhBMP-2 antibodies. Of these 4 rabbits, 1 developed anti-rhBMP antibodies after the first exposure and 3 developed antibodies after the second surgery. Eight rabbits (n = 8/32, 25%) developed collagen antibodies with 7 rabbits developing antibodies after the first exposure and 1 rabbit developing antibodies after the second exposure. The development of antibodies did not effect fusion rates. No rabbit demonstrated evidence of a systemic or anaphylactic reaction to repeat exposure to rhBMP-2. rhBMP-2 appears to be successful in promoting intertransverse fusions when used in both primary and repeat fusion environments. The infrequent development of antibodies to rhBMP-2 after

  16. Chronic ethanol consumption increases the levels of chemerin in the serum and adipose tissue of humans and rats

    Institute of Scientific and Technical Information of China (English)

    Rui-zhen REN; Xu ZHANG; Jin XU; Hai-qing ZHANG; Chun-xiao YU; Ming-feng CAO; Ling GAO; Qing-bo GUAN; Jia-jun ZHAO

    2012-01-01

    Chemerin is a new adipokine involved in adipogenesis and insulin resistance.Since ethanol affects the insulin sensitivity that is closely associated with adipokines.The aim of this study was to investigate the effects of ethanol on chemerin in humans and rats.Methods:In the human study,148 men who consumed alcohol for more than 3 years and 55 men who abstained from alcohol were included.Based on ethanol consumption per day,the drinkers were classified into 3 groups:low-dose (<15 g/d),middle-dose (15-47.9 g/d) and high-dose (≥48 g/d).Anthropometric measurementsand serum parameters were collected.In the rat study,27 male Wistar rats were randomly divided into 4 groups administered water or ethanol (0.5,2.5,or 5 g·kg-1·d-1) for 22 weeks.The chemerin levels in the sera,visceral adipose tissue (VAT) and liver were measured using ELISA.Results:In the high-dose group of humans and middle- and high-dose groups of rats,chronic ethanol consumption significantly increased the serum chemerin level.Both the middle- and high-dose ethanol significantly increased the chemerin level in the VAT of rats.In humans,triglyceride,fasting glucose,insulin and HOMA-IR were independently associated with chemerin.In rats,the serum chemerin level was positively correlated with chemerin in the VAT after adjustments for the liver chemerin (r=+0.768).High-dose ethanol significantly increased the body fat in humans and the VAT in rats.Conclusion:Chronic ethanol consumption dose-dependently increases the chemerin levels in the serum and VAT.The serum chemerin level is associated with metabolic parameters in humans.The increased serum chemerin level is mainly attributed to an elevation of chemerin in the VAT after the ethanol treatment.

  17. Biomonitoring studies should be used by regulatory agencies to assess human exposure levels and safety of bisphenol A.

    Science.gov (United States)

    Vandenberg, Laura N; Chahoud, Ibrahim; Padmanabhan, Vasantha; Paumgartten, Francisco J R; Schoenfelder, Gilbert

    2010-08-01

    Within the past 3 years, four major evaluations of bisphenol A (BPA) safety have been undertaken. However, these assessments have arrived at quite different conclusions regarding the safety of BPA at current human exposure levels. We compared the reasons provided by the European Food Safety Authority (EFSA) BPA risk assessment panel for their conclusion that human exposures are negligible with the conclusions reached by the other panels, with all panels having the same body of literature at their disposal. The EFSA panel dismissed > or = 80 biomonitoring studies that documented significant levels of BPA exposure in humans, including internal exposures to unconjugated BPA, on the basis that they did not match a model of BPA metabolism. Instead, the EFSA panel relied on two toxicokinetic studies-conducted in 15 adults administered BPA-to draw conclusions about exposure levels in the population, including exposures of neonates. As with all exposure assessments, models should be developed to explain actual data that are collected. In the case of BPA, samples from a large number of human subjects clearly indicate that humans are internally exposed to unconjugated BPA. The dismissal of these biomonitoring studies simply because their results do not conform to a model violates scientific principles. Expert panels should evaluate all data-including human biomonitoring studies-to make informed risk assessments.

  18. The Norwegian human milk study HUMIS variations in levels of chlorinated pesticides, PCBs and PBDEs in Norwegian breast milk

    Energy Technology Data Exchange (ETDEWEB)

    Polder, A.; Loeken, K. [The Norwegian School of Veterinary Science, Oslo (Norway); Thomsen, C.; Becher, G.; Eggesboe, M. [Norwegian Inst. of Public Health, Oslo (Norway); Skaare, J.U. [National Veterinary Inst., Oslo (Norway)

    2004-09-15

    Organochlorine pesticides (OCPs), polychlorinated, -dibenzo-pdioxins (PCDDs), -dibenzofurans (PCDFs), -biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are among the persistent organic pollutants (POPs) that have been found to accumulate in human breast milk. Because nursing children are exposed to these chemicals through the contaminated breast milk, health authorities worldwide are concerned for the infants' intake and therefore human milk monitoring programs are performed in many countries. While restrictions and bans resulted in a decline of organochlorines (OCs) in human milk during the last decades, an increasing trend has been found for PBDEs. The main goals of ''The Norwegian Human Milk Study, HUMIS'' are: to elucidate the human exposure in Norway to POPs, to identify dietary habits and other lifestyle factors that are associated with high levels of POPs in human milk, and to study the impact of exposure to the these contaminants on child health. This study reports preliminary results of recent levels of POPs in human milk in 4 different counties in Norway.

  19. Modular use of human body models of varying levels of complexity: Validation of head kinematics.

    Science.gov (United States)

    Decker, William; Koya, Bharath; Davis, Matthew L; Gayzik, F Scott

    2017-05-29

    The significant computational resources required to execute detailed human body finite-element models has motivated the development of faster running, simplified models (e.g., GHBMC M50-OS). Previous studies have demonstrated the ability to modularly incorporate the validated GHBMC M50-O brain model into the simplified model (GHBMC M50-OS+B), which allows for localized analysis of the brain in a fraction of the computation time required for the detailed model. The objective of this study is to validate the head and neck kinematics of the GHBMC M50-O and M50-OS (detailed and simplified versions of the same model) against human volunteer test data in frontal and lateral loading. Furthermore, the effect of modular insertion of the detailed brain model into the M50-OS is quantified. Data from the Navy Biodynamics Laboratory (NBDL) human volunteer studies, including a 15g frontal, 8g frontal, and 7g lateral impact, were reconstructed and simulated using LS-DYNA. A five-point restraint system was used for all simulations, and initial positions of the models were matched with volunteer data using settling and positioning techniques. Both the frontal and lateral simulations were run with the M50-O, M50-OS, and M50-OS+B with active musculature for a total of nine runs. Normalized run times for the various models used in this study were 8.4 min/ms for the M50-O, 0.26 min/ms for the M50-OS, and 0.97 min/ms for the M50-OS+B, a 32- and 9-fold reduction in run time, respectively. Corridors were reanalyzed for head and T1 kinematics from the NBDL studies. Qualitative evaluation of head rotational accelerations and linear resultant acceleration, as well as linear resultant T1 acceleration, showed reasonable results between all models and the experimental data. Objective evaluation of the results for head center of gravity (CG) accelerations was completed via ISO TS 18571, and indicated scores of 0.673 (M50-O), 0.638 (M50-OS), and 0.656 (M50-OS+B) for the 15g frontal impact

  20. Effect of stimulus parameters and contraction level on inhibitory responses in human jaw-closing muscles: Implications for contingent stimulation

    DEFF Research Database (Denmark)

    Jadidi, F; Wang, K; Arendt-Nielsen, Lars

    2009-01-01

      Objective: Examine the effect of stimulus duration as well as stimulus intensity and level of muscle contraction on the inhibitory responses in human jaw-closing muscles. Design: The inhibitory jaw-reflexes, ES1 and ES2, were recorded in the surface electromyogram (EMG) of masseter and temporalis...... results suggest that the ES2 reflex response is associated with the duration of the electrical stimuli, the intensity level but not the contraction level. In contrast, the inhibitory effects of ultra-long stimuli (450 ms) are not specifically related to the intensity level suggesting that this is a non...

  1. Effects of low-level laser therapy on stem cells from human exfoliated deciduous teeth

    Science.gov (United States)

    FERNANDES, Ana Paula; JUNQUEIRA, Marina de Azevedo; MARQUES, Nádia Carolina Teixeira; MACHADO, Maria Aparecida Andrade Moreira; SANTOS, Carlos Ferreira; OLIVEIRA, Thais Marchini; SAKAI, Vivien Thiemy

    2016-01-01

    ABSTRACT Low-Level Laser Therapy stimulates the proliferation of a variety of types of cells. However, very little is known about its effect on stem cells from human exfoliated deciduous teeth (SHED). Objective This study aimed to evaluate the influence of different laser therapy energy densities on SHED viability and proliferation. Material and Methods SHED were irradiated according to the groups: I (1.2 J/cm2 - 0.5 mW – 10 s), II (2.5 J/cm2 – 10 mW – 10 s), III (3.7 J/cm2 – 15 mW – 10 s), IV (5.0 J/cm2 – 20 mW – 10 s), V (6.2 J/cm2 – 25 mW – 10 s), and VI (not irradiated – control group). Cell viability was assessed 6 and 24 h after irradiation measuring the mitochondrial activity and using the Crystal Violet assay. Cell proliferation was assessed after 24, 48, and 72 h of irradiation by SRB assay. Results MTT assay demonstrated differences from 6 to 24 hours after irradiation. After 24 h, groups I and IV showed higher absorbance values than those of control group. Crystal Violet assay showed statistically differences in the absorbance rate from 6 to 24 h after irradiation for groups III and VI. At 24 h after irradiation, Group III absorbance rate was greater than that of groups I, II, and IV. Group VI absorbance rate was greater than that of groups I and IV. SRB assay showed that the group I had higher rates than those of groups II, III, V, and VI, at 24 h after irradiation. After 48 h, group I exhibited the greatest cell proliferation rate followed by groups III, V, and VI. After 72 h, group III exhibited the lowest cell proliferation rate than those of groups II, IV, and V. Conclusions The Low-Level Laser Therapy energy densities used in this study did not cause loss of cell viability and stimulated SHED proliferation within the parameters described in this study. PMID:27556203

  2. Vitamin D Levels Are Associated with Cardiac Autonomic Activity in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Linda Ellis

