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Sample records for receptor c-reactive protein

  1. Electronegative Low-Density Lipoprotein Increases C-Reactive Protein Expression in Vascular Endothelial Cells through the LOX-1 Receptor

    OpenAIRE

    Chu, Chih-Sheng; Wang, Yu-Chen; Lu, Long-Sheng; Walton, Brian; Yilmaz, H. Ramazan; Huang, Roger Y.; Sawamura, Tatsuya; Dixon, Richard A. F.; Lai, Wen-Ter; Chen, Chu-Huang; Lu, Jonathan

    2013-01-01

    Objectives Increased plasma C-reactive protein (CRP) levels are associated with the occurrence and severity of acute coronary syndrome. We investigated whether CRP can be generated in vascular endothelial cells (ECs) after exposure to the most electronegative subfraction of low-density lipoprotein (LDL), L5, which is atherogenic to ECs. Because L5 and CRP are both ligands for the lectin-like oxidized LDL receptor-1 (LOX-1), we also examined the role of LOX-1. Methods and Results Plasma LDL sa...

  2. Biological variation and reference intervals for circulating osteopontin, osteoprotegerin, total soluble receptor activator of nuclear factor kappa B ligand and high-sensitivity C-reactive protein

    DEFF Research Database (Denmark)

    Sennels, H P; Jacobsen, Søren; Jensen, T

    2007-01-01

    Objective. Monitoring inflammatory diseases and osteoclastogenesis with osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor kappa B ligand (total sRANKL) and high-sensitivity C-reactive protein (hsCRP) has recently attracted increased interest. The purpose...

  3. C-reactive (CRP) protein in transfusion dependent thalassaemic patients

    International Nuclear Information System (INIS)

    Jokhio, R.; Mughal, Z.U.N.

    2009-01-01

    In thalassaemic patients iron overload, secondary to blood transfusion, results toxic effects by producing reactive radicals. Iron overload can be studied using serum ferritin level which has a direct correlation with the body's iron status. While oxidative damage can be studied using biomarker of inflammation like hsC-reactive proteins. Blood samples of 55 thalassaemic patients (39 males, 16 females) were collected from Fatmid Foundation (Hyderabad). The samples were analyzed for CBC, serum ferritin level and hsC-reactive proteins. High mean serum ferritin levels was found in all the patients regardless of the frequency of blood transfusion (4774.2135+-3143.3040 mu g/L), indicating the iron overload. High mean hsC-reactive protein was found (2.5151+-1.3712) with a positive correlation with ferritin (r= 0.8371198, p= 0.0000) and platelets (r= 0.43293443, p=0.000962175). C-reactive proteins serve as biomarker of various inflammatory conditions, progression of cardiovascular diseases and as indicator of morbidity and mortality. High C-reactive proteins in these patients indicate ongoing iron overload toxicity related damage in these patients. The estimation of hsC-reactive proteins and other biomarkers of inflammation and oxidation may help in better management of these patients. (author)

  4. C-reactive protein, fibrinogen, and cardiovascular disease prediction

    DEFF Research Database (Denmark)

    Kaptoge, Stephen; Di Angelantonio, Emanuele; Pennells, Lisa

    2012-01-01

    There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events.......There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events....

  5. C reactive protein and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Vestbo, Jørgen; Zacho, Jeppe

    2011-01-01

    It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design.......It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design....

  6. Relationship between C-Reactive Protein and Body Mass Index in ...

    African Journals Online (AJOL)

    Background. C-reactive protein is an acute-phase protein synthesized in the liver and its release is stimulated by cytokines (interleukin 6 and tumour necrosis factor alpha). Baseline levels of C-reactive protein in apparently healthy men and women predict long-term risk of a first myocardial infarction. In older men and ...

  7. C-reactive protein and later preeclampsia

    DEFF Research Database (Denmark)

    Rebelo, Fernanda; Schlüssel, Michael M; Vaz, Juliana S

    2013-01-01

    This study aims to determine whether high C-reactive protein (CRP) concentration during pregnancy is associated with later preeclampsia and whether weight status (BMI) is a potential modifier of the relation between CRP and preeclampsia....

  8. Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists

    International Nuclear Information System (INIS)

    Zhang Songwen; Liu Qiangyuan; Wang Juan; Harnish, Douglas C.

    2009-01-01

    C-reactive protein (CRP), a human acute-phase protein, is a risk factor for future cardiovascular events and exerts direct pro-inflammatory and pro-atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily, plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver, whereas no effect was observed in FXR knockout mice. These data provide new evidence for direct anti-inflammatory properties of FXR.

  9. Serum lipids modify periodontal infection - C-reactive protein association.

    Science.gov (United States)

    Haro, Anniina; Saxlin, Tuomas; Suominen, Anna-Liisa; Ylöstalo, Pekka; Leiviskä, Jaana; Tervonen, Tellervo; Knuuttila, Matti

    2012-09-01

    To investigate whether low-grade inflammation-related factors such as serum low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) modify the association between periodontal infection and C-reactive protein. This study was based on a subpopulation of the Health 2000 Survey, which consisted of dentate, non-diabetic, non-rheumatic subjects who were 30-49 years old (n = 2710). The extent of periodontal infection was measured by means of the number of teeth with periodontal pocket ≥4 mm and teeth with periodontal pocket ≥6 mm and systemic inflammation using high sensitive C-reactive protein. The extent of periodontal infection was associated with elevated levels of C-reactive protein among those subjects whose HDL-C value was below the median value of 1.3 mmol/l or LDL-C above the median value of 3.4 mmol/l. Among those with HDL-C ≥ 1.3 mmol/l or LDL-C ≤ 3.4 mmol/l, the association between periodontal infection and serum concentrations of C-reactive protein was practically non-existent. This study suggests that the relation of periodontal infection to the systemic inflammatory condition is more complicated than previously presumed. The findings of this study suggest that the possible systemic effect of periodontal infection is dependent on serum lipid composition. © 2012 John Wiley & Sons A/S.

  10. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein

    NARCIS (Netherlands)

    Ridker, Paul M.; Danielson, Eleanor; Fonseca, Francisco A. H.; Genest, Jacques; Gotto, Antonio M.; Kastelein, John J. P.; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J.; Macfadyen, Jean G.; Nordestgaard, Børge G.; Shepherd, James; Willerson, James T.; Glynn, Robert J.; Ridker, P. M.; Fonseca, F. A. H.; Genest, J.; Gotto, A. M.; Koenig, W.; Libby, P.; Lorenzatti, A. J.; Nordestgaard, B. G.; Shepherd, J.; Willerson, J. T.; Danielson, E.; Glynn, R. J.; MacFadyen, J. G.; Mora, S.; Collins, R.; Bailey, K.; Gersh, B.; Lamas, G.; Smith, S.; Vaughan, D.; Mahaffey, K.; Brown, P.; Montgomery, D.; Wilson, M.; Wood, F.; Altamirano, J.; Boskis, P.; Colombo, H.; Cuneo, C.; Diaz, M.; Esper, R.; Trip, M.; Hoekstra, J.; Koch, S.; Lucas, M.; van de Beek, M.

    2008-01-01

    BACKGROUND: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels

  11. Depressive symptoms and C-reactive protein in a Brazilian urban community

    Directory of Open Access Journals (Sweden)

    W.W. Dressler

    2006-08-01

    Full Text Available Psychological depression is an independent risk factor for coronary artery disease. C-reactive protein has been implicated as a mediator of the effect of psychological depression. Several studies have found that individuals, especially men, who report higher levels of psychological depression also have higher levels of C-reactive protein. The current study was undertaken to replicate these results in a Brazilian population, in which there is a much wider range of variation in both background characteristics (such as socioeconomic status and coronary artery disease risk factors. A sample of 271 individuals was interviewed using the Center for Epidemiological Studies Depression Scale. Fasting blood samples were obtained and evaluated for C-reactive protein (assessed by a turbidimetric immunoassay using a Dade Behring kit analysis in a subsample (N = 258 of individuals. The mean ± SD C-reactive protein for the entire sample was 0.43 ± 0.44, with 0.42 ± 0.48 for men and 0.43 ± 0.42 mg/L for women. Data were analyzed using multiple regression analysis, controlling for age, sex, body mass index, socioeconomic status, tobacco use, and both total cholesterol and low-density lipoprotein cholesterol. Higher reported depressive symptoms were correlated with higher C-reactive protein for men (partial r = 0.298, P = 0.004 and with lower C-reactive protein for women (partial r = -0.154, P = 0.059. The differences in the associations for men and women could be a result of differential effects of sex hormones on stress reactivity and immune response. On the other hand, this difference in the associations may be related to gender differences in the disclosure of emotion and the effect that self-disclosure has on physical health and immune response.

  12. Human serum protein and C-reactive protein levels among HIV ...

    African Journals Online (AJOL)

    Human serum protein and C-reactive protein levels were determined among HIV patients visiting St Camillus Hospital, Uromi, Edo State, Nigeria, between January to March, 2013. Fifty (50) HIV patients (20 males; 30 females) and 50 control subjects (24 males; 26 females) were enrolled for this study. The clinical status of ...

  13. Predictive value of C-reactive protein in critically ill patients after abdominal surgery

    Directory of Open Access Journals (Sweden)

    Frédéric Sapin

    Full Text Available OBJECTIVES: The development of sepsis after abdominal surgery is associated with high morbidity and mortality. Due to inflammation, it may be difficult to diagnose infection when it occurs, but measurement of C-reactive protein could facilitate this diagnosis. In the present study, we evaluated the predictive value and time course of C-reactive protein in relation to outcome in patients admitted to the intensive care unit (ICU after abdominal surgery. METHODS: We included patients admitted to the ICU after abdominal surgery over a period of two years. The patients were divided into two groups according to their outcome: favorable (F; left the ICU alive, without modification of the antibiotic regimen and unfavorable (D; death in the ICU, surgical revision with or without modification of the antibiotic regimen or just modification of the regimen. We then compared the highest C-reactive protein level on the first day of admission between the two groups. RESULTS: A total of 308 patients were included: 86 patients had an unfavorable outcome (group D and 222 had a favorable outcome (group F. The groups were similar in terms of leukocytosis, neutrophilia, and platelet count. C-reactive protein was significantly higher at admission in group D and was the best predictor of an unfavorable outcome, with a sensitivity of 74% and a specificity of 72% for a threshold of 41 mg/L. No changes in C-reactive protein, as assessed based on the delta C-reactive protein, especially at days 4 and 5, were associated with a poor prognosis. CONCLUSIONS: A C-reactive protein cut-off of 41 mg/L during the first day of ICU admission after abdominal surgery was a predictor of an adverse outcome. However, no changes in the C-reactive protein concentration, especially by day 4 or 5, could identify patients at risk of death.

  14. Quantitative measurements of C-reactive protein using silicon nanowire arrays

    Directory of Open Access Journals (Sweden)

    Min-Ho Lee

    2008-03-01

    Full Text Available Min-Ho Lee, Kuk-Nyung Lee, Suk-Won Jung, Won-Hyo Kim, Kyu-Sik Shin, Woo-Kyeong SeongKorea Electronics Technology Institute, Gyeonggi, KoreaAbstract: A silicon nanowire-based sensor for biological application showed highly desirable electrical responses to either pH changes or receptor-ligand interactions such as protein disease markers, viruses, and DNA hybridization. Furthermore, because the silicon nanowire can display results in real-time, it may possess superior characteristics for biosensing than those demonstrated in previously studied methods. However, despite its promising potential and advantages, certain process-related limitations of the device, due to its size and material characteristics, need to be addressed. In this article, we suggest possible solutions. We fabricated silicon nanowire using a top-down and low cost micromachining method, and evaluate the sensing of molecules after transfer and surface modifications. Our newly designed method can be used to attach highly ordered nanowires to various substrates, to form a nanowire array device, which needs to follow a series of repetitive steps in conventional fabrication technology based on a vapor-liquid-solid (VLS method. For evaluation, we demonstrated that our newly fabricated silicon nanowire arrays could detect pH changes as well as streptavidin-biotin binding events. As well as the initial proof-of-principle studies, C-reactive protein binding was measured: electrical signals were changed in a linear fashion with the concentration (1 fM to 1 nM in PBS containing 1.37 mM of salts. Finally, to address the effects of Debye length, silicon nanowires coupled with antigen proteins underwent electrical signal changes as the salt concentration changed.Keywords: silicon nanowire array, C-reactive protein, vapor-liquid-solid method

  15. The diagnostic value of c-reactive protein estimation in differentiating bacterial from viral meningitis

    International Nuclear Information System (INIS)

    Sheikh, A.

    2001-01-01

    Objective: To evaluate the efficacy of serum and CSF C-reactive protein (C-rp) in differentiating bacterial from viral meningitis. Design: An observational, respective hospital-based study. Place and duration of study: It was conducted at the Department of Medicine and Department of Pediatrics, Shaikh Zayed Postgraduate Medical Institute Lahore, Over a Period of one year between march, 1999 and March, 2000. Subject and Methods: A randomized group of thirty patients, who presented with clinical features, suggestive of meningitis, were included in the study. C-reactive protein determinations were performed by latex agglutination method on the serum and cerebrospinal fluid (CSF) of these patients. Results: In the present study, c-reactive protein was found to be a more sensitive test for differentiating bacterial from non-bacterial meningitis on initial examination than the usual conventional methods used to diagnose bacterial meningitis. CSF C-reactive protein had a greater sensitivity (92% as compared to serum C-reactive protein (71%). Conclusion: C-reactive protein determination in CSF was found to be a useful indicator of bacterial meningitis that can be used to distinguish it from viral meningitis. (author)

  16. Comparative study of C-Reactive Protein and other biochemical ...

    African Journals Online (AJOL)

    Serum levels of C-reactive proteins (CRP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total protein, albumin and globulins were investigated using high sensitivity Immunoturbidometric and colorimetric techniques in individuals with hepatitis (n=50), Malaria (n=50) and 40 control subjects in age ...

  17. Association between C-reactive protein and features of the metabolic syndrome

    DEFF Research Database (Denmark)

    Fröhlich, M; Imhof, A; Berg, Gabriele

    2000-01-01

    OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence...... C-reactive protein and TC (R = 0.19), TG (R = 0.29), BMI (R = 0.32), glucose (R = 0.11), and uric acid (R = 0.14) (all P

  18. Level of C - reactive protein as an indicator for prognosis of premature uterine contractions.

    Science.gov (United States)

    Najat Nakishbandy, Bayar M; Barawi, Sabat A M

    2014-01-01

    high concentrations of maternal C-reactive protein have been associated with adverse pregnancy outcome, and premature uterine contraction may be predicted by elevated levels of C-reactive protein. This may ultimately be simple and cost-effective enough to introduce as a low-risk screening program. an observational case control study was performed from May 1st, 2010 to December 1st, 2010 at Maternity Teaching Hospital-Erbil/ Kurdistan Region/ Iraq. The sample size was (200) cases. Hundred of them were presented with premature uterine contractions at 24(+0)-36(+6) weeks. The other hundred were control group at same gestational ages. The level of C-reactive protein was determined in both groups and both groups were followed till delivery. (93) out of (100) women with premature uterine contractions had elevated level of C-Reactive protein and 91% delivered prematurely while in the control group only (9) out of (100) women had elevated level of C-reactive protein and only 8% of them delivered preterm. Differences were statistically highly significant. C-reactive protein can be used as a biomarker in prediction of premature delivery when it is associated with premature uterine contractions. As well it can be used as a screening test to detect cases that are at risk of premature delivery.

  19. Neighborhood Walkable Urban Form and C-Reactive Protein

    Science.gov (United States)

    Background: Walkable urban form predicts physical activity and lower body mass index, which lower C-reactive protein (CRP). However, urban form is also related to pollution, noise, social and health behavior, crowding, and other stressors, which may complement or contravene walka...

  20. Effects of periodontal therapy on C-reactive protein and HDL in serum of subjects with periodontitis.

    Science.gov (United States)

    Leite, Anne Carolina Eleutério; Carneiro, Valéria Martins de Araújo; Guimarães, Maria do Carmo Machado

    2014-01-01

    To investigate the effects of nonsurgical periodontal therapy on levels of high-sensitivity C-reactive protein in the sera and its association with body mass index and high density lipoprotein in subjects with severe periodontitis. Sera from 28 subjects (mean age: 34.36±6.24; 32% men) with severe periodontitis and 27 healthy controls (mean age: 33.18±6.42; 33% men) were collected prior to periodontal therapy. Blood samples were obtained from 23 subjects who completed therapy (9-12 months). Oral and systemic parameters such as the number of blood cells, glucose examination, lipid profile, and high-sensitivity C-reactive protein levels accessed by high-sensitivity immunonephelometry assay, were included. Before therapy, in the periodontitis group, the ratio of subjects with high-sensitivity C-reactive protein C-reactive protein C-reactive protein C-reactive protein >0.3 mg/dL (28.91±6.03) (Pperiodontitis, periodontal therapy was associated with decreased levels of circulating high-sensitivity C-reactive protein and increase of high density lipoprotein in serum. The clinical trial was registered at http://www.clinicaltrials.gov.br/, No. RBR-24T799.

  1. The endothelial protein C receptor and activated protein C play a limited role in host defense during experimental tuberculosis

    NARCIS (Netherlands)

    Kager, Liesbeth M.; Roelofs, Joris J. T. H.; de Vos, Alex F.; Wieland, Catharina W.; Schouten, Marcel; Meijers, Joost C. M.; Isermann, Berend; van't Veer, Cornelis; Esmon, Charles T.; van der Poll, Tom

    2013-01-01

    The protein C (PC) system is an important regulator of both coagulation and inflammation. Activated PC (APC), together with its receptor the endothelial protein C receptor (EPCR), has anticoagulant and anti-inflammatory properties. During tuberculosis (TB), a devastating chronic pulmonary disease

  2. C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction

    NARCIS (Netherlands)

    Kaptoge, Stephen; Di Angelantonio, Emanuele; Pennells, Lisa; Wood, Angela M.; White, Ian R.; Gao, Pei; Walker, Matthew; Thompson, Alexander; Sarwar, Nadeem; Caslake, Muriel; Butterworth, Adam S.; Amouyel, Philippe; Assmann, Gerd; Bakker, Stephan J. L.; Barr, Elizabeth L. M.; Barrett-Connor, Elizabeth; Benjamin, Emelia J.; Bjorkelund, Cecilia; Brenner, Hermann; Brunner, Eric; Clarke, Robert; Cooper, Jackie A.; Cremer, Peter; Cushman, Mary; Dagenais, Gilles R.; D'Agostino, Ralph B.; Dankner, Rachel; Davey-Smith, George; Deeg, Dorly; Dekker, Jacqueline M.; Engstrom, Gunnar; Folsom, Aaron R.; Fowkes, F. Gerry R.; Gallacher, John; Gaziano, J. Michael; Giampaoli, Simona; Gillum, Richard F.; Hofman, Albert; Howard, Barbara V.; Ingelsson, Erik; Iso, Hiroyasu; Jorgensen, Torben; Kiechl, Stefan; Kitamura, Akihiko; Kiyohara, Yutaka; Koenig, Wolfgang; Kromhout, Daan; Kuller, Lewis H.; Lawlor, Debbie A.; Meade, Tom W.

    2012-01-01

    Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of

  3. C- Reactive Protein in Tuberculosis and Human Immunodeficiency ...

    African Journals Online (AJOL)

    This study was conducted to evaluate C-reactive protein (CRP) levels in Mycobacterium tuberculosis and human immunodeficiency virus (HIV) infections and the follow-up therapeutic response to tuberculosis (TB) among patients aged 19-68 years attending out-patient clinics of two hospitals in Abeokuta, Southwestern ...

  4. Increased Body Mass Index, Elevated C-reactive Protein, and Short Telomere Length

    DEFF Research Database (Denmark)

    Rode, Line; Nordestgaard, Børge G; Weischer, Maren

    2014-01-01

    -reactive protein. SETTING AND DESIGN: We studied 45,069 individuals from the Copenhagen General Population Study with measurements of leukocyte telomere length, BMI, and C-reactive protein in a Mendelian randomization study. Using the three obesity-associated polymorphisms FTO rs9939609, MC4R rs17782313, and TMEM...

  5. Resting serum concentration of high-sensitivity C-reactive protein ...

    African Journals Online (AJOL)

    Resting serum concentration of high-sensitivity C-reactive protein (hs-CRP) in sportsmen and untrained male adults. F.A. Niyi-Odumosu, O. A. Bello, S.A. Biliaminu, B.V. Owoyele, T.O. Abu, O.L. Dominic ...

  6. Association of C-reactive protein positivity among groups of patients with knee osteoarthritis in Erbil

    Directory of Open Access Journals (Sweden)

    Helen Ahmed Pirdawood

    2017-08-01

    Full Text Available Background and objective: Osteoarthritis is the most common joint disease and a leading cause of disability. Increased circulating levels of C-reactive protein have been associated with prevalent knee osteoarthritis. This study aimed to assess the association between C- reactive protein positivity in patients with knee osteoarthritis in Erbil Methods: Data from100 participants in this case-control study were enrolled from May 1st to December 1st, 2015 in Rizgary Teaching Hospital in Erbil city. Data were divided into two groups. The cases included 50 patients (17 male and 33 female with a mean age of 58.9 ±3.8 years and diagnosed with primary knee osteoarthritis of one or both knee joints. Controls included 50 persons (17 male and 33 female with a mean age of 58.1 ±3.9 years without knee osteoarthritis and matched for age, sex, and body mass index. C-reactive protein qualitatively measured. Patients were radiologically assessed by Kellgren and Lawrence grading scale (grade 0-4. Results: C-reactive protein was positive in 41 out of 50 (82% of knee osteoarthritis patients compared to 3 out of 50 (6% of healthy controls (P = 0.001. C- reactive protein positivity among knee osteoarthritis patients were significantly associated with body mass index, positive family history of knee osteoarthritis, duration of diseases, and Kellgren and Lawrence grade (P 0.05. Conclusion: C-reactive protein positivity was significantly associated with knee osteoarthritis compared to healthy controls. Furthermore, body mass index, positive family history of knee osteoarthritis, early osteoarthritis, and Kellgren and Lawrence grade II, were significantly associated with positive C-reactive protein in knee osteoarthritis.

  7. Comparison of C-reactive protein and high-sensitivity C-reactive protein levels in patients on hemodialysis

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2012-01-01

    Full Text Available Chronic inflammation is highly prevalent in patients on hemodialysis (HD, as evidenced by increased levels of C-reactive protein (CRP. We compared CRP to high-sensitivity C-reactive protein (hs-CRP to determine whether it has any clinical implications and prognostic significance in terms of mortality. CRP was measured using a standard immunoturbidometric assay on the COBAS; INTEGRA system and hs-CRP was measured using the Dade Behring on the Konelab Nephelometer in 50 patients on HD. CRP (≥6 mg/L and hs-CRP (≥3 mg/L levels were elevated in 30% and 54% of the patients, respectively. A significant correlation was noted between hs-CRP and CRP levels (r = 0.98, P <0.001. Deming regression analysis showed that the slope was near one (r = 0.90; 0.83-0.94 and that the intercept was small. Multivariate regression confirmed that age above 40 years (RR = 3.69, P = 0.027 and duration on HD greater than five years (RR = 3.71, P = 0.028 remained significant independent predictors of serum hs-CRP. Thirteen patients died during follow-up (26%. Multivariate Cox regression demonstrated that hs-CRP (RR = 1.062, P = 0.03 and CRP levels (RR = 1.057, P = 0.009 and age (RR = 1.078, P = 0.001 were the most powerful predictors of mortality. The CRP standard assay presents a reasonable alternative to the hs-CRP assay in patients on HD. The advantages of the CRP standard assay are its online and real-time availability as well as lower costs, particularly in developing countries.

  8. The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): Interference of C-reactive protein.

    Science.gov (United States)

    Liu, Jie; Li, Fanfan; Shu, Kuangyi; Chen, Tao; Wang, Xiaoou; Xie, Yaoqi; Li, Shanshan; Zhang, Zhaohua; Jin, Susu; Jiang, Minghua

    2018-05-13

    To investigate the effect of C-reactive protein on the activated partial thromboplastin time (APTT) (different activators) in different detecting systems. The C-reactive protein and coagulation test of 112 patients with the infectious disease were determined by automation protein analyzer IMMAG 800 and automation coagulation analyzer STA-R Evolution, respectively. The pooled plasma APTT with different concentrations of C-reactive protein was measured by different detecting system: STA-R Evolution (activator: silica, kaolin), Sysmex CS-2000i (activator: ellagic acid), and ACL TOP 700 (activator: colloidal silica). In addition, the self-made platelet lysate (phospholipid) was added to correct the APTT prolonged by C-reactive protein (150 mg/L) on STA-R Evolution (activator: silica) system. The good correlation between C-reactive protein and APTT was found on the STA-R Evolution (activator: silica) system. The APTT on the STA-R Evolution (activator: silica) system was prolonged by 24.6 second, along with increasing C-reactive protein concentration. And the APTT of plasma containing 150 mg/L C-reactive protein was shortened by 3.4-6.9 second when the plasma was mixed with self-made platelet lysate. However, the APTT was prolonged unobviously on other detecting systems including STA-R Evolution (activator: kaolin), Sysmex CS-2000i, and ACL TOP 700. C-reactive protein interferes with the detection of APTT, especially in STA-R Evolution (activator: silica) system. The increasing in C-reactive protein results in a false prolongation of the APTT (activator: silica), and it is most likely that C-reactive protein interferes the coagulable factor binding of phospholipid. © 2018 Wiley Periodicals, Inc.

  9. Binding of C-reactive protein to human polymorphonuclear leukocytes: evidence for association of binding sites with Fc receptors

    International Nuclear Information System (INIS)

    Mueller, H.; Fehr, J.

    1986-01-01

    The functional similarities between C-reactive protein (CRP) and IgG raised the question as to whether human phagocytes are stimulated by CRP in the same way as by binding of antigen-complexes or aggregated IgG to their Fc receptors. Studies with the use of highly purified 125 I-labeled CRP showed specific and saturable binding to human polymorphonuclear leukocytes (PNM) with a K/sub D/ of 10.5 +/- 5.7 x 10 -8 M only when carried out in heat-inactivated plasma. The number of specific binding sites per cell was estimated at 1 to 3 x 10 6 . Competitive inhibition of CRP binding by antigen-complexed or aggregated IgG suggests CRP binding sites to be associated IgG suggests CRP binding sites to be associated with PMN Fc receptors. Only when assayed in heat-inactivated plasma did CRP binding induce adherence of cells to tissue culture dishes. However, no metabolic and potentially cytotoxic simulation of PMN was detected during CRP plasma-dependent attachment to surfaces: induction of aggregation, release of secondary granule constituents, and activation of the hexose monophosphate pathway were not observed. These results imply that CRP-PMN interactions is dependent on an additional factor present in heat-inactivated plasma and is followed only by a complement-independent increase in PMN attachment to surfaces. Because CRP was found to be deposits at sites of tissue injury, the CRP-mediated adherence of PMN may be an important step in localizing an inflammatory focus

  10. Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction

    International Nuclear Information System (INIS)

    Sjoewall, Christopher; Wetteroe, Jonas; Bengtsson, Torbjoern; Askendal, Agneta; Almroth, Gunnel; Skogh, Thomas; Tengvall, Pentti

    2007-01-01

    C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fcγ receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups

  11. predictors of c-reactive protein response in children infected

    African Journals Online (AJOL)

    2014-01-01

    Jan 1, 2014 ... Results: The predictors of the C-reactive protein response in malaria (CRP ≥ 10mg/l) were fever (t = 6.867; ..... The lack of a significant difference between the ... infections - A major cause of death among children in Africa.

  12. Plasma levels of C-Reactive Protein and Fibrinogen in Pulmonary ...

    African Journals Online (AJOL)

    In this study, we determined the changes in plasma C- reactive protein (C-RP) and Fibrinogen levels in Drug sensitive Tuberculosis (DSTB) patients at diagnosis, Multi drug resistant tuberculosis (MDRTB) patients at diagnosis and during chemotherapy. Twenty-four (24) patients MDRTB patients and 24 newly diagnosed ...

  13. Effects of atorvastatin on human c reactive protein metabolism

    Science.gov (United States)

    Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goals were to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Eight subjects with combined hyperlipidemia (5 men and 3 postmenopausal women) were enrolled in a randomized, placebo-controlled...

  14. Vitamin D and C-Reactive Protein: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Marte C Liefaard

    Full Text Available Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein. We studied the association between serum 25-hydroxyvitamin D and C-reactive protein through linear regression in 9,649 participants of the Rotterdam Study, an observational, prospective population-based cohort study. We used genetic variants related to vitamin D and CRP to compute a genetic risk score and perform bi-directional Mendelian randomization analysis. In linear regression adjusted for age, sex, cohort and other confounders, natural log-transformed CRP decreased with 0.06 (95% CI: -0.08, -0.03 unit per standard deviation increase in 25-hydroxyvitamin D. Bi-directional Mendelian randomization analyses showed no association between the vitamin D genetic risk score and lnCRP (Beta per SD = -0.018; p = 0.082 or the CRP genetic risk score and 25-hydroxyvitamin D (Beta per SD = 0.001; p = 0.998. In conclusion, higher levels of Vitamin D are associated with lower levels of C-reactive protein. In this study we did not find evidence for this to be the result of a causal relationship.

  15. High-sensitivity C-reactive protein predicts target organ damage in Chinese patients with metabolic syndrome

    DEFF Research Database (Denmark)

    Zhao, Zhigang; Nie, Hai; He, Hongbo

    2007-01-01

    with metabolic syndrome. A total of 1082 consecutive patients of Chinese origin were screened for the presence of metabolic syndrome according to the National Cholesterol Education Program's Adult Treatment Panel III. High-sensitivity C-reactive protein and target organ damage, including cardiac hypertrophy......Observational studies established high-sensitivity C-reactive protein as a risk factor for cardiovascular events in the general population. The goal of this study was to determine the relationship between target organ damage and high-sensitivity C-reactive protein in a cohort of Chinese patients......, carotid intima-media thickness, and renal impairment, were investigated. The median (25th and 75th percentiles) of high-sensitivity C-reactive protein in 619 patients with metabolic syndrome was 2.42 mg/L (0.75 and 3.66 mg/L) compared with 1.13 mg/L (0.51 and 2.46 mg/L) among 463 control subjects (P

  16. Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Bartels, Else M.; Bliddal, Henning

    2012-01-01

    To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs.......To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs....

  17. Prognostic value of sustained elevated C-reactive protein levels in patients with acute aortic intramural hematoma.

    Science.gov (United States)

    Kitai, Takeshi; Kaji, Shuichiro; Kim, Kitae; Ehara, Natsuhiko; Tani, Tomoko; Kinoshita, Makoto; Furukawa, Yutaka

    2014-01-01

    The appropriate management of aortic intramural hematoma is still controversial, because a variety of aortic events can arise during follow-up in some patients. However, simplified identification of these patients remains challenging. The present study aimed to determine the prognostic significance of serial C-reactive protein measurements for the prediction of adverse events in patients with acute aortic intramural hematoma. A total of 180 patients with aortic intramural hematoma were retrospectively reviewed. The C-reactive protein data were obtained at admission and 2 days, 1 week, and 2 weeks from the onset, and the maximum value was obtained during the acute phase. Adverse aorta-related events were defined by a composite of aortic rupture, aortic aneurysm, and surgical or endovascular aortic repair. The C-reactive protein value was 3.0 ± 4.6, 8.7 ± 5.9, 9.0 ± 5.5, and 5.7 ± 4.5 mg/dL on admission and 2 days, 1 week, and 2 weeks from the onset, respectively. The maximal value of C-reactive protein was 12.4 ± 6.3 mg/dL at a mean of 4 days from the onset. Patients with elevated C-reactive protein levels (≥7.2 mg/dL) at 2 weeks had significantly greater rates of aorta-related events (P analysis, an elevated C-reactive protein level at 2 weeks (hazard ratio, 3.16; P value compared with the development of an ulcer-like projection (chi-square, 16.94 for ulcer-like projection only vs 34.32 with the addition of C-reactive protein at 2 weeks, P < .001). C-reactive protein was a simple and useful marker providing incremental prognostic information compared with the development of an ulcer-like projection in patients with aortic intramural hematoma. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  18. Association between Depression and C-Reactive Protein

    Directory of Open Access Journals (Sweden)

    Yunsheng Ma

    2011-01-01

    Full Text Available Objective. Depression has been associated with increased cardiovascular disease risk, and a depression-related elevation of high sensitivity C-reactive protein (hs-CRP has been proposed as a possible mechanism. The objective of this paper is to examine association between depression and high sensitivity C-reactive protein (hs-CRP. Methods. Subjects consisted of 508 healthy adults (mean age 48.5 years; 49% women, 88% white residing in central Massachusetts. Data were collected at baseline and at quarterly intervals over a one-year period per individual. Multivariable linear mixed models were used to assess the association for the entire sample and by gender. Results. The mean Beck Depression Inventory score was 5.8 (standard deviation (SD 5.4; median 4.3, and average serum hs-CRP was 1.8 mg/L (SD 1.7; median 1.2. Results from the multivariable linear mixed models show that individuals with higher depression scores have higher levels of hs-CRP. Analyses by gender show persistence of an independent association among women, but not among men. Body mass index (BMI = weight(kg/height(m2 appears to be a partial mediator of this relationship. Conclusion. Depression score was correlated to hs-CRP levels in women. Further studies are required to elucidate the biological mechanisms underlying these associations and their implications.

  19. Serum C-reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice.

    Science.gov (United States)

    Avan, Amir; Tavakoly Sany, Seyedeh Belin; Ghayour-Mobarhan, Majid; Rahimi, Hamid Reza; Tajfard, Mohammad; Ferns, Gordon

    2018-06-22

    Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high-sensitivity assays for serum C-reactive protein have shown a consistent association between cardiovascular disease risk and serum C-reactive protein concentrations. C-reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C-reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C-reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C-reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C-reactive protein genetic polymorphisms on baseline plasma C-reactive protein levels. © 2018 Wiley Periodicals, Inc.

  20. Predictive value of c-reactive protein for thrombolytic therapy in acute myocardial infarction

    International Nuclear Information System (INIS)

    Majeed, N.; Bashir, F.

    2014-01-01

    The serum levels of C-reactive protein on admission may predict the efficacy of reperfusion in patients with acute myocardial infarction. Objectives: This study was conducted to know the predictive value of CRP for success of thrombolysis and to know the prognostic value of C-reactive protein in patients having acute myocardial infarction. Study Design: It was single center, open labeled cross sectional study. Materials and Methods: Sixty patients of acute myocardial infarction diagnosed on clinical and ECG criteria, who received thrombolytic therapy with strepto- kinase, were included in the study. The diagnosis of acute rnyocardial infarction was made on clinical para meters and ECG criteria. The ECG changes were noted before starting thrombolysis. The baseline sample for C-reactive protein (CRP,) was taken before starting thrombolysis. The time duration between onset of symptoms and start of thrombolysis was also noted. The thrombolysis was done with streptokinase infusion, 1.5 million units diluted in 100ml normal saline, intravenously over one hour. The ECG was repeated after six hours of completion of thrombolysis and, changes were noted and compared with ECG changes before thrombolysis. Now second sample for C-reactive protein (CRP2) was taken after six hours of completion of thrombolysis. CRP was measured by a high sensitivity assay which can accurately measure basal levels of CRP throughout the currently accepted cardiovascular risk assessment range (0.20 - 10.0 mg/L). According to ECG findings after thrombolysis, all patients were divided into two groups. Group A was considered as successful group to thrombolysis, in whom ECG changes were settled. Group B was considered as unsuccessful group to thrombolysis, in whom ECG changes remained same as before thrombolysis. Both values of C-reactive protein, CRP, and CRP2 were compared in both groups group A and group B. Results: Plasma CRP values before and after thrombolysis had strong predictive value for

  1. C-Reactive Protein in Healthy Adult Nigerians | Baba | Nigerian ...

    African Journals Online (AJOL)

    Background: C-reactive protein (CRP) is an acute phase reactant produced in the liver in response to tissue injury or systemic inflammation, its release is stimulated by cytokines (interleukin-6 and tumour necrosis factor-alpha). Elevated CRP levels have been linked to an increased risk of later development of diabetes ...

  2. The impact of CCR5-Δ32 deletion on C-reactive protein levels and cardiovascular disease

    DEFF Research Database (Denmark)

    Dinh, Khoa Manh; Pedersen, Ole B; Petersen, Mikkel S

    2015-01-01

    BACKGROUND AND PURPOSE: The C-C chemokine receptor 5-Δ32 deletion (CCR5-Δ32) has been associated with lower levels of C-reactive protein (CRP), but the effect on cardiovascular diseases is uncertain. This study addresses the impact of CCR5-Δ32 on the risk of low-grade inflammation...... and hospitalization with cardiovascular diseases in a large cohort of blood donors. METHODS: Genotyping of 15,206 healthy participants from The Danish Blood Donor Study for CCR5-Δ32 was performed and combined with CRP measurements and questionnaire data. Cardiovascular disease diagnoses were identified by ICD-10......: In this cohort, carriers of the CCR5-Δ32 deletion had normal CRP levels but a borderline significant increased risk of cardiovascular diseases....

  3. Milk C-reactive protein in canine mastitis.

    Science.gov (United States)

    Vasiu, Iosif; Dąbrowski, Roman; Martinez-Subiela, Silvia; Ceron, Jose J; Wdowiak, Anna; Pop, Raul Alexandru; Brudaşcă, Florinel Gheorghe; Pastor, Josep; Tvarijonaviciute, Asta

    2017-04-01

    Presence of mastitis in lactating bitches can become life threatening for both the bitch and pups. The aim of the present study was to evaluate a possible utility of C-reactive protein (CRP) in both milk and serum for canine mastitis diagnosis. Our study showed that milk CRP levels ranged between 0.1 and 4.9μg/mL and from 0.3 to 40.0μg/mL in healthy and diseased bitches (Pcanine mastitis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. C-reactive protein: an aid for diagnosis of acute appendicitis

    International Nuclear Information System (INIS)

    Ahmed, N.

    2017-01-01

    Delayed or wrong diagnosis of acute appendicitis in patients results in complications like perforation, gangrene, etc. which carries a significant amount of morbidity and mortality to the patients. Thus, timely diagnosis of acute appendicitis is crucial to prevent these complications. Recently, it was found that serum C-reactive protein (CRP) individually can be a useful marker, thus in resource limited settings (i.e., access to ultrasonography) simple laboratory investigation can be of extreme utility for the diagnosis of acute appendicitis. Current study aimed to ascertain and determine the role of C Reactive Protein (CRP) as a complementary test to decrease the rate of negative appendectomies in tertiary care hospitals of Pakistan. Methods: Using non-probability consecutive sampling, 112 patients with the initial diagnosis of acute appendicitis on history and clinical examination were enrolled. A blood sample was taken for serum level of CRP. Results: Mean age was 20.8+-8.6 years and 51 (45.5 %) patients were males. Pathologic review revealed 100 cases (89.3%) of acute appendicitis, 4 patients (3.6%) had perforated appendix while 8 patients (7.1%) had normal appendix. Sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of C reactive protein >24 mg/lit taking histology as gold standard came out 25.9%, 100%, 100%, 9.4% and 31.25% respectively. Conclusion: It was concluded that CRP >48 mg/lit is an indication of perforated appendix and when the surgeon is in fix whether to go conservatively or apply some intervention, CRP can be a good diagnostic aid. (author)

  5. Role of plasma adiponectin /C-reactive protein ratio in obesity and ...

    African Journals Online (AJOL)

    African Health Sciences ... Objective(s): We examined relations between fasting plasma adiponectin (ADIP), C-reactive protein (CRP) ... Methods: Fasting plasma ADIP, CRP, Insulin (IN), HOMA-IR, lipid profiles, body fat percent (%BF), waist ...

  6. Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort.

    Science.gov (United States)

    Canetta, Sarah; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; Leiviskä, Jaana; Kellendonk, Christoph; McKeague, Ian W; Brown, Alan S

    2014-09-01

    The objective of the present study was to investigate an association between early gestational C-reactive protein, an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank. A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized. A total of 777 schizophrenia cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects in the analysis. Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens. Increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10-1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status. This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.

  7. Protein kinase C alpha controls erythropoietin receptor signaling.

    NARCIS (Netherlands)

    M.M. von Lindern (Marieke); M. Parren-Van Amelsvoort (Martine); T.B. van Dijk (Thamar); E. Deiner; B. Löwenberg (Bob); E. van den Akker (Emile); S. van Emst-de Vries (Sjenet); P.J. Willems (Patrick); H. Beug (Hartmut)

    2000-01-01

    textabstractProtein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We

  8. C-reactive protein in patients with aggressive periodontitis

    Directory of Open Access Journals (Sweden)

    Jaroslav Mysak

    2017-12-01

    Full Text Available Background/purpose: The aim of this study was to evaluate and compare the systemic levels of C-reactive protein (CRP in peripheral blood samples of patients with aggressive periodontitis during the first twelve months of periodontal treatment, at exactly six month interval measurements, and compare them with clinical periodontal parameters. Materials and methods: All patients (N = 45 were examined prior to the initiation of periodontal treatment. Patients were divided into two groups GAgP (Generalised form of aggressive periodontitis, N = 23 and group LAgP (Localised form of aggressive periodontitis, N = 22. Control group (CON included 60 individuals with healthy periodontium. The levels of CRP were determined in both groups GAgP and LAgP three times in 6 month intervals during the periodontal treatment. Results: CRP is a plasma protein that reflects the extent of the acute phase response to inflammation and is one of the markers of choice for monitoring this response. In our study, CRP levels decreased in course of periodontal treatment in both groups (GAgP and LAgP in a similar way as bleeding on probing (BOP and probing pocket depth (PPD indices. Conclusion: Our study results showed that CRP levels, as well as bleeding on probing (BOP and probing pocket depth (PPD, indices decreased in course of periodontal treatment in patients with generalised and localised aggressive periodontitis. Therefore this marker might be exploitable as a means to evaluate periodontal health in patients with aggressive periodontitis. Keywords: aggressive periodontitis, C-reactive protein, periodontal index, cardiovascular diseases

  9. Serum C-reactive protein levels in pre-dialysis chronic kidney ...

    African Journals Online (AJOL)

    Background: Cardiovascular disease is the major cause of hospitalization and mortality in chronic kidney disease (CKD). C- reactive protein (CRP) is a marker of cardiovascular disease and predictor of mortality in CKD patients. CKD patients with elevated CRP should be identified early with institution of measures to treat ...

  10. Serum C-reactive protein levels in pre-dialysis chronic kidney ...

    African Journals Online (AJOL)

    2016-03-01

    Mar 1, 2016 ... SUMMARY. Background: Cardiovascular disease is the major cause of hospitalization and mortality in chronic kidney disease. (CKD). C-reactive protein (CRP) is a marker of cardiovascular disease and predictor of mortality in CKD patients. CKD patients with elevated CRP should be identified early with ...

  11. Serum C-reactive protein levels in pre-dialysis chronic kidney ...

    African Journals Online (AJOL)

    2016-03-01

    Mar 1, 2016 ... 1Department of Internal Medicine, Kidney Care Centre, Ondo, Ondo State, Nigeria. ... C-reactive protein (CRP) is a marker of cardiovascular disease and predictor of mortality in CKD patients. ... Methods: This was a case-control study involving 80 consecutive CKD patients and 40 control subjects without.

  12. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data

    DEFF Research Database (Denmark)

    Wensley, Frances; Gao, Pei; Burgess, Stephen

    2011-01-01

    To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease.......To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease....

  13. C-Reactive Protein Levels in the Brugada Syndrome

    Directory of Open Access Journals (Sweden)

    Aimé Bonny

    2011-01-01

    Full Text Available Background. Inflammation in the Brugada syndrome (BrS and its clinical implication have been little studied. Aims. To assess the level of inflammation in BrS patients. Methods. All studied BrS patients underwent blood samples drawn for C-reactive protein (CRP levels at admission, prior to any invasive intervention. Patients with a previous ICD placement were controlled to exclude those with a recent (<14 days shock. We divided subjects into symptomatic (syncope or aborted sudden death and asymptomatic groups. In a multivariable analysis, we adjusted for significant variables (age, CRP ≥ 2 mg/L. Results. Fifty-four subjects were studied (mean age 45 ± 13 years, 49 (91% male. Twenty (37% were symptomatic. Baseline characteristics were similar in both groups. Mean CRP level was 1,4 ± 0,9 mg/L in asymptomatic and 2,4 ± 1,4 mg/L in symptomatic groups (P = .003. In the multivariate model, CRP concentrations ≥ 2 mg/L remained an independent marker for being symptomatic (P = .018; 95% CI: 1.3 to 19.3. Conclusion. Inflammation seems to be more active in symptomatic BrS. C-reactive protein concentrations ≥ 2 mg/L might be associated with the previous symptoms in BrS. The value of inflammation as a risk factor of arrhythmic events in BrS needs to be studied.

  14. High-Sensitivity C-Reactive Protein as a Predictor of Cardiovascular Events after ST-Elevation Myocardial Infarction

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Daniel Rios Pinto; Ramos, Adriane Monserrat; Vieira, Pedro Lima; Menti, Eduardo; Bordin, Odemir Luiz Jr.; Souza, Priscilla Azambuja Lopes de; Quadros, Alexandre Schaan de; Portal, Vera Lúcia, E-mail: veraportal.pesquisa@gmail.com [Programa de Pós-Graduação em Ciências da Saúde: Cardiologia - Instituto de Cardiologia/Fundação Universitária de Cardiologia, Porto Alegre, RS (Brazil)

    2014-07-15

    The association between high-sensitivity C-reactive protein and recurrent major adverse cardiovascular events (MACE) in patients with ST-elevation myocardial infarction who undergo primary percutaneous coronary intervention remains controversial. To investigate the potential association between high-sensitivity C-reactive protein and an increased risk of MACE such as death, heart failure, reinfarction, and new revascularization in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. This prospective cohort study included 300 individuals aged >18 years who were diagnosed with ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention at a tertiary health center. An instrument evaluating clinical variables and the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was used. High-sensitivity C-reactive protein was determined by nephelometry. The patients were followed-up during hospitalization and up to 30 days after infarction for the occurrence of MACE. Student's t, Mann-Whitney, chi-square, and logistic regression tests were used for statistical analyses. P values of ≤0.05 were considered statistically significant. The mean age was 59.76 years, and 69.3% of patients were male. No statistically significant association was observed between high-sensitivity C-reactive protein and recurrent MACE (p = 0.11). However, high-sensitivity C-reactive protein was independently associated with 30-day mortality when adjusted for TIMI [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.07-1.51; p = 0.005] and GRACE (OR, 1.26; 95% CI, 1.06-1.49; p = 0.007) risk scores. Although high-sensitivity C-reactive protein was not predictive of combined major cardiovascular events within 30 days after ST-elevation myocardial infarction in patients who underwent primary angioplasty and stent implantation, it was an independent predictor

  15. Comparison of pre- and post-levothyroxine high-sensitivity c-reactive protein and fetuin-a levels in subclinical hypothyroidism

    Directory of Open Access Journals (Sweden)

    Oktay Bilgir

    2015-02-01

    Full Text Available OBJECTIVE: The objective of this trial was to determine the levels of inflammatory markers, high-sensitivity C-reactive protein and fetuin-A pre- and post-levothyroxine treatment in cases of subclinical hypothyroidism. MATERIALS AND METHODS: A total of 32 patients with a diagnosis of subclinical hypothyroidism and a control group of 30 healthy individuals were tested for high-sensitivity C-reactive protein and fetuin-A, followed by the administration of 50 µg of levothyroxine in the patient group for 3 months. During the post-treatment stage, high-sensitivity C-reactive protein and fetuin-A levels in the patient group were re-assessed and compared with pre-treatment values. RESULTS: Pre-treatment levels of both high-sensitivity C-reactive protein and fetuin-A were observed to be higher in the patient group than in the control group. The decrease in high-sensitivity C-reactive protein levels during the post-treatment stage was not statistically significant. However, the decrease observed in post-treatment fetuin-A levels was found to be statistically significant. CONCLUSION: The decrease in fetuin-A levels in subclinical hypothyroidism cases indicates that levothyroxine treatment exerts anti-inflammatory and anti-apoptotic effects. Although the decrease in high-sensitivity C-reactive protein levels was statistically non-significant, it is predicted to reach significance with sustained treatment.

  16. Protein kinase C alpha controls erythropoietin receptor signaling

    NARCIS (Netherlands)

    von Lindern, M.; Parren-van Amelsvoort, M.; van Dijk, T.; Deiner, E.; van den Akker, E.; van Emst-de Vries, S.; Willems, P.; Beug, H.; Löwenberg, B.

    2000-01-01

    Protein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We analyzed the effect of PKC inhibitors

  17. Trichoderma G protein-coupled receptors: functional characterisation of a cAMP receptor-like protein from Trichoderma atroviride.

    Science.gov (United States)

    Brunner, Kurt; Omann, Markus; Pucher, Marion E; Delic, Marizela; Lehner, Sylvia M; Domnanich, Patrick; Kratochwill, Klaus; Druzhinina, Irina; Denk, Dagmar; Zeilinger, Susanne

    2008-12-01

    Galpha subunits act to regulate vegetative growth, conidiation, and the mycoparasitic response in Trichoderma atroviride. To extend our knowledge on G protein signalling, we analysed G protein-coupled receptors (GPCRs). As the genome sequence of T. atroviride is not publicly available yet, we carried out an in silico exploration of the genome database of the close relative T. reesei. Twenty genes encoding putative GPCRs distributed over eight classes and additional 35 proteins similar to the Magnaporthe grisea PTH11 receptor were identified. Subsequently, four T. atroviride GPCR-encoding genes were isolated and affiliated to the cAMP receptor-like family by phylogenetic and topological analyses. All four genes showed lowest expression on glycerol and highest mRNA levels upon carbon starvation. Transcription of gpr3 and gpr4 responded to exogenously added cAMP and the shift from liquid to solid media. gpr3 mRNA levels also responded to the presence of fungal hyphae or cellulose membranes. Further characterisation of mutants bearing a gpr1-silencing construct revealed that Gpr1 is essential for vegetative growth, conidiation and conidial germination. Four genes encoding the first GPCRs described in Trichoderma were isolated and their expression characterized. At least one of these GPCRs is important for several cellular processes, supporting the fundamental role of G protein signalling in this fungus.

  18. C-reactive Protein and Disease Outcome in Nigerian Sickle Cell ...

    African Journals Online (AJOL)

    Background: Evidence suggests that sickle cell disease (SCD) is associated with a chronic inflammatory state. C.reactive protein (CRP) is known to modulate inflammation. Its role in the chronic inflammation of SCD may make it valuable as a therapeutic target. Aim: The aim was to determine CRP levels in SCD subjects in ...

  19. Novel Phosphorylation and Ubiquitination Sites Regulate Reactive Oxygen Species-dependent Degradation of Anti-apoptotic c-FLIP Protein*

    Science.gov (United States)

    Wilkie-Grantham, Rachel P.; Matsuzawa, Shu-Ichi; Reed, John C.

    2013-01-01

    The cytosolic protein c-FLIP (cellular Fas-associated death domain-like interleukin 1β-converting enzyme inhibitory protein) is an inhibitor of death receptor-mediated apoptosis that is up-regulated in a variety of cancers, contributing to apoptosis resistance. Several compounds found to restore sensitivity of cancer cells to TRAIL, a TNF family death ligand with promising therapeutic potential, act by targeting c-FLIP ubiquitination and degradation by the proteasome. The generation of reactive oxygen species (ROS) has been implicated in c-FLIP protein degradation. However, the mechanism by which ROS post-transcriptionally regulate c-FLIP protein levels is not well understood. We show here that treatment of prostate cancer PPC-1 cells with the superoxide generators menadione, paraquat, or buthionine sulfoximine down-regulates c-FLIP long (c-FLIPL) protein levels, which is prevented by the proteasome inhibitor MG132. Furthermore, pretreatment of PPC-1 cells with a ROS scavenger prevented ubiquitination and loss of c-FLIPL protein induced by menadione or paraquat. We identified lysine 167 as a novel ubiquitination site of c-FLIPL important for ROS-dependent degradation. We also identified threonine 166 as a novel phosphorylation site and demonstrate that Thr-166 phosphorylation is required for ROS-induced Lys-167 ubiquitination. The mutation of either Thr-166 or Lys-167 was sufficient to stabilize c-FLIP protein levels in PPC-1, HEK293T, and HeLa cancer cells treated with menadione or paraquat. Accordingly, expression of c-FLIP T166A or K167R mutants protected cells from ROS-mediated sensitization to TRAIL-induced cell death. Our findings reveal novel ROS-dependent post-translational modifications of the c-FLIP protein that regulate its stability, thus impacting sensitivity of cancer cells to TRAIL. PMID:23519470

  20. The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death.

    Science.gov (United States)

    Gray, Sarah; Axelsson, Bertil

    2018-01-01

    Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context. A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Östersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin death was noted. The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (pdeath, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively. Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

  1. Ankle brachial index, C-reactive protein, and central augmentation index to identify individuals with severe atherosclerosis

    DEFF Research Database (Denmark)

    Eldrup, Nikolaj; Sillesen, Henrik; Prescott, Eva

    2006-01-01

    We examined the ability of ankle brachial index, C-reactive protein and central augmentation index to identify individuals in the general population with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular disease.......We examined the ability of ankle brachial index, C-reactive protein and central augmentation index to identify individuals in the general population with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular disease....

  2. Diagnostic properties of C-reactive protein for detecting pneumonia in children

    NARCIS (Netherlands)

    Koster, M.J.; Broekhuizen, B.D.L.; Minnaard, M.C.; Balemans, W.A.; Hopstaken, R.M.; de Jong, P.A.; Verheij, Th.J.M.

    BACKGROUND: The diagnostic value of C-reactive protein (CRP) level for pneumonia in children is unknown. As a first step in the assessment of the value of CRP, a diagnostic study was performed in children at an emergency department (ED). METHODS: In this cross-sectional study, data were

  3. The value of C-reactive protein in emergency medicine

    Directory of Open Access Journals (Sweden)

    Yu-Jang Su

    2014-01-01

    Full Text Available C-reactive protein (CRP is a commonly used tool in emergency department (ED, especially in febrile and infectious patients. It was identified in 1930 and was subsequently classified into an “acute phase protein”, an early indicator of infectious or inflammatory situations in the ED, CRP must be a diagnostic reference and no single value can be indicated to rule in or rule out a specific diagnosis or disease. CRP is a comprehensively assisted tool for evaluation and diagnosis of tissue damage (rheumatologic diseases, stroke, cancer, pancreatitis, burn injury, sepsis and gout and infection (urinary tract infection, pelvic inflammatory disease, meningitis and lung infection. It can be used for treatment monitoring and severity evaluation in pneumonia, pancreatitis, pelvic inflammatory disease (PID, and urinary tract infections (UTI. Otherwise, it also plays the role of prognostic indicator of acute coronary syndrome. C-reactive protein adds little to the diagnosis of pneumonia, urinary tract infections, and pancreatitis. A single CRP value should not straightly make the decision to treat these patients. That is, CRP has no role in diagnosing these clinical entities, and a normal CRP level should never delay antibiotic coverage in ED. Faster and more interpretable tools such as image studies (X-ray, sonography and computed tomography are available to help diagnose suspected cases of aortic dissection, appendicitis, cholecystitis, pancreatitis, pneumonia and stroke in ED.

  4. C-reactive protein and bacterial meningitis

    DEFF Research Database (Denmark)

    Gerdes, Lars Ulrik; Jørgensen, P E; Nexø, E

    1998-01-01

    The aim of the study was to review published articles on the diagnostic accuracy of C-reactive protein (CRP) tests with cerebrospinal fluid and serum in diagnosing bacterial meningitis. The literature from 1980 and onwards was searched using the electronic databases of MEDLINE, and we used summary...... measured in serum, and 4 in which it had been measured in both cerebrospinal fluid and serum. The odds ratio for bacterial meningitis versus aseptic meningitis for a positive CRP test with cerebrospinal fluid was estimated at 241 (95% confidence interval [CI]: 59-980), and the central tendencies.......06-0.08, respectively, the post-test probability of not having bacterial meningitis given a negative test is very high (> or = 97%), in the range of a pre-test probability (prevalence of bacterial meningitis) from 10 to 30%, whereas the post-test probability of bacterial meningitis given a positive test is considerably...

  5. The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death.

    Directory of Open Access Journals (Sweden)

    Sarah Gray

    Full Text Available Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context.A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Östersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin <30 g/L was referred to as "laboratory cachexia". Also, the number of days from the first found "laboratory cachexia" until death was noted.The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (p<0.01. The majority of patients (75% had an onset of "laboratory cachexia" within 0-120 days prior to death, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively.Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

  6. Canine Pancreas-Specific Lipase and C-reactive Protein in Dogs Treated With Anticonvulsants (Phenobarbital and Potassium Bromide).

    Science.gov (United States)

    Albarracín, Viviana; Teles, Mariana; Meléndez-Lazo, Antonio; Rodón, Jaume; Pastor, Josep

    2015-06-01

    Animals treated with anticonvulsant drugs may have increased canine pancreas-specific lipase (cPLI) values. Inflammatory conditions and specifically acute pancreatitis are of major concern in these animals. Elevation in C-reactive protein is being associated with inflammatory status in dogs and it has been correlated with the clinical severity of pancreatitis. In the present study, we investigated if there is a correlation between the cPLI increase, changes in C-reactive protein and hepatic enzymes, as well as the incidence of severe acute pancreatitis (AP) in dogs with anticonvulsant treatment (phenobarbital, or potassium bromide or both). Increased values of pancreas-specific lipase were found in 6.8% of the animals in treatment with anticonvulsants, and this increase is correlated with the increase in triglycerides, alkaline phosphatase, and alanine aminotransferase but not with C-reactive protein levels, which suggests a possible induction or release phenomenon rather than a clear severe AP. C-reactive protein levels did not affect cPLI values on the population studied. Only 2 animals had clinical and analytical data suggestive of AP, indicating a low prevalence (0.6%). In conclusion, cPLI may be increased in a low percentage of animals with anticonvulsants treatment and its increase may not be associated with severe AP. It may be induced by the anticonvulsants drugs; however, further studies are advised to rule out other possible causes that increased cPLI. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer

    DEFF Research Database (Denmark)

    Allin, Kristine H; Nordestgaard, Børge G; Flyger, Henrik

    2011-01-01

    We examined whether plasma C-reactive protein (CRP) levels at the time of diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and recurrence of breast cancer.......We examined whether plasma C-reactive protein (CRP) levels at the time of diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and recurrence of breast cancer....

  8. Structure of metabotropic glutamate receptor C-terminal domains in contact with interacting proteins

    Directory of Open Access Journals (Sweden)

    Ralf eEnz

    2012-04-01

    Full Text Available Metabotropic glutamate receptors (mGluRs regulate intracellular signal pathways that control several physiological tasks, including neuronal excitability, learning and memory. This is achieved by the formation of synaptic signal complexes, in which mGluRs assemble with functionally related proteins such as enzymes, scaffolds and cytoskeletal anchor proteins. Thus, mGluR associated proteins actively participate in the regulation of glutamatergic neurotransmission. Importantly, dysfunction of mGluRs and interacting proteins may lead to impaired signal transduction and finally result in neurological disorders, e.g. night blindness, addiction, epilepsy, schizophrenia, autism spectrum disorders and Parkinson´s disease. In contrast to solved crystal structures of extracellular N-terminal domains of some mGluR types, only a few studies analyzed the conformation of intracellular receptor domains. Intracellular C-termini of most mGluR types are subject to alternative splicing and can be further modified by phosphorylation and SUMOylation. In this way, diverse interaction sites for intracellular proteins that bind to and regulate the glutamate receptors are generated. Indeed, most of the known mGluR binding partners interact with the receptors´ C-terminal domains. Within the last years, different laboratories analyzed the structure of these domains and described the geometry of the contact surface between mGluR C-termini and interacting proteins. Here, I will review recent progress in the structure characterization of mGluR C-termini and provide an up-to-date summary of the geometry of these domains in contact with binding partners.

  9. C-reactive protein as a prognostic indicator for rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

    Science.gov (United States)

    Lee, Han Hee; Park, Jae Myung; Lee, Soon-Wook; Kang, Seung Hun; Lim, Chul-Hyun; Cho, Yu Kyung; Lee, Bo-In; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gyu

    2015-05-01

    In patients with acute nonvariceal upper gastrointestinal bleeding, rebleeding after an initial treatment is observed in 10-20% and is associated with mortality. To investigate whether the initial serum C-reactive protein level could predict the risk of rebleeding in patients with acute nonvariceal upper gastrointestinal bleeding. This was a retrospective study using prospectively collected data for upper gastrointestinal bleeding. Initial clinical characteristics, endoscopic features, and C-reactive protein levels were compared between those with and without 30-day rebleeding. A total of 453 patients were included (mean age, 62 years; male, 70.9%). The incidence of 30-day rebleeding was 15.9%. The mean serum C-reactive protein level was significantly higher in these patients than in those without rebleeding (Pupper gastrointestinal bleeding, indicating a possible role as a useful screening indicator for predicting the risk of rebleeding. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  10. Use of plasma C-reactive protein, procalcitonin, neutrophils,macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Andersen, Ove; Kronborg, Gitte

    2007-01-01

    the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination. Methods: This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency...... department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel...... with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC...

  11. Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

    Directory of Open Access Journals (Sweden)

    Datis Kharrazian

    2017-01-01

    Full Text Available Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw and modified (cooked and roasted foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease.

  12. Metabolic syndrome, C-reactive protein and cardiovascular risk in psoriasis patients: a cross-sectional study*

    Science.gov (United States)

    Paschoal, Renato Soriani; Silva, Daniela Antoniali; Cardili, Renata Nahas; Souza, Cacilda da Silva

    2018-01-01

    Background Psoriasis has been associated with co-morbidities and elevated cardiovascular risk. Objectives To analyze the relationships among metabolic syndrome, cardiovascular risk, C-reactive protein, gender, and Psoriasis severity. Methods In this cross-sectional study, plaque Psoriasis patients (n=90), distributed equally in gender, were analyzed according to: Psoriasis Area and Severity Index, cardiovascular risk determined by the Framingham risk score and global risk assessment, C-reactive protein and metabolic syndrome criteria (NCEPT-ATP III). Results Metabolic syndrome frequency was 43.3% overall, without significance between genders (P=0.14); but women had higher risk for obesity (OR 2.56, 95%CI 1.02-6.41; P=0.04) and systemic arterial hypertension (OR 3.29, 95%CI 1.39-7.81; P=0.006). The increase in the Psoriasis Area and Severity Index also increased the risk for metabolic syndrome (OR 1.060, 95%CI 1.006-1.117; P=0.03). Absolute 10-year cardiovascular risk was higher in males (P=0.002), but after global risk assessment, 51.1% patients, 52.2% women, were re-classified as high-intermediate cardiovascular risk; without significance between genders (P=0.83). C-reactive protein level was elevated nearly six-fold overall, higher in metabolic syndrome (P=0.05), systemic arterial hypertension (P=0.004), and high-intermediate 10-year cardiovascular risk patients (Preactive protein patients (t=1.98; P=0.05). Study limitations Restricted sample, hospital-based and representative of a single center and no specification of psoriatic arthritis. Conclusions Psoriasis, metabolic syndrome, systemic arterial hypertension and age share the increase in C-reactive protein, which could implicate in additional burden for increasing the cardiovascular risk and be an alert for effective interventions. PMID:29723366

  13. The effects of probiotic yoghurt on C-Reactive Protein in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    hanoyesadat Ejtahed

    2013-09-01

    Conclusion: Consumption of probiotic yoghurt improved C-Reactive Protein concentration in type 2 diabetic patients. Probiotic yoghurt consumption is recommended as auxiliary therapy in type 2 diabetic patients.

  14. Longitudinal changes in C-reactive protein, proform of eosinophil major basic protein, and pregnancy-associated plasma protein-A during weight changes in obese children

    DEFF Research Database (Denmark)

    Lausten-Thomsen, Ulrik; Gamborg, Michael; Bøjsøe, Christine

    2015-01-01

    BACKGROUND: Childhood obesity is associated with several complications, including cardiovascular comorbidity. Several biomarkers, such as high-sensitive C-reactive protein (hs-CRP), proform of eosinophil major basic protein (Pro-MBP) and pregnancy associated plasma protein-A (PAPP-A), have equally...

  15. C-reactive protein as a marker of infection in children with severe acute malnutrition in Khartoum state, Sudan

    Directory of Open Access Journals (Sweden)

    Abdelmoneim E.M. Kheir

    2017-08-01

    Full Text Available Severe acute malnutrition and acute systemic infection are often synergistic in children and lead to considerable mortality. The main aim of this research was to determine whether children with severe acute malnutrition can mount an acute phase reactant response measured by C-reactive protein. This was a descriptive, cross-sectional, hospital-based study that was carried out in the five main children hospitals in Khartoum state, from November 1st, 2012 to March 1st, 2013. 132 children with severe acute malnutrition were included in the study. Data collection included history, examination and C-reactive protein measurement. The data were analyzed using Statistical Package for Social Sciences (SPSS for descriptive and inferential statistics. The main results revealed that 93(70.5% children between 12-23 months of age and most of them had marasmus. Diarrhoea was the commonest presenting symptoms in 86.4%, followed by fever and vomiting. Most of the children (82.6% had positive C-reactive protein with variable levels. In conclusion malnourished children are able to synthesize C-reactive protein in response to an infectious process and the magnitude of this response is increased in those with severe infections.

