bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil #
Authors: Ha Nghi B. , Ha Nghiem B. , Garcia Ruel T. , Trinh Huy N. , Vu Andrew A. , Nguyen Huy A. , Nguyen Khanh K. , Levitt Brian S. , Nguyen Mindie H. 
Published: April 2009

Abstract
Renal dysfunction has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and clinical importance may be underappreciated given the lack of long-term follow-up and data outside of a clinical trial setting. Our goal was to examine the severity and incidence of renal dysfunction in a real-life setting for patients treated with ADV and whose baseline estimated glomerular filtration rate (eGFR) was >50 mL/minute. We performed a cohort study of 290 chronic hepatitis B patients: 145 patients treated with 10 mg ADV and 145 patients unexposed to ADV at two community clinics, who were matched for age (±10 years), sex, and baseline eGFR. The exposed and unexposed populations were well-matched with a similar mean age (46–47 years), proportion of male patients (76.5%), baseline serum creatinine (0.97–0.99 mg/dL), and baseline creatinine clearance (85.0–85.4 mL/minute). The incidence density for renal dysfunction defined by treatment termination and/or development of eGFR ≤50 mL/minute was five cases per 100 patient-years in the exposed group compared with 1.36 cases per 100 patient-years in the unexposed group (P = 0.02). The relative risk of exposed to unexposed was 3.68 (95% confidence interval 1.1–19.3). On Cox proportional hazard analysis also inclusive of sex, ADV was a significant predictor of significant renal dysfunction (hazard ratio [HR] 3.94, P = 0.03). There were also significant trends for age >50 years (HR 3.49, P = 0.087), mild renal impairment at baseline (HR 4.49, P = 0.073), and hypertension and/or diabetes mellitus (HR 2.36, P = 0.074). Conclusion: ADV is an independent predictor for significant deterioration of renal function. Patients on ADV should be monitored, especially patients who are older, have baseline renal insufficiency, or have hypertension and/or diabetes mellitus. (Hepatology 2009.)
Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed # †
Authors: Tripathi Dhiraj , Ferguson James W. , Kochar Narendra , Leithead Joanna A. , Therapondos George , Mcavoy Norma C. , Stanley Adrian J. , Forrest Ewan H. , Hislop William S. , Mills Peter R. , Hayes Peter C. 
Published: April 2009

Abstract
Current therapy for preventing the first variceal bleed includes beta-blocker and variceal band ligation (VBL). VBL has lower bleeding rates, with no differences in survival, whereas beta-blocker therapy can be limited by side effects. Carvedilol, a non-cardioselective vasodilating beta-blocker, is more effective in reducing portal pressure than propranolol; however, there have been no clinical studies assessing the efficacy of carvedilol in primary prophylaxis. The goal of this study was to compare carvedilol and VBL for the prevention of the first variceal bleed in a randomized controlled multicenter trial. One hundred fifty-two cirrhotic patients from five different centers with grade II or larger esophageal varices were randomized to either carvedilol 12.5 mg once daily or VBL performed every 2 weeks until eradication using a multibander device. Seventy-seven patients were randomized to carvedilol and 75 to VBL. Baseline characteristics did not differ between the groups (alcoholic liver disease, 73%; median Child-Pugh score, 8; median age, 54 years; median follow-up, 20 months). On intention-to-treat analysis, carvedilol had lower rates of the first variceal bleed (10% versus 23%; relative hazard 0.41; 95% confidence interval 0.19-0.96 [P = 0.04]), with no significant differences in overall mortality (35% versus 37%, P = 0.71), and bleeding-related mortality (3% versus 1%, P = 0.26). Six patients in the VBL group bled as a result of banding ulcers. Per-protocol analysis revealed no significant differences in the outcomes. Conclusion: Carvedilol is effective in preventing the first variceal bleed. Carvedilol is an option for primary prophylaxis in patients with high-risk esophageal varices. (Hepatology 2009.)
Adipokines in liver diseases #
Authors: Marra Fabio , Bertolani Cristiana 
Published: April 2009