    2013-06-01

    Full Text Available Vitamin D deficiency (≤50nmol/L 25-hydroxy vitamin D is a cardiovascular (CV risk factor that affects approximately one billion people worldwide, particularly those affected by chronic kidney disease (CKD. Individuals with CKD demonstrate abnormal cardiac autonomic nervous system activity, which has been linked to the significant rates of CV-related mortality in this population. Whether vitamin D deficiency has a direct association with regulation of cardiac autonomic activity has never been explored in humans. Methods: Thirty-four (34 healthy, normotensive subjects were studied and categorized based on 25-hydroxy vitamin D deficiency (deficient vs. non-deficient, n = 7 vs. 27, as well as 1,25-dihydroxy vitamin D levels (above vs. below 25th percentile, n = 8 vs. 26. Power spectral analysis of electrocardiogram recordings provided measures of cardiac autonomic activity across low frequency (LF and high frequency (HF, representative of vagal contribution bands, representative of the sympathetic and vagal limbs of the autonomic nervous system when transformed to normalized units (nu, respectively, as well as overall cardiosympathovagal balance (LF:HF during graded angiotensin II (AngII challenge (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min. Results: At baseline, significant suppression of sympathovagal balance was observed in the 25-hydroxy vitamin D-deficient participants (LF:HF, p = 0.02 vs. non-deficient, although no other differences were observed throughout AngII challenge. Participants in the lowest 1,25-dihydroxy VD quartile experienced significant withdrawal of inhibitory vagal control, as well as altered overall sympathovagal balance throughout AngII challenge (HF, mean difference = −6.98 ± 3 nu, p = 0.05; LF:HF, mean difference = 0.34 ± 0.1, p = 0.043 vs. above 25th percentile. Conclusions: Vitamin D deficiency is associated with suppression of resting cardiac autonomic activity, while low 1,25-dihydroxy vitamin D levels are

  3. Contamination levels of human pharmaceutical compounds in French surface and drinking water.

    Science.gov (United States)

    Mompelat, S; Thomas, O; Le Bot, B

    2011-10-01

    The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit of quantification for surface water and 14% for drinking water). Psychostimulants, non-steroidal anti-inflammatory drugs, iodinated contrast media and anxiolytic drugs were the main therapeutic classes of human pharmaceutical compounds detected in the surface water and drinking water. The results for surface water were close to results from previous studies in spite of differences in prescription rates of human pharmaceutical compounds in different countries. The removal rate of human pharmaceutical compounds at 11 water treatment units was also determined. Only caffeine proved to be resistant to drinking water treatment processes (with a minimum rate of 5%). Other human pharmaceutical compounds seemed to be removed more efficiently (average elimination rate of over 50%) by adsorption onto activated carbon and oxidation/disinfection with ozone or chlorine (not taking account of the disinfection by-products). These results add to the increasing evidence of the occurrence of human pharmaceutical compounds in drinking water that may represent a threat to human beings exposed to a cocktail of human pharmaceutical compounds and related metabolites and by-products in drinking water.

  4. Establishing the baseline level of repetitive element expression in the human cortex

    National Research Council Canada - National Science Library

    Tyekucheva, Svitlana; Yolken, Robert H; McCombie, W Richard; Parla, Jennifer; Kramer, Melissa; Wheelan, Sarah J; Sabunciyan, Sarven

    2011-01-01

    .... Hence, we performed whole transcriptome sequencing to investigate the expression of repetitive elements in human frontal cortex using postmortem tissue obtained from the Stanley Medical Research Institute...

  5. Speech and gesture interfaces for squad-level human-robot teaming

    Science.gov (United States)

    Harris, Jonathan; Barber, Daniel

    2014-06-01

    As the military increasingly adopts semi-autonomous unmanned systems for military operations, utilizing redundant and intuitive interfaces for communication between Soldiers and robots is vital to mission success. Currently, Soldiers use a common lexicon to verbally and visually communicate maneuvers between teammates. In order for robots to be seamlessly integrated within mixed-initiative teams, they must be able to understand this lexicon. Recent innovations in gaming platforms have led to advancements in speech and gesture recognition technologies, but the reliability of these technologies for enabling communication in human robot teaming is unclear. The purpose for the present study is to investigate the performance of Commercial-Off-The-Shelf (COTS) speech and gesture recognition tools in classifying a Squad Level Vocabulary (SLV) for a spatial navigation reconnaissance and surveillance task. The SLV for this study was based on findings from a survey conducted with Soldiers at Fort Benning, GA. The items of the survey focused on the communication between the Soldier and the robot, specifically in regards to verbally instructing them to execute reconnaissance and surveillance tasks. Resulting commands, identified from the survey, were then converted to equivalent arm and hand gestures, leveraging existing visual signals (e.g. U.S. Army Field Manual for Visual Signaling). A study was then run to test the ability of commercially available automated speech recognition technologies and a gesture recognition glove to classify these commands in a simulated intelligence, surveillance, and reconnaissance task. This paper presents classification accuracy of these devices for both speech and gesture modalities independently.

  6. Validation of methods for measurement of insulin secretion in humans in vivo

    DEFF Research Database (Denmark)

    Kjems, L L; Christiansen, E; Vølund, A;

    2000-01-01

    of these mathematical techniques for quantification of insulin secretion have been tested in dogs, but not in humans. In the present studies, we examined the validity of both methods to recover the known infusion rates of insulin and C-peptide mimicking ISR during an oral glucose tolerance test. ISR from both......To detect and understand the changes in beta-cell function in the pathogenesis of type 2 diabetes, an accurate and precise estimation of prehepatic insulin secretion rate (ISR) is essential. There are two common methods to assess ISR, the deconvolution method (by Eaton and Polonsky......)-considered the "gold standard"-and the combined model (by Vølund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity...

  7. [Humans or material? Three levels of the discourse about the stem cell research from theological-ethical view].

    Science.gov (United States)

    Ernst, Stephan

    2004-01-01

    In the debate on the ethical evaluation of the stem cell research three levels can be differentiated. The first level of argumentation is that of weighing up goods: The possible therapeutical success for thousands of humans seems to justify the consumption of a few embryos. It is show, that this, however, already presupposes - on a second argumentation level - a judgement on the moral status of the embryo. Different moments of time, when human dignity and life protection are ascribe to the embryo, have already been discussed, but in spite of all rationality of the arguments a consensus has not been reached. On this third level of argumentation two fundamental meanings of reality can be differentiated. The empirical-observing and the communicative-participating view. These lead to a different moral evaluation of the embryo. This contribution votes for the priority of the communicative-participating view. It receives addition support by theology and Christian faith.

  8. Ontology-based high-level context inference for human behavior identification

    NARCIS (Netherlands)

    Villalonga, Claudia; Razzaq, Muhammad Asif; Ali Khan, Wajahat; Pomares, Hector; Rojas, Ignacio; Lee, Sungyoung; Banos Legran, Oresti

    2016-01-01

    Recent years have witnessed a huge progress in the utomatic identification of individual primitives of human behavior, such as activities or locations. However, the complex nature of human behavior demands more abstract contextual information for its analysis. This work presents an ontology-based

  9. Cadmium, Zinc, and Selenium Levels in Carcinoma of the Human Prostate

    Science.gov (United States)

    2008-04-01

    prostate . Cancer 13, 550-554. 27. van Sande M. and van Camp K. (1985) Lipids in human benign prostatic hypertrophy . Urol. Res. 13, 73-76. ...performed for prostate cancer, taken from an area distant from a localized cancer focus and having no evidence of prostatic hypertrophy . The...Carcinoma of the Human Prostate PRINCIPAL INVESTIGATOR: Andrey Sarafanov, Ph.D. Jose A

  10. Effects of beta interferon on human fibroblasts at different population doubling levels. Proliferation, cell volume, thymidine uptake, and DNA synthesis

    OpenAIRE

    1984-01-01

    Cellular aging had no effect on the ability of beta interferon to increase cell volume and population doubling time in 76-109 cells, a line of human skin fibroblasts. However, DNA synthesis in cells at high population doubling levels (PDL 55-70) was inhibited after 72 h of beta interferon treatment (1,000 U/ml) while no inhibition of DNA synthesis was observed in cells at middle population doubling levels (PDL 30-40).

  11. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    NARCIS (Netherlands)

    Pfleger, C; Kaas, A; Hansen, L; Alizadeh, B; Hougaard, P; Holl, R; Kolb, H; Roep, B O; Mortensen, H B; Schloot, N C

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated longi

  12. Effect of major and minor surgery on plasma levels of arginine, citrulline, nitric oxide metabolites, and ornithine in humans.

    Science.gov (United States)

    Hol, Jaap W; van Lier, Felix; Valk, Madelous; Klimek, Markus; Stolker, Robert J; Fekkes, Durk

    2013-12-01

    To determine the effect of surgical invasiveness on plasma levels of arginine, citrulline, ornithine, and nitric oxide (NO) in humans. Surgical trauma may have a profound effect on the metabolism of NO. However, human studies reported both increased and decreased NO levels after hemorrhagic shock. Arginine, citrulline, and ornithine are key amino acids involved in NO metabolism, but studies evaluating these amino acids together with NO and during 2 types of surgery are lacking. This study tests the hypothesis that major surgery has a more profound effect on plasma levels of arginine, citrulline, NO, and ornithine than minor surgery. Fifteen patients undergoing minor surgery (vulvectomy) and 13 patients undergoing major surgery (laparotomy) were prospectively followed up for 4 days. Plasma was collected for evaluation of levels of arginine, citrulline, NO, and ornithine. Throughout the experiment, arginine levels did not significantly differ between experimental groups. Perioperative plasma citrulline levels were significantly lower in the laparotomy group than in the vulvectomy group, whereas both groups showed a decrease in citrulline levels at the end of the operation and 24 hours postoperatively. Roughly the same pattern was seen for plasma NO and ornithine levels. However, ornithine levels in the laparotomy group showed a more drastic decrease at the end of the operation and 24 hours postoperatively than citrulline and NO levels. The level of surgical invasiveness has the most profound effect on plasma levels of ornithine. In addition, heavier surgical trauma is paired with lower postoperative levels of citrulline and NO metabolites than lighter surgery. It is suggested that surgical trauma stimulates the laparotomy group to consume significantly more ornithine, possibly for use in wound healing.

  13. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S

    2011-01-01

    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...... an inverse correlation between anti-dsDNA antibodies and the DNA concentration in the circulation in both murine and human serum samples. High titer of anti-DNA antibodies in human sera correlated with reduced levels of circulating chromatin, and in lupus prone mice with deposition within glomeruli....... The inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect...