  16. Imaging of persistent cAMP signaling by internalized G protein-coupled receptors.

    Science.gov (United States)

    Calebiro, Davide; Nikolaev, Viacheslav O; Lohse, Martin J

    2010-07-01

    G protein-coupled receptors (GPCRs) are the largest family of plasma membrane receptors. They mediate the effects of several endogenous cues and serve as important pharmacological targets. Although many biochemical events involved in GPCR signaling have been characterized in great detail, little is known about their spatiotemporal dynamics in living cells. The recent advent of optical methods based on fluorescent resonance energy transfer allows, for the first time, to directly monitor GPCR signaling in living cells. Utilizing these methods, it has been recently possible to show that the receptors for two protein/peptide hormones, the TSH and the parathyroid hormone, continue signaling to cAMP after their internalization into endosomes. This type of intracellular signaling is persistent and apparently triggers specific cellular outcomes. Here, we review these recent data and explain the optical methods used for such studies. Based on these findings, we propose a revision of the current model of the GPCR-cAMP signaling pathway to accommodate receptor signaling at endosomes.

  17. The correlation between hs C-reactive protein and left ventricular mass in obese women

    Directory of Open Access Journals (Sweden)

    Idrus Alwi

    2006-06-01

    Full Text Available Plasma C-reactive protein (CRP concentrations are increased in obese individuals. In this study, we examined the correlation between hsCRP and left ventricular mass (LV mass. Fourty five healthy obese women and fourty five healthy non obese women as the controls group were studied by echocardiography and hsCRP. There was no significant correlation between hsCRP and left ventricular mass in obese women (r = 0.29, p 0.06. There was a significant correlation between hs CRP and body mass index (r = 0.46, p 0,002, and also hsCRP and visceral fat (r= 0.33, p 0.03. (Med J Indones 2006; 15:100-4 Keywords: hs C-reactive protein, LV mass, obese women

  18. The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

    Science.gov (United States)

    Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

    2014-01-01

    Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

  19. Effect of Aerobic Exercise on C-reatine reactive protein and Index of ...

    African Journals Online (AJOL)

    Lamina

    Subjects in the interval group involved in interval training (60-79% maximum heart ... of exercise training on C-reactive protein, erectile function index, SBP, DBP ... patients with cardiac disease have shown a high .... low intensity of between 35-59% of their HR max .... Aging and Body Composition Study (Health ABC) (40),.

  20. Comparison of high-sensitivity C-reactive protein and fetuin-A levels before and after treatment for subjects with subclinical hyperthyroidism.

    Science.gov (United States)

    Bilgir, Oktay; Bilgir, Ferda; Topcuoglu, Tuba; Calan, Mehmet; Calan, Ozlem

    2014-03-01

    This study was designed to show the effect of propylthiouracil treatment on sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels on subjects with subclinical hyperthyroidism. After checking sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels of 35 patients with subclinical hyperthyroidism, each was given 50 mg tablets of propylthiouracil three times daily. After 3 months, sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels were then compared to the levels before treatment. Although high-sensitivity C-reactive protein and sCD40L levels were normal in the subclinical hyperthyroidism patients compared to the healthy controls, fetuin-A levels were statistically significantly higher (*p = 0.022). After treatment, fetuin-A levels of subclinical hyperthyroidism patients decreased statistically significantly compared to the levels before treatment (**p = 0.026). sCD40L and high-sensitivity C-reactive protein levels did not have a statistically significant difference compared to the control group and post-propylthiouracil treatment. In subclinical hyperthyroidism patients, high fetuin-A levels before propylthiouracil treatment and decreases in these levels after treatment in cases with subclinical hyperthyroidism indicated the possibility of preventing long-term cardiac complications with propylthiouracil treatment.

  1. Analysis of antigenic cross-reactivity between subgroup C avian pneumovirus and human metapneumovirus by using recombinant fusion proteins.

    Science.gov (United States)

    Luo, L; Sabara, M I; Li, Y

    2009-10-01

    Avian pneumovirus subgroup C (APV/C) has recently been reported to be more closely related to human metapneumovirus (hMPV) as determined by sequence analysis. To examine the antigenic relationship between APV/C and hMPV, the APV/C fusion (F) gene was cloned and expressed as an uncleaved glycoprotein in a baculovirus system. The reactivity of the APV/C F protein with antibodies against APV subgroups A, B, C, and hMPV was examined by Western blot analysis. The results showed that the expressed APV/C F protein was not only recognized by APV/C-specific antibodies but also by antibodies raised against hMPV. Previously expressed recombinant hMPV F protein also reacted with APV/C-specific antibodies, suggesting that there was significant antigenic cross-reactivity and a potential evolutionary relationship between hMPV and APV/C. Interestingly, the recombinant F proteins from APV/C and hMPV were not recognized by polyclonal antibodies specific to APV subgroups A and B.

  2. High-sensitivity C-reactive protein and risk of sepsis.

    Directory of Open Access Journals (Sweden)

    Henry E Wang

    Full Text Available Conventional C-reactive protein assays have been used to detect or guide the treatment of acute sepsis. The objective of this study was to determine the association between elevated baseline high-sensitivity C-reactive protein (hsCRP and the risk of future sepsis events.We studied data from 30,239 community dwelling, black and white individuals, age ≥45 years old enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS cohort. Baseline hsCRP and participant characteristics were determined at the start of the study. We identified sepsis events through review of hospital records. Elevated hsCRP was defined as values >3.0 mg/L. Using Cox regression, we determined the association between elevated hsCRP and first sepsis event, adjusting for sociodemographic factors (age, sex, race, region, education, income, health behaviors (tobacco and alcohol use, chronic medical conditions (coronary artery disease, diabetes, dyslipidemia, hypertension, chronic kidney disease, chronic lung disease and statin use.Over the mean observation time of 5.7 years (IQR 4.5-7.1, 974 individuals experienced a sepsis event, and 11,447 (37.9% had elevated baseline hsCRP (>3.0 mg/L. Elevated baseline hsCRP was independently associated with subsequent sepsis (adjusted HR 1.56; 95% CI 1.36-1.79, adjusted for sociodemographics, health behaviors, chronic medical conditions and statin use.Elevated baseline hsCRP was associated with increased risk of future sepsis events. hsCRP may help to identify individuals at increased risk for sepsis.

  3. Interaction of Hepatitis C virus proteins with pattern recognition receptors

    Directory of Open Access Journals (Sweden)

    Imran Muhammad

    2012-06-01

    Full Text Available Abstract Hepatitis C virus (HCV is an important human pathogen that causes acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. This positive stranded RNA virus is extremely efficient in establishing persistent infection by escaping immune detection or hindering the host immune responses. Recent studies have discovered two important signaling pathways that activate the host innate immunity against viral infection. One of these pathways utilizes members of Toll-like receptor (TLR family and the other uses the RNA helicase retinoic acid inducible gene I (RIG-I as the receptors for intracellular viral double stranded RNA (dsRNA, and activation of transcription factors. In this review article, we summarize the interaction of HCV proteins with various host receptors/sensors through one of these two pathways or both, and how they exploit these interactions to escape from host defense mechanisms. For this purpose, we searched data from Pubmed and Google Scholar. We found that three HCV proteins; Core (C, non structural 3/4 A (NS3/4A and non structural 5A (NS5A have direct interactions with these two pathways. Core protein only in the monomeric form stimulates TLR2 pathway assisting the virus to evade from the innate immune system. NS3/4A disrupts TLR3 and RIG-1 signaling pathways by cleaving Toll/IL-1 receptor domain-containing adapter inducing IFN-beta (TRIF and Cardif, the two important adapter proteins of these signaling cascades respectively, thus halting the defense against HCV. NS5A downmodulates the expressions of NKG2D on natural killer cells (NK cells via TLR4 pathway and impairs the functional ability of these cells. TLRs and RIG-1 pathways have a central role in innate immunity and despite their opposing natures to HCV proteins, when exploited together, HCV as an ever developing virus against host immunity is able to accumulate these mechanisms for near unbeatable survival.

  4. Culture and the Immune System: Cultural Consonance in Social Support and C-reactive Protein in Urban Brazil.

    Science.gov (United States)

    Dressler, William W; Balieiro, Mauro C; Ribeiro, Rosane P; Dos Santos, José Ernesto

    2016-06-01

    In this article, we examine the distribution of a marker of immune system stimulation-C-reactive protein-in urban Brazil. Social relationships are associated with immunostimulation, and we argue that cultural dimensions of social support, assessed by cultural consonance, are important in this process. Cultural consonance is the degree to which individuals, in their own beliefs and behaviors, approximate shared cultural models. A measure of cultural consonance in social support, based on a cultural consensus analysis regarding sources and patterns of social support in Brazil, was developed. In a survey of 258 persons, the association of cultural consonance in social support and C-reactive protein was examined, controlling for age, sex, body mass index, low-density lipoprotein cholesterol, depressive symptoms, and a social network index. Lower cultural consonance in social support was associated with higher C-reactive protein. Implications of these results for future research are discussed. © 2016 by the American Anthropological Association.

  5. C-reactive protein collaborates with plasma lectins to boost immune response against bacteria

    DEFF Research Database (Denmark)

    Ng, Patricia M L; Le Saux, Agnès; Lee, Chia M

    2007-01-01

    Although human C-reactive protein (CRP) becomes upregulated during septicemia, its role remains unclear, since purified CRP showed no binding to many common pathogens. Contrary to previous findings, we show that purified human CRP (hCRP) binds to Salmonella enterica, and that binding is enhanced ...

  6. C-reactive protein levels and treatment resistance in schizophrenia - A Danish population-based cohort study

    DEFF Research Database (Denmark)

    Horsdal, Henriette Thisted; Wimberley, Theresa; Benros, Michael Eriksen

    2017-01-01

    -time schizophrenia diagnosis and a baseline C-reactive protein measurement (a commonly available marker of systemic inflammation) from 2000 to 2012. We defined treatment resistance as the earliest observed instance of either clozapine initiation or hospital admission due to schizophrenia after having received......OBJECTIVE: Schizophrenia is associated with increased levels of inflammatory markers. However, it remains unclear whether inflammatory markers are associated with treatment-resistant schizophrenia. METHODS: We conducted a population-based follow-up study among individuals with a first...... (4.0 vs. 3.1 mg/L, p = .13) was observed among the 52 (13.3%) treatment-resistant individuals. Increased levels of C-reactive protein (above 3 mg/L) at baseline were not associated with treatment resistance (adjusted hazard ratio = 0.99, 95% confidence interval [0.56, 1.73]). CONCLUSIONS: C...

  7. Reactivation of desensitized formyl peptide receptors by platelet activating factor: a novel receptor cross talk mechanism regulating neutrophil superoxide anion production.

    Directory of Open Access Journals (Sweden)

    Huamei Forsman

    Full Text Available Neutrophils express different chemoattractant receptors of importance for guiding the cells from the blood stream to sites of inflammation. These receptors communicate with one another, a cross talk manifested as hierarchical, heterologous receptor desensitization. We describe a new receptor cross talk mechanism, by which desensitized formyl peptide receptors (FPRdes can be reactivated. FPR desensitization is induced through binding of specific FPR agonists and is reached after a short period of active signaling. The mechanism that transfers the receptor to a non-signaling desensitized state is not known, and a signaling pathway has so far not been described, that transfers FPRdes back to an active signaling state. The reactivation signal was generated by PAF stimulation of its receptor (PAFR and the cross talk was uni-directional. LatrunculinA, an inhibitor of actin polymerization, induced a similar reactivation of FPRdes as PAF while the phosphatase inhibitor CalyculinA inhibited reactivation, suggesting a role for the actin cytoskeleton in receptor desensitization and reactivation. The activated PAFR could, however, reactivate FPRdes also when the cytoskeleton was disrupted prior to activation. The receptor cross talk model presented prophesies that the contact on the inner leaflet of the plasma membrane that blocks signaling between the G-protein and the FPR is not a point of no return; the receptor cross-talk from the PAFRs to the FPRdes initiates an actin-independent signaling pathway that turns desensitized receptors back to a signaling state. This represents a novel mechanism for amplification of neutrophil production of reactive oxygen species.

  8. Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

    NARCIS (Netherlands)

    Kim, E.S.; Cha, Y.; Ham, M.; Jung, J.; Kim, S.G.; Hwang, S.; Kleemann, R.; Moon, A.

    2014-01-01

    A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for

  9. Periodontal inflamed surface area and C-reactive protein as predictors of HbA1c : a study in Indonesia

    NARCIS (Netherlands)

    Susanto, Hendri; Nesse, Willem; Dijkstra, Pieter U.; Hoedemaker, Evelien; van Reenen, Yvonne Huijser; Agustina, Dewi; Vissink, Arjan; Abbas, Frank

    Periodontitis may exert an infectious and inflammatory burden, evidenced by increased C-reactive protein (CRP). This burden may impair blood glucose control (HbA1c). The aim of our study was to analyze whether periodontitis severity as measured with the periodontal inflamed surface area (PISA) and

  10. Capacitive immunosensor for C-reactive protein quantification

    KAUST Repository

    Sapsanis, Christos

    2015-08-02

    We report an agglutination-based immunosensor for the quantification of C-reactive protein (CRP). The developed immunoassay sensor requires approximately 15 minutes of assay time per sample and provides a sensitivity of 0.5 mg/L. We have measured the capacitance of interdigitated electrodes (IDEs) and quantified the concentration of added analyte. The proposed method is a label free detection method and hence provides rapid measurement preferable in diagnostics. We have so far been able to quantify the concentration to as low as 0.5 mg/L and as high as 10 mg/L. By quantifying CRP in serum, we can assess whether patients are prone to cardiac diseases and monitor the risk associated with such diseases. The sensor is a simple low cost structure and it can be a promising device for rapid and sensitive detection of disease markers at the point-of-care stage.

  11. Serum levels of C-reactive protein in adolescents with periodontitis

    DEFF Research Database (Denmark)

    López, Rodrigo; Baelum, Vibeke; Hedegaard, Chris Juul

    2011-01-01

    Background: The results of several cross-sectional studies suggested a relationship between periodontitis and higher serum levels of C-reactive protein (CRP). Most of these studies were restricted to adult study groups with severe periodontal inflammation, and the potential effects of confounding...... ng/ml (31 to 183 ng/ml), respectively (P = 0.8). Conclusions: Serum levels of CRP were not significantly higher among subjects with periodontitis than among controls. However, a statistically significant positive association between percentages of sites with bleeding on probing and log...

  12. Expression, crystallization and preliminary crystallographic analysis of C-reactive protein from zebrafish

    International Nuclear Information System (INIS)

    Chen, Rong; Qi, Jianxun; Yao, Shugang; Pan, Xiaocheng; Gao, Feng; Xia, Chun

    2011-01-01

    Crystals of native and selenomethionine-substituted C-reactive protein from zebrafish diffracted to 2.3 and 1.7 Å resolution, respectively, and belonged to space group R3 with one molecule per asymmetric unit. The Matthews coefficient was calculated to be 3.28 Å 3 Da −1 . C-reactive protein (CRP) is an acute phase protein that is found in blood, the concentration of which in plasma rises rapidly in response to inflammation. It functions as a pattern-recognition molecule, recognizing dead cells and various pathogenic agents and eliminating them by utilizing the classical complement pathway and activating macrophages. CRP is phylogenetically highly conserved in invertebrates and mammals. To date, information on the CRP gene has been reported from numerous species of animals, but little is known about the structure of CRP from species other than humans. In order to solve the structure of CRP from bony fish, the CRP gene from zebrafiah (Danio rerio) was cloned and expressed in Escherichia coli. The zebrafish CRP (Dare-CRP) was then purified and crystallized. The crystal diffracted to 2.3 Å resolution and belonged to space group R3, with unit-cell parameters a = b = 114.7, c = 61.0 Å. The Matthews coefficient and solvent content were calculated to be 3.28 Å 3 Da −1 and 62.55%, respectively. Determination of the zebrafish CRP structure should be helpful in investigating the evolution of CRPs in the innate immune system

  13. The role of C-reactive protein and polyarginine in tumor immunotherapy.

    Science.gov (United States)

    Rizk, S L; Mold, C; Haklin, M; Roseman, D L

    1986-07-01

    C-reactive protein (CRP) is an acute-phase reactant whose serum level rises rapidly in response to tissue injury. C-reactive protein binding to cells can activate the classical complement pathway, and enhance opsonophagocytosis. The polycation poly-L-arginine (PLA) can artificially fix CRP to target cells. The effects of CRP and PLA on tumor growth were evaluated, both independently and synergistically, using the V X 2 tumor line in the rabbit host. Ten normal animals and seven acute-phase animals were bilaterally inoculated with V X 2 cells (control side) and PLA-treated V X 2 cells (experimental side). Tumor growth was significantly retarded on the treatment side (P less than 0.005), in both animal groups. It is concluded that topical PLA is a potent inhibitor of V X 2 tumor growth. Comparison of normal and acute-phase animals revealed no persistent difference in tumor growth for either cell inoculum. Similarly, cell treatment with topical CRP did not inhibit tumor growth, whether PLA was present or not. Thus, circulating and topical CRP did not alter the rate of V X 2 tumor growth. PLA cytotoxicity remains to be evaluated when the agent is administered orthotopically, selectively, or systemically.

  14. Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Škop, V.; Trnovská, J.; Oliyarnyk, O.; Marková, I.; Malínská, H.; Kazdová, L.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Kůdela, M.; Pravenec, Michal; Šilhavý, Jan

    2016-01-01

    Roč. 65, č. 6 (2016), s. 891-899 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT14325 Institutional support: RVO:67985823 Keywords : fenofibrate * rosuvastatin * C-reactive protein * transgenic * spontaneously hypertensive rat * inflammation * hepatotoxic Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.461, year: 2016

  15. P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report.

    Science.gov (United States)

    Wu, Hong; Nie, Yijun; Xiong, Huangui; Liu, Shuangmei; Li, Guilin; Huang, An; Guo, Lili; Wang, Shouyu; Xue, Yun; Wu, Bing; Peng, Lichao; Song, Miaomiao; Li, Guodong; Liang, Shangdong

    2015-12-01

    Chronic inflammation plays a major role in development of type 2 diabetes mellitus (T2DM). C-reactive protein (CRP) and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) are directly involved in the occurrence of insulin resistance. Increased extracellular ATP levels can amplify the inflammatory response in vivo via the P2X7 receptor. The present study aimed to assess the relationship between P2X7 receptor expression in human peripheral blood monocytes and plasma levels of TNF-α, IL-1β, and CRP in T2DM patients. The results showed the association of increased P2X7 receptor expression of monocytes with high serum CRP, TNF-α, and IL-1β levels. TNF-α and IL-1β levels were lowest in healthy subjects; in T2DM patients, these inflammatory markers were less abundant in individuals with normal CRP levels compared to those with high CRP contents. In contrast, IL-10 levels in T2DM patients with high CRP levels were dramatically decreased. P2X7 receptor expression in monocytes from T2DM patients with high CRP levels was significantly increased in comparison with healthy individuals and T2DM patients with normal CRP levels. These findings indicated that P2X7 receptor in peripheral blood monocytes may be involved in the pathological changes of T2DM, particularly affecting patients with high CRP levels.

  16. Evaluation of the C-reactive protein serum levels in periodontitis patients with or without atherosclerosis.

    Science.gov (United States)

    Thakare, Kaustubh S; Deo, Vikas; Bhongade, Manohar L

    2010-01-01

    Several studies suggested an association between periodontal disease and cardiovascular disease (CVD). C- reactive protein is elevated in periodontitis patients and has been found to be a predictor of increased risk for cardiovascular disease. Since, CRP is known to play a role in pathogenesis of atherosclerosis, the present study was undertaken to evaluate the serum levels of CRP in periodontitis patients with or without atherosclerosis. A total of 45 patients, 15 chronic periodontitis patients with atherosclerosis (Group A), 15 chronic periodontitis patients with no history of any systemic disease (Group B), and 15 clinically healthy individuals with no history of periodontal or systemic disease (Group C) within age range of 30 to 55 years were selected for the study. PI, PBI, PPD, CAL and radiographic marginal alveolar bone level were assessed in all the three groups. CRP levels were assessed with 'Turbi-latex' kit using turbidimetric analysis. The mean CAL recorded was 4.9mm in group A, 4.6mm in group B and 1.9 mm in group C. The mean radiographic marginal bone level was 45 to 50% in group A, 45 to 50% in group B and 90 to 95% in group C. Mean serum C-reactive protein level was significantly higher in group A (8.9 mg/l), as compared to group B (4.9 mg/l) as well as group C (0.9 mg/l). Within the limits of this study it was concluded that periodontitis may add to the inflammatory burden of the individual and may result in increased risk of atherosclerosis based on serum C-reactive protein concentrations.

  17. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Hansen, T.W.; Olsen, M.H.; Rasmussen, S.

    2008-01-01

    BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors...

  18. Production of C-reactive protein by human lymphocytes

    International Nuclear Information System (INIS)

    Kuta, A.E.; Baum, L.L.

    1986-01-01

    C-reactive protein (CRP) is a major acute phase serum protein in humans; it is detectable at very high concentrations during infection and tissue trauma. This protein is a pentame composed of five identical, 21,500 MW subunits. CRP is detectable on the surface of approximately 4% of normal peripheral blood lymphocytes (PBL). CRP binds its physiological ligands in a Ca ++ dependent manner; removal of Ca ++ does not alter the expression of CRP on the lymphocyte surface. Recently, investigators in this laboratory reported substantial inhibition of natural killer cell (NK) activity with anti-CRP antibodies. The following studies were undertaken to determine the origin of surface-CRP (S-CRP) found on normal PBL. Cells were incubated in methionine-free DMEM supplemented with 35 S-methionine. Cells were lysed and subjected to immunoprecipitation with anti-CRP and Staphylococcus aureus; immunoprecipitates were analyzed by SDS-PAGE and autoradiography. Data presented here suggested that lymphocytes, in particular, LGL produce small amounts of CRP and express it on their surface. Lymphocytes do not appear to secrete CRP since no CRP could be detected in culture supernatants. In addition, preliminary evidence indicates that peripheral blood monocytes produce no detectable CRP. Present studies utilizing Northern blot analysis are underway in order to detect CRP-mRNA

  19. Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian randomization of 47,000 individuals from the general population

    DEFF Research Database (Denmark)

    Marott, Sarah C W; Nordestgaard, Børge G; Zacho, Jeppe

    2010-01-01

    The purpose of this study was to test whether the association of C-reactive protein (CRP) with increased risk of atrial fibrillation is a robust and perhaps even causal association.......The purpose of this study was to test whether the association of C-reactive protein (CRP) with increased risk of atrial fibrillation is a robust and perhaps even causal association....

  20. Metabolic syndrome and C-reactive protein in bank employees

    Directory of Open Access Journals (Sweden)

    Cattafesta M

    2016-05-01

    Full Text Available Monica Cattafesta,1 Nazaré Souza Bissoli,2 Luciane Bresciani Salaroli,1,31Postgraduate Program in Nutrition and Health, 2Postgraduate Program in Physiological Sciences, 3Postgraduate Program in Public Health, Department of Health Integrated Education, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil Background: The ultrasensitive C-reactive protein (us-CRP is used for the diagnosis of cardiovascular disease, but it is not well described as a marker for the diagnosis of metabolic syndrome (MS. Methods: An observational and transversal study of bank employees evaluated anthropometric, hemodynamic, and biochemical data. CRP values were determined using commercial kits from Roche Diagnostics Ltd, and MS criteria were analyzed according to National Cholesterol Education Program’s – Adult Treatment Panel III (NCEP/ATP III. Results: A total of 88 individuals had MS, and 77.3% (n=68 of these showed alterations of us-CRP (P=0.0001, confidence interval [CI] 0.11–0.34. Individuals with MS had higher mean values of us-CRP in global measures (P=0.0001 and stratified by sex (P=0.004 than individuals without the syndrome. This marker exhibited significant differences with varying criteria for MS, such as waist circumference (P=0.0001, triglycerides (P=0.002, and diastolic blood pressure (P=0.007, and the highest levels of us-CRP were found in individuals with more MS criteria. Conclusion: us-CRP was strongly associated with the presence of MS and MS criteria in this group of workers. us-CRP is a useful and effective marker for identifying the development of MS and may be used as a reference in routine care. Keywords: C-reactive protein, bank employees, metabolic syndrome, inflammation mediators, occupational health

  1. A robust quantitative solid phase immunoassay for the acute phase protein C-reactive protein (CRP) based on cytidine 5 '-diphosphocholine coupled dendrimers

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Pedersen, H. G.; Jensen, A. L.

    2009-01-01

    C-reactive protein (CRP) is an important acute phase protein, being used as a sensitive indicator of inflammation and infection and is also associated with the risk of cardiovascular problems. The present paper describes a robust and sensitive ELISA for CRP, based on the affinity of CRP for phosp......C-reactive protein (CRP) is an important acute phase protein, being used as a sensitive indicator of inflammation and infection and is also associated with the risk of cardiovascular problems. The present paper describes a robust and sensitive ELISA for CRP, based on the affinity of CRP...... was applied to determination of pig and human CRP using commercially available antibodies against human CRP. The assay was shown to be more sensitive than previously published immunoassays employing albumin-coupled cytidine diphosphocholine. The coating was stable for at least 30 days at room temperature...

  2. C-reactive protein in relation to early atherosclerosis and periodontitis.

    Science.gov (United States)

    Yakob, Maha; Meurman, Jukka H; Jogestrand, Tomas; Nowak, Jacek; Söder, Per-Östen; Söder, Birgitta

    2012-02-01

    Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

  3. Highly-sensitive C-reactive protein, a biomarker of cardiovascular disease risk, in radically-treated differentiated thyroid carcinoma patients after repeated thyroid hormone withholding.

    Science.gov (United States)

    Piciu, A; Piciu, D; Marlowe, R J; Irimie, A

    2013-02-01

    In patients radically treated for differentiated thyroid carcinoma, we assessed the response of highly-sensitive C-reactive protein, an inflammatory biomarker for cardiovascular risk, after thyroid hormone withholding ("deprivation"), as well as factors potentially influencing this response. We included 52 adults (mean age 45.6±14.0 years, 35 females) who were disease-free after total thyroidectomy, radioiodine ablation and chronic thyroid hormone therapy. They were lifelong non-smokers without apparent inflammatory comorbidity, cardiovascular history beyond pharmacotherapy-controlled hypertension, anti-dyslipidemic medication, or C-reactive protein >10 mg/L in any study measurement. The index deprivation lasted ≥2 weeks, elevating serum thyrotropin >40 mIU/L or ≥100 × the individual's suppressed level. We examined the relationship of age, number of prior deprivations, and gender with the magnitude of post-deprivation C-reactive protein concentration through multivariable statistical analyses using the F test on linear regression models. Post-deprivation, C-reactive protein reached intermediate cardiovascular risk levels (based on general population studies involving chronic elevation), 1-3 mg/L, in 44.2% of patients and high-risk levels, >3 mg/L, in another 17.3%. Mean C-reactive protein was 1.77±1.50 mg/L, differing significantly in females (2.12±1.66 mg/L) vs. males (1.05±0.69 mg/L, P <0.001). In multivariable analysis, patients ≤45 years old (odds ratio, 95% confidence interval 0.164 [0.049-0.548]) were less likely, and females, more likely (3.571 [1.062-12.009]) to have post-deprivation C-reactive protein ≥1 mg/L. Thyroid hormone withdrawal frequently elevated C-reactive protein to levels that when present chronically, were associated with increased cardiovascular risk in general population studies. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  4. C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

    DEFF Research Database (Denmark)

    Zimmermann, Esther; Anty, Rodolphe; Tordjman, Joan

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH), but th......Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH...

  5. Association between C-reactive protein and features of the metabolic syndrome

    DEFF Research Database (Denmark)

    Fröhlich, M; Imhof, A; Berg, Gabriele

    2000-01-01

    OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence...... concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P metabolic syndrome...

  6. C-reactive protein, procalcitonin, clinical pulmonary infection score, and pneumonia severity scores in nursing home acquired pneumonia.

    Science.gov (United States)

    Porfyridis, Ilias; Georgiadis, Georgios; Vogazianos, Paris; Mitis, Georgios; Georgiou, Andreas

    2014-04-01

    Patients with nursing home acquired pneumonia (NHAP) present a distinct group of lower respiratory track infections with different risk factors, clinical presentation, and mortality rates. To evaluate the diagnostic value of clinical pulmonary infection score (CPIS), C-reactive protein, and procalcitonin and to compare the accuracy of pneumonia severity scores (confusion, urea nitrogen, breathing frequency, blood pressure, ≥ 65 y of age [CURB-65]; pneumonia severity index; NHAP index; systolic blood pressure, multilobar involvement, albumin, breathing frequency, tachycardia, confusion, oxygen, arterial pH [SMART-COP]; and systolic blood pressure, oxygen, age > 65 y, breathing frequency [SOAR]) in predicting in-patient mortality from NHAP. Nursing home residents admitted to the hospital with acute respiratory illness were enrolled in the study. Subjects were classified as having NHAP (Group A) or other pulmonary disorders (Group B). Clinical, imaging, and laboratory data were assessed to compute CPIS and severity scores. C-reactive protein and procalcitonin were measured by immunonephelometry and immunoassay, respectively. Fifty-eight subjects were diagnosed with NHAP (Group A) and 29 with other pulmonary disorders (Group B). The mean C-reactive protein ± SD was 16.38 ± 8.6 mg/dL in Group A and 5.2 ± 5.6 mg/dL in Group B (P 1.1 ng/mL was an independent predictor of in-patient mortality. Of the pneumonia severity scores, CURB-65 showed greater accuracy in predicting in-patient mortality (area under the curve of 0.68, 95% CI 0.53-0.84, P = .06). CPIS, procalcitonin, and C-reactive protein are reliable for the diagnosis of NHAP. Procalcitonin and CURB-65 are accurate in predicting in-patient mortality in NHAP.

  7. C-reactive protein, Rheumatoid factor and circulatory immune complex as markers for monitoring treatment of infective endocarditis

    International Nuclear Information System (INIS)

    Alavi, S.M.; Ahmadi, F.; Nashibi, R.

    2010-01-01

    Objectives: To evaluate the diagnostic usefulness of serum C-reactive protein (CRP), rheumatoid factor (RF) and circulatory immune complex (CIC) determinations in monitoring the outcome of infective endocarditis (IE). Methodology: In this prospective analytic descriptive study CRP, RF and CIC were measured on admission and 4 weeks after initiation of standard antibiotic regimen in 30 hospitalized patients with IE in an educational hospital between 2006 and 2007 in Ahvaz a city south west Iran . Duke criteria were used for diagnosis of IE. CRP and RF were examined using quantitative neflometry (Binding site kit, UK) and CIC was detected by semi quantitative immune diffusion (Baharafshan SIRD kit, Iran). Data were evaluated using statistical analyses in SPSS (version 12, USA) software for windows. Results: The fall in serum C-reactive protein or RF was significant (P= 0.05). Only two of the 30 patients, who had elevated CRP, RF and CIC week four failed to response and one needed cardiac surgery. Conclusions: The C-reactive protein proved to be a good tool for monitoring the treatment of IE. Also RF proved useful in the assessment of patients with IE, but the value of CIC was negligible. (author)

  8. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels : a randomized, diet-controlled intervention study

    NARCIS (Netherlands)

    Sierksma, A.; Gaag, M.S. van der; Kluft, C.; Hendriks, H.F.J.

    2002-01-01

    Objective: To evaluate the effect of moderate alcohol consumption on the acute phase proteins C-reactive protein and fibrinogen. Design: Randomized, diet-controlled, cross-over study. Setting: The study was performed at TNO Nutrition and Food Research, Zeist, The Netherlands. Subjects: Ten

  9. The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids

    Directory of Open Access Journals (Sweden)

    Ngai John

    2006-12-01

    Full Text Available Abstract Background Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs: the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis – which also included a set of 34 C family GPCRs from fugu – places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s, these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

  10. Comparison of serum amyloid A and C-reactive protein as diagnostic markers of systemic inflammation in dogs

    DEFF Research Database (Denmark)

    Christensen, Michelle Brønniche; Langhorn, Rebecca; Goddard, Amelia

    2014-01-01

    The diagnostic performance of canine serum amyloid A (SAA) was compared with that of C-reactive protein (CRP) in the detection of systemic inflammation in dogs. Sera from 500 dogs were retrospectively included in the study. C-reactive protein and SAA were measured using validated automated assays....... The overlap performance, clinical decision limits, overall diagnostic performance, correlations, and agreement in the clinical classification between these 2 diagnostic markers were compared. Significantly higher concentrations of both proteins were detected in dogs with systemic inflammation (SAA range: 48.......75 to > 2700 mg/L; CRP range: 0.4 to 907.4 mg/L) compared to dogs without systemic inflammation (SAA range: 1.06 to 56.4 mg/L; CRP range: 0.07 to 24.7 mg/L). Both proteins were shown to be sensitive and specific markers of systemic inflammation in dogs. Significant correlations and excellent diagnostic...

  11. Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes

    DEFF Research Database (Denmark)

    Prins, Bram P; Abbasi, Ali; Wong, Anson

    2016-01-01

    BACKGROUND: C-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal. METHODS AND FINDINGS: We performed Mendelian randomization (MR) analyses using two genetic risk scores (GRSs) as inst...

  12. C-reactive protein as a predictor of chorioamnionitis.

    Science.gov (United States)

    Smith, Erik J; Muller, Corinna L; Sartorius, Jennifer A; White, David R; Maslow, Arthur S

    2012-10-01

    Chorioamnionitis (CAM) affects many pregnancies complicated by preterm premature rupture of membranes (PPROM). Finding a serum factor that could accurately predict the presence of CAM could potentially lead to more efficient management of PPROM and improved neonatal outcomes. To determine if C-reactive protein (CRP) is an effective early marker of CAM in patients with PPROM. A retrospective evaluation of pregnant women with PPROM at Geisinger Medical Center in Danville, Pennsylvania, between January 2005 and January 2009. Nonparametric statistical tests (ie, Wilcoxon rank sum and Spearman rank correlation) were used to compare distributions that were skewed. Characteristics of the study population were compared using 2-sample t tests for continuous variables and Fisher exact tests for discrete variables. Logistic regression analysis was used to generate receiver operating characteristic curves and obtain area under the curve estimates in stepwise fashion for predicting histologic CAM. A secondary analysis compared the characteristics among patients with clinical CAM, histologic CAM, or non-CAM. The total population of 73 women was subdivided into patients with histologic CAM (n=26) and patients without histologic CAM (ie, no evidence of CAM on placental pathology; n=47). There was no difference between groups in CRP levels, days of pregnancy latency, white blood cell count, smoking status, antibiotic administration, or steroid benefit. The group with histologic CAM delivered at earlier gestational ages: mean (standard deviation) age was 29.5 (4.4) weeks vs 31.9 (3.5) weeks (P=.02). For our primary analysis, we found no difference in CRP levels (P=.32). Receiver operating characteristic curve plots of CRP levels, temperature at delivery, and white blood cell count resulted in an area under the curve estimate of 0.696, which was 70% predictive of histologic CAM. In the secondary analysis, after adjusting for gestational age, the estimated hazard ratio for CRP change

  13. Transduction proteins of olfactory receptor cells: identification of guanine nucleotide binding proteins and protein kinase C

    International Nuclear Information System (INIS)

    Anholt, R.R.H.; Mumby, S.M.; Stoffers, D.A.; Girard, P.R.; Kuo, J.F.; Snyder, S.H.

    1987-01-01

    The authors have analyzed guanine nucleotide binding proteins (G-proteins) in the olfactory epithelium of Rana catesbeiana using subunit-specific antisera. The olfactory epithelium contained the α subunits of three G-proteins, migrating on polyacrylamide gels in SDS with apparent molecular weights of 45,000, 42,000, and 40,000, corresponding to G/sub s/, G/sub i/, and G/sub o/, respectively. A single β subunit with an apparent molecular weight of 36,000 was detected. An antiserum against the α subunit of retinal transducin failed to detect immunoreactive proteins in olfactory cilia detached from the epithelium. The olfactory cilia appeared to be enriched in immunoreactive G/sub sα/ relative to G/sub ichemical bond/ and G/sub ochemical bond/ when compared to membranes prepared from the olfactory epithelium after detachment of the cilia. Bound antibody was detected by autoradiography after incubation with [ 125 I]protein. Immunohistochemical studies using an antiserum against the β subunit of G-proteins revealed intense staining of the ciliary surface of the olfactory epithelium and of the axon bundles in the lamina propria. In contrast, an antiserum against a common sequence of the α subunits preferentially stained the cell membranes of the olfactory receptor cells and the acinar cells of Bowman's glands and the deep submucosal glands. In addition to G-proteins, they have identified protein kinase C in olfactory cilia via a protein kinase C specific antiserum and via phorbol ester binding. However, in contrast to the G-proteins, protein kinase C occurred also in cilia isolated from respiratory epithelium

  14. Interindividual variation in the response by fibrinogen, C-reactive protein and interleukin-6 to yellow fever vaccination

    NARCIS (Netherlands)

    Verschuur, M.; Beek, M.T. van der; Tak, H.S.; Visser, L.G.; Maat, M.P.M. de

    2004-01-01

    The acute phase reaction is important in many disease processes. Habitual levels of the acute phase proteins fibrinogen, C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with an increased risk of cardiovascular disease, but the dynamic variation of plasma levels of acute phase

  15. Evaluation of C-Reactive Protein Level in Patients with Pain Form of Temporomandibular Joint Dysfunction

    Directory of Open Access Journals (Sweden)

    Malgorzata Pihut

    2018-01-01

    Full Text Available Temporomandibular joint dysfunction is a functional disorder concerned with the abnormal functioning of the muscles of the stomatognathic system and temporomandibular joints involved in the dynamic movements of the jaw and surrounding structures. The aim of the study was to compare the level of C-reactive protein in patients with pain and painless forms of temporomandibular joint dysfunction. Materials and methods. The study group consisted of 72 patients who reported to the prosthetic treatment because of temporomandibular joint dysfunction. The study group included 36 patients with pain form of dysfunction, and the control group included 36 patients with painless form of disorder. Each patient underwent specialized examination of functional disorders in order to diagnose the type of dysfunction and was commissioned to carry out a study of the blood test concerned with evaluation of the C-reactive protein (CRP level in the same analytical laboratory. The results of the investigation were subjected to statistical analysis. The research obtained approval from the Ethics Committee of the Jagiellonian University (KBET/125/L/2013. Level of Evidence for primary research was established as type V. Results. The mean values of C-reactive protein levels in both groups were in the normal range and did not differ statistically significantly, which indicates the fact that the pain form of the temporomandibular joint disorders is not associated with inflammation of the soft tissues of the joint. Conclusion. Painful form of the temporomandibular joint dysfunctions is not connected with the inflammation of joints.

  16. Role of post-translational modifications on structure, function and pharmacology of class C G protein-coupled receptors

    DEFF Research Database (Denmark)

    Nørskov-Lauritsen, Lenea; Bräuner-Osborne, Hans

    2015-01-01

    taste receptors (T1R1-3), one calcium-sensing (CaS) receptor, one GPCR, class C, group 6, subtype A (GPRC6) receptor, and seven orphan receptors. G protein-coupled receptors undergo a number of post-translational modifications, which regulate their structure, function and/or pharmacology. Here, we...

  17. Soluble membrane receptors, interleukin 6, procalcitonin and C reactive protein as prognostic markers in patients with severe sepsis and septic shock.

    Directory of Open Access Journals (Sweden)

    Juan-Jesús Ríos-Toro

    Full Text Available The objective of this study was to explore the diagnostic and prognostic value of soluble triggering receptor expressed on myeloid cell 1 (sTREM-1, soluble cluster of differentiation 14 (sCD14, soluble cluster of differentiation 163 (sCD163, interleukin-6 (IL-6, procalcitonin (PCT, and C-reactive protein (CRP serum levels for patients with severe sepsis and septic shock in an intensive care unit (ICU.Fifty patients admitted at the ICU with the diagnosis of severe sepsis or septic shock were studied. SOFA and APACHE II scores as well as serum biomarkers were measured at days 0, 2 and 5. The influence of these variables on 28-day mortality was analyzed. Twenty healthy individuals served as controls.Baseline serum concentrations of sTREM-1, sCD163, IL-6 and PCT correlated with SOFA score. Only sTREM-1 levels correlated with APACHE II score. The 28-day mortality rate for all patients was 42%. The absence of risk factors for infection, presence of septic shock, baseline values of sCD14 and decrease of PCT and IL-6 from baseline to day 5 were variables associated to mortality in the univariate analysis. The unique independent factor associated to mortality in the multivariate analysis was a decrease of PCT higher than 50% from days 0 to 5.Serum levels of sTREM-1 are correlated with the severity of sepsis. A 50% decrease of PCT was the unique variable associated with survival in the multivariate analysis.

  18. G protein-coupled receptor 30 (GPR30) forms a plasma membrane complex with membrane-associated guanylate kinases (MAGUKs) and protein kinase A-anchoring protein 5 (AKAP5) that constitutively inhibits cAMP production.

    Science.gov (United States)

    Broselid, Stefan; Berg, Kelly A; Chavera, Teresa A; Kahn, Robin; Clarke, William P; Olde, Björn; Leeb-Lundberg, L M Fredrik

    2014-08-08

    GPR30, or G protein-coupled estrogen receptor, is a G protein-coupled receptor reported to bind 17β-estradiol (E2), couple to the G proteins Gs and Gi/o, and mediate non-genomic estrogenic responses. However, controversies exist regarding the receptor pharmacological profile, effector coupling, and subcellular localization. We addressed the role of the type I PDZ motif at the receptor C terminus in receptor trafficking and coupling to cAMP production in HEK293 cells and CHO cells ectopically expressing the receptor and in Madin-Darby canine kidney cells expressing the native receptor. GPR30 was localized both intracellularly and in the plasma membrane and subject to limited basal endocytosis. E2 and G-1, reported GPR30 agonists, neither stimulated nor inhibited cAMP production through GPR30, nor did they influence receptor localization. Instead, GPR30 constitutively inhibited cAMP production stimulated by a heterologous agonist independently of Gi/o. Moreover, siRNA knockdown of native GPR30 increased cAMP production. Deletion of the receptor PDZ motif interfered with inhibition of cAMP production and increased basal receptor endocytosis. GPR30 interacted with membrane-associated guanylate kinases, including SAP97 and PSD-95, and protein kinase A-anchoring protein (AKAP) 5 in the plasma membrane in a PDZ-dependent manner. Knockdown of AKAP5 or St-Ht31 treatment, to disrupt AKAP interaction with the PKA RIIβ regulatory subunit, decreased inhibition of cAMP production, and St-Ht31 increased basal receptor endocytosis. Therefore, GPR30 forms a plasma membrane complex with a membrane-associated guanylate kinase and AKAP5, which constitutively attenuates cAMP production in response to heterologous agonists independently of Gi/o and retains receptors in the plasma membrane. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Validation of commercially available automated canine-specific immunoturbidimetric method for measuring canine C-reactive protein

    DEFF Research Database (Denmark)

    Hillström, Anna; Hagman, Ragnvi; Tvedten, Harold

    2014-01-01

    BACKGROUND: Measurement of C-reactive protein (CRP) is used for diagnosing and monitoring systemic inflammatory disease in canine patients. An automated human immunoturbidimetric assay has been validated for measuring canine CRP, but cross-reactivity with canine CRP is unpredictable. OBJECTIVE......: The purpose of the study was to validate a new automated canine-specific immunoturbidimetric CRP method (Gentian cCRP). METHODS: Studies of imprecision, accuracy, prozone effect, interference, limit of quantification, and stability under different storage conditions were performed. The new method was compared...... with a human CRP assay previously validated for canine CRP determination. Samples from 40 healthy dogs were analyzed to establish a reference interval. RESULTS: Total imprecision was

  20. C-reactive Protein −717A>G and −286C>T>A Gene Polymorphism and Ischemic Stroke

    OpenAIRE

    Yan Liu; Pei-Liang Geng; Fu-Qin Yan; Tong Chen; Wei Wang; Xu-Dong Tang; Jing-Chen Zheng; Wei-Ping Wu; Zhen-Fu Wang

    2015-01-01

    Background: Inflammation plays a pivotal role in the formation and progression of ischemic stroke. Recently, more and more epidemiological studies have focused on the association between C-reactive protein (CRP) −717A > G and −286C > T > A genetic polymorphisms and ischemic stroke. However, the findings of these researches are not conclusive. Methods: We performed a meta-analysis to determine whether these two polymorphisms are associated with the risk of ischemic stroke. Eligible studies...

  1. Genetically elevated C-reactive protein and ischemic vascular disease

    DEFF Research Database (Denmark)

    Zacho, J.; Tybjaerg-Hansen, A.; Jensen, J.S.

    2008-01-01

    Background: Elevated levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. We tested whether this is a causal association. Methods: We studied 10,276 persons from a general population cohort, including 1786 in whom...... ischemic heart disease developed and 741 in whom ischemic cerebrovascular disease developed. We examined another 31,992 persons from a cross-sectional general population study, of whom 2521 had ischemic heart disease and 1483 had ischemic cerebrovascular disease. Finally, we compared 2238 patients...... with ischemic heart disease with 4474 control subjects and 612 patients with ischemic cerebrovascular disease with 1224 control subjects. We measured levels of high-sensitivity CRP and conducted genotyping for four CRP polymorphisms and two apolipoprotein E polymorphisms. Results: The risk of ischemic heart...

  2. Major Depression, C-Reactive Protein, and Incident Ischemic Heart Disease in Healthy Men and Women

    NARCIS (Netherlands)

    Surtees, Paul G.; Wainwright, Nicholas W. J.; Boekholdt, S. Matthijs; Luben, Robert N.; Wareham, Nicholas J.; Khaw, Kay-Tee

    2008-01-01

    Objective: To investigate how C-reactive protein (CRP) and major depressive disorder (MDD) relate to each other and to incident ischemic heart disease (IHD). Studies have shown that both depression and raised CRP concentration predict IHD and that elevated CRP is linked with increased risk of

  3. C-reactive protein alterations in bipolar disorder: a meta-analysis.

    Science.gov (United States)

    Dargél, Aroldo A; Godin, Ophelia; Kapczinski, Flávio; Kupfer, David J; Leboyer, Marion

    2015-02-01

    There is growing evidence that bipolar disorder (BD) is associated with inflammation, including abnormal levels of acute-phase C-reactive protein (CRP). Our meta-analysis was conducted to estimate the size of the association between CRP levels and BD, accounting also for subgroup differences (mood phases and treatment). MEDLINE, EMBASE, PsycINFO, and ISI Web of Science and references of identified articles were searched up to June 2013 using the keywords (bipolar disorder) AND (C-reactive protein OR CRP). English language studies measuring blood levels of CRP in patients with BD and control subjects were selected, 136 abstracts were reviewed, 20 articles retrieved, and 11 studies included. Two independent reviewers extracted data. All studies were included in the primary analyses, and between-group differences for subanalyses were also reported. This meta-analysis was performed using random-effects models. Eleven studies comprising 1,618 subjects were eligible for inclusion. Overall, CRP levels were significantly elevated in patients with BD versus controls (standardized mean difference [SMD] = 0.39; 95% CI, 0.24 to 0.55; P < .0001). CRP levels were significantly higher in manic (SMD = 0.73; 95% CI, 0.44 to 1.02; P < .001) and euthymic (SMD = 0.26; 95% CI, 0.01 to 0.51; P = .04), but not in depressed (SMD = 0.28; 95% CI, -0.17 to 0.73; P = .22) patients with BD compared to controls. CRP levels were unrelated to use of lithium or antipsychotic medication. This meta-analysis supports an association between increased CRP levels and BD. Given that an elevated level of CRP is a marker of low-grade inflammation and a risk factor for cardiovascular and malignant diseases, measurement of CRP level might be relevant to the clinical care of bipolar patients. © Copyright 2015 Physicians Postgraduate Press, Inc.

  4. Prognostic implications of plasma fibrinogen and serum C- reactive ...

    African Journals Online (AJOL)

    reactive protein levels in non-small cell lung cancer resection and ... Abstract. Purpose: To investigate the prognostic implications of plasma fibrinogen and serum C-reactive protein ... The possibility of complete resection and associated findings are reported. Results: ... operable using pre-operative chemotherapy and/or ...

  5. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen.

    Science.gov (United States)

    Wu, T; Trevisan, M; Genco, R J; Falkner, K L; Dorn, J P; Sempos, C T

    2000-02-01

    Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

  6. External Quality Control for Dried Blood Spot Based C-reactive Protein Assay: Experience from the Indonesia Family Life Survey and the Longitudinal Aging Study in India

    Science.gov (United States)

    Hu, Peifeng; Herningtyas, Elizabeth H.; Kale, Varsha; Crimmins, Eileen M.; Risbud, Arun R.; McCreath, Heather; Lee, Jinkook; Strauss, John; O’Brien, Jennifer C.; Bloom, David E.; Seeman, Teresa E.

    2015-01-01

    Measurement of C-reactive protein, a marker of inflammation, in dried blood spots has been increasingly incorporated in community-based social surveys internationally. Although the dried blood spot based CRP assay protocol has been validated in the United States, it remains unclear whether laboratories in other less developed countries can generate C-reactive protein results of similar quality. We therefore conducted external quality monitoring for dried blood spot based C-reactive protein measurement for the Indonesia Family Life Survey and the Longitudinal Aging Study in India. Our results show that dried blood spot based C-reactive protein results in these two countries have excellent and consistent correlations with serum-based values and dried blood spot based results from the reference laboratory in the United States. Even though the results from duplicate samples may have fluctuations in absolute values over time, the relative order of C-reactive protein levels remains similar and the estimates are reasonably precise for population-based studies that investigate the association between socioeconomic factors and health. PMID:25879265

  7. In patients with neovascular age-related macular degeneration, physical activity may influence C-reactive protein levels

    DEFF Research Database (Denmark)

    Subhi, Yousif; Singh, Amardeep; Falk, Mads Krüger

    2014-01-01

    Association of neovascular age-related macular degeneration (AMD) with C-reactive protein (CRP) was previously reported, indicating a relation to systemic low-grade inflammation. However, visual impairment limits physical activity, and physical activity modulates CRP levels. Here, we investigated...

  8. Alteration of Airway Reactivity and Reduction of Ryanodine Receptor Expression by Cigarette Smoke in Mice.

    Science.gov (United States)

    Donovan, Chantal; Seow, Huei Jiunn; Royce, Simon G; Bourke, Jane E; Vlahos, Ross

    2015-10-01

    Small airways are a major site of airflow limitation in chronic obstructive pulmonary disease (COPD). Despite the detrimental effects of long-term smoking in COPD, the effects of acute cigarette smoke (CS) exposure on small airway reactivity have not been fully elucidated. Balb/C mice were exposed to room air (sham) or CS for 4 days to cause airway inflammation. Changes in small airway lumen area in response to contractile agents were measured in lung slices in situ using phase-contrast microscopy. Separate slices were pharmacologically maintained at constant intracellular Ca(2+) using caffeine/ryanodine before contractile measurements. Gene and protein analysis of contractile signaling pathways were performed on separate lungs. Monophasic contraction to serotonin became biphasic after CS exposure, whereas contraction to methacholine was unaltered. This altered pattern of contraction was normalized by caffeine/ryanodine. Expression of contractile agonist-specific receptors was unaltered; however, all isoforms of the ryanodine receptor were down-regulated. This is the first study to show that acute CS exposure selectively alters small airway contraction to serotonin and down-regulates ryanodine receptors involved in maintaining Ca(2+) oscillations in airway smooth muscle. Understanding the contribution of ryanodine receptors to altered airway reactivity may inform the development of novel treatment strategies for COPD.

  9. [Relationship between periodontitis and levels of high-sensitivity C-reactive protein].

    Science.gov (United States)

    Pan, Heng-biao; Chen, Hui; Zhou, Na; Jin, Dan; Zhang, Jing; Peng, Chun-mei

    2010-08-01

    To evaluate the relationship between periodontitis and the traditional risk factors of coronary heart disease (CHD), as well as the role in the mechanisms responsible for high-sensitivity C-reactive protein (hsCRP) in the relationship of peridontitis and CHD. A periodontal examination was conducted on a total of 356 subjects, and community periodontal index of treatment needs (CPITN) was obtained from each subject. Periodontal status was categorized into TN periodontal, hsCRP concentration and routinely CHD serological indexes. In the groups of TN periodontal pockets were found in the Group hsCRP > or = 3.0 mg x L(-1) (P periodontal disease.

  10. Uncoupling protein 2 G(-866A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients C-reactive protein in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Cocozza Sergio

    2010-10-01

    Full Text Available Abstract Background This study evaluated the relationship between the G(-866A polymorphism of the uncoupling protein 2 (UCP2 gene and high-sensitivity C reactive protein (hs-CRP plasma levels in diabetic patients. Methods We studied 383 unrelated people with type 2 diabetes aged 40-70 years. Anthropometry, fasting lipids, glucose, HbA1c, and hs-CRP were measured. Participants were genotyped for the G (-866A polymorphism of the uncoupling protein 2 gene. Results Hs-CRP (mg/L increased progressively across the three genotype groups AA, AG, or GG, being respectively 3.0 ± 3.2, 3.6 ± 5.0, and 4.8 ± 5.3 (p for trend = 0.03. Since hs-CRP values were not significantly different between AA and AG genotype, these two groups were pooled for further analyses. Compared to participants with the AA/AG genotypes, homozygotes for the G allele (GG genotype had significantly higher hs-CRP levels (4.8 ± 5.3 vs 3.5 ± 4.7 mg/L, p = 0.01 and a larger proportion (53.9% vs 46.1%, p = 0.013 of elevated hs-CRP (> 2 mg/L. This was not explained by major confounders such as age, gender, BMI, waist circumference, HbA1c, smoking, or medications use which were comparable in the two genotype groups. Conclusions The study shows for the first time, in type 2 diabetic patients, a significant association of hs-CRP levels with the G(-866A polymorphism of UCP2 beyond the effect of major confounders.

  11. A highly conserved glycine within linker I and the extreme C terminus of G protein alpha subunits interact cooperatively in switching G protein-coupled receptor-to-effector specificity

    DEFF Research Database (Denmark)

    Kostenis, Evi; Martini, Lene; Ellis, James

    2004-01-01

    Numerous studies have attested to the importance of the extreme C terminus of G protein alpha subunits in determining their selectivity of receptor recognition. We have previously reported that a highly conserved glycine residue within linker I is important for constraining the fidelity of receptor...... recognition by Galpha(q) proteins. Herein, we explored whether both modules (linker I and extreme C terminus) interact cooperatively in switching G protein-coupled receptor (GPCR)-to-effector specificity and created as models mutant Galpha(q) proteins in which glycine was replaced with various amino acids...... and the C-terminal five Galpha(q) residues with the corresponding Galpha(i) or Galpha(s) sequence. Coupling properties of the mutated Galpha(q) proteins were determined after coexpression with a panel of 13 G(i)-and G(s) -selective receptors and compared with those of Galpha proteins modified in only one...

  12. A library of 7TM receptor C-terminal tails - Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, A.; Sondergaard, B.P.; Ersbøll, Bjarne Kjær

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK1 receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  13. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, Arne; Søndergaard, Birgitte P; Ersbøll, Bjarne

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK(1) receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  14. Fluorescent detection of C-reactive protein using polyamide beads

    Science.gov (United States)

    Jagadeesh, Shreesha; Chen, Lu; Aitchison, Stewart

    2016-03-01

    Bacterial infection causes Sepsis which is one of the leading cause of mortality in hospitals. This infection can be quantified from blood plasma using C - reactive protein (CRP). A quick diagnosis at the patient's location through Point-of- Care (POC) testing could give doctors the confidence to prescribe antibiotics. In this paper, the development and testing of a bead-based procedure for CRP quantification is described. The size of the beads enable them to be trapped in wells without the need for magnetic methods of immobilization. Large (1.5 mm diameter) Polyamide nylon beads were used as the substrate for capturing CRP from pure analyte samples. The beads captured CRP either directly through adsorption or indirectly by having specific capture antibodies on their surface. Both methods used fluorescent imaging techniques to quantify the protein. The amount of CRP needed to give a sufficient fluorescent signal through direct capture method was found suitable for identifying bacterial causes of infection. Similarly, viral infections could be quantified by the more sensitive indirect capture method. This bead-based assay can be potentially integrated as a disposable cartridge in a POC device due to its passive nature and the small quantities needed.

  15. Nuclease-resistant c-di-AMP derivatives that differentially recognize RNA and protein receptors

    Science.gov (United States)

    Meehan, Robert E.; Torgerson, Chad D.; Gaffney, Barbara L.; Jones, Roger A.; Strobel, Scott A.

    2016-01-01

    The ability of bacteria to sense environmental cues and adapt is essential for their survival. The use of second-messenger signaling molecules to translate these cues into a physiological response is a common mechanism employed by bacteria. The second messenger 3’-5’-cyclic diadenosine monophosphate (c-di-AMP) has been linked to a diverse set of biological processes involved in maintaining cell viability and homeostasis, as well as pathogenicity. A complex network of both protein and RNA receptors inside the cell activate specific pathways and mediate phenotypic outputs in response to c-di-AMP. Structural analysis of these RNA and protein receptors has revealed the different recognition elements employed by these effectors to bind the same small molecule. Herein, using a series of c-di-AMP analogs, we probed the interactions made with a riboswitch and a phosphodiesterase protein to identify the features important for c-di-AMP binding and recognition. We found that the ydaO riboswitch binds c-di-AMP in two discrete sites with near identical affinity and a Hill coefficient of 1.6. The ydaO riboswitch distinguishes between c-di-AMP and structurally related second messengers by discriminating against an amine at the C2 position, more than a carbonyl at the C6 position. We also identified phosphate-modified analogs that bind both the ydaO RNA and GdpP protein with high affinity, while symmetrically-modified ribose analogs exhibited a substantial decrease in ydaO affinity, but retained high affinity for GdpP. These ligand modifications resulted in increased resistance to enzyme-catalyzed hydrolysis by the GdpP enzyme. Together, these data suggest that these c-di-AMP analogs could be useful as chemical tools to specifically target subsections of the second-messenger signaling pathways. PMID:26789423

  16. C-reactive protein, inflammation and coronary heart disease

    Directory of Open Access Journals (Sweden)

    Amit Kumar Shrivastava

    2015-06-01

    Full Text Available Inflammation is widely considered to be an important contributing factor of the pathophysiology of coronary heart disease (CHD, and the inflammatory cascade is particularly important in the atherosclerotic process. In consideration of the important role that inflammatory processes play in CHD, recent work has been focused on whether biomarkers of inflammation may help to improve risk stratification and identify patient groups who might benefit from particular treatment strategies. Of these biomarkers, C-reactive protein (CRP has emerged as one of the most important novel inflammatory markers. CRP an acute phase protein is synthesized by hepatocytes in response to proinflammatory cytokines, in particular interleukin-6. Many large-scale prospective studies demonstrate that CRP strongly and independently predicts adverse cardiovascular events, including myocardial infarction, ischemic stroke, and sudden cardiac death in individuals both with and without overt CHD. CRP is believed to be both a marker and a mediator of atherosclerosis and CHD. CRP plays a pivotal role in many aspects of atherogenesis including, activation of complement pathway, lipids uptake by macrophage, release of proinflammatory cytokines, induces the expression of tissue factor in monocytes, promotes the endothelial dysfunction and inhibits nitric oxide production. The commercial availability of CRP high sensitive assays has made screening for this marker simple, reliable, and reproducible and can be used as a clinical guide to diagnosis, management, and prognosis of CHD.

  17. Evaluation of C-reactive protein as an inflammatory biomarker in rabbits for vaccine nonclinical safety studies

    NARCIS (Netherlands)

    Destexhe, E.; Prinsen, M.K.; Schöll, I. van; Kuper, C.F.; Garçon, N.; Veenstra, S.; Segal, L.

    2013-01-01

    Introduction: Inflammatory reactions are one of the potential safety concerns that are evaluated in the framework of vaccine safety testing. In nonclinical studies, the assessment of the inflammation relies notably on the measurement of biomarkers. C-reactive protein (CRP) is an acute-phase plasma

  18. Solid phase radioimmunoassays for human C-reactive protein

    International Nuclear Information System (INIS)

    Shine, B.; Beer, F.C. de; Pepys, M.B.

    1981-01-01

    Two new, rapid and sensitive radioimmunoassays for human C-reactive protein (CRP) have been established using antiserum coupled to magnetizable cellulose particles, which facilitate phase separation. A single antibody method, using solid phase anti-CRP, provides a sensitivity of 50 μg/l with a 1-h incubation time and intra- and inter-assay coefficients of variation of 10%. A double antibody method, using fluid phase rabbit anti-CRP serum and solid phase sheep anti-rabbit IgG serum, provides a sensitivity of 3 μg/l with an overnight incubation and intra- and inter-assay coefficients of variation of 10%. Among 468 sera from normal adult volunteer blood donors the median CRP concentration was 800 μg/l, interquartile range 340-1700 μg/l and range 70-29,000 μg/l. Ninety percent of samples contained less than 3 mg/l and 99% less than 10 mg/l. Low levels (14-650 μg/l) of CRP were detected both in amniotic fluids and in cerebrospinal fluids. (Auth.)

  19. Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain.

    Science.gov (United States)

    Navarro, Gemma; Cordomí, Arnau; Brugarolas, Marc; Moreno, Estefanía; Aguinaga, David; Pérez-Benito, Laura; Ferre, Sergi; Cortés, Antoni; Casadó, Vicent; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Pardo, Leonardo; McCormick, Peter J; Franco, Rafael

    2018-02-28

    G-protein-coupled receptor (GPCR) heteromeric complexes have distinct properties from homomeric GPCRs, giving rise to new receptor functionalities. Adenosine receptors (A 1 R or A 2A R) can form A 1 R-A 2A R heteromers (A 1 -A 2A Het), and their activation leads to canonical G-protein-dependent (adenylate cyclase mediated) and -independent (β-arrestin mediated) signaling. Adenosine has different affinities for A 1 R and A 2A R, allowing the heteromeric receptor to detect its concentration by integrating the downstream G i - and G s -dependent signals. cAMP accumulation and β-arrestin recruitment assays have shown that, within the complex, activation of A 2A R impedes signaling via A 1 R. We examined the mechanism by which A 1 -A 2A Het integrates G i - and G s -dependent signals. A 1 R blockade by A 2A R in the A 1 -A 2A Het is not observed in the absence of A 2A R activation by agonists, in the absence of the C-terminal domain of A 2A R, or in the presence of synthetic peptides that disrupt the heteromer interface of A 1 -A 2A Het, indicating that signaling mediated by A 1 R and A 2A R is controlled by both G i and G s proteins. We identified a new mechanism of signal transduction that implies a cross-communication between G i and G s proteins guided by the C-terminal tail of the A 2A R. This mechanism provides the molecular basis for the operation of the A 1 -A 2A Het as an adenosine concentration-sensing device that modulates the signals originating at both A 1 R and A 2A R.

  20. Early rise in C-reactive protein is a marker for infective complications in laparoscopic colorectal surgery.

    LENUS (Irish Health Repository)

    Nason, Gregory J

    2014-02-01

    Infective complications are the most significant cause of morbidity associated with elective colorectal surgery. It can sometimes be difficult to differentiate complications from the normal postoperative course. C-reactive protein (CRP) is an acute phase reactant which has been reported to be predictive of postoperative infective complications.

  1. An unusual protein kinase phosphorylates the chemotactic receptor of Dictystelium discoideum

    International Nuclear Information System (INIS)

    Meier, K.; Klein, C.

    1988-01-01

    The authors report the cAMP-dependent phosphorylation of the chemotactic receptor of Dictyostelium discoideum in partially purified plasma membranes. The protein kinase responsible for receptor phosphorylation is associated with this fraction and preferentially phosphorylates the ligand-occupied form of the receptor. 8-Azido[ 32 P]cAMP labeling of the cell surface has shown that the cAMP receptor exists in two forms. A 45-kDa protein is predominant on unstimulated cells. cAMP stimulation results in an increased receptor phosphorylation such that the receptor migrates on NaDodSO 4 /PAGE as a 47-kDa protein. Phosphorylation of the chemotactic receptor is not detected in membrane preparations unless cAMP is added to the incubation mixture. Only under those conditions is the phosphorylated 47-kDa form observed. The requirement for cAMP reflects the fact that the kinase involved preferentially uses the ligand-occupied receptor as a substrate. In vitro phosphorylation of the receptor does not involve tyrosine residues. The enzyme does not appear to be a cAMP- or cGMP-dependent protein kinase nor is it sensitive to guanine nucleotides, Ca 2+ /calmodulin, Ca 2+ /phospholipid, or EGTA. Similarities with the β-adrenergic receptor protein kinase are discussed

  2. C-reactive protein as a marker of periodontal disease.

    Science.gov (United States)

    Kanaparthy, Rosaiah; Kanaparthy, Aruna; Mahendra, Muktishree

    2012-01-01

    Periodontal subgingival pathogens affect local and systemic immune and inflammatory response and cause the release of cytokines; this results in periodontal destruction and initiation of an acute phase systemic inflammatory response characterized by the release of C-reactive proteins (CRP). This study set out to evaluate the serum concentration of CRP that can be used as a marker of periodontal disease as well as a risk indicator for cardiovascular disease. Based on their periodontal status, 45 patients were divided into three groups. The following clinical parameters were recorded: plaque index, gingival index, bleeding index, probing pocket depth, and clinical attachment levels. Scoring was done on six tooth surfaces for all teeth. For the CRP assessment, blood samples were collected from subjects at the time of clinical examination. The results indicated an increase in serum CRP levels in patients with generalized aggressive periodontitis and chronic periodontitis as compared to controls.

