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| 1 | Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension显示文摘AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension. | Denise Schaffner Adhara Lazaro Peter Deibert Peter Hasselblatt Patrick Stoll Lisa Fauth Manfred W Baumstark Irmgard Merfort Annette Schmitt-Graeff Wolfgang Kreisel | 2018 | World Journal of Gastroenterology2018，24，38： | 2 |
| 2 | Exogenous cytokinin application to Actinidia chinensis var. deliciosa ‘Hayward’ fruit promotes fruit expansion through water uptake显示文摘Exogenous application of a cytokinin-like compound forchlorfenuron(CPPU)can promote fruit growth,although often at the expense of dry matter(DM),an important indicator of fruit quality.Actinidia chinensis var.deliciosa‘Hayward’fruit are very responsive to CPPU treatments,but the mechanism underlying the significant fruit weight increase and associated decrease in DM is unclear.In this study,we hypothesised that CPPU-enhanced growth increases fruit carbohydrate demand,but limited carbohydrate supply resulted in decreased fruit DM.During fruit development,CPPU effects on physical parameters,metabolites,osmotic pressure and transcriptional changes were assessed under conditions of both standard and a high carbohydrate supply.We showed that CPPU increased fruit fresh weight but the dramatic DM decrease was not carbohydrate limited.Enhanced glucose and fructose concentrations contributed to an increase in soluble carbohydrate osmotic pressure,which was correlated with increased water accumulation in CPPU-treated fruit and up-regulation of water channel aquaporin gene PIP2.4 at 49 days after anthesis.Transcipt analysis suggested that the molecular mechanism contributing to increased glucose and fructose concentrations was altered by carbohydrate supply.At standard carbohydrate supply,the early glucose increase in CPPU fruit was associated with reduced starch synthesis and increased starch degradation.When carbohydrate supply was high,the early glucose increase in CPPU fruit was associated with a general decrease in starch synthesis but up-regulation of vacuolar invertase and fructokinase genes.We conclude that CPPU affected fruit expansion by increasing the osmotically-driven water uptake and its effect was not carbohydrate supply-limited. | Simona Nardozza Helen L Boldingh Mark W Wohlers Andrew P Gleave Zhiwei Luo Guglielmo Costa Elspeth A MacRae Michael J Clearwater Annette C Richardson | 2017 | Horticulture Research2017，4，1： | 2 |
| 3 | Nanorover for Mars 显示文摘 | BRIAN W ANNETTE N RICK W A | 1997 | Space Technology1997，17，3： | 1 |
| 4 | A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis显示文摘 | JONKER Johan W MYOUNG SUH Jae ATKINS Annette R | | 0，，7398： | 1 |
| 5 | Solid lipod nanoparticles (SLN) for controlled drug delivery-drug release and release mechanism显示文摘 | Annette M Schwarz C Mehnert W | 1998 | Eur J Pharm Biopharm1998，45，2： | 1 |
| 6 | In vitro activities of terbinafine in combination with fluconazole,itraconazole,voriconazole,and posaconazole against clinical isolates of Candida glabrata with decreased susceptibility to azole显示文摘 | Perea S Gonzalez G Annette W | 2002 | J Clin Microbiol2002，40，： | 1 |
| 7 | The advantages of the ITS2 region of the nuclear rDNA cistron for analysis of phylogenetic relationships of insects:a Drosophila examople显示文摘 | Irene Young Annette W Coleman | 2004 | Molecular Phylogenetics and Evolutions2004，30，： | 1 |
| 8 | The Top level Global Research System, 1997-1999: Centers, Net works and Nodality: An Analysis Based on Bibliomet ric Indicators显示文摘 | CHRISTIAN W M ANNETTE W S | 2002 | Urban Studies2002，39，56： | 1 |
| 9 | Epitheloides H?mangioendotheliom des Herzens in Assoziation mit einem myelodysplastischen Syndrom显示文摘 | A. Agaimy Annette Kaiser P. H. Wünsch | 2002 | Zeitschrift für Kardiologie2002，，4： | 1 |
| 10 | A PPAR',/- FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis 显示文摘 | JOHAN W J JAE M S ANNETTE R A | 2012 | Nature2012，485，7398： | 1 |