  14. 阻塞性睡眠呼吸暂停对2型糖尿病患者C肽水平的影响%Impact of obstructive sleep apnea on C-peptide in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    杨敏; 蔺静; 郭燕

    2011-01-01

    目的 评价未经治疗的阻塞性睡眠呼吸暂停(OSA)对2型糖尿病患者反映胰岛功能的指标C肽的影响.方法 60例2型糖尿病患者行多导睡眠图(PSG)检查,并抽血检测C肽.根据呼吸暂停-低通气指数(AHI)将受试者分为4组:无OSA组(AHI<5)20例;轻度OSA组(5≤AHI<15)21例;中度OSA组(15≤AHI<30)12例;重度OSA组(AHI≥30)7例.结果 校正了年龄、体重指数(BMI)、腰围、空腹血糖、空腹胰岛素、病程及PSG显示的总睡眠时间后,OSA严重程度与C肽水平存在相关性(F=5.16,P=0.009).与无OSA组相比,轻度OSA组校正后的空腹C肽平均下降0.13 nmol/L(F=3.78,P=0.032),中度OSA组校正后的空腹C肽平均下降0.18 nmol/L(F=3.16,P=0.048),重度OSA组校正后的空腹C肽平均下降0.25 nmol/L(F=5.32,P=0.001).结论 2型糖尿病患者胰岛功能下降与其合并OSA的严重程度相关.%Objective To determine the impact of obstructive sleep apnea(OSA) on C-peptide,the major clinical indicator of islet function in patients with type 2 diabetes. Methods Polysomnography was performed and C-peptide was measured in 60 patients with type 2 diabetes. Four groups were separated according to apnea-hyponea index (AHI):20 patients in group without OSA (AHI <5 ),21 patients in mild OSA group (5 ≤ AHI < 15 ), 12 patients in moderate OSA (15 ≤ AHI < 30 )group, 7 patients in severe OSA group ( AHI ≥30). Results Severity of OSA was associated with C-peptide, after adjusting age, body mass index( BMI ), waist circumference, fasting plasma glucose, fasting insulin, years of diabetes and total sleep time. Compared with patients without OSA, the adjusted mean C-peptide decreased 0.13 nmol/L( F = 3.78,P =0.032) in mild OSA group,0. 18 nmol/L ( F = 3.16, P = 0. 048 ) in moderate OSA group, and 0.25 nmoL/L ( F = 5.32, P = 0.001 ) in severe OSA group. Conclusion In patients with type 2 diabetes, severity of OSA is associated with poorer islet function.

  15. Circulating levels of GH-releasing hormone and GH during human pregnancy.

    Science.gov (United States)

    Mazlan, M; Spence-Jones, C; Chard, T; Landon, J; McLean, C

    1990-04-01

    To study the potential role of GH-releasing hormone (GHRH) in maintaining circulating levels of GH during pregnancy, 302 maternal plasma samples were collected from non-fasted subjects at various stages of pregnancy and assayed for GHRH using a 'two-site' immunoradiometric assay. The GH and placental lactogen levels were also determined. In addition, maternal plasma samples taken during labour, amniotic fluid and cord blood were also assayed for these hormones. Maternal plasma GHRH levels were similar to non-pregnant levels throughout gestation despite fluctuations in GH values which were always higher than non-pregnant levels. There was no significant difference between GHRH levels in maternal plasma and cord blood although high GH levels were observed in the latter. These findings suggest that peripheral GHRH levels do not play an important role in maintaining circulating GH levels during pregnancy.

  16. Combining metagenomics, metatranscriptomics and viromics to explore novel microbial interactions: towards a systems-level understanding of human microbiome.

    Science.gov (United States)

    Bikel, Shirley; Valdez-Lara, Alejandra; Cornejo-Granados, Fernanda; Rico, Karina; Canizales-Quinteros, Samuel; Soberón, Xavier; Del Pozo-Yauner, Luis; Ochoa-Leyva, Adrián

    2015-01-01

    The advances in experimental methods and the development of high performance bioinformatic tools have substantially improved our understanding of microbial communities associated with human niches. Many studies have documented that changes in microbial abundance and composition of the human microbiome is associated with human health and diseased state. The majority of research on human microbiome is typically focused in the analysis of one level of biological information, i.e., metagenomics or metatranscriptomics. In this review, we describe some of the different experimental and bioinformatic strategies applied to analyze the 16S rRNA gene profiling and shotgun sequencing data of the human microbiome. We also discuss how some of the recent insights in the combination of metagenomics, metatranscriptomics and viromics can provide more detailed description on the interactions between microorganisms and viruses in oral and gut microbiomes. Recent studies on viromics have begun to gain importance due to the potential involvement of viruses in microbial dysbiosis. In addition, metatranscriptomic combined with metagenomic analysis have shown that a substantial fraction of microbial transcripts can be differentially regulated relative to their microbial genomic abundances. Thus, understanding the molecular interactions in the microbiome using the combination of metagenomics, metatranscriptomics and viromics is one of the main challenges towards a system level understanding of human microbiome.

  17. Effect of in vitro estrogenic pesticides on human oestrogen receptor α and β mRNA levels

    DEFF Research Database (Denmark)

    Theander Grünfeld, Heidi; Bonefeld-Jørgensen, Eva Cecilie

    2004-01-01

    Nine widely distributed pesticides were recently demonstrated to posses potential estrogenic properties in oestrogen receptor (ER) transactivation and/or E-screen assays. We tested the effect of these nine pesticides on the human ERα and ERβ mRNA steady state levels in the mamma cancer fibroblast...

  18. [The dependence of the level of chromosome aberrations in human lymphocytes on the duration of their cultivation under ultraviolet irradiation].

    Science.gov (United States)

    Rushkovskiĭ, S R; Bezrukov, V F; Bariliak, I R

    1998-01-01

    The effect of duration of cultivation of lymphocytes of human UV-irradiated peripheral blood on the chromosomal aberration rate was studied. Under prolonged cultivation the more irradiated blood samples revealed higher level of chromosomal aberrations. The existence of UV-induced delayed chromosomal instability is supposed that may be found under prolonged cultivation. The mechanisms of this phenomenon are discussed.

  19. UNEARTHING GLOBAL FINANCIAL INCLUSION LEVELS AND ANALYSIS OF FINANCIAL INCLUSION AS A MEDIATING FACTOR IN GLOBAL HUMAN DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Roshny Unnikrishnan

    2015-04-01

    Full Text Available This study is a result of the author’s inquisition to unearth the current values of Global Financial Inclusion and its relationship with economic growth measured by Gross Domestic product(GDP and human development measured by United Nations Human Development Index (HDI. The Financial Inclusion (FI levels are measured using Index for Financial Inclusion .The relationship between GDP and HDI with FI as mediator, using multiple regression, is validated on a global level based on data of 162 countries for the year 2011. An overall global mediation analysis is undertaken to establish Financial Inclusion as a mediating factor and partial mediation on human development is validated. The study is valid and unique in the global context of income inequality prevailing in developed, developing and underdeveloped countries as it validates the argument that an impressive GDP performance does not ensure equity in economic growth.

  20. Categorial Ontology of Complex Systems, Meta-Systems and Levels: The Emergence of Life, Human Consciousness and Society

    Directory of Open Access Journals (Sweden)

    James F. Glazebrook

    2010-06-01

    Full Text Available Relational structures of organisms and the human mind are naturally represented in terms of novel variable topology concepts, non-Abelian categories and Higher Dimensional Algebra{ relatively new concepts that would be defined in
    this tutorial paper. A unifying theme of local-to-global approaches to organismic development, evolution and human consciousness leads to novel patterns of relations that emerge in super- and ultra- complex systems in terms of compositions of local procedures [1]. The claim is defended in this paper that human consciousness is unique and should be viewed as an ultra-complex, global process of processes, at a meta-level not sub{summed by, but compatible with, human brain dynamics [2]-[5]. The emergence of consciousness and its existence
    are considered to be dependent upon an extremely complex structural and functional unit with an asymmetric network topology and connectivities{the human brain. However, the appearance of human consciousness is shown to be critically dependent upon societal co-evolution, elaborate language-symbolic communication and `virtual', higher dimensional, non{commutative processes involving separate space and time perceptions. Theories of the mind are approached from the theory of levels and ultra-complexity viewpoints that throw
    new light on previous semantic models in cognitive science. Anticipatory systems and complex causality at the top levels of reality are discussed in the context of psychology, sociology and ecology. A paradigm shift towards non-commutative, or more generally, non-Abelian theories of highly complex dynamics [6] is suggested to unfold now in physics, mathematics, life and cognitive sciences, thus leading to the realizations of higher dimensional algebras in neurosciences and psychology, as well as in human genomics, bioinformatics and interactomics. The presence of strange attractors in modern society dynamics gives rise to very serious concerns for the future

  1. Fractal multi-level organisation of human groups in a virtual world

    CERN Document Server

    Fuchs, Benedikt; Thurner, Stefan

    2014-01-01

    Humans are fundamentally social. They have progressively dominated their environment by the strength and creativity provided by and within their grouping. It is well recognised that human groups are highly structured, and the anthropological literature has loosely classified them according to their size and function, such as support cliques, sympathy groups, bands, cognitive groups, tribes, linguistic groups and so on. Recently, combining data on human grouping patterns in a comprehensive and systematic study, Zhou et al. identified a quantitative discrete hierarchy of group sizes with a preferred scaling ratio close to $3$, which was later confirmed for hunter-gatherer groups and for other mammalian societies. Using high precision large scale Internet-based social network data, we extend these early findings on a very large data set. We analyse the organisational structure of a complete, multi-relational, large social multiplex network of a human society consisting of about 400,000 odd players of a massive m...

  2. in human sperm motility and level of calcium and magnesium in ...

    African Journals Online (AJOL)

    J. Valsa

    2015-11-06

    Nov 6, 2015 ... and magnesium in seminal plasma during this period was also seen to understand the role of ..... Major function of male accessory organs, prostate and seminal ... a hydrolyzing enzyme present in human sperm membrane. It.

  3. Genetic synthetic lethality screen at the single gene level in cultured human cells

    OpenAIRE

    Simons, Arnold H.; Dafni, Naomi; Dotan, Iris; Oron, Yoram; Canaani, Dan

    2001-01-01

    Recently, we demonstrated the feasibility of a chemical synthetic lethality screen in cultured human cells. We now demonstrate the principles for a genetic synthetic lethality screen. The technology employs both an immortalized human cell line deficient in the gene of interest, which is complemented by an episomal survival plasmid expressing the wild-type cDNA for the gene of interest, and the use of a novel GFP-based double-label fluorescence system. Dominant negative genetic suppressor elem...