  3. Serum C-reactive protein concentration in preeclamptic women: Effect on pregnancy outcome

    Directory of Open Access Journals (Sweden)

    Sharmin Sultana

    2016-07-01

    Full Text Available Background: Preeclampsia is a multisystem disorder of unknown etiology characterized by development of hyperten­sion to the extent of 140/90 mm of Hg or more with proteinuria after the 20th gestational week in a previously normoten­sive and non protein uric women. According to the National High blood presure Working group (NHBPEP and Ameri­can college of obstetricans and Gynecologiests (ACOG hypertension in pregnancy is defined as a diastolic blood pressure of 90 mm Hg or higher after 20 weeks of gestation in a woman with previously normal blood pressure (NHBPEP, 2000; ACOG, 2002. If the disease is allowed to progress to the HELLP syndrome or eclampsia, maternal morbidity and mortality increases. The majority of perinatal losses are related to placental insufficiency, which causes intrauterine growth retardation, prematurity associated with preterm delivery, or abruptio placentae. Objectives: This study tried to explore the effect of serum C reactive protein concentration in preeclamptic women and its effect on pregnancy outcome.Methods: This case control study included 60 third trimester pregnant women (30 normotensive and 30 preeclamptic who attended Department of Obstetrics and Gynaecology, BIRDEM and DMCH, during July 2009 and June 2010. Estimation of serum C reactive protein (CRP concentrations was done by liquid phase immunoprecipitation assay and turbulometry at DMC.Results: Mean (±SD age showed no significant difference between groups; however, BMI, SBP, DBP and CRP were significantly (P<0.001 high in case group. Gravidity and ANC showed no significant variation between groups. CRP concentration was significantly high case group. Gestational age was significantly low in case group resulting in higher preterm delivery. No significant variation was observed regarding fetal outcome; however, birth weight was significantly low and neonatal complication was also significantly high in case group.Conclusion: CRP concentration was high in

  4. Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein

    International Nuclear Information System (INIS)

    Gray, P.W.; Barrett, K.; Chantry, D.; Turner, M.; Feldmann, M.

    1990-01-01

    The cDNA for one of the receptors for human tumor necrosis factor (TNF) has been isolated. This cDNA encodes a protein of 455 amino acids that is divided into an extracellular domain of 171 residues and a cytoplasmic domain of 221 residues. The extracellular domain has been engineered for expression in mammalian cells, and this recombinant derivative binds TNFα with high affinity and inhibits its cytotoxic activity in vitro. The TNF receptor exhibits similarity with a family of cell surface proteins that includes the nerve growth factor receptor, the human B-cell surface antigen CD40, and the rat T-cell surface antigen OX40. The TNF receptor contains four cysteine-rich subdomains in the extracellular portion. Mammalian cells transfected with the entire TNF receptor cDNA bind radiolabeled TNFα with an affinity of 2.5 x 10 -9 M. This binding can be competitively inhibited with unlabeled TNFα or lymphotoxin (TNFβ)

  5. Cloning of Human Tumor Necrosis Factor (TNF) Receptor cDNA and Expression of Recombinant Soluble TNF-Binding Protein

    Science.gov (United States)

    Gray, Patrick W.; Barrett, Kathy; Chantry, David; Turner, Martin; Feldmann, Marc

    1990-10-01

    The cDNA for one of the receptors for human tumor necrosis factor (TNF) has been isolated. This cDNA encodes a protein of 455 amino acids that is divided into an extracellular domain of 171 residues and a cytoplasmic domain of 221 residues. The extracellular domain has been engineered for expression in mammalian cells, and this recombinant derivative binds TNFα with high affinity and inhibits its cytotoxic activity in vitro. The TNF receptor exhibits similarity with a family of cell surface proteins that includes the nerve growth factor receptor, the human B-cell surface antigen CD40, and the rat T-cell surface antigen OX40. The TNF receptor contains four cysteine-rich subdomains in the extra-cellular portion. Mammalian cells transfected with the entire TNF receptor cDNA bind radiolabeled TNFα with an affinity of 2.5 x 10-9 M. This binding can be competitively inhibited with unlabeled TNFα or lymphotoxin (TNFβ).

  6. Serum C-reactive protein and C-reactive gene (-717C>T polymorphism are not associated with periodontitis in Indonesian male patients

    Directory of Open Access Journals (Sweden)

    Antonius Winoto Suhartono

    2015-09-01

    Full Text Available Background: Periodontitis is an inflammatory disease caused by periodontal pathogens and influenced by multiple risk factors such as genetics, smoking habit, age and systemic diseases. The inflammatory cascade is characterized by the release of C-reactive protein (CRP. Periodontitis has been reported to have plausible links to increased level of CRP, which in turn has been associated to elevated risk of  cardiovascular disease (CVD. Purpose: The purpose of this study was t o investigate the relationship amongst the severity of periodontitis, CRP level in blood and CRP (-717 C>T gene polymorphism in male Indonesian smokers and non-smokers. Method: The severity of periodontitis was assessed for 97 consenting male Indonesian smokers and non-smokers. The CRP level of the subjects was determined by using immuno-turbidimetric assay performed in PARAHITA Diagnostic Center Laboratory ISO 9001: 2000 Cert No. 15225/2. The rate of CRP (-717C>T gene polymorphism was determined by using PCR-RFLP in Oral Biology Laboratory, Faculty of Dentistry, Universitas Indonesia. Result: The results suggest that the CRP protein level is not significantly associated with the tested CRP gene polymorphism (p>0.05. Also, while the severity of periodontitis increased significantly with subject age, the CRP level in blood serum was not significantly related to the severity of  periodontitis. The genotypes of the tested polymorphism did not show significant association with the severity of periodontitis either in smokers or in the combined population including smokers and non-smokers. The results naturally do not exclude such associations, but suggest that to discern the differences the sample size must be considerably increased. Conclusion: The CRP (-717C>T gene polymorphism and CRP level in blood serum were not found to be associated with the severity of periodontitis in male smokers or in the combined population of smokers and non-smokers.

  7. C-reactive protein interaction with macrophages: in vitro induction of tumor cytotoxicity, and characterization of C-reactive protein binding to macrophages

    International Nuclear Information System (INIS)

    Zahedi, K.A.

    1987-01-01

    The ability of C-reactive protein (CRP) to activate macrophages to tumoricidal state was examined. CRP was able to activate macrophages to kill tumor cells. The activation was shown to be due to CRP and not to low levels of other activators present in the CRP preparations, since specific removal of CRP led to abrogation of the CRP mediated activation of macrophages. The role of lipopolysaccharide (LPS) as a contaminating activator was eliminated by showing the ability of CRP preparations to activate macrophages from LPS non-responsive strains of mice, and to activate macrophages under conditions which specifically inactivated or removed the contaminating LPS. In order to exclude the possibility of indirect activation of macrophages by other cells present in the peritoneal exudate cell population, effect of CRP on pure macrophages was examined. Bone marrow derived macrophages as well as well as macrophage cell lines exhibited a significant increase in their capacity to kill tumor cells after treatment with CRP. The nature of CRP and macrophage interaction was examined using radioiodinated CRP. Labelled CRP bound specifically to macrophages and macrophage cell lines

  8. C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

    Science.gov (United States)

    Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

    2016-11-01

    It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

  9. Comparative Evaluation of C-Reactive Protein and WBC Count in Fascial Space Infections of Odontogenic Origin.

    Science.gov (United States)

    Bagul, Ravikiran; Chandan, Sanjay; Sane, Vikrant Dilip; Patil, Sujay; Yadav, Dinesh

    2017-06-01

    To assess efficacy of C-reactive protein levels as monitoring tools for patients with fascial space infections of odontogenic origin. A randomized prospective study was conducted on 20 patients suffering from fascial space infection of odontogenic origin, in the department of Oral and Maxillofacial Surgery Bharati Vidyapeeth dental college and hospital, Pune, Patients between 18 and 60 years of age of both the sexes were selected. All patients were treated and observed by the same surgeon. Patient's venous blood sample was collected pre-operatively and on 2nd and 5th post-operative days for evaluation of WBC count and C-reactive protein (CRP). All patients were encouraged for strict follow-up protocol. Where the results of WBC count and CRP when compared it was seen that the mean values of WBC were normal in 15 cases and abnormal in 5 cases on day 0, day 2 and day 5; whereas the mean values of CRP were abnormal on day 0 and day 2 and were within normal limit on day 5 in all cases. The findings of this prospective analysis indicate that White blood cells and C-reactive protein are effective markers for determining severity of infection, efficacy of treatment regime for patients with fascial space infections of odontogenic origin. Thus the markers also help in making treatment of patients with fascial space infections of odontogenic origin more cost effective and they also help protecting patients from side effects of excess drugs usage. Thus we conclude that CRP should be incorporated as monitoring tools for managing patients with fascial space infections of odontogenic origin.

  10. Label-Free Electrochemical Immunoassay for C-Reactive Protein

    Directory of Open Access Journals (Sweden)

    Madasamy Thangamuthu

    2018-03-01

    Full Text Available C-reactive protein (CRP is one of the most expressed proteins in blood during acute phase inflammation, and its minute level increase has also been recognized for the clinical diagnosis of cardio vascular diseases. Unfortunately, the available commercial immunoassays are labour intensive, require large sample volumes, and have practical limitations, such as low stability and high production costs. Hence, we have developed a simple, cost effective, and label-free electrochemical immunoassay for the measurement of CRP in a drop of serum sample using an immunosensor strip made up of a screen printed carbon electrode (SPE modified with anti-CRP functionalized gold nanoparticles (AuNPs. The measurement relies on the decrease of the oxidation current of the redox indicator Fe3+/Fe2+, resulting from the immunoreaction between CRP and anti-CRP. Under optimal conditions, the present immunoassay measures CRP in a linear range from 0.4–200 nM (0.047–23.6 µg mL−1, with a detection limit of 0.15 nM (17 ng mL−1, S/N = 3 and sensitivity of 90.7 nA nM−1, in addition to a good reproducibility and storage stability. The analytical applicability of the presented immunoassay is verified by CRP measurements in human blood serum samples. This work provides the basis for a low-priced, safe, and easy-to-use point-of-care immunosensor assay to measure CRP at clinically relevant concentrations.

  11. Increased systemic elastase and C-reactive protein in aggressive periodontitis (CLOI-D-00160R2).

    Science.gov (United States)

    Wohlfeil, Martin; Scharf, Susanne; Siegelin, Yasemin; Schacher, Beate; Oremek, Gerhard M; Sauer-Eppel, Hildegund; Schubert, Ralf; Eickholz, Peter

    2012-08-01

    The inflammatory mediators, serum elastase and C-reactive protein (CRP), are associated with an increased risk for coronary heart disease. Thus, the aim of this study is to compare systemic inflammatory mediators in periodontally healthy controls (C), patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. C [periodontal pocket probing depth (PPD)  30% of sites; age >35 years), and AgP (clinically healthy; PDD ≥ 3.6 mm at >30% of sites, bone loss ≥50% at ≥2 teeth; age ≤35 years) were examined clinically, and the body mass index was assessed. Blood was sampled for assessment of serum levels of elastase, CRP, lipopolysaccharide binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts. Thirty C, 31 ChP, and 29 AgP were analyzed. Elastase, CRP, LBP, and IL-6 levels were elevated in AgP compared to C (p C. AgP patients exhibit a stronger systemic inflammatory burden than C patients.

  12. Variation in C-reactive protein following weight loss in obese insulin resistant postmenopausal women: is there an independent contribution of lean body mass?

    Science.gov (United States)

    Barsalani, R; Riesco, É; Perreault, K; Imbeault, P; Brochu, M; Dionne, I J

    2015-03-01

    We showed that obese insulin resistant postmenopausal women are characterized by higher lean body mass and elevated C-reactive protein. Although counterintuitive, we hypothesized that losses in muscle mass following caloric restriction and increase in muscle quality will be associated with improvements in glucose homeostasis through decreases in C-reactive protein. To determine 1) if improvements in C-reactive protein concentrations occurs through losses in lean body mass; and 2) if decreases in C-reactive protein levels contribute to improvements in insulin sensitivity. 50 postmenopausal women (body mass index>26 kg/m(²)) with impaired glucose disposal (program. Outcome measures were: Glucose disposal rate: M value (by hyperinsulinemic-euglycemic clamp), body composition (total, trunk, and appendicluar). LBM and FM by DXA), LBM index (LBM (kg)/height (m(2)), body fat distribution (VAT and SAT by CT scan) and plasma high-sensitive C-reactive protein (hsCRP) and interleukin-6 (Il-6). Significant correlations were observed between Δ hsCRP levels with Δ Il-6 (r=0.33, p≤0.05), Δ total LBM index (r=0.44, p≤0.01), Δ trunk LBM (r=0.38, p≤0.01) Δ SAT (r=0.35, p≤0.05) and ∆ glucose disposal rate (r=- 0.44, p≤0.01). After including all the correlated variables in Stepwise linear regression model, Δ LBM index was the only independent predictor of the reduction in hsCRP levels (R(2)=0.20, p≤0.01). Losses in total lean body mass are independently associated with improvements in inflammatory state (CRP levels) in obese postmenopausal women with impaired glucose disposal. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Cytokine and C-reactive protein profiles induced by porcine circovirus type 2 experimental infection in 3-week-old piglets

    DEFF Research Database (Denmark)

    Stevenson, L.S.; McCullough, K.; Vincent, I.

    2006-01-01

    The purpose of this study was to determine serum profiles of cytokines at a protein level and C-reactive protein (CRP) during the development of postweaning multisystemic wasting syndrome (PMWS) in experimentally inoculated pigs. Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined...

  14. [Relationship between C-reactive protein gene polymorphaisms and chronic periodontitis].

    Science.gov (United States)

    Liu, Juan; Meng, Shu; Ding, Yi; Wu, Ya-fei

    2010-06-01

    To investigate the relationship between C-reactive protein (CRP) + 1444C/T, CRP+1059G/C polymorphisms and chronic periodontitis (CP) in a Han Chinese population. Clinical periodontal parameters [attachment loss (AL) probing depth (PD) and bleeding on probing (BOP)], and serum CRP levels were examined in CP patients (n = 126) and healthy subjects (n = 113). The mean serum CRP level [(1.74 ± 1.67) mg/L] was significantly higher in the CP group than in the control group [(0.57 ± 0.39) mg/L], P C allele was 6.7% (17/252) in the CP group and 4.9% (11/226) in the control group. The percentage of CRP + 1444 T allele was 6.3% (16/252) in the CP group and 5.3% (12/226) in the control group (P > 0.5). There was no significant difference between groups in both allele frequencies (P > 0.5). The association of CRP + 1059G/C, CRP + 1444 C/T polymorphisms with CP was not found in a regression model (P > 0.5). The presence of a CRP + 1059C-allele was associated with lower serum CRP levels and the presence of a CRP + 1444T-allele was associated with higher serum CRP levels. However, the data suggested that CRP + 1059G/C, CRP + 1444 C/T polymorphisms were not significantly associated with serum CRP levels of chronic periodontitis patients in ethnic Han Chinese.

  15. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer

    DEFF Research Database (Denmark)

    Allin, Kristine H; Nordestgaard, Børge G

    2011-01-01

    The aim of this review is to summarize present evidence of an association between circulating levels of C-reactive protein (CRP) and cancer risk, and to evaluate whether elevated circulating CRP levels cause cancer. Additionally, the review provides background information on the acute......-phase response, chronic inflammation, the molecular biology, function and measurement of CRP, circulating levels of CRP in health and disease, the principle of Mendelian randomization, the association between circulating levels of CRP and cancer prognosis, and cancer biomarkers. In the Copenhagen General...... increased risk of death from breast cancer compared to patients with CRP levels...

  16. C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H: Implications for retinal inflammation

    NARCIS (Netherlands)

    Swinkels, M. (Maurice); Zhang, J.H. (Justine H.); Tilakaratna, V. (Viranga); Black, G. (Graeme); Perveen, R. (Rahat); McHarg, S. (Selina); Inforzato, A. (Antonio); Day, A.J. (Anthony J.); Clark, S.J. (Simon J.)

    2018-01-01

    textabstractRetinal inflammation plays a key role in the progression of age-related macular degeneration (AMD), a condition that leads to loss of central vision. The deposition of the acute phase pentraxin C-reactive protein (CRP) in the macula activates the complement system, thereby contributing

  17. Prognostic influence of pre-operative C-reactive protein in node-negative breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Isabel Sicking

    Full Text Available The importance of inflammation is increasingly noticed in cancer. The aim of this study was to analyze the prognostic influence of pre-operative serum C-reactive protein (CRP in a cohort of 148 lymph node-negative breast cancer patients. The prognostic significance of CRP level for disease-free survival (DFS, metastasis-free survival (MFS and overall survival (OS was evaluated using univariate and multivariate Cox regression, also including information on age at diagnosis, tumor size, tumor grade, estrogen receptor (ER, progesterone receptor (PR and human epidermal growth factor receptor 2 (HER2 status, proliferation index (Ki67 and molecular subtype, as well as an assessment of the presence of necrosis and inflammation in the tumor tissue. Univariate analysis showed that CRP, as a continuous variable, was significantly associated with DFS (P = 0.002, hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.02-1.07 and OS (P = 0.036, HR= 1.03, 95% CI = 1.00-1.06, whereas a trend was observed for MFS (P = 0.111. In the multivariate analysis, CRP retained its significance for DFS (P = 0.033, HR= 1.01, 95% CI = 1.00-1.07 as well as OS (P = 0.023, HR= 1.03, 95% CI = 1.00-1.06, independent of established prognostic factors. Furthermore, large-scale gene expression analysis by Affymetrix HG-U133A arrays was performed for 72 (48.6% patients. The correlations between serum CRP and gene expression levels in the corresponding carcinoma of the breast were assessed using Spearman's rank correlation, controlled for false-discovery rate. No significant correlation was observed between CRP level and gene expression indicative of an ongoing local inflammatory process. In summary, pre-operatively elevated CRP levels at the time of diagnosis were associated with shorter DFS and OS independent of established prognostic factors in node-negative breast cancer, supporting a possible link between inflammation and

  18. C Reactive protein and disease severity in bronchiolitis

    Directory of Open Access Journals (Sweden)

    S. Costa

    2009-01-01

    Full Text Available A diagnosis of bronchiolitis is made clinically and the use of supportive laboratory examinations, including the quantification of C reactive protein (CRP, is not well established.The aim of this study was to evaluate the correlation between CRP value and indirect markers of disease severity in patients with bronchiolitis.This study included the patients diagnosed with bronchiolitis admitted to the Pediatrics Department of S. João Hospital in 2006. A retrospective review was made through analysing clinical files.176 patients aged 0 to 36 months (median of 4 months were included. 63.1% were males. CRP level was measured in 94.3% of the patients, with values ranging from zero to 256 mg/L and a median of 11 mg/L.CRP value in this population had a statistically significant relation with admission to Intensive Care Unit (ICU (p=0.008, length of hospital stay (p=0.025 and need for supplementary oxygen during hospital stay (p=0.022.This work raises the hypothesis that the CRP value on admission might be a marker of disease severity and have prognostic significance in patients with bronchiolitis. Further investigation is necessary to validate these results and exclude the potential confounding effect of associated infections. Resumo: O diagnóstico de bronquiolite aguda é essencialmente clínico. A utilidade de exames laboratoriais, em particular do doseamento da proteína C reactiva (PCR, não está bem estabelecida.O objectivo deste trabalho foi avaliar a relação entre o valor da PCR e os marcadores indirectos de gravidade em doentes com diagnóstico de bronquiolite.Foram incluídos no estudo todos os doentes admitidos no Serviço de Pediatria do HSJ durante o ano de 2006 e que tiveram como diagnóstico principal bronquiolite, tendo sido feita uma revisão retrospectiva do processo clínico desses doentes.Foram incluídos 176 doentes com idades compreendidas entre zero e 36 meses (mediana de 4 meses; 63,1% eram do sexo masculino. O doseamento da

  19. Label-free detection of C-reactive protein using reflectometric interference spectroscopy-based sensing system

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyung Woo; Sakata, Yasuhiko [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan); Kurihara, Yoshikazu [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan); KONICA MINOLTA OPTO, Inc., 1 Sakura-machi, Hino-shi, Tokyo 191-8511 (Japan); Ooya, Tooru [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan); Takeuchi, Toshifumi, E-mail: takeuchi@gold.kobe-u.ac.jp [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan)

    2012-05-30

    Highlights: Black-Right-Pointing-Pointer A new RIfS-based label-free biosensing system for C-reactive protein was developed. Black-Right-Pointing-Pointer Silicon-based inexpensive chips and the simple optical setup were employed. Black-Right-Pointing-Pointer Owing to the TMS treatment and the use of protein A, the sensitivity was enhanced. Black-Right-Pointing-Pointer It can be applied to other target as a substitute of SPR-based expensive sensors. - Abstract: Reflectometric interference spectroscopy (RIfS) is a label-free, time-resolved technique, and suitable for detecting antibody-antigen interaction. This work describes a continuous flow biosensor for C-reactive protein (CRP), involving an effective immobilization method of a monoclonal antibody against CRP (anti-CRP) to achieve highly sensitive RIfS-based detection of CRP. The silicon nitride-coated silicon chip (SiN chip) for the RIfS sensing was first treated with trimethylsilylchloride (TMS), followed by UV-light irradiation to in situ generation of homogeneous silanols on the surface. Following amination by 3-aminopropyltriethoxysilane, carboxymethyldextran (CMD) was grafted, and subsequently, protein A was immobilized to create the oriented anti-CRP surface. The immobilization process of protein A and anti-CRP was monitored with the RIfS system by consecutive injections of an amine coupling reagent, protein A and anti-CRP, respectively, to confirm the progress of each step in real time. The sensitivity was enhanced when all of the processes were adopted, suggesting that the oriented immobilization of anti-CRP via protein A that was coupled with the grafted CMD on the aminated surface of TMS-treated SiN chip. The feasibility of the present sensing system was demonstrated on the detection of CRP, where the silicon-based inexpensive chips and the simple optical setup were employed. It can be applied to other target molecules in various fields of life science as a substitute of surface plasmon resonance

  20. β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat.

    Science.gov (United States)

    Wohleb, Eric S; Hanke, Mark L; Corona, Angela W; Powell, Nicole D; Stiner, La'Tonia M; Bailey, Michael T; Nelson, Randy J; Godbout, Jonathan P; Sheridan, John F

    2011-04-27

    Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.

  1. Modified C-reactive protein is expressed by stroke neovessels and is a potent activator of angiogenesis in vitro.

    Science.gov (United States)

    Slevin, Mark; Matou-Nasri, Sabine; Turu, Marta; Luque, Ana; Rovira, Norma; Badimon, Lina; Boluda, Susana; Potempa, Lawrence; Sanfeliu, Coral; de Vera, Nuria; Krupinski, Jerzy

    2010-01-01

    Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen-glucose deprivation and mCRP (but not column purified nCRP) associated with the endothelial cell surface, and was angiogenic to vascular endothelial cells, stimulating migration and tube formation in matrigel more strongly than fibroblast growth factor-2. The mechanism of signal transduction was not through the CD16 receptor. Western blotting showed that mCRP stimulated phosphorylation of the key down-stream mitogenic signalling protein ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the angiogenic effects of mCRP. We propose that mCRP may contribute to the neovascularization process and because of its abundant presence, be important in modulating angiogenesis in both acute stroke and later during neuro-recovery.

  2. Effect of mobile phone use on salivary concentrations of protein, amylase, lipase, immunoglobulin A, lysozyme, lactoferrin, peroxidase and C-reactive protein of the parotid gland.

    Science.gov (United States)

    Hashemipour, M S; Yarbakht, M; Gholamhosseinian, A; Famori, H

    2014-05-01

    The possibility of side effects associated with the electromagnetic waves emitted from mobile phones is a controversial issue. The present study aimed to evaluate the effect of mobile phone use on parotid gland salivary concentrations of protein, amylase, lipase, immunoglobulin A, lysozyme, lactoferrin, peroxidase and C-reactive protein. Stimulated salivary samples were collected simultaneously from both parotid glands of 86 healthy volunteers. Salivary flow rate and salivary concentrations of proteins, amylase, lipase, lysozyme, lactoferrin, peroxidase, C-reactive protein and immunoglobulin A, were measured. Data were analysed using t-tests and one-way analyses of variance. Salivary flow rate and parotid gland salivary concentrations of protein were significantly higher on the right side compared to the left in those that predominantly held mobile phones on the right side. In addition, there was a decrease in concentrations of amylase, lipase, lysozyme, lactoferrin and peroxidase. The side of dominant mobile phone use was associated with differences in salivary flow rate and parotid gland salivary concentrations, in right-dominant users. Although mobile phone use influenced salivary composition, the relationship was not significant.

  3. Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFκB-C/EBP-β complex formation

    NARCIS (Netherlands)

    Kleemann, R.; Gervois, P.P.; Verschuren, L.; Staels, B.; Princen, H.M.G.; Kooistra, T.

    2003-01-01

    C-reactive protein (CRP) is a major acute-phase protein in humans. Elevated plasma CRP levels are a risk factor for cardiovascular disease. CRP is predominantly expressed in hepatocytes and is induced by interleukin-1 (IL-1) and IL-6 under inflammatory situations, such as the acute phase. Fibrates

  4. Effects of Different Exercise Intensities with Isoenergetic Expenditures on C-Reactive Protein and Blood Lipid Levels

    Science.gov (United States)

    Tsao, Te Hung; Yang, Chang Bin; Hsu, Chin Hsing

    2012-01-01

    We investigated the effects of different exercise intensities on C-reactive protein (CRP), and whether changes in CRP levels correlated with blood lipid levels. Ten men exercised at 25%, 65%, and 85% of their maximum oxygen consumption rates. Participants' blood was analyzed for CRP and blood lipid levels before and after the exercise sessions.…

  5. Aptamer-conjugated live human immune cell based biosensors for the accurate detection of C-reactive protein

    OpenAIRE

    Hwang, Jangsun; Seo, Youngmin; Jo, Yeonho; Son, Jaewoo; Choi, Jonghoon

    2016-01-01

    C-reactive protein (CRP) is a pentameric protein that is present in the bloodstream during inflammatory events, e.g., liver failure, leukemia, and/or bacterial infection. The level of CRP indicates the progress and prognosis of certain diseases; it is therefore necessary to measure CRP levels in the blood accurately. The normal concentration of CRP is reported to be 1?3?mg/L. Inflammatory events increase the level of CRP by up to 500 times; accordingly, CRP is a biomarker of acute inflammator...

  6. An Evaluation of Serum Procalcitonin and C-Reactive Protein Levels as Diagnostic and Prognostic Biomarkers of Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Szederjesi Janos

    2015-10-01

    Full Text Available Background: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR, urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body. The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis.

  7. Sport-based physical activity recommendations and modifications in C-reactive protein and arterial thickness.

    Science.gov (United States)

    Cayres, Suziane Ungari; de Lira, Fabio Santos; Kemper, Han C G; Codogno, Jamile Sanches; Barbosa, Maurício Fregonesi; Fernandes, Romulo Araújo

    2018-04-01

    We analyzed the effects of 1 year of engagement in ≥ 300 min/week of organized sports on inflammatory levels and vascular structure in adolescents. The sample was composed of 89 adolescents (11.6 ± 0.7 years old [43 boys and 46 girls]), stratified according to engagement in ≥ 300 min/week of sport practice during at least 12 months of follow-up (n = 15, sport practice; n = 74, non-sport practice). Arterial thickness (carotid and femoral) was assessed by ultrasound scan, while high sensitive C-reactive protein levels were used to assess inflammatory status. Trunk fatness (densitometry scanner), biological maturation (age at peak height velocity), blood pressure, and skipping breakfast were treated as covariates. Independently of body fatness and biological maturation, the group engaged in sports presented a higher reduction in C-reactive protein (mean difference -1.559 mg/L [95%CI -2.539 to -0.579]) than the non-sport group (mean difference -0.414 mg/L [95%CI -0.846 to 0.017]) (p = 0.040). There was a significant relationship between changes in C-reactive protein and changes in femoral intima-media thickness in the non-sport group (r = 0.311 [95%CI 0.026 to 0.549]). Inflammation decreased in adolescents engaged in organized sports, independently of trunk fatness and biological maturation. Moreover, inflammation was related to arterial thickening only in adolescents not engaged in sports. What is Known: • Intima media thickness is a relevant marker of cardiovascular disease in pediatric groups, being affected by obesity and inflammation. • The importance of monitoring inflammatory markers from childhood is enhanced by the fact that alterations in these inflammatory markers in early life predict inflammation and alterations in carotid IMT in adulthood. What is New: • Anti-inflammatory properties related to physical exercise performed at moderate intensity, on inflammation and alterations in IMT are not clear in pediatric

  8. High-sensitive C-reactive protein is associated with reduced lung function in young adults

    DEFF Research Database (Denmark)

    Rasmussen, Finn; Mikkelsen, Dennis; Hancox, Robert

    2009-01-01

    levels of CRP at age 20 yrs were associated with a greater reduction in both FEV(1) and forced vital capacity between ages 20 and 29 yrs. The findings show that higher levels of C-reactive protein in young adults are associated with subsequent decline in lung function, suggesting that low-grade systemic...... inflammation in young adulthood may lead to impaired lung function independently of the effects of smoking, obesity, cardiorespiratory fitness, asthma and eosinophilic inflammation....

  9. Effect of nigella sativa seeds extract on serum c-reactive protein in albino rats

    International Nuclear Information System (INIS)

    Bashir, M.U.; Qureshi, H.

    2014-01-01

    C-reactive protein (CRP) is an acute phase protein. It predicts future risk of cardiovascular diseases. Different medicinal plants and their active ingredients possess the ability to reduce serum CRP levels and hence inflammatory disorders and cardiovascular diseases. In our study, ethanolic extract of Nigella sativa seeds was evaluated in albino rats for its possible effect on serum CRP levels. Objective: The objective of this study was to determine the effect of ethanolic extract of Nigella sativa seeds on an acute inflammatory biomarker/mediator, C-reactive protein (CRP) in albino rats. Study Design: Randomized controlled trial (RCT). Place and Duration of Study: Physiology Department, Services Institute of Medical Sciences (SIMS), Lahore; from September to November, 2009. Subjects and Methods: The study was carried out on 90 male albino rats. Five percent (5%) formalin in a dose of 50 meu1 was injected into sub-plantar surface of right hind paw of each rat to produce inflammation. The rats were randomly divided into three groups of thirty each. Group A was given normal saline (control); group B was given Nigella sativa seed extract; and group C received diclofenac sodium, as a reference drug. CRP levels in each group were measured from blood samples taken 25 hours after giving formalin. Results: The ethanolic extract of Nigella sativa seeds, given intraperitoneally, caused highly significant (p<0.001) reduction in serum CRP levels as compared to control group. The reduction in CRP levels by ethanolic extract of Nigella sativa was also significantly (p<0.05) more than that produced by diclofenac sodium. Conclusion: Our results suggest that Nigella sativa possesses ability to reduce serum CRP levels significantly, after production of artificial inflammation, in albino rats. (author)

  10. C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach

    DEFF Research Database (Denmark)

    Dahl, Morten; Vestbo, Jørgen; Zacho, Jeppe

    2011-01-01

    Background It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design. Methods The authors measured high......-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32¿652 individuals from the Copenhagen General Population Study. Results Elevated...... plasma CRP >3 mg/l compared with Study and the Copenhagen General Population Study, respectively. Genotype combinations...

  11. C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease

    DEFF Research Database (Denmark)

    Madsen, Trine; Skou, Helle Aarup; Hansen, Vibeke Ellegaard

    2001-01-01

    The acute-phase reactant C-reactive protein (CRP) has emerged as an independent risk factor for coronary artery disease. Experimental and clinical studies provide evidence of anti-inflammatory effects of n-3 polyunsaturated fatty acids (PUFA) derived from fish. We have studied the effect of marin.......003). The inverse correlation between CRP and DHA may reflect an anti-inflammatory effect of DHA in patients with stable coronary artery disease and suggest a novel mechanism by which fish consumption may decrease the risk of coronary artery disease. (C) 2001 by Excerpta Medica, Inc....

  12. Plasminogen activator inhibitor-2 polymorphism associates with recurrent coronary event risk in patients with high HDL and C-reactive protein levels.

    Directory of Open Access Journals (Sweden)

    James P Corsetti

    Full Text Available The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C and C-reactive protein (CRP and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2 were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1, a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095 and LRP-1 (LRP1, rs1800156 as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272, p22phox (CYBA, rs4673, and thrombospondin-4 (THBS4, rs1866389. Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014 along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked

  13. Evaluation of plasma C-reactive protein levels in pregnant women with and without periodontal disease: A comparative study.

    Science.gov (United States)

    Sharma, Anupriya; Ramesh, Amitha; Thomas, Biju

    2009-09-01

    Circulating C-reactive protein (CRP) levels are a marker of systemic inflammation and are associated with periodontal disease, a chronic bacterial infection associated with elevation of proinflammatory cytokines and prostaglandins. CRP has been associated with adverse pregnancy outcomes, including preterm delivery, preeclampsia, and intrauterine growth restriction. Furthermore, periodontal disease has been associated with increased risk of preterm low birth weight, low birth weight, and preterm birth. The present study was conducted to assess plasma CRP levels in pregnant women with and without periodontal disease; to evaluate the effect of periodontal therapy on the incidence of preterm delivery; and to compare the incidence of preterm delivery in pregnant women with and without periodontal disease. A total of 90 pregnant women aged between 18-35 years with gestational age between 12-28 weeks were recruited and divided into three equal groups (control group, study group, treatment group) of 30 each. Blood samples were taken for estimation of C-reactive protein levels from all groups at 12-20 weeks of gestation, determined using ultrasensitive turbidimetric immunoassay (QUANTIA-CRP US). The treatment group comprised plaque control, scaling, and root planning and daily rinsing with 0.2% chlorhexidine mouth before 28 weeks of gestation. The mean value of C-reactive protein levels in subjects with periodontal disease was higher compared to control group i.e., 1.20 +/- 0.247 mg/dl and 1.22 +/- 0.250 mg/dl, respectively, compared to 0.713 +/- 0.139 mg/ dl (P = 0.001). The mean value of CRP levels before treatment was greater than the mean value after treatment i.e., 1.22 +/- 0.25 compared to 0.84 +/- 0.189 (P periodontal disease group (study group) compared to 8.3% in the control group (P = 0.001). The incidence of preterm delivery in the treatment group was 15.0% compared to 31.7% in the nontreatment group (study group). The findings from the study suggest that

  14. A Letter to the Editor: Using C-reactive protein to suggest an alternative explanation of the findings of Simanek et al

    DEFF Research Database (Denmark)

    Mortensen, Laust Hvas

    2011-01-01

    , Zacho J, Friberg J, Jensen GB, Tybjaerg-Hansen A, Benn M (2010) Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian randomization of 47,000 individuals from the general population. J Am Coll Cardiol 56: 789-795. S0735-1097(10)02305-3 [pii];10.1016/j.jacc.2010.02.066 [doi]. 9....... Timpson NJ, Lawlor DA, Harbord RM, Gaunt TR, Day IN, Palmer LJ, Hattersley AT, Ebrahim S, Lowe GD, Rumley A, Davey SG (2005) C-reactive protein and its role in metabolic syndrome: mendelian randomisation study. Lancet 366: 1954-1959. S0140-6736(05)67786-0 [pii];10.1016/S0140-6736(05)67786-0 [doi]. 10...

  15. Association of Periodontal Diseases with Elevation of Serum C-reactive Protein and Body Mass Index.

    Science.gov (United States)

    Chitsazi, Mohammad Taghi; Pourabbas, Reza; Shirmohammadi, Adileh; Ahmadi Zenouz, Gazaleh; Vatankhah, Amir Hossein

    2008-01-01

    C-reactive protein (CRP) is a well-known acute-phase reactant produced by the liver in response to inflammation caused by various stimuli. Periodontal disease is a chronic infection of tooth-supporting structures characterized by attachment loss and alveolar bone loss. The aim of this study was to assess the relationship between serum C-reactive protein levels and periodontal diseases. The study was conducted on 166 patients referring to Tabriz Faculty of Dentistry. The age range was between 35 and 59 years. 83 subjects with periodontitis according to NHANES III index as test group and 83 healthy individuals as controls participated in this study. Body mass index (BMI), waist circumference (WC), probing depth, attachment loss and CRP levels were measured in both test and control groups. Data was analyzed with Student's t-test, odds ratio (OR), Chi-square test and Spearman's correlation coefficient, using SPSS 13.0 software. The results revealed a statistically significant difference between all of the analyzed variables in test and control groups (P periodontitis and attachment loss (r = 0.662, P = 0.00). Excluding overweight, the association between all the variables was statistically significant (P periodontal disease is correlated with CRP elevation and dis-eases associated with obesity.

  16. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis

    DEFF Research Database (Denmark)

    Kaptoge, Stephen; Di Angelantonio, Emanuele; Lowe, Gordon

    2010-01-01

    Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances....

  17. Does C-reactive protein independently predict mortality in adult community-acquired bacteremia patients with known sepsis severity?

    DEFF Research Database (Denmark)

    Gradel, Kim O; Jensen, Thøger G; Kolmos, Hans J

    2013-01-01

    We evaluated whether sepsis severity and C-reactive protein (CRP) level on admission prognostically corroborated or annulled each other in adult patients with incident community-acquired bacteremia (Funen, Denmark, 2000-2008). We used logistic regression and area under the receiver operating.......06), thus CRP contributed as much as sepsis severity to prognosis....

  18. Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding

    Directory of Open Access Journals (Sweden)

    Robert Gustafsson

    2018-04-01

    Full Text Available Botulinum neurotoxins (BoNTs are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G. Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C as their protein receptors. We here present a high resolution (2.0 Å co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain. The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction. Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.

  19. Elevated C-reactive protein, depression, somatic diseases, and all-cause mortality

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Orsted, David Dynnes; Nordestgaard, Børge Grønne

    2014-01-01

    BACKGROUND: Elevated levels of plasma C-reactive protein (CRP) have been associated with many diseases including depression, but it remains unclear whether this association is causal. We tested the hypothesis that CRP is causally associated with depression, and compared these results to those...... for cancer, ischemic heart disease, chronic obstructive pulmonary disease, and all-cause mortality. METHODS: We performed prospective and instrumental variable analyses using plasma CRP levels and four CRP genotypes on 78,809 randomly selected 20- to 100-year-old men and women from the Danish general...... population. End points included hospitalization or death with depression and somatic diseases, prescription antidepressant medication use, and all-cause mortality. RESULTS: A doubling in plasma CRP yielded an observed odds ratio (OR) of 1.28 (95% confidence interval [CI]: 1.23-1.33) for hospitalization...

  20. Variation in C - reactive protein response according to host and mycobacterial characteristics in active tuberculosis

    OpenAIRE

    Brown, James; Clark, Kristina; Smith, Colette; Hopwood, Jennifer; Lynard, Oliver; Toolan, Michael; Creer, Dean; Barker, Jack; Breen, Ronan; Brown, Tim; Cropley, Ian; Lipman, Marc

    2016-01-01

    Background The C - reactive protein (CRP) response is often measured in patients with active tuberculosis (TB) yet little is known about its relationship to clinical features in TB, or whether responses differ between ethnic groups or with different Mycobacterium tuberculosis (M.tb) strain types. We report the relationship between baseline serum CRP prior to treatment and disease characteristics in a metropolitan population with TB resident in a low TB incidence region. Methods People treated...

  1. Purification of the active C5a receptor from human polymorphonuclear leukocytes as a receptor - Gi complex

    International Nuclear Information System (INIS)

    Rollins, T.E.; Siciliano, S.; Kobayashi, S.; Cianciarulo, D.N.; Bonilla-Argudo, V.; Collier, K.; Springer, M.S.

    1991-01-01

    The authors have isolated, in an active state, the C5a receptor from human polymorphonuclear leukocytes. The purification was achieved in a single step using a C5a affinity column in which the C5a molecule was coupled to the resin through its N terminus. The purified receptor, like the crude solubilized molecule, exhibited a single class of high-affinity binding sites with a K d of 30 pM. Further, the binding of C5a retained its sensitivity to guanine nucleotides, implying that the purified receptor contained a guanine nucleotide-binding protein (G protein). SDS/PAGE revealed the presence of three polypeptides with molecular masses of 42, 40, and 36 kDa, which were determined to be the C5a-binding subunit and the α and β subunits of G i , respectively. The 36- and 40-kDa polypeptides were identified by immunoblotting and by the ability of pertussis toxin to ADP-ribosylate the 40-kDa molecule. These results confirm their earlier hypothesis that the receptor exists as a complex with a G protein in the presence or absence of C5a. The tight coupling between the receptor and G protein should make possible the identification of the G protein(s) involved in the transduction pathways used by C5a to produce its many biological effects

  2. The Complementary Role of High Sensitivity C-Reactive Protein in the Diagnosis and Severity Assessment of Autism

    Science.gov (United States)

    Khakzad, Mohammad Reza; Javanbakht, Maryam; Shayegan, Mohammad Reza; Kianoush, Sina; Omid, Fatemeh; Hojati, Maryam; Meshkat, Mojtaba

    2012-01-01

    C-reactive protein (CRP) is a beneficial diagnostic test for the evaluation of inflammatory response. Extremely low levels of CRP can be detected using high-sensitivity CRP (hs-CRP) test. A considerable body of evidence has demonstrated that inflammatory response has an important role in the pathophysiology of autism. In this study, we evaluated…

  3. The porcine acute phase response to infection with Actinobacillus pleuropneumoniae. Haptoglobin, C-reactive protein, major acute phase protein and serum amyloid a protein are sensitive indicators of infection

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Klausen, Joan; Nielsen, J.P.

    1998-01-01

    response peaking at around 2 days after infection. Haptoglobin, C-reactive protein (CRP), and major acute phase protein (MAP) responded with large increases in serum levels, preceding the development of specific antibodies by 4-5 days. Serum amyloid A protein (SAA) was also strongly induced. The increase......, kinetics of induction and normalization were different between these proteins. It is concluded that experimental Ap-infection by the aerosol route induces a typical acute phase reaction in the pig, and that pig Hp, CRP, MAP, and SAA are major acute phase reactants. These findings indicate the possibility...

  4. Neuronal low-density lipoprotein receptor-related protein 1 binds and endocytoses prion fibrils via receptor cluster 4

    DEFF Research Database (Denmark)

    Jen, Angela; Parkyn, Celia J; Mootoosamy, Roy C

    2010-01-01

    For infectious prion protein (designated PrP(Sc)) to act as a template to convert normal cellular protein (PrP(C)) to its distinctive pathogenic conformation, the two forms of prion protein (PrP) must interact closely. The neuronal receptor that rapidly endocytoses PrP(C) is the low......-density lipoprotein receptor-related protein 1 (LRP1). We show here that on sensory neurons LRP1 is also the receptor that binds and rapidly endocytoses smaller oligomeric forms of infectious prion fibrils, and recombinant PrP fibrils. Although LRP1 binds two molecules of most ligands independently to its receptor...... both prion and LRP1 biology....

  5. Endothelial Protein C Receptor and Pediatric Arterial Stroke

    Directory of Open Access Journals (Sweden)

    Nejat Akar

    2013-03-01

    Full Text Available Objective: The aim of this study was to investigate the endothelial protein C receptor (EPCR gene A3 haplotype and plasma soluble EPCR (sEPCR levels in Turkish pediatric arterial stroke patients. Materials and Methods: We analyzed 44 pediatric arterial stroke patients and 75 healthy controls. Following DNA isolation, genotyping of the A3 haplotype was determined via PCR and RFLP. Additionally, fasting sEPCR levels were determined via ELISA. Results: There wasn’t a significant difference in the sEPCR level between the control and patient groups, although the sEPCR level was higher in the patient group. We didn’t observe a difference in the distribution of the CC and CG/GG genotypes between the control and patient groups. Conclusion: Further study on sEPCR levels at the onset of pediatric stroke is needed in order to reach a more definitive conclusion.

  6. The routine use of C-reactive protein in forensic investigations

    DEFF Research Database (Denmark)

    Astrup, B S; Thomsen, Jørgen Lange

    2007-01-01

    with special reference to the cause of death and survival time, Forensic Sci. Int. 130 (2002) 160-166; L. Uhlin-Hansen, C-reactive protein (CRP), a comparison of pre- and post-mortem blood levels, Forensic Sci. Int. 124 (2001) 32-35]. We have analysed the routine use of CRP in non-selected cases. Scarcity...... of blood available for analysis is a common problem in forensic investigation, and in response to this we have developed a method using liver as a source. In 50 consecutive autopsy cases, we have evaluated method, validated results and discussed their interpretation. In three cases the analysis......, and liver is a good post-mortem alternative when blood is not available. We conclude that CRP measurements are easy, viable and inexpensive in a forensic setting, and that the number of cases with CRP elevation is high in a non-selected forensic material. In cases of doubt, marked elevation of CRP...

  7. C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease : Data from the prospective PREVEND cohort

    NARCIS (Netherlands)

    Geluk, C.A.; Post, W.J.; Hillege, H.L.; Tio, R.A.; Tijssen, J.G.; van Dijk, R.B.; Dijk, Willem; Bakker, S.J.; de Jong, P.E.; van Gilst, W.H.; Zijlstra, F.

    Aims: High sensitive-C-reactive protein (hs-CRP) is associated with coronary risk, which may be explained by an association with (unstable) coronary artery disease (CAD). Until now, histopathological and angiographic studies have failed to consistently demonstrate a strong relationship. However,

  8. Are oxidized low-density lipoprotein and C-reactive protein markers of atherosclerosis in nephrotic children?

    OpenAIRE

    Rybi-Szumińska, A.; Wasilewska, A.; Michaluk-Skutnik, J.; Osipiuk-Remża, B.; Fiłonowicz, R.; Zając, M.

    2014-01-01

    Background Lipid disorders are known to be linked to disturbance in oxidative reactions and play an important role in the progression and complications of idiopathic nephrotic syndrome (INS). Aims The aim of this study was to assess oxidized low-density lipoprotein (oxLDL), high-sensitive C-reactive protein (hs-CRP) serum concentrations and other parameters of lipid metabolism in children with INS during relapse and remission of proteinuria. Methods The examination was performed on 23 childre...

  9. Effects of nutritional supplementation on periodontal parameters, carotenoid antioxidant levels, and serum C-reactive protein.

    Science.gov (United States)

    Harpenau, Lisa A; Cheema, Abida T; Zingale, Joseph A; Chambers, David W; Lundergan, William P

    2011-05-01

    Few studies have focused on the role of nutrition in periodontal disease. The purpose of this trial was to determine the effect of a nutritional supplement on gingival inflammation, bleeding, probing depth, clinical attachment level, carotenoid antioxidant level, and C-reactive protein. The test supplement, consisting of a standard multivitamin formula, as well as several phytonutrients associated with antiinflammatory/antioxidant effects, provided modest benefits in reducing inflammation; however, further studies with larger populations and longer intervention are warranted.

  10. Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kajiya, T.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Malínská, H.; Oliyarnyk, O.; Kazdová, L.; Fan, J.; Wang, J.; Kurtz, T. W.

    2011-01-01

    Roč. 57, č. 4 (2011), s. 731-737 ISSN 0194-911X R&D Projects: GA MZd(CZ) NS9759; GA MŠk(CZ) ME08006; GA MŠk(CZ) 1M0520; GA ČR(CZ) GAP301/10/0290; GA ČR GAP303/10/0505; GA AV ČR(CZ) IAA500110805 Grant - others:EC(XE) HEALTH-F4-2010-241504 Institutional research plan: CEZ:AV0Z50110509 Keywords : C-reactive protein * metabolic syndrome * transgenic rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 6.207, year: 2011

  11. C 反应蛋白在糖尿病视网膜病变中的预测价值%The value of C reactive protein in predicting diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    余旭耀

    2014-01-01

    Objective To explore the value of C-reactive protein in prediction of diabetic retinopathy .Methods From 2012 March to 2013 October ,101 case of type 2 diabetes patients were admitted to Department of Endocri-nology .according to patients with diabetic retinopathy ,the patients were divided into disease group (diabetic retinop-athy ,42 cases )and non disease group (59 cases without diabetic retinopathy ) ,respectively detect level of serum C-reactive protein in two groups of patients .Results The C-reactive protein in the serum of lesions group and no lesion serum were (2 .11 ± 0 .81)mg/L and (2 .98 ± 0 .93) mg/L group ,C-reactive protein of disease group was significant-ly higher than those of non disease patients (P<0 .05);with the retinopathy grade rising ,C-reactive protein is rising successively .Conclusion The level of C-reactive protein in serum of Patients with diabetic retinopathy would be in-creased ,gradually increasing with retinopathy classification upgraded ;it suggested that the levels of C reactive protein in type 2 diabetes mellitus retinopathy severity has some predictive value .%目的:探讨C反应蛋白和糖化血红蛋白检测在糖尿病患者视网膜病变中的临床价值。方法选取2012年3月至2013年10月该院内分泌科收治的2型糖尿病患者101例,根据患者视网膜病变并发情况,分为病变组(合并视网膜病变)42例和无病变组(未合并视网膜病变)59例,分别检测两组患者血清 C反应蛋白水平。结果病变组与无病变组患者血清C反应蛋白分别为(2.11±0.81)m g/L和(2.98±0.93)m g/L ,病变组显著高于无病变组,差异有统计学意义(P<0.05),同时随着患者视网膜病变分级的升高,C反应蛋白水平依次升高。结论糖尿病患者合并视网膜病变后血清C反应蛋白水平显著升高,并随着视网膜病变分期的升高而逐渐增强,提示C反应蛋白水平对2型糖尿病患者视网膜病变的严重程度具有一定的临床价值。

  12. In Silico Post Genome-Wide Association Studies Analysis of C-Reactive Protein Loci Suggests an Important Role for Interferons

    NARCIS (Netherlands)

    Vaez, Ahmad; Jansen, Rick; Prins, Bram P.; Hottenga, Jouke-Jan; de Geus, Eco J. C.; Boomsma, Dorret I.; Penninx, Brenda W. J. H.; Nolte, Ilja M.; Snieder, Harold; Alizadeh, Behrooz Z.

    Background Genome-wide association studies (GWASs) have successfully identified several single nucleotide polymorphisms (SNPs) associated with serum levels of C-reactive protein (CRP). An important limitation of GWASs is that the identified variants merely flag the nearby genomic region and do not

  13. In Silico Post Genome-Wide Association Studies Analysis of C-Reactive Protein Loci Suggests an Important Role for Interferons

    NARCIS (Netherlands)

    Vaez, A.; Jansen, R.; Prins, B.P.; Hottenga, J.J.; de Geus, E.J.C.; Boomsma, D.I.; Penninx, B.W.J.H.; Nolte, I.M.; Snieder, H.; Alizadeh, BZ

    2015-01-01

    Background - Genome-wide association studies (GWASs) have successfully identified several single nucleotide polymorphisms (SNPs) associated with serum levels of C-reactive protein (CRP). An important limitation of GWASs is that the identified variants merely flag the nearby genomic region and do not

  14. C-reactive protein implications in new-onset hypertension in a healthy population initially aged 65 years : the Proof study

    NARCIS (Netherlands)

    Dauphinot, Virginie; Roche, Frederic; Kossovsky, Michel P.; Schott, Anne-Marie; Pichot, Vincent; Gaspoz, Jean-Michel; Gosse, Philippe; Barthelemy, Jean-Claude

    Background Because inflammation is known to be related with several cardiovascular diseases, we sought to determine whether C-reactive protein (CRP) might precede the onset of hypertension. Methods The study population was selected from the Proof study cohort including 1011 individuals initially

  15. Canine serum C-reactive protein as a quantitative marker of the inflammatory stimulus of aseptic elective soft tissue surgery

    DEFF Research Database (Denmark)

    Kjelgaard-Hansen, Mads; Strøm, Henriette; Mikkelsen, Lars F.

    2013-01-01

    C-reactive protein (CRP) is an established serum marker for the presence of systemic inflammation in dogs. Results from previous experimental and clinical studies suggest that CRP concentrations also quantitatively reflect the degree and progress of an inflammatory process, suggesting its use...

  16. Evaluation of plasma C-reactive protein levels in pregnant women with and without periodontal disease: A comparative study

    Directory of Open Access Journals (Sweden)

    Sharma Anupriya

    2009-01-01

    Full Text Available Background and Objectives: Circulating C-reactive protein (CRP levels are a marker of systemic inflammation and are associated with periodontal disease, a chronic bacterial infection associated with elevation of proinflammatory cytokines and prostaglandins. CRP has been associated with adverse pregnancy outcomes, including preterm delivery, preeclampsia, and intrauterine growth restriction. Furthermore, periodontal disease has been associated with increased risk of preterm low birth weight, low birth weight, and preterm birth. The present study was conducted to assess plasma CRP levels in pregnant women with and without periodontal disease; to evaluate the effect of periodontal therapy on the incidence of preterm delivery; and to compare the incidence of preterm delivery in pregnant women with and without periodontal disease. Materials and Methods: A total of 90 pregnant women aged between 18-35 years with gestational age between 12-28 weeks were recruited and divided into three equal groups (control group, study group, treatment group of 30 each. Blood samples were taken for estimation of C-reactive protein levels from all groups at 12-20 weeks of gestation, determined using ultrasensitive turbidimetric immunoassay (QUANTIA-CRP US. The treatment group comprised plaque control, scaling, and root planning and daily rinsing with 0.2% chlorhexidine mouth before 28 weeks of gestation. Results: The mean value of C-reactive protein levels in subjects with periodontal disease was higher compared to control group i.e., 1.20 ± 0.247 mg/dl and 1.22 ± 0.250 mg/dl, respectively, compared to 0.713 ± 0.139 mg/ dl ( P = 0.001. The mean value of CRP levels before treatment was greater than the mean value after treatment i.e., 1.22 ± 0.25 compared to 0.84 ± 0.189 ( P < 0.001. The incidence of preterm delivery (< 37 weeks was 31.7% in the periodontal disease group (study group compared to 8.3% in the control group ( P = 0.001. The incidence of preterm

  17. C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance

    Directory of Open Access Journals (Sweden)

    Rachel V. Jimenez

    2018-03-01

    Full Text Available C-reactive protein (CRP is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE in CRP transgenic mice by shifting CD4+ T cells away from the TH1 and toward the TH2 subset. Notably, this action required the inhibitory Fcγ receptor IIB (FcγRIIB, but did not require high levels of human CRP. Herein, we sought to determine if CRP’s influence in EAE might be explained by CRP acting on dendritic cells (DC; antigen presenting cells known to express FcγRIIB. We found that CRP (50 µg/ml reduced the yield of CD11c+ bone marrow-derived DCs (BMDCs and CRP (≥5 μg/ml prevented their full expression of major histocompatibility complex class II and the co-stimulatory molecules CD86 and CD40. CRP also decreased the ability of BMDCs to stimulate antigen-driven proliferation of T cells in vitro. Importantly, if the BMDCs were genetically deficient in mouse FcγRIIB then (i the ability of CRP to alter BMDC surface phenotype and impair T cell proliferation was ablated and (ii CD11c-driven expression of a human FCGR2B transgene rescued the CRP effect. Lastly, the protective influence of CRP in EAE was fully restored in mice with CD11c-driven human FcγRIIB expression. These findings add to the growing evidence that CRP has important biological effects even in the absence of an acute phase response, i.e., CRP acts as a tonic suppressor of the adaptive immune system. The ability of CRP to suppress development, maturation, and function of DCs implicates CRP in the maintenance of peripheral T cell tolerance.

  18. Early diagnosis value of C-reactive protein in the acute pancreatitis

    International Nuclear Information System (INIS)

    Liu Zhen; Ruan Hui

    2010-01-01

    Objective: To investigate pairs of C-reactive protein (CRP) in acute pancreatitis(AP) diagnosis and disease evaluation of the value of research. Methods: One hundred and fifty cases of AP in two groups were divided into mild AP (MAP) and severe AP (SAP), in the 1 st, 3 rd, 5 th, 7 th, 9 th days after admission tests of CRP levels, dynamic observation and comparative analysis were performed. Results: CRP in all AP patients after admission was significantly higher, levels in SAP group serum CRP reached an average of (106.3 ± 15.4) mg/L which was significantly higher than that the MAP group (21.5 ± 7.6) mg/L (P < 0.01). Conclusion: CRP can be used as an early diagnosis of AP and SAP severity assessment and a prognosis indicators. (authors)

  19. Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica patients.

    Science.gov (United States)

    Uher, Tomas; Bob, Petr

    2013-03-01

    There is evidence that neuropathic pain component in low back pain (LBP) patients is associated with higher ratings of comorbidities such as depression and anxiety disorders. In line with current findings, the purpose of this clinical study is to examine a hypothesis regarding a relationship of neuropathic pain component, depression, and other psychopathological symptoms in a specific group of LBP patients with sciatica pain. With respect to findings that depression is related to inflammatory changes, and inflammatory mediators may play a role in neuropathic pain generation, we have assessed also serum C-reactive protein (CRP). Results of the present study show that increased neuropathic pain component in sciatica patients is associated with elevated levels of depression, anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study indicate that CRP levels in sciatica patients are closely associated with neuropathic pain.

  20. A Conformational Change in C-Reactive Protein Enhances Leukocyte Recruitment and Reactive Oxygen Species Generation in Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Jan R. Thiele

    2018-04-01

    Full Text Available IntroductionC-reactive protein circulates as a pentameric protein (pCRP. pCRP is a well-established diagnostic marker as plasma levels rise in response to tissue injury and inflammation. We recently described pro-inflammatory properties of CRP, which are mediated by conformational changes from pCRP to bioactive isoforms expressing pro-inflammatory neo-epitopes [pCRP* and monomeric C-reactive protein (mCRP]. Here, we investigate the role of CRP isoforms in renal ischemia/reperfusion injury (IRI.MethodsRat kidneys in animals with and without intraperitoneally injected pCRP were subjected to IRI by the time of pCRP exposure and were subsequently analyzed for monocyte infiltration, caspase-3 expression, and tubular damage. Blood urea nitrogen (BUN was analyzed pre-ischemia and post-reperfusion. CRP effects on leukocyte recruitment were investigated via intravital imaging of rat-striated muscle IRI. Localized conformational CRP changes were analyzed by immunohistochemistry using conformation specific antibodies. 1,6-bis(phosphocholine-hexane (1,6-bisPC, which stabilizes CRP in its native pentameric form was used to validate CRP effects. Leukocyte activation was assessed by quantification of reactive oxygen species (ROS induction by CRP isoforms ex vivo and in vitro through electron spin resonance spectroscopy. Signaling pathways were analyzed by disrupting lipid rafts with nystatin and subsequent ROS detection. In order to confirm the translational relevance of our findings, biopsies of microsurgical human free tissue transfers before and after IRI were examined by immunofluorescence for CRP deposition and co-localization of CD68+ leukocytes.ResultsThe application of pCRP aggravates tissue damage in renal IRI. 1,6-bisPC reverses these effects via inhibition of the conformational change that leads to exposure of pro-inflammatory epitopes in CRP (pCRP* and mCRP. Structurally altered CRP induces leukocyte–endothelial interaction and induces ROS

  1. C-reactive protein (+1444C>T) polymorphism influences CRP response following a moderate inflammatory stimulus.

    Science.gov (United States)

    D'Aiuto, Francesco; Casas, Juan P; Shah, Tina; Humphries, Steve E; Hingorani, Aroon D; Tonetti, Maurizio S

    2005-04-01

    Elevations in C-reactive protein (CRP) concentration are associated with an increased risk of future coronary events in prospective studies and it has been suggested that CRP could be used to aid risk prediction. A +1444C>T polymorphism in the CRP gene has been associated with differences in CRP concentration. We investigated the effect of this polymorphism on the CRP response to periodontal therapy, an intermediate inflammatory stimulus. Clinical parameters, CRP, and interleukin-6 (IL-6) concentrations were evaluated in 55 consecutive patients suffering from periodontitis at baseline, 1, 7 and 30 days after an intensive course of periodontal treatment. In a multivariate analysis individuals homozygous for the +1444T allele showed higher CRP concentrations (day 1, 21.10+/-4.81 mg/L and day 7, 4.89+/-0.74 mg/L) compared with C-allele carriers (day 1, 12.37+/-1.61 mg/L and day 7, 3.08+/-2.00 mg/L). This effect was independent of conventional cardiovascular risk factors and inflammatory factors known to affect CRP concentrations. CRP genotype may need to be considered when CRP values are used in coronary risk prediction.

  2. Time-Resolved Fluorescence Immunoassay for C-Reactive Protein Using Colloidal Semiconducting Nanoparticles

    Directory of Open Access Journals (Sweden)

    Pekka Hänninen

    2011-11-01

    Full Text Available Besides the typical short-lived fluorescence with decay times in the nanosecond range, colloidal II/VI semiconductor nanoparticles dispersed in buffer also possess a long-lived fluorescence component with decay times in the microsecond range. Here, the signal intensity of the long-lived luminescence at microsecond range is shown to increase 1,000-fold for CdTe nanoparticles in PBS buffer. This long-lived fluorescence can be conveniently employed for time-gated fluorescence detection, which allows for improved signal-to-noise ratio and thus the use of low concentrations of nanoparticles. The detection principle is demonstrated with a time-resolved fluorescence immunoassay for the detection of C-reactive protein (CRP using CdSe-ZnS nanoparticles and green light excitation.

  3. C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques

    DEFF Research Database (Denmark)

    Pilely, Katrine; Fumagalli, Stefano; Rosbjerg, Anne

    2017-01-01

    Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are seru...

  4. Collaborative pooled analysis of data on C-reactive protein gene variants and coronary disease: judging causality by Mendelian randomisation

    DEFF Research Database (Denmark)

    Danesh, J.; Hingorani, A.; Wensley, F.

    2008-01-01

    Many prospective studies have reported associations between circulating C-reactive protein (CRP) levels and risk of coronary heart disease (CHD), but causality remains uncertain. Studies of CHD are being conducted that involve measurement of common polymorphisms of the CRP gene known to be associ...

  5. Elevated C-reactive protein and hypoalbuminemia measured before resection of colorectal liver metastases predict postoperative survival.

    Science.gov (United States)

    Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

    2010-01-01

    Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score measured before resection of colorectal liver metastasis (CRLM), can predict postoperative survival. Sixty-three consecutive patients who underwent curative resection for CRLM were investigated. GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminemia (l) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. Significant factors concerning survival were the number of liver metastases (p = 0.0044), carcinoembryonic antigen level (p = 0.0191), GPS (p = 0.0029), grade of liver metastasis (p = 0.0033), and the number of lymph node metastases around the primary cancer (p = 0.0087). Multivariate analysis showed the two independent prognostic variables: liver metastases > or =3 (relative risk 2.83) and GPS1/2 (relative risk 3.07). GPS measured before operation and the number of liver metastases may be used as novel predictors of postoperative outcomes in patients who underwent curative resection for CRLM. Copyright 2010 S. Karger AG, Basel.

  6. Moderate, but not vigorous, intensity exercise training reduces C-reactive protein.

    Science.gov (United States)

    Fedewa, Michael V; Hathaway, Elizabeth D; Higgins, Simon; Forehand, Ronald L; Schmidt, Michael D; Evans, Ellen M

    2018-06-01

    Sprint interval cycle training is a contemporary popular mode of training but its relative efficacy, under conditions of matched energy expenditure, to reduce risk factors for cardiometabolic disease is incompletely characterised, especially in young women. The purpose of this investigation was to determine the relative efficacy of six weeks of moderate-intensity cycling (MOD-C) and vigorous sprint-interval cycling (VIG-SIC) on lipid profile, insulin (INS) and insulin resistance using the homeostatic model assessment (HOMA-IR) and C-reactive protein (CRP) in inactive, overweight/obese (OW/OB) young women. Participants (BMI ≥25 kg/m 2 , waist circumference ≥88 cm) were randomly assigned to MOD-C (20-30 min at 60-70% of heart rate reserve(HRR)) or VIG-SIC (5-7 repeated bouts 30-second maximal effort sprints, followed by four minutes of active recovery) supervised training three days/week for six weeks, with each group matched on energy expenditure. Adiposity (%Fat) was measured using dual x-ray absorptiometry. Forty-four participants (20.4 ± 1.6 years, 65.9% Caucasian, 29.8 ± 4.1 kg/m 2 ) were included in the analysis. The improvement in CRP observed in the MOD-C group was larger than the VIG-C group (p = .034). Overall, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels improved following training (p  .05). These results indicate MOD-C training may be more effective in reducing CRP than VIG-SIC.