| 11 | Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study显示文摘 | Mark S Kipnes Arthur Krosnick Marc S Rendell John W Egan Annette L Mathisen Roberta L Schneider | 2001 | The American Journal of Medicine2001，，1： | 1 |
| 12 | Racial/ethnic disparities in hepatocellular carcinoma treatment and survival in California, 1988-2012显示文摘AIM To describe racial/ethnic differences in treatment and survival among liver cancer patients in a populationbased cancer registry.METHODS Invasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White(White, n = 12710), Hispanic(n = 8500), Chinese(n = 2723), non-Hispanic Black(Black, n = 2609), Vietnamese(n = 2063), Filipino(n = 1479), Korean(n = 1099), Japanese(n = 658), American Indian/Alaskan Native(AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian(n = 233), South Asian(n = 190), Hawai`ian/Pacific Islander(n = 172), Thai(n = 95), and Other Asian(n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause mortality.RESULTS After adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio(OR) = 0.30, 95%CI: 0.17-0.53], Cambodian(OR = 0.65, 95%CI: 0.45-0.96), AIAN(OR = 0.66, 95%CI: 0.46-0.93), Black(OR = 0.76, 95%CI: 0.67-0.86), and Hispanic(OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese(OR = 1.58, 95%CI: 1.42-1.77), Koreans(OR = 1.45, 95%CI: 1.24-1.70), Japanese(OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese(OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio(HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians(HR = 1.35, 95%CI: 1.16-1.58), and Blacks(HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese(HR = 0.82, 95%CI: 0.77-0.86), Filipinos(HR = 0.84, 95%CI: 0.78-0.90), Vietnamese(HR = 0.85, 95%CI: 0.80-0.90), Koreans(HR = 0.90, 95%CI: 0.83-0.97), and Hispanics(HR = 0.91, 95%CI: 0.88-0.94); results were similar for all-cause mortality.CONCLUSION Disaggregated data revealed substantial racial/ethnic differences in liver cancer treatment and survival, demonstrating the need for development of targeted interventions to mitigate disparities. | Susan L Stewart Sandy L Kwong Christopher L Bowlus Tung T Nguyen Annette E Maxwell Roshan Bastani Eric W Chak Moon S Chen Jr | 2016 | World Journal of Gastroenterology2016，22，38： | 1 |
| 13 | Prevalence and prognosis of asymptomatic vertebral artery origin stenosis in patients with clinically manifestarterial disease显示文摘 | Annette CH Bart W Ale A | 2011 | Stroke2011，42，： | 1 |
| 14 | Quantitative relationship between water-depth and sub-fossil ostracod assemblages in Lake Donggi Cona, Qinghai Province, China显示文摘 | Steffen Mischke Ulrich B??neck Bernhard Diekmann Ulrike Herzschuh Huijun Jin Annette Kramer Bernd Wünnemann Chengjun Zhang | 2010 | Journal of Paleolimnology2010，，3： | 1 |
| 15 | Detection of rancidity in freeze stored turkey meat using acommercial gas-sensor array system显示文摘 | John-Erik H Frank L Jens P W Annette V | 2006 | Sensors and Actuators2006，116，12： | 1 |
| 16 | Modeling and validation of the thermal effects on gas turbine transients显示文摘 | Annette E N Christoph W M Stephan S | | 0，，03： | 1 |
| 17 | Serum AdiPocyte Fatty Acid Binding Protein as a New Biomarker Predicting the DeveloPment of TyPe 2 Diabetes显示文摘 | Tso Annette W K Xu Ai min Sham Pak C etal | 2007 | Diabetes Care2007，，： | 1 |
| 18 | Fate and stability of nonextractable residues of PAH on contaminated soils under environmental stress conditions显示文摘 | ANNETTE E REINHARD W BERND M | 1998 | Environ Sci Technol1998，32，： | 1 |
| 19 | Immunomodulatory effect of plasraids co-expressing cytokines in classical porcine fever virus subunit gp55/E2-DNA vaccination显示文摘 | Daniel W Elisenda A Annette M | 2005 | Vet Res2005，36，4： | 1 |
| 20 | Inhibition of endothelin-I -mediated contraction of hepatic stellate cells by FXR ligand 显示文摘 | JIANG L RAMALINGA K ANNETTE W | 2010 | PLoS One2010，5，13： | 1 |
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