Abstract
Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases. (Hepatology 2009.)
Notch2 signaling promotes biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice #
Authors: Tchorz Jan S. , Kinter Jochen , Müller Matthias , Tornillo Luigi , Heim Markus H. , Bettler Bernhard 
Published: April 2009

Abstract
Intrahepatic bile duct (IHBD) development begins with the differentiation of hepatoblasts into a single continuous biliary epithelial cell (BEC) layer, called the ductal plate. During ductal plate remodeling, tubular structures arise at distinct sites of the ductal plate, forming bile ducts that dilate into the biliary tree. Alagille syndrome patients, who suffer from bile duct paucity, carry Jagged1 and Notch2 mutations, indicating that Notch2 signaling is important for IHBD development. To clarify the role of Notch2 in BEC differentiation, tubulogenesis, and BEC survival, we developed a mouse model for conditional expression of activated Notch2 in the liver. We show that expression of the intracellular domain of Notch2 (Notch2ICD) differentiates hepatoblasts into BECs, which form additional bile ducts in periportal regions and ectopic ducts in lobular regions. Additional ducts in periportal regions are maintained into adulthood and connect to the biliary tight junction network, resulting in an increased number of bile ducts per portal tract. Remarkably, Notch2ICD-expressing ductal plate remnants were not eliminated during postnatal development, implicating Notch2 signaling in BEC survival. Ectopic ducts in lobular regions did not persist into adulthood, indicating that local signals in the portal environment are important for maintaining bile ducts. Conclusion: Notch2 signaling regulates BEC differentiation, the induction of tubulogenesis during IHBD development, and BEC survival. (Hepatology 2009.)
Fenofibrate differentially regulates plasminogen activator inhibitor-1 gene expression via adenosine monophosphate–activated protein kinase–dependent induction of orphan nuclear receptor small heterodimer partner #
Authors: Chanda Dipanjan , Lee Chul Ho , Kim Yong-Hoon , Noh Jung-Ran , Kim Don-Kyu , Park Ji-Hoon , Hwang Jung Hwan , Lee Mi-Ran , Jeong Kyeong-Hoon , Lee In-Kyu , Kweon Gi Ryang , Shong Minho , Oh Goo-Taeg , Chiang John Y. L. , Choi Hueng-Sik 
Published: April 2009

Abstract
Plasminogen activator inhibitor type I (PAI-1) is a marker of the fibrinolytic system and serves as a possible predictor for hepatic metabolic syndromes. Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is a drug used for treatment of hyperlipidemia. Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in transcriptional repression of crucial genes involved in various metabolic pathways. In this study, we show that fenofibrate increased SHP gene expression in cultured liver cells and in the normal and diabetic mouse liver by activating the adenosine monophosphate–activated protein kinase (AMPK) signaling pathway in a PPARα-independent manner. Administration of transforming growth factor beta (TGF-β) or a methionine-deficient and choline-deficient (MCD) diet to induce the progressive fibrosing steatohepatitis model in C57BL/6 mice was significantly reversed by fenofibrate via AMPK-mediated induction of SHP gene expression with a dramatic decrease in PAI-1 messenger RNA (mRNA) and protein expression along with other fibrotic marker genes. No reversal was observed in SHP null mice treated with fenofibrate. Treatment with another PPARα agonist, WY14643, showed contrasting effects on these marker gene expressions in wild-type and SHP null mice, demonstrating the specificity of fenofibrate in activating AMPK signaling. Fenofibrate exhibited a differential inhibitory pattern on PAI-1 gene expression depending on the transcription factors inhibited by SHP. Conclusion: By demonstrating that a PPARα-independent fenofibrate-AMPK-SHP regulatory cascade can play a key role in PAI-1 gene down-regulation and reversal of fibrosis, our study suggests that various AMPK activators regulating SHP might provide a novel pharmacologic option in ameliorating hepatic metabolic syndromes. (Hepatology 2009.)
Krüppel‐like factor 12 plays a significant role in poorly differentiated gastric cancer progression
Authors: Nakamura Yu , Migita Toshiro , Hosoda Fumie , Okada Naoko , Gotoh Masahiro , Arai Yasuhito , Fukushima Michiyo , Ohki Misao , Miyata Satoshi , Takeuchi Kengo , Imoto Issei , Katai Hitoshi , Yamaguchi Toshiharu , Inazawa Johji , Hirohashi Setsuo , Ishikawa Yuichi , Shibata Tatsuhiro 
Published: April 2009

AbstractGastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy‐number alterations in 50 primary poorly differentiated gastric cancers using an array‐based comparative genomic hybridization (array‐CGH). Many genetic changes were identified, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Krüppel‐like factor 12 (KLF12) induced significant growth‐arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ‐521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a significant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures. © 2009 UICC
Population dynamics of serologically identified coinfections with human papillomavirus types 11, 16, 18 and 31 in fertile‐aged Finnish women
Authors: Kaasila Marjo , Koskela Pentti , Kirnbauer Reinhard , Pukkala Eero , Surcel Heljä‐Marja , Lehtinen Matti 
Published: April 2009

AbstractLicensed human papillomavirus (HPV) vaccines are expected to prevent high‐risk (hr) HPV‐infections (most notably types 16 and 18). Whether HPV vaccination will change the distribution of hrHPVs at the population level is open, since competition between HPV types is not well understood. Two stratified random subcohorts (1983–1997 and 1995–2003) of 7,815 and 3,252 women with a minimum of 2 pregnancies (<32 years) were selected from the Finnish Maternity Cohort. Using ELISA based on virus‐like particles (VLP), we determined antibodies to HPV11, 16, 18 and 31 in paired sera of the women and used Poisson regression models to estimate the risk of further infection with other HPV types in those positive for HPV16 or HPV18 at baseline. Baseline HPV16 seropositivity was associated with increased risk of later infections with HPV18 (3.1, 95% CI: 1.7, 5.6). HPV18 seropositivity was associated with increased risk of HPV16 (3.9, 95% CI: 2.5, 6.1). Our observations favor a coinfection rather than superinfection model for the different HPV types and are not suggestive for type‐replacement following HPV vaccination. © 2009 UICC
The CDH1‐160C>A polymorphism is a risk factor for colorectal cancer
Authors: Pittman Alan M. , Twiss Philip , Broderick Peter , Lubbe Steven , Chandler Ian , Penegar Steven , Houlston Richard S. 
Published: April 2009

AbstractPart of the inherited susceptibility to colorectal cancer (CRC) is caused by the coinheritance of common low risk variants. E‐cadherin (CDH1) has an established role in CRC; somatic inactivation of CDH1 is a common early event, and germline mutations can cause early‐onset CRC. The ‐160C>A promoter variant (rs16260) of CDH1 has been reported to influence CDH1 transcription and thereby represents a strong candidate for a predisposition locus. To examine this proposition, we conducted a two‐staged association study based on genotyping a total of 5,679 CRC cases and 5,412 controls for rs16260. CDH1‐160C>A genotype was associated with CRC risk (ptrend = 0.001). Compared to common homozygotes, the odds ratios (ORs) of CRC associated with heterozygous and homozygote variant genotype were 0.90 (95% confidence interval [CI]: 0.84–0.97) and 0.81 (95% CI: 0.71–0.93), respectively. In combination with the previously identified 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 risk variants, the risk of CRC increases with an increasing numbers of variant alleles for the 7 loci (ORper allele = 1.16; 95% CI: 1.13–1.19; ptrend = 1.68 × 10−34). These data indicate CDH1‐160C>A is a risk factor for CRC, and because a high proportion of the European population are carriers of at‐risk genotypes, the variant is likely to contribute substantially to the development of CRC. Furthermore, our study underscores the importance of conducting association studies using large sample series to demonstrate polymorphic variants conferring modest relative risks. © 2009 UICC
Epigenetic silencing of argininosuccinate synthetase confers resistance to platinum‐induced cell death but collateral sensitivity to arginine auxotrophy in ovarian cancer
Authors: Nicholson Linda J. , Smith Paul R. , Hiller Louise , Szlosarek Peter W. , Kimberley Christopher , Sehouli Jalid , Koensgen Dominique , Mustea Alexander , Schmid Peter , Crook Tim 
Published: April 2009