  7. Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

    International Nuclear Information System (INIS)

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien; Ju, Tsai-Kai; Huang, Yuan-Li; Lee, Ming-Shyue; Chen, Jiun-Hong; Lee, Hsinyu

    2013-01-01

    Highlights: •LPA induces ROS generation through LPA 1 and LPA 3 . •LPA induces ROS generation by activating PLC. •PKCζ mediates LPA-induced ROS generation. -- Abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA 1 and LPA 3 siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway

  8. Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Ju, Tsai-Kai [Instrumentation Center, National Taiwan University, Taipei, Taiwan, ROC (China); Technology Commons, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Huang, Yuan-Li [Department of Biotechnology, Asia University, Taichung, Taiwan, ROC (China); Lee, Ming-Shyue [Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC (China); Chen, Jiun-Hong [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Lee, Hsinyu, E-mail: hsinyu@ntu.edu.tw [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Center for Biotechnology, National Taiwan University, Taipei, Taiwan, ROC (China); Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan, ROC (China)

    2013-11-01

    Highlights: •LPA induces ROS generation through LPA{sub 1} and LPA{sub 3}. •LPA induces ROS generation by activating PLC. •PKCζ mediates LPA-induced ROS generation. -- Abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA{sub 1} and LPA{sub 3} siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway.

  9. Evaluation of salivary oxidate stress biomarkers, nitric oxide and C-reactive protein in patients with oral lichen planus and burning mouth syndrome.

    Science.gov (United States)

    Tvarijonaviciute, Asta; Aznar-Cayuela, Cristina; Rubio, Camila P; Ceron, José J; López-Jornet, Pia

    2017-05-01

    The aim of this study was to evaluate oxidative stress factors and C-reactive protein in the saliva of patients with oral lichen planus (OLP) and burning mouth syndrome (BMS). This consecutive, cross-sectional study included 20 patients with OLP, 19 with burning mouth syndrome (BMS), and 31 control subjects. The oral cavity of each patient was examined and patients responded to a quality of life questionnaire (OHIP-14) and the xerostomia inventory. The following parameters were measured in whole non-stimulated saliva: trolox equivalent antioxidant capacity (TEAC); total antioxidant capacity (TAC); cupric reducing antioxidant capacity (CUPRAC); ferric reducing ability of plasma (FRAP); C-reactive protein (CRP); nitric oxide; nitrates; and nitrites. The OLP group presented statistically significant differences in reactive oxygen species (ROS) (29 600 cps) in comparison with the control group (39 679 cps) (P < 0.05). In the BMS group, ROS was 29 707 cps with significant difference in comparison with the control group (P < 0.05). Significantly higher salivary nitric oxide (145.7 μmol) and nitrite (141.0 μmol) levels were found in OLP patients in comparison with control group (P < 0.05). Increases in nitric oxide and C-reactive protein were found in the saliva of OLP patients in comparison with BMS and control patients. Further studies are required to confirm these findings. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Association of pentraxin and high-sensitive C-reactive protein as inflammatory biomarkers in patients with chronic periodontitis and peripheral arterial disease.

    Science.gov (United States)

    Boyapati, Ramanarayana; Chinthalapani, Srikanth; Ramisetti, Arpita; Salavadhi, Shyam Sunder; Ramachandran, Radhika

    2018-01-01

    Inflammation is a common feature of both peripheral artery disease (PAD) and periodontal disease. The aim of this study is to evaluate the relationship between PAD and periodontal disease by examining the levels of inflammatory cytokines, pentraxin-3 (PTX-3), and high-sensitive C-reactive protein from serum. A total of 50 patients were included in this cross-sectional study. Patients were divided into two groups: those with PAD (test group) and those with the non-PAD group (control group) based on ankle-brachial index values. Periodontal examinations and biochemical analysis for PTX-3 and high-sensitive C-reactive protein were performed to compare the two groups. All the obtained data were sent for statistical analyses using SPSS version 18. In the clinical parameters, there is statistically significant difference present between plaque index, clinical attachment loss, and periodontal inflammatory surface area with higher mean values in patients with PAD having periodontitis. There is statistical significant ( P C-reactive protein (hs-CRP), and PTX-3. PTX-3 and acute-phase cytokine such as hs-CRP can be regarded as one of the best indicators to show the association between the PAD and periodontitis followed by hs-CRP, TC, very LDL (VLDL), and LDL. However, high-density lipoprotein (HDL) is a poor indicator for its association with chronic periodontitis and PAD.

  11. Structural evaluation of a nanobody targeting complement receptor Vsig4 and its cross reactivity.

    Science.gov (United States)

    Wen, Yurong; Ouyang, Zhenlin; Schoonooghe, Steve; Luo, Siyu; De Baetselier, Patrick; Lu, Wuyuan; Muyldermans, Serge; Raes, Geert; Zheng, Fang

    2017-06-01

    Vsig4 is a recently identified immune regulatory protein related to the B7 family with dual functionality: a negative regulator of T cell activation and a receptor for the complement components C3b and C3c. Here we present a structural evaluation of a nanobody, Nb119, against the extracellular IgV domain protein of both mouse and human recombinant Vsig4, which have a high degree of sequence identity. Although mouse and human Vsig4 bind to Nb119 with a 250 times difference in dissociation constants, the interaction results in a highly identical assembly with a RMSD of 0.4Å. The molecular determinants for Vsig4 recognition and cross reactivity unveiled by the atomic structure of Nb119 in complex with mVsig4 and hVsig4 afford new insights useful for the further optimization of the nanobody for potential use in humans. Additionally, structural analysis of the Vsig4-Nb119 complexes indicates that Nb119 occupies the interface on Vsig4 recognized by the macroglobulin-like domains MG4 and MG5 of C3b. Thus an affinity-improved Nb119 may have the potential to influence the activation of both T cells and complement. Copyright © 2016. Published by Elsevier GmbH.

  12. Albumin and C-reactive protein have prognostic significance in patients with community-acquired pneumonia.

    Science.gov (United States)

    Lee, Jae Hyuk; Kim, Jooyeong; Kim, Kyuseok; Jo, You Hwan; Rhee, JoongEui; Kim, Tae Youn; Na, Sang Hoon; Hwang, Seung Sik

    2011-06-01

    This study aims to determine the association of commonly used biochemical markers, such as albumin and C-reactive protein (CRP), with mortality and the prognostic performance of these markers combined with the pneumonia severity index (PSI) for mortality and adverse outcomes in patients with community-acquired pneumonia (CAP). The data were gathered prospectively for patients hospitalized with CAP via the emergency department. Laboratory values, including CRP and albumin, clinical variables, and the PSI were measured. Primary outcomes were 28-day mortality and survival times. Secondary outcome was admission to the intensive care unit, vasopressor use, or the need for mechanical ventilation during the hospital stay. A total of 424 patients were included. The 28-day mortality was 13.7%. C-reactive protein and albumin were significantly different between survivors and nonsurvivors. In logistic regression analysis, CRP and albumin were independently associated with 28-day mortality (P scale. The Cox proportional hazards analysis showed that high serum albumin (≥3.3 mg/dL) had a hazard ratio of 0.5 (95% confidence interval, 0.3-0.9), and high CRP (≥14.3 mg/dL) had a hazard ratio of 2.0 (95% confidence interval, 1.1-3.4). For predicting secondary outcome, adding albumin to PSI increased areas under the curve significantly, but CRP did not. Albumin and CRP were associated with 28-day mortality in hospitalized patients with CAP, and these markers increased prognostic performance when combined with the PSI scale. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  13. Evaluation of C-reactive protein and interleukin-6 in the peripheral blood of patients with chronic periodontitis.

    Science.gov (United States)

    Gani, Dhruva Kumar; Lakshmi, Deepa; Krishnan, Rama; Emmadi, Pamela

    2009-05-01

    The aim of the present study was to investigate systemic levels of inflammatory markers of cardiovascular diseases like C-reactive protein and interleukin-6 in patients with chronic periodontitis, in comparison to periodontally healthy individuals. A total of 42 individuals, both males and females above the age of 30 years, were included in the study. Healthy controls (Group I, n = 14), chronic localized periodontitis (Group II, n = 14), and chronic generalized periodontitis (Group III, n = 14), all without any medical disorder, were recruited. Peripheral blood samples were taken and C-reactive protein (CRP) levels were estimated in the serum samples by using the Particle-Enhanced Turbidimetric Immunoassay (PETIA) technique. Serum samples of Interleukin-6 (IL-6) were assayed by using the Chemiluminescent Immunoassay (IMMULITE) technique. When mean CRP levels were compared between the groups, group III showed statistical significance when compared to group I (P = 0.04). Group III had a higher median IL-6 level (6.35 pg/mL) than Group II (Periodontitis results in higher systemic levels of CRP and IL-6. These elevated inflammatory factors may increase inflammatory activity in atherosclerotic lesions and potentially increasing the risk for cardiovascular events.

  14. Immunoassay of C-reactive protein by hot electron induced electrochemiluminescence using integrated electrodes with hydrophobic sample confinement

    Energy Technology Data Exchange (ETDEWEB)

    Ylinen-Hinkka, T., E-mail: tiina.ylinen-hinkka@aalto.fi [Laboratory of Analytical Chemistry, Aalto University School of Chemical Technology, P.O. Box 16100, FI-00076 Aalto (Finland); Niskanen, A.J.; Franssila, S. [Department of Materials Science and Engineering, Aalto University School of Chemical Technology, P.O. Box 16200, FI-00076 Aalto (Finland); Kulmala, S. [Laboratory of Analytical Chemistry, Aalto University School of Chemical Technology, P.O. Box 16100, FI-00076 Aalto (Finland)

    2011-09-19

    Highlights: {center_dot} C-reactive protein has been determined in the concentration range 0.01-10 mg L{sup -1} using an electrochemiluminescence microchip which employs integrated electrodes with hydrophobic sample confinement. {center_dot} This arrangement enables very simple and fast CRP analysis amenable to point-of-care applications. - Abstract: C-reactive protein (CRP) was determined in the concentration range 0.01-10 mg L{sup -1} using hot electron induced electrochemiluminescence (HECL) with devices combining both working and counter electrodes and sample confinement on a single chip. The sample area on the electrodes was defined by a hydrophobic ring, which enabled dispensing the reagents and the analyte directly on the electrode. Immunoassay of CRP by HECL using integrated electrodes is a good candidate for a high-sensitivity point-of-care CRP-test, because the concentration range is suitable, miniaturisation of the measurement system has been demonstrated and the assay method with integrated electrodes is easy to use. High-sensitivity CRP tests can be used to monitor the current state of cardiovascular disease and also to predict future cardiovascular problems in apparently healthy people.

  15. Serum, plasma, and dried blood spot high sensitivity C-reactive protein enzyme immunoassay for population research

    OpenAIRE

    Brindle, Eleanor; Fujita, Masako; Shofer, Jane; O’Connor, Kathleen A.

    2010-01-01

    C-reactive protein (CRP) is used as a biomarker of morbidity and mortality risk in studies of population health, and is essential to interpretation of several micronutrient biomarkers. There is thus need for a robust high sensitivity CRP (hsCRP) measurement method for large-scale, non-clinical studies. We developed an efficient, inexpensive assay suitable for quantifying CRP across the physiological range using any blood specimen type. The ELISA uses readily available monoclonal antibodies to...

  16. Potential Mediators between Fibromyalgia and C-Reactive protein: Results from a Large U.S. Community Survey

    OpenAIRE

    Feinberg, Termeh; Sambamoorthi, Usha; Lilly, Christa; Innes, Kim Karen

    2017-01-01

    Background Fibromyalgia, a potentially debilitating chronic pain syndrome of unknown etiology, may be characterized by inflammation. In this study, we investigated the relation of FMS to serum C-reactive protein (CRP) in a large population of adults (18+) and investigated the influence of other factors on this relationship, including BMI, comorbidities, as well as mood and sleep disturbance. Methods Participants were 52,535 Ohio Valley residents (Fibromyalgia n?=?1125). All participants compl...

  17. The multiligand α2-macroglobulin receptor/low density lipoprotein receptor-related protein

    DEFF Research Database (Denmark)

    Gliemann, Jørgen; Nykjær, Anders; Petersen, Claus Munck

    1994-01-01

    The fusion of separate lines of research has greatly helped in elucidating the function of the giant members of the low density lipoprotein (LDL) receptor (LDLR) supergene family. The cDNA encoding a large protein structurally closely related to LDLR, and hence named LDLR-related protein (LRP......), was cloned by Herz et al. in 1988.'Evidence was provided demonstrating that LRP can function as a receptor for chylomicron remnants@-migrating very low density lipoproteins (P-VLDL) rich in apolipoprotein E (apoE)?' The a2-macroglobulin (a2M) receptor (a2MR) was purified from rat livep and human p l a~e n t...... from the observation that affinity-purified a2MR/LRP contains a 40-kDa5.8 or 39-kDa6.' protein, designated a2MRAP, in addition to the a2MFULRP a- and P-chains. cDNA cloning" disclosed the 323-residue protein as both the human homologue of mouse heparin binding protein 44 (see reference 11) and...

  18. Correlation between Plaque Composition as assessed by Virtual Histology and C-reactive Protein

    International Nuclear Information System (INIS)

    Siqueira, Dimytri Alexandre de Alvim; Sousa, Amanda Guerra Moraes R.; Costa Junior, José de Ribamar; Costa, Ricardo Alves da; Staico, Rodolfo; Tanajura, Luis Fernando Leite; Centemero, Marinella Patrizia; Feres, Fausto; Abizaid, Alexandre Antonio Cunha; Sousa, J. Eduardo Moraes R.

    2013-01-01

    Previous studies have shown that coronary plaque composition plays a pivotal role in plaque instability, and imaging modalities and serum biomarkers have been investigated to identify vulnerable plaque. Virtual histology IVUS (VH-IVUS) characterizes plaque components as calcified, fibrotic, fibrofatty, or necrotic core. C-reactive protein (hsCRP) is an independent risk factor and a powerful predictor of future coronary events. However, a relationship between inflammatory response indicated by CRP and plaque characteristics in ACS patients remains not well established. To determine, by using VH-IVUS, the relation between coronary plaque components and plasma high-sensitivity CRP levels in patients with acute coronary syndromes (ACS). 52 patients with ACS were enrolled in this prospective study. Electrocardiographically-gated VH-IVUS were performed in the culprit lesion before PCI. Blood sample was drawn from all patients before the procedure and after 24 hours, and hs-CRP levels were determined. Mean age was 55.3±4.9 years, 76.9% were men and 30.9% had diabetes. Mean MLA was 3.9±1.3 mm 2 , and plaque burden was 69±11.3%, as assessed by IVUS. VH-IVUS analysis at the minimum luminal site identified plaque components: fibrotic (59.6±15.8%), fibrofatty (7.6±8.2%), dense calcium (12.1±9.2%) and necrotic core (20.7±12.7%). Plasma hs-CRP (mean 16.02±18.07 mg/L) did not correlate with necrotic core (r=-0.089, p = 0.53) and other plaque components. In this prospective study with patients with ACS, the predominant components of the culprit plaque were fibrotic and necrotic core. Serum hs C-reactive protein levels did not correlate with plaque composition

  19. Correlation between Plaque Composition as assessed by Virtual Histology and C-reactive Protein

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Dimytri Alexandre de Alvim, E-mail: dimytri@cardiol.br; Sousa, Amanda Guerra Moraes R.; Costa Junior, José de Ribamar; Costa, Ricardo Alves da; Staico, Rodolfo; Tanajura, Luis Fernando Leite; Centemero, Marinella Patrizia; Feres, Fausto; Abizaid, Alexandre Antonio Cunha; Sousa, J. Eduardo Moraes R. [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP (Brazil)

    2013-07-15

    Previous studies have shown that coronary plaque composition plays a pivotal role in plaque instability, and imaging modalities and serum biomarkers have been investigated to identify vulnerable plaque. Virtual histology IVUS (VH-IVUS) characterizes plaque components as calcified, fibrotic, fibrofatty, or necrotic core. C-reactive protein (hsCRP) is an independent risk factor and a powerful predictor of future coronary events. However, a relationship between inflammatory response indicated by CRP and plaque characteristics in ACS patients remains not well established. To determine, by using VH-IVUS, the relation between coronary plaque components and plasma high-sensitivity CRP levels in patients with acute coronary syndromes (ACS). 52 patients with ACS were enrolled in this prospective study. Electrocardiographically-gated VH-IVUS were performed in the culprit lesion before PCI. Blood sample was drawn from all patients before the procedure and after 24 hours, and hs-CRP levels were determined. Mean age was 55.3±4.9 years, 76.9% were men and 30.9% had diabetes. Mean MLA was 3.9±1.3 mm{sup 2}, and plaque burden was 69±11.3%, as assessed by IVUS. VH-IVUS analysis at the minimum luminal site identified plaque components: fibrotic (59.6±15.8%), fibrofatty (7.6±8.2%), dense calcium (12.1±9.2%) and necrotic core (20.7±12.7%). Plasma hs-CRP (mean 16.02±18.07 mg/L) did not correlate with necrotic core (r=-0.089, p = 0.53) and other plaque components. In this prospective study with patients with ACS, the predominant components of the culprit plaque were fibrotic and necrotic core. Serum hs C-reactive protein levels did not correlate with plaque composition.

  20. Increased levels of C-reactive protein and leukocyte count are poor predictors of anastomotic leakage following laparoscopic colorectal resection

    DEFF Research Database (Denmark)

    Pedersen, Torben; Roikjær, Ole; Jess, Per

    2012-01-01

    Laparoscopic procedure and fast-track regimen with short post-operative hospital stay are gaining ground in colorectal surgery. The aim of the present study was to determine whether the levels of C-reactive protein (CRP) and white blood cell counts (WBC) have a role as early predictors of post...

  1. Purification of the active C5a receptor from human polymorphonuclear leukocytes as a receptor - G sub i complex

    Energy Technology Data Exchange (ETDEWEB)

    Rollins, T.E.; Siciliano, S.; Kobayashi, S.; Cianciarulo, D.N.; Bonilla-Argudo, V.; Collier, K.; Springer, M.S. (Merck Sharp and Dohme Research Lab., Rahway, NJ (United States))

    1991-02-01

    The authors have isolated, in an active state, the C5a receptor from human polymorphonuclear leukocytes. The purification was achieved in a single step using a C5a affinity column in which the C5a molecule was coupled to the resin through its N terminus. The purified receptor, like the crude solubilized molecule, exhibited a single class of high-affinity binding sites with a K{sub d} of 30 pM. Further, the binding of C5a retained its sensitivity to guanine nucleotides, implying that the purified receptor contained a guanine nucleotide-binding protein (G protein). SDS/PAGE revealed the presence of three polypeptides with molecular masses of 42, 40, and 36 kDa, which were determined to be the C5a-binding subunit and the {alpha} and {beta} subunits of G{sub i}, respectively. The 36- and 40-kDa polypeptides were identified by immunoblotting and by the ability of pertussis toxin to ADP-ribosylate the 40-kDa molecule. These results confirm their earlier hypothesis that the receptor exists as a complex with a G protein in the presence or absence of C5a. The tight coupling between the receptor and G protein should make possible the identification of the G protein(s) involved in the transduction pathways used by C5a to produce its many biological effects.

  2. Changes in Periodontal Parameters and C-Reactive Protein After Pregnancy.

    Science.gov (United States)

    Raga, Lucía Gil; Mínguez, Ignacio; Caffesse, Raul; Llambés, Fernando

    2016-12-01

    This study assesses hormonal, inflammatory, and periodontal changes in pregnant women and postpartum in the absence of periodontal treatment, and seeks to determine any correlations among these parameters. A longitudinal, observational study of 117 pregnant women (aged 23 to 42 years) was undertaken in a private gynecologic center between weeks 32 and 35 of pregnancy and 6 to 8 weeks after delivery. Levels of progesterone and C-reactive protein (CRP) in plasma were determined, as well as periodontal indices, including: 1) plaque index (PI); 2) bleeding on probing (BOP); 3) probing depth (PD); and 4) clinical attachment level (CAL). Postpartum progesterone and CRP declined sharply from 90.85 ± 42.51 ng/mL and 3.73 ± 4.01 mg/L to 0.77 ± 1.43 ng/mL and 1.43 ± 1.67 mg/L, respectively. There was also a significant improvement in all periodontal indices (P 6 mm decreased significantly (P periodontal treatment. Decrease in CRP was related to an improvement in periodontal bleeding.

  3. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

    DEFF Research Database (Denmark)

    Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

    2015-01-01

    We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes......, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress...

  4. [C-reactive protein changes with antihypertensive and statin treatment].

    Science.gov (United States)

    Rodilla, Enrique; Gómez-Belda, Ana; Costa, José A; Aragó, Miriam; Miralles, Amparo; González, Carmen; Pascual, José M

    2005-10-29

    The aim of this study was to evaluate the modifications of high sensitivity C-reactive protein (CRP) with antihypertensive and statin treatment in a hypertensive population with a wide range of coronary risks (CR). Retrospective follow-up study in 665 hypertensive patients: 556 (52% male) without dyslipidemia and CR (Framingham at 10 years) of 8.3 (7.6) as a control group (C) and 109 (61% male) with dyslipidemia and CR of 13.1 (8.8) who were treated with statins (T). Statins treatment was established according to NCEP-ATP-III. In both groups, the antihypertensive treatment was optimized in order to achieve blood pressure (BP) control (< 140/90 mmHg). A lipid profile and high sensitivity CRP (analyzed by nephelometry) was performed at the beginning and at the end of follow up [14.3 (3.6) months]. CRP levels were reduced in the T group -0.17 (0.2) mg/L vs. 0.14 (0.09) mg/L (p = 0.003, Mann-Whitney) in C. The lessening of CRP was not related to the reduction of lipids levels: total cholesterol (r = 0.06; p = 0.49), LDL-C (r = 0.11; p = 0.24), triglycerides (r = -0.02; p = 0.81) (Spearman), or to the reduction of systolic BP (r = -0.07; p = 0.44) and diastolic BP (r = -0.121; p = 0.21). The T group was treated with more antihypertensive drugs than C (2.2 [2.3] vs. 2.5 [1.2]; p = 0.02). Patients treated with ECA inhibitors or angiotensin II antagonist showed a tendency to decreasing the CRP levels more (p = 0.08). In hypertensive populations, statins induce a reduction of CRP levels. The reduction is not related to the lowering of lipids levels or BP values. The effect of statins on the reduction of CRP in hypertensive patients is not related to the lowering of lipids or BP.

  5. Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Ekström, Mattias

    2010-01-01

    The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Su...

  6. C-Reactive Protein and Coronary Heart Disease: All Said—Is Not It?

    Directory of Open Access Journals (Sweden)

    Frederik Strang

    2014-01-01

    Full Text Available C-reactive protein (CRP and coronary heart disease (CHD have been the subject of intensive investigations over the last decades. Epidemiological studies have shown an association between moderately elevated CRP levels and incident CHD whereas genetic studies have shown that polymorphisms associated with elevated CRP levels do not increase the risk of ischemic vascular disease, suggesting that CRP might be a bystander rather than a causal factor in the progress of atherosclerosis. Beside all those epidemiological and genetic studies, the experimental investigations also try to reveal the role of CRP in the progress of atherosclerosis. This review will highlight the complex results of genomic, epidemiological, and experimental studies on CRP and will show why further studies investigating the relationship between CRP and atherosclerosis might be needed.

  7. Complement system proteins which interact with C3b or C4b A superfamily of structurally related proteins

    DEFF Research Database (Denmark)

    Reid, K B M; Bentley, D R; Campbell, R D

    1986-01-01

    Recent cDNA sequencing data has allowed the prediction of the entire amino acid sequences of complement components factor B and C2, the complement control proteins factor H and C4b-binding protein and a partial sequence for the Cab/C4b receptor CR1. These proteins all contain internal repeating u...

  8. Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor α-subunits and platelet glycoprotein IIb

    International Nuclear Information System (INIS)

    Fitzgerald, L.A.; Poncz, M.; Steiner, B.; Rall, S.C. Jr.; Bennett, J.S.; Phillips, D.R.

    1987-01-01

    The fibronectin receptor (FnR), the vitronectin receptor (VnR), and the platelet membrane glycoprotein (GP) IIb-IIIa complex are members of a family of cell adhesion receptors, which consist of noncovalently associated α- and β-subunits. The present study was designed to compare the cDNA-derived protein sequences of the α-subunits of human FnR, VnR, and platelet GP IIb. cDNA clones for the α-subunit of the FnR (FnR/sub α/) were obtained from a human umbilical vein endothelial (HUVE) cell library by using an oligonucleotide probe designed from a peptide sequence of platelet GP IIb. cDNA clones for platelet GP IIb were isolated from a cDNA expression library of human erythroleukemia cells by using antibodies. cDNA clones of the VnR α-subunit (VnR/sub α/) were obtained from the HUVE cell library by using an oligonucleotide probe from the partial cDNA sequence for the VnR/sub α/. Translation of these sequences showed that the FNR/sub α/, the VnR/sub α/, and GP IIb are composed of disulfide-linked large (858-871 amino acids) and small (137-158 amino acids) chains that are posttranslationally processed from a single mRNA. A single hydrophobic segment located near the carboxyl terminus of each small chain appears to be a transmembrane domain. The large chains appear to be entirely extracellular, and each contains four repeated putative Ca 2+ -binding domains of about 30 amino acids that have sequence similarities to other Ca 2+ -binding proteins. The identity among the protein sequences of the three receptor α-subunits ranges from 36.1% to 44.5%, with the Ca 2+ -binding domains having the greatest homology. These proteins apparently evolved by a process of gene duplication

  9. Representation Learning for Class C G Protein-Coupled Receptors Classification

    Directory of Open Access Journals (Sweden)

    Raúl Cruz-Barbosa

    2018-03-01

    Full Text Available G protein-coupled receptors (GPCRs are integral cell membrane proteins of relevance for pharmacology. The complete tertiary structure including both extracellular and transmembrane domains has not been determined for any member of class C GPCRs. An alternative way to work on GPCR structural models is the investigation of their functionality through the analysis of their primary structure. For this, sequence representation is a key factor for the GPCRs’ classification context, where usually, feature engineering is carried out. In this paper, we propose the use of representation learning to acquire the features that best represent the class C GPCR sequences and at the same time to obtain a model for classification automatically. Deep learning methods in conjunction with amino acid physicochemical property indices are then used for this purpose. Experimental results assessed by the classification accuracy, Matthews’ correlation coefficient and the balanced error rate show that using a hydrophobicity index and a restricted Boltzmann machine (RBM can achieve performance results (accuracy of 92.9% similar to those reported in the literature. As a second proposal, we combine two or more physicochemical property indices instead of only one as the input for a deep architecture in order to add information from the sequences. Experimental results show that using three hydrophobicity-related index combinations helps to improve the classification performance (accuracy of 94.1% of an RBM better than those reported in the literature for class C GPCRs without using feature selection methods.

  10. Activated protein C (APC) can increase bone anabolism via a protease-activated receptor (PAR)1/2 dependent mechanism.

    Science.gov (United States)

    Shen, Kaitlin; Murphy, Ciara M; Chan, Ben; Kolind, Mille; Cheng, Tegan L; Mikulec, Kathy; Peacock, Lauren; Xue, Meilang; Park, Sang-Youel; Little, David G; Jackson, Chris J; Schindeler, Aaron

    2014-12-01

    Activated Protein C (APC) is an anticoagulant with strong cytoprotective properties that has been shown to promote wound healing. In this study APC was investigated for its potential orthopedic application using a Bone Morphogenetic Protein 2 (rhBMP-2) induced ectopic bone formation model. Local co-administration of 10 µg rhBMP-2 with 10 µg or 25 µg APC increased bone volume at 3 weeks by 32% (N.S.) and 74% (pAPC are largely mediated by its receptors endothelial protein C receptor (EPCR) and protease-activated receptors (PARs). Cultured pre-osteoblasts and bone nodule tissue sections were shown to express PAR1/2 and EPCR. When pre-osteoblasts were treated with APC, cell viability and phosphorylation of ERK1/2, Akt, and p38 were increased. Inhibition with PAR1 and sometimes PAR2 antagonists, but not with EPCR blocking antibodies, ameliorated the effects of APC on cell viability and kinase phosphorylation. These data indicate that APC can affect osteoblast viability and signaling, and may have in vivo applications with rhBMP-2 for bone repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Receptor activity modifying proteins (RAMPs) interact with the VPAC1 receptor: evidence for differential RAMP modulation of multiple signalling pathways

    International Nuclear Information System (INIS)

    Christopoulos, G.; Morfis, M.; Sexton, P.M.; Christopoulos, A.; Laburthe, M.; Couvineau, A.

    2001-01-01

    Full text: Receptor activity modifying proteins (RAMP) constitute a family of three accessory proteins that affect the expression and/or phenotype of the calcitonin receptor (CTR) or CTR-like receptor (CRLR). In this study we screened a range of class II G protein-coupled receptors (PTH1, PTH2, GHRH, VPAC1, VPAC2 receptors) for possible RAMP interactions by measurement of receptor-induced translocation of c-myc tagged RAMP1 or HA tagged RAMP3. Of these, only the VPAC1 receptor caused significant translocation of c-myc-RAMP1 or HA-RAMP3 to the cell surface. Co-transfection of VPAC1 and RAMPs did not alter 125 I-VIP binding and specificity. VPAC1 receptor function was subsequently analyzed through parallel determinations of cAMP accumulation and phosphoinositide (PI) hydrolysis in the presence and absence of each of the three RAMPs. In contrast to CTR-RAMP interaction, where there was an increase in cAMP Pharmacologisand a decrease in PI hydrolysis, VPAC1-RAMP interaction was characterized by a specific increase in agonist-mediated PI hydrolysis when co-transfected with RAMP2. This change was due to an enhancement of Emax with no change in EC 50 value for VIP. No significant change in cAMP accumulation was observed. This is the first demonstration of an interaction of RAMPs with a G protein-coupled receptor outside the CTR family and may suggest a more generalized role for RAMPs in modulating G protein-coupled receptor signaling. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  12. Activation of G-proteins by receptor-stimulated nucleoside diphosphate kinase in Dictyostelium.

    Science.gov (United States)

    Bominaar, A A; Molijn, A C; Pestel, M; Veron, M; Van Haastert, P J

    1993-01-01

    Recently, interest in the enzyme nucleoside diphosphate kinase (EC2.7.4.6) has increased as a result of its possible involvement in cell proliferation and development. Since NDP kinase is one of the major sources of GTP in cells, it has been suggested that the effects of an altered NDP kinase activity on cellular processes might be the result of altered transmembrane signal transduction via guanine nucleotide-binding proteins (G-proteins). In the cellular slime mould Dictyostelium discoideum, extracellular cAMP induces an increase of phospholipase C activity via a surface cAMP receptor and G-proteins. In this paper it is demonstrated that part of the cellular NDP kinase is associated with the membrane and stimulated by cell surface cAMP receptors. The GTP produced by the action of NDP kinase is capable of activating G-proteins as monitored by altered G-protein-receptor interaction and the activation of the effector enzyme phospholipase C. Furthermore, specific monoclonal antibodies inhibit the effect of NDP kinase on G-protein activation. These results suggest that receptor-stimulated NDP kinase contributes to the mediation of hormone action by producing GTP for the activation of GTP-binding proteins. Images PMID:8389692

  13. C-reactive protein levels in patients with aggressive periodontitis.

    Science.gov (United States)

    Salzberg, Trang N; Overstreet, Benjamin T; Rogers, Jeffrey D; Califano, Joseph V; Best, Al M; Schenkein, Harvey A

    2006-06-01

    Sera from patients with periodontal infections contain elevated levels of C-reactive protein (CRP) compared to periodontally healthy individuals. Most studies to date have included patients with chronic periodontitis, and few investigators have studied CRP levels in subjects with aggressive periodontitis (AgP). The purpose of this study was to determine the relative levels of serum CRP in AgP patients and periodontally healthy subjects and to examine patients' characteristics that might account for intergroup differences. Serum samples were collected from 93 patients with generalized AgP (GAgP), from 97 patients with localized AgP (LAgP), and from 91 healthy controls (non-periodontitis [NP]). Periodontal examination consisted of plaque index, gingival index, probing depth, bleeding index, and attachment loss measurements. Current smoking was assessed by determination of serum cotinine levels by enzyme-linked immunosorbent assay (ELISA), and serum CRP levels were determined using a high-sensitivity ELISA assay. The three groups were significantly different from one another (P periodontal and demographic variables and current smoking, both mean probing depth and periodontal diagnosis remained correlated with CRP levels. Patients with AgP have statistically significant elevations in serum CRP levels compared to subjects without periodontitis. Elevated CRP in these subjects might represent a contribution of periodontal infections to systemic inflammation in relatively young individuals.

  14. Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population.

    Science.gov (United States)

    Coen, Paul M; Flynn, Michael G; Markofski, Melissa M; Pence, Brandt D; Hannemann, Robert E

    2010-12-01

    Statin treatment and exercise training can reduce markers of inflammation when administered separately. The purpose of this study was to determine the effect of rosuvastatin treatment and the addition of exercise training on circulating markers of inflammation including C-reactive protein (CRP), monocyte toll-like receptor 4 (TLR4) expression, and CD14+CD16+ monocyte population size. Thirty-three hypercholesterolemic and physically inactive subjects were randomly assigned to rosuvastatin (R) or rosuvastatin/exercise (RE) groups. A third group of physically active hypercholesterolemic subjects served as a control (AC). The R and RE groups received rosuvastatin treatment (10 mg/d) for 20 weeks. From week 10 to week 20, the RE group also participated in an exercise training program (3d/wk). Measurements were made at baseline (Pre), week 10 (Mid), and week 20 (Post), and included TLR4 expression on CD14+ monocytes and CD14+CD16+ monocyte population size as determined by 3-color flow cytometry. Serum CRP was quantified by enzyme-linked immunosorbent assay. TLR4 expression on CD14+ monocytes was higher in the R group at week 20. When treatment groups (R and RE) were combined, serum CRP was lower across time. Furthermore, serum CRP and inflammatory monocyte population size were lower in the RE group compared with the R group at the Post time point. When all groups (R, RE, and AC) were combined, TLR4 expression was greater on inflammatory monocytes (CD14+CD16+) compared with classic monocytes (CD14+CD16⁻) at all time points. In conclusion, rosuvastatin may influence monocyte inflammatory response by increasing TLR4 expression on circulating monocytes. The addition of exercise training to rosuvastatin treatment further lowered CRP and reduced the size of the inflammatory monocyte population, suggesting an additive anti-inflammatory effect of exercise. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Differential regulation of synaptic and extrasynaptic α4 GABA(A) receptor populations by protein kinase A and protein kinase C in cultured cortical neurons.

    Science.gov (United States)

    Bohnsack, John Peyton; Carlson, Stephen L; Morrow, A Leslie

    2016-06-01

    The GABAA α4 subunit exists in two distinct populations of GABAA receptors. Synaptic GABAA α4 receptors are localized at the synapse and mediate phasic inhibitory neurotransmission, while extrasynaptic GABAA receptors are located outside of the synapse and mediate tonic inhibitory transmission. These receptors have distinct pharmacological and biophysical properties that contribute to interest in how these different subtypes are regulated under physiological and pathological states. We utilized subcellular fractionation procedures to separate these populations of receptors in order to investigate their regulation by protein kinases in cortical cultured neurons. Protein kinase A (PKA) activation decreases synaptic α4 expression while protein kinase C (PKC) activation increases α4 subunit expression, and these effects are associated with increased β3 S408/409 or γ2 S327 phosphorylation respectively. In contrast, PKA activation increases extrasynaptic α4 and δ subunit expression, while PKC activation has no effect. Our findings suggest synaptic and extrasynaptic GABAA α4 subunit expression can be modulated by PKA to inform the development of more specific therapeutics for neurological diseases that involve deficits in GABAergic transmission. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Rapid and quantitative detection of C-reactive protein based on quantum dots and immunofiltration assay

    Directory of Open Access Journals (Sweden)

    Zhang PF

    2015-09-01

    Full Text Available Pengfei Zhang,1,* Yan Bao,1,* Mohamed Shehata Draz,2,3,* Huiqi Lu,1 Chang Liu,1 Huanxing Han11Center for Translational Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 2Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Faculty of Science, Tanta University, Tanta, Egypt*These authors contributed equally to this workAbstract: Convenient and rapid immunofiltration assays (IFAs enable on-site “yes” or “no” determination of disease markers. However, traditional IFAs are commonly qualitative or semi-quantitative and are very limited for the efficient testing of samples in field diagnostics. Here, we overcome these limitations by developing a quantum dots (QDs-based fluorescent IFA for the quantitative detection of C-reactive proteins (CRP. CRP, the well-known diagnostic marker for acute viral and bacterial infections, was used as a model analyte to demonstrate performance and sensitivity of our developed QDs-based IFA. QDs capped with both polyethylene glycol (PEG and glutathione were used as fluorescent labels for our IFAs. The presence of the surface PEG layer, which reduced the non-specific protein interactions, in conjunction with the inherent optical properties of QDs, resulted in lower background signal, increased sensitivity, and ability to detect CRP down to 0.79 mg/L with only 5 µL serum sample. In addition, the developed assay is simple, fast and can quantitatively detect CRP with a detection limit up to 200 mg/L. Clinical test results of our QD-based IFA are well correlated with the traditional latex enhance immune-agglutination aggregation. The proposed QD-based fluorescent IFA is very promising, and potentially will be adopted for multiplexed immunoassay and in field point-of-care test.Keywords: C-reactive proteins, point-of-care test, Glutathione capped QDs, PEGylation

  17. Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein

    DEFF Research Database (Denmark)

    Muñoz, A; Zenke, M; Gehring, U

    1988-01-01

    mutations present in the carboxy-terminal half of P75gag-v-erbA co-operate in abolishing hormone binding, and that the ligand-binding domain resides in a position analogous to that of steroid receptors. Furthermore, a point mutation that is located between the putative DNA and ligand-binding domains of P75......To identify and characterize the hormone-binding domain of the thyroid hormone receptor, we analyzed the ligand-binding capacities of proteins representing chimeras between the normal receptor and P75gag-v-erbA, the retrovirus-encoded form deficient in binding ligand. Our results show that several......gag-v-erbA and that renders it biologically inactive fails to affect hormone binding by the c-erbA protein. These results suggest that the mutation changed the ability of P75gag-v-erbA to affect transcription since it also had no effect on DNA binding. Our data also suggest that hormone...

  18. Arsenite activates NFκB through induction of C-reactive protein

    International Nuclear Information System (INIS)

    Druwe, Ingrid L.; Sollome, James J.; Sanchez-Soria, Pablo; Hardwick, Rhiannon N.; Camenisch, Todd D.; Vaillancourt, Richard R.

    2012-01-01

    C-reactive protein (CRP) is an acute phase protein in humans. Elevated levels of CRP are produced in response to inflammatory cytokines and are associated with atherosclerosis, hypertension, cardiovascular disease and insulin resistance. Exposure to inorganic arsenic, a common environmental toxicant, also produces cardiovascular disorders, namely atherosclerosis and is associated with insulin-resistance. Inorganic arsenic has been shown to contribute to cardiac toxicities through production of reactive oxygen species (ROS) that result in the activation of NFκB. In this study we show that exposure of the hepatic cell line, HepG2, to environmentally relevant levels of arsenite (0.13 to 2 μM) results in elevated CRP expression and secretion. ROS analysis of the samples showed that a minimal amount of ROS are produced by HepG2 cells in response to these concentrations of arsenic. In addition, treatment of FvB mice with 100 ppb sodium arsenite in the drinking water for 6 months starting at weaning age resulted in dramatically higher levels of CRP in both the liver and inner medullary region of the kidney. Further, mouse Inner Medullary Collecting Duct cells (mIMCD-4), a mouse kidney cell line, were stimulated with 10 ng/ml CRP which resulted in activation of NFκB. Pretreatment with 10 nM Y27632, a known Rho-kinase inhibitor, prior to CRP exposure attenuated NFκB activation. These data suggest that arsenic causes the expression and secretion of CRP and that CRP activates NFκB through activation of the Rho-kinase pathway, thereby providing a novel pathway by which arsenic can contribute to metabolic syndrome and cardiovascular disease. -- Highlights: ► Exposure to arsenic can induce the expression and secretion of CRP. ► Mice treated with NaAsO 2 showed higher levels of CRP in both the liver and kidney. ► mIMCD-3 were stimulated with CRP which resulted in activation of NFκB. ► CRP activates NFκB through activation of the Rho-kinase pathway. ► Data provide

  19. Arsenite activates NFκB through induction of C-reactive protein

    Energy Technology Data Exchange (ETDEWEB)

    Druwe, Ingrid L.; Sollome, James J.; Sanchez-Soria, Pablo; Hardwick, Rhiannon N.; Camenisch, Todd D.; Vaillancourt, Richard R., E-mail: vaillancourt@pharmacy.arizona.edu

    2012-06-15

    C-reactive protein (CRP) is an acute phase protein in humans. Elevated levels of CRP are produced in response to inflammatory cytokines and are associated with atherosclerosis, hypertension, cardiovascular disease and insulin resistance. Exposure to inorganic arsenic, a common environmental toxicant, also produces cardiovascular disorders, namely atherosclerosis and is associated with insulin-resistance. Inorganic arsenic has been shown to contribute to cardiac toxicities through production of reactive oxygen species (ROS) that result in the activation of NFκB. In this study we show that exposure of the hepatic cell line, HepG2, to environmentally relevant levels of arsenite (0.13 to 2 μM) results in elevated CRP expression and secretion. ROS analysis of the samples showed that a minimal amount of ROS are produced by HepG2 cells in response to these concentrations of arsenic. In addition, treatment of FvB mice with 100 ppb sodium arsenite in the drinking water for 6 months starting at weaning age resulted in dramatically higher levels of CRP in both the liver and inner medullary region of the kidney. Further, mouse Inner Medullary Collecting Duct cells (mIMCD-4), a mouse kidney cell line, were stimulated with 10 ng/ml CRP which resulted in activation of NFκB. Pretreatment with 10 nM Y27632, a known Rho-kinase inhibitor, prior to CRP exposure attenuated NFκB activation. These data suggest that arsenic causes the expression and secretion of CRP and that CRP activates NFκB through activation of the Rho-kinase pathway, thereby providing a novel pathway by which arsenic can contribute to metabolic syndrome and cardiovascular disease. -- Highlights: ► Exposure to arsenic can induce the expression and secretion of CRP. ► Mice treated with NaAsO{sub 2} showed higher levels of CRP in both the liver and kidney. ► mIMCD-3 were stimulated with CRP which resulted in activation of NFκB. ► CRP activates NFκB through activation of the Rho-kinase pathway. ► Data

  20. C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

    NARCIS (Netherlands)

    Kapur, Rick; Heitink-Polle, Katja M. J.; Porcelijn, Leendert; Bentlage, Arthur E. H.; Bruin, MCA; Visser, Remco; Roos, Dirk; Schasfoort, Richard B. M.; de Haas, Masja; van der Schoot, C. Ellen; Vidarsson, Gestur

    2015-01-01

    Immune-mediated platelet destruction is most frequently caused by allo-or autoantibodies via Fc gamma receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein

  1. Expression of G(alpha)(s) proteins and TSH receptor signalling in hyperfunctioning thyroid nodules with TSH receptor mutations.

    Science.gov (United States)

    Holzapfel, Hans-Peter; Bergner, Beate; Wonerow, Peter; Paschke, Ralf

    2002-07-01

    Constitutively activating mutations of the thyrotrophin receptor (TSHR) are the main molecular cause of hyperfunctioning thyroid nodules (HTNs). The G protein coupling is an important and critical step in the TSHR signalling which mainly includes G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins. We investigated the in vitro consequences of overexpressing G(alpha) proteins on signalling of the wild-type (WT) or mutated TSHR. Moreover, we investigated whether changes in G(alpha) protein expression are pathophysiologically relevant in HTNs or cold thyroid nodules (CTNs). Wild-type TSH receptor and mutated TSH receptors were coexpressed with G(alpha)(s), G(alpha)(i) or G(alpha)(q)/11, and cAMP and inositol phosphate (IP) production was measured after stimulation with TSH. The expression of G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins was examined by Western blotting in 28 HTNs and 14 CTNs. Coexpression of G(alpha)(s) with the WT TSH receptor in COS 7 cells significantly increased the basal and TSH-stimulated cAMP accumulation while coexpression of the G(alpha)(q) or G(alpha)11 protein significantly increased the production of cAMP and inositol triphosphate (IP(3)). The coexpression of the TSH receptor mutants (I486F, DEL613-621), known to couple constitutively to G(alpha)(s) and G(alpha)(q) with G(alpha)(s) and G(alpha)(q)/11, significantly increased the basal and stimulated cAMP and IP(3) accumulation. Coexpression of the TSH receptor mutant V556F with G(alpha)(s) only increased the basal and stimulated cAMP production while its coexpression with G(alpha)(q)/11 increased the basal and stimulated IP(3) signalling. The expression of G(alpha)(s) protein subunits determined by Western blotting was significantly decreased in 14 HTNs with a constitutively activating TSH receptor mutation in comparison with the corresponding surrounding tissue, while in 14 HTNs without TSH receptor or G(alpha)(s) protein mutation and in 14 CTNs the expression of G

  2. Association of canine obesity with reduced serum levels of C-reactive protein.

    Science.gov (United States)

    Veiga, Angela P M; Price, Christopher A; de Oliveira, Simone T; Dos Santos, Andréa P; Campos, Rómulo; Barbosa, Patricia R; González, Félix H D

    2008-03-01

    The prevalence of obesity is increasing in dogs as well as in humans. C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. The objective of the present study was to determine if serum CRP levels are altered in obese dogs. Fifteen lean (control group) and 16 overweight (obese group) dogs were examined. Blood samples were collected under fasted conditions for serum determination of CRP, glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated that obese dogs were insulin resistant because serum insulin and insulin/glucose ratios were higher than in lean dogs (P obese dogs than in controls (P obese group compared with the control group. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs.

  3. Potential Mediators between Fibromyalgia and C-Reactive protein: Results from a Large U.S. Community Survey.

    Science.gov (United States)

    Feinberg, Termeh; Sambamoorthi, Usha; Lilly, Christa; Innes, Kim Karen

    2017-07-07

    Fibromyalgia, a potentially debilitating chronic pain syndrome of unknown etiology, may be characterized by inflammation. In this study, we investigated the relation of FMS to serum C-reactive protein (CRP) in a large population of adults (18+) and investigated the influence of other factors on this relationship, including BMI, comorbidities, as well as mood and sleep disturbance. Participants were 52,535 Ohio Valley residents (Fibromyalgia n = 1125). All participants completed a comprehensive health survey (2005-2006) part of the C8 Health Project; serum levels of CRP were obtained, as was history of Fibromyalgia physician diagnosis. Logistic and linear regressions were used for this cross-sectional analysis. Mean CRP was higher among participants reporting Fibromyalgia than those without (5.54 ± 9.8 vs.3.75 ± 7.2 mg/L, p BMI) and comorbidities to the model markedly weakened this relationship (AORs, respectively, for highest vs lowest CRP quartile = 1.2 (CI 1.0,1.4) and 1.1 (CI 0.9,1.3). In contrast, inclusion of mood and sleep impairment only modestly reduced the adjusted risk estimate (AORs for highest vs. lowest quartile = 1.3 (CI 1.1,1.5) for each)). Findings from this large cross-sectional study indicate a significant positive cross-sectional association of Fibromyalgia to serum C-reactive protein may be explained, in part, by BMI and comorbidity. Prospective research is needed to confirm this, and clarify the potential mediating influence of obesity and comorbid conditions on this relationship.

  4. A Comparative Analysis of the Mechanism of Toll-Like Receptor-Disruption by TIR-Containing Protein C from Uropathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Anna Waldhuber

    2016-02-01

    Full Text Available The TIR-containing protein C (TcpC of uropathogenic Escherichia coli strains is a powerful virulence factor by impairing the signaling cascade of Toll-like receptors (TLRs. Several other bacterial pathogens like Salmonella, Yersinia, Staphylococcus aureus but also non-pathogens express similar proteins. We discuss here the pathogenic potential of TcpC and its interaction with TLRs and TLR-adapter proteins on the molecular level and compare its activity with the activity of other bacterial TIR-containing proteins. Finally, we analyze and compare the structure of bacterial TIR-domains with the TIR-domains of TLRs and TLR-adapters.

  5. A molecular pharmacologist's guide to G protein-coupled receptor crystallography

    NARCIS (Netherlands)

    Piscitelli, Chayne L.; Kean, James; de Graaf, C.; Deupi, Xavier

    2015-01-01

    G protein-coupled receptor (GPCR) structural biology has progressed dramatically in the last decade. There are now over 120 GPCR crystal structures deposited in the Protein Data Bank of 32 different receptors from families scattered across the phylogenetic tree, including class B, C, and Frizzled

  6. Selection of symptomatic patients with Crohn's disease for abdominopelvic computed tomography: role of serum C-reactive protein.

    LENUS (Irish Health Repository)

    Desmond, Alan N

    2012-11-01

    Results of previous studies have shown that repeated abdominopelvic computed tomography (CT) examinations can lead to substantial cumulative diagnostic radiation exposure in patients with Crohn\\'s disease (CD). Improved selection of patients referred for CT will reduce unnecessary radiation exposure. This study examines if serum C-reactive protein (CRP) concentration predicts which symptomatic patients with CD are likely to have significant disease activity or disease complications (such as abscess) detected on abdominopelvic CT.

  7. The superfamily of C3b/C4b-binding proteins

    DEFF Research Database (Denmark)

    Kristensen, Torsten; D'Eustachio, P; Ogata, R T

    1987-01-01

    The determination of primary structures by amino acid and nucleotide sequencing for the C3b-and/or C4b-binding proteins H, C4BP, CR1, B, and C2 has revealed the presence of a common structural element. This element is approximately 60 amino acids long and is repeated in a tandem fashion, commencing...... at the amino-terminal end of each molecule. Two other complement components, C1r and C1s, have two of these repeating units in the carboxy-terminal region of their noncatalytic A chains. Three noncomplement proteins, beta 2-glycoprotein I (beta 2I), the interleukin 2 receptor (IL 2 receptor), and the b chain...... of factor XIII, have 4, 2 and 10 of these repeating units, respectively. These proteins obviously belong to the above family, although there is no evidence that they interact with C3b and/or C4b. Human haptoglobin and rat leukocyte common antigen also contain two and three repeating units, respectively...

  8. C-reactive protein level in coronary artery disease and its correlation with serum d-dimer

    International Nuclear Information System (INIS)

    Gul, C.; Marwat, Z.I.; Israr, M.; Hanif, R.; Arshad, M.

    2017-01-01

    C-reactive protein concentration has continuous associations with risk of coronary artery disease, ischemic stroke and death from several cancers. In addition, several studies have shown that CRP could be used to predict first ever myocardial infarction and stroke in healthy subjects, as well as outcome in acute setting. High levels of another biomarker, D-dimer, have been found to be independently associated with occurrence of coronary events. Methods: This correlational study was carried out at the Department of Cardiology, Ayub Teaching Hospital Abbottabad, in collaboration with the department of Biochemistry Postgraduate Medical Institute Lahore from 15th July 2013 to 15th May 2014. Patients aged 30 years or more of either gender having coronary artery disease was included in the study. Their serum D-dimer levels and C-reactive protein levels were measured for correlation with coronary artery disease. Results: A total of 50 patients of CAD were included in this study. Out of these 30 (60 percent) were males and 20 (40 percent) were females. Elevated CRP levels and D-dimer levels were noted in all of these patients. Pearson correlation coefficient test was performed on both CRP and D-dimer levels. Pearson correlation coefficient was calculated to be r= -0.1522 and when a p value was calculated, it was found to be 0.292 which implied that the results were not significant. Conclusion: This study showed that there is no correlation between CRP levels and D-dimer levels in patients with Coronary Artery Disease. (author)

  9. A C-terminal segment of the V{sub 1}R vasopressin receptor is unstructured in the crystal structure of its chimera with the maltose-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Adikesavan, Nallini Vijayarangan; Mahmood, Syed Saad; Stanley, Nithianantham; Xu, Zhen; Wu, Nan [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Thibonnier, Marc [Department of Medicine, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Shoham, Menachem, E-mail: mxs10@case.edu [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States)

    2005-04-01

    The 1.8 Å crystal structure of an MBP-fusion protein with the C-terminal cytoplasmic segment of the V1 vasopressin receptor reveals that the receptor segment is unstructured. The V{sub 1} vascular vasopressin receptor (V{sub 1}R) is a G-protein-coupled receptor (GPCR) involved in the regulation of body-fluid osmolality, blood volume and blood pressure. Signal transduction is mediated by the third intracellular loop of this seven-transmembrane protein as well as by the C-terminal cytoplasmic segment. A chimera of the maltose-binding protein (MBP) and the C-terminal segment of V{sub 1}R has been cloned, expressed, purified and crystallized. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 51.10, b = 66.56, c = 115.72 Å, β = 95.99°. The 1.8 Å crystal structure reveals the conformation of MBP and part of the linker region of this chimera, with the C-terminal segment being unstructured. This may reflect a conformational plasticity in the C-terminal segment that may be necessary for proper function of V{sub 1}R.

  10. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    Czech Academy of Sciences Publication Activity Database

    Malínská, H.; Oliyarnyk, O.; Škop, V.; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, L.; Pravenec, Michal

    2016-01-01

    Roč. 11, č. 3 (2016), e0150924 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * spontaneously hypertensive rat * transgenic * C-reactive protein * dicarbonyl stress * metformin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.806, year: 2016

  11. Diagnostic value of C-reactive protein to rule out infectious complications after major abdominal surgery: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Gans, Sarah L.; Atema, Jasper J.; van Dieren, Susan; Groot Koerkamp, Bas; Boermeester, Marja A.

    2015-01-01

    Infectious complications occur frequently after major abdominal surgery and have a major influence on patient outcome and hospital costs. A marker that can rule out postoperative infectious complications (PICs) could aid patient selection for safe and early hospital discharge. C-reactive protein

  12. Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; O'Connor, Jemma L; Phillips, Andrew N

    2016-01-01

    BACKGROUND: Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels are linked to adverse outcomes in human immunodeficiency virus (HIV) infection, but the strength of their associations with different clinical end points warrants investigation. METHODS: Participants...

  13. Serum levels of C-reactive protein in adolescents with periodontitis.

    Science.gov (United States)

    López, Rodrigo; Baelum, Vibeke; Hedegaard, Chris Juul; Bendtzen, Klaus

    2011-04-01

    The results of several cross-sectional studies suggested a relationship between periodontitis and higher serum levels of C-reactive protein (CRP). Most of these studies were restricted to adult study groups with severe periodontal inflammation, and the potential effects of confounding factors were frequently overlooked. A case-referent study comprised of 87 adolescent cases who presented with clinical attachment loss ≥3 mm recorded in ≥2 of 16 teeth and 73 controls who did not fulfill these criteria was nested in a fully enumerated adolescent population. Venous blood samples were obtained, and CRP levels were quantified, using a high-sensitive bead-based flow cytometric assay. The Mann-Whitney U test was used to assess overall differences between groups. The median serum CRP values for cases and controls were 64 ng/ml (interquartile range: 27 to 234 ng/ml) and 55 ng/ml (31 to 183 ng/ml), respectively (P = 0.8). Serum levels of CRP were not significantly higher among subjects with periodontitis than among controls. However, a statistically significant positive association between percentages of sites with bleeding on probing and log-transformed CRP values was observed.

  14. C-reactive protein and migraine. Facts or speculations?

    Science.gov (United States)

    Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco

    2014-09-01

    Abstract Migraine is a highly prevalent and frequently disabling disorder. Since the pathogenesis of this condition has a strong inflammatory component and migraine is significantly associated with cardiovascular disease, we assess whether C-reactive protein (CRP) may be epidemiologically or casually linked with migraine. An electronic search on Medline, Scopus and Web of Science produced 17 studies reporting original data about the epidemiological association between CRP and migraine (1 retrospective, 1 interventional, 14 cross-sectional and 1 both interventional and cross-sectional). When all studies reporting sufficient data about CRP values were pooled (n=12; 6980 cases and 38,975 controls), the concentration of CRP was found to be significantly higher in patients with migraine than in controls (weighted mean difference 1.12 mg/L; 95% CI 1.01-1.25 mg/L; p<0.001). In further analysis of studies containing separate data for migraine with and without aura (n=7), CRP values remained significantly higher in both migraineur patients with aura (n=1939; weighted mean difference 0.88 mg/L; 95% CI 0.63-1.14 mg/L; p<0.001) or without aura (n=2483; weighted mean difference 1.04 mg/L; 95% CI 0.78-1.30 mg/L; p<0.001) when compared with controls (n=29,354). Despite a large inter-study heterogeneity (99.3%), our analysis provides evidence of a potential epidemiological association between increased concentration of CRP and migraine, thus paving the way for further clinical investigations about therapeutic agents that may contextually decrease the risk of cardiovascular disease and reduce the burden of migraine.

  15. The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine

    Directory of Open Access Journals (Sweden)

    Chang Mi-Kyung

    2012-10-01

    Full Text Available Abstract Rationale C-reactive protein (CRP and lysophosphatidylcholine (LPC are phosphorylcholine-(PC-containing oxidized phospholipids (oxPLs found in oxidized LDL (oxLDL, which trigger pro-atherogenic activities of macrophages during the process of atherosclerosis. It has been previously reported that CRP binds to the PC head group of oxLDL in a calcium-dependent manner. The aim of this study was to investigate the importance of binding between CRP and LPC to the pro-atherogenic activities of macrophages. Objectives and findings A chemiluminescent immunoassay and HPLC showed that human recombinant CRP formed a stable complex with LPC in the presence of calcium. The Kd value of the binding of the CRP-LPC complex to the receptors FcγRIA or FcγRIIA was 3–5 fold lower than that of CRP alone. The CRP-LPC complex triggered less potent generation of reactive oxygen species and less activation of the transcription factors AP-1 and NF-kB by human monocyte-derived macrophages in comparison to CRP or LPC alone. However, CRP did not affect activities driven by components of oxLDL lacking PC, such as upregulation of PPRE, ABCA1, CD36 and PPARγ and the enhancement of cholesterol efflux by human macrophages. The presence of CRP inhibited the association of Dil-labelled oxLDL to human macrophages. Conclusions The formation of complexes between CRP and PC-containing oxPLs, such as LPC, suppresses the pro-atherogenic effects of CRP and LPC on macrophages. This effect may in part retard the progression of atherosclerosis.

  16. Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

    Directory of Open Access Journals (Sweden)

    Zhigang Li

    2013-10-01

    Full Text Available Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65 is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs. Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression.

  17. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine Willum; Olsen, Michael H

    2008-01-01

    were recorded at baseline. CRP was determined by a high-sensitivity assay, and IR was determined by the homoeostasis model assessment (HOMA-IR) method. RESULTS: Over a median follow-up of 9.4 years, the incidence of the prespecified CV event, defined as the composite event of CV death, nonfatal...... and HOMA-IR, the hazard ratio (95% confidence interval) of a CV event was 1.33 (1.14-1.55; PHOMA-IR level. CONCLUSION......BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors...

  18. C-Reactive Protein (CRP) and its Association with Periodontal Disease: A Brief Review.

    Science.gov (United States)

    Bansal, Tushika; Pandey, Anita; D, Deepa; Asthana, Ashish K

    2014-07-01

    Periodontal disease is a chronic infection of the gums characterised by a loss of attachment between the tooth and bone, and bone loss. C-reactive protein (CRP) elevation is a part of the acute phase response to acute and chronic inflammation. Many epidemiological studies have shown that serum CRP levels were elevated in patients with chronic periodontitis. CRP levels increase to hundreds of μg/ml within hours following infection. It out-performs erythrocyte sedimentation rate (ESR) in terms of responsiveness and specificity for inflammation. While CRP elevation is suggestive of inflammation or infection in the appropriate clinical context, it can also occur with obesity and renal dysfunction. Conversely, a lack of CRP elevation in inflammation may be seen with hepatic failure, as well as during flares of conditions such as systemic lupus erythematosus.

  19. Increased Baseline C-Reactive Protein Concentrations Are Associated with Increased Risk of Infections

    DEFF Research Database (Denmark)

    Zacho, Jeppe; Benfield, Thomas; Tybjærg-Hansen, Anne

    2016-01-01

    BACKGROUND: The acute-phase reactant C-reactive protein (CRP) increases rapidly during an infection. We tested the hypothesis that chronic low-level increases in CRP are associated with an increased risk of infectious disease. METHODS: We studied 9660 individuals from a prospective general...... population cohort, including 3592 in whom infectious disease developed, and another 60 896 individuals from a cross-sectional general population study, of whom 13 332 developed infectious disease; 55% were women, and the mean age was 57 years. Hospital diagnoses of infections in 1977-2010 were based....... RESULTS: Individuals with CRP >3 mg/L had 1.2 and 1.7 times increased risk of infectious disease, in the prospective general population cohort and the cross-sectional general population study, respectively, compared with individuals with CRP

  20. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Vestbo, Jørgen; Lange, Peter

    2007-01-01

    RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have an ongoing systemic inflammation, which can be assessed by measuring serum C-reactive protein (CRP). OBJECTIVE: To determine whether increased serum CRP in individuals with airway obstruction predicts future hospitalization...... and death from COPD. METHODS: We performed a cohort study with a median of 8-yr follow-up of 1,302 individuals with airway obstruction selected from the ongoing Copenhagen City Heart Study. MEASUREMENTS AND MAIN RESULTS: We measured serum CRP at baseline, and recorded COPD admissions and deaths as outcomes...... consumption, and ischemic heart disease, the hazard ratios for hospitalization and death due to COPD were increased at 1.4 (95% confidence interval, 1.0-2.0) and 2.2 (1.2-3.9) in individuals with baseline CRP > 3 mg/L versus

  1. Urinary albumin excretion and its relation with C-reactive protein and the metabolic syndrome in the prediction Of type 2 diabetes

    NARCIS (Netherlands)

    Brantsma, AH; Bakker, SJL; Hillege, HL; De Zeeuw, D; De Jong, PE; Gansevoort, RT

    2005-01-01

    OBJECTIVE - To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - We used data from the Prevention of Renal and Vascular End Stage Disease

  2. Severe malaria is associated with parasite binding to endothelial protein C receptor

    DEFF Research Database (Denmark)

    Turner, Louise; Lavstsen, Thomas; Berger, Sanne S

    2013-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year. Sequestration is mediated by specific interactions between members of the P....... falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins...

  3. Impact of vitamin D status and obesity on C-reactive protein in kidney-transplant patients

    DEFF Research Database (Denmark)

    Ewers, B.; Gasbjerg, A.; Zerahn, B.

    2008-01-01

    and Patients: Data were collected between December 2005 and April 2006 from 161 adult (aged >18 years) kidney-transplant patients (mean age, 53.1 years; SD, 11.5 years; females/males, 78/83), with a median kidney-graft age of 7.0 years and serum CRP levels :... was found. Fat mass correlated positively with CRP, suggesting that obesity may increase the risk of cardiovascular disease and chronic allograft rejection in kidney-transplant patients. (C) 2008 by the National Kidney Foundation, Inc Udgivelsesdato: 2008/5......Objective: We examined whether vitamin D status and obesity are associated with low-grade systemic inflammation, as assessed by serum concentrations of C-reactive protein (CRP) in an adult population of kidney-transplant patients. Design: This was a single-center, cross-sectional study. Setting...

  4. Prognostic implications of plasma fibrinogen and serum C- reactive ...

    African Journals Online (AJOL)

    Key words: Plasma fibrinogen, serum C-reactive protein, biomarker, non-small cell lung cancer. Tropical Journal of Pharmaceutical Research ... demonstrated in colorectal [11], cervical, oesophageal [12], and pancreatic cancers .... demographic and clinical characteristic features of the patients involved are shown in Table ...

  5. G protein-coupled receptors: the inside story.

    Science.gov (United States)

    Jalink, Kees; Moolenaar, Wouter H

    2010-01-01

    Recent findings necessitate revision of the traditional view of G protein-coupled receptor (GPCR) signaling and expand the diversity of mechanisms by which receptor signaling influences cell behavior in general. GPCRs elicit signals at the plasma membrane and are then rapidly removed from the cell surface by endocytosis. Internalization of GPCRs has long been thought to serve as a mechanism to terminate the production of second messengers such as cAMP. However, recent studies show that internalized GPCRs can continue to either stimulate or inhibit cAMP production in a sustained manner. They do so by remaining associated with their cognate G protein subunit and adenylyl cyclase at endosomal compartments. Once internalized, the GPCRs produce cellular responses distinct from those elicited at the cell surface.

  6. Association of cardiac myosin binding protein-C with the ryanodine receptor channel: putative retrograde regulation?

    Science.gov (United States)

    Stanczyk, Paulina J; Seidel, Monika; White, Judith; Viero, Cedric; George, Christopher H; Zissimopoulos, Spyros; Lai, F Anthony

    2018-06-21

    The cardiac muscle ryanodine receptor-Ca 2+ release channel (RyR2) constitutes the sarcoplasmic reticulum (SR) Ca 2+ efflux mechanism that initiates myocyte contraction, while cardiac myosin binding protein-C (cMyBP-C) mediates regulation of acto-myosin cross-bridge cycling. In this report, we provide the first evidence for the presence of direct interaction between these two proteins, forming a RyR2:cMyBP-C complex. The C-terminus of cMyBP-C binds with the RyR2 N-terminus in mammalian cells and is not mediated by a fibronectin-like domain. Notably, we detected complex formation between both recombinant cMyBP-C and RyR2, as well as with the native proteins in cardiac tissue. Cellular Ca 2+ dynamics in HEK293 cells is altered upon co-expression of cMyBP-C and RyR2, with lowered frequency of RyR2-mediated spontaneous Ca 2+ oscillations, suggesting cMyBP-C exerts a potential inhibitory effect on RyR2-dependent Ca 2+ release. Discovery of a functional RyR2 association with cMyBP-C provides direct evidence for a putative mechanistic link between cytosolic soluble cMyBP-C and SR-mediated Ca 2+ release, via RyR2. Importantly, this interaction may have clinical relevance to the observed cMyBP-C and RyR2 dysfunction in cardiac pathologies, such as hypertrophic cardiomyopathy. © 2018. Published by The Company of Biologists Ltd.