  4. Work level related human factors for enterprise architecture as organisational strategy

    CSIR Research Space (South Africa)

    Gilliland, S

    2015-10-01

    Full Text Available -space bound and affected by human identities, roles and communication in its different forms (words, gestures, body-language, etc.) Context (organisational, environmental and social) will always have a direct influence on EA acceptance... about actions, unacknowledged conditions or unintended consequences of their actions) Human action is not controllable but change which inevitable happens and may be the cause of resistance and anxiety can be minimized if EA is accepted...

  5. Contamination levels of human pharmaceutical compounds in French surface and drinking water.

    OpenAIRE

    Mompelat, S.; Thomas, Olivier; Le Bot, Barbara

    2011-01-01

    International audience; The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit o...

  6. The Observance of Human Rights and Freedoms in the Extradition Proceedings at National and International Levels

    Directory of Open Access Journals (Sweden)

    Mariana (Mitra Radu

    2013-08-01

    Full Text Available The fundamental rights and freedoms contained in international documents may be the object of the denial of an extradition request as independent exceptions, even if they are not covered by extradition treaties. The right to life is a fundamental human right whose protection must be achieved in the extradition proceedings. By Law no. 30/1994, Romania ratified the Convention for the Protection of Human Rights and Fundamental Freedoms, adopted by the Council of Europe.

  7. Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγnull mice treated with alogliptin

    Directory of Open Access Journals (Sweden)

    Jurczyk A

    2013-12-01

    Full Text Available Agata Jurczyk,1 Philip diIorio,1 Dean Brostowin,1 Linda Leehy,1 Chaoxing Yang,1 Fumihiko Urano,2 David M Harlan,3 Leonard D Shultz,4 Dale L Greiner,1 Rita Bortell1 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 2Department of Medicine, Washington University School of Medicine, St Louis, MO, 3Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 4The Jackson Laboratory, Bar Harbor, ME, USA Purpose: Dipeptidyl-peptidase-4 (DPP-4 inhibitors are known to increase insulin secretion and beta cell proliferation in rodents. To investigate the effects on human beta cells in vivo, we utilize immunodeficient mice transplanted with human islets. The study goal was to determine the efficacy of alogliptin, a DPP-4 inhibitor, to enhance human beta cell function and proliferation in an in vivo context using diabetic immunodeficient mice engrafted with human pancreatic islets. Methods: Streptozotocin-induced diabetic NOD-scid IL2rγnull (NSG mice were transplanted with adult human islets in three separate trials. Transplanted mice were treated daily by gavage with alogliptin (30 mg/kg/day or vehicle control. Islet graft function was compared using glucose tolerance tests and non-fasting plasma levels of human insulin and C-peptide; beta cell proliferation was determined by bromodeoxyuridine (BrdU incorporation. Results: Glucose tolerance tests were significantly improved by alogliptin treatment for mice transplanted with islets from two of the three human islet donors. Islet-engrafted mice treated with alogliptin also had significantly higher plasma levels of human insulin and C-peptide compared to vehicle controls. The percentage of insulin+BrdU+ cells in human islet grafts from alogliptin-treated mice was approximately 10-fold more than from vehicle control mice, consistent with a significant increase in human beta cell proliferation. Conclusion: Human islet-engrafted immunodeficient mice

  8. The Human Brain Does Not Need High Levels of Motivation to Learn a Foreign Language: Motivation Has Had its Day

    Directory of Open Access Journals (Sweden)

    Kieran Green

    2016-10-01

    Full Text Available Language is nature in action and something humans do.  This literature review presents evidence from the literature that suggests that learning a foreign language in a classroom situation does not require high levels of student motivation.  It is instead suggested that high levels of motivation are needed to make progress when a teacher is using traditional teaching methods.  It is shown that all healthy human brains are excellent at learning and using language, and high levels of motivation to learn a foreign language are not required if teaching practices and materials replicate natural learning experiences, and class participation is ensured.  This work is of great importance to teachers as it demonstrates that teachers would help students more by investing their time in developing class materials than by worrying about student motivation. Keywords:  foreign language, cognitive linguistics, language evolution, language learnability, language usability, motivation

  9. Over-expression of CXCR4, a stemness enhancer, in human blastocysts by low level laser irradiation

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Tahmasbi

    2013-09-01

    Full Text Available The key role of chemokine receptor CXCR4 in the maintenance of stemness property of stem cells has been shown recently. The low level laser irradiation (LLLI is being used currently in a wide variety of clinical cases as a therapeutic tool for wound healing, relieving pain and destroying tumor cells. The aim of this study was to evaluate the effect of LLLI mimicking low level laser therapy (LLLT on the expression level of CXCR4 gene a few hours after irradiation on human blastocysts. After the development of human embryos to the first grade blastocyst stage, they were irradiated with a low power Ga-Al-As laser at a continuous wavelength of 650 nm and a power output of 30 mW. The total RNA of the irradiated blastocysts and control groups were isolated in groups of 1x2 J/cm2, 2x2 J/cm2, 1x4 J/cm2 and 2x4 J/cm2 LLLI. Specific Real-Time PCR primers were designed to amplify all the two CXCR4 isoforms yet identified. RNA amplifications were done for all the groups. We showed for the first time that LLLI makes the human blastocysts to increase the expression level of CXCR4 a few hours after irradiation. Moreover, it was shown that two irradiation doses with one day interval can cause a significant increase in CXCR4 expression level in human blastocysts. This study revealed that LLLI could be a proliferation motivator for embryonic cell divisions through enhanced over-expression of CXCR4 level.

  10. Dioxin and PCB levels in human samples from the Greek population

    Energy Technology Data Exchange (ETDEWEB)

    Leondiadis, L.; Vassiliadou, I.; Costopoulou, D.; Papadopoulos, A. [Mass Spectrometry and Dioxin Analysis Lab. - NCSR Demokritos, Athens (Greece)

    2004-09-15

    Polychlorinated biphenyls (PCBs) are commercial chemical substances produced in a large scale since 1930, with a wide range of applications in industry, such as for coolant fluids in transformers and dielectric fluids in capacitors. After their health effects became apparent, PCB production was banned in the late 1970s. However, humans are still exposed through PCB leakage of old capacitors and transformers and disposal of contaminated materials. Dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs)), are formed as undesirable by-products mainly during the production of chlorinated chemicals and during the combustion of municipal and hazardous waste. Due to potential health hazard (dermal toxicity, immunotoxicity, reproductive effects, teratogenicity, endocrine disruption and carcinogenicity), their monitoring in humans is of high general concern. Enough information on POP presence in human tissues from industrialized countries is available to suggest that the concentration of these compounds has decreased during the last 10 years. Monitoring of human exposure to PCBs and dioxins, contaminants that accumulate in lipid tissue, is most conveniently performed by analysis of blood plasma or blood serum. Monitoring of dioxins in human milk is of also great importance, since it is especially feared that lactational exposure to dioxins and related compounds may adversely affect brain development and the immune system of infants and children. The present study includes the analyses of non-ortho, mono-ortho, indicator PCBs, and PCDD/Fs in human blood and human milk samples collected between November 2002 and February 2004 and is the first study of this kind to be undertaken in Greece.

  11. Basic level category structure emerges gradually across human ventral visual cortex.

    Science.gov (United States)

    Iordan, Marius Cătălin; Greene, Michelle R; Beck, Diane M; Fei-Fei, Li

    2015-07-01

    Objects can be simultaneously categorized at multiple levels of specificity ranging from very broad ("natural object") to very distinct ("Mr. Woof"), with a mid-level of generality (basic level: "dog") often providing the most cognitively useful distinction between categories. It is unknown, however, how this hierarchical representation is achieved in the brain. Using multivoxel pattern analyses, we examined how well each taxonomic level (superordinate, basic, and subordinate) of real-world object categories is represented across occipitotemporal cortex. We found that, although in early visual cortex objects are best represented at the subordinate level (an effect mostly driven by low-level feature overlap between objects in the same category), this advantage diminishes compared to the basic level as we move up the visual hierarchy, disappearing in object-selective regions of occipitotemporal cortex. This pattern stems from a combined increase in within-category similarity (category cohesion) and between-category dissimilarity (category distinctiveness) of neural activity patterns at the basic level, relative to both subordinate and superordinate levels, suggesting that successive visual areas may be optimizing basic level representations.

  12. Physical activity affects plasma coenzyme Q10 levels differently in young and old humans.

    Science.gov (United States)

    Del Pozo-Cruz, Jesús; Rodríguez-Bies, Elisabet; Ballesteros-Simarro, Manuel; Navas-Enamorado, Ignacio; Tung, Bui Thanh; Navas, Plácido; López-Lluch, Guillermo

    2014-04-01

    Coenzyme Q (Q) is a key lipidic compound for cell bioenergetics and membrane antioxidant activities. It has been shown that also has a central role in the prevention of oxidation of plasma lipoproteins. Q has been associated with the prevention of cholesterol oxidation and several aging-related diseases. However, to date no clear data on the levels of plasma Q during aging are available. We have measured the levels of plasmatic Q10 and cholesterol in young and old individuals showing different degrees of physical activity. Our results indicate that plasma Q10 levels in old people are higher that the levels found in young people. Our analysis also indicates that there is no a relationship between the degree of physical activity and Q10 levels when the general population is studied. However, very interestingly, we have found a different tendency between Q10 levels and physical activity depending on the age of individuals. In young people, higher activity correlates with lower Q10 levels in plasma whereas in older adults this ratio changes and higher activity is related to higher plasma Q10 levels and higher Q10/Chol ratios. Higher Q10 levels in plasma are related to lower lipoperoxidation and oxidized LDL levels in elderly people. Our results highlight the importance of life habits in the analysis of Q10 in plasma and indicate that the practice of physical activity at old age can improve antioxidant capacity in plasma and help to prevent cardiovascular diseases.

  13. Human serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in Uyghurs from Sinkiang-Uighur Autonomous Region, China: background levels study.