AbstractEvidence indicates that acquired resistance of cancers to chemotherapeutic agents can occurviaepigenetic mechanisms. Down‐regulation of expression of argininosuccinate synthetase (ASS1), the rate‐limiting enzyme in the biosynthesis of arginine, has been associated with the development of platinum resistance in ovarian cancer treated with platinum‐based chemotherapy. The aim of the present study was to analyse epigenetic regulation of ASS1 in ovarian cancer tissue taken at diagnosis and relapse and determine its significance as a predictor of clinical outcome in patients treated with platinum‐based chemotherapy. In addition, expression and epigenetic regulation of ASS1 were analysed in human ovarian cancer cell lines, and ASS1 expression correlated with the ability of the lines to grow in media containing cisplatin, carboplatin or taxol or in arginine‐depleted media. Our results show that aberrant methylation in the ASS1 promoter correlated with transcriptional silencing in ovarian cancer cell lines. ASS1 silencing conferred selective resistance to platinum‐based drugs and conferred arginine auxotrophy and sensitivity to arginine deprivation. In ovarian cancer, ASS1 methylation at diagnosis was associated with significantly reduced overall survival (p= 0.01) and relapse‐free survival (p= 0.01). In patients who relapse, ASS1 methylation was significantly more frequent at relapse (p= 0.008). These data establish epigenetic inactivation of ASS1 as a determinant of response to platinum chemotherapy and imply that transcriptional silencing of ASS1 contributes to treatment failure and clinical relapse in ovarian cancer. The collateral sensitivity of cells lacking endogenous ASS1 to arginine depletion suggests novel therapeutic strategies for the management of relapsed ovarian cancer. © 2009 UICC
Modification of polyurethane to reduce occlusion of enteral feeding tubes
Authors: Gaither Kari A. , Tarasevich Barbara J. , Goheen Steven C. 
Published: April 2009

AbstractFeeding tubes are used to supply nutritional formula to immobilized patients. The most common cause for failure of enteral feeding tubes is their occlusion. The purpose of this study was to examine whether occlusion of enteral feeding tubes could be minimized using an additive. An open, intermittent enteral feeding system was simulated in the laboratory and data were collected over a period ranging from 2 to 6 days. Feeding formula was cycled through a feeding tube in either the presence or absence of simulated gastric acid in an effort to generate a reproducible occlusion. Pressures in the tube were measured frequently throughout these cycles. We observed pressure spikes with each cycle, but never a complete occlusion. Pressure spikes formed only when simulated gastric acid was mixed with the feeding solution. Large amounts of feeding formula adsorbed onto polyurethane (PU) surfaces in the presence of gastric acid. Also, this subtle change in surface chemistry significantly affected the number of pressure spikes observed. The maximum pressure required to maintain flow in the tube was reduced by about half from 2.0 psi to 0.8 psi when polyvinyl alcohol (PVA) was added. The addition of PVA to PU also reduced the contact angle from 83° (untreated) to ∼64° in the presence of PVA. Furthermore, when formula was added to PU in the presence of PVA the thickness of the layer that remained on the surface was almost 10 times greater in controls than on PVA‐treated surfaces. These results suggest that a treatment that increases the hydrophilicity of the feeding tube may help minimize clogging. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2009
Regeneration of ischemic heart using hyaluronic acid‐based injectable hydrogel
Authors: Yoon So Jeong , Fang Yong Hu , Lim Choon Hak , Kim Bum Shik , Son Ho Sung , Park Yongdoo , Sun Kyung 
Published: April 2009