  7. Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280).

    Science.gov (United States)

    Li, Ming; Li, Chuanyu; Weingarten, Paul; Bunzow, James R; Grandy, David K; Zhou, Qun Yong

    2002-03-01

    Proteins that bind to G protein-coupled receptors have been identified as regulators of receptor localization and signaling. In our previous studies, a cytoskeletal protein, actin-binding protein 280 (ABP-280), was found to associate with the third cytoplasmic loop of dopamine D(2) receptors. In this study, we demonstrate that ABP-280 also interacts with dopamine D(3) receptors, but not with D(4) receptors. Similar to the dopamine D(2) receptor, the D(3)/ABP-280 association is of signaling importance. In human melanoma M2 cells lacking ABP-280, D(3) receptors were unable to inhibit forskolin-stimulated cyclic AMP (cAMP) production significantly. D(4) receptors, however, exhibited a similar degree of inhibition of forskolin-stimulated cAMP production in ABP-280-deficient M2 cells and ABP-280-replent M2 subclones (A7 cells). Further experiments revealed that the D(3)/ABP-280 interaction was critically dependent upon a 36 amino acid carboxyl domain of the D(3) receptor third loop, which is conserved in the D(2) receptor but not in the D(4) receptor. Our results demonstrate a subtype-specific regulation of dopamine D(2)-family receptor signaling by the cytoskeletal protein ABP-280.

  8. C-reactive protein a better indicator of inflammation after third molar ...

    African Journals Online (AJOL)

    operative pain and pre-operative levels of C-reactive and post-operative pain and swelling in impacted third molar surgery. Materials and Methods: In this prospective study subjects were patients indicated for mandibular third molar extraction.

  9. C-reactive protein gene polymorphisms and myocardial infarction risk: a meta-analysis and meta-regression.

    Science.gov (United States)

    Zhu, Yanbin; Liu, Tongku; He, Haitao; Sun, Yuqing; Zhuo, Fengling

    2013-12-01

    C-reactive protein (CRP), the classic acute-phase protein, plays an important role in the etiology of myocardial infarction (MI). Emerging evidence has shown that the common polymorphisms in the CRP gene may influence an individual's susceptibility to MI; but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the associations between CRP gene polymorphisms and MI risk. A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before June 1st, 2013. Crude odds ratio (OR) with 95% confidence interval (CI) were calculated. Nine case-control studies were included with a total of 2992 MI patients and 4711 healthy controls. The meta-analysis results indicated that CRP rs3093059 (T>C) polymorphism was associated with decreased risk of MI, especially among Asian populations. However, similar associations were not observed in CRP rs1800947 (G>C) and rs2794521 (G>A) polymorphisms (all p>0.05) among both Asian and Caucasian populations. Univariate and multivariate meta-regression analyses showed that ethnicity may be a major source of heterogeneity. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis indicates that CRP rs3093059 (T>C) polymorphism may be associated with decreased risk of MI, especially among Asian populations.

  10. C-reactive protein velocity to distinguish febrile bacterial infections from non-bacterial febrile illnesses in the emergency department

    OpenAIRE

    Paran, Yael; Yablecovitch, Doron; Choshen, Guy; Zeitlin, Ina; Rogowski, Ori; Ben-Ami, Ronen; Katzir, Michal; Saranga, Hila; Rosenzweig, Tovit; Justo, Dan; Orbach, Yaffa; Halpern, Pinhas; Berliner, Shlomo

    2009-01-01

    Introduction C-reactive protein (CRP) is a real-time and low-cost biomarker to distinguish febrile bacterial infections from non-bacterial febrile illnesses. We hypothesised that measuring the velocity of the biomarker instead of its absolute serum concentration could enhance its ability to differentiate between these two conditions. Methods We prospectively recruited adult patients (age ? 18 years) who presented to the emergency department with fever. We recorded their data regarding the ons...

  11. Highly sensitive C-reactive protein (CRP) assay using metal-enhanced fluorescence (MEF)

    International Nuclear Information System (INIS)

    Zhang, Yi; Keegan, Gemma L.; Stranik, Ondrej; Brennan-Fournet, Margaret E.; McDonagh, Colette

    2015-01-01

    Fluorescence has been extensively employed in the area of diagnostic immunoassays. A significant enhancement of fluorescence can be achieved when noble metal nanoparticles are placed in close proximity to fluorophores. This effect, referred to as metal-enhanced fluorescence (MEF), has the potential to produce immunoassays with a high sensitivity and a low limit of detection (LOD). In this study, we investigate the fluorescence enhancement effect of two different nanoparticle systems, large spherical silver nanoparticles (AgNPs) and gold edge-coated triangular silver nanoplates, and both systems were evaluated for MEF. The extinction properties and electric field enhancement of both systems were modeled, and the optimum system, spherical AgNPs, was used in a sandwich immunoassay for human C-reactive protein with a red fluorescent dye label. A significant enhancement in the fluorescence was observed, which corresponded to an LOD improvement of ∼19-fold compared to a control assay without AgNPs

  12. Highly sensitive C-reactive protein (CRP) assay using metal-enhanced fluorescence (MEF)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi; Keegan, Gemma L., E-mail: gemmakeegan@gmail.com [Dublin City University, School of Physical Sciences, Biomedical Diagnostics Institute (Ireland); Stranik, Ondrej [Leibniz Institute of Photonic Technology, Department of NanoBiophotonics (Germany); Brennan-Fournet, Margaret E. [CMP-EMSE, MOC, Department of Bioelectronics, Ecole Nationale Superieure des Mines (France); McDonagh, Colette [Dublin City University, School of Physical Sciences, Biomedical Diagnostics Institute (Ireland)

    2015-07-15

    Fluorescence has been extensively employed in the area of diagnostic immunoassays. A significant enhancement of fluorescence can be achieved when noble metal nanoparticles are placed in close proximity to fluorophores. This effect, referred to as metal-enhanced fluorescence (MEF), has the potential to produce immunoassays with a high sensitivity and a low limit of detection (LOD). In this study, we investigate the fluorescence enhancement effect of two different nanoparticle systems, large spherical silver nanoparticles (AgNPs) and gold edge-coated triangular silver nanoplates, and both systems were evaluated for MEF. The extinction properties and electric field enhancement of both systems were modeled, and the optimum system, spherical AgNPs, was used in a sandwich immunoassay for human C-reactive protein with a red fluorescent dye label. A significant enhancement in the fluorescence was observed, which corresponded to an LOD improvement of ∼19-fold compared to a control assay without AgNPs.

  13. The Strength of Family Ties: Perceptions of Network Relationship Quality and Levels of C-Reactive Proteins in the North Texas Heart Study.

    Science.gov (United States)

    Uchino, Bert N; Ruiz, John M; Smith, Timothy W; Smyth, Joshua M; Taylor, Daniel J; Allison, Matthew; Ahn, Chul

    2015-10-01

    Although the quality of one's social relationships has been linked to important physical health outcomes, less work has been conducted examining family and friends that differ in their underlying positivity and negativity. The main aim of this study was to examine the association between supportive, aversive, and ambivalent family/friends with levels of C-reactive proteins. Three hundred participants from the North Texas Heart Study completed the social relationships index and a blood draw to assess high-sensitivity C-reactive proteins (hs-CRPs). After standard controls, the number of supportive family members predicted lower hs-CRP levels, whereas the number of ambivalent family members predicted higher hs-CRP levels. These links were independent of depressive symptoms and perceived stress. These data highlight the importance of considering specific types of relationships and their underlying positive and negative aspects in research on social ties and physical health.

  14. Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma

    DEFF Research Database (Denmark)

    Nielsen, Lise; Toft, Nils; Eckersall, David

    2007-01-01

    Background: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. Objective: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. Animals: Twenty......-two dogs with untreated multicentric lymphoma. Methods: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. Results: Before therapy, a statistically significant majority...... of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P

  15. Elevated C-Reactive Protein Levels, Psychological Distress, and Depression in 73 131 Individuals

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nielsen, Sune Fallgaard

    2013-01-01

    and depression. DESIGN We performed cross-sectional and prospective analyses of CRP levels in 4 clinically relevant categories using data from 2 general population studies. SETTING The Copenhagen General Population and the Copenhagen City Heart studies. PARTICIPANTS We examined 73 131 men and women aged 20......CONTEXT The pathogenesis of depression is not fully understood, but studies suggest that low-grade systemic inflammation contributes to the development of depression. OBJECTIVE To test whether elevated plasma levels of C-reactive protein (CRP) are associated with psychological distress...... to 100 years. MAIN OUTCOME MEASURES We ascertained psychological distress with 2 single-item self-reports and depression using self-reported antidepressant use, register-based prescription of antidepressants, and register-based hospitalization with depression. RESULTS In cross-sectional analyses...

  16. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    LENUS (Irish Health Repository)

    Shrotriya, Shiva

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.

  17. Direct protein-protein interaction between PLCγ1 and the bradykinin B2 receptor-Importance of growth conditions

    International Nuclear Information System (INIS)

    Duchene, Johan; Chauhan, Sharmila D.; Lopez, Frederic; Pecher, Christiane; Esteve, Jean-Pierre; Girolami, Jean-Pierre; Bascands, Jean-Loup; Schanstra, Joost P.

    2005-01-01

    Recently, we have described a novel protein-protein interaction between the G-protein coupled bradykinin B2 receptor and tyrosine phosphatase SHP-2 via an immunoreceptor tyrosine-based inhibition motif (ITIM) sequence located in the C-terminal part of the B2 receptor and the Src homology (SH2) domains of SHP-2. Here we show that phospholipase C (PLC)γ1, another SH2 domain containing protein, can also interact with this ITIM sequence. Using surface plasmon resonance analysis, we observed that PLCγ1 interacted with a peptide containing the phosphorylated form of the bradykinin B2 receptor ITIM sequence. In CHO cells expressing the wild-type B2 receptor, bradykinin-induced transient recruitment and activation of PLCγ1. Interestingly, this interaction was only observed in quiescent and not in proliferating cells. Mutation of the key ITIM residue abolished this interaction with and activation of PLCγ1. Finally we also identified bradykinin-induced PLCγ1 recruitment and activation in primary culture renal mesangial cells

  18. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein

    DEFF Research Database (Denmark)

    Jacobsen, Linda; Madsen, P; Moestrup, S K

    1996-01-01

    the corresponding cDNA. The gene, designated SORL1, maps to chromosome 11q 23/24 and encodes a 2214-residue type 1 receptor containing a furin cleavage site immediately preceding the N terminus determined in the purified protein. The receptor, designated sorLA-1, has a short cytoplasmic tail containing a tyrosine...... density lipoprotein receptor gene family receptors, and 3) six tandemly arranged fibronectin type III repeats also found in certain neural adhesion proteins. sorLA-1 may therefore be classified as a hybrid receptor. Northern blotting revealed specific mRNA transcripts in brain, spinal cord, and testis......The 39-40-kDa receptor-associated protein (RAP) binds to the members of the low density lipoprotein receptor gene family and functions as a specialized endoplasmic reticulum/Golgi chaperone. Using RAP affinity chromatography, we have purified a novel approximately 250-kDa brain protein and isolated...

  19. Aromatic interactions impact ligand binding and function at serotonin 5-HT2C G protein-coupled receptors: receptor homology modelling, ligand docking, and molecular dynamics results validated by experimental studies

    Science.gov (United States)

    Córdova-Sintjago, Tania; Villa, Nancy; Fang, Lijuan; Booth, Raymond G.

    2014-02-01

    The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 G protein-coupled receptor (GPCR) family consists of types 2A, 2B, and 2C that share ∼75% transmembrane (TM) sequence identity. Agonists for 5-HT2C receptors are under development for psychoses; whereas, at 5-HT2A receptors, antipsychotic effects are associated with antagonists - in fact, 5-HT2A agonists can cause hallucinations and 5-HT2B agonists cause cardiotoxicity. It is known that 5-HT2A TM6 residues W6.48, F6.51, and F6.52 impact ligand binding and function; however, ligand interactions with these residues at the 5-HT2C receptor have not been reported. To predict and validate molecular determinants for 5-HT2C-specific activation, results from receptor homology modelling, ligand docking, and molecular dynamics simulation studies were compared with experimental results for ligand binding and function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT2C receptors.

  20. Acrolein stimulates the synthesis of IL-6 and C-reactive protein (CRP) in thrombosis model mice and cultured cells.

    Science.gov (United States)

    Saiki, Ryotaro; Hayashi, Daisuke; Ikuo, Yukiko; Nishimura, Kazuhiro; Ishii, Itsuko; Kobayashi, Kaoru; Chiba, Kan; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2013-12-01

    Measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction with high sensitivity and specificity. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP in thrombosis model mice and cultured cells. In mice with photochemically induced thrombosis, acrolein produced at the locus of infarction increased the level of IL-6 and then CRP in plasma. This was confirmed in cell culture systems - acrolein stimulated the production of IL-6 in mouse neuroblastoma Neuro-2a cells, mouse macrophage-like J774.1 cells, and human umbilical vein endothelial cells (HUVEC), and IL-6 in turn stimulated the production of CRP in human hepatocarcinoma cells. The level of IL-6 mRNA was increased by acrolein through an increase in phosphorylation of the transcription factors, c-Jun, and NF-κB p65. Furthermore, CRP stimulated IL-6 production in mouse macrophage-like J774.1 cells and HUVEC. IL-6 functioned as a protective factor against acrolein toxicity in Neuro-2a cells and HUVEC. These results show that acrolein stimulates the synthesis of IL-6 and CRP, which function as protecting factors against acrolein toxicity, and that the combined measurement of PC-Acro, IL-6, and CRP is effective for identification of silent brain infarction. The combined measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP, and indeed acrolein increased IL-6 synthesis and IL-6 in turn increased CRP synthesis. Furthermore, IL-6 decreased acrolein toxicity in several cell lines. © 2013 International Society for Neurochemistry.

  1. Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 receptor-Gi protein complex.

    Science.gov (United States)

    Mnpotra, Jagjeet S; Qiao, Zhuanhong; Cai, Jian; Lynch, Diane L; Grossfield, Alan; Leioatts, Nicholas; Hurst, Dow P; Pitman, Michael C; Song, Zhao-Hui; Reggio, Patricia H

    2014-07-18

    In this study, we applied a comprehensive G protein-coupled receptor-Gαi protein chemical cross-linking strategy to map the cannabinoid receptor subtype 2 (CB2)-Gαi interface and then used molecular dynamics simulations to explore the dynamics of complex formation. Three cross-link sites were identified using LC-MS/MS and electrospray ionization-MS/MS as follows: 1) a sulfhydryl cross-link between C3.53(134) in TMH3 and the Gαi C-terminal i-3 residue Cys-351; 2) a lysine cross-link between K6.35(245) in TMH6 and the Gαi C-terminal i-5 residue, Lys-349; and 3) a lysine cross-link between K5.64(215) in TMH5 and the Gαi α4β6 loop residue, Lys-317. To investigate the dynamics and nature of the conformational changes involved in CB2·Gi complex formation, we carried out microsecond-time scale molecular dynamics simulations of the CB2 R*·Gαi1β1γ2 complex embedded in a 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer, using cross-linking information as validation. Our results show that although molecular dynamics simulations started with the G protein orientation in the β2-AR*·Gαsβ1γ2 complex crystal structure, the Gαi1β1γ2 protein reoriented itself within 300 ns. Two major changes occurred as follows. 1) The Gαi1 α5 helix tilt changed due to the outward movement of TMH5 in CB2 R*. 2) A 25° clockwise rotation of Gαi1β1γ2 underneath CB2 R* occurred, with rotation ceasing when Pro-139 (IC-2 loop) anchors in a hydrophobic pocket on Gαi1 (Val-34, Leu-194, Phe-196, Phe-336, Thr-340, Ile-343, and Ile-344). In this complex, all three experimentally identified cross-links can occur. These findings should be relevant for other class A G protein-coupled receptors that couple to Gi proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization

    DEFF Research Database (Denmark)

    Xiang, B; Yu, G H; Guo, J

    2001-01-01

    The purpose of the current study is to investigate the effect of opioid-independent, heterologous activation of protein kinase C (PKC) on the responsiveness of opioid receptor and the underlying molecular mechanisms. Our result showed that removing the C terminus of delta opioid receptor (DOR......) containing six Ser/Thr residues abolished both DPDPE- and phorbol 12-myristate 13-acetate (PMA)-induced DOR phosphorylation. The phosphorylation levels of DOR mutants T352A, T353A, and T358A/T361A/S363S were comparable to that of the wild-type DOR, whereas S344G substitution blocked PMA-induced receptor......, and ionomycin resulted in DOR internalization that required phosphorylation of Ser-344. Expression of dominant negative beta-arrestin and hypertonic sucrose treatment blocked PMA-induced DOR internalization, suggesting that PKC mediates DOR internalization via a beta-arrestin- and clathrin-dependent mechanism...

  3. LPS-Toll-Like Receptor-Mediated Signaling on Expression of Protein S and C4b-Binding Protein in the Liver

    Directory of Open Access Journals (Sweden)

    Tatsuya Hayashi

    2010-01-01

    Full Text Available Protein S (PS, mainly synthesized in hepatocytes and endothelial cells, plays a critical role as a cofactor of anticoagulant activated protein C (APC. PS activity is regulated by C4b-binding protein (C4BP, structurally composed of seven α-chains (C4BPα and a β-chain (C4BPβ. In this paper, based primarily on our previous studies, we review the lipopolysaccharide (LPS-induced signaling which affects expression of PS and C4BP in the liver. Our in vivo studies in rats showed that after LPS injection, plasma PS levels are significantly decreased, whereas plasma C4BP levels first are transiently decreased after 2 to 12 hours and then significantly increased after 24 hours. LPS decreases PS antigen and mRNA levels in both hepatocytes and sinusoidal endothelial cells (SECs, and decreases C4BP antigen and both C4BPα and C4BPβ mRNA levels in hepatocytes. Antirat CD14 and antirat Toll-like receptor (TLR-4 antibodies inhibited LPS-induced NFκB activation in both hepatocytes and SECs. Furthermore, inhibitors of NFκB and MEK recovered the LPS-induced decreased expression of PS in both cell types and the LPS-induced decreased expression of C4BP in hepatocytes. These data suggest that the LPS-induced decrease in PS expression in hepatocytes and SECs and LPS-induced decrease in C4BP expression in hepatocytes are mediated by MEK/ERK signaling and NFκB activation and that membrane-bound CD14 and TLR-4 are involved in this mechanism.

  4. Functional expression of the 5-HT1c receptor in neuronal and nonneuronal cells

    International Nuclear Information System (INIS)

    Julius, D.; MacDermott, A.B.; Jessel, T.M.; Huang, K.; Molineaux, S.; Schieren, I.; Axel, R.

    1988-01-01

    The isolation of the genes encoding the multiple serotonin receptor subtypes and the ability to express these receptors in new cellular environments will help to elucidate the molecular mechanisms of action of serotonin in the mammalian brain. The cloning of most neurotransmitter receptors has required the purification of receptor, the determination of partial protein sequence, and the synthesis of oligonucleotide probes with which to obtain cDNA or genomic clones. However, the serotonin receptors have not been purified and antibodies have not been generated. The authors therefore designed a cDNA expression system that permits the identification of functional cDNA clones encoding serotonin receptors in the absence of protein sequence information. They have combined cloning in RNA expression vectors with an electrophysiological assay in oocytes to isolate a functional cDNA clone encoding the entire 5-HT 1c receptor. The sequence of this clone reveals that the 5-HT 1c receptor belongs to a family of G-protein-coupled receptors that are thought to traverse the membrane seven times. Mouse fibroblasts transformed with this clone bind serotonergic ligands and respond to serotonin with an elevation in intracellular calcium. Moreover, in situ hybridization and Northern blot analysis indicate that the 5-HT 1c receptor mRNA is expressed in a wide variety of neurons in the rat central nervous system, suggesting that this receptor plays a prominent role in neuronal function

  5. High sensitivity C reactive protein as a prognostic marker in patients with mild to moderate aortic valve stenosis during lipid-lowering treatment

    DEFF Research Database (Denmark)

    Blyme, Adam; Asferg, Camilla; Nielsen, Olav W

    2015-01-01

    AIMS: To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS). METHODS AND RESULTS: In 1620 SEAS patients, we m...

  6. Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex

    DEFF Research Database (Denmark)

    Olsen, M.H.; Hansen, T.W.; Christensen, M.K.

    2008-01-01

    BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated...

  7. Shc adaptor proteins are key transducers of mitogenic signaling mediated by the G protein-coupled thrombin receptor

    DEFF Research Database (Denmark)

    Chen, Y; Grall, D; Salcini, A E

    1996-01-01

    The serine protease thrombin activates G protein signaling systems that lead to Ras activation and, in certain cells, proliferation. Whereas the steps leading to Ras activation by G protein-coupled receptors are not well defined, the mechanisms of Ras activation by receptor tyrosine kinases have......-insensitive proteins appear to mediate this effect, since (i) pertussis toxin pre-treatment of cells does not blunt the action of thrombin and (ii) Shc phosphorylation on tyrosine can be stimulated by the muscarinic m1 receptor. Shc phosphorylation does not appear to involve protein kinase C, since the addition of 4...

  8. Discriminatory potential of C-reactive protein, cytokines, and fecal markers in infectious gastroenteritis in adults.

    Science.gov (United States)

    Weh, Julia; Antoni, Christoph; Weiß, Christel; Findeisen, Peter; Ebert, Matthias; Böcker, Ulrich

    2013-09-01

    This study evaluates potential markers in blood and stools for their ability to distinguish bacterial from viral gastroenteritis. A total of 108 patients were prospectively recruited, of which 27 showed bacterial, 30 viral, and 51 no detectable pathogen, respectively. Cytokines, C-reactive protein (CRP), and white blood cells as well as the 2 fecal markers lactoferrin and calprotectin were determined. Statistics comprised Kruskal-Wallis test and U test in addition to an assessment of receiver operating characteristic. Interferon γ (IFNγ) levels were significantly increased in the viral group compared to the bacterial and nonspecific group. For the bacterial group, both fecal markers lactoferrin and calprotectin as well as CRP were significantly higher in comparison to the other 2 groups. To differentiate between bacterial and viral gastroenteritis, CRP, serum IFNγ, and the fecal proteins lactoferrin and calprotectin may be useful. A corresponding algorithm should be evaluated prospectively. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. The association between serum C-reactive protein and macronutrients and antioxidants intake in hemodialysis patients.

    Science.gov (United States)

    Kooshki, A; Samadipour, E; Akbarzadeh, R

    2015-01-01

    Background: Despite the high levels of inflammation in hemodialysis patients and the effects of diet on systemic inflammation, such as the development of atherosclerosis and cardiovascular disease, few studies have evaluated the relationship of macronutrients and antioxidants intake with serum C-reactive protein (CRP). Therefore, this study assessed the relationship between serum high sensitivity CRP (hs-CRP) with macronutrients and antioxidants intake and serum albumin. Methods: This cross-sectional study used census sampling to select 75 hemodialysis patients (35 men and 40 women) who attended the hemodialysis department of Vaseie Hospital of Sabzevar, Iran. After obtaining the written consent, all the patients were interviewed and dietary data was collected by using a semi-quantitative food frequency questionnaire including 160 food items. Diet analysis was performed with Nutritionist IV. Before being connected to the dialysis machine, 5 cc fasting blood samples were obtained from all participants and serum hs-CRP and albumin levels were measured. All the statistical analyses were conducted with SPSS -for Windows, version 16.0. Results: The patients' mean body mass index was 20.09 ± 3.27 kg/ m2. The participants' intake of antioxidants and all macronutrients, except for carbohydrates and proteins, was less than the standard levels. Moreover, the hs-CRP had significant inverse relationships with serum albumin (P=0.0001) and vitamin E and C intakes but was not significant. Also, a significant relationship was observed between hs-CRP levels and the intake of energy (P=0.002) and protein (P=0.0001). Conclusion: Our findings indicated hs-CRP levels of hemodialysis patients to have significant inverse relationships with serum albumin and vitamin E and C intakes but was not significant. Also, a significant relationship was observed between hs-CRP levels and the intake of energy and protein.

  10. A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans

    Science.gov (United States)

    Zou, Wei; Shen, Ao; Dong, Xintong; Tugizova, Madina; Xiang, Yang K; Shen, Kang

    2016-01-01

    Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a multi-protein receptor-ligand complex that also contains two transmembrane ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA-1. The activation of DMA-1 strictly requires all three ligands, which establishes a combinatorial code to precisely target and pattern dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.18345.001 PMID:27705746

  11. Sensitive detection of C-reactive protein using optical fiber Bragg gratings.

    Science.gov (United States)

    Sridevi, S; Vasu, K S; Asokan, S; Sood, A K

    2015-03-15

    An accurate and highly sensitive sensor platform has been demonstrated for the detection of C-reactive protein (CRP) using optical fiber Bragg gratings (FBGs). The CRP detection has been carried out by monitoring the shift in Bragg wavelength (ΔλB) of an etched FBG (eFBG) coated with an anti-CRP antibody (aCRP)-graphene oxide (GO) complex. The complex is characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy. A limit of detection of 0.01mg/L has been achieved with a linear range of detection from 0.01mg/L to 100mg/L which includes clinical range of CRP. The eFBG sensor coated with only aCRP (without GO) show much less sensitivity than that of aCRP-GO complex coated eFBG. The eFBG sensors show high specificity to CRP even in the presence of other interfering factors such as urea, creatinine and glucose. The affinity constant of ∼1.1×10(10)M(-1) has been extracted from the data of normalized shift (ΔλB/λB) as a function of CRP concentration. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. C-reactive protein, physical activity and cardiorespiratory fitness in Portuguese adolescents: a cross-sectional study.

    Science.gov (United States)

    Agostinis Sobrinho, Cesar Aparecido; Moreira, Carla Marisa Maia; Mota, Jorge Augusto Pinto da Silva; Santos, Rute Marina Roberto

    2015-09-01

    The goal of this study was to investigate the association of physical activity (PA) and cardiorespiratory fitness with C-reactive protein (CRP) concentration in adolescents. The sample included 386 Portuguese adolescents (n = 207, female), age 12-18 years, assessed in the year 2012. The PA was assessed with the use of accelerometers, and the cardiorespiratory fitness was assessed by the Fitnessgram Pacer test. Blood samples were collected after a 10-hour fasting, and high-sensitivity PCR concentration was further assessed. Significant associations between CRP and cardiorespiratory fitness were found for females (r = -0.313; p genders. Therefore, CRP is apparently negatively associated with cardiorespiratory fitness, with differences between males and females; for females it seems less dependent than BMI.

  13. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2010-02-12

    Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

  14. A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs

    Directory of Open Access Journals (Sweden)

    Ugander Martin

    2006-11-01

    Full Text Available Abstract Background A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. Methods Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group. At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P Results At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p = 0.004 and the insulin response was significantly lower in the Paleolithic group (p = 0.001. The geometric mean of C-reactive protein was 82% lower (p = 0.0007 and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p = 0.007. In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets

  15. Covalent modification of cytochrome c by reactive metabolites of furan.

    Science.gov (United States)

    Phillips, Martin B; Sullivan, Mathilde M; Villalta, Peter W; Peterson, Lisa A

    2014-01-21

    Metabolism of the hepatotoxicant furan leads to protein adduct formation in the target organ. The initial bioactivation step involves cytochrome P450-catalyzed oxidation of furan, generating cis-2-butene-1,4-dial (BDA). BDA reacts with lysine to form pyrrolin-2-one adducts. Metabolic studies indicate that BDA also reacts with glutathione (GSH) to generate 2-(S-glutathionyl)butanedial (GSH-BDA), which then reacts with lysine to form GSH-BDA-lysine cross-links. To explore the relative reactivity of these two reactive intermediates, cytochrome c was reacted with BDA in the presence and absence of GSH. As judged by MALDI-TOF mass spectrometry, BDA reacts extensively with cytochrome c to form adducts that add 66 Da to the protein, consistent with the formation of pyrrolinone adducts. Addition of GSH to the reaction mixture reduced the overall extent of adduct formation. The mass of the adducted protein was shifted by 355 Da as expected for GSH-BDA-protein cross-link formation. LC-MS/MS analysis of the tryptic digests of the alkylated protein indicated that the majority of adducts occurred on lysine residues, with BDA reacting less selectively than GSH-BDA. Both types of adducts may contribute to the toxic effects of furan.

  16. Effect of fluoxetine and adenosine receptor NECA agonist on G alpha q/11 protein of C6 glioma cells

    Czech Academy of Sciences Publication Activity Database

    Kovářů, H.; Kovářů, F.; Lisá, Věra

    2012-01-01

    Roč. 33, č. 6 (2012), s. 614-618 ISSN 0172-780X Institutional support: RVO:67985823 Keywords : C6 glioma cells * SSRI antidepressant * G alpha q/11 signalling * G protein coupled receptor Subject RIV: ED - Physiology Impact factor: 0.932, year: 2012

  17. On-chip determination of C-reactive protein using magnetic particles in continuous flow.

    Science.gov (United States)

    Phurimsak, Chayakom; Tarn, Mark D; Peyman, Sally A; Greenman, John; Pamme, Nicole

    2014-11-04

    We demonstrate the application of a multilaminar flow platform, in which functionalized magnetic particles are deflected through alternating laminar flow streams of reagents and washing solutions via an external magnet, for the rapid detection of the inflammatory biomarker, C-reactive protein (CRP). The two-step sandwich immunoassay was accomplished in less than 60 s, a vast improvement on the 80-300 min time frame required for enzyme-linked immunosorbent assays (ELISA) and the 50 min necessary for off-chip magnetic particle-based assays. The combination of continuous flow and a stationary magnet enables a degree of autonomy in the system, while a detection limit of 0.87 μg mL(-1) makes it suitable for the determination of CRP concentrations in clinical diagnostics. Its applicability was further proven by assaying real human serum samples and comparing those results to values obtained using standard ELISA tests.

  18. Receptor Activity-modifying Protein-directed G Protein Signaling Specificity for the Calcitonin Gene-related Peptide Family of Receptors.

    Science.gov (United States)

    Weston, Cathryn; Winfield, Ian; Harris, Matthew; Hodgson, Rose; Shah, Archna; Dowell, Simon J; Mobarec, Juan Carlos; Woodlock, David A; Reynolds, Christopher A; Poyner, David R; Watkins, Harriet A; Ladds, Graham

    2016-10-14

    The calcitonin gene-related peptide (CGRP) family of G protein-coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in a Gα s -mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gα s and Gα q but also identify a Gα i component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMP-dependent signaling bias among the Gα s , Gα i , and Gα q/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase

    Directory of Open Access Journals (Sweden)

    Guan Kunliang

    2003-06-01

    Full Text Available Abstract Background G protein-coupled receptors (GPCRs interact with heterotrimeric GTP-binding proteins (G proteins to modulate acute changes in intracellular messenger levels and ion channel activity. In contrast, long-term changes in cellular growth, proliferation and differentiation are often mediated by tyrosine kinase receptors and certain GPCRs by activation of mitogen-activated protein (MAP kinases. Complex interactions occur between these signaling pathways, but the specific mechanisms of such regulatory events are not well-understood. In particular it is not clear whether GPCRs are modulated by tyrosine kinase receptor-MAP kinase pathways. Results Here we describe tyrosine kinase receptor regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT2C receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and insulin-like growth factor type 1 (IGF-1 on the 5-HT2C receptor is dependent on tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin had no effect on another GPCR that shares the same G protein signaling pathway as the 5-HT2C receptor. This effect is also direct: activated MAP kinase mimicked the effect of insulin, and removing a putative MAP kinase site from the 5-HT2C receptor abolished the effect of insulin. Conclusion These results show that insulin signaling can inhibit 5-HT2C receptor activity and suggest that MAP kinase may play a direct role in regulating the function of a specific GPCR.

  20. C-reactive protein in patients with Guillain Barré syndrome

    Directory of Open Access Journals (Sweden)

    Chetana Vaishnavi

    2014-01-01

    Full Text Available Context: C-reactive protein (CRP is an acute phase reactant, widely used as a biomarker for various infectious and inflammatory conditions. Guillain-Barrι syndrome (GBS is an acute, autoimmune, polyradiculoneuropathy, triggered by infectious agents such as Campylobacter jejuni. GBS is generally precipitated 1-3 weeks following C. jejuni infection which suggests a humoral immunopathogenic mechanism. Aims: Basal CRP levels were estimated in sera of patients with GBS and compared with adequate controls. Settings & Design: The study population was divided into 4 groups: (i GBS group included 45 newly diagnosed GBS patients; (ii Neurological control (NC group comprised of 59 patients with non-paralytic neurological symptoms/disorders; (iii Non-neurological controls (NNC comprised of 43 patients having no neurological symptoms and (iv Healthy controls (HC comprised of 101 healthy subjects. Materials and Methods: CRP was evaluated using slide latex agglutination test (LAT and enzyme linked immunosorbent assay (ELISA. Statistical Analysis: Statistical analysis was done by the Chi-square test. Results: CRP by LAT was positive in 24.4% GBS group, 34% NC group and 44% NNC group. The range of titer in CRP positive samples in the three patient groups (GBS, NC, NNC was at concentration of 0.6 mg/dl to 19.2 mg/dl. Similar results were also obtained by ELISA in the patient groups. None of the HC subjects was positive for detectable levels of CRP. High basal level of CRP was detected in patients with GBS. Conclusion: Autoimmune conditions like GBS can stimulate the production of a high level of inflammation resulting in an increase in the CRP production.

  1. C-Reactive Protein Predicts Progression of Peripheral Arterial Disease in Patients with Type 2 Diabetes: A 5-Year Follow-Up Study

    Directory of Open Access Journals (Sweden)

    Popović Ljiljana

    2014-09-01

    Full Text Available Background: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP is a risk factor for the peripheral arterial disease (PAD in diabetes. This study aimed to evaluate the possible predictive significance of hs-CRP for the development and progression of PAD in patients with type 2 diabetes (T2D.

  2. [Relationship between high-sensitivity C-reactive protein and obesity/metabolic syndrome in children].

    Science.gov (United States)

    Chen, Fangfang; Wang, Wenpeng; Teng, Yue; Hou, Dongqing; Zhao, Xiaoyuan; Yang, Ping; Yan, Yinkun; Mi, Jie

    2014-06-01

    To explore the relationship between high-sensitivity C-reactive protein (hsCRP) and obesity/metabolic syndrome (MetS) related factors in children. 403 children aged 10-14 and born in Beijing were involved in this study. Height, weight, waist circumference, fat mass percentage (Fat%), blood pressure (BP), hsCRP, triglyceride (TG), total cholesterol (TC), fasting plasma glucose (FPG), high and low density lipoprotein cholesterol (HDL-C, LDL-C) were observed among these children. hsCRP was transformed with base 10 logarithm (lgCRP). MetS was defined according to the International Diabetes Federation 2007 definition. Associations between MetS related components and hsCRP were tested using partial correlation analysis, analysis of covariance and linear regression models. 1) lgCRP was positively correlated with BMI, waist circumference, Fat%,BP, FPG, LDL-C and TC while negatively correlated with HDL-C. With BMI under control, the relationships disappeared, but LDL-C (r = 0.102). 2) The distributions of lgCRP showed obvious differences in all the metabolic indices, in most groups, respectively. With BMI under control, close relationships between lgCRP and high blood pressure/high TG disappeared and the relationship with MetS weakened. 3) Through linear regression models, factors as waist circumference, BMI, Fat% were the strongest factors related to hsCRP, followed by systolic BP, HDL-C, diastolic BP, TG and LDL-C. With BMI under control, the relationships disappeared, but LDL-C(β = 0.045). hsCRP was correlated with child obesity, lipid metabolism and MetS. Waist circumference was the strongest factors related with hsCRP. Obesity was the strongest and the independent influencing factor of hsCRP.

  3. A comparison of osteoprotegerin with adiponectin and high-sensitivity C-reactive protein (hsCRP) as a marker for insulin resistance.

    LENUS (Irish Health Repository)

    O'Sullivan, Eoin P

    2013-01-01

    Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reactive protein (hsCRP). Osteoprotegerin (OPG) has been shown to be elevated in type 2 diabetes, but whether it reflects underlying IR is unclear. We aimed to compare the ability of serum OPG with adiponectin and hsCRP to act as a marker for IR in individuals with normal and abnormal glucose tolerance.

  4. Cloning of human genes encoding novel G protein-coupled receptors

    Energy Technology Data Exchange (ETDEWEB)

    Marchese, A.; Docherty, J.M.; Heiber, M. [Univ. of Toronto, (Canada)] [and others

    1994-10-01

    We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q2.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1. 31 refs., 5 figs., 1 tab.

  5. Overexpression of the endothelial protein C receptor is detrimental during pneumonia-derived gram-negative sepsis (Melioidosis.

    Directory of Open Access Journals (Sweden)

    Liesbeth M Kager

    Full Text Available The endothelial protein C receptor (EPCR enhances anticoagulation by accelerating activation of protein C to activated protein C (APC and mediates anti-inflammatory effects by facilitating APC-mediated signaling via protease activated receptor-1. We studied the role of EPCR in the host response during pneumonia-derived sepsis instigated by Burkholderia (B. pseudomallei, the causative agent of melioidosis, a common form of community-acquired Gram-negative (pneumosepsis in South-East Asia.Soluble EPCR was measured in plasma of patients with septic culture-proven melioidosis and healthy controls. Experimental melioidosis was induced by intranasal inoculation of B. pseudomallei in wild-type (WT mice and mice with either EPCR-overexpression (Tie2-EPCR or EPCR-deficiency (EPCR(-/-. Mice were sacrificed after 24, 48 or 72 hours. Organs and plasma were harvested to measure colony forming units, cellular influxes, cytokine levels and coagulation parameters. Plasma EPCR-levels were higher in melioidosis patients than in healthy controls and associated with an increased mortality. Tie2-EPCR mice demonstrated enhanced bacterial growth and dissemination to distant organs during experimental melioidosis, accompanied by increased lung damage, neutrophil influx and cytokine production, and attenuated coagulation activation. EPCR(-/- mice had an unremarkable response to B. pseudomallei infection as compared to WT mice, except for a difference in coagulation activation in plasma.Increased EPCR-levels correlate with accelerated mortality in patients with melioidosis. In mice, transgenic overexpression of EPCR aggravates outcome during Gram-negative pneumonia-derived sepsis caused by B. pseudomallei, while endogenous EPCR does not impact on the host response. These results add to a better understanding of the regulation of coagulation during severe (pneumosepsis.

  6. Elemental Zinc Is Inversely Associated with C-Reactive Protein and Oxidative Stress in Chronic Liver Disease.

    Science.gov (United States)

    Uddin, Md Giash; Hossain, Mohammad Salim; Rahman, Md Atiqur; Uddin, A H M Mazbah; Bhuiyan, Md Shafiullah

    2017-08-01

    Chronic liver disease (CLD) is associated with the destruction of liver parenchyma cell. It is the main cause of morbidity and mortality in most of the developed countries. Oxidative stress and altered levels of different trace elements in serum have been documented for different diseases including inflammation and many liver diseases. This study aims to evaluate the serum level of malondialdehyde (MDA), nitric oxide (NO), antioxidant vitamin C, C-reactive protein (CRP), and zinc (Zn) in CLD patients and to establish a correlation among the study parameters with the severity of inflammatory conditions of CLD. In this study, CLD patients and healthy volunteers were recruited. Total cholesterol and triglyceride were determined by colorimeter using enzymatic method. Serum non-enzymatic antioxidant vitamin C, reactive oxygen species nitric oxide (NO), and malondialdehyde (MDA) were determined by UV-spectrophotometric method. Trace element (Zn) levels were determined by graphite furnace atomic absorption spectroscopy. Independent sample t test and Pearson's correlation test were performed for statistical analysis using the statistical software package SPSS, Version 20. Studies showed that the MDA (p CLD patients than in control subjects. The antioxidant vitamin C (p CLD patients than in control subjects. Elemental Zn showed an inverse relationship with MDA, NO, and CRP but positively correlated with antioxidant capacity, whereas MDA showed a positive correlation with CRP level. Thus, we conclude that attenuated level of Zn and antioxidant in serum play an important role in the inflammatory status of CLD patients by elevating the concentration of MDA, NO, and CRP.

  7. Association between lectin complement pathway initiators, C-reactive protein and left ventricular remodeling in myocardial infarction-a magnetic resonance study

    DEFF Research Database (Denmark)

    Schoos, Mikkel Malby; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole

    2013-01-01

    Lectin complement pathway (LP) activation is an important mechanism in myocardial ischemia reperfusion injury (IRI). LP is activated via the recognition molecules mannose-binding lectin (MBL), ficolins-2 and-3 and is regulated by MBL/Ficolin-associated Protein-1 (MAP-1). Also, C-reactive protein...... (CRP) and ficolin-2 interact in vitro, but the role of the ficolins in IRI is unknown.Methods and results In 55 patients with ST segment elevation myocardial infarction, we investigated the association of LP components and CRP in plasma samples with left ventricular (LV) end systolic and diastolic......-activation in IRI and LV remodeling....

  8. CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

    DEFF Research Database (Denmark)

    Ammitzbøll, Christian Gytz; Steffensen, Rudi; Bøgsted, Martin

    2014-01-01

    investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. RESULTS: The minor allele of rs1205 C > T was associated......INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision...

  9. Endo- and exocytic rate constants for spontaneous and protein kinase C-activated T cell receptor cycling

    DEFF Research Database (Denmark)

    Menné, Charlotte; Møller Sørensen, Tine; Siersma, Volkert

    2002-01-01

    To determine the rate constants of spontaneous and activated TCR cycling, we examined TCR endo- and exocytosis in the human T cell line Jurkat by three different methods. Using a simple kinetic model for TCR cycling and non-linear regression analyses, we found that the spontaneous endocytic rate...... constant of the TCR was low (approximately 0.012 min(-1)) whereas the spontaneous exocytic rate constant was similar to that of other cycling receptors (approximately 0.055 min(-1)). Following protein kinase C activation (PKC) the endocytic rate constant was increased tenfold (to approximately 0.128 min(-1......)) whereas the exocytic rate constant was unaffected. Thus, the TCR becomes a rapidly cycling receptor with kinetics similar to classical cycling receptors subsequent to PKC activation. This results in a reduction of the half-life of cell surface expressed TCR from approximately 58 to 6 min and allows rapid...

  10. Functional relevance of G-protein-coupled-receptor-associated proteins, exemplified by receptor-activity-modifying proteins (RAMPs).

    Science.gov (United States)

    Fischer, J A; Muff, R; Born, W

    2002-08-01

    The calcitonin (CT) receptor (CTR) and the CTR-like receptor (CRLR) are close relatives within the type II family of G-protein-coupled receptors, demonstrating sequence identity of 50%. Unlike the interaction between CT and CTR, receptors for the related hormones and neuropeptides amylin, CT-gene-related peptide (CGRP) and adrenomedullin (AM) require one of three accessory receptor-activity-modifying proteins (RAMPs) for ligand recognition. An amylin/CGRP receptor is revealed when CTR is co-expressed with RAMP1. When complexed with RAMP3, CTR interacts with amylin alone. CRLR, initially classed as an orphan receptor, is a CGRP receptor when co-expressed with RAMP1. The same receptor is specific for AM in the presence of RAMP2. Together with human RAMP3, CRLR defines an AM receptor, and with mouse RAMP3 it is a low-affinity CGRP/AM receptor. CTR-RAMP1, antagonized preferentially by salmon CT-(8-32) and not by CGRP-(8-37), and CRLR-RAMP1, antagonized by CGRP-(8-37), are two CGRP receptor isotypes. Thus amylin and CGRP interact specifically with heterodimeric complexes between CTR and RAMP1 or RAMP3, and CGRP and AM interact with complexes between CRLR and RAMP1, RAMP2 or RAMP3.

  11. High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis.

    Science.gov (United States)

    Persson, G Rutger; Pettersson, Thomas; Ohlsson, Ola; Renvert, Stefan

    2005-03-01

    Serum high-sensitivity C-reactive protein (hsC-rp) is a non-specific marker of inflammation. Elevated hsC-rp levels are found in subjects with cardiovascular diseases (CVDs). Periodontitis may influence hsC-rp levels. To assess periodontal status and hsC-rp serum levels in consecutive subjects hospitalized and diagnosed with acute myocardial infarction (AMI) (n=85) and in a group of carefully matched subjects (gender, age social, ethnic, and smoking habits) without clinical evidence of CVD (n=63). hsC-rp levels, other routine serum values, and clinical periodontal conditions were studied. Subjects with AMI had higher hsC-rp levels than control subjects (pperiodontitis (30% or more sites with>4.0 mm loss of alveolar bone) had serum hsC-rp>1.8 mg/l was 1.5 (95% CI: 1.1-7.3, pperiodontal parameters in an explanatory model to hsC-rp values. Only the serum leucocyte (white blood cell (WBC)) counts were explanatory to hsC-rp values (beta standard coefficient=0.45, t=3.2, pperiodontitis (pperiodontitis in subjects with no evidence of CVD. (3) Periodontal parameters are not explanatory to elevated serum hsC-rp values if serum WBC and low-density lipoprotein counts are included in the regression model. Copyright 2005 Blackwell Munksgaard.

  12. Effect of nonsurgical periodontal treatment on C-reactive protein levels in maintenance hemodialysis patients.

    Science.gov (United States)

    Yazdi, Farin Kiany; Karimi, Noozhan; Rasouli, Manoochehr; Roozbeh, Jamshid

    2013-01-01

    C-reactive protein (CRP) has been implicated as a possible mediator of the association between periodontitis and several systemic diseases. This study evaluated the impact of nonsurgical periodontal treatment on the serum levels of CRP in chronic kidney disease (CKD) patients on hemodialysis. A total of 77 CKD patients on hemodialysis were included in this study. At baseline, periodontal examination was assessed for all the patients, and chronic periodontitis was defined through clinical attachment level and probing pocket depth, according to the American Association of Periodontology. Nonsurgical periodontal treatment was performed and serum levels of CRP were evaluated at baseline and 8 weeks after periodontal treatment. Periodontal treatment resulted in significant reductions in CRP levels (p periodontitis. Periodontitis is an important source of systemic inflammation in CKD patients. Nonsurgical periodontal treatment can effectively reduce the serum level of CRP in these patients.

  13. The added value of C-reactive protein measurement in diagnosing pneumonia in primary care

    DEFF Research Database (Denmark)

    Minnaard, Margaretha C; de Groot, Joris A H; Hopstaken, Rogier M

    2017-01-01

    BACKGROUND: C-reactive protein (CRP) is increasingly being included in the diagnostic work-up for community-acquired pneumonia in primary care. Its added diagnostic value beyond signs and symptoms, however, remains unclear. We conducted a meta-analysis of individual patient data to quantify...... to a basic signs-and-symptoms prediction model was assessed. Outcome measures were improvement in discrimination between patients with and without pneumonia in primary care and improvement in risk classification, both within the individual studies and across studies. RESULTS: Authors of 8 eligible studies (n...... = 5308) provided their data sets. In all of the data sets, discrimination between patients with and without pneumonia improved after CRP measurement was added to the prediction model (extended model), with a mean improvement in the area under the curve of 0.075 (range 0.02-0.18). In a hypothetical cohort...

  14. A review of C-reactive protein: A diagnostic indicator in periodontal medicine

    Directory of Open Access Journals (Sweden)

    Renuka Devi Ramamoorthy

    2012-01-01

    Full Text Available Periodontitis is a local inflammatory process mediating the destruction of periodontal tissues, triggered by bacterial insult. Recent evidence suggests the presence of chronic inflammatory periodontal disease may significantly affect systemic health conditions such as coronary heart disease, stroke, or adverse pregnancy outcome. C-reactive protein (CRP is an acute phase protein which reflects a measure of the acute phase response. CRP is used as one of the markers of choice in monitoring the acute phase response because it increases to a relatively high concentration compared to basal concentration. CRP has been shown to predict cardiovascular (CV mortality in recent studies, and elevated CRP levels have been observed in middle-aged patients with periodontitis. Combination of chronic infections like periodontitis with elevated CRP is associated with higher chronic heart diseases. The recognition of the relationship between periodontal diseases and atherosclerotic events is relatively recent and mostly based on the inflammatory hypothesis of atherosclerosis. Periodontal disease is one of the risk factors for cardiovascular disease and possibly one of its causes. Hence, even associations of modest magnitude have a large impact. The cost to the society directly attributable to atherosclerotic sequelae is very large. Periodontitis is treatable; moreover, it is preventable. Experimental conformation of this shows that another widely prevalent and preventable contributor to the burden of cardiovascular disease would be added to the options available of the clinicians and public health practitioners for the control of the epidemic of cardiovascular disease.

  15. Cloning of the human androgen receptor cDNA

    International Nuclear Information System (INIS)

    Govindan, M.V.; Burelle, M.; Cantin, C.; Kabrie, C.; Labrie, F.; Lachance, Y.; Leblanc, G.; Lefebvre, C.; Patel, P.; Simard, J.

    1988-01-01

    The authors discuss how in order to define the functional domains of the human androgen receptor, complementary DNA (cDNA) clones encoding the human androgen receptor (hAR) have been isolated from a human testis λgtll cDNA library using synthetic oligonnucleotide probes, homologous to segments of the human glucocorticoid, estradiol and progesterone receptors. The cDNA clones corresponding to the human glucocorticoid, estradiol and progesterone receptors were eliminated after cross-hybridization with their respective cDNA probes and/or after restriction mapping of the cDNA clones. The remaining cDNA clones were classified into different groups after analysis by restriction digestion and cross-hybridization. Two of the largest cDNA clones from each group were inserted into an expression vector in both orientations. The linearized plasmids were used as templates in in vitro transcription with T7 RNA polymerase. Subsequent in vitro translation of the purified transcripts in rabbit reticulocyte lysate followed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) permitted the characterization of the encoded polyeptides. The expressed proteins larger than 30,000 Da were analyzed for their ability to bind tritium-labelled dihydrotestosterone ([ 3 H] DHT) with high affinity and specificity

  16. Ligand-induced dynamics of heterotrimeric G protein-coupled receptor-like kinase complexes.

    Directory of Open Access Journals (Sweden)

    Meral Tunc-Ozdemir

    Full Text Available Arabidopsis, 7-transmembrane Regulator of G signaling protein 1 (AtRGS1 modulates canonical G protein signaling by promoting the inactive state of heterotrimeric G protein complex on the plasma membrane. It is known that plant leucine-rich repeat receptor-like kinases (LRR RLKs phosphorylate AtRGS1 in vitro but little is known about the in vivo interaction, molecular dynamics, or the cellular consequences of this interaction.Therefore, a subset of the known RLKs that phosphorylate AtRGS1 were selected for elucidation, namely, BAK1, BIR1, FLS2. Several microscopies for both static and dynamic protein-protein interactions were used to follow in vivo interactions between the RLKs and AtRGS1 after the presentation of the Pathogen-associated Molecular Pattern, Flagellin 22 (Flg22. These microscopies included Förster Resonance Energy Transfer, Bimolecular Fluoresence Complementation, and Cross Number and Brightness Fluorescence Correlation Spectroscopy. In addition, reactive oxygen species and calcium changes in living cells were quantitated using luminometry and R-GECO1 microscopy.The LRR RLKs BAK1 and BIR1, interact with AtRGS1 at the plasma membrane. The RLK ligand flg22 sets BAK1 in motion toward AtRGS1 and BIR1 away, both returning to the baseline orientations by 10 minutes. The C-terminal tail of AtRGS1 is important for the interaction with BAK1 and for the tempo of the AtRGS1/BIR1 dynamics. This window of time corresponds to the flg22-induced transient production of reactive oxygen species and calcium release which are both attenuated in the rgs1 and the bak1 null mutants.A temporal model of these interactions is proposed. flg22 binding induces nearly instantaneous dimerization between FLS2 and BAK1. Phosphorylated BAK1 interacts with and enables AtRGS1 to move away from BIR1 and AtRGS1 becomes phosphorylated leading to its endocytosis thus leading to de-repression by permitting AtGPA1 to exchange GDP for GTP. Finally, the G protein complex

  17. Diagnostic Value of Serial Measurement of C-Reactive Protein in the Detection of a Surgical Complication after Laparoscopic Bowel Resection for Endometriosis

    DEFF Research Database (Denmark)

    Riiskjær, Mads; Forman, Axel; Kesmodel, Ulrik Schiøler

    2016-01-01

    AIMS: The study aimed to assess the diagnostic value of serial monitoring of biochemical inflammatory markers (C-reactive protein (CRP) and white blood cell (WBC) count) in the postoperative diagnosis of anastomotic leakage or ureteral injury after bowel resection for deep infiltrating endometrio......AIMS: The study aimed to assess the diagnostic value of serial monitoring of biochemical inflammatory markers (C-reactive protein (CRP) and white blood cell (WBC) count) in the postoperative diagnosis of anastomotic leakage or ureteral injury after bowel resection for deep infiltrating...... endometriosis. METHODS: This is a review of prospectively collected data from 217 patients who underwent laparoscopic bowel resection for endometriosis from January 2009 to April 2015. Patients with an anastomotic leakage or ureteral injury were identified and classified. RESULTS: The frequency of anastomotic...... leakage requiring reoperation was 8.3%. The frequency of ureteral injury was 4.6%. Median time to diagnosis was 6 days for anastomotic leakage and 8 days for ureteral injury. The daily mean values of serum CRP were significantly higher in patients with a surgical complication starting at the second...

  18. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.

    Directory of Open Access Journals (Sweden)

    Gunnar Kleinau

    Full Text Available In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR and different subtypes of G-proteins. The thyrotropin receptor (TSHR binds G-proteins promiscuously and activates both Gs (cAMP and Gq (IP. Our goal was to dissect selectivity patterns for both pathways in the intracellular region of this receptor. We were particularly interested in the participation of poorly investigated receptor parts.We systematically investigated the amino acids of intracellular loop (ICL 1 and helix 8 using site-directed mutagenesis alongside characterization of cAMP and IP accumulation. This approach was guided by a homology model of activated TSHR in complex with heterotrimeric Gq, using the X-ray structure of opsin with a bound G-protein peptide as a structural template.We provide evidence that ICL1 is significantly involved in G-protein activation and our model suggests potential interactions with subunits G alpha as well as G betagamma. Several amino acid substitutions impaired both IP and cAMP accumulation. Moreover, we found a few residues in ICL1 (L440, T441, H443 and helix 8 (R687 that are sensitive for Gq but not for Gs activation. Conversely, not even one residue was found that selectively affects cAMP accumulation only. Together with our previous mutagenesis data on ICL2 and ICL3 we provide here the first systematically completed map of potential interfaces between TSHR and heterotrimeric G-protein. The TSHR/Gq-heterotrimer complex is characterized by more selective interactions than the TSHR/Gs complex. In fact the receptor interface for binding Gs is a subset of that for Gq and we postulate that this may be true for other GPCRs coupling these G-proteins. Our findings support that G-protein coupling and preference is dominated by specific structural features at the intracellular region of the activated GPCR but is completed by additional complementary recognition patterns between receptor and G-protein

  19. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.

    Science.gov (United States)

    Kleinau, Gunnar; Jaeschke, Holger; Worth, Catherine L; Mueller, Sandra; Gonzalez, Jorge; Paschke, Ralf; Krause, Gerd

    2010-03-18

    In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR) and different subtypes of G-proteins. The thyrotropin receptor (TSHR) binds G-proteins promiscuously and activates both Gs (cAMP) and Gq (IP). Our goal was to dissect selectivity patterns for both pathways in the intracellular region of this receptor. We were particularly interested in the participation of poorly investigated receptor parts.We systematically investigated the amino acids of intracellular loop (ICL) 1 and helix 8 using site-directed mutagenesis alongside characterization of cAMP and IP accumulation. This approach was guided by a homology model of activated TSHR in complex with heterotrimeric Gq, using the X-ray structure of opsin with a bound G-protein peptide as a structural template.We provide evidence that ICL1 is significantly involved in G-protein activation and our model suggests potential interactions with subunits G alpha as well as G betagamma. Several amino acid substitutions impaired both IP and cAMP accumulation. Moreover, we found a few residues in ICL1 (L440, T441, H443) and helix 8 (R687) that are sensitive for Gq but not for Gs activation. Conversely, not even one residue was found that selectively affects cAMP accumulation only. Together with our previous mutagenesis data on ICL2 and ICL3 we provide here the first systematically completed map of potential interfaces between TSHR and heterotrimeric G-protein. The TSHR/Gq-heterotrimer complex is characterized by more selective interactions than the TSHR/Gs complex. In fact the receptor interface for binding Gs is a subset of that for Gq and we postulate that this may be true for other GPCRs coupling these G-proteins. Our findings support that G-protein coupling and preference is dominated by specific structural features at the intracellular region of the activated GPCR but is completed by additional complementary recognition patterns between receptor and G-protein subtypes.

  20. Association between insulin resistance and c-reactive protein among Peruvian adults

    Directory of Open Access Journals (Sweden)

    Gelaye Bizu

    2010-05-01

    Full Text Available Abstract Objective Insulin resistance (IR, a reduced physiological response of peripheral tissues to the action of insulin, is one of the major causes of type 2 diabetes. We sought to evaluate the relationship between serum C-reactive protein (CRP, a marker of systemic inflammation, and prevalence of IR among Peruvian adults. Methods This population based study of 1,525 individuals (569 men and 956 women; mean age 39 years old was conducted among residents in Lima and Callao, Peru. Fasting plasma glucose, insulin, and CRP concentrations were measured using standard approaches. Insulin resistance was assessed using the homeostasis model (HOMA-IR. Categories of CRP were defined by the following tertiles: 2.53 mg/l. Logistic regression procedures were employed to estimate odds ratios (OR and 95% confidence intervals (CI. Results Elevated CRP were significantly associated with increased mean fasting insulin and mean HOMA-IR concentrations (p 2.53 mg/l (upper tertile had a 2.18-fold increased risk of IR (OR = 2.18 95% CI 1.51-3.16 as compared with those in the lowest tertile ( Conclusion Our observations among Peruvians suggest that chronic systemic inflammation, as evidenced by elevated CRP, may be of etiologic importance in insulin resistance and diabetes.

  1. Effect of locally delivered tetracycline hydrochloride as an adjunct to scaling and root planing on Hba1c, C-reactive protein, and lipid profile in type 2 diabetes: A clinico-biochemical study

    Directory of Open Access Journals (Sweden)

    Vidya Dodwad

    2012-01-01

    Full Text Available Aim: The aim was to assess the levels of HbA1c, C-reactive protein, and lipid profile in patients with type 2 diabetes mellitus by treating the pockets using collagen impregnated sustained release resorbable tetracycline fiber (periodontal plus AB fiber following scaling and root planing (SRP. Materials and Methods: A total of 40 patients with type 2 diabetes mellitus were randomly distributed into two groups receiving either SRP and tetracycline fiber or SRP alone. Patients were evaluated clinically with gingival index, plaque index, probing depth, and relative attachment level, and bio-chemically with HbA1c, C Reactive Protein, and lipid profile at baseline, 1 month, and 3 months. Results: Significant reduction in all the clinical parameters was seen in the tetracycline group compared to the control group. Bio-chemical analysis also revealed similar results except for cholesterol and High density lipoprotein who did not show any significant reduction. Conclusion: Locally delivered tetracycline as a better treatment modality compared to SRP alone.

  2. Dissociation of activated protein C functions by elimination of protein S cofactor enhancement.

    LENUS (Irish Health Repository)

    Harmon, Shona

    2008-11-07

    Activated protein C (APC) plays a critical anticoagulant role in vivo by inactivating procoagulant factor Va and factor VIIIa and thus down-regulating thrombin generation. In addition, APC bound to the endothelial cell protein C receptor can initiate protease-activated receptor-1 (PAR-1)-mediated cytoprotective signaling. Protein S constitutes a critical cofactor for the anticoagulant function of APC but is not known to be involved in regulating APC-mediated protective PAR-1 signaling. In this study we utilized a site-directed mutagenesis strategy to characterize a putative protein S binding region within the APC Gla domain. Three single amino acid substitutions within the APC Gla domain (D35T, D36A, and A39V) were found to mildly impair protein S-dependent anticoagulant activity (<2-fold) but retained entirely normal cytoprotective activity. However, a single amino acid substitution (L38D) ablated the ability of protein S to function as a cofactor for this APC variant. Consequently, in assays of protein S-dependent factor Va proteolysis using purified proteins or in the plasma milieu, APC-L38D variant exhibited minimal residual anticoagulant activity compared with wild type APC. Despite the location of Leu-38 in the Gla domain, APC-L38D interacted normally with endothelial cell protein C receptor and retained its ability to trigger PAR-1 mediated cytoprotective signaling in a manner indistinguishable from that of wild type APC. Consequently, elimination of protein S cofactor enhancement of APC anticoagulant function represents a novel and effective strategy by which to separate the anticoagulant and cytoprotective functions of APC for potential therapeutic gain.

  3. The Role of Cgrp-Receptor Component Protein (Rcp in Cgrp-Mediated Signal Transduction

    Directory of Open Access Journals (Sweden)

    M. A. Prado

    2001-01-01

    Full Text Available The calcitonin gene-related peptide (CGRP-receptor component protein (RCP is a 17-kDa intracellular peripheral membrane protein required for signal transduction at CGRP receptors. To determine the role of RCP in CGRP-mediated signal transduction, RCP was depleted from NIH3T3 cells using antisense strategy. Loss of RCP protein correlated with loss of cAMP production by CGRP in the antisense cells. In contrast, loss of RCP had no effect on CGRP-mediated binding; therefore RCP is not acting as a chaperone for the CGRP receptor. Instead, RCP is a novel signal transduction molecule that couples the CGRP receptor to the cellular signal transduction machinery. RCP thus represents a prototype for a new class of signal transduction proteins that are required for regulation of G protein-coupled receptors.

  4. Rab GTPases Regulate Endothelial Cell Protein C Receptor-Mediated Endocytosis and Trafficking of Factor VIIa

    Science.gov (United States)

    Nayak, Ramesh C.; Keshava, Shiva; Esmon, Charles T.; Pendurthi, Usha R.; Rao, L. Vijaya Mohan

    2013-01-01

    Recent studies have established that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR). FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand complex. Rab GTPases are known to play a crucial role in the endocytic and exocytic pathways of receptors or receptor/ligand complexes. The present study was undertaken to investigate the role of Rab GTPases in the intracellular trafficking of EPCR and FVIIa. CHO-EPCR cells and human umbilical vein endothelial cells (HUVEC) were transduced with recombinant adenoviral vectors to express wild-type, constitutively active, or dominant negative mutant of various Rab GTPases. Cells were exposed to FVIIa conjugated with AF488 fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescence confocal microscopy. In cells expressing wild-type or constitutively active Rab4A, internalized AF488-FVIIa accumulated in early/sorting endosomes and its entry into the recycling endosomal compartment (REC) was inhibited. Expression of constitutively active Rab5A induced large endosomal structures beneath the plasma membrane where EPCR and FVIIa accumulated. Dominant negative Rab5A inhibited the endocytosis of EPCR-FVIIa. Expression of constitutively active Rab11 resulted in retention of accumulated AF488-FVIIa in the REC, whereas expression of a dominant negative form of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and prevented entry of internalized FVIIa into the REC. Expression of dominant negative Rab11 also inhibited the transport of FVIIa across the endothelium. Overall our data show that Rab GTPases regulate the internalization and intracellular trafficking of EPCR-FVIIa. PMID:23555015

  5. Serum C-Reactive Protein (CRP), Target for Therapy or Trouble?

    Science.gov (United States)

    Kraus, Virginia B; Jordan, Joanne M

    2007-02-07

    High sensitivity serum C-reactive protein (hs-CRP) has come into clinical use as a marker of risk for cardiovascular disease (CVD). In addition to a role as a marker of disease, CRP has also been implicated in the pathogenesis of CVD. Specific small-molecule inhibitors of CRP have recently been developed with the intent of mitigating cardiac damage during acute myocardial infarction. However, the use of CRP, both as a risk marker and a disease target are controversial for several reasons. Serum hs-CRP concentrations can be elevated on the basis of genetics, female gender, and non-Caucasian ethnicity. It is not clear, in these contexts, that elevations of hs-CRP have any pathological significance. As a non-specific indicator of inflammation, CRP is also not a specific indicator of a single disease state such as cardiovascular disease but elevated concentrations can be seen in association with other comorbidities including obesity and pulmonary disease. In sharp contrast to the proposed inhibition of CRP for cardiovascular disease treatment, the infusion of CRP has been shown to have profound therapeutic benefits for autoimmune disease and septic shock. The balance between the risks and benefits of these competing views of the role of CRP in disease and disease therapy is reminiscent of the ongoing controversy regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal disease and their cardiovascular side effects. Soon, NSAIDs may not be the only agents about which Rheumatologists and Cardiologists may spar.