    Science.gov (United States)

    Zeng, Xiao-Wen; Qian, Zhengmin; Vaughn, Michael; Xian, Hong; Elder, Keith; Rodemich, Eugene; Bao, Jia; Jin, Yi-He; Dong, Guang-Hui

    2015-03-01

    Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), are a family of commonly used industrial chemicals whose persistence and ubiquity in blood samples of humans and wildlife have become a growing concern. Despite PFOS and PFOA having been found in human blood and tissue samples from occupationally exposed workers and the general worldwide population, little systematic knowledge has accrued with respect to exposure levels in Uyghurs in the Sinkiang-Uighur Autonomous Region of China, which is predominantly agricultural and pastoral. Our goal was to provide background data for biological monitoring in the general population of this region. In this study, 110 self-reported healthy human serum samples were collected from nonoccupationally exposed Uyghurs volunteers and analyzed by microbore HPLC-electrospray tandem mass spectrometry. Among the 110 blood specimens, PFOS was detected in 102 samples (93%) and ranged from the lower limit of quantification of 0.01 to 22.63 μg/L with a median of 1.93 μg/L (interquartile range 1.00-3.43 μg/L). The median was higher among males (2.39 μg/L; interquartile range 1.23-4.40 μg/L) than that among females (1.20 μg/L; interquartile range 0.83-2.77 μg/L). No significant difference was observed with respect to age. The concentration of PFOA was lower than that of PFOS and was found only in seven samples (6%) at concentrations above the limit of quantification. This study is the first investigation to reveal serum PFOS and PFOA levels in the general population of Uyghurs. PFOS and PFOA concentrations found in the present investigation were lower than those found in recent studies consisting of subjects from different geographic locations (PFOS 5.0-44.7 μg/L, PFOA 1.5-10 μg/L).

  14. Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Jenab, Mazda; Riboli, Elio; Cleveland, Rebecca J.; Norat, Teresa; Rinaldi, Sabina; Biessy, Carine; Tjonneland, Ann; Olsen, Anja; Overvad, Kim; Gronbaek, Henning; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Linseisen, Jakob; Boeing, Heiner; Pischon, Tobias; Trichopoulos, Dimitrios; Oikonomou, Eleni; Trichopoulou, Antonia; Panico, Salvatore; Vineis, Paolo; Berrino, Franco; Tumino, Rosario; Masala, Giovanna; Peters, Petra H.; van Gils, Carla H.; Bueno-de-Mesquita, H. Bas; Ocke, Marga C.; Lund, Eiliv; Mendez, Michelle A.; Tormo, Maria Jose; Barricarte, Aurelio; Martinez-Garcia, Carmen; Dorronsoro, Miren; Ramon Quiros, Jose; Hallmans, Goran; Palmqvist, Richard; Berglund, Goran; Manjer, Jonas; Key, Timothy; Allen, Naomi E.; Bingham, Sheila; Khaw, Kay-Tee; Cust, Anne; Kaaks, Rudolf

    2007-01-01

    Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of

  15. Level of Knowledge about Human Papillomavirus Infection among Women of Kashan City, Iran

    OpenAIRE

    Nekooi M.S. BSc; Ayazi Sh. BSc,; Gandomi M. BSc,; Moosavi S.Gh. MSc,; Fakhri A.* PhD

    2016-01-01

    Aims A few studies concentrate on the level of knowledge of HPV. This study was conducted to evaluate the level of knowledge about HPV, its risk factors, and its relation with cervical cancer in women of Kashan City, Iran. Instrument & Methods This descriptive cross-sectional study was conducted in January 2015 in the population of the women of Kashan City, Iran, and 200 persons were selected by simple sampling method. The level of knowledge about HPV and cervical cancer were ...

  16. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome

    DEFF Research Database (Denmark)

    Pedersen, Jakob Skou; Valen, Eivind; Velazquez, Amhed Missael Vargas;

    2014-01-01

    data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery...... of the expected signals at promoter regions, exon/intron boundaries, and CTCF sites. The top-scoring nucleosome calls revealed distinct DNA positioning biases, attesting to nucleotide-level accuracy. The ancient methylation levels exhibited high conservation over time, clustering closely with modern hair tissues...

  17. A real-time human-perception interface for task-level control of a robot in unfamiliar environments

    Science.gov (United States)

    Miles, Eric Scott

    Recent advances in the development of semi-autonomous robotic systems offer numerous potential advantages in many engineering and science endeavors. Significant reductions in cost, time and risk, as well as increased capability, can be obtained by utilizing intelligent machines to assist humans. However, the use of robots also introduces many challenging issues, including the need for high-bandwidth stable control despite communication delays and operator fatigue. In response to these challenges, the Stanford Aerospace Robotics Laboratory has pioneered the Task-Level Control architecture, which enables humans to direct, from a strategic level, sophisticated tasks that a robot then executes autonomously. The research reported here is intended to extend the Task-Level Control architecture significantly--by using human perception in a natural way--to work well in unfamiliar environments. An unfamiliar environment is defined to be one about which it is impossible to have perfect and complete knowledge before developing and deploying a robotic system. Clearly, every work environment is, to some extent, unfamiliar. This research has shown that drawing intimately, in real time, upon a human's deep visual perception is extremely effective in overcoming such unfamiliarity. A novel interactive vision-based operator interface for directing a highly autonomous robot operating in an unfamiliar environment is presented. Intuitive interaction with a live-video display from cameras on board the robot is used in combination with stereo-vision algorithms to maintain the operator's attention at the overall object-level during the modeling process. With this interface, the human's remarkable ability to discern entire object-level constructs is utilized to produce quick, cogent and robust models of unexpected and unknown objects in the environment. Once unfamiliar objects have been suitably modeled, tasks involving those objects can be directed via the Task-Level Control architecture

  18. Human Capital Constraints in South Africa: A Firm-Level Analysis

    Directory of Open Access Journals (Sweden)

    Ewert P. J. Kleynhans

    2012-03-01

    Full Text Available This paper examines human capital constraints in the South Africaneconomy, and the austerity of these constraints on firms in the country.The two key human capital constraints explored in this article arethe inadequately educated workforce and labour market distortions.Regression analysis was applied to examine determinants of increasedlabour productivity in manufacturing firms. Education and labourmarket distortions were found to have a varying influence on outputper worker. Principal Component Analysis (pca of the explanatoryvariables achieved similar results. This study found that the highest percentageof the total variance is explained by latent variables that incorporateeducation, training, compensation, region and Sector EducationTraining Authority (seta support and effectiveness.

  19. Elevated levels of G-quadruplex formation in human stomach and liver cancer tissues.

    Science.gov (United States)

    Biffi, Giulia; Tannahill, David; Miller, Jodi; Howat, William J; Balasubramanian, Shankar

    2014-01-01

    Four-stranded G-quadruplex DNA secondary structures have recently been visualized in the nuclei of human cultured cells. Here, we show that BG4, a G-quadruplex-specific antibody, can be used to stain DNA G-quadruplex structures in patient-derived tissues using immunohistochemistry. We observe a significantly elevated number of G-quadruplex-positive nuclei in human cancers of the liver and stomach as compared to background non-neoplastic tissue. Our results suggest that G-quadruplex formation can be detected and measured in patient-derived material and that elevated G-quadruplex formation may be a characteristic of some cancers.

  20. Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi; Pirisi, Lucia [Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC (United States); Creek, Kim E., E-mail: creekk@sccp.sc.edu [Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC (United States)

    2013-09-15

    We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer. - Highlights: • Ski oncoprotein levels increase during progression of HPV16-transformed cells. • Ski and phospho-Ski protein levels are cell cycle dependent. • Ski knock-down in HPV16-transformed keratinocytes inhibited cell proliferation. • Cervical cancer samples overexpress Ski.

  1. Activation of p53 in Human and Murine Cells by DNA-Damaging Agents Differentially Regulates Aryl Hydrocarbon Receptor Levels.

    Science.gov (United States)

    Panchanathan, Ravichandran; Liu, Hongzhu; Choubey, Divaker

    2015-01-01

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates multiple cellular processes. The anticancer drug doxorubicin (DOX) can activate AhR-mediated transcription of target genes. Because DOX in cells activates a DNA damage response involving ataxia telangiectasia-mutated (ATM)-mediated activation of p53, we investigated whether the activation of the p53 in cells by DNA-damaging agents such as DOX or bleomycin could regulate the AhR levels. Here we report that activation of p53 by DNA-damaging agents in human cells increased levels of AhR through a posttranscriptional mechanism. Accordingly, fibroblasts from ATM patients, which are defective in p53 activation, expressed reduced constitutive levels of AhR and treatment of cells with bleomycin did not appreciably increase the AhR levels. Further, activation of p53 in cells stimulated the expression of AhR target genes. In murine cells, activation of p53 reduced the levels of AhR messenger RNA and protein and reduced the expression of AhR target genes. Our observations revealed that activation of p53 in human and murine cells differentially regulates AhR levels.

  2. Enhanced constitutive invasion activity in human nontumorigenic keratinocytes exposed to a low level of barium for a long time.

    Science.gov (United States)

    Thang, Nguyen D; Yajima, Ichiro; Ohnuma, Shoko; Ohgami, Nobutaka; Kumasaka, Mayuko Y; Ichihara, Gaku; Kato, Masashi

    2015-02-01

    We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion. © 2013 Wiley Periodicals, Inc.

  3. Pollution level and human health risk assessment of some pesticides and polychlorinated biphenyls in Nantong of Southeast China.

    Science.gov (United States)

    Wang, Na; Yi, Li; Shi, Lili; Kong, Deyang; Cai, Daoji; Wang, Donghua; Shan, Zhengjun

    2012-01-01

    Food consumption is one of the key exposure routes of humans to contaminants. This article evaluated the residue levels of 51 pesticides and 16 polychlorinated biphenyls (PCBs) in selected fish and food items which were commonly consumed in the Nantong area of Jiangsu Province, Southeast China. The 51 pesticides and 16 PCBs were analyzed by highly sensitive gas chromatography-tandem mass spectrometry (GC-MS/MS). The results showed that organochlorine pesticides such as dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB) and mirex and other pesticides including chlorpyrifos, pyrethroid pesticides, metolachlor, pyridaben and trifluralin were frequently detected in the samples, which was consistent with the accumulation level and characteristics of these toxic chemicals in human adipose tissue of people living in Nantong. Meanwhile, correlation of the residue level of toxic chemicals with their physical chemical properties and historic use pattern in Nantong area was observed. Combined with dietary survey results at the same sampling locations, human health risk assessment of ingestion through the dietary route was performed. The results suggested that the non-cancer risks of the chemicals investigated can be considered negligible in the Nantong area, however, the cancer risks from lifetime dietary exposure to DDTs and HCB have exceeded the acceptable levels.