AbstractAn injectable hydrogel was applied to regenerate a myocardial infarction and functional recovery of the heart. A myocardial infarction was induced in rat by circumflex artery ligation. A hyaluronic acid‐based hydrogel was injected into the epicardium of the infarcted area. Then, cardiac functions and regeneration of the myocardium in sham‐operated (SHAM), myocardial infarction (MI), and gel‐injected group (GEL) (n = 6) were evaluated 4 weeks after the injection. Measurements of the thickness of the wall showed that the thickness in the GEL group increased by up to 200% compared with that in the MI group (p < 0.001). The infarcted area of the left ventricular in the GEL group decreased by 53% compared with the MI group (p < 0.001). The number of arterioles and capillaries in the border zone of the GEL group increased by 152% and 148%, whereas the apoptotic index decreased by 42% (p < 0.05). Measurement of the heart functions, such as ejection fraction, arterial elastance (Ea), dP/dt max, and dP/dt min, indicated that the injection of a hydrogel significantly facilitated the functional recovery compared with the MI group. Because of its simplicity, easy applicability, and a great regenerating potential, this injectable hydrogel promises as a treatment for myocardial infarction. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2009
Use of chitosan membrane associated with polypropylene mesh to prevent peritoneal adhesion in rats
Authors: Paulo Neusa Margarida , de Brito e Silva Marcelo Seixo , Moraes Ângela Maria , Rodrigues Ana Paula , de Menezes Liliana Borges , Miguel Marina Pacheco , de Lima Flávia Gontijo , de Morais Faria Aline , Lima Lívia Maria Lindoso 
Published: April 2009

AbstractThe correction of wall abdominal defects often requires the use of implants such as polypropylene meshes. In spite of presenting good tissue acceptance, these biomaterials can migrate to adjacent viscera, promote enterocutaneos fistulas, tissue adherence and visceral erosions. In this work, the barrier effect of chitosan films associated with polypropylene meshes on adhesion formation experimentally induced in Wistar rats was evaluated. The animals were divided into two groups with 10 animals each. Animals in the CPP group were implanted with chitosan films associated with polypropylene meshes, whereas the ones in the PP group received only polypropylene meshes. After 8 days, the animals were submitted to euthanasia using CO2 and a descriptive study focusing adhesion formation, visceral involvement with sutures and mesh peritonization was performed. Also, subimplanted material was collected for histopathology analysis. The results showed that the CPP group presented weak adhesions to the omentum over the stitch knots in eight animals. In all animals, the meshes were peritonized, not allowing their visualization after removing the chitosan films. In the PP group, six animals presented intestinal adhesions to the meshes and, in one of them, hepatic adhesion to the mesh was observed, besides omentum adhesion on more than 50% of the mesh area. The protective effect of chitosan films when sutured over polypropylene meshes, as well as no exacerbation of inflammation associated to the peritoneal lesions was statistically demonstrated. Therefore, chitosan films can indeed minimize the formation of peritoneal adhesions induced by polypropylene meshes in rats. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2009
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
Authors: Morris Garrett M. , Huey Ruth , Lindstrom William , Sanner Michel F. , Belew Richard K. , Goodsell David S. , Olson Arthur J. 
Published: April 2009

AbstractWe describe the testing and release of AutoDock4 and the accompanying graphical user interface AutoDockTools. AutoDock4 incorporates limited flexibility in the receptor. Several tests are reported here, including a redocking experiment with 188 diverse ligand‐protein complexes and a cross‐docking experiment using flexible sidechains in 87 HIV protease complexes. We also report its utility in analysis of covalently bound ligands, using both a grid‐based docking method and a modification of the flexible sidechain technique. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009