  6. Procalcitonin and C-reactive protein in urinary tract infection diagnosis.

    Science.gov (United States)

    Xu, Rui-Ying; Liu, Hua-Wei; Liu, Ji-Ling; Dong, Jun-Hua

    2014-05-30

    Urinary infections are a common type of pediatric disease, and their treatment and prognosis are closely correlated with infection location. Common clinical manifestations and laboratory tests are insufficient to differentiate between acute pyelonephritis and lower urinary tract infection. This study was conducted to explore a diagnostic method for upper and lower urinary tract infection differentiation. The diagnostic values of procalcitonin (PCT) and C-reactive protein (CRP) were analyzed using the receiver operating characteristic curve method for upper and lower urinary tract infection differentiation. PCT was determined using chemiluminescent immunoassay. The PCT and CRP values in children with acute pyelonephritis were significantly higher than those in children with lower urinary tract infection (3.90 ± 3.51 ng/ml and 68.17 ± 39.42 mg/l vs. 0.48 ± 0.39 ng/ml and 21.39 ± 14.92 mg/l). The PCT values were correlated with the degree of renal involvement, whereas the CRP values failed to show such a significant correlation. PCT had a sensitivity of 90.47% and a specificity of 88% in predicting nephropathia, whereas CRP had sensitivity of 85.71% and a specificity of 48%. Both PCT and CRP can be used for upper and lower urinary tract infection differentiation, but PCT has higher sensitivity and specificity in predicting pyelonephritis than CRP. PCT showed better results than CRP. PCT values were also correlated with the degree of renal involvement.

  7. Late midlife C-reactive protein and interleukin-6 in middle aged danish men in relation to body size history within and across generations

    DEFF Research Database (Denmark)

    Pedersen, Jolene Lee Masters; Budtz-Jørgensen, Esben; Mortensen, Erik Lykke

    2016-01-01

    OBJECTIVE: The aim was to estimate the effects of ponderal index at birth and body mass index (BMI) in early adulthood on C-reactive protein (CRP) and interleukin-6 (IL-6) and to quantify the effects through subsequent measures of body size. In a subanalysis, the contributions of maternal BMI to ...

  8. The clinical value of determination of serum troponin I and hypersensitive C-reactive protein around extracorporeal circulation

    International Nuclear Information System (INIS)

    Wang Rui; Cao Yong; Yan Ji

    2005-01-01

    To explore the clinical value of determination of serum troponin I (cTnI) and hyper-sensitive C-reactive protein(hs-CRP) around extracorporeal circulation, cTnI and hs-CRP were determined in 46 patients with congenital heart disease before and after the surgery (0, 24h, 3d, 7d, 15d respectively). At the same time, electrocardiogram(ECG), hemo dynamics and other adverse events were recorded. Before the surgery results of cTnI and hs-CRP were in nor- mal range, wheraas after surgery the level of cTnI went up, reached its peak at 24h, and returned normal on d7. The level of hs-CRP begin to increase at 24h, returned normal on dT. Its level was higher in patients with postoperative infection than that in patients without infection, however, it returned normal after anti-inflammatory treatment. Therefore, cTnI and hs-CRP may be taken as diagnostic criteria of prognosis in patient after extracorporea circulation surgery. Postoperative infection around extracorporeal circulation surgery could be prevented by monitring hs-CRP concentration. (authors)

  9. High – Sensitivity C - reactive protein is associated with Traditional Cardiovascular Risk Factors in Indians with Type 2 Diabetes Mellitus

    OpenAIRE

    Asegaonkar, Shilpa B; Bavikar, Jayashree Suhas; Marathe, Amruta; Tekade, Mangesh; Asegaonkar, Balaji N.; Jayashree, Bardapurkar

    2013-01-01

    Background: India is experiencing twin epidemic of type 2 diabetes mellitus and cardiovascular diseases imposing huge toll on healthcare system. In type 2 diabetes 65-80% deaths occur due to cardiovascular disease whose etiology cannot be explained by chronic hyperglycemia, dyslipedemia and traditional cardiac risk factors. To improve risk stratification serum high-sensitivity C- reactive protein estimation is an adjunct to other risk factors. Study design: O.P.D. based Cross sectional study....

  10. G-protein coupling of cannabinoid receptors

    International Nuclear Information System (INIS)

    Glass, M.

    2001-01-01

    Full text: Since the cloning of the cannabinoid CB1 and CB2 receptors in the early 1990's extensive research has focused on understanding their signal transduction pathways. While it has been known for sometime that both receptors can couple to intracellular signalling via pertussis toxin sensitive G-proteins (Gi/Go), the specificity and kinetics of these interactions have only recently been elucidated. We have developed an in situ reconstitution approach to investigating receptor-G-protein interactions. This approach involves chaotropic extraction of receptor containing membranes in order to inactivate or remove endogenous G-proteins. Recombinant or isolated brain G-proteins can then be added back to the receptors, and their activation monitored through the binding of [ 35 S]-GTPγS. This technique has been utilised for an extensive study of cannabinoid receptor mediated activation of G-proteins. In these studies we have established that CB1 couples with high affinity to both Gi and Go type G-proteins. In contrast, CB2 couples strongly to Gi, but has a very low affinity for Go. This finding correlated well with the previous findings that while CB1 and CB2 both couple to the inhibition of adenylate cyclase, CB1 but not CB2 could also inhibit calcium channels. We then examined the ability of a range of cannabinoid agonists to activate the Gi and Go via CB1. Conventional receptor theory suggests that a receptor is either active or inactive with regard to a G-protein and that the active receptor activates all relevant G-proteins equally. However, in this study we found that agonists could produce different degrees of activation, depending on which G-protein was present. Further studies have compared the ability of the two endocannabinoids to drive the activation of Gi or Go. These studies show that agonists can induce multiple forms of activated receptor that differ in their ability to catalyse the activation of Gi or Go. The ability of an agonist to drive a receptor

  11. RTA, a candidate G protein-coupled receptor: Cloning, sequencing, and tissue distribution

    International Nuclear Information System (INIS)

    Ross, P.C.; Figler, R.A.; Corjay, M.H.; Barber, C.M.; Adam, N.; Harcus, D.R.; Lynch, K.R.

    1990-01-01

    Genomic and cDNA clones, encoding a protein that is a member of the guanine nucleotide-binding regulatory protein (G protein)-coupled receptor superfamily, were isolated by screening rat genomic and thoracic aorta cDNA libraries with an oligonucleotide encoding a highly conserved region of the M 1 muscarinic acetylcholine receptor. Sequence analyses of these clones showed that they encode a 343-amino acid protein (named RTA). The RTA gene is single copy, as demonstrated by restriction mapping and Southern blotting of genomic clones and rat genomic DNA. RTA RNA sequences are relatively abundant throughout the gut, vas deferens, uterus, and aorta but are only barely detectable (on Northern blots) in liver, kidney, lung, and salivary gland. In the rat brain, RTA sequences are markedly abundant in the cerebellum. TRA is most closely related to the mas oncogene (34% identity), which has been suggested to be a forebrain angiotensin receptor. They conclude that RTA is not an angiotensin receptor; to date, they have been unable to identify its ligand

  12. Cardiorespiratory fitness, pulmonary function and C-reactive protein levels in nonsmoking individuals with diabetes

    International Nuclear Information System (INIS)

    Francisco, C.O.; Catai, A.M.; Moura-Tonello, S.C.G.; Lopes, S.L.B.; Benze, B.G.; Del Vale, A.M.; Leal, A.M.O.

    2014-01-01

    The objective of this study was to evaluate cardiorespiratory fitness and pulmonary function and the relationship with metabolic variables and C-reactive protein (CRP) plasma levels in individuals with diabetes mellitus (DM). Nineteen men with diabetes and 19 age- and gender-matched control subjects were studied. All individuals were given incremental cardiopulmonary exercise and pulmonary function tests. In the exercise test, maximal workload (158.3±22.3 vs 135.1±25.2, P=0.005), peak heart rate (HR peak : 149±12 vs 139±10, P=0.009), peak oxygen uptake (VO 2peak : 24.2±3.2 vs 18.9±2.8, P<0.001), and anaerobic threshold (VO 2VT : 14.1±3.4 vs 12.2±2.2, P=0.04) were significantly lower in individuals with diabetes than in control subjects. Pulmonary function test parameters, blood pressure, lipid profile (triglycerides, HDL, LDL, and total cholesterol), and CRP plasma levels were not different in control subjects and individuals with DM. No correlations were observed between hemoglobin A1C (HbA1c), CRP and pulmonary function test and cardiopulmonary exercise test performance. In conclusion, the results demonstrate that nonsmoking individuals with DM have decreased cardiorespiratory fitness that is not correlated with resting pulmonary function parameters, HbA1c, and CRP plasma levels

  13. Cardiorespiratory fitness, pulmonary function and C-reactive protein levels in nonsmoking individuals with diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Francisco, C.O.; Catai, A.M.; Moura-Tonello, S.C.G. [Universidade Federal de São Carlos, Departamento de Fisioterapia, São Carlos, SP, Brasil, Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Lopes, S.L.B. [Universidade Federal de São Carlos, Departamento de Medicina, São Carlos, SP, Brasil, Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Benze, B.G. [Universidade Federal de São Carlos, Departamento de Estatística, São Carlos, SP, Brasil, Departamento de Estatística, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Del Vale, A.M.; Leal, A.M.O. [Universidade Federal de São Carlos, Departamento de Medicina, São Carlos, SP, Brasil, Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

    2014-04-15

    The objective of this study was to evaluate cardiorespiratory fitness and pulmonary function and the relationship with metabolic variables and C-reactive protein (CRP) plasma levels in individuals with diabetes mellitus (DM). Nineteen men with diabetes and 19 age- and gender-matched control subjects were studied. All individuals were given incremental cardiopulmonary exercise and pulmonary function tests. In the exercise test, maximal workload (158.3±22.3 vs 135.1±25.2, P=0.005), peak heart rate (HR{sub peak}: 149±12 vs 139±10, P=0.009), peak oxygen uptake (VO{sub 2peak}: 24.2±3.2 vs 18.9±2.8, P<0.001), and anaerobic threshold (VO{sub 2VT}: 14.1±3.4 vs 12.2±2.2, P=0.04) were significantly lower in individuals with diabetes than in control subjects. Pulmonary function test parameters, blood pressure, lipid profile (triglycerides, HDL, LDL, and total cholesterol), and CRP plasma levels were not different in control subjects and individuals with DM. No correlations were observed between hemoglobin A1C (HbA1c), CRP and pulmonary function test and cardiopulmonary exercise test performance. In conclusion, the results demonstrate that nonsmoking individuals with DM have decreased cardiorespiratory fitness that is not correlated with resting pulmonary function parameters, HbA1c, and CRP plasma levels.

  14. C-reactive protein bearing cells are a subpopulation of natural killer cell precursors

    International Nuclear Information System (INIS)

    Baum, L.L.; Krueger, N.X.

    1986-01-01

    Cell surface C-reactive protein (S-CRP) is expressed on the surface membrane of a small percentage of lymphocytes. Anti-CRP inhibits natural killer (NK) function. Since NK effectors are heterogeneous, they suspected that the cells expressing S-CRP (CRP + ) might respond differently to stimulation than the NK effectors lacking S-CRP (CRP - ). Methods were developed to separate CRP + and CRP - lymphocytes and their functional responses were examined and compared. These techniques are dependent upon the binding of CRP to its ligands, C-polysaccharide (CPS) or Phosphocholine (PC). The first method involves rosette formation with CPS coupled autologous red blood cells; the second method utilizes the binding of CRP + lymphocytes to PC-sepharose. Lymphocytes separated using either of these techniques yield similar results. CRP - lymphocytes respond to 3 day incubation with PHA or Il-2 by producing effectors which kill 51 Cr labeled K562 tumor cells, CRP + precursors do not. CRP + lymphocytes respond to a 5 day incubation with inactivated K562 by producing effectors which kill K562; CRP - precursors do not. NK functional activity of both is increased by incubation with interferon. This ability to respond differently to stimulation suggests that CRP + and CRP - cells are functionally distinct

  15. Adolescent sympathetic activity and salivary C-reactive protein: The effects of parental behavior.

    Science.gov (United States)

    Nelson, Benjamin W; Byrne, Michelle L; Simmons, Julian G; Whittle, Sarah; Schwartz, Orli S; Reynolds, Eric C; O'Brien-Simpson, Neil M; Sheeber, Lisa; Allen, Nicholas B

    2017-10-01

    This study utilized a novel multisystem approach to investigate the effect of observed parental behavior on the relationship between biological mechanisms associated with disease processes (i.e., autonomic physiology and immune response) among their adolescent children. Thirty-three adolescents (23 males), aged 11-13, and their parents participated in a laboratory session in which adolescents provided baseline measures of autonomic (sympathetic) activity, and adolescents and 1 parent participated in a laboratory based dyadic conflict resolution interaction task. This included 3 male parent/male adolescent dyads, 20 female parent/male adolescent dyads, 3 male parent/female adolescent dyads, and 7 female parent/female adolescent dyads. Approximately 3 years later, adolescents provided a salivary measure of C-Reactive Protein (sCRP) to index inflammation. Analyses revealed a positive association between sympathetic activity and sCRP, as well as a moderating role of positive parental behavior in this relationship, such that the association between sympathetic activity and sCRP was greater among adolescents whose parents displayed shorter duration of positive affect. Overall findings indicate parental behavior may influence the association between adolescent sympathetic activity and inflammatory processes. These findings have important implications for understanding the impact of psychosocial factors on biological mechanisms of disease. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Comparative evaluation of levels of C-reactive protein and PMN in periodontitis patients related to cardiovascular disease.

    Science.gov (United States)

    Anitha, G; Nagaraj, M; Jayashree, A

    2013-05-01

    Numerous cross-sectional studies have suggested that chronic periodontitis is a risk factor for cardiovascular diseases. There is evidence that periodontitis and cardiovascular diseases are linked by inflammatory factors including C-reactive protein. The purpose of the study was to investigate the levels of CRP and PNM cells as a marker of inflammatory host response in the serum of chronic periodontitis patients and in patients with CVD. Study population included 75 patients; both male and female above 35 years were included for the study. The patients were divided into three groups of 25 each - Group I: Chronic periodontitis patients with CVD, Group II: Chronic periodontitis patients without CVD and Group III: Control subjects (without chronic periodontitis and CVD). Patients with chronic periodontitis had ≥8 teeth involved with probing depth (PD) ≥5 mm involved. The control group had PD ≤ 3 mm and no CVD. Venous blood was collected from the patients and C-reactive protein levels were analyzed by immunoturbidimetry. PMN was recorded by differential count method. On comparison, OHI-S Index, GI, mean PD, CRP and PMN values showed significant difference from Group I to III. CRP level was highly significant in Group I when compared with Group II and Group III. PMN level was highly significant in Group I when compared with Group III PMN level which was not significant. This study indicated that periodontitis may add the inflammation burden of the individual and may result in increased levels of CVD based on serum CRP levels. Thus, controlled prospective trials with large sample size should be carried out to know the true nature of the relationship if indeed one exists.

  17. Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients.

    Science.gov (United States)

    Rahmani, Asghar; Moradkhani, Atefeh; Hafezi Ahmadi, Mohammad Reza; Jafari Heirdarlo, Ali; Abangah, Ghobad; Asadollahi, Khairollah; Sayehmiri, Kourosh

    2016-01-01

    Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean ± SD of hs-CRP among men and women were 2.85 ± 2.84 mg/dl and 2.80 ± 4.80 mg/dl (p = 0.047) respectively. Mean ± SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83 ± 3.80 mg/dl, 3.52 ± 5.1 mg/dl, 2.22 ± 2.3 mg/dl and 5.3 ± 5.04 mg/dl respectively. Relationship between hs-CRP and inflammation activities (p gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis.

  18. Lipopolysaccharide-binding protein for monitoring of postoperative sepsis: complemental to C-reactive protein or redundant?

    Directory of Open Access Journals (Sweden)

    Klaus Tschaikowsky

    Full Text Available INTRODUCTION: To prospectively evaluate the performance of Lipopolysaccharide-Binding Protein (LBP in prediction of hospital mortality and its correlation to C-reactive Protein (CRP, we studied sixty consecutive, postoperative patients with sepsis admitted to the university hospital intensive care unit. MEASUREMENTS AND METHODS: Plasma LBP and CRP were serially measured from day(d1 (onset of sepsis to d14 in parallel with clinical data until d28. Predictive value and correlation of LBP and CRP were analyzed by Receiver Operating Characteristic (ROC curve analysis and Pearson's test, respectively. MAIN RESULTS: LBP and CRP showed the highest levels on d2 or d3 after the onset of sepsis with no significant difference between survivors and nonsurvivors. Only at d7, nonsurvivors had significantly (p = .03 higher levels of CRP than survivors. Accordingly, in ROC analysis, concentration of CRP and LBP on d7 poorly discriminated survivors from nonsurvivors (area under curve = .62 and .55, respectively without significant difference between LBP- and CRP-ROC curves for paired comparison. LBP and CRP plasma levels allocated to quartiles correlated well with each other (r(2 = .95; p = .02. Likewise, changes in plasma concentrations of LBP and CRP from one observation to the next showed a marked concordance as both parameters concomitantly increased or decreased in 76% of all cases. CONCLUSIONS: During the first 14 days of postoperative sepsis, LBP plasma concentrations showed a time course that was very similar to CRP with a high concordance in the pattern of day-to-day changes. Furthermore, like CRP, LBP does not provide a reliable clue for outcome in this setting.

  19. C-Reactive Protein and Cytokines in Polytrauma

    Directory of Open Access Journals (Sweden)

    E. K Gumanenko

    2007-01-01

    Full Text Available Objective: to study the association of C-reactive protein (CRP with cytokines in polytrauma.Subjects and methods. Eighty-four victims with severe concomitant injury were examined. Twenty-five (29.7% patients developed sepsis, death being observed in 83.3%. CRP was daily determined in the sera of the victims, by using CRP latex test kits (HUMATEX, Germany. On days 1, 3, 7, 10, and 15 after injury, serum and lymphocytic culture IL-2, IL-4, TNF-a, IFN-y, and HLA-DR were studied on an automatic Elx 800 Universal Microplate Reader enzyme immunoassay analyzer (BIO-TEK INSTRUMENTS, Inc., USA, by applying enzyme immunoassay systems (OOO «Cytokine», Saint Petersburg, Russia.Results. No complications were observed with a CRP level of 40 mg/l on day 1 and its further reduction. The CRP level of 40 mg/l on day 1 (without use of glucocorticoids and its prolonged increase were determined in visceral inflammatory and infectious complications. The CRP level of 120 mg/l within the first 7 days was noted in subsequently developed sepsis. Glucocorticoids and specific immune drugs resulted in a reduction or complete disappearance of CRP. When the latter were discontinued, CRP appeared in the quantity reflecting the effect of treatment. In the absence of multiple organ dysfunctions, the level of CRP decreased as the infectious process diminished. The low level of CRP and the activation of an infectious process suggest the areactivity of an organism. With the CRP level of 40 mg/l, the spontaneous production and level of blood IL-4 increased less significantly, whereas those of IFN-y rose more substantially; the induced activity of TNF-a also more drastically decreased (by 10 times versus 2.2 with a CRP level of 40 mg/l. Irrespective of the level of CRP, the induced activity of IL-4 decreased by 59%, suggesting immunosuppression. There was no association of CRP with IL-2 and HLA-DR.Conclusion. Daily blood CRP analysis in injury makes it possible to predict visceral

  20. Childhood maltreatment severity is associated with elevated C-reactive protein and body mass index in adults with schizophrenia and bipolar diagnoses.

    Science.gov (United States)

    Aas, Monica; Dieset, Ingrid; Hope, Sigrun; Hoseth, Eva; Mørch, Ragni; Reponen, Elina; Steen, Nils Eiel; Laskemoen, Jannicke Fjæra; Ueland, Thor; Aukrust, Pål; Agartz, Ingrid; Andreassen, Ole A; Melle, Ingrid

    2017-10-01

    Several studies have described an association between childhood maltreatment and inflammatory markers in the psychotic disorders (schizophrenia [SZ] and bipolar disorder [BD]). Previous studies have been relatively small (childhood abuse severity and clinical diagnosis on inflammatory markers were investigated in a large sample (n=483) of patients with a disorder on the psychosis spectrum and in healthy controls (HCs). Plasma levels of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], soluble tumor necrosis factor receptor type 1 [TNFR-R1], glycoprotein 130 [gp130]) were analyzed, and BMI and data on childhood trauma events, on the basis of the Childhood Trauma Questionnaire (CTQ), were obtained from all participants. Patients had increased levels of hs-CRP (Pchildhood maltreatment experiences (Pchildhood abuse (up to three types of abuse: sexual abuse, physical abuse, and emotional abuse) was associated with elevated BMI (f=8.46, Pchildhood abuse were found for elevated hs-CRP (f=4.76, P<0.001, Cohen's d=0.4). Differences among the groups disappeared when BMI was added to the model. Trauma-altered immune activation via elevated hs-CRP in patients with SZ and BD may be mediated by higher BMI; however, the direction of this association needs further clarification. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The effect of periodontal treatment on C-reactive protein: A clinical study.

    Science.gov (United States)

    Kumar, Santosh; Shah, Samir; Budhiraja, Shilpa; Desai, Khushboo; Shah, Chirag; Mehta, Dhaval

    2013-07-01

    Chronic periodontitis in amultifactorial inflammatory disease which is caused by various microorganisms. Many studies have found close association between chronic periodontitis and C-reactive protein (CRP). CRPis an inflammatory marker which increases in all inflammatory condition. The present clinical study was designed to show the effect of periodontal treatment on the CRP levels of gingival crevicular fluid and to determine the effect of nonsurgical therapy in minimizing the CRP levels in chronic generalized periodontitis. Gingival crevicular fluid was collected using a micro capillary pipette that was hand calibrated at every 1 mm till 10 mm, from selected sites in the subjects on the 1st, 14th and 45th days. Decreased CRP levels of gingival crevicular fluid were observed at the end of the study. There was a 37% reduction in probing pocket depth and 45% gain in clinical attachment level and a reduction of about 57% after 14 days and 90% reduction of CRP levels in gingival crevicular fluid after 45 days. Thus, the results show that the presence of CRP level is more significant in gingival crevicular fluid and confirms the underlying inflammatory component of the disease activity in chronic periodontitis.

  2. C-reactive protein, marker for evaluation of systemic inflammatory response in preeclampsia.

    Science.gov (United States)

    Mihu, D; Costin, N; Mihu, Carmen Mihaela; Blaga, Ligia Daniela; Pop, Raluca Bogdana

    2008-01-01

    Determination by a high sensitivity technique of serum C-reactive protein (CRP), a sensitive marker of inflammation in women with preeclampsia compared to normal pregnancy and investigation of the relationship between CRP and the severity of the preeclamptic syndrome. The study included 40 women with preeclampsia and 40 control subjects with normal pregnancies in the last trimester of pregnancy. The serum CRP concentration was determined using the universal high sensitivity immunoturbidimetric assay. The serum CRP concentration was significantly higher (p preclampsia (5.69 +/- 1.8 mg/L) compared to normal pregnancy (2.89 +/- 1.2 mg/L). In women with preeclampsia, CRP correlated positively and significantly with diastolic blood pressure, proteinuria and uric acid levels. Maternal CRP values also correlated negatively and significantly with fetal weight at birth. Our results demonstrate that serum CRP is increased in preeclampsia and represents a marker of the severity of the preeclamptic syndrome and of fetal weight at birth. Taking into consideration these observations and the fact that CRP testing is rapid and relatively inexpensive, we recommend the use of this acute phase reagent in clinical practice, in all women with preeclampsia in order to establish the prognosis of the disease.

  3. Association of connexin43 with a receptor protein tyrosine phosphatase

    NARCIS (Netherlands)

    Giepmans, Ben N G; Feiken, Elles; Gebbink, Martijn F B G; Moolenaar, Wouter H

    2003-01-01

    Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by certain G protein-coupled receptor agonists, including lysophosphatidic acid, endothelin and thrombin. Our previous studies have implicated the c-Src protein tyrosine kinase in mediating closure of Cx43 based gap

  4. The repeatability of interleukin-6, tumor necrosis factor-α, and C-reactive protein in COPD patients over one year

    Directory of Open Access Journals (Sweden)

    Umme Kolsum

    2009-04-01

    Full Text Available Umme Kolsum, Kay Roy, Cerys Starkey, Zoë Borrill, Nick Truman, Jørgen Vestbo, Dave SinghNorth West Lung Research Centre, University of Manchester, South Manchester University Hospitals Trust, Wythenshawe, Manchester, UKBackground: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and C-reactive protein (CRP over one year and examined the relationships between these systemic markers in COPD.Methods: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-α were measured. Repeatability was expressed by intraclass correlation coefficient (Ri and the Bland–Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits.Results: There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001 between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α. CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively. There were no other significant associations between the systemic markers at either of the visits.Conclusions: Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients. We have also shown that a robust and repeatable association between IL-6 and CRP exists.Keywords: interleukin-6, tumor necrosis factor-α, C-reactive protein, repeatability, COPD   

  5. Does high C-reactive protein concentration increase atherosclerosis? The Whitehall II Study.

    Directory of Open Access Journals (Sweden)

    Mika Kivimäki

    Full Text Available BACKGROUND: C-reactive protein (CRP, a marker of systemic inflammation, is associated with risk of coronary events and sub-clinical measures of atherosclerosis. Evidence in support of this link being causal would include an association robust to adjustments for confounders (multivariable standard regression analysis and the association of CRP gene polymorphisms with atherosclerosis (Mendelian randomization analysis. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 3 tag single nucleotide polymorphisms (SNPs [+1444T>C (rs1130864; +2303G>A (rs1205 and +4899T>G (rs 3093077] in the CRP gene and assessed CRP and carotid intima-media thickness (CIMT, a structural marker of atherosclerosis, in 4941 men and women aged 50-74 (mean 61 years (the Whitehall II Study. The 4 major haplotypes from the SNPs were consistently associated with CRP level, but not with other risk factors that might confound the association between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was associated both with CIMT in age and sex adjusted standard regression analyses and with potential confounding factors. However, the association of CRP with CIMT attenuated to the null with adjustment for confounding factors in both prospective and cross-sectional analyses. When examined using genetic variants as the instrument for serum CRP, there was no inferred association between CRP and CIMT. CONCLUSIONS/SIGNIFICANCE: Both multivariable standard regression analysis and Mendelian randomization analysis suggest that the association of CRP with carotid atheroma indexed by CIMT may not be causal.

  6. Increased serum C-reactive protein concentrations in dogs with congestive heart failure due to myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Reimann, M. J.; Ljungvall, I.; Hillstrom, A.

    2016-01-01

    Cardiovascular disease in humans and dogs is associated with mildly increased circulating concentrations of C-reactive protein (CRP). Few studies have evaluated associations between circulating CRP and canine myxomatous mitral valve disease (MMVD) and the results reported have been divergent....... The aim of this study was to investigate whether serum concentrations of CRP, determined using a novel automated canine-specific high -sensitivity CRP assay (Gentian hsCRP), were associated with severity of MMVD and selected clinical variables in dogs. The study included 188 client-owned dogs...... with different severities of MMVD. Dogs were classified based on ACVIM consensus statement guidelines (group A, n = 58; group BI, n = 56; group B2, n = 38; group C, n = 36). Data were analysed using descriptive statistics and multiple regression analysis. Dogs with congestive heart failure (CHF; group C) had...

  7. Emerging roles of the neurotrophin receptor TrkC in synapse organization.

    Science.gov (United States)

    Naito, Yusuke; Lee, Alfred Kihoon; Takahashi, Hideto

    2017-03-01

    Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ). TrkC-PTPσ specifically induces excitatory synapses in a kinase domain-independent manner. TrkC has distinct extracellular domains for PTPσ- and NT-3-binding and thus may bind both ligands simultaneously. Indeed, NT-3 enhances the TrkC-PTPσ interaction, thus facilitating synapse induction at the pre-synaptic side and increasing pre-synaptic vesicle recycling in a kinase-independent fashion. A crystal structure study has revealed the detailed structure of the TrkC-PTPσ complex as well as competitive modulation of TrkC-mediated synaptogenesis by heparan sulfate proteoglycans (HSPGs), which bind the same domain of TrkC as PTPσ. Thus, there is strong evidence supporting a role for the TrkC-PTPσ complex in mechanisms underlying the fine turning of neural connectivity. Furthermore, disruption of the TrkC-PTPσ complex may be the underlying cause of certain psychiatric disorders caused by mutations in the gene encoding TrkC (NTRK3), supporting its role in cognitive functions. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  8. The functional significance of the autolysis loop in protein C and activated protein C.

    Science.gov (United States)

    Yang, Likui; Manithody, Chandrashekhara; Rezaie, Alireza R

    2005-07-01

    The autolysis loop of activated protein C (APC) is five residues longer than the autolysis loop of other vitamin K-dependent coagulation proteases. To investigate the role of this loop in the zymogenic and anticoagulant properties of the molecule, a protein C mutant was constructed in which the autolysis loop of the protein was replaced with the corresponding loop of factor X. The protein C mutant was activated by thrombin with approximately 5-fold higher rate in the presence of Ca2+. Both kinetics and direct binding studies revealed that the Ca2+ affinity of the mutant has been impaired approximately 3-fold. The result of a factor Va degradation assay revealed that the anticoagulant function of the mutant has been improved 4-5-fold in the absence but not in the presence of protein S. The improvement was due to a better recognition of both the P1-Arg506 and P1-Arg306 cleavage sites by the mutant protease. However, the plasma half-life of the mutant was markedly shortened due to faster inactivation by plasma serpins. These results suggest that the autolysis loop of protein C is critical for the Ca(2+)-dependence of activation by thrombin. Moreover, a longer autolysis loop in APC is not optimal for interaction with factor Va in the absence of protein S, but it contributes to the lack of serpin reactivity and longer half-life of the protease in plasma.

  9. TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis.

    Science.gov (United States)

    van der Meer, Jonathan H M; van der Poll, Tom; van 't Veer, Cornelis

    2014-04-17

    TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K-dependent proteins Gas6 and protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a proinflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S(+/-), Gas6(-/-), TAM(-/-), and variations of these). In this manner, we aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation, and cancer growth, their modulation could make interesting therapeutic targets in thromboembolic disease, atherosclerosis, sepsis, autoimmune disease, and cancer.

  10. Circadian Misalignment Increases C-Reactive Protein and Blood Pressure in Chronic Shift Workers.

    Science.gov (United States)

    Morris, Christopher J; Purvis, Taylor E; Mistretta, Joseph; Hu, Kun; Scheer, Frank A J L

    2017-04-01

    Shift work is a risk factor for inflammation, hypertension, and cardiovascular disease. This increased risk cannot be fully explained by classical risk factors. Shift workers' behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in shift workers, independent of differences in work stress, food quality, and other factors that are likely to differ between night and day shifts. Thus, our objectives were to determine the independent effect of circadian misalignment on 24-h high-sensitivity C-reactive protein (hs-CRP; a marker of systemic inflammation) and blood pressure levels-cardiovascular disease risk factors-in chronic shift workers. Chronic shift workers undertook two 3-day laboratory protocols that simulated night work, comprising 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment), using a randomized, crossover design. Circadian misalignment increased 24-h hs-CRP by 11% ( p shift workers. This may help explain the increased inflammation, hypertension, and cardiovascular disease risk in shift workers.

  11. The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

    DEFF Research Database (Denmark)

    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

  12. The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

    DEFF Research Database (Denmark)

    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

  13. Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial.

    Science.gov (United States)

    Do, Nga T T; Ta, Ngan T D; Tran, Ninh T H; Than, Hung M; Vu, Bich T N; Hoang, Long B; van Doorn, H Rogier; Vu, Dung T V; Cals, Jochen W L; Chandna, Arjun; Lubell, Yoel; Nadjm, Behzad; Thwaites, Guy; Wolbers, Marcel; Nguyen, Kinh V; Wertheim, Heiman F L

    2016-09-01

    Inappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is difficult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam. We did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1-65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecified in the protocol and the statistical analysis plan. All analyses were done on the intention-to-treat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579. Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics

  14. Diagnostic properties of C-reactive protein for detecting pneumonia in children.

    Science.gov (United States)

    Koster, Madieke J; Broekhuizen, Berna D L; Minnaard, Margaretha C; Balemans, Walter A F; Hopstaken, Rogier M; de Jong, Pim A; Verheij, Theo J M

    2013-07-01

    The diagnostic value of C-reactive protein (CRP) level for pneumonia in children is unknown. As a first step in the assessment of the value of CRP, a diagnostic study was performed in children at an emergency department (ED). In this cross-sectional study, data were retrospectively collected from children presenting with suspected pneumonia at the ED of Antonius Hospital Nieuwegein in The Netherlands between January 2007 and January 2012. Diagnostic outcome was pneumonia yes/no according to independent radiologist. (Un)adjusted association between CRP level and pneumonia and diagnostic value of CRP were calculated. Of 687 presenting children, 286 underwent both CRP measurement and chest radiography. 148 had pneumonia (52%). The proportion of pneumonia increased with CRP level. Negative predictive values declined, but positive predictive values increased with higher CRP thresholds. Univariable odds ratio for the association between CRP level and pneumonia was 1.2 (95% CI 1.11-1.21) per 10 mg/L increase. After adjustment for baseline characteristics CRP level remained associated with pneumonia. CRP level has independent diagnostic value for pneumonia in children presenting at the ED with suspected pneumonia, but low levels do not exclude pneumonia in this setting. These results prompt evaluation of CRP in primary care children with LRTI. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. No link of serotonin 2C receptor editing to serotonin transporter genotype

    NARCIS (Netherlands)

    Lyddon, R.; Cuppen, E.; Haroutunian, V.; Siever, L.J.; Dracheva, S.

    2010-01-01

    RNA editing is a post-transcriptional process, which has the potential to alter the function of encoded proteins. In particular, serotonin 2C receptor (5-HT2cR) mRNA editing can produce 24 protein isoforms of varying functionality. Rodent studies have shown that 5-HT2cR editing is dynamically

  16. Gs protein peptidomimetics as allosteric modulators of the β2-adrenergic receptor

    DEFF Research Database (Denmark)

    Boyhus, Lotte Emilie; Danielsen, Mia; Bengtson, Nina Smidt

    2018-01-01

    A series of Gs protein peptidomimetics were designed and synthesised based on the published X-ray crystal structure of the active state β2-Adrenergic receptor (β2AR) in complex with the Gs protein (PDB 3SN6). We hypothesised that such peptidomimetics may function as allosteric modulators...... that target the intracellular Gs protein binding site of the β2AR. Peptidomimetics were designed to mimic the 15 residue C-Terminal α-helix of the Gs protein and were pre-organised in a helical conformation by (i, i + 4)-stapling using copper catalysed azide alkyne cycloaddition. Linear and stapled...... be able to compete with the native Gs protein for the intracellular binding site to block ISO-induced cAMP formation, but are unable to stabilise an active-like receptor conformation....

  17. Human autoantibodies against Clq: lack of cross reactivity with the collectins mannan-binding protein, lung surfactant protein A and bovine conglutinin.

    Science.gov (United States)

    Mårtensson, U; Thiel, S; Jensenius, J C; Sjöholm, A G

    1996-03-01

    The collectins, a group of humoral C-type lectins, have globular and collagen-like regions and share structural features with the complement protein C1q. The question was asked if autoantibodies to the collagen-like region of C1q (anti-C1qCLR) might cross-react with collectins, such as mannan-binding protein (MBP), lung surfactant protein A (SP-A) and bovine conglutinin (BK). Anti-C1qCLR antibodies of the systemic lupus erythematosus (SLE) type and anti-C1qCLR antibodies of the hypocomplementemic urticarial vasculitis syndrome (HUVS) type were investigated. Cross-absorption and elution experiments combined with antibody detection by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis gave no evidence of cross-reactive anti-C1qCLR antibodies. However, one serum with HUVS type anti-C1qCLR antibodies contained anti-MBP antibodies that were cross-reactive with SP-A. Judging from results of ELISA inhibition experiments and immunoblot analysis, four SLE sera contained antibodies to native BK, while two sera with HUVS type anti-C1qCLR antibodies contained antibodies to epitopes of denatured BK. This might imply that autoimmunity to collagen-like structures is not restricted to C1qCLR in HUVS and HUVS/SLE overlap syndromes.

  18. Functional importance of the Ala(116)-Pro(136) region in the calcium-sensing receptor. Constitutive activity and inverse agonism in a family C G-protein-coupled receptor

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Spalding, T A; Burstein, E S

    2000-01-01

    The calcium-sensing receptor (CaR) belongs to family C of the G-protein-coupled receptor superfamily. To date 14 activating mutations in CaR showing increased sensitivity to Ca(2+) have been identified in humans with autosomal dominant hypocalcemia. Four of these activating mutations are found......, suppressed the elevated basal response of the constitutively activated Ca/1a mutants demonstrating inverse agonist activity of CPCCOEt. Taken together, our results demonstrate that the Ala(116)-Pro(136) region is of key importance for the maintenance of the inactive conformation of CaR....

  19. Serum C-Reactive Protein (CRP, Target for Therapy or Trouble?

    Directory of Open Access Journals (Sweden)

    Virginia B. Kraus

    2006-01-01

    Full Text Available High sensitivity serum C-reactive protein (hs-CRP has come into clinical use as a marker of risk for cardiovascular disease (CVD. In addition to a role as a marker of disease, CRP has also been implicated in the pathogenesis of CVD. Specific small-molecule inhibitors of CRP have recently been developed with the intent of mitigating cardiac damage during acute myocardial infarction. However, the use of CRP, both as a risk marker and a disease target are controversial for several reasons. Serum hs-CRP concentrations can be elevated on the basis of genetics, female gender, and non-Caucasian ethnicity. It is not clear, in these contexts, that elevations of hs-CRP have any pathological significance. As a non-specific indicator of inflammation, CRP is also not a specific indicator of a single disease state such as cardiovascular disease but elevated concentrations can be seen in association with other comorbidities including obesity and pulmonary disease. In sharp contrast to the proposed inhibition of CRP for cardiovascular disease treatment, the infusion of CRP has been shown to have profound therapeutic benefits for autoimmune disease and septic shock. The balance between the risks and benefits of these competing views of the role of CRP in disease and disease therapy is reminiscent of the ongoing controversy regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs for musculoskeletal disease and their cardiovascular side effects. Soon, NSAIDs may not be the only agents about which Rheumatologists and Cardiologists may spar.

  20. Association of serum uric acid with high-sensitivity C-reactive protein in postmenopausal women.

    Science.gov (United States)

    Raeisi, A; Ostovar, A; Vahdat, K; Rezaei, P; Darabi, H; Moshtaghi, D; Nabipour, I

    2017-02-01

    To explore the independent correlation between serum uric acid and low-grade inflammation (measured by high-sensitivity C-reactive protein, hs-CRP) in postmenopausal women. A total of 378 healthy Iranian postmenopausal women were randomly selected in a population-based study. Circulating hs-CRP levels were measured by highly specific enzyme-linked immunosorbent assay method and an enzymatic calorimetric method was used to measure serum levels of uric acid. Pearson correlation coefficient, multiple linear regression and logistic regression models were used to analyze the association between uric acid and hs-CRP levels. A statistically significant correlation was seen between serum levels of uric acid and log-transformed circulating hs-CRP (r = 0.25, p uric acid levels (β = 0.20, p uric acid levels (odds ratio =1.52, 95% confidence interval 1.18-1.96). Higher serum uric acid levels were positively and independently associated with circulating hs-CRP in healthy postmenopausal women.

  1. C-REACTIVE PROTEIN IN BACTERIAL MENINGITIS: DOSE IT HELP TO DIFFERENTIATE BACTERIAL FROM VIRAL MENINGITIS?

    Directory of Open Access Journals (Sweden)

    AR EMAMI NAEINI

    2001-03-01

    Full Text Available Introduction. Central nervous system infections are among the most serious conditions in of medical practice. C-reactive Protein has recently been evaluated in terms of its ability to diffeccentiate bacterial from nonbacterial central nervous system inflammations.
    Methods. We studied the frequency of positive CRP in 61 patients who had signs of meningitis. All the specimens referred to one laboratory and were examined by Slide method.
    Results. Positive CRP was found in 97.6 percent of those who were finally diagnosed as bacterial meningitis. The frequency of CRP for other types of meningitis was 16.6 percent (P < 0.05.
    Discussion. In the absence of infection, CSF is free of CRP. Positive CRP may help to the differentiate the different types of meningitis.

  2. Energy balance and macronutrient distribution in relation to C-reactive protein and HbA1c levels among patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Hiba Bawadi

    2016-05-01

    Full Text Available Background: Recently growing evidence indicates that obesity and diabetes are states of inflammation associated with elevated circulation of inflammatory mediators. Excess adiposity and oxidative stress, induced by feeding, may also lead to a state of low-grade inflammation. Objective: This study aimed at investigating energy balance and distribution in relation to low-grade inflammation among patients with type 2 diabetes. Design: A cross-sectional study included 198 male and female patients with type 2 diabetes. Patients’ weight, height, waist circumference, total body fat and truncal fat percent, energy, and macronutrient intake were measured. Venous blood specimens were collected, and levels of HbA1c and serum levels of high-sensitivity C-reactive protein (hs-CRP were determined. Results: After adjusting for covariates (body mass index, total body fat, and truncal fat, energy balance was positively correlated with hs-CRP and HbA1c. A positive energy balance was also associated with increased waist circumference and truncal fat percent (p<0.05. Total energy intake, percent energy from fat (p=0.04, and percent energy from proteins (p=0.03, but not percent energy from carbohydrates (p=0.12, were also correlated with higher hs-CRP levels among poorly glycemic-controlled patients. Conclusion: Positive energy balance is associated with elevations in hs-CRP. Increased energy intake and increased percentages of energy from fat and protein are associated with elevated hs-CRP among patients with poor glycemic control.

  3. Filling and mining the reactive metabolite target protein database.

    Science.gov (United States)

    Hanzlik, Robert P; Fang, Jianwen; Koen, Yakov M

    2009-04-15

    The post-translational modification of proteins is a well-known endogenous mechanism for regulating protein function and activity. Cellular proteins are also susceptible to post-translational modification by xenobiotic agents that possess, or whose metabolites possess, significant electrophilic character. Such non-physiological modifications to endogenous proteins are sometimes benign, but in other cases they are strongly associated with, and are presumed to cause, lethal cytotoxic consequences via necrosis and/or apoptosis. The Reactive Metabolite Target Protein Database (TPDB) is a searchable, freely web-accessible (http://tpdb.medchem.ku.edu:8080/protein_database/) resource that attempts to provide a comprehensive, up-to-date listing of known reactive metabolite target proteins. In this report we characterize the TPDB by reviewing briefly how the information it contains came to be known. We also compare its information to that provided by other types of "-omics" studies relevant to toxicology, and we illustrate how bioinformatic analysis of target proteins may help to elucidate mechanisms of cytotoxic responses to reactive metabolites.

  4. Effects of C-reactive protein on adipokines genes expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Guoyue, E-mail: yuanguoyue@hotmail.com [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Jia, Jue; Di, Liangliang [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Zhou, Libin [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China); Dong, Sijing; Ye, Jingjing; Wang, Dong; Yang, Ling; Wang, Jifang [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Li, Lianxi [Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, 600, Yishan Road, Shanghai 200233 (China); Yang, Ying [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China); Mao, Chaoming [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Chen, Mingdao, E-mail: mingdaochensh@yahoo.com [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer CRP increases TNF-{alpha} and IL-6 genes expression in matured 3T3-L1 adipocytes. Black-Right-Pointing-Pointer CRP suppresses adiponectin, leptin and PPAR-{gamma} mRNA levels in matured 3T3-L1 cells. Black-Right-Pointing-Pointer Wortmannin reverses effects of CRP on adiponectin, TNF-{alpha} and leptin mRNA levels. Black-Right-Pointing-Pointer CRP may regulate IR, obesity and metabolic syndrome by this mechanism. -- Abstract: Adipose tissue is now recognized to be an important endocrine organ, secreting a variety of adipokines that are involved in the regulation of energy metabolism, insulin resistance and metabolic syndrome. C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. A number of studies have shown that elevation of CRP concentrations is an independent predictive parameter of type 2 diabetes mellitus, which is also strongly associated with various components of the metabolic syndrome. The aim of the present study is to investigate the effects of CRP on adipokines genes expression in 3T3-L1 adipocytes. Quantitative real-time PCR analysis revealed that CRP inhibited adiponectin, leptin and peroxisome proliferator-activated receptor-gamma (PPAR-{gamma}) genes expression and raised tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) mRNA levels in matured 3T3-L1 adipocytes in a dose and time-dependent manner. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by wortmannin partially reversed the effects of CRP on adiponectin, TNF-{alpha} and leptin genes expression. These results collectively suggest that CRP regulates adiponectin, TNF-{alpha}, leptin, IL-6 and PPAR-{gamma} genes expression, and that might represent a mechanism by which CRP regulates insulin resistance, obesity and metabolic syndrome.

  5. Effects of C-reactive protein on adipokines genes expression in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Yuan, Guoyue; Jia, Jue; Di, Liangliang; Zhou, Libin; Dong, Sijing; Ye, Jingjing; Wang, Dong; Yang, Ling; Wang, Jifang; Li, Lianxi; Yang, Ying; Mao, Chaoming; Chen, Mingdao

    2012-01-01

    Highlights: ► CRP increases TNF-α and IL-6 genes expression in matured 3T3-L1 adipocytes. ► CRP suppresses adiponectin, leptin and PPAR-γ mRNA levels in matured 3T3-L1 cells. ► Wortmannin reverses effects of CRP on adiponectin, TNF-α and leptin mRNA levels. ► CRP may regulate IR, obesity and metabolic syndrome by this mechanism. -- Abstract: Adipose tissue is now recognized to be an important endocrine organ, secreting a variety of adipokines that are involved in the regulation of energy metabolism, insulin resistance and metabolic syndrome. C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. A number of studies have shown that elevation of CRP concentrations is an independent predictive parameter of type 2 diabetes mellitus, which is also strongly associated with various components of the metabolic syndrome. The aim of the present study is to investigate the effects of CRP on adipokines genes expression in 3T3-L1 adipocytes. Quantitative real-time PCR analysis revealed that CRP inhibited adiponectin, leptin and peroxisome proliferator-activated receptor-gamma (PPAR-γ) genes expression and raised tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA levels in matured 3T3-L1 adipocytes in a dose and time-dependent manner. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by wortmannin partially reversed the effects of CRP on adiponectin, TNF-α and leptin genes expression. These results collectively suggest that CRP regulates adiponectin, TNF-α, leptin, IL-6 and PPAR-γ genes expression, and that might represent a mechanism by which CRP regulates insulin resistance, obesity and metabolic syndrome.

  6. Periodontal inflamed surface area and C-reactive protein as predictors of HbA1c: a study in Indonesia.

    Science.gov (United States)

    Susanto, Hendri; Nesse, Willem; Dijkstra, Pieter U; Hoedemaker, Evelien; van Reenen, Yvonne Huijser; Agustina, Dewi; Vissink, Arjan; Abbas, Frank

    2012-08-01

    Periodontitis may exert an infectious and inflammatory burden, evidenced by increased C-reactive protein (CRP). This burden may impair blood glucose control (HbA1c). The aim of our study was to analyze whether periodontitis severity as measured with the periodontal inflamed surface area (PISA) and CRP predict HbA1c levels in a group of healthy Indonesians and a group of Indonesians treated for type 2 diabetes mellitus (DM2). A full-mouth periodontal examination, including probing pocket depth, gingival recession, clinical attachment loss, plaque index and bleeding on probing, was performed in 132 healthy Indonesians and 101 Indonesians treated for DM2. Using these data, PISA was calculated. In addition, HbA1c and CRP were analyzed. A validated questionnaire was used to assess smoking, body mass index (BMI), education and medical conditions. In regression analyses, it was assessed whether periodontitis severity and CRP predict HbA1c, controlling for confounding and effect modification (i.e., age, sex, BMI, pack years, and education). In healthy Indonesians, PISA and CRP predicted HbA1c as did age, sex, and smoking. In Indonesians treated for DM2, PISA did not predict HbA1c. Periodontitis may impair blood glucose regulation in healthy Indonesians in conjunction with elevated CRP levels. The potential effect of periodontitis on glucose control in DM2 patients may be masked by DM2 treatment. periodontitis may impair blood glucose control through exerting an inflammatory and infectious burden evidenced by increased levels of CRP.

  7. Effect of water pipe tobacco smoking on plasma high sensitivity C reactive protein level and endothelial function compared to cigarette smoking

    OpenAIRE

    Osama Ali Diab; Elzahraa Mohamed Abdelrahim; Mohamed Esmail

    2015-01-01

    Background: Cigarette smoking is a well known risk factor for cardiovascular disease, however, little is known regarding water pipe (WP) smoking. High sensitivity C-reactive protein (hs-CRP) and flow mediated dilatation (FMD) are well recognized methods to assess cardiovascular risks. Objectives: To study the effect of WP smoking on hs-CRP level and endothelial function compared to cigarette smoking. Methods: The study included 77 male subjects (30 WP smokers, 30 cigarette smokers, and ...

  8. Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2 mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1 receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.

  9. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H

    1985-01-01

    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...... of the cellular localization, expression and structure of the C3 receptors, especially the C3b (CR1) receptor, has been considerably extended in the last few years, whereas our understanding of the physiological role of these receptors is still fragmentary. However, it is becoming increasingly evident...

  10. JC virus antibody index in natalizumab-treated patients: correlations with John Cunningham virus DNA and C-reactive protein level

    Directory of Open Access Journals (Sweden)

    Lanzillo R

    2014-10-01

    Full Text Available Roberta Lanzillo,1 Raffaele Liuzzi,2 Luca Vallefuoco,3 Marcello Moccia,1 Luca Amato,1 Giovanni Vacca,1 Veria Vacchiano,1 Giuseppe Portella,3 Vincenzo Brescia Morra1 1Neurological Sciences Department, Federico II University, 2Institute of Biostructure and Bioimaging, National Research Council, 3Clinical Pathology Department, Federico II University, Naples, ItalyAbstract: Natalizumab-treated patients have a higher risk of developing progressive multifocal leukoencephalopathy. Exposure to John Cunningham virus (JCV is a prerequisite for PML (progressive multifocal leukoencephalopathy. To assess JCV exposure in multiple sclerosis patients, we performed a serological examination, obtained the antibody index, performed real-time polymerase chain reaction (PCR to detect JCV DNA in plasma and urine, and investigated the role of ultrasensitive C-reactive protein (usCRP as a possible biological marker of JCV reactivation. We retrospectively analyzed consecutive natalizumab-treated multiple sclerosis patients who underwent a JCV antibody test through a two-step enzyme-linked immunosorbent assay (STRATIFY test to the measure of serum usCRP levels, and to perform blood and urine JCV PCR. The studied cohort included 97 relapsing–remitting patients (60 women. Fifty-two patients (53.6% tested positive for anti-JCV antibodies. PCR showed JCV DNA in the urine of 30 out of 83 (36.1% patients and 28 out of 44 seropositive patients (63.6%, with a 6.7% false-negative rate for the STRATIFY test. Normalized optical density values were higher in urinary JCV DNA-positive patients (P<0.0001. Interestingly, the level of usCRP was higher in urinary JCV DNA-positive patients and correlated to the number of DNA copies in urine (P=0.028. As expected, patients' age correlated with JCV seropositivity and with JC viruria (P=0.02 and P=0.001, respectively. JC viruria was significantly correlated with a high JCV antibody index and high serum usCRP levels. We suggest that PCR and

  11. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Directory of Open Access Journals (Sweden)

    Tae Sik Goh

    2017-01-01

    Full Text Available IL-7 signaling via IL-7Rα and common γ-chain (γc is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα.

  12. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Science.gov (United States)

    Goh, Tae Sik; Jo, Yuna; Lee, Byunghyuk; Kim, Geona; Hwang, Hyunju; Ko, Eunhee; Kang, Seung Wan; Oh, Sae-Ock; Baek, Sun-Yong; Yoon, Sik; Lee, Jung Sub

    2017-01-01

    IL-7 signaling via IL-7Rα and common γ-chain (γc) is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα. PMID:28127156

  13. Serum C-reactive protein concentration and genotype in relation to ischemic stroke subtype.

    Science.gov (United States)

    Ladenvall, Claes; Jood, Katarina; Blomstrand, Christian; Nilsson, Staffan; Jern, Christina; Ladenvall, Per

    2006-08-01

    C-reactive protein (CRP) has evolved as an inflammatory risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at the CRP locus have been found to be associated with CRP levels. The aim of the present study was to investigate CRP levels and genetic variants in etiological subtypes of ischemic stroke. The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) comprises 600 consecutive ischemic stroke cases (18 to 69 years) and 600 matched controls from western Sweden. Stroke subtypes were defined by the TOAST classification. Serum CRP levels were determined by a high-sensitivity immunometric assay. CRP levels were significantly higher for all ischemic stroke subtypes compared with controls, both in the acute phase and at the 3-month follow-up. After adjustment for traditional risk factors, CRP at follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR, 1.25; 95% CI, 1.09 to 1.43) and large-vessel disease (OR, 1.48; 95% CI, 1.09 to 2.00). The CRP -286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms showed significant associations with CRP levels. However, neither CRP genotypes nor haplotypes showed an association to overall ischemic stroke. This is the first large study on CRP in different TOAST subtypes in a young ischemic stroke population. CRP levels differed between etiological subtypes of ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at follow-up was associated with overall ischemic stroke and the large-vessel disease subtype. Genetic variants at the CRP locus were associated with CRP levels, but no association was detected for overall ischemic stroke.

  14. Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists.

    Science.gov (United States)

    Cheng, Jianjun; McCorvy, John D; Giguere, Patrick M; Zhu, Hu; Kenakin, Terry; Roth, Bryan L; Kozikowski, Alan P

    2016-11-10

    On the basis of the structural similarity of our previous 5-HT 2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT 2C agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus β-arrestin recruitment. The most functionally selective compound (+)-7e produced weak β-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT 2C agonists possessing weak β-arrestin recruitment can produce distinct receptor desensitization properties.

  15. Identifying neuropeptide and protein hormone receptors in Drosophila melanogaster by exploiting genomic data

    DEFF Research Database (Denmark)

    Hauser, Frank; Williamson, Michael; Cazzamali, Giuseppe

    2006-01-01

    insect genome, that of the fruitfly Drosophila melanogaster, was sequenced in 2000, and about 200 GPCRs have been annnotated in this model insect. About 50 of these receptors were predicted to have neuropeptides or protein hormones as their ligands. Since 2000, the cDNAs of most of these candidate...... receptors have been cloned and for many receptors the endogenous ligand has been identified. In this review, we will give an update about the current knowledge of all Drosophila neuropeptide and protein hormone receptors, and discuss their phylogenetic relationships. Udgivelsesdato: 2006-Feb...

  16. Physical activity, C-reactive protein levels and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study

    NARCIS (Netherlands)

    Boekholdt, S. Matthijs; Sandhu, Manjinder S.; Day, Nicholas E.; Luben, Robert; Bingham, Sheila A.; Peters, Ron J. G.; Wareham, Nicholas J.; Khaw, Kay-Tee

    2006-01-01

    BACKGROUND: Physical activity is inversely associated with the risk of future coronary artery disease. Whether this relationship is in part mediated by lower levels of systemic inflammation, as indicated by C-reactive protein concentrations, is unknown. METHODS: We performed a nested case-control

  17. Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling.

    Science.gov (United States)

    Semack, Ansley; Sandhu, Manbir; Malik, Rabia U; Vaidehi, Nagarajan; Sivaramakrishnan, Sivaraj

    2016-08-19

    Although the importance of the C terminus of the α subunit of the heterotrimeric G protein in G protein-coupled receptor (GPCR)-G protein pairing is well established, the structural basis of selective interactions remains unknown. Here, we combine live cell FRET-based measurements and molecular dynamics simulations of the interaction between the GPCR and a peptide derived from the C terminus of the Gα subunit (Gα peptide) to dissect the molecular mechanisms of G protein selectivity. We observe a direct link between Gα peptide binding and stabilization of the GPCR conformational ensemble. We find that cognate and non-cognate Gα peptides show deep and shallow binding, respectively, and in distinct orientations within the GPCR. Binding of the cognate Gα peptide stabilizes the agonist-bound GPCR conformational ensemble resulting in favorable binding energy and lower flexibility of the agonist-GPCR pair. We identify three hot spot residues (Gαs/Gαq-Gln-384/Leu-349, Gln-390/Glu-355, and Glu-392/Asn-357) that contribute to selective interactions between the β2-adrenergic receptor (β2-AR)-Gαs and V1A receptor (V1AR)-Gαq The Gαs and Gαq peptides adopt different orientations in β2-AR and V1AR, respectively. The β2-AR/Gαs peptide interface is dominated by electrostatic interactions, whereas the V1AR/Gαq peptide interactions are predominantly hydrophobic. Interestingly, our study reveals a role for both favorable and unfavorable interactions in G protein selection. Residue Glu-355 in Gαq prevents this peptide from interacting strongly with β2-AR. Mutagenesis to the Gαs counterpart (E355Q) imparts a cognate-like interaction. Overall, our study highlights the synergy in molecular dynamics and FRET-based approaches to dissect the structural basis of selective G protein interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. C-reactive Protein -717A>G and -286C>T>A Gene Polymorphism and Ischemic Stroke.

    Science.gov (United States)

    Liu, Yan; Geng, Pei-Liang; Yan, Fu-Qin; Chen, Tong; Wang, Wei; Tang, Xu-Dong; Zheng, Jing-Chen; Wu, Wei-Ping; Wang, Zhen-Fu

    2015-06-20

    Inflammation plays a pivotal role in the formation and progression of ischemic stroke. Recently, more and more epidemiological studies have focused on the association between C-reactive protein (CRP) -717A > G and -286C > T > A genetic polymorphisms and ischemic stroke. However, the findings of these researches are not conclusive. We performed a meta-analysis to determine whether these two polymorphisms are associated with the risk of ischemic stroke. Eligible studies were identified from the database of PubMed, Medline, Embase, Web of Science, CNKI, Weipu, and Wanfang. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Four articles were included in our study, including 1926 cases and 2678 controls for -717A > G polymorphism, 652 cases and 1103 controls for -286C > T > A polymorphism. The results of meta-analysis showed that single nucleotide polymorphism (SNP) -717A > G was not significantly associated with the risk of ischemic stroke (GG vs. AA, OR = 1.12, 95% CI = 0.83-1.50, P = 0.207; GG + GA vs. AA, OR = 1.04, 95% CI = 0.93-1.17, P = 0.533; GG vs. GA + AA, OR = 1.10, 95% CI = 0.82-1.47, P = 0.220). Meta-analysis of SNP - 286C > T > A also demonstrated no statistical evidence of a significant association with the risk of ischemic stroke (AA vs. CC, OR = 0.86, 95% CI = 0.59-1.25, P = 0.348; AA vs. CC, OR = 0.92, 95% CI = 0.80-1.06, P = 0.609; AA vs. CC, OR = 0.89, 95% CI = 0.62-1.30, P = 0.374). This meta-analysis demonstrated little evidence to support a role of CRP gene -717A > G, -286C > T > A polymorphisms in ischemic stroke predisposition. However, to draw comprehensive and more reliable conclusions, further larger studies are needed to validate the association between CRP gene polymorphisms and ischemic stroke in various ethnic groups.

  19. Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer Gαiβγ: identification of key CB1 contacts with the C-terminal helix α5 of Gαi.

    Science.gov (United States)

    Shim, Joong-Youn; Ahn, Kwang H; Kendall, Debra A

    2013-11-08

    The cannabinoid (CB1) receptor is a member of the rhodopsin-like G protein-coupled receptor superfamily. The human CB1 receptor, which is among the most expressed receptors in the brain, has been implicated in several disease states, including drug addiction, anxiety, depression, obesity, and chronic pain. Different classes of CB1 agonists evoke signaling pathways through the activation of specific subtypes of G proteins. The molecular basis of CB1 receptor coupling to its cognate G protein is unknown. As a first step toward understanding CB1 receptor-mediated G protein signaling, we have constructed a ternary complex structural model of the CB1 receptor and Gi heterotrimer (CB1-Gi), guided by the x-ray structure of β2-adrenergic receptor (β2AR) in complex with Gs (β2AR-Gs), through 824-ns duration molecular dynamics simulations in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer environment. We identified a group of residues at the juxtamembrane regions of the intracellular loops 2 and 3 (IC2 and IC3) of the CB1 receptor, including Ile-218(3.54), Tyr-224(IC2), Asp-338(6.30), Arg-340(6.32), Leu-341(6.33), and Thr-344(6.36), as potential key contacts with the extreme C-terminal helix α5 of Gαi. Ala mutations of these residues at the receptor-Gi interface resulted in little G protein coupling activity, consistent with the present model of the CB1-Gi complex, which suggests tight interactions between CB1 and the extreme C-terminal helix α5 of Gαi. The model also suggests that unique conformational changes in the extreme C-terminal helix α5 of Gα play a crucial role in the receptor-mediated G protein activation.

  20. Covalent modification of mutant rat P2X2 receptors with a thiol-reactive fluorophore allows channel activation by zinc or acidic pH without ATP.

    Directory of Open Access Journals (Sweden)

    Shlomo S Dellal

    Full Text Available Rat P2X2 receptors open at an undetectably low rate in the absence of ATP. Furthermore, two allosteric modulators, zinc and acidic pH, cannot by themselves open these channels. We describe here the properties of a mutant receptor, K69C, before and after treatment with the thiol-reactive fluorophore Alexa Fluor 546 C(5-maleimide (AM546. Xenopus oocytes expressing unmodified K69C were not activated under basal conditions nor by 1,000 µM ATP. AM546 treatment caused a small increase in the inward holding current which persisted on washout and control experiments demonstrated this current was due to ATP independent opening of the channels. Following AM546 treatment, zinc (100 µM or acidic external solution (pH 6.5 elicited inward currents when applied without any exogenous ATP. In the double mutant K69C/H319K, zinc elicited much larger inward currents, while acidic pH generated outward currents. Suramin, which is an antagonist of wild type receptors, behaved as an agonist at AM546-treated K69C receptors. Several other cysteine-reactive fluorophores tested on K69C did not cause these changes. These modified receptors show promise as a tool for studying the mechanisms of P2X receptor activation.

  1. Interleukin-6 and C-Reactive Protein Levels and 9-Year Cognitive Decline in Community-Dwelling Older Women: The Women's Health and Aging Study II.

    Science.gov (United States)

    Palta, Priya; Xue, Qian-Li; Deal, Jennifer A; Fried, Linda P; Walston, Jeremy D; Carlson, Michelle C

    2015-07-01

    Elevated inflammation is a proposed mechanism relating chronic diseases to cognitive dysfunction. The objective of this study was to test the hypothesis that greater levels of inflammation, as measured by the proinflammatory cytokine interleukin-6 (IL-6) and C-reactive protein, are associated with faster rates of cognitive decline among cognitively intact community-dwelling older women. We analyzed 336 women from the Women's Health and Aging Study II. Cognitive assessments were performed at baseline and every 18-36 months, and included the following domains: immediate and delayed memory (Hopkins Verbal Learning Test), psychomotor speed (Trail Making Test, Part A), and executive function (Trail Making Test, Part B). Aggregate measures of IL-6 and C-reactive protein, based on the average from visits one and two, were analyzed categorically. Random effects models were employed to test the relationship between tertiles of each inflammatory marker and changes in cognitive domain scores over 9 years. Moderate and high levels of IL-6 predicted early declines in psychomotor speed by 1.0 connection/min per year. There were no differences in baseline scores or rates of change across tertiles of IL-6 in memory or executive function. No differences were observed across tertiles of C-reactive protein for all cognitive domains. Higher levels of serum IL-6 were associated with greater declines in psychomotor speed over 9 years. This finding could suggest that elevated IL-6 may result in microvascular changes that may lead to damage of myelin sheaths that line neuronal axons, leading to decreased neuron propagation and impaired processing speed; however, mechanistic studies are needed to evaluate these hypotheses. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Usefulness of estimation of blood procalcitonin concentration versus C-reactive protein concentration and white blood cell count for therapeutic monitoring of sepsis in neonates

    Directory of Open Access Journals (Sweden)

    Agnieszka Kordek

    2014-12-01

    Full Text Available Aim: This study was intended to assess the clinical usefulness of blood procalcitonin (PCT concentrations for the diagnosis and therapeutic monitoring of nosocomial neonatal sepsis.Material/Methods: The enrolment criterion was sepsis clinically manifesting after three days of life. PCT concentrations were measured in venous blood from 52 infected and 88 uninfected neonates. The results were interpreted against C-reactive protein (CRP concentrations and white blood cell counts (WBC.Results: Differences between the two groups in PCT and CRP concentrations were highly significant. No significant differences between the groups were noted for WBC. The threshold value on the receiver operator characteristic curve was 2.06 ng/mL for PCT (SE 75%; SP 80.68%; PPV 62.22%; NPV 88.75%; AUC 0.805, 5.0 mg/L for CRP (SE 67.44%; SP 73.68%; PPV 42.02%; NPV 88.89%; AUC 0.801, and 11.9 x109/L for WBC (SE 51.16%; SP 50.68%; PPV 23.16%; NPV 78.13%; AUC 0.484. Procalcitonin concentrations decreased 24 hours after initiation of antibiotic therapy and reverted to the control level after 5-7 days. C-reactive protein concentrations began to decline after two days of antibiotic therapy but were still higher than in the control group after 5-7 days of treatment. No significant changes in WBC during the treatment were observed.Conclusions: Procalcitonin concentrations in blood appear to be of use for the diagnosis and therapeutic monitoring of nosocomial infections in neonates as this parameter demonstrates greater sensitivity and specificity than C-reactive protein. White blood cell counts appear to be of little diagnostic value in the early phase of infection or for therapeutic monitoring.