  4. Pollution level and human health risk assessment of some pesticides and polychlorinated biphenyls in Nantong of Southeast China

    Institute of Scientific and Technical Information of China (English)

    Na Wang; Li Yi; Lili Shi; Deyang Kong; Daoji Cai; Donghua Wang; Zhengjun Shan

    2012-01-01

    Food consumption is one of the key exposure routes of humans to contaminants.This article evaluated the residue levels of 51 pesticides and 16 polychlorinated biphenyls (PCBs) in selected fish and food items which were commonly consumed in the Nantong area of Jiangsu Province,Southeast China.The 51 pesticides and 16 PCBs were analyzed by highly sensitive gas chromatographytandem mass spectrometry (GC-MS/MS).The results showed that organochlorine pesticides such as dichlorodiphenyltrichloroethanes (DDTs),hexachlorocyclohexanes (HCHs),hexachlorobenzene (HCB) and mirex and other pesticides including chlorpyrifos,pyrethroid pesticides,metolachlor,pyridaben and trifluralin were frequently detected in the samples,which was consistent with the accumulation level and characteristics of these toxic chemicals in human adipose tissue of people living in Nantong.Meanwhile,correlation of the residue level of toxic chemicals with their physical chemical properties and historic use pattern in Nantong area was observed.Combined with dietary survey results at the same sampling locations,human health risk assessment of ingestion through the dietary route was performed.The results suggested that the non-cancer risks of the chemicals investigated can be considered negligible in the Nantong area,however,the cancer risks from lifetime dietary exposure to DDTs and HCB have exceeded the acceptable levels.

  5. Untargeted metabolomic analysis of human serum samples associated with exposure levels of Persistent organic pollutants indicate important perturbations in Sphingolipids and Glycerophospholipids levels.

    Science.gov (United States)

    Carrizo, Daniel; Chevallier, Olivier P; Woodside, Jayne V; Brennan, Sarah F; Cantwell, Marie M; Cuskelly, Geraldine; Elliott, Christopher T

    2017-02-01

    Persistent organic pollutants (POPs) are distributed globally and are associated with adverse health effects in humans. A study combining gas chromatography-mass spectrometry (GC-MS), high resolution mass spectrometry (UPLC-QTof-MS) and chemometrics for the analysis of adult human serum samples was undertaken. Levels of serum POPs found were in the low range of what has been reported in similar populations across Europe (median 33.84 p, p'-DDE, 3.02 HCB, 83.55 β-HCH, 246.62 PCBs ng/g lipids). Results indicated that compounds concentrations were significantly different between the two groups of POPs exposure (high vs low) and classes (DDE, β-HCH, HCB, PCBs). Using orthogonal partial last-squares discriminant analysis (OPLS-DA), multivariate models were created for both modes of acquisition and POPs classes, explaining the maximum amount of variation between sample groups (positive mode R2 = 98-90%; Q2 = 94-75%; root mean squared error of validation (RMSEV) = 12-20%: negative mode R2 = 98-91%; Q2 = 94-81%; root mean squared error of validation (RMSEV) = 10-19%. In the serum samples analyzed, a total 3076 and 3121 ions of interest were detected in positive and negative mode respectively. Of these, 40 were found to be significantly different (p < 0.05) between exposure levels. Sphingolipids and Glycerophospholipids lipids families were identified and found significantly (p < 0.05) different between high and low POPs exposure levels. This study has shown that the elucidation of metabolomic fingerprints may have the potential to be classified as biomarkers of POPs exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids

    NARCIS (Netherlands)

    Kersten, S.; Lichtenstein, L.; Steenbergen, E.; Mudde, K.; Hendriks, H.F.J.; Hesselink, M.K.; Schrauwen, P.; Müller, M.

    2009-01-01

    OBJECTIVE-: Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, v

  7. Environmental variation of arsenic levels in human blood determined by neutron activation analysis

    DEFF Research Database (Denmark)

    Heydorn, Kaj

    1970-01-01

    from Taiwan followed a logarithmic normal distribution, and no difference was found between Blackfoot patients and their healthy family members. However, their overall arsenic levels were higher than the Taiwan average, presumably because of arsenic in their drinking water. Much lower levels were found...

  8. Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Terence C. Tang; Ronnie T. Poon; Cecilia P. Lau; Dan Xie; Sheung Tat Fan

    2005-01-01

    AIM: Recent studies suggested that cyclooxygenase-2(COX-2) enhances tumor angiogenesis via upregulationof vascular endothelial growth factor (VEGF). AlthoughCOX-2 expression has been demonstrated in hepatocellularcarcinoma (HCC), the significance of COX-2 in progressionof HCC remains unclear. This study evaluated the clinico-pathological correlation of COX-2 level and its relationshipwith VEGF level in HCC.METHODS: Fresh tumor tissues were obtained from 100patients who underwent resection of HCC. COX-2 proteinexpression was examined by immunohistochemistry, andquantitatively by an enzyme immunometric assay (EIA)of tumor cytosolic COX-2 levels. Tumor cytosolic VEGFlevels were measured by an ELISA.RESULTS: Immunostaining showed expression of COX-2in tumor cells. Tumor cytosolic COX-2 levels correlatedwith VEGF levels (r = 0.469, P<0.001). Correlation withclinicopathological features showed significantly highertumor cytosolic COX-2 levels in the presence of multipletumors (P = 0.027), venous invasion (P = 0.030),microsatellite lesions (P = 0.037) and advanced tumorstage (P = 0.008). Higher tumor cytosolic COX-2 levelswere associated with worse patient survival.CONCLUSION: This study shows that elevated tumorCOX-2 levels correlate with elevated VEGF levels andinvasiveness in HCC, suggesting that COX-2 plays a significantrole in the progression of HCC.

  9. Serum vitamin D levels are not altered after controlled diesel exhaust exposures in healthy human subjects

    Science.gov (United States)

    Past research has suggested that exposure to urban air pollution may be associated with vitamin D deficiency in human populations. Vitamin D is widely known for its importance in bone growth/remodeling, muscle metabolism, and its ability to promote calcium absorption in the gut; ...

  10. Human Language, Unit II: Language Curriculum, Level C [Grade Three]; Teacher's Guide.

    Science.gov (United States)

    Oregon Univ., Eugene. Oregon Elementary English Project.

    Developed by the Oregon Elementary English Project, the lessons in this second of a two-part unit on the human language intended for grades three and four revolve around the character Sad Sam, who gets lost in the woods and happens to observe four animals (bears, raccoons, geese, and robins). Having been introduced to Sad Sam in lesson 1, the…

  11. Human Pose Estimation from Silhouettes. A Consistent Approach Using Distance Level Sets

    NARCIS (Netherlands)

    Sminchisescu, C.; Telea, A.

    2002-01-01

    We present a novel similarity measure (likelihood) for estimating three-dimensional human pose from image silhouettes in model-based vision applications. One of the challenges in such approaches is the construction of a model-to-image likelihood that truly reflects the good configurations of the pro

  12. Utilizing Service Learning in a College-Level Human Sexuality Course

    Science.gov (United States)

    Jenkins, Dusty D.

    2017-01-01

    Implementing service learning into college courses has been shown to have positive benefits for both students and community members; however, service learning has not been largely evaluated in the literature on human sexuality courses. Thus, the purpose of the current study was to design, implement, and evaluate a service learning project in a…

  13. Increased levels of endothelin ETB receptor mRNA in human omental arteries after organ culture

    DEFF Research Database (Denmark)

    Möller, S; Adner, M; Edvinsson, L

    1998-01-01

    1. Using competitive reverse transcription-polymerase chain reaction (RT-PCR) and in vitro pharmacology, smooth muscle endothelin ETB receptor expression was studied in segments of human omental artery, fresh and after organ culture for 1 and 5 days. 2. The competitive RT-PCR assay used in the pr...

  14. Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

    Science.gov (United States)

    Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

  15. Re-evaluation of human-toxicological maximum permissible risk levels

    NARCIS (Netherlands)

    Baars AJ; Theelen RMC; Janssen PJCM; Hesse JM; Apeldoorn ME van; Meijerink MCM; Verdam L; Zeilmaker MJ; CSR

    2001-01-01

    Soil Intervention Values are generic soil quality standards based on potential risks to humans and eco-systems. These values are used to determine whether or not contaminated soils meet the criteria for "serious soil contamination" as stated in the Dutch Soil Protection Act. With reference to poten

  16. Fractal multi-level organisation of human groups in a virtual world

    Science.gov (United States)

    Fuchs, Benedikt; Sornette, Didier; Thurner, Stefan

    2014-10-01

    Humans are fundamentally social. They form societies which consist of hierarchically layered nested groups of various quality, size, and structure. The anthropologic literature has classified these groups as support cliques, sympathy groups, bands, cognitive groups, tribes, linguistic groups, and so on. Anthropologic data show that, on average, each group consists of approximately three subgroups. However, a general understanding of the structural dependence of groups at different layers is largely missing. We extend these early findings to a very large high-precision large-scale internet-based social network data. We analyse the organisational structure of a complete, multi-relational, large social multiplex network of a human society consisting of about 400,000 odd players of an open-ended massive multiplayer online game for which we know all about their various group memberships at different layers. Remarkably, the online players' society exhibits the same type of structured hierarchical layers as found in hunter-gatherer societies. Our findings suggest that the hierarchical organisation of human society is deeply nested in human psychology.

  17. Utilizing Service Learning in a College-Level Human Sexuality Course

    Science.gov (United States)

    Jenkins, Dusty D.

    2017-01-01

    Implementing service learning into college courses has been shown to have positive benefits for both students and community members; however, service learning has not been largely evaluated in the literature on human sexuality courses. Thus, the purpose of the current study was to design, implement, and evaluate a service learning project in a…

  18. High-level expression of human calmodulin in E. coli and its effects on cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Xiao Jun Li; Jian Guo Wu; Jun Ling Si; Da Wen Guo; Jian Ping Xu

    2000-01-01

    Calmodulin (CaM), widely distributed in almost all eukaryotic cells, is a major intracellular calcium receptor responsible for mediating the Ca2 + signal to a multitude of different enzyme systems and is thought to play a vital role in the regulation of cell proliferative cycle[1,2]. Recently, many studies showed that CaM is also present in extracellular fluid such as cell culture media and normal body fluid and has been reported to stimulate proliferation in a range of normal and neoplastic cells, apparently acting as an autocrine growth factor[3-11]. In 1988, Crocker et al reported for the first time that addition of extracellular pure pig brain CaM could promote DNA synthesis and cell [7]proliferation in K562 human leukaemic lymphocytes[7].After that, more and more research was done on extracellular CaM and evidences demonstrated that extracellular CaM could also stimulate cell proliferation in normal human umbilical vein endothelial cells[5], keratinocytes[4], suspension-cultured cells of Angelica Dahurica, etc[6]. CaM is a monomeric protein of 148 amino acids that contains four homologous Ca2 + -binding domains. CaM has been highly conserved throughout the evolution. Only 1 out of 148 amino acids of human CaM is different from that of fish CaM. Complementary DNAs encoding rat, eel, chicken, human, and trypanosome CaM have been cloned.