  3. Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling.

    Science.gov (United States)

    Inda, Carolina; Dos Santos Claro, Paula A; Bonfiglio, Juan J; Senin, Sergio A; Maccarrone, Giuseppina; Turck, Christoph W; Silberstein, Susana

    2016-07-18

    Corticotropin-releasing hormone receptor 1 (CRHR1) activates G protein-dependent and internalization-dependent signaling mechanisms. Here, we report that the cyclic AMP (cAMP) response of CRHR1 in physiologically relevant scenarios engages separate cAMP sources, involving the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). cAMP produced by tmACs and sAC is required for the acute phase of extracellular signal regulated kinase 1/2 activation triggered by CRH-stimulated CRHR1, but only sAC activity is essential for the sustained internalization-dependent phase. Thus, different cAMP sources are involved in different signaling mechanisms. Examination of the cAMP response revealed that CRH-activated CRHR1 generates cAMP after endocytosis. Characterizing CRHR1 signaling uncovered a specific link between CRH-activated CRHR1, sAC, and endosome-based signaling. We provide evidence of sAC being involved in an endocytosis-dependent cAMP response, strengthening the emerging model of GPCR signaling in which the cAMP response does not occur exclusively at the plasma membrane and introducing the notion of sAC as an alternative source of cAMP. © 2016 Inda et al.

  4. Solid-phase immunoradiometric assay for C-reactive protein using magnetisable cellulose particles

    International Nuclear Information System (INIS)

    Beer, F.C. de; Pepys, M.B.

    1982-01-01

    An immunoradiometric assay (IRMA) for C-reactive protein (CRP) was developed using magnetisable cellulose particles as the solid-phase support for anti-CRP antibodies. 125 I-labelled immunopurified anti-CRP antibody was used to quantitate the amount of CRP taken up by the solid phase. Unbound label was easily and rapidly removed by decantation after sedimenting the particles on a magnet. The assay could detect 1 μg CRP/l and had a range of up to 10 mg/l with the portion of the standard curve between 10 μg/l and 2-3 mg/l being linear. Fifty samples per hour could be processed manually from serum to CRP result with an intra-assay CV of 5.2% and an inter-assay CV of 10.0%, based on 5 replicates of 5 samples with CRP levels between 2 mg/l and 180 mg/l run in 5 separate assays. Fifty clinical samples were assayed in parallel with a standard electroimmunoassay and yielded a linear correlation coefficient (r) of 0.975 and a slope of 0.98. With its single, brief incubation step including all reagents and its simple phase separation procedure the present method may be the assay of choice when precise measurement of CRP concentrations is required rapidly. (Auth.)

  5. 64 kDa protein is a candidate for a thyrotropin-releasing hormone receptor in prolactin-producing rat pituitary tumor cells (GH4C1 cells)

    International Nuclear Information System (INIS)

    Wright, M.; Hogset, A.; Alestrom, P.; Gautvik, K.M.

    1988-01-01

    A thyrotropin-releasing hormone (TRH) binding protein of 64 kDa has been identified by covalently crosslinking [ 3 H]TRH to GH4C1 cells by ultraviolet illumination. The crosslinkage of [ 3 H]TRH is UV-dose dependent and is inhibited by an excess of unlabeled TRH. A 64 kDa protein is also detected on immunoblots using an antiserum raised against GH4C1 cell surface epitopes. In a closely related cell line (GH12C1) which does not bind [ 3 H]TRH, the 64 kDa protein cannot be demonstrated by [ 3 H]TRH crosslinking nor by immunoblotting. These findings indicate that the 64 kDa protein is a candidate for a TRH-receptor protein in GH4C1 cells

  6. The reactive metabolite target protein database (TPDB)--a web-accessible resource.

    Science.gov (United States)

    Hanzlik, Robert P; Koen, Yakov M; Theertham, Bhargav; Dong, Yinghua; Fang, Jianwen

    2007-03-16

    The toxic effects of many simple organic compounds stem from their biotransformation to chemically reactive metabolites which bind covalently to cellular proteins. To understand the mechanisms of cytotoxic responses it may be important to know which proteins become adducted and whether some may be common targets of multiple toxins. The literature of this field is widely scattered but expanding rapidly, suggesting the need for a comprehensive, searchable database of reactive metabolite target proteins. The Reactive Metabolite Target Protein Database (TPDB) is a comprehensive, curated, searchable, documented compilation of publicly available information on the protein targets of reactive metabolites of 18 well-studied chemicals and drugs of known toxicity. TPDB software enables i) string searches for author names and proteins names/synonyms, ii) more complex searches by selecting chemical compound, animal species, target tissue and protein names/synonyms from pull-down menus, and iii) commonality searches over multiple chemicals. Tabulated search results provide information, references and links to other databases. The TPDB is a unique on-line compilation of information on the covalent modification of cellular proteins by reactive metabolites of chemicals and drugs. Its comprehensiveness and searchability should facilitate the elucidation of mechanisms of reactive metabolite toxicity. The database is freely available at http://tpdb.medchem.ku.edu/tpdb.html.

  7. Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

    Science.gov (United States)

    Sonego, Andreza B; Gomes, Felipe V; Del Bel, Elaine A; Guimaraes, Francisco S

    2016-08-01

    Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30min before haloperidol administration. Also, CBD, administered 2.5h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neurons

    Directory of Open Access Journals (Sweden)

    Yuan Jian

    2010-06-01

    Full Text Available Abstract Background The downstream of tyrosine kinase/docking protein (Dok adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase. The tropomyosin-related kinase (Trk receptor family, which has three members (TrkA, TrkB and TrkC, are receptor tyrosine kinases that play pivotal roles in many stages of nervous system development, such as differentiation, migration, axon and dendrite projection and neuron patterning. Upon related neurotrophin growth factor stimulation, dimerisation and autophosphorylation of Trk receptors can occur, recruiting adaptor proteins to mediate signal transduction. Results In this report, by using yeast two-hybrid assays, glutathione S-transferase (GST precipitation assays and coimmunoprecipitation (Co-IP experiments, we demonstrate that Dok6 selectively binds to the NPQY motif of TrkC through its phosphotyrosine-binding (PTB domain in a kinase activity-dependent manner. We further confirmed their interaction by coimmunoprecipitation and colocalisation in E18.5 mouse cortex neurons, which provided more in vivo evidence. Next, we demonstrated that Dok6 is involved in neurite outgrowth in mouse cortex neurons via the RNAi method. Knockdown of Dok6 decreased neurite outgrowth in cortical neurons upon neurotrophin 3 (NT-3 stimulation. Conclusions We conclude that Dok6 interacts with the NPQY motif of the TrkC receptor through its PTB domain in a kinase activity-dependent manner, and works as a novel substrate of the TrkC receptor involved in NT-3-mediated neurite outgrowth in mouse cortex neurons.

  9. C-reactive protein testing in patients with acute rhinosinusitis leads to a reduction in antibiotic use

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars; Arranz, Javier

    2012-01-01

    OBJECTIVE: To evaluate the effect of C-reactive protein (CRP) testing on the antibiotic prescribing in patients with acute rhinosinusitis. METHODS: Audit-based study carried out in primary care centres in Spain. GPs registered episodes of rhinosinusitis during 3-week period before and after...... an intervention. Two types of intervention were considered: full intervention group (FIG) consisting in individual feedback based on results from the first registry, courses in rational antibiotic prescribing, guidelines, patient information leaflets, workshops on rapid tests and use of the CRP test. GPs...... in the partial intervention group (PIG) underwent all the above intervention except for the workshop and they did not have access to CRP. Multilevel logistic regression analysis was performed considering the prescription of antibiotics as the dependent variable. RESULTS: Two hundred and ten physicians were...

  10. Effects of Antisense Oligonucleotides against C-Reactive Protein on the Development of Atherosclerosis in WHHL Rabbits

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    Qi Yu

    2014-01-01

    Full Text Available Increased plasma levels of C-reactive protein (CRP are closely associated with cardiovascular diseases, but whether CRP is directly involved in the pathogenesis of atherosclerosis is still under debate. Many controversial and contradictory results using transgenic mice and rabbits have been published but it is also unclear whether CRP lowering can be used for the treatment of atherosclerosis. In the current study, we examined the effects of the rabbit CRP antisense oligonucleotides (ASO on the development of atherosclerosis in WHHL rabbits. CRP ASO treatment led to a significant reduction of plasma CRP levels; however, both aortic and coronary atherosclerotic lesions were not significantly changed compared to those of control WHHL rabbits. These results suggest that inhibition of plasma CRP does not affect the development of atherosclerosis in WHHL rabbits.

  11. C-reactive protein, heart rate variability and prognosis in community subjects with no apparent heart disease

    DEFF Research Database (Denmark)

    Sajadieh, A; Nielsen, OW; Rasmussen, Verner

    2006-01-01

    OBJECTIVES: Increased C-reactive protein (CRP) and reduced heart rate variability (HRV) both indicate poor prognosis. An inverse association between HRV and CRP has been reported, suggesting an interaction between inflammatory and autonomic systems. However, the prognostic impact of this interact...... of four HRV measures were significantly associated with increased rate of death or myocardial infarction. In a Cox model with CRP >or=2.5 microg mL(-1), standard deviation for the mean value of the time between normal complexes...... examinations, and 24-h Holter monitoring. Four time domain measures of HRV were studied. All were prospectively followed for up to 5 years. RESULTS: Mean age was 64 years (55-75). During the follow-up, 46 total deaths and 11 cases of definite acute myocardial infarction were observed. Both CRP and three...

  12. Lifestyle and clinical factors associated with elevated C-reactive protein among newly diagnosed Type 2 diabetes mellitus patients

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Mor, Anil; Rungby, Jørgen

    2014-01-01

    BACKGROUND: We aimed to examine the prevalence of and modifiable factors associated with elevated C-reactive Protein (CRP), a marker of inflammation, in men and women with newly diagnosed Type 2 Diabetes mellitus (DM) in a population-based setting. METHODS: CRP was measured in 1,037 patients (57...... was primarily elevated among patients with no regular physical activity (aRR 1.5 (95% CI 1.1-1.9)), previous cardiovascular disease (aRR1.5 (95% CI 1.2-1.9) and other comorbidity. For both genders, elevated CRP was 1.4-fold increased in those with weight gain >30 kg since age 20 years. Sensitivity analyses...

  13. PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

    Science.gov (United States)

    Dunn, Henry A; Ferguson, Stephen S G

    2015-10-01

    G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and

  14. Detection of Islet Cell Immune Reactivity with Low Glycemic Index Foods: Is This a Concern for Type 1 Diabetes?

    Directory of Open Access Journals (Sweden)

    Datis Kharrazian

    2017-01-01

    Full Text Available Dietary management of autoimmune diabetes includes low glycemic foods classified from the glycemic index, but it does not consider the role that immunoreactive foods may play with the immunological etiology of the disease. We measured the reactivity of either monoclonal or polyclonal affinity-purified antibodies to insulin, insulin receptor alpha, insulin receptor beta, zinc transporter 8 (ZnT8, tyrosine phosphatase-based islet antigen 2 (IA2, and glutamic acid decarboxylase (GAD 65 and 67 against 204 dietary proteins that are commonly consumed. Dietary protein determinants included unmodified (raw and modified (cooked and roasted foods, herbs, spices, food gums, brewed beverages, and additives. There was no immune reactivity between insulin or insulin receptor beta and dietary proteins. However, we identified strong to moderate immunological reactivity with antibodies against insulin receptor alpha, ZnT8, IA2, GAD-65, and GAD-67 with several dietary proteins. We also identified 49 dietary proteins found in foods classified as low glycemic foods with immune reactivity to autoimmune target sites. Laboratory analysis of immunological cross-reactivity between pancreas target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune diabetes.

  15. Quantitative measurement of cell membrane receptor internalization by the nanoluciferase reporter: Using the G protein-coupled receptor RXFP3 as a model.

    Science.gov (United States)

    Liu, Yu; Song, Ge; Shao, Xiao-Xia; Liu, Ya-Li; Guo, Zhan-Yun

    2015-02-01

    Nanoluciferase (NanoLuc) is a newly developed small luciferase reporter with the brightest bioluminescence to date. In the present work, we developed NanoLuc as a sensitive bioluminescent reporter to measure quantitatively the internalization of cell membrane receptors, based on the pH dependence of the reporter activity. The G protein-coupled receptor RXFP3, the cognate receptor of relaxin-3/INSL7, was used as a model receptor. We first generated stable HEK293T cells that inducibly coexpressed a C-terminally NanoLuc-tagged human RXFP3 and a C-terminally enhanced green fluorescent protein (EGFP)-tagged human RXFP3. The C-terminal EGFP-tag and NanoLuc-tag had no detrimental effects on the ligand-binding potency and intracellular trafficking of RXFP3. Based on the fluorescence of the tagged EGFP reporter, the ligand-induced RXFP3 internalization was visualized directly under a fluorescence microscope. Based on the bioluminescence of the tagged NanoLuc reporter, the ligand-induced RXFP3 internalization was measured quantitatively by a convenient bioluminescent assay. Coexpression of an EGFP-tagged inactive [E141R]RXFP3 had no detrimental effect on the ligand-binding potency and ligand-induced internalization of the NanoLuc-tagged wild-type RXFP3, suggesting that the mutant RXFP3 and wild-type RXFP3 worked independently. The present bioluminescent internalization assay could be extended to other G protein-coupled receptors and other cell membrane receptors to study ligand-receptor and receptor-receptor interactions. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. C-reactive protein as a systemic marker of inflammation in periodontitis.

    Science.gov (United States)

    Pejcic, A; Kesic, L J; Milasin, J

    2011-03-01

    Periodontitis has been identified as a potential risk factor for systemic pathologies such as cardiovascular disease (CVD). The aims of this investigation were to assess the relationship between periodontitis and systemic inflammatory factor, as well as to discover whether there is a relation to the severity of periodontitis and to the periodontopathogens. Periodontal examinations and serum C-reactive protein (CRP) level measurements were performed in 50 patients with periodontitis. Periodontal health indicators included the gingival bleeding on probing index and periodontal disease status. The patients with moderate periodontitis had low attachment loss and pocket depth periodontitis had high attachment loss and pocket depth >5 mm. The control group comprised 25 volunteers with healthy gingiva, gingival sulcus periodontal parameters and CRP levels were significantly higher in the patients with periodontitis. Patients who had severe periodontitis, with high levels of mean clinical attachment loss, and subjects with moderate periodontitis had higher mean CRP levels. The percentage of subjects with elevated levels of CRP >5 mg/l was greater in the higher clinical attachment loss group compared to the group with lower attachment loss. The presence of P. gingivalis and A. actinomycetemcomitans were also associated with elevated CRP levels and poor periodontal status. Periodontitis and the presence of P. gingivalis are associated with an enhanced inflammatory response expressed by higher CRP levels. The association of periodontitis with CRP levels appears to be a contributing factor for CVD and might be a possible intermediate pathway in this association.

  17. COMPARISONS OF SERUM C-REACTIVE PROTEIN IN YOUNG SOCCER PLAYERS AND NON-ATHLETES

    Directory of Open Access Journals (Sweden)

    M. Siahkouhian

    2011-11-01

    Full Text Available The aim of this study was to compare the plasma concentration of high sensitive C-reactive protein (hs-CRP, white blood cells (WBC, uric acid, and total cholesterol (TC between soccer players and non-athletes. We also intended to evaluate the relations of blood markers with ·VO2max and body composition variables. This cross-sectional study involved professional soccer players (n=40 and sedentary young men (n=60, aged 18-22 years. Blood markers such as CRP, WBC, uric acid, and TC were determined by laboratory tests. Cardiorespiratory fitness (VO2max, body mass index (BMI and fat tissue (FM were determined by the standard test protocols. There were no significant differences between CRP levels of soccer players and non-athletes (0.32±0.13 vs. 0.34±0.19 mg/dl. CRP correlated significantly with FM among soccer players (r=0.482, p≤0.002. Our results also showed a significant correlation between TC and VO2max in soccer players (r=0.469, p≤0.002. Our results showed that long-term soccer training may have no significant effect on the CRP level

  18. The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria

    DEFF Research Database (Denmark)

    Shabani, Estela; Opoka, Robert O; Bangirana, Paul

    2016-01-01

    The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data abo...

  19. Evaluation of Serum Levels of Pregnancy Associated Plasma Protein-A, Tumor Necrosis Factor-alpha and Highly Sensitive C-Reactive Protein in Diabetic Children

    International Nuclear Information System (INIS)

    Abdel-Messeih, PH.L.; El-safie, A.I.; Said, A.I.

    2011-01-01

    Recent evidence favours the primary role of cellular auto immunity and its humoral mediators in the pathogenesis and follow up of children with type 1 diabetes mellitus (type 1 DM). The present study is carried out to investigate serum levels of pregnancy associated plasma protein-A (PAPP-A), tumor necrosis factor-alpha (TNF-alpha ) and highly sensitive C-reactive protein (hs-CRP) in children with type 1 DM. Potential role of body mass index (BMI) was evaluated. Circulating levels of TNF-alpha, PAPP-A and hs-CRP are significantly increased in children with type 1 DM as compared with healthy subjects suggesting activation of inflammatory immune response system. A significant negative correlation was obtained between TNF-alpha and BMI in diabetic patients. This is highly suggestive of the availability of these non invasive indices to help further examining type 1 DM pathophysiology and monitoring pharmacological interventions to interfere with disease development and progression.

  20. High sensitivity C-reactive protein distribution in the elderly: the Bambuí Cohort Study, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Assunção, L.G.S. [Programa de Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Eloi-Santos, S.M. [Programa de Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Peixoto, S.V. [Departamento de Enfermagem Aplicada, Escola de Enfermagem, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG (Brazil); Lima-Costa, M.F. [Departamento de Medicina Preventiva e Social, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG (Brazil); Vidigal, P.G. [Programa de Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-09-28

    The measurement of the serum concentration of the acute-phase reactant C-reactive protein (CRP) provides a useful marker in clinical practice. However, the distribution of CRP is not available for all age and population groups. This study assessed the distribution of high sensitivity CRP (hs-CRP) by gender and age in 1470 elderly individuals from a Brazilian community that participates in the Bambuí Cohort Study. Blood samples were collected after 12 h of fasting and serum samples were stored at -70°C. Measurements were made with a commercial hs-CRP immunonephelometric instrument. More than 50% of the results were above 3.0 mg/L for both genders. Mean hs-CRP was higher in women (3.62 ± 2.58 mg/L) than in men (3.03 ± 2.50 mg/L). This difference was observed for all ages, except for the over-80 age group. This is the first population-based study to describe hs-CRP values in Latin American elderly subjects. Our results indicate that significant gender differences exist in the distribution of hs-CRP, and suggest that gender-specific cut-off points for hs-CRP would be necessary for the prediction of cardiovascular risks.

  1. High sensitivity C-reactive protein distribution in the elderly: the Bambuí Cohort Study, Brazil

    International Nuclear Information System (INIS)

    Assunção, L.G.S.; Eloi-Santos, S.M.; Peixoto, S.V.; Lima-Costa, M.F.; Vidigal, P.G.

    2012-01-01

    The measurement of the serum concentration of the acute-phase reactant C-reactive protein (CRP) provides a useful marker in clinical practice. However, the distribution of CRP is not available for all age and population groups. This study assessed the distribution of high sensitivity CRP (hs-CRP) by gender and age in 1470 elderly individuals from a Brazilian community that participates in the Bambuí Cohort Study. Blood samples were collected after 12 h of fasting and serum samples were stored at -70°C. Measurements were made with a commercial hs-CRP immunonephelometric instrument. More than 50% of the results were above 3.0 mg/L for both genders. Mean hs-CRP was higher in women (3.62 ± 2.58 mg/L) than in men (3.03 ± 2.50 mg/L). This difference was observed for all ages, except for the over-80 age group. This is the first population-based study to describe hs-CRP values in Latin American elderly subjects. Our results indicate that significant gender differences exist in the distribution of hs-CRP, and suggest that gender-specific cut-off points for hs-CRP would be necessary for the prediction of cardiovascular risks

  2. C-reactive protein inhibits survivin expression via Akt/mTOR pathway downregulation by PTEN expression in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Beom Seob Lee

    Full Text Available C-reactive protein (CRP is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We demonstrated that treatment of CRP resulted in a significant decrease of survivin protein expression in a concentration-dependent manner in cardiac myocytes. The upstream signaling proteins of survivin, such as Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP increased the protein and mRNA levels of PTEN. The siRNA transfection or specific inhibitor treatment for PTEN restored the CRP-induced downregulation of Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK-specific inhibitor also blocked the p53 phosphorylation and PTEN expression induced by CRP. Our study provides a novel insight into CRP-induced downregulation of survivin protein expression in cardiac myocytes through mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by expression of PTEN.

  3. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: Evidence for more than one receptor class

    International Nuclear Information System (INIS)

    Gronwald, R.G.K.; Grant, F.J.; Haldeman, B.A.; Hart, C.E.; O'Hara, P.J.; Hagen, F.S.; Ross, R.; Bowen-Pope, D.F.; Murray, M.J.

    1988-01-01

    The complete nucleotide sequence of a cDNA encoding the human platelet-derived growth factor (PDGF) receptor is presented. The cDNA contains an open reading frame that codes for a protein of 1106 amino acids. Comparison to the mouse PDGF receptor reveals an overall amino acid sequence identity of 86%. This sequence identity rises to 98% in the cytoplasmic split tyrosine kinase domain. RNA blot hybridization analysis of poly(A) + RNA from human dermal fibroblasts detects a major and a minor transcript using the cDNA as a probe. Baby hamster kidney cells, transfected with an expression vector containing the receptor cDNA, express an ∼ 190-kDa cell surface protein that is recognized by an anti-human PDGF receptor antibody. The recombinant PDGF receptor is functional in the transfected baby hamster kidney cells as demonstrated by ligand-induced phosphorylation of the receptor. Binding properties of the recombinant PDGF receptor were also assessed with pure preparations of BB and AB isoforms of PDGF. Unlike human dermal fibroblasts, which bind both isoforms with high affinity, the transfected baby hamster kidney cells bind only the BB isoform of PDGF with high affinity. This observation is consistent with the existence of more than one PDGF receptor class

  4. Does C-reactive Protein Add Prognostic Value to GRACE Score in Acute Coronary Syndromes?

    International Nuclear Information System (INIS)

    Correia, Luis Cláudio Lemos; Vasconcelos, Isis; Garcia, Guilherme; Kalil, Felipe; Ferreira, Felipe; Silva, André; Oliveira, Ruan; Carvalhal, Manuela; Freitas, Caio; Noya-Rabelo, Márcia Maria

    2014-01-01

    The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score

  5. Does C-reactive Protein Add Prognostic Value to GRACE Score in Acute Coronary Syndromes?

    Energy Technology Data Exchange (ETDEWEB)

    Correia, Luis Cláudio Lemos, E-mail: lccorreia@terra.com.br; Vasconcelos, Isis; Garcia, Guilherme; Kalil, Felipe; Ferreira, Felipe; Silva, André; Oliveira, Ruan; Carvalhal, Manuela; Freitas, Caio; Noya-Rabelo, Márcia Maria [Escola Bahiana de Medicina e Saúde Pública, Salvador, BA (Brazil); Hospital São Rafael, Salvador, BA (Brazil)

    2014-05-15

    The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score.

  6. Glucocorticoid acts on a putative G protein-coupled receptor to rapidly regulate the activity of NMDA receptors in hippocampal neurons.

    Science.gov (United States)

    Zhang, Yanmin; Sheng, Hui; Qi, Jinshun; Ma, Bei; Sun, Jihu; Li, Shaofeng; Ni, Xin

    2012-04-01

    Glucocorticoids (GCs) have been demonstrated to act through both genomic and nongenomic mechanisms. The present study demonstrated that corticosterone rapidly suppressed the activity of N-methyl-D-aspartate (NMDA) receptors in cultured hippocampal neurons. The effect was maintained with corticosterone conjugated to bovine serum albumin and blocked by inhibition of G protein activity with intracellular GDP-β-S application. Corticosterone increased GTP-bound G(s) protein and cyclic AMP (cAMP) production, activated phospholipase Cβ(3) (PLC-β(3)), and induced inositol-1,4,5-triphosphate (IP(3)) production. Blocking PLC and the downstream cascades with PLC inhibitor, IP(3) receptor antagonist, Ca(2+) chelator, and protein kinase C (PKC) inhibitors prevented the actions of corticosterone. Blocking adenylate cyclase (AC) and protein kinase A (PKA) caused a decrease in NMDA-evoked currents. Application of corticosterone partly reversed the inhibition of NMDA currents caused by blockage of AC and PKA. Intracerebroventricular administration of corticosterone significantly suppressed long-term potentiation (LTP) in the CA1 region of the hippocampus within 30 min in vivo, implicating the possibly physiological significance of rapid effects of GC on NMDA receptors. Taken together, our results indicate that GCs act on a putative G protein-coupled receptor to activate multiple signaling pathways in hippocampal neurons, and the rapid suppression of NMDA activity by GCs is dependent on PLC and downstream signaling.

  7. Protein Connectivity in Chemotaxis Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Stephan Eismann

    2015-12-01

    Full Text Available The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.

  8. Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models

    Directory of Open Access Journals (Sweden)

    Alexander J. Szalai

    2014-01-01

    Full Text Available Raised blood C-reactive protein (CRP level is a predictor of cardiovascular events, but whether blood CRP is causal in the disease process is unknown. The latter would best be defined by pharmacological inhibition of the protein in the context of a randomized case-control study. However, no CRP specific drug is currently available so such a prospective study cannot be performed. Blood CRP is synthesized primarily in the liver and the liver is an organ where antisense oligonucleotide (ASO drugs accumulate. Taking advantage of this we evaluated the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage. Treating rats for 4 weeks with a rat CRP-specific ASO achieved >60% reduction of blood CRP. Notably, this effect was associated with improved heart function and pathology following myocardial infarction (induced by ligation of the left anterior descending artery. Likewise in human CRP transgenic mice treated for 2 weeks with a human CRP-specific ASO, blood human CRP was reduced by >70% and carotid artery patency was improved (2 weeks after surgical ligation. CRP specific ASOs might pave the way towards a placebo-controlled trial that could clarify the role of CRP in cardiovascular disease.

  9. Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yankee, Thomas M; Solow, Sasha A; Draves, Kevin D; Clark, Edward A

    2003-01-01

    Adapter proteins play a critical role in regulating signals triggered by Ag receptor cross-linking. These small molecules link receptor proximal events with downstream signaling pathways. In this study, we explore the expression and function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related adaptor downstream of Shc adapter protein in human B cells. GrpL is expressed in naive B cells and is down-regulated following B cell Ag receptor ligation. By contrast, germinal center and memory B cells express little or no GrpL. Using human B cell lines, we detected constitutive interactions between GrpL and B cell linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa, hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2 domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular signal-related kinase and p38 mitogen-activated protein kinase phosphorylation. Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor-mediated signaling events.

  10. Concordance of haemoglobin A1c, blood pressure and C-reactive protein between children and their parents in Chinese households.

    Science.gov (United States)

    Dong, F; Howard, A G; Herring, A H; Adair, L S; Thompson, A L; Popkin, B M; Aiello, A E; Zhang, B; Gordon-Larsen, P

    2017-10-01

    China has the world's highest diabetes prevalence, which along with hypertension and inflammation continues to grow particularly among children. Little is known about the strength of the association of these cardiometabolic risk factors between parents and their children; thus, the potential of household-based strategies to reduce risk is unknown. The objective of the study is to examine the parent-child association for haemoglobin A1c (HbA1c), blood pressure (BP) and C-reactive protein (CRP) in a large, geographically diverse Chinese sample. In 940 parent-child pairs (children aged 7-17 years) who participated in the 2009 China Health and Nutrition Survey, we measured each individual's HbA1c and CRP using fasting blood and BP. We used sex-specific random-effects linear regression to examine the parent-child association for these risk factors, accounting for within-family clustering. Child's HbA1c was positively associated with parental HbA1c. Beta coefficients ranged from 0.06 (95% CI 0.03-0.12) for father-daughter to 0.43 (95% CI 0.28-0.58) for mother-son pairs. We also detected a positive mother-daughter association for BP and positive father-child associations for CRP. The statistically significant parent-child association for HbA1c, BP and CRP in Chinese families suggests that household-based interventions could be useful for confronting the high rates of diabetes, hypertension and inflammation in China. © 2016 The Authors. Pediatric Obesity published by John Wiley & Sons, Ltd on behalf of World Obesity Federation.

  11. Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP.

    Directory of Open Access Journals (Sweden)

    Souvik Basak

    Full Text Available Oxidative damage to microbial hosts often occurs under stressful conditions during bioprocessing. Classical strain engineering approaches are usually both time-consuming and labor intensive. Here, we aim to improve E. coli performance under oxidative stress via engineering its global regulator cAMP receptor protein (CRP, which can directly or indirectly regulate redox-sensing regulators SoxR and OxyR, and other ~400 genes in E. coli. Error-prone PCR technique was employed to introduce modifications to CRP, and three mutants (OM1~OM3 were identified with improved tolerance via H(2O(2 enrichment selection. The best mutant OM3 could grow in 12 mM H(2O(2 with the growth rate of 0.6 h(-1, whereas the growth of wild type was completely inhibited at this H(2O(2 concentration. OM3 also elicited enhanced thermotolerance at 48°C as well as resistance against cumene hydroperoxide. The investigation about intracellular reactive oxygen species (ROS, which determines cell viability, indicated that the accumulation of ROS in OM3 was always lower than in WT with or without H(2O(2 treatment. Genome-wide DNA microarray analysis has shown not only CRP-regulated genes have demonstrated great transcriptional level changes (up to 8.9-fold, but also RpoS- and OxyR-regulated genes (up to 7.7-fold. qRT-PCR data and enzyme activity assay suggested that catalase (katE could be a major antioxidant enzyme in OM3 instead of alkyl hydroperoxide reductase or superoxide dismutase. To our knowledge, this is the first work on improving E. coli oxidative stress resistance by reframing its transcription machinery through its native global regulator. The positive outcome of this approach may suggest that engineering CRP can be successfully implemented as an efficient strain engineering alternative for E. coli.

  12. Synthesis of an endothelial cell mimicking surface containing thrombomodulin and endothelial protein C receptor

    Science.gov (United States)

    Kador, Karl Erich

    Synthetic materials for use in blood contacting applications have been studied for many years with limited success. One of the main areas of need for these materials is the design of synthetic vascular grafts for use in the hundreds of thousands of patients who have coronary artery bypass grafting, many without suitable veins for autologous grafts. The design of these grafts is constrained by two common modes of failure, the formation of intimal hyperplasia (IH) and thrombosis. IH formation has been previously linked to a mismatching of the mechanical properties of the graft and has been overcome by creating grafts using materials whose compliance mimics that of the native artery. Several techniques and surface modification have been designed to limit thrombosis on the surface of synthetic materials. One which has shown the greatest promise is the immobilization of Thrombomodulin (TM), a protein found on the endothelial cell membrane lining native blood vessels involved in the activation of the anticoagulant Protein C (PC). While TM immobilization has been shown to arrest thrombin formation and limit fibrous formations in in-vitro and in-vivo experiments, it has shown to be transport limiting under arterial flow. On the endothelial cell surface, TM is co-localized with Endothelial Protein C Receptor (EPCR), which increases PC transport onto the cell surface and increases PC activation via TM between 20-100 fold. This dissertation will describe the chemical modification of medical grade polyurethane (PU), whose compliance has been shown to match that of native arteries. This modification will enable the immobilization of two proteins on an enzymatically relevant scale estimated at less than 10 nm. This dissertation will further describe the immobilization of the proteins TM and EPCR, and analyze the ability of a surface co-immobilized with these proteins to activate the anticoagulant PC. Finally, it will compare the ability of this co-immobilized surface to delay

  13. Low carbohydrate, high fat diet increases C-reactive protein during weight loss.

    Science.gov (United States)

    Rankin, Janet W; Turpyn, Abigail D

    2007-04-01

    Chronic inflammation is associated with elevated risk of heart disease and may be linked to oxidative stress in obesity. Our objective was to evaluate the effect of weight loss diet composition (low carbohydrate, high fat, LC or high carbohydrate, low fat, HC) on inflammation and to determine whether this was related to oxidative stress. Twenty nine overweight women, BMI 32.1 +/- 5.4 kg/m(2), were randomly assigned to a self-selected LC or HC diet for 4 wks. Weekly group sessions and diet record collections helped enhance compliance. Body weight, markers of inflammation (serum interleukin-6, IL-6; C-reactive protein, CRP) oxidative stress (urinary 8-epi-prostaglandin F2alpha, 8-epi) and fasting blood glucose and free fatty acids were measured weekly. The diets were similar in caloric intake (1357 kcal/d LC vs. 1361 HC, p=0.94), but differed in macronutrients (58, 12, 30 and 24, 59, 18 for percent of energy as fat, carbohydrate, and protein for LC and HC, respectively). Although LC lost more weight (3.8 +/- 1.2 kg LC vs. 2.6 +/- 1.7 HC, p=0.04), CRP increased 25%; this factor was reduced 43% in HC (p=0.02). For both groups, glucose decreased with weight loss (85.4 vs. 82.1 mg/dl for baseline and wk 4, p<0.01), while IL-6 increased (1.39 to 1.62 pg/mL, p=0.04). Urinary 8-epi varied differently over time between groups (p<0.05) with no consistent pattern. Diet composition of the weight loss diet influenced a key marker of inflammation in that LC increased while HC reduced serum CRP but evidence did not support that this was related to oxidative stress.

  14. Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction.

    Science.gov (United States)

    Erkenekli, K; Keskin, U; Uysal, B; Kurt, Y G; Sadir, S; Çayci, T; Ergün, A; Erkaya, S; Danişman, N; Uygur, D

    2015-04-01

    The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system.

  15. Relationship of C-reactive protein, metabolic syndrome and diabetes mellitus: potential role of statins.

    Science.gov (United States)

    Nash, David T

    2005-12-01

    Atherosclerosis and the metabolic derangements of insulin resistance, metabolic syndrome and diabetes mellitus are all associated with underlying inflammatory processes. C-reactive protein (CRP), a marker of inflammation, has been shown to be a strong independent predictor of vascular events. It adds to cardiovascular disease risk at all levels of low-density-lipoprotein cholesterol and Framingham risk scores, and elevated levels are also associated with increasing severity of the metabolic syndrome. The development of a simple, stable, noninvasive test to measure high-sensitivity CRP has provided a clinical tool that may have an important role in the identification and assessment of individuals likely to develop cardiovascular or metabolic disease. The role of CRP in predicting cardiovascular risk is less clear in African Americans, however, than in white populations. Statins and thiazolidinediones are being investigated for their potential role in the prevention and treatment of the inflammatory processes involved in the metabolic syndrome and cardiovascular disease. In the future, assessment of CRP levels may contribute importantly to clinical decision-making in reducing cardiovascular risk.

  16. Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis.

    Science.gov (United States)

    Ramanathan, Kumaresan; Padmanabhan, Giri; Vijayaraghavan, Bhooma

    2016-05-01

    Severe peritonitis causing death is one of the most devastating complications of peritoneal dialysis (PD). Since the predictive value of C-reactive protein (CRP) in PD fluid has not been assessed, the objective of the present study is to evaluate its predictive value and clinical correlation in patients on PD with peritonitis. One hundred and twenty patients on continuous ambulatory PD (CAPD) were enrolled and their serum and fluid CRP (Fl. CRP) were evaluated at the start of CAPD. All patients who developed peritonitis were further evaluated for serum and fluid CRP. The patients were categorized into four groups, namely: normal patients (control group), patients with peritonitis, patients with peritonitis leading to catheter removal, and death due to peritonitis. Sixty-five patients developed peritonitis of whom, catheter removal was performed in eight patients. Five patients died due to peritonitis-related complications. Fl. CRP showed a significant difference among the three groups, unlike S. CRP. Estimation of CRP in the peritoneal fluid may be a useful marker to monitor the onset of peritonitis.

  17. Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

    Directory of Open Access Journals (Sweden)

    Robert Root-Bernstein

    2017-10-01

    Full Text Available Human immunodeficiency virus (HIV hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR. This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS. Quantitative enzyme-linked immunoadsorption assays (ELISA demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections.

  18. Population pharmacokinetics and pharmacodynamics of teicoplanin in neonates: making better use of C-reactive protein to deliver individualized therapy.

    Science.gov (United States)

    Ramos-Martín, V; Neely, M N; McGowan, P; Siner, S; Padmore, K; Peak, M; Beresford, M W; Turner, M A; Paulus, S; Hope, W W

    2016-11-01

    There is uncertainty about the optimal teicoplanin regimens for neonates. The study aim was to determine the population pharmacokinetics (PK) of teicoplanin in neonates, evaluate currently recommended regimens and explore the exposure-effect relationships. An open-label PK study was conducted. Neonates from 26 to 44 weeks post-menstrual age were recruited (n = 18). The teicoplanin regimen was a 16 mg/kg loading dose, followed by 8 mg/kg once daily. Therapeutic drug monitoring and dose adjustment were not conducted. A standard two-compartment PK model was developed, followed by models that incorporated weight. A PK/pharmacodynamic (PD) model with C-reactive protein serial measurements as the PD input was fitted to the data. Monte Carlo simulations (n = 5000) were performed using Pmetrics. The AUCs at steady state and the proportion of patients achieving the recommended drug exposures (i.e. C min >15 mg/L) were determined. The study was registered in the European Clinical Trials Database Registry (EudraCT: 2012-005738-12). The PK allometric model best accounted for the observed data. The PK parameters medians were: clearance = 0.435 × (weight/70) 0.75 (L/h); volume = 0.765 (L); K cp  = 1.3 (h -1 ); and K pc  = 0.629 (h -1 ). The individual time-course of C-reactive protein was well described using the Bayesian posterior estimates for each patient. The simulated median AUC 96-120 was 302.3 mg·h/L and the median C min at 120 h was 12.9 mg/L; 38.8% of patients attained a C min >15 mg/L by 120 h. Teicoplanin population PK is highly variable in neonates, weight being the best descriptor of PK variability. A low percentage of neonates were able to achieve C min >15 mg/L. The routine use of therapeutic drug monitoring and improved knowledge on the PD of teicoplanin is required. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e

  19. Prognostic Value of C-Reactive Protein, Leukocytes, and Vitamin D in Severe Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Moberg, Mia; Vestbo, Jørgen; Martinez, Gerd

    2014-01-01

    Inflammatory biomarkers predict mortality and hospitalisation in chronic obstructive pulmonary disease (COPD). Yet, it remains uncertain if biomarkers in addition to reflecting disease severity add new prognostic information on severe COPD. We investigated if leukocytes, C-reactive protein (CRP......), and vitamin D were independent predictors of mortality and hospitalisation after adjusting for disease severity with an integrative index, the i-BODE index. In total, 423 patients participating in a pulmonary rehabilitation programme, with a mean value of FEV1 of 38% of predicted, were included. Mean followup...... was 45 months. During the follow-up period, 149 deaths (35%) were observed and 330 patients (78.0%) had at least one acute hospitalisation; 244 patients (57.7%) had at least one hospitalisation due to an exacerbation of COPD. In the analysis (Cox proportional hazards model) fully adjusted for age, sex...

  20. Gonadal cell surface receptor for plasma retinol-binding protein

    International Nuclear Information System (INIS)

    Krishna Bhat, M.; Cama, H.R.

    1979-01-01

    A specific membrane receptor for plasma retinol-binding protein has been demonstrated in testicular cells. Prealbumin-2 did not show any specific binding to the membrane. The affinity of retinol-binding protein for receptor drastically decreases upon delivery of retinol and the retinol-binding protein does not enter the cell. The mechanism of delivery of retinol to the target cell by plasma retinol-binding protein has been investigated. The process involves two steps; direct binding of retinol-binding protein to the receptor and uptake of retinol by the target cell with a concomitant drastic reduction in the affinity of the retinol-binding protein to the receptor. Probably the second step of the process needs a cytosolic factor, possibly the cellular retinol-binding protein or an enzyme. The binding of retinol-binding protein to the receptor is saturable and reversible. The interaction shows a Ksub(d) value of 2.1x10 -10 . The specific binding of a retinol-binding protein with great affinity has been employed in the development of a method for radioassay of the receptor. The receptor level of the gonadal cell has been found to vary with the stage of differentiation. The receptor concentrations in 11-week-old birds and adult birds are comparable. Testosterone treatment of 11-week-old birds produced a substantial increase in the receptor concentration over control, while the protein content increased marginally, indicating that, probably, synthesis of the receptor is specifcally induced by testosterone during spermatogenesis, and the concentration of receptor is relatively higher before the formation of the acrosome. (Auth.)

  1. Cyclic AMP-receptor protein activates aerobactin receptor IutA expression in Vibrio vulnificus.

    Science.gov (United States)

    Kim, Choon-Mee; Kim, Seong-Jung; Shin, Sung-Heui

    2012-04-01

    The ferrophilic bacterium Vibrio vulnificus can utilize the siderophore aerobactin of Escherichia coli for iron acquisition via its specific receptor IutA. This siderophore piracy by V. vulnificus may contribute to its survival and proliferation, especially in mixed bacterial environments. In this study, we examined the effects of glucose, cyclic AMP (cAMP), and cAMP-receptor protein (Crp) on iutA expression in V. vulnificus. Glucose dose-dependently repressed iutA expression. A mutation in cya encoding adenylate cyclase required for cAMP synthesis severely repressed iutA expression, and this change was recovered by in trans complementing cya or the addition of exogenous cAMP. Furthermore, a mutation in crp encoding Crp severely repressed iutA expression, and this change was recovered by complementing crp. Accordingly, glucose deprivation under iron-limited conditions is an environmental signal for iutA expression, and Crp functions as an activator that regulates iutA expression in response to glucose availability.

  2. Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease. A nested case-control study

    DEFF Research Database (Denmark)

    Gram, J; Bladbjerg, E-M; Møller, L

    2000-01-01

    OBJECTIVES: To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects. DESIGN: Nested case-control study. Follow-up periods 7-15 years. SUBJECTS: Included in the study were 133 cases with coronary heart disease...... and 258 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C-reactive protein (CRP) and tissue-type plasminogen activator (t-PA) were measured with ELISA methods in stored serum.......005) and it was present in both the 7-9 years follow-up cohort (CRP: P = 0.014; t-PA: P = 0.001) and the 15 years follow-up cohort (CRP: P = 0.027; t-PA: P = 0.012). The best predictor of CRP was t-PA, whilst the best predictor of t-PA was triglycerides. In a logistic regression analysis model, t-PA still came out...

  3. High-affinity RNA aptamers to C-reactive protein (CRP): newly developed pre-elution methods for aptamer selection

    International Nuclear Information System (INIS)

    Orito, N; Umekage, S; Sakai, E; Tanaka, T; Kikuchi, Y; Sato, K; Kawauchi, S; Tanaka, H

    2012-01-01

    We have developed a modified SELEX (systematic evolution of ligands by exponential enrichment) method to obtain RNA aptamers with high affinity to C-reactive protein (CRP). CRP is a clinical biomarker present in plasma, the level of which increases in response to infections and noninfectious inflammation. The CRP level is also an important prognostic indicator in patients with several syndromes. At present, CRP content in blood is measured immunochemically using antibodies. To develop a more sensitive method using RNA aptamers, we have attempted to obtain high-affinity RNA aptamers to CRP. We succeeded in obtaining an RNA aptamer with high affinity to CRP using a CRP-immobilized Sepharose column and pre-elution procedure. Pre-elution is a method that removes the weak binding portion from a selected RNA population by washing for a short time with buffer containing CRP. By surface plasmon-resonance (SPR) analysis, the affinity constant of this aptamer for CRP was calculated to be K D = 2.25x10 -9 (M). The secondary structure, contact sites with CRP protein, and application of this aptamer will be described.

  4. Proliferation of NS0 cells in protein-free medium: the role of cell-derived proteins, known growth factors and cellular receptors.

    Science.gov (United States)

    Spens, Erika; Häggström, Lena

    2009-05-20

    NS0 cells proliferate without external supply of growth factors in protein-free media. We hypothesize that the cells produce their own factors to support proliferation. Understanding the mechanisms behind this autocrine regulation of proliferation may open for the novel approaches to improve animal cell processes. The following proteins were identified in NS0 conditioned medium (CM): cyclophilin A, cyclophilin B (CypB), cystatin C, D-dopachrome tautomerase, IL-25, isopentenyl-diphosphate delta-isomerase, macrophage migration inhibitory factor (MIF), beta(2)-microglobulin, Niemann pick type C2, secretory leukocyte protease inhibitor, thioredoxin-1, TNF-alpha, tumour protein translationally controlled 1 and ubiquitin. Further, cDNA microarray analysis indicated that the genes for IL-11, TNF receptor 6, TGF-beta receptor 1 and the IFN-gamma receptor were transcribed. CypB, IFN-alpha/beta/gamma, IL-11, IL-25, MIF, TGF-beta and TNF-alpha as well as the known growth factors EGF, IGF-I/II, IL-6, leukaemia inhibitory factor and oncostatin M (OSM) were excluded as involved in autocrine regulation of NS0 cell proliferation. The receptors for TGF-beta, IGF and OSM are however present in NS0 cell membranes since TGF-beta(1) caused cell death, and IGF-I/II and OSM improved cell growth. Even though no ligand was found, the receptor subunit gp130, active in signal transduction of the IL-6 like proteins, was shown to be essential for NS0 cells as demonstrated by siRNA gene silencing.

  5. Socioeconomic position, health behaviors, and C-reactive protein: A moderated-mediation analysis

    Science.gov (United States)

    Kershaw, Kiarri N.; Mezuk, Briana; Abdou, Cleopatra M.; Rafferty, Jane A.; Jackson, James S.

    2010-01-01

    Objective We sought to understand the link between low SEP and cardiovascular disease (CVD) by examining the association between SEP, health-related coping behaviors, and C-reactive protein (CRP), an inflammatory marker and independent risk factor for CVD in a US sample of adults. Design We used a multiple mediation model to evaluate how these behaviors work in concert to influence CRP levels and whether these relationships were moderated by gender and race/ethnicity. Main outcome measures CRP levels were divided into two categories: elevated CRP (3.1–10.0 mg/L) and normal CRP (≤ 3.0 mg/L). Results Both poverty and low educational attainment were associated with elevated CRP, and these associations were primarily explained through higher levels of smoking and lower levels of exercise. In the education model, poor diet also emerged as a significant mediator. These behaviors accounted for 87.9% of the total effect of education on CRP and 55.8% the total effect of poverty on CRP. We also found significant moderation of these mediated effects by gender and race/ethnicity. Conclusion These findings demonstrate the influence of socioeconomically-patterned environmental constraints on individual-level health behaviors. Specifically, reducing socioeconomic inequalities may have positive effects on CVD disparities through reducing cigarette smoking and increasing vigorous exercise. PMID:20496985

  6. Serum C-reactive protein concentrations in healthy Miniature Schnauzer dogs.

    Science.gov (United States)

    Wong, Valerie M; Kidney, Beverly A; Snead, Elisabeth C R; Myers, Sherry L; Jackson, Marion L

    2011-09-01

    C-reactive protein (CRP) is a sensitive marker for inflammation in people and dogs. In people, an association between CRP concentration and atherosclerosis has been reported. Atherosclerosis is rare in dogs, but the Miniature Schnauzer breed may be at increased risk for developing this vascular disease. It is not known if CRP concentrations in Miniature Schnauzer dogs differ from those in other dog breeds. Our objectives were to validate an automated human CRP assay for measuring CRP in dogs and compare CRP concentrations in healthy Miniature Schnauzer dogs with those in non-Miniature Schnauzer breeds. Sera from 37 non-Miniature Schnauzer dogs with inflammatory disease were pooled and used to validate a human CRP immunoturbidimetric assay for measuring canine CRP. Blood was collected from 20 healthy Miniature Schnauzer dogs and 41 healthy dogs of other breeds. Median serum CRP concentration of healthy Miniature Schnauzer dogs was compared with that of healthy non-Miniature Schnauzer dogs. The human CRP assay measured CRP reliably with linearity between 0 and 20 mg/L. CRP concentration for healthy Miniature Schnauzer dogs (median 4.0 mg/L, minimum-maximum 0-18.2 mg/L) was significantly higher than for the healthy non-Miniature Schnauzer dogs (median 0.1 mg/L, minimum-maximum 0-10.7 mg/L); 17 of the 20 Miniature Schnauzer dogs had values that overlapped with those of the non-Miniature Schnauzer dogs. Median CRP concentration of Miniature Schnauzer dogs was slightly higher than that of other breeds of dogs. A relationship between higher CRP concentration in Miniature Schnauzer dogs and idiopathic hyperlipidemia, pancreatitis, and possible increased risk for atherosclerosis remains to be determined. ©2011 American Society for Veterinary Clinical Pathology.

  7. C-reactive protein in antiphospholipid syndrome: relationship with cardiovascular pathology

    Directory of Open Access Journals (Sweden)

    N V Seredavkina

    2009-01-01

    Full Text Available Objective. To assess relationship of high sensitivity C reactive protein (hsCRP level in pts with antiphospholipid syndrome (APS with clinico-laboratory features and cardiovascular pathology. Material and methods. 206 pts were included. 58 from them had primary APS (PAPS, 72 –systemic lupus erythematosus (SLE with APS and 76 – SLE. 29 from 76 pts of the latter group were positive on anticardiolipin antibodies (ACA – SLE with antiphospholipid antibodies (APhL and 47 – low positive or negative on ACA – SLE without APhL. 72 persons without autoimmune diseases were included into control group. CRP (with high sensitivity immuno-nephelometric assay, APhL (with solid phase immuno-enzyme assay, plasma lipids were evaluated, sonography with measurement of intima-media complex (IMC thickness of common carotid arteries, carotid artery bulbs and internal carotid arteries, electrocardiography (ECG, echocardiography (EchoCG, Holter ECG monitoring were performed. Results. HsCRP serum level in pts was significantly higher than in control: 2,55 [0,71; 7,04] mg/l (varied from 0,15 to 39,85 vs 0,68 [0,26; 1,97] mg/l (varied from 0,1 to 9,61, p<0,001. Most high hsCRP concentration was found in SLE with APS (p=0,02. HsCRP level in pts with PAPS with history of combined or isolated arterial thrombosis was significantly higher than in pts with SLE and APS having the same localization of thrombosis. HsCRP concentration less than 3 mg/l correlated with duration of postthrombotic period in pts with PAPS. HsCRP level also correlated with triglyceride concentration, body mass index, summated coronary risk and magistral arteries IMC thickness. Conclusion. HsCRP elevation in pts with APS was associated with development of combined and arterial thrombosis as well as with traditional risk factors of atherosclerosis.

  8. C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy.

    Science.gov (United States)

    Cekić, Sonja; Cvetković, Tatjana; Jovanović, Ivan; Jovanović, Predrag; Pesić, Milica; Stanković Babić, Gordana; Milenković, Svetislav; Risimić, Dijana

    2014-08-20

    The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

  9. Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans.

    Science.gov (United States)

    Rodrigues, Sarina M; Saslow, Laura R; Garcia, Natalia; John, Oliver P; Keltner, Dacher

    2009-12-15

    Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the "Reading the Mind in the Eyes" Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles.

  10. Dissecting signaling and functions of adhesion G protein-coupled receptors

    DEFF Research Database (Denmark)

    Araç, Demet; Aust, Gabriela; Calebiro, Davide

    2012-01-01

    G protein-coupled receptors (GPCRs) comprise an expanded superfamily of receptors in the human genome. Adhesion class G protein-coupled receptors (adhesion-GPCRs) form the second largest class of GPCRs. Despite the abundance, size, molecular structure, and functions in facilitating cell and matrix...... contacts in a variety of organ systems, adhesion-GPCRs are by far the most poorly understood GPCR class. Adhesion-GPCRs possess a unique molecular structure, with extended N-termini containing various adhesion domains. In addition, many adhesion-GPCRs are autoproteolytically cleaved into an N......-terminal fragment (NTF, NT, α-subunit) and C-terminal fragment (CTF, CT, β-subunit) at a conserved GPCR autoproteolysis-inducing (GAIN) domain that contains a GPCR proteolysis site (GPS). These two features distinguish adhesion-GPCRs from other GPCR classes. Though active research on adhesion-GPCRs in diverse areas...

  11. Gender, obesity and repeated elevation of C-reactive protein: data from the CARDIA cohort.

    Directory of Open Access Journals (Sweden)

    Shinya Ishii

    Full Text Available C-reactive Protein (CRP measurements above 10 mg/L have been conventionally treated as acute inflammation and excluded from epidemiologic studies of chronic inflammation. However, recent evidence suggest that such CRP elevations can be seen even with chronic inflammation. The authors assessed 3,300 participants in The Coronary Artery Risk Development in Young Adults study, who had two or more CRP measurements between 1992/3 and 2005/6 to a investigate characteristics associated with repeated CRP elevation above 10 mg/L; b identify subgroups at high risk of repeated elevation; and c investigate the effect of different CRP thresholds on the probability of an elevation being one-time rather than repeated. 225 participants (6.8% had one-time and 103 (3.1% had repeated CRP elevation above 10 mg/L. Repeated elevation was associated with obesity, female gender, low income, and sex hormone use. The probability of an elevation above 10 mg/L being one-time rather than repeated was lowest (51% in women with body mass index above 31 kg/m(2, compared to 82% in others. These findings suggest that CRP elevations above 10 mg/L in obese women are likely to be from chronic rather than acute inflammation, and that CRP thresholds above 10 mg/L may be warranted to distinguish acute from chronic inflammation in obese women.

  12. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction.

    Science.gov (United States)

    Tomàs, Josep M; Garcia, Neus; Lanuza, Maria A; Nadal, Laura; Tomàs, Marta; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh) receptors (subtypes mAChR; M 1 , M 2 and M 4 ), adenosine receptors (AR; A 1 and A 2A ) and the tropomyosin-related kinase B receptor (TrkB), among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC), to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A 1 , M 1 and TrkB operate mainly by stimulating PKC whereas A 2A , M 2 and M 4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC) in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ). This hypothesis is supported by: (i) the tonic effect (shown by using selective inhibitors) of several membrane receptors that accelerates axon loss between postnatal days P5-P9; (ii) the synergistic, antagonic and modulatory effects (shown by paired inhibition) of the receptors on axonal loss; (iii) the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv) the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and

  13. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Josep M. Tomàs

    2017-08-01

    Full Text Available Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh receptors (subtypes mAChR; M1, M2 and M4, adenosine receptors (AR; A1 and A2A and the tropomyosin-related kinase B receptor (TrkB, among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC, to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A1, M1 and TrkB operate mainly by stimulating PKC whereas A2A, M2 and M4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ. This hypothesis is supported by: (i the tonic effect (shown by using selective inhibitors of several membrane receptors that accelerates axon loss between postnatal days P5–P9; (ii the synergistic, antagonic and modulatory effects (shown by paired inhibition of the receptors on axonal loss; (iii the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and various

  14. G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs).

    Science.gov (United States)

    Li, Lingyong; Homan, Kristoff T; Vishnivetskiy, Sergey A; Manglik, Aashish; Tesmer, John J G; Gurevich, Vsevolod V; Gurevich, Eugenia V

    2015-04-24

    G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in homologous desensitization of GPCRs. It is widely assumed that most GRKs selectively phosphorylate only active GPCRs. Here, we show that although this seems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of several GPCRs, including β2-adrenergic and M2 muscarinic receptors, which are commonly used as representative models for GPCRs. Agonist-independent GPCR phosphorylation cannot be explained by constitutive activity of the receptor or membrane association of the GRK, suggesting that it is an inherent ability of GRK5/6. Importantly, phosphorylation of the inactive β2-adrenergic receptor enhanced its interactions with arrestins. Arrestin-3 was able to discriminate between phosphorylation of the same receptor by GRK2 and GRK5, demonstrating preference for the latter. Arrestin recruitment to inactive phosphorylated GPCRs suggests that not only agonist activation but also the complement of GRKs in the cell regulate formation of the arrestin-receptor complex and thereby G protein-independent signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. The Secreted Protein C1QL1 and Its Receptor BAI3 Control the Synaptic Connectivity of Excitatory Inputs Converging on Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Séverine M. Sigoillot

    2015-02-01

    Full Text Available Precise patterns of connectivity are established by different types of afferents on a given target neuron, leading to well-defined and non-overlapping synaptic territories. What regulates the specific characteristics of each type of synapse, in terms of number, morphology, and subcellular localization, remains to be understood. Here, we show that the signaling pathway formed by the secreted complement C1Q-related protein C1QL1 and its receptor, the adhesion-GPCR brain angiogenesis inhibitor 3 (BAI3, controls the stereotyped pattern of connectivity established by excitatory afferents on cerebellar Purkinje cells. The BAI3 receptor modulates synaptogenesis of both parallel fiber and climbing fiber afferents. The restricted and timely expression of its ligand C1QL1 in inferior olivary neurons ensures the establishment of the proper synaptic territory for climbing fibers. Given the broad expression of C1QL and BAI proteins in the developing mouse brain, our study reveals a general mechanism contributing to the formation of a functional brain.

  16. C-reactive protein and white blood cell count do not improve clinical decision-making in acute appendicitis

    DEFF Research Database (Denmark)

    Tind, Sofie; Lassen, Annmarie Touborg; Zimmermann-Nielsen, Erik

    2015-01-01

    INTRODUCTION: Acute appendicitis (AA) remains a diagnostic challenge as indicated by the high rate of unnecessary surgery. Blood samples, primarily C-reactive protein (CRP) and leucocyte counts, are used as a diagnostic supplement despite their relatively low sensitivities and specificities...... the blood results and re-evaluate their diagnosis. The surgeon's diagnosis before and after was compared with the final diagnosis defined by surgical findings or follow-up. The gold standard was any degree of appendicitis on histology. RESULTS: A total of 226 patients were included of whom 91 (40.3%) had...... appendicitis on histology. The surgeons changed their diagnosis in nine cases after assessing blood samples. The changes in the proportion of correct diagnoses, sensitivity, specificity and predictive values after assessing blood samples were not significant. CONCLUSIONS: The results of CRP and leucocyte...

  17. Antifungal Effect of Arabidopsis SGT1 Proteins via Mitochondrial Reactive Oxygen Species.

    Science.gov (United States)

    Park, Seong-Cheol; Cheong, Mi Sun; Kim, Eun-Ji; Kim, Jin Hyo; Chi, Yong Hun; Jang, Mi-Kyeong

    2017-09-27

    The highly conserved SGT1 (suppressor of the G2 alleles of skp1) proteins from Arabidopsis are known to contribute to plant resistance to pathogens. While SGT1 proteins respond to fungal pathogens, their antifungal activity is not reported and the mechanism for this inhibition is not well understood. Therefore, recombinant Arabidopsis SGT1 proteins were cloned, expressed, and purified to evaluate their antifungal activity, resulting in their potent inhibition of pathogen growth. Dye-labeled proteins are localized to the cytosol of Candida albicans cells without the disruption of the cell membrane. Moreover, we showed that entry of the proteins into C. albicans cells resulted in the accumulation of reactive oxygen species (ROS) and cell death via altered mitochondrial potential. Morphological changes of C. albicans cells in the presence of proteins were visualized by scanning electron microscopy. Our data suggest that AtSGT1 proteins play a critical role in plant resistance to pathogenic fungal infection and they can be classified to a new plant antifungal protein.

  18. Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.

    Science.gov (United States)

    Huang, Xiao X; McCaughan, Geoffrey W; Shackel, Nicholas A; Gorrell, Mark D

    2007-09-01

    Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.

  19. A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians

    DEFF Research Database (Denmark)

    Wolford, Johanna K; Gruber, Jonathan D; Ossowski, Victoria M

    2003-01-01

    of diabetes, independent of adiposity. Because CRP is located on 1q21, we considered it a potential positional candidate gene for T2DM. We therefore evaluated CRP and the nearby serum amyloid P-component, APCS, which is structurally similar to CRP, as candidate diabetes susceptibility genes. Approximately 10......Linkage analysis has identified a susceptibility locus for type 2 diabetes mellitus (T2DM) on chromosome 1q21-q23 in several populations. Results from recent prospective studies indicate that increased levels of C-reactive protein (CRP), a marker of immune system activation, are predictive...... disequilibrium clusters. We genotyped representative SNPs in approximately 1300 Pima samples and found a single variant in the CRP promoter (SNP 133552) that was associated with T2DM (P=0.014), as well as a common haplotype (CGCG) that was associated with both T2DM (P=0.029) and corrected insulin response...

  20. C-reactive protein + 1059 G>C polymorphism in type 2 diabetes and coronary artery disease patients.

    Science.gov (United States)

    Kaur, Ramandeep; Matharoo, Kawaljit; Sharma, Rubina; Bhanwer, A J S

    2013-12-01

    Human C-reactive protein (CRP) is an acute phase reactant involved in chronic and acute inflammation. CRP is associated with metabolic syndrome, obesity, atherosclerosis, unstable angina, insulin resistance and diabetes. The present study evaluates the association of + 1059 G>C silent polymorphism in exon 2 of CRP gene in 581 cases [CAD (206), T2D (266), T2D with CAD (109)] and 235 controls in the population of Punjab (North-West India). The frequency of + 1059 G allele is highest in CAD (98.3%) followed by T2D (98.1%), T2D + CAD cases (97.7%) and controls (94.7%). G-allele is associated with increased risk of T2D [P = 0.003, OR = 2.93 (1.39-6.17)] and CAD [P = 0.004, OR = 3.25 (1.39-7.60)] in comparison to controls. Recessive model shows that GG genotype increases the risk of CAD by 4 fold (P = 0.003, OR = 4.19, 1.62-10.80), T2D by 3 fold (P = 0.008, OR = 3.23, 1.36-7.60) and T2D + CAD by 3.5 fold (P = 0.029, OR = 3.64, 1.14-11.66). Factor analyses show that BMI, WC, and WHR are core predictors for CAD and T2D, whereas CHO, TG and VLDL for T2D + CAD. The present study concludes that GG genotype of CRP + 1059 G>C polymorphism and clustering of obesity and dyslipidemia underlie the risk towards CAD, T2D and T2D + CAD in the North-West Indian population of Punjab.

  1. Serum Bilirubin and Their Association With C-Reactive Protein in Patients With Migraine.

    Science.gov (United States)

    Peng, You-Fan; Xie, Li-Qiu; Xiang, Yang; Xu, Gui-Dan

    2016-11-01

    Increased levels of C-reactive protein (CRP) have been considered as a marker in assessing neurogenic inflammation of migraine patients. An inverse relationship between serum bilirubin and CRP has been observed in various diseases. Therefore, we analyzed serum bilirubin levels in migraine patients, and investigated the relationship between serum bilirubin and CRP in migraineurs. A total of 86 newly diagnosed migraine patients were consecutively recruited to this study. Significantly lower median serum total bilirubin, conjugated bilirubin (CB) and unconjugated bilirubin were found in patients with migraine than healthy controls, and the levels of CRP were significantly higher in migraine patients than healthy controls. A negative correlation between CRP and CB was observed in patients with migraine (r = -0.255, P = 0.018). In a multiple linear regression model, the concentrations of CRP remained negatively correlated with CB. Our study demonstrates that serum bilirubin concentrations are decreased in migraineurs, and CB levels were found to be positively correlated with CRP in migraine patents. However, larger cross-sectional and prospective studies are needed to establish whether serum bilirubin may be a useful biomarker for assessing neurogenic inflammation in migraine patients and eventually guiding the therapy. © 2016 Wiley Periodicals, Inc.

  2. Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression

    International Nuclear Information System (INIS)

    Ohno, Masae; Kunimoto, Masaaki; Nishizuka, Makoto; Osada, Shigehiro; Imagawa, Masayoshi

    2009-01-01

    The farnesoid X receptor (FXR; NR1H4) is a member of the nuclear receptor superfamily and regulates the expression of genes involved in enterohepatic circulation and the metabolism of bile acids. Based on functional analyses, nuclear receptors are divided into regions A-F. To explore the cofactors interacting with FXR, we performed a pull-down assay using GST-fused to the N-terminal A/B region and the C region, which are required for the ligand-independent transactivation and DNA-binding, respectively, of FXR, and nuclear extracts from HeLa cells. We identified DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku80, and Ku70 as FXR associated factors. These proteins are known to have an important role in DNA repair, recombination, and transcription. DNA-PKcs mainly interacted with the A/B region of FXR, whereas the Ku proteins interacted with the C region and with the D region (hinge region). Chromatin immunoprecipitation assays revealed that the Ku proteins associated with FXR on the bile salt export pump (BSEP) promoter. Furthermore, we demonstrated that ectopic expression of the Ku proteins decreased the promoter activity and expression of BSEP gene mediated by FXR. These results suggest that the Ku proteins function as corepressors for FXR.