  19. Guidance document on the derivation of maximum permissible risk levels for human intake of soil contaminants

    NARCIS (Netherlands)

    Janssen PJCM; Speijers GJA; CSR

    1997-01-01

    This report contains a basic step-to-step description of the procedure followed in the derivation of the human-toxicological Maximum Permissible Risk (MPR ; in Dutch: Maximum Toelaatbaar Risico, MTR) for soil contaminants. In recent years this method has been applied for a large number of compounds

  20. Fractal multi-level organisation of human groups in a virtual world.

    Science.gov (United States)

    Fuchs, Benedikt; Sornette, Didier; Thurner, Stefan

    2014-10-06

    Humans are fundamentally social. They form societies which consist of hierarchically layered nested groups of various quality, size, and structure. The anthropologic literature has classified these groups as support cliques, sympathy groups, bands, cognitive groups, tribes, linguistic groups, and so on. Anthropologic data show that, on average, each group consists of approximately three subgroups. However, a general understanding of the structural dependence of groups at different layers is largely missing. We extend these early findings to a very large high-precision large-scale internet-based social network data. We analyse the organisational structure of a complete, multi-relational, large social multiplex network of a human society consisting of about 400,000 odd players of an open-ended massive multiplayer online game for which we know all about their various group memberships at different layers. Remarkably, the online players' society exhibits the same type of structured hierarchical layers as found in hunter-gatherer societies. Our findings suggest that the hierarchical organisation of human society is deeply nested in human psychology.

  1. Screening-level assays for potentially human-infectious environmental Legionella spp.

    Science.gov (United States)

    In spite of the fact that Legionella species can be isolated from nonclinical settings, there is no standard method to determine whether environmental legionellae may be infectious to humans. In this study, an in vivo murine model of pneumonia and three in vitro proliferation as...

  2. Human Sexuality. A Resource Guide for Parents and Teachers on Teaching...High School Level.

    Science.gov (United States)

    Utah State Office of Education, Salt Lake City.

    This guide provides information and resources that will facilitate parents' ability to help adolescents understand human sexuality within the context of home and family values and ideals. It provides teachers with resources to facilitate the decision making process. Contents are organized within a framework of objectives and guidelines for both…

  3. Effects of Exercise and Dietary Protein Levels on Body Composition in Humans

    Science.gov (United States)

    1978-07-01

    on urea elimination in starva- tion. Ztschr Biol 2:307, 1866. 3. ATWATER, W.O. The demands of the body for nourishment and dietary standards, Fifteenth...H.C., and J.C. WINTER. Efficiency of maize protein in adult human nutrition. J Biol Chem 35:301, 1918. 8. CHITTENDEN, R.H. Physiological economy in

  4. Determination of element levels in human serum: Total reflection X-ray fluorescence applications

    Science.gov (United States)

    Majewska, U.; Łyżwa, P.; Łyżwa, K.; Banaś, D.; Kubala-Kukuś, A.; Wudarczyk-Moćko, J.; Stabrawa, I.; Braziewicz, J.; Pajek, M.; Antczak, G.; Borkowska, B.; Góźdź, S.

    2016-08-01

    Deficiency or excess of elements could disrupt proper functioning of the human body and could lead to several disorders. Determination of their concentrations in different biological human fluids and tissues should become a routine practice in medical treatment. Therefore the knowledge about appropriate element concentrations in human organism is required. The purpose of this study was to determine the concentration of several elements (P, S, Cl, K, Ca, Cr, Fe, Cu, Zn, Se, Br, Rb, Pb) in human serum and to define the reference values of element concentration. Samples of serum were obtained from 105 normal presumably healthy volunteers (66 women aged between 15 and 78 years old; 39 men aged between 15 and 77 years old). Analysis has been done for the whole studied population and for subgroups by sex and age. It is probably first so a wide study of elemental composition of serum performed in the case of Świętokrzyskie region. Total reflection X-ray fluorescence (TXRF) method was used to perform the elemental analysis. Spectrometer S2 Picofox (Bruker AXS Microanalysis GmbH) was used to identify and measure elemental composition of serum samples. Finally, 1st and 3rd quartiles were accepted as minimum and maximum values of concentration reference range.

  5. Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

    NARCIS (Netherlands)

    Strawbridge, Rona J.; Dupuis, Josee; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John R.; Travers, Mary E.; Bouatia-Naji, Nabila; Dimas, Antigone S.; Nica, Alexandra; Wheeler, Eleanor; Chen, Han; Voight, Benjamin F.; Taneera, Jalal; Kanoni, Stavroula; Peden, John F.; Turrini, Fabiola; Gustafsson, Stefan; Zabena, Carina; Almgren, Peter; Barker, David J. P.; Barnes, Daniel; Dennison, Elaine M.; Eriksson, Johan G.; Eriksson, Per; Eury, Elodie; Folkersen, Lasse; Fox, Caroline S.; Frayling, Timothy M.; Goel, Anuj; Gu, Harvest F.; Horikoshi, Momoko; Isomaa, Bo; Jackson, Anne U.; Jameson, Karen A.; Kajantie, Eero; Kerr-Conte, Julie; Kuulasmaa, Teemu; Kuusisto, Johanna; Loos, Ruth J. F.; Luan, Jian'an; Makrilakis, Konstantinos; Manning, Alisa K.; Teresa Martinez-Larrad, Maria; Narisu, Narisu; Mannila, Maria Nastase; Ohrvik, John; Osmond, Clive; Pascoe, Laura; Payne, Felicity; Sayer, Avan A.; Sennblad, Bengt; Silveira, Angela; Stancakova, Alena; Stirrups, Kathy; Swift, Amy J.; Syvanen, Ann-Christine; Tuomi, Tiinamaija; van 't Hooft, Ferdinand M.; Walker, Mark; Weedon, Michael N.; Xie, Weijia; Zethelius, Bjorn; Ongen, Halit; Malarstig, Anders; Hopewell, Jemma C.; Saleheen, Danish; Chambers, John; Parish, Sarah; Danesh, John; Kooner, Jaspal; Ostenson, Claes-Goran; Lind, Lars; Cooper, Cyrus C.; Serrano-Rios, Manuel; Ferrannini, Ele; Forsen, Tom J.; Clarke, Robert; Franzosi, Maria Grazia; Seedorf, Udo; Watkins, Hugh; Froguel, Philippe; Johnson, Paul; Deloukas, Panos; Collins, Francis S.; Laakso, Markku; Dermitzakis, Emmanouil T.; Boehnke, Michael; McCarthy, Mark I.; Wareham, Nicholas J.; Groop, Leif; Pattou, Francois; Gloyn, Anna L.; Dedoussis, George V.; Lyssenko, Valeriya; Meigs, James B.; Barroso, Ines; Watanabe, Richard M.; Ingelsson, Erik; Langenberg, Claudia; Hamsten, Anders; Florez, Jose C.

    2011-01-01

    OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about

  6. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    R.J. Strawbridge (Rona); J. Dupuis (Josée); I. Prokopenko (Inga); A.M. Barker (Adam); E. Ahlqvist (Emma); D. Rybin (Denis); J.R. Petrie (John); N. Bouatia-Naji (Nabila); A.S. Dimas (Antigone); E. Wheeler (Eleanor); H. Chen (Han); B.F. Voight (Benjamin); J. Taneera (Jalal); S. Kanoni (Stavroula); J. Peden (John); F. Turrini (Fabiola); S. Gustafsson (Stefan); C. Zabena (Carina); P. Almgren (Peter); G.V. Dedoussis (George); D. Barnes (Daniel); E.M. Dennison (Elaine); K. Hagen (Knut); P. Eriksson (Per); E. Eury (Elodie); L. Folkersen (Lasse); C.S. Fox (Caroline); T.M. Frayling (Timothy); A. Goel (Anuj); M. Horikoshi (Momoko); B. Isomaa (Bo); A.U. Jackson (Anne); K. Jameson (Karen); E. Kajantie (Eero); J. Kerr-Conte (Julie); L. Groop (Leif); J. Kuusisto (Johanna); R.J.F. Loos (Ruth); J. Luan; K. Makrilakis (Konstantinos); A.K. Manning (Alisa); M.T. Martinez-Larrad (Maria Teresa); N. Narisu (Narisu); J. Öhrvik (John); C. Osmond (Clive); L. Pascoe (Laura); F. Payne (Felicity); A.A. Sayer; B. Sennblad (Bengt); C. Cooper (Charles); K. Stirrups (Kathy); A.J. Swift (Amy); A.C. Syvänen; T. Tuomi (Tiinamaija); F. van't Hooft (Ferdinand); M. Walker (Mark); M.N. Weedon (Michael); W. Xie (Weijia); B. Zethelius (Björn); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.P. Morris (Andrew); C. Dina (Christian); R.P. Welch (Ryan); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); N. Amin (Najaf); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steven); O.M. Hofmann (Oliver); L. Qi (Lu); A.V. Segrè (Ayellet); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); B. Balkau (Beverley); N. Narisu (Narisu); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); A.L. Elliott (Amanda); M.R. Erdos (Michael); C.S. Franklin (Christopher); M. Ganser (Martha); C. Gieger (Christian); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C.J. Groves (Christopher); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); T. Jorgensen (Torben); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); M.N. Weedon (Michael); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); P. Nilsson (Peter); K.R. Owen (Katharine); J.R.B. Perry (John); A.K. Petersen; C. Platou (Carl); C. Proença (Christine); W. Rathmann (Wolfgang); R.R. Frants (Rune); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); B. Thorand (Barbara); J. Tichet (Jean); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G.B. Walters (Bragi); C. Wijmenga (Cisca); S. Cauchi (Stephane); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (T.); W.A. Hide (Winston); G.A. Hitman (Graham); A. Hofman (Albert); K. Hveem (Kristian); M. Laakso (Markku); K.L. Mohlke (Karen L.); A.D. Morris (Andrew); C.N.A. Palmer (Colin); L.D. Stein (Lincoln); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); R.M. Watanabe (Richard); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); H. Campbell (Harry); M.J. Daly (Mark); A.T. Hattersley (Andrew); F.B. Hu (Frank B.); J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); I. Barroso (Inês); L. Groop (Leif); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James F.); T. Illig (Thomas); P. Froguel (Philippe); C.M. van Duijn (Cock); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark I.); E.K. Speliotes (Elizabeth); S.I. Berndt (Sonja); K.L. Monda (Keri); H.L. Allen; R. Mägi (Reedik); J.C. Randall (Joshua); S. Vedantam (Sailaja); T.W. Winkler (Thomas W.); T. Workalemahu (Tsegaselassie); I.M. Heid (Iris); A.R. Wood (Andrew); R.J. Weyant (Robert); K. Estrada Gil (Karol); L. Liang (Liming); J. Nemesh (James); J.H. Park; T.O. Kilpeläinen (Tuomas); J. Yang (Jian); M.F. Feitosa (Mary Furlan); Z. Kutalik (Zoltán)

    2011-01-01

    textabstractOBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new

  7. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    R.J. Strawbridge (Rona); J.R. Petrie (John); T. Forsen (Tom); C. Cooper (Cyrus); M. Franzosi; A. Hamsten (Anders); E. Ferrannini (Ele); M.S. Rios; C.-G. Östenson (Claes-Göran); K. Makrilakis (Konstantinos); T.J. Forsen (Tom); C. Osmond (Clive); C. Cooper (Charles); E.M. Dennison (Elaine); K. Jameson (Karen); A.A. Sayer; T. Kuulasmaa (Teemu); A. Stancáková (Alena); L. Lind (Lars); M.N. Mannila (Maria Nastase); H. Gu (Harvest); B. Zethelius (Björn); F. Turrini (Fabiola); R.J.F. Loos (Ruth); L. Pascoe (Laura); A.C. Syvanen; E. Ahlqvist (Emma); M. Horikoshi (Momoko); D. Barnes (Daniel); C. Han (Chen); A.K. Manning (Alisa); D. Rybin (Denis); S. Kanoni (Stavroula); A.M. Barker (Adam); W. Xie (Weijia); E. Eury (Elodie); J. Kerr-Conte (Julie); F. Pattou (François); P.R.V. Johnson (Paul); M. Travers (Mary); R.R. Frants (Rune); P. Eriksson (Per); L. Folkersen (Lasse); F.M. van't Hooft (Ferdinand); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steve); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noisël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); A.L. Elliott (Amanda); C. Fox (Craig); C.S. Franklin (Christopher); M. Ganser (Martha); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); A.U. Jackson (Anne); P.R.V. Johnson (Paul R.); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John R.); A.K. Petersen; C.P. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G. Bragi Walters (G.); M.N. Weedon (Michael); C. Wijmenga (Cisca); R.N. Bergman (Richard); S. Cauchi (Stephane); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); D. Hunter (David); K. Hveem (Kristian); K.L. Mohlke (Karen); A.D. Morris (Andrew); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); M. Walker (Mark); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); M.J. Daly (Mark); A.T. Hattersley (Andrew); F. Hu; J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); J.C. Florez (Jose); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James F); T. Illig (Thomas); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark); E.K. Speliote (Elizabeth); C.J. Wille (Cristen); S.I. Bernd (Sonja); K.L. Mond (Keri); G. Thorleifsso (Gudmar); H. Lango Allen (Hana); C.M. Lindgre (Cecilia); J. Lua (Jian'an); R. Mäg (Reedik); J.C. Randal (Joshua); S. Vedanta (Sailaja); T.W. Winkle (Thomas); T. Workalemah (Tsegaselassie); I.M. Hei (Iris); V. Steinthorsdotti (Valgerdur); H.M. Stringha (Heather); M.N. Weedo (Michael); E. Wheeler (Eleanor); M.M. Woo (Margaret M.); T. Ferreir (Teresa); R.J. Weyan (Robert); A.V. Segrè (Ayellet); K. Estrad (Karol); J. Luan; J. Nemes (James); J.-H. Par (Ju-Hyun); S. Gustafsson (Stefan); T.O. Kilpeläine (Tuomas); J. Yang (Joanna); N. Bouatia-Naji (Nabila); T. Esko (Tõnu); M.F. Feitosa (Mary Furlan); Z. Kutalik (Zoltán); M. Mangino (Massimo); S. Raychaudhuri (Soumya); R.P. Welch (Ryan); J.H. Zhao; K.K.H. Aben (Katja); D. Absher (Devin); N. Amin (Najaf); A.L. Dixon (Anna); E. Fisher (Eva); N.L. Glazer (Nicole); M.E. Goddard (Michael); N.L. Heard-Costa (Nancy); V. Hoesel (Volker); J.J. Hottenga (Jouke Jan); A. Johansson (Åsa); T. Johnson (Toby); S. Ketkar (Shamika); C. Lamina (Claudia); S. Li (Shengxu); M.F. Moffatt (Miriam); R.H. Myers (Richard); N. Narisu (Narisu); J.R.B. 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Rice (Catherine); F.R. Rosendaal (Frits); D. Rubin (Diana); M.L. Sampietro (Maria Lourdes); M.S. Sandhu (Manjinder); E.E. Schadt (Eric); A. Schäfer (Arne); A. Schillert (Arne); J. Schrezenmeir (Jürgen); S.M. Schwartz (Stephen); D.S. Siscovick (David); M. Sivananthan (Mohan); S. Sivapalaratnam (Suthesh); A.V. Smith (Albert Vernon); T.B. Smith (Tamara); J.D. Snoep (Jaapjan); N. Soranzo (Nicole); J.A. Spertus (John); K. Stark (Klaus); K. Stirrups (Kathy); M. Stoll (Monika); W.H.W. Tang (Wilson); S. Tennstedt (Stephanie); G. Thorgeirsson (Gudmundur); G. Thorleifsson (Gudmar); M. Tomaszewski (Maciej); A.M. van Rij (Andre); B.F. Voight (Benjamin); N.J. Wareham (Nick); G.A. Wells (George); P.S. Wild (Philipp); C. Willenborg (Christina); B.J. Wright (Benjamin); S. Ye (Shu); T. Zeller (Tanja); A. Ziegler (Andreas); F. Cambien (François); A.H. Goodall (Alison); L.A. Cupples (Adrienne); T. Quertermous (Thomas); W. März (Winfried); C. Hengstenberg (Christian); S. Blankenberg (Stefan); W.H. Ouwehand (Willem); A. Hall (Anne); J.R. Thompson (John); K. Stefansson (Kari); R. Roberts (Robert); U. Thorsteinsdottir (Unnur); C.J. O'Donnell (Christopher); R. McPherson (Ruth); N.J. Samani (Nilesh); J. Hopewell; S. Parish (Sharon); A. Offer (Alison); L. Bowman; P. Sleight (Peter); S. Armitage (Shane); R. Peto (R.); R. Collins (Rory); J.C. Chambers (John); N. Ahmed (Nabeel); M. Caulfield (Mark); P. Donnelly (Peter); P. Elliott (Paul); P. Froguel (Philippe); M.I. McCarthy (Mark); N.J. Samani (Nilesh); J. Scott (James); J.S. Sehmi (Joban); W. Zhang (Weihua); J.S. Kooner (Jaspal); R.J. Strawbridge (Rona); M. Sabater-Lleal (Maria); A. Mälarstig (Anders); B. Sennblad (Bengt); J. Öhrvik (John); A. Silveira (Angela); F. van't Hooft (Ferdinand); P. Eriksson (Per); A. Hamsten (Anders); M.-L. Hellénius (Mai-Lis); G. Olsson; S. Rust (Stephan); G. Assmann (Gerd); U. Seedorf (Udo); S. Barlera (Simona); M.G. Franzosi; G. Tognoni; R. Clarke (Robert); P. Linksted (Pamela); J. Hopewell; F.S. Collins (Francis); J. Peden (John); A. Goel (Anuj); H. Ongen (Halit); T. Kyriakou (Theodosios); F. Green (Fiona); M. Farrall (Martin); H. Watkins (Hugh); D. Saleheen; A. Rasheed (Asif); M.A. Zaidi (Aghar); N. Shah (Nisha); M. Samuel (Maria); C.B. Mallick (Chandana Basu); M. Azhar (Muhammad); K.S. Zaman (Khan Shah); A. Samad (Adbus); M. Ishaq (Muhammad); A. Gardezi (Ali); F.-R. Memon (Fazal-ur-Rehman); N.J. Samani (Nilesh); R. Frossard; P. Deloukas (Panagiotis); J. Danesh (John)

    2011-01-01

    markdownabstractOBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new

  8. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    R.J. Strawbridge (Rona); J.R. Petrie (John); T. Forsen (Tom); C. Cooper (Cyrus); M. Franzosi; A. Hamsten (Anders); E. Ferrannini (Ele); M.S. Rios; C.-G. Östenson (Claes-Göran); K. Makrilakis (Konstantinos); T.J. Forsen (Tom); C. Osmond (Clive); C. Cooper (Charles); E.M. Dennison (Elaine); K. Jameson (Karen); A.A. Sayer; T. Kuulasmaa (Teemu); A. Stancáková (Alena); L. Lind (Lars); M.N. Mannila (Maria Nastase); H. Gu (Harvest); B. Zethelius (Björn); F. Turrini (Fabiola); R.J.F. Loos (Ruth); L. Pascoe (Laura); A.C. Syvanen; E. Ahlqvist (Emma); M. Horikoshi (Momoko); D. Barnes (Daniel); C. Han (Chen); A.K. Manning (Alisa); D. Rybin (Denis); S. Kanoni (Stavroula); A.M. Barker (Adam); W. Xie (Weijia); E. Eury (Elodie); J. Kerr-Conte (Julie); F. Pattou (François); P.R.V. Johnson (Paul); M. Travers (Mary); R.R. Frants (Rune); P. Eriksson (Per); L. Folkersen (Lasse); F.M. van't Hooft (Ferdinand); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steve); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noisël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); A.L. Elliott (Amanda); C. Fox (Craig); C.S. Franklin (Christopher); M. Ganser (Martha); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); A.U. Jackson (Anne); P.R.V. Johnson (Paul R.); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John R.); A.K. Petersen; C.P. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G. Bragi Walters (G.); M.N. Weedon (Michael); C. Wijmenga (Cisca); R.N. Bergman (Richard); S. Cauchi (Stephane); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); D. Hunter (David); K. Hveem (Kristian); K.L. Mohlke (Karen); A.D. Morris (Andrew); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); M. Walker (Mark); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); M.J. Daly (Mark); A.T. Hattersley (Andrew); F. Hu; J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); J.C. Flor