  3. The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses

    Science.gov (United States)

    Garcia, Rolando A. G.; Vasudevan, Kuzhalini; Buonanno, Andres

    2000-01-01

    Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1–4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain. Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90, PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with β2-syntrophin, which has a single PDZ domain. As with N-methyl-d-aspartate (NMDA) receptors, ErbB4 interacts with the first two PDZ domains of PSD-95. Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals. The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity. PMID:10725395

  4. Association of the C-Reactive Protein Gene (CRP rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis

    Directory of Open Access Journals (Sweden)

    Ewa Wypasek

    2015-10-01

    Full Text Available Elevation in C-reactive protein (CRP levels have been shown in patients with aortic valve stenosis (AS. Minor allele of the CRP gene (CRP rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96 vs. 1.68 (0.98–2.90 mg/L, p < 0.001 and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01 compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

  5. High sensitivity C-reactive protein distribution in the elderly: the Bambuí Cohort Study, Brazil

    Directory of Open Access Journals (Sweden)

    L.G.S. Assunção

    2012-12-01

    Full Text Available The measurement of the serum concentration of the acute-phase reactant C-reactive protein (CRP provides a useful marker in clinical practice. However, the distribution of CRP is not available for all age and population groups. This study assessed the distribution of high sensitivity-CRP (hs-CRP by gender and age in 1470 elderly individuals from a Brazilian community that participates in the Bambuí Cohort Study. Blood samples were collected after 12 h of fasting and serum samples were stored at -70°C. Measurements were made with a commercial hs-CRP immunonephelometric instrument. More than 50% of the results were above 3.0 mg/L for both genders. Mean hs-CRP was higher in women (3.62 ± 2.58 mg/L than in men (3.03 ± 2.50 mg/L. This difference was observed for all ages, except for the over-80 age group. This is the first population-based study to describe hs-CRP values in Latin American elderly subjects. Our results indicate that significant gender differences exist in the distribution of hs-CRP, and suggest that gender-specific cut-off points for hs-CRP would be necessary for the prediction of cardiovascular risks.

  6. c-reactive protein — biological functions, cardiovascular disease ...

    African Journals Online (AJOL)

    disease and physical exercise. S J Semple (Dtech) ... measured within exercise studies to provide evidence that ... sociated with cellular injury and the release of pro-inflamma- .... reactive oxygen species.17 In addition, psychological stress,.

  7. Spectral methods for study of the G-protein-coupled receptor rhodopsin. II. Magnetic resonance methods

    Science.gov (United States)

    Struts, A. V.; Barmasov, A. V.; Brown, M. F.

    2016-02-01

    This article continues our review of spectroscopic studies of G-protein-coupled receptors. Magnetic resonance methods including electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) provide specific structural and dynamical data for the protein in conjunction with optical methods (vibrational, electronic spectroscopy) as discussed in the accompanying article. An additional advantage is the opportunity to explore the receptor proteins in the natural membrane lipid environment. Solid-state 2H and 13C NMR methods yield information about both the local structure and dynamics of the cofactor bound to the protein and its light-induced changes. Complementary site-directed spin-labeling studies monitor the structural alterations over larger distances and correspondingly longer time scales. A multiscale reaction mechanism describes how local changes of the retinal cofactor unlock the receptor to initiate large-scale conformational changes of rhodopsin. Activation of the G-protein-coupled receptor involves an ensemble of conformational substates within the rhodopsin manifold that characterize the dynamically active receptor.

  8. The reactive metabolite target protein database (TPDB – a web-accessible resource

    Directory of Open Access Journals (Sweden)

    Dong Yinghua

    2007-03-01

    Full Text Available Abstract Background The toxic effects of many simple organic compounds stem from their biotransformation to chemically reactive metabolites which bind covalently to cellular proteins. To understand the mechanisms of cytotoxic responses it may be important to know which proteins become adducted and whether some may be common targets of multiple toxins. The literature of this field is widely scattered but expanding rapidly, suggesting the need for a comprehensive, searchable database of reactive metabolite target proteins. Description The Reactive Metabolite Target Protein Database (TPDB is a comprehensive, curated, searchable, documented compilation of publicly available information on the protein targets of reactive metabolites of 18 well-studied chemicals and drugs of known toxicity. TPDB software enables i string searches for author names and proteins names/synonyms, ii more complex searches by selecting chemical compound, animal species, target tissue and protein names/synonyms from pull-down menus, and iii commonality searches over multiple chemicals. Tabulated search results provide information, references and links to other databases. Conclusion The TPDB is a unique on-line compilation of information on the covalent modification of cellular proteins by reactive metabolites of chemicals and drugs. Its comprehensiveness and searchability should facilitate the elucidation of mechanisms of reactive metabolite toxicity. The database is freely available at http://tpdb.medchem.ku.edu/tpdb.html

  9. Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2.

    Science.gov (United States)

    Li, Qun; Laumonnier, Yves; Syrovets, Tatiana; Simmet, Thomas

    2011-11-01

    To identify proteins that interact with the C-terminal fragment of annexin A2 (A2IC), generated by plasmin cleavage of the plasmin receptor, a heterotetramer (AA2t) containing annexin A2. The gene that encodes the A2IC fragment was obtained from PCR-amplified cDNA isolated from human monocytes, and was ligated into the pBTM116 vector using a DNA ligation kit. The resultant plasmid (pBTM116-A2IC) was sequenced with an ABI PRISM 310 Genetic Analyzer. The expression of an A2IC bait protein fused with a LexA-DNA binding domain (BD) was determined using Western blot analysis. The identification of proteins that interact with A2IC and are encoded in a human monocyte cDNA library was performed using yeast two-hybrid screening. The DNA sequences of the relevant cDNAs were determined using an ABI PRISM BigDye terminator cycle sequencing ready reaction kit. Nucleotide sequence databases were searched for homologous sequences using BLAST search analysis (http://www.ncbi.nlm.nih.gov). Confirmation of the interaction between the protein LexA-A2IC and each of cathepsin S and SNX17 was conducted using a small-scale yeast transformation and X-gal assay. The yeast transformed with plasmids encoding the bait proteins were screened with a human monocyte cDNA library by reconstituting full-length transcription factors containing the GAL4-active domain (GAL4-AD) as the prey in a yeast two-hybrid approach. After screening 1×10(7) clones, 23 independent β-Gal-positive clones were identified. Sequence analysis and a database search revealed that 15 of these positive clones matched eight different proteins (SNX17, ProCathepsin S, RPS2, ZBTB4, OGDH, CCDC32, PAPD4, and actin which was already known to interact with annexin A2). A2IC A2IC interacts with various proteins to form protein complexes, which may contribute to the molecular mechanism of monocyte activation induced by plasmin. The yeast two-hybrid system is an efficient approach for investigating protein interactions.

  10. Delta receptor antagonism, ethanol taste reactivity, and ethanol consumption in outbred male rats.

    Science.gov (United States)

    Higley, Amanda E; Kiefer, Stephen W

    2006-11-01

    Naltrexone, a nonspecific opioid antagonist, produces significant changes in ethanol responsivity in rats by rendering the taste of ethanol aversive as well as producing a decrease in voluntary ethanol consumption. The present study investigated the effect of naltrindole, a specific antagonist of delta opioid receptors, on ethanol taste reactivity and ethanol consumption in outbred rats. In the first experiment, rats received acute treatment of naltrexone, naltrindole, or saline followed by the measurement of ethanol consumption in a short-term access period. The second experiment involved the same treatments and investigated ethanol palatability (using the taste-reactivity test) as well as ethanol consumption. Results indicated that treatment with 3 mg/kg naltrexone significantly affected palatability (rendered ethanol more aversive, Experiment 2) and decreased voluntary ethanol consumption (Experiments 1 and 2). The effects of naltrindole were inconsistent. In Experiment 1, 8 mg/kg naltrindole significantly decreased voluntary ethanol consumption but this was not replicated in Experiment 2. The 8 mg/kg dose produced a significant increase in aversive responding (Experiment 2) but did not affect ingestive responding. Lower doses of naltrindole (2 and 4 mg/kg) were ineffective in altering rats' taste-reactivity response to and consumption of ethanol. While these data suggest that delta receptors are involved in rats' taste-reactivity response to ethanol and rats' ethanol consumption, it is likely that multiple opioid receptors mediate both behavioral responses.

  11. The heterotrimeric G protein Gβ1 interacts with the catalytic subunit of protein phosphatase 1 and modulates G protein-coupled receptor signaling in platelets.

    Science.gov (United States)

    Pradhan, Subhashree; Khatlani, Tanvir; Nairn, Angus C; Vijayan, K Vinod

    2017-08-11

    Thrombosis is caused by the activation of platelets at the site of ruptured atherosclerotic plaques. This activation involves engagement of G protein-coupled receptors (GPCR) on platelets that promote their aggregation. Although it is known that protein kinases and phosphatases modulate GPCR signaling, how serine/threonine phosphatases integrate with G protein signaling pathways is less understood. Because the subcellular localization and substrate specificity of the catalytic subunit of protein phosphatase 1 (PP1c) is dictated by PP1c-interacting proteins, here we sought to identify new PP1c interactors. GPCRs signal via the canonical heterotrimeric Gα and Gβγ subunits. Using a yeast two-hybrid screen, we discovered an interaction between PP1cα and the heterotrimeric G protein Gβ 1 subunit. Co-immunoprecipitation studies with epitope-tagged PP1c and Gβ 1 revealed that Gβ 1 interacts with the PP1c α, β, and γ1 isoforms. Purified PP1c bound to recombinant Gβ 1 -GST protein, and PP1c co-immunoprecipitated with Gβ 1 in unstimulated platelets. Thrombin stimulation of platelets induced the dissociation of the PP1c-Gβ 1 complex, which correlated with an association of PP1c with phospholipase C β3 (PLCβ3), along with a concomitant dephosphorylation of the inhibitory Ser 1105 residue in PLCβ3. siRNA-mediated depletion of GNB1 (encoding Gβ 1 ) in murine megakaryocytes reduced protease-activated receptor 4, activating peptide-induced soluble fibrinogen binding. Thrombin-induced aggregation was decreased in PP1cα -/- murine platelets and in human platelets treated with a small-molecule inhibitor of Gβγ. Finally, disruption of PP1c-Gβ 1 complexes with myristoylated Gβ 1 peptides containing the PP1c binding site moderately decreased thrombin-induced human platelet aggregation. These findings suggest that Gβ 1 protein enlists PP1c to modulate GPCR signaling in platelets.

  12. Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze

    Directory of Open Access Journals (Sweden)

    Kim Ryang

    2011-02-01

    Full Text Available Abstract Background Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory. Results We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1 and L-type voltage gated calcium channels (LVGCCs in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis. Conclusions Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

  13. The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

    KAUST Repository

    Wheeler, Janet I.

    2017-05-08

    The brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a member of the leucine rich repeat receptor like kinase family. The intracellular kinase domain of BRI1 is an active kinase and also encapsulates a guanylate cyclase catalytic centre. Using liquid chromatography tandem mass spectrometry, we confirmed that the recombinant cytoplasmic domain of BRI1 generates pmol amounts of cGMP per μg protein with a preference for magnesium over manganese as a co-factor. Importantly, a functional BRI1 kinase is essential for optimal cGMP generation. Therefore, the guanylate cyclase activity of BRI1 is modulated by the kinase while cGMP, the product of the guanylate cyclase, in turn inhibits BRI1 kinase activity. Furthermore, we show using Arabidopsis root cell cultures that cGMP rapidly potentiates phosphorylation of the downstream substrate BRASSINOSTEROID SIGNALING KINASE 1 (BSK1). Taken together, our results suggest that cGMP acts as a modulator that enhances downstream signaling while dampening signal generation from the receptor. This article is protected by copyright. All rights reserved.

  14. The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

    KAUST Repository

    Wheeler, Janet I.; Wong, Aloysius Tze; Marondedze, Claudius; Groen, Arnoud J.; Kwezi, Lusisizwe; Freihat, Lubna; Vyas, Jignesh; Raji, Misjudeen; Irving, Helen R.; Gehring, Christoph A

    2017-01-01

    The brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a member of the leucine rich repeat receptor like kinase family. The intracellular kinase domain of BRI1 is an active kinase and also encapsulates a guanylate cyclase catalytic centre. Using liquid chromatography tandem mass spectrometry, we confirmed that the recombinant cytoplasmic domain of BRI1 generates pmol amounts of cGMP per μg protein with a preference for magnesium over manganese as a co-factor. Importantly, a functional BRI1 kinase is essential for optimal cGMP generation. Therefore, the guanylate cyclase activity of BRI1 is modulated by the kinase while cGMP, the product of the guanylate cyclase, in turn inhibits BRI1 kinase activity. Furthermore, we show using Arabidopsis root cell cultures that cGMP rapidly potentiates phosphorylation of the downstream substrate BRASSINOSTEROID SIGNALING KINASE 1 (BSK1). Taken together, our results suggest that cGMP acts as a modulator that enhances downstream signaling while dampening signal generation from the receptor. This article is protected by copyright. All rights reserved.

  15. AlGaN/GaN High Electron Mobility Transistor-Based Biosensor for the Detection of C-Reactive Protein.

    Science.gov (United States)

    Lee, Hee Ho; Bae, Myunghan; Jo, Sung-Hyun; Shin, Jang-Kyoo; Son, Dong Hyeok; Won, Chul-Ho; Jeong, Hyun-Min; Lee, Jung-Hee; Kang, Shin-Won

    2015-07-28

    In this paper, we propose an AlGaN/GaN high electron mobility transistor (HEMT)-based biosensor for the detection of C-reactive protein (CRP) using a null-balancing circuit. A null-balancing circuit was used to measure the output voltage of the sensor directly. The output voltage of the proposed biosensor was varied by antigen-antibody interactions on the gate surface due to CRP charges. The AlGaN/GaN HFET-based biosensor with null-balancing circuit applied shows that CRP can be detected in a wide range of concentrations, varying from 10 ng/mL to 1000 ng/mL. X-ray photoelectron spectroscopy was carried out to verify the immobilization of self-assembled monolayer with Au on the gated region.

  16. Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

    LENUS (Irish Health Repository)

    Dillon, J P

    2012-02-03

    Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.

  17. Changes in serum cystatin C, creatinine, and C-reactive protein after cardiopulmonary bypass in patients with normal preoperative kidney function.

    Science.gov (United States)

    Svensson, Anders S; Kvitting, John-Peder Escobar; Kovesdy, Csaba P; Cederholm, Ingemar; Szabó, Zoltán

    2016-06-01

    The use of cardiopulmonary bypass (CPB) can cause changes in serum creatinine and cystatin C independent of glomerular filtration rate. We aimed to quantify the temporal changes of these biomarkers and C-reactive protein (CRP) after CPB. This was a prospective study at an academic medical centre between April and October 2013. We compared postoperative changes in serum creatinine and cystatin C in 38 patients with normal preoperative kidney function who underwent cardiac surgery using CPB and did not develop perioperative acute kidney injury (AKI). The effect of inflammation on intra-individual changes was examined in mixed effects regressions, using measurements of pre- and postoperative CRP. Both serum creatinine (79.9 ± 22.7 vs. 92.6 ± 21.4 µmol/L, P = 0.001) and cystatin C (1.16 ± 0.39 vs. 1.33 ± 0.37 mg/L, P = 0.012) decreased significantly in the first 8 h postoperatively compared to preoperatively, as a result of haemodilution. Thereafter serum creatinine returned to preoperative levels, whereas serum cystatin C continued to rise and was significantly elevated at 72 h post-CPB compared to preoperative levels (1.53 ± 0.48 vs. 1.33 ± 0.37 mg/L, P = 0.003). CRP levels increased significantly post-CPB and were significantly associated with increases in both serum creatinine and cystatin C. Serum creatinine and cystatin C appear not to be interchangeable biomarkers during and immediately after CPB. Processes unrelated to kidney function such as acute inflammation have a significant effect on post-CPB changes in these biomarkers, and may result in significant increases in serum cystatin C that could erroneously be interpreted as AKI. © 2015 Asian Pacific Society of Nephrology.

  18. Pre-operative high sensitive C-reactive protein predicts cardiovascular events after coronary artery bypass grafting surgery: A prospective observational study

    Directory of Open Access Journals (Sweden)

    Balciunas Mindaugas

    2009-01-01

    Full Text Available C-reactive protein is a powerful independent predictor of cardiovascular events in patients with coronary artery disease. The relation between C-reactive protein (CRP concentration and in-hospital outcome, after coronary artery bypass grafting (CABG, has not yet been established. The study aims to evaluate the predictive value of pre-operative CRP for in-hospital cardiovascular events after CABG surgery. High-sensitivity CRP (hs-CRP levels were measured pre-operatively on the day of surgery in 66 patients scheduled for elective on pump CABG surgery. Post-operative cardiovascular events such as death from cardiovascular causes, ischemic stroke, myocardial damage, myocardial infarction and low output heart failure were recorded. During the first 30 days after surgery, 54 patients were free from observed events and 14 developed the following cardiovascular events: 10 (15% had myocardial damage, four (6% had low output heart failure and two (3% suffered stroke. No patients died during the follow-up period. Serum concentration of hs-CRP ≥ 3.3 mg/l (cut-off point obtained by ROC analysis was related to higher risk of post-operative cardiovascular events (36% vs 6%, P = 0.01, myocardial damage (24% vs 6%, P = 0.04 and low output heart failure (12% vs 0%, P = 0.04. Multivariate logistic regression analysis showed that hs-CRP ≥ 3.3 mg/l ( P = 0.002, O.R.: 19.3 (95% confidence interval (CI 2.9-128.0, intra-operative transfusion of red blood cells ( P = 0.04, O.R.: 9.9 (95% C.I. 1.1-85.5 and absence of diuretics in daily antihypertensive treatment ( P = 0.02, O.R.: 15.1 (95% C.I. 1.4-160.6 were independent predictors of combined cardiovascular event. Patients having hs-CRP value greater or equal to 3.3 mg/l pre-operatively have an increased risk of post-operative cardiovascular events after on pump coronary artery bypass grafting surgery.

  19. A urokinase receptor-associated protein with specific collagen binding properties

    DEFF Research Database (Denmark)

    Behrendt, N; Jensen, O N; Engelholm, L H

    2000-01-01

    membrane-bound lectin with hitherto unknown function. The human cDNA was cloned and sequenced. The protein, designated uPARAP, is a member of the macrophage mannose receptor protein family and contains a putative collagen-binding (fibronectin type II) domain in addition to 8 C-type carbohydrate recognition...... domains. It proved capable of binding strongly to a single type of collagen, collagen V. This collagen binding reaction at the exact site of plasminogen activation on the cell may lead to adhesive functions as well as a contribution to cellular degradation of collagen matrices....

  20. Nonstructural 5A Protein of Hepatitis C Virus Interferes with Toll-Like Receptor Signaling and Suppresses the Interferon Response in Mouse Liver.

    Directory of Open Access Journals (Sweden)

    Takeya Tsutsumi

    Full Text Available The hepatitis C virus nonstructural protein NS5A is involved in resistance to the host immune response, as well as the viral lifecycle such as replication and maturation. Here, we established transgenic mice expressing NS5A protein in the liver and examined innate immune responses against lipopolysaccharide (LPS in vivo. Intrahepatic gene expression levels of cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ were significantly suppressed after LPS injection in the transgenic mouse liver. Induction of the C-C motif chemokine ligand 2, 4, and 5 was also suppressed. Phosphorylation of the signal transducer and activator of transcription 3, which is activated by cytokines, was also reduced, and expression levels of interferon-stimulated genes, 2'-5' oligoadenylate synthase, interferon-inducible double-stranded RNA-activated protein kinase, and myxovirus resistance 1 were similarly suppressed. Since LPS binds to toll-like receptor 4 and stimulates the downstream pathway leading to induction of these genes, we examined the extracellular signal-regulated kinase and IκB-α. The phosphorylation levels of these molecules were reduced in transgenic mouse liver, indicating that the pathway upstream of the molecules was disrupted by NS5A. Further analyses revealed that the interaction between interleukin-1 receptor-associated kinase-1 and tumor necrosis factor receptor associated factor-6 was dispersed in transgenic mice, suggesting that NS5A may interfere with this interaction via myeloid differentiation primary response gene 88, which was shown to interact with NS5A. Since the gut microbiota, a source of LPS, is known to be associated with pathological conditions in liver diseases, our results suggest the involvement of NS5A in the pathogenesis of HCV infected-liver via the suppression of innate immunity.

  1. C-reactive protein levels: a prognostic marker for patients with head and neck cancer?

    Science.gov (United States)

    Kruse, Astrid L; Luebbers, Heinz T; Grätz, Klaus W

    2010-08-02

    Recent advances in understanding complex tumor interactions have led to the discovery of an association between inflammation and cancer, in particular for colon and lung cancer, but only a very few have dealt with oral cancer. Therefore, the aim of the current study was to investigate the significance of preoperative C-reactive protein (CRP) levels as a parameter for development of lymph node metastases or recurrence. In 278 patients with oral cancer, preoperative CRP levels were compared with development of recurrence and metastasis. In 27 patients from the normal CRP group, and in 21 patients from the elevated CRP group, local recurrence was observed. Concerning lymph node metastases, 37 patients were in the normal group and 9 patients in the elevated CRP group. No significant correlation could be found between elevated CRP levels and metastasis (p = 0.468) or recurrence (p = 0.137). Our findings do not appear to support a correlation between preoperative CRP levels and development of recurrence or metastases. In further studies, CRP levels in precancerous lesions and in Human Papilloma Virus (HPV) positive patients with oral squamous cell carcinoma (SCC) should be studied.

  2. Molecular evolution of a chordate specific family of G protein-coupled receptors

    Directory of Open Access Journals (Sweden)

    Leese Florian

    2011-08-01

    Full Text Available Abstract Background Chordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental complexity in vertebrates, since mutations modifying the function of a duplicated protein can lead to novel functions, improving the evolutionary success. Results We analyzed here the evolution of the GPRC5 family of G protein-coupled receptors by comprehensive similarity searches and found that the receptors are only present in chordates and that the size of the receptor family expanded, likely due to genome duplication events in the early history of vertebrate evolution. We propose that a single GPRC5 receptor coding gene originated in a stem chordate ancestor and gave rise by duplication events to a gene family comprising three receptor types (GPRC5A-C in vertebrates, and a fourth homologue present only in mammals (GPRC5D. Additional duplications of GPRC5B and GPRC5C sequences occurred in teleost fishes. The finding that the expression patterns of the receptors are evolutionarily conserved indicates an important biological function of these receptors. Moreover, we found that expression of GPRC5B is regulated by vitamin A in vivo, confirming previous findings that linked receptor expression to retinoic acid levels in tumor cell lines and strengthening the link between the receptor expression and the development of a complex nervous system in chordates, known to be dependent on retinoic acid signaling. Conclusions GPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non

  3. Protective Effects of BDNF against C-Reactive Protein-Induced Inflammation in Women

    Directory of Open Access Journals (Sweden)

    Nicole Noren Hooten

    2015-01-01

    Full Text Available Background. Since high sensitivity C-reactive protein (hsCRP is predictive of cardiovascular events, it is important to examine the relationship between hsCRP and other inflammatory and oxidative stress markers linked to cardiovascular disease (CVD etiology. Previously, we reported that hsCRP induces the oxidative stress adduct 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodG and that these markers are significantly associated in women. Recent data indicates that brain-derived neurotrophic factor (BDNF may have a role in CVD. Methods and Results. We examined BDNF levels in 3 groups of women that were age- and race-matched with low (3–20 mg/L, and high (>20 mg/L hsCRP (n=39 per group and found a significant association between hsCRP, BDNF, and 8-oxodG. In African American females with high hsCRP, increases in BDNF were associated with decreased serum 8-oxodG. This was not the case in white women where high hsCRP was associated with high levels of BDNF and high levels of 8-oxodG. BDNF treatment of cells reduced CRP levels and inhibited CRP-induced DNA damage. Conclusion. We discovered an important relationship between hsCRP, 8-oxodG, and BDNF in women at hsCRP levels >3 mg/L. These data suggest that BDNF may have a protective role in counteracting the inflammatory effects of hsCRP.

  4. C-reactive protein and high mobility group box 1 in dogs with gastric dilatation and volvulus.

    Science.gov (United States)

    Uhrikova, Ivana; Rauserova-Lexmaulova, Leona; Rehakova, Kristina; Scheer, Peter; Doubek, Jaroslav

    2015-01-01

    To (1) measure C-reactive protein (CRP) and high mobility group box 1 (HMGB1) and (2) evaluate their prognostic value and relationship to severity of systemic inflammatory response syndrome, routine hematological and acid-base parameters in dogs with gastric dilatation volvulus (GDV). Prospective observational study from September 2010 to June 2012. Veterinary teaching hospital. Forty-one client-owned dogs with GDV. None. Blood was collected before surgery (baseline), postsurgery, 6-10 hours postsurgery, and 18-22 hours postsurgery. CRP and HMGB1 were measured in all samples, and routine hematological, biochemical, and acid-base analyses were performed. Only baseline and postsurgery samples were used from nonsurvivors (n = 10). CRP increased significantly from postsurgery sampling to 18-22 hours postsurgery, while HMGB1 did not change over time. There was a significant difference in HMGB1 between survivors and nonsurvivors over time. Both proteins correlated with systemic inflammatory response syndrome severity, total leukocyte, segmented neutrophils, and band counts. HMGB1 correlated also with acid-base parameters (pH, bicarbonate, base excess). HMGB1 and CRP behaved differently in regards to their kinetic patterns, with HMGB1 appearing to better reflect the severity of tissue injury in dogs with GDV than CRP. © Veterinary Emergency and Critical Care Society 2015.

  5. Interleukin-6, C-reactive protein, and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells in patients after laparoscopic vs. conventional bowel resection - A randomized study

    NARCIS (Netherlands)

    Dunker, M. S.; ten Hove, T.; Bemelman, W. A.; Slors, J. F. M.; Gouma, D. J.; van Deventer, S. J. H.

    2003-01-01

    PURPOSE: The aim of the study was to investigate the effect of surgical trauma in terms of approach (laparoscopic vs. conventional surgery) and extent of bowel resection (ileocolic resection vs. colectomy) on interleukin-6 level, C-reactive protein level, and expression of human leukocyte antigen-DR

  6. C REACTIVE PROTEIN AND CARDIOVASCULAR RISK IN CASES WITH DIABETES MALLITUS TYPE II

    Directory of Open Access Journals (Sweden)

    Munevera Bećarević

    2013-09-01

    Full Text Available Introduction: Factors of cardiovascular risk (CVR are often grouped in cases with diabetes mellitus (DM with significant increasment of risk for CV disease . The aim of this research is to determine the frequency of CVR and and total CVR in cases with DM and to investigate connection of CRP of other factors of CVR in total cardiovascular risks. Material and methods: In 92 cases with DM weist values were taken as well as body mass index (BMI, blood pressure, sugar in blood, cholesterol, triglycerides, C reactive protein (CRP and according to SCORE system the 10 year period of CVR were determined. Results: Out of 92 tested cases with age 55,22± 8,3 years, 63,05% were males and 36,95% were women, 81,5% were with values of sugar in blood >7mmol/l, 44,6% were with values of HbA1C>7% and 63,0% >6,5%. The value of cholesterol were >4,5mmol/l in 87%, triglycerides >1,7mmol/l in 78.3% of tested cases. 81,5% of tested cases were overweight and 49% with larger weight values. Average cardiovascular factor according to SCORE system was 3, 92± 3,7% with significant difference among sexes (M-4,86; W-2,32, p3mg/l 52% of tested cases were with high cardiovascular risk. There is significant positive correlation between CRP and cholesterol level (p<0, 01, triglycerides, blood in sugar, HbA1c and upper values of blood pressure (p<0, 05. Significant correlation between CRP and total cardiovascular risk (p=0, 63 was not evident. Conclusion: Cases with diabetes mellitus have high level of non regulated cardiovascular risk factors. Even though there is significant correlation between CRP and and pressure values, sugar in blood, HbA1c, cholesterol, triglycerides, significant correlation between CRP and total cardiovascular risk in cases with diabetes mellitus is not evident.

  7. Efficient subgroup C avian sarcoma and leukosis virus receptor activity requires the IgV domain of the Tvc receptor and proper display on the cell membrane.

    Science.gov (United States)

    Munguia, Audelia; Federspiel, Mark J

    2008-11-01

    We recently identified and cloned the receptor for subgroup C avian sarcoma and leukosis viruses [ASLV(C)], i.e., Tvc, a protein most closely related to mammalian butyrophilins, which are members of the immunoglobulin protein family. The extracellular domain of Tvc contains two immunoglobulin-like domains, IgV and IgC, which presumably each contain a disulfide bond important for native function of the protein. In this study, we have begun to identify the functional determinants of Tvc responsible for ASLV(C) receptor activity. We found that the IgV domain of the Tvc receptor is responsible for interacting with the glycoprotein of ASLV(C). Additional experiments demonstrated that a domain was necessary as a spacer between the IgV domain and the membrane-spanning domain for efficient Tvc receptor activity, most likely to orient the IgV domain a proper distance from the cell membrane. The effects on ASLV(C) glycoprotein binding and infection efficiency were also studied by site-directed mutagenesis of the cysteine residues of Tvc as well as conserved amino acid residues of the IgV Tvc domain compared to other IgV domains. In this initial analysis of Tvc determinants important for interacting with ASLV(C) glycoproteins, at least two aromatic amino acid residues in the IgV domain of Tvc, Trp-48 and Tyr-105, were identified as critical for efficient ASLV(C) infection. Interestingly, one or more aromatic amino acid residues have been identified as critical determinants in the other ASLV(A-E) receptors for a proper interaction with ASLV glycoproteins. This suggests that the ASLV glycoproteins may share a common mechanism of receptor interaction with an aromatic residue(s) on the receptor critical for triggering conformational changes in SU that initiate the fusion process required for efficient virus infection.

  8. Efficient Subgroup C Avian Sarcoma and Leukosis Virus Receptor Activity Requires the IgV Domain of the Tvc Receptor and Proper Display on the Cell Membrane▿

    Science.gov (United States)

    Munguia, Audelia; Federspiel, Mark J.

    2008-01-01

    We recently identified and cloned the receptor for subgroup C avian sarcoma and leukosis viruses [ASLV(C)], i.e., Tvc, a protein most closely related to mammalian butyrophilins, which are members of the immunoglobulin protein family. The extracellular domain of Tvc contains two immunoglobulin-like domains, IgV and IgC, which presumably each contain a disulfide bond important for native function of the protein. In this study, we have begun to identify the functional determinants of Tvc responsible for ASLV(C) receptor activity. We found that the IgV domain of the Tvc receptor is responsible for interacting with the glycoprotein of ASLV(C). Additional experiments demonstrated that a domain was necessary as a spacer between the IgV domain and the membrane-spanning domain for efficient Tvc receptor activity, most likely to orient the IgV domain a proper distance from the cell membrane. The effects on ASLV(C) glycoprotein binding and infection efficiency were also studied by site-directed mutagenesis of the cysteine residues of Tvc as well as conserved amino acid residues of the IgV Tvc domain compared to other IgV domains. In this initial analysis of Tvc determinants important for interacting with ASLV(C) glycoproteins, at least two aromatic amino acid residues in the IgV domain of Tvc, Trp-48 and Tyr-105, were identified as critical for efficient ASLV(C) infection. Interestingly, one or more aromatic amino acid residues have been identified as critical determinants in the other ASLV(A-E) receptors for a proper interaction with ASLV glycoproteins. This suggests that the ASLV glycoproteins may share a common mechanism of receptor interaction with an aromatic residue(s) on the receptor critical for triggering conformational changes in SU that initiate the fusion process required for efficient virus infection. PMID:18768966

  9. Time variability of C-reactive protein: implications for clinical risk stratification.

    Directory of Open Access Journals (Sweden)

    Peter Bogaty

    Full Text Available C-reactive protein (CRP is proposed as a screening test for predicting risk and guiding preventive approaches in coronary artery disease (CAD. However, the stability of repeated CRP measurements over time in subjects with and without CAD is not well defined. We sought to determine the stability of serial CRP measurements in stable subjects with distinct CAD manifestations and a group without CAD while carefully controlling for known confounders.We prospectively studied 4 groups of 25 stable subjects each 1 a history of recurrent acute coronary events; 2 a single myocardial infarction ≥7 years ago; 3 longstanding CAD (≥7 years that had never been unstable; 4 no CAD. Fifteen measurements of CRP were obtained to cover 21 time-points: 3 times during one day; 5 consecutive days; 4 consecutive weeks; 4 consecutive months; and every 3 months over the year. CRP risk threshold was set at 2.0 mg/L. We estimated variance across time-points using standard descriptive statistics and Bayesian hierarchical models.Median CRP values of the 4 groups and their pattern of variability did not differ substantially so all subjects were analyzed together. The median individual standard deviation (SD CRP values within-day, within-week, between-weeks and between-months were 0.07, 0.19, 0.36 and 0.63 mg/L, respectively. Forty-six percent of subjects changed CRP risk category at least once and 21% had ≥4 weekly and monthly CRP values in both low and high-risk categories.Considering its large intra-individual variability, it may be problematic to rely on CRP values for CAD risk prediction and therapeutic decision-making in individual subjects.

  10. Obese Hypertensive Men Have Plasma Concentrations of C-Reactive Protein Similar to That of Obese Normotensive Men

    DEFF Research Database (Denmark)

    Asferg, Camilla L; Andersen, Ulrik B; Linneberg, Allan

    2014-01-01

    BACKGROUND: Low-grade chronic inflammation is a characteristic feature of obesity, the most important lifestyle risk factor for hypertension. Elevated plasma concentrations of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of hypertension, but elevated...... plasma CRP concentrations are also closely associated with obesity. It is uncertain whether CRP is directly involved in the pathogenesis of hypertension or is only a marker of other pathogenic processes closely related to obesity. METHODS: We studied 103 obese men (body mass index (BMI) ≥ 30.0 kg/m(2......)); 63 of these men had 24-hour ambulatory blood pressure (ABP) ≥ 130/80 mm Hg and comprised the obese hypertensive (OHT) group. The 40 remaining obese men had 24-hour ABP obese normotensive (ONT) group. Our control group comprised 27 lean normotensive (LNT) men. All...

  11. Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease

    DEFF Research Database (Denmark)

    O'Doherty, Mark G; Jørgensen, Torben; Borglykke, Anders

    2014-01-01

    Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single 'baseline' measurement and such analyses cannot account for possible changes in these which...... may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between......, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity....

  12. Serum C-reactive protein as a diagnostic biomarker in dogs with bacterial respiratory diseases.

    Science.gov (United States)

    Viitanen, S J; Laurila, H P; Lilja-Maula, L I; Melamies, M A; Rantala, M; Rajamäki, M M

    2014-01-01

    C-reactive protein (CRP) is a major acute-phase protein in dogs. Serum concentrations are low in healthy animals, but increase rapidly after inflammatory stimuli. The aim of the study was to investigate CRP concentrations in various respiratory diseases of dogs and to determine if CRP can be used as a biomarker in the diagnosis of bacterial respiratory diseases. A total of 106 privately owned dogs with respiratory diseases (17 with bacterial tracheobronchitis [BTB], 20 with chronic bronchitis [CB], 20 with eosinophilic bronchopneumopathy [EBP], 12 with canine idiopathic pulmonary fibrosis [CIPF], 15 with cardiogenic pulmonary edema [CPE], and 22 with bacterial pneumonia [BP]) and 72 healthy controls. The study was conducted as a prospective cross-sectional observational study. CRP was measured in serum samples. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and selected diagnostic methods such as cytological and microbiological analysis of respiratory samples, echocardiography, and histopathology. Dogs with BP had significantly higher CRP concentrations (median, 121 mg/L; interquartile range, 68-178 mg/L) than dogs with BTB (23, 15-38, P = .0003), CB (13, 8-14, P < .0001), EBP (5, 5-15, P < .0001), CIPF (17, 10-20, P < .0001), or CPE (19, 13-32, P < .0001) and healthy controls (14, 8-20, P < .0001). Dogs with BTB had significantly higher CRP concentrations than dogs with CB (P = .001) or EBP (P < .0001) and healthy controls (P = .029). These results indicate that CRP has potential for use as an additional biomarker, especially in the diagnostics of BP. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  13. cDNA for the human β2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor

    International Nuclear Information System (INIS)

    Kobilka, B.K.; Dixon, R.A.F.; Frielle, T.

    1987-01-01

    The authors have isolated and sequenced a cDNA encoding the human β 2 -adrenergic receptor. The deduced amino acid sequence (413 residues) is that of a protein containing seven clusters of hydrophobic amino acids suggestive of membrane-spanning domains. While the protein is 87% identical overall with the previously cloned hamster β 2 -adrenergic receptor, the most highly conserved regions are the putative transmembrane helices (95% identical) and cytoplasmic loops (93% identical), suggesting that these regions of the molecule harbor important functional domains. Several of the transmembrane helices also share lesser degrees of identity with comparable regions of select members of the opsin family of visual pigments. They have localized the gene for the β 2 -adrenergic receptor to q31-q32 on chromosome 5. This is the same position recently determined for the gene encoding the receptor for platelet-derived growth factor and is adjacent to that for the FMS protooncogene, which encodes the receptor for the macrophage colony-stimulating factor

  14. Potential cellular receptors involved in hepatitis C virus entry into cells

    Directory of Open Access Journals (Sweden)

    Muellhaupt Beat

    2005-04-01

    Full Text Available Abstract Hepatitis C virus (HCV infects hepatocytes and leads to permanent, severe liver damage. Since the genomic sequence of HCV was determined, progress has been made towards understanding the functions of the HCV-encoded proteins and identifying the cellular receptor(s responsible for adsorption and penetration of the virus particle into the target cells. Several cellular receptors for HCV have been proposed, all of which are associated with lipid and lipoprotein metabolism. This article reviews the cellular receptors for HCV and suggests a general model for HCV entry into cells, in which lipoproteins play a crucial role.

  15. An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor Uncoordinated-5C-induced Signaling That Merges with Amyloid β Precursor Protein Signaling.

    Science.gov (United States)

    Hashimoto, Yuichi; Toyama, Yuka; Kusakari, Shinya; Nawa, Mikiro; Matsuoka, Masaaki

    2016-06-03

    A missense mutation (T835M) in the uncoordinated-5C (UNC5C) netrin receptor gene increases the risk of late-onset Alzheimer disease (AD) and also the vulnerability of neurons harboring the mutation to various insults. The molecular mechanisms underlying T835M-UNC5C-induced death remain to be elucidated. In this study, we show that overexpression of wild-type UNC5C causes low-grade death, which is intensified by an AD-linked mutation T835M. An AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1, inhibit this death. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of death-associated protein kinase 1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid β precursor protein (APP). Notably, netrin1 also binds to APP and partially inhibits the death-signaling cascade, induced by APP. These results may provide new insight into the amyloid β-independent pathomechanism of AD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Effects of carprofen and meloxicam on C-reactive protein, ceruloplasmin, and fibrinogen concentrations in dogs undergoing ovariohysterectomy.

    Science.gov (United States)

    Kum, Cavit; Voyvoda, Huseyin; Sekkin, Selim; Karademir, Umit; Tarimcilar, Tugrul

    2013-10-01

    To evaluate the effects of perioperative oral administration of carprofen and meloxicam on concentrations of 3 acute-phase proteins in dogs undergoing elective ovariohysterectomy (OVH). 18 healthy adult anestrous female dogs undergoing elective OVH. Dogs were allocated to 3 groups (6 dogs/group). A placebo treatment, carprofen (2.0 mg/kg), or meloxicam (0.2 mg/kg) was orally administered to the dogs of the respective groups. The initial doses were administered 30 minutes before premedication prior to OVH; additional doses were administered once daily for 4 days after surgery. Blood samples were collected 45 minutes before premedication and 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after the end of OVH; samples were used for measurement of total WBC and neutrophil counts and concentrations of C-reactive protein (CRP), ceruloplasmin, and fibrinogen. Values did not differ significantly among groups for WBC and neutrophil counts, serum concentrations of CRP and ceruloplasmin, and plasma concentrations of fibrinogen. Concentrations of all inflammatory markers, except serum ceruloplasmin, increased significantly following OVH, but in a similar manner for each group. No significant changes were detected in serum ceruloplasmin concentrations over time. Perioperative administration of both carprofen and meloxicam did not significantly affect the concentrations of CRP, ceruloplasmin, and fibrinogen in dogs undergoing OVH. Thus, use of carprofen or meloxicam should not affect clinical interpretation of results for these 3 acute-phase proteins.

  17. Feeding common carp Cyprinus carpio with b-glucan supplemented \\ud diet stimulates C-reactive protein and complement immune acute\\ud phase responses following PAMPs injection

    OpenAIRE

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna J.; Shrive, Annette K.; Hoole, Dave

    2014-01-01

    The effect of β-glucan as a feed additive on the serum and gene profile of C-reactive protein (CRP) and complement acute phase responses was ascertained in common carp Cyprinus carpio. In addition effects of subsequent intraperitoneal injections of pathogen-associated molecular patterns (PAMPs), i.e. LPS or poly(I:C), to mimic bacterial or viral infection respectively, were studied. Carp were first orally fed with β-glucan (MacroGard®) with a daily β-glucan intake of 6 mg per kg body weight o...

  18. Local C-Reactive Protein Expression in Obliterative Lesions and the Bronchial Wall in Posttransplant Obliterative Bronchiolitis

    Directory of Open Access Journals (Sweden)

    Outi E. Päiväniemi

    2009-01-01

    Full Text Available The local immunoreactivity of C-reactive protein (CRP was studied in a heterotopic porcine model of posttranplant obliterative bronchiolitis (OB. Bronchial allografts and control autografts were examined serially 2–28 days after subcutaneous transplantation. The autografts stayed patent. In the allografts, proliferation of inflammatory cells (P<.0001 and fibroblasts (P=.02 resulted in occlusion of the bronchial lumens (P<.01. Influx of CD4+ (P<.001 and CD8+ (P<.0001 cells demonstrated allograft immune response. CRP positivity simultaneously increased in the bronchial walls (P<.01, in macrophages, myofibroblasts, and endothelial cells. Local CRP was predictive of features characteristic of OB (R=0.456–0.879, P< .05−P<.0001. Early obliterative lesions also showed CRP positivity, but not mature, collagen-rich obliterative plugs (P<.05. During OB development, CRP is localized in inflammatory cells, myofibroblasts and endothelial cells probably as a part of the local inflammatory response.

  19. C-reactive Protein −717A>G and −286C>T>A Gene Polymorphism and Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2015-01-01

    Full Text Available Background: Inflammation plays a pivotal role in the formation and progression of ischemic stroke. Recently, more and more epidemiological studies have focused on the association between C-reactive protein (CRP −717A > G and −286C > T > A genetic polymorphisms and ischemic stroke. However, the findings of these researches are not conclusive. Methods: We performed a meta-analysis to determine whether these two polymorphisms are associated with the risk of ischemic stroke. Eligible studies were identified from the database of PubMed, Medline, Embase, Web of Science, CNKI, Weipu, and Wanfang. We calculated odds ratios (ORs with 95% confidence intervals (CIs to assess the strength of the association. Results: Four articles were included in our study, including 1926 cases and 2678 controls for −717A > G polymorphism, 652 cases and 1103 controls for −286C > T > A polymorphism. The results of meta-analysis showed that single nucleotide polymorphism (SNP −717A > G was not significantly associated with the risk of ischemic stroke (GG vs. AA, OR = 1.12, 95% CI = 0.83-1.50, P = 0.207; GG + GA vs. AA, OR = 1.04, 95% CI = 0.93-1.17, P = 0.533; GG vs. GA + AA, OR = 1.10, 95% CI = 0.82-1.47, P = 0.220. Meta-analysis of SNP − 286C > T > A also demonstrated no statistical evidence of a significant association with the risk of ischemic stroke (AA vs. CC, OR = 0.86, 95% CI = 0.59-1.25, P = 0.348; AA vs. CC, OR = 0.92, 95% CI = 0.80-1.06, P = 0.609; AA vs. CC, OR = 0.89, 95% CI = 0.62-1.30, P = 0.374. Conclusions: This meta-analysis demonstrated little evidence to support a role of CRP gene −717A > G, −286C > T > A polymorphisms in ischemic stroke predisposition. However, to draw comprehensive and more reliable conclusions, further larger studies are needed to validate the association between CRP gene polymorphisms and ischemic stroke in various ethnic groups.

  20. Polyphenol-enriched berry extracts naturally modulate reactive proteins in model foods.

    Science.gov (United States)

    Lila, Mary Ann; Schneider, Maggie; Devlin, Amy; Plundrich, Nathalie; Laster, Scott; Foegeding, E Allen

    2017-12-13

    Healthy foods like polyphenol-rich berries and high quality edible proteins are in demand in today's functional food marketplace, but it can be difficult to formulate convenient food products with physiologically-relevant amounts of these ingredients and still maintain product quality. In part, this is because proteins can interact with other food ingredients and precipitate destabilizing events, which can disrupt food structure and diminish shelf life. Proteins in foods can also interact with human receptors to provoke adverse consequences such as allergies. When proteins and polyphenols were pre-aggregated into stable colloidal particles prior to use as ingredients, highly palatable food formulations (with reduced astringency of polyphenols) could be prepared, and the overall structural properties of food formulations were significantly improved. All of the nutritive and phytoactive benefits of the proteins and concentrated polyphenols remained highly bioavailable, but the protein molecules in the particle matrix did not self-aggregate into networks or react with other food ingredients. Both the drainage half-life (a marker of structural stability) and the yield stress (resistance to flow) of model foams made with the protein-polyphenol particles were increased in a dose-dependent manner. Of high significance in this complexation process, the reactive allergenic epitopes of certain proteins were effectively blunted by binding with polyphenols, attenuating the allergenicity of the food proteins. Porcine macrophages produced TNF-α proinflammatory cytokine when provoked with whey protein, but, this response was blocked completely when the cells were stimulated with particles that complexed whey protein with cinnamon-derived polyphenols. Cytokine and chemokine production characteristic of allergic reactions were blocked by the polyphenols, allowing for the potential creation of hypoallergenic protein-berry polyphenol enriched foods.

  1. Analysis of the association opportunistic infections with c-reactive protein focus toxoplasma, cytomegalovirus, rubella,and hepatitis in human immunodeficiency virus

    Science.gov (United States)

    Khadijah, K. H.; Ferica, K.; Katu, S.; Halim, R.; Mubin, A. H.

    2018-03-01

    Opportunistic infections occur more often severe in people with HIV. C-reactive protein is known to have a prognostic value in HIV and those with HIV-related opportunistic infections. High level of CRP will increase therisk of infection toxoplasma, CMV, rubella,and hepatitis in HIV.Analyzing association of opportunistic infections toxoplasma, CMV, rubella,and hepatitis with the level of CRP in HIV, a cross-sectional analytic study wasduring January-July 2017 on both outpatientand inpatient HIV subjects at Wahidin Sudirohusodo Hospital, Makassar. Each HIV patient is categorized into agroup of opportunistic infections: toxoplasma, CMV, rubella, hepatitis. CRP levels will be assessed in each group, defined by normal values 0.05).

  2. Complete cDNA sequence coding for human docking protein

    Energy Technology Data Exchange (ETDEWEB)

    Hortsch, M; Labeit, S; Meyer, D I

    1988-01-11

    Docking protein (DP, or SRP receptor) is a rough endoplasmic reticulum (ER)-associated protein essential for the targeting and translocation of nascent polypeptides across this membrane. It specifically interacts with a cytoplasmic ribonucleoprotein complex, the signal recognition particle (SRP). The nucleotide sequence of cDNA encoding the entire human DP and its deduced amino acid sequence are given.

  3. Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

    NARCIS (Netherlands)

    Keeling, Stephanie O.; Landewe, Robert; van der Heijde, Desiree; Bathon, Joan; Boers, Maarten; Garnero, Patrick; Geusens, Piet; El-Gabalawy, Hani; Inman, Robert D.; Kraus, Virginia B.; Kvien, Tore K.; Mease, Philip J.; Ostergaard, Mikkel; Ritchlin, Chris; Syversen, Silje W.; Maksymowych, Walter P.

    2007-01-01

    A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively

  4. Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death.

    Science.gov (United States)

    Li, Zheng; Wang, Ji-Wei; Wang, Wei-Zhi; Zhi, Xiao-Fei; Zhang, Qun; Li, Bo-Wen; Wang, Lin-Jun; Xie, Kun-Ling; Tao, Jin-Qiu; Tang, Jie; Wei, Song; Zhu, Yi; Xu, Hao; Zhang, Dian-Cai; Yang, Li; Xu, Ze-Kuan

    2016-10-01

    Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. AlGaN/GaN High Electron Mobility Transistor-Based Biosensor for the Detection of C-Reactive Protein

    Directory of Open Access Journals (Sweden)

    Hee Ho Lee

    2015-07-01

    Full Text Available In this paper, we propose an AlGaN/GaN high electron mobility transistor (HEMT-based biosensor for the detection of C-reactive protein (CRP using a null-balancing circuit. A null-balancing circuit was used to measure the output voltage of the sensor directly. The output voltage of the proposed biosensor was varied by antigen-antibody interactions on the gate surface due to CRP charges. The AlGaN/GaN HFET-based biosensor with null-balancing circuit applied shows that CRP can be detected in a wide range of concentrations, varying from 10 ng/mL to 1000 ng/mL. X-ray photoelectron spectroscopy was carried out to verify the immobilization of self-assembled monolayer with Au on the gated region.

  6. Mechanisms of G Protein-Coupled Estrogen Receptor-Mediated Spinal Nociception

    DEFF Research Database (Denmark)

    Deliu, Elena; Brailoiu, G. Cristina; Arterburn, Jeffrey B.

    2012-01-01

    . Cytosolic calcium concentration elevates faster and with higher amplitude following G-1 intracellular microinjections compared to extracellular exposure, suggesting subcellular GPER functionality. Thus, GPER activation results in spinal nociception, and the downstream mechanisms involve cytosolic calcium......Human and animal studies suggest that estrogens are involved in the processing of nociceptive sensory information and analgesic responses in the central nervous system. Rapid pronociceptive estrogenic effects have been reported, some of which likely involve G protein-coupled estrogen receptor (GPER......) activation. Membrane depolarization and increases in cytosolic calcium and reactive oxygen species (ROS) levels are markers of neuronal activation, underlying pain sensitization in the spinal cord. Using behavioral, electrophysiological, and fluorescent imaging studies, we evaluated GPER involvement...

  7. Low pretreatment levels of myeloid-related protein-8/14 and C-reactive protein predict poor adherence to treatment with tumor necrosis factor inhibitors in juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Alberdi-Saugstrup, Mikel; Nielsen, Susan; Mathiessen, Pernille

    2017-01-01

    inhibitor treatment in JIA patients naive to biologics and investigated if baseline myeloid-related protein (MRP)-8/14 and C-reactive protein (CRP) were predictive of treatment response. One hundred fifty-two patients were included in a unicenter observational, prospective study from 2002 to 2015, excluding......, and 90 were achieved by 61, 55, 38, and 10 % of the patients, and 23 % achieved a status of ID. Treatment adherence: 51 % withdrew from treatment due to lack of clinical effect, while 32 % continued treatment or withdrew due to disease remission. Increased MRP-8/14 concentrations at treatment initiation...... was associated with ID after 1 year (OR 1.55, CI 1.06–2.25, p = 0.02). Treatment withdrawal due to lack of effect was associated with low baseline levels of both MRP-8/14 (685 vs. 1235 ng/ml, p 

  8. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

    2017-05-02

    Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

  9. Interactions between C-Reactive Protein Genotypes with Markers of Nutritional Status in Relation to Inflammation

    Directory of Open Access Journals (Sweden)

    Cornelie Nienaber-Rousseau

    2014-11-01

    Full Text Available Inflammation, as indicated by C-reactive protein concentrations (CRP, is a risk factor for chronic diseases. Both genetic and environmental factors affect susceptibility to inflammation. As dietary interventions can influence inflammatory status, we hypothesized that dietary effects could be influenced by interactions with single nucleotide polymorphisms (SNPs in the CRP gene. We determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black South Africans and analyzed their effect on CRP. Interactions were observed for several genotypes with obesity in determining CRP. Lipid intake modulated the pro-inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid and monounsaturated fatty acid intake in those homozygous for the polymorphic allele at rs2808630 was associated with a larger increase in CRP. Those harboring the minor alleles at rs3093058 and rs3093062 presented with significantly higher CRP in the presence of increased triglyceride or cholesterol intake. When harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was, however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence the CRP. This investigation highlights the impact that nutritional status can have on reducing the inherent genetic susceptibility to a heightened systemic inflammatory state.

  10. Rapid and quantitative detection of C-reactive protein using quantum dots and immunochromatographic test strips

    Directory of Open Access Journals (Sweden)

    Cheng X

    2014-12-01

    Full Text Available Xianglin Cheng,1,* Xu Pu,2,* Pen Jun,3 XiaoBo Zhu,3 Di Zhu,4 Ming Chen1 1Department of Laboratory Medicine, First Affiliated Hospital of Yangtze University, Jingzhou, 2Department of Laboratory Medicine, RenMin Hospital of Wuhan University, Wuhan, 3Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA *These authors contributed equally to this study and share first authorship Background: Rapid immunochromatographic tests can detect disease markers in 10–15 minutes, which facilitates clinical diagnosis and treatment programs. However, most immunochromatographic tests employ gold nanoparticles as reporters, and these have only moderate sensitivity and act as qualitative methods for analyzing high biomarker concentrations. Methods: In this study, we introduce quantum dots (QDs as fluorescent probes and immunochromatographic strips to develop quantitative fluorescence point-of-care tests (QF-POCT to analyze C-reactive protein (CRP levels. Goat anti-rabbit IgG and rabbit IgG were used as control antibodies, and mouse monoclonal CRP antibody pairs were used for disease marker detection. One monoclonal CRP antibody was conjugated with QDs and served as a signal antibody, and the other monoclonal CRP antibody was dispensed onto the nitrocellulose membrane and served as a capturing antibody. In the presence of CRP, the fluorescence intensity of the monoclonal antibody-CRP-monoclonal antibody sandwich complex captured on the nitrocellulose membrane was determined using the fluorescence strip reader. Results: QF-POCT assays could quantitatively analyze the concentration of CRP in 15 minutes had a detection limit of 0.25 mg/L, and had a wide detection linearity range (0.5–300 mg/L. The intra-assay and interassay

  11. Functionalization of whey proteins by reactive supercritical fluid extrusion

    Directory of Open Access Journals (Sweden)

    Khanitta Ruttarattanamongkol

    2012-09-01

    Full Text Available Whey protein, a by-product from cheese-making, is often used in a variety of food formulations due to its unsurpassednutritional quality and inherent functional properties. However, the possibilities for the improvement and upgrading of wheyprotein utilization still need to be explored. Reactive supercritical fluid extrusion (SCFX is a novel technique that has beenrecently reported to successfully functionalize commercially available whey proteins into a product with enhanced functionalproperties. The specific goal of this review is to provide fundamental understanding of the reinforcement mechanism andprocessing of protein functionalization by reactive SCFX process. The superimposed extrusion variables and their interactionmechanism affect the physico-chemical properties of whey proteins. By understanding the structure, functional properties andprocessing relationships of such materials, the rational design criteria for novel functionalized proteins could be developedand effectively utilized in food systems.

  12. Association Between Smoking and Serum GlycA and High-Sensitivity C-Reactive Protein Levels: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    Science.gov (United States)

    Kianoush, Sina; Bittencourt, Marcio S; Lotufo, Paulo A; Bensenor, Isabela M; Jones, Steven R; DeFilippis, Andrew P; Toth, Peter P; Otvos, James D; Tibuakuu, Martin; Hall, Michael E; Harada, Paulo H N; Blaha, Michael J

    2017-08-23

    Inflammation is suggested to be a central feature of atherosclerosis, particularly among smokers. We studied whether inflammatory biomarkers GlycA and high-sensitivity C-reactive protein are associated with cigarette smoking. A total of 11 509 participants, 6774 from the MESA (Multi-Ethnic Study of Atherosclerosis) and 4735 from ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health) were included. We evaluated the cross-sectional association between multiple measures of smoking behavior and the inflammatory biomarkers, GlycA and high-sensitivity C-reactive protein, using regression models adjusted for demographic, anthropometric, and clinical characteristics. Participants were 57.7±11.1 years old and 46.4% were men. Never, former, and current smokers comprised 51.7%, 34.0%, and 14.3% of the population, respectively. Multivariable-adjusted mean absolute difference in GlycA levels (μmol/L) with 95% confidence interval (CI) were higher for former (4.1, 95% CI, 1.7-6.6 μmol/L) and current smokers (19.9, 95% CI, 16.6-23.2 μmol/L), compared with never smokers. Each 5-unit increase in pack-years of smoking was associated with higher GlycA levels among former (0.7, 95% CI, 0.3-1.1 μmol/L) and current smokers (1.6, 95% CI, 0.8-2.4 μmol/L). Among former smokers, each 5-year increase in time since quitting smoking was associated with lower GlycA levels (-1.6, 95% CI, -2.4 to -0.8 μmol/L) and each 10-unit increase in number of cigarettes/day was associated with higher GlycA among current smokers (2.8, 95% CI, 0.5-5.2 μmol/L). There were similar significant associations between all measures of smoking behavior, and both log-transformed GlycA and high-sensitivity C-reactive protein. Acute and chronic exposure to tobacco smoking is associated with inflammation, as quantified by both GlycA and high-sensitivity C-reactive protein. These biomarkers may have utility for the study and regulation of novel and traditional tobacco products. © 2017 The Authors

  13. The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.

    Science.gov (United States)

    Singh, Jaskirat; Wen, Xiaohui; Scales, Suzie J

    2015-12-04

    The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Predictive value of C-reactive protein/albumin ratio in acute pancreatitis.

    Science.gov (United States)

    Kaplan, Mustafa; Ates, Ihsan; Akpinar, Muhammed Yener; Yuksel, Mahmut; Kuzu, Ufuk Baris; Kacar, Sabite; Coskun, Orhan; Kayacetin, Ertugrul

    2017-08-15

    Serum C-reactive protein (CRP) increases and albumin decreases in patients with inflammation and infection. However, their role in patients with acute pancreatitis is not clear. The present study was to investigate the predictive significance of the CRP/albumin ratio for the prognosis and mortality in acute pancreatitis patients. This study was performed retrospectively with 192 acute pancreatitis patients between January 2002 and June 2015. Ranson scores, Atlanta classification and CRP/albumin ratios of the patients were calculated. The CRP/albumin ratio was higher in deceased patients compared to survivors. The CRP/albumin ratio was positively correlated with Ranson score and Atlanta classification in particular and with important prognostic markers such as hospitalization time, CRP and erythrocyte sedimentation rate. In addition to the CRP/albumin ratio, necrotizing pancreatitis type, moderately severe and severe Atlanta classification, and total Ranson score were independent risk factors of mortality. It was found that an increase of 1 unit in the CRP/albumin ratio resulted in an increase of 1.52 times in mortality risk. A prediction value about CRP/albumin ratio >16.28 was found to be a significant marker in predicting mortality with 92.1% sensitivity and 58.0% specificity. It was seen that Ranson and Atlanta classification were higher in patients with CRP/albumin ratio >16.28 compared with those with CRP/albumin ratio ≤16.28. Patients with CRP/albumin ratio >16.28 had a 19.3 times higher chance of death. The CRP/albumin ratio is a novel but promising, easy-to-measure, repeatable, non-invasive inflammation-based prognostic score in acute pancreatitis. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

  15. Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.

    Science.gov (United States)

    Roskoski, Robert

    2005-11-11

    Signaling by stem cell factor and Kit, its receptor, plays important roles in gametogenesis, hematopoiesis, mast cell development and function, and melanogenesis. Moreover, human and mouse embryonic stem cells express Kit transcripts. Stem cell factor exists as both a soluble and a membrane-bound glycoprotein while Kit is a receptor protein-tyrosine kinase. The complete absence of stem cell factor or Kit is lethal. Deficiencies of either produce defects in red and white blood cell production, hypopigmentation, and sterility. Gain-of-function mutations of Kit are associated with several human neoplasms including acute myelogenous leukemia, gastrointestinal stromal tumors, and mastocytomas. Kit consists of an extracellular domain, a transmembrane segment, a juxtamembrane segment, and a protein kinase domain that contains an insert of about 80 amino acid residues. Binding of stem cell factor to Kit results in receptor dimerization and activation of protein kinase activity. The activated receptor becomes autophosphorylated at tyrosine residues that serve as docking sites for signal transduction molecules containing SH2 domains. The adaptor protein APS, Src family kinases, and Shp2 tyrosyl phosphatase bind to phosphotyrosine 568. Shp1 tyrosyl phosphatase and the adaptor protein Shc bind to phosphotyrosine 570. C-terminal Src kinase homologous kinase and the adaptor Shc bind to both phosphotyrosines 568 and 570. These residues occur in the juxtamembrane segment of Kit. Three residues in the kinase insert domain are phosphorylated and attract the adaptor protein Grb2 (Tyr703), phosphatidylinositol 3-kinase (Tyr721), and phospholipase Cgamma (Tyr730). Phosphotyrosine 900 in the distal kinase domain binds phosphatidylinositol 3-kinase which in turn binds the adaptor protein Crk. Phosphotyrosine 936, also in the distal kinase domain, binds the adaptor proteins APS, Grb2, and Grb7. Kit has the potential to participate in multiple signal transduction pathways as a result of

  16. Development of C-reactive protein certified reference material NMIJ CRM 6201-b: optimization of a hydrolysis process to improve the accuracy of amino acid analysis.

    Science.gov (United States)

    Kato, Megumi; Kinumi, Tomoya; Yoshioka, Mariko; Goto, Mari; Fujii, Shin-Ichiro; Takatsu, Akiko

    2015-04-01

    To standardize C-reactive protein (CRP) assays, the National Metrology Institute of Japan (NMIJ) has developed a C-reactive protein solution certified reference material, CRM 6201-b, which is intended for use as a primary reference material to enable the SI-traceable measurement of CRP. This study describes the development process of CRM 6201-b. As a candidate material of the CRM, recombinant human CRP solution was selected because of its higher purity and homogeneity than the purified material from human serum. Gel filtration chromatography was used to examine the homogeneity and stability of the present CRM. The total protein concentration of CRP in the present CRM was determined by amino acid analysis coupled to isotope-dilution mass spectrometry (IDMS-AAA). To improve the accuracy of IDMS-AAA, we optimized the hydrolysis process by examining the effect of parameters such as the volume of protein samples taken for hydrolysis, the procedure of sample preparation prior to the hydrolysis, hydrolysis temperature, and hydrolysis time. Under optimized conditions, we conducted two independent approaches in which the following independent hydrolysis and liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) were combined: one was vapor-phase acid hydrolysis (130 °C, 24 h) and hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) method, and the other was microwave-assisted liquid-phase acid hydrolysis (150 °C, 3 h) and pre-column derivatization liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The quantitative values of the two different amino acid analyses were in agreement within their uncertainties. The certified value was the weighted mean of the results of the two methods. Uncertainties from the value-assignment method, between-method variance, homogeneity, long-term stability, and short-term stability were taken into account in evaluating the uncertainty for a certified value. The certified value and the

  17. Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

    Science.gov (United States)

    Madiraju, Padma; Hossain, Ekhtear; Anand-Srivastava, Madhu B

    2018-02-07

    We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP 4-23 , attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP 4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O 2 - ), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP 4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP 4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO - ) in VSMC which were restored to control levels by C-ANP 4-23 treatment. Furthermore, C-ANP 4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP 4-23 , via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP 4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

  18. Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels

    International Nuclear Information System (INIS)

    Lin, Zi-Ying; Liang, Zhen-Xing; Zhuang, Pei-Lin; Chen, Jie-Wei; Cao, Yun; Yan, Li-Xu; Yun, Jing-Ping; Xie, Dan; Cai, Mu-Yan

    2016-01-01

    Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients’ cancer-specific survival and recurrence-free survival rates. High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management

  19. The viral G protein-coupled receptor ORF74 unmasks phospholipase C signaling of the receptor tyrosine kinase IGF-1R.

    NARCIS (Netherlands)

    de Munnik, S.M.; van der Lee, R.; Velders, D.M.; van Offenbeek, J.; Smits-de Vries, L.; Leurs, R.; Smit, M.J.; Vischer, H.F.

    2016-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) encodes the constitutively active G protein-coupled receptor ORF74, which is expressed on the surface of infected host cells and has been linked to the development of the angioproliferative tumor Kaposi's sarcoma. Furthermore, the insulin-like growth

  20. The Decrease in C-reactive Protein Concentration after Diet and Physical Activity Induced Weight Reduction is Associated with Changes in Plasma Lipids, but not Interleukin-6 or Adiponectin

    Czech Academy of Sciences Publication Activity Database

    Dvořáková-Lorenzová, A.; Suchánek, P.; Havel, P.J.; Stávek, P.; Karasová, L.; Valenta, Zdeněk; Tintěra, J.; Poledne, R.

    2006-01-01

    Roč. 55, č. 3 (2006), s. 359-365 ISSN 0026-0495 R&D Projects: GA MZd NJ6361 Institutional research plan: CEZ:AV0Z10300504 Keywords : subclinical inflamation * cardiovascular disease * metabolic syndrome * C-reactive protein * lipid metabolism Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.497, year: 2006