bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of Hepatitis B e Antigen–Negative Chronic Hepatitis B on Long-Term Nucleos(t)ide Analog Therapy Starting With Lamivudine *
Authors: Papatheodoridis George V. , Dimou Evangelini , Dimakopoulos Konstantinos , Manolakopoulos Spilios , Rapti Irene , Kitis George , Tzourmakliotis Dimitrios , Manesis Emanuel , Hadziyannis Stephanos J. 
Published: June 2005

Abstract

We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 ± 1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n = 209) and 1 untreated (n = 195). Virological or biochemical remission rate at 48 months under lamivudine was 34% or 36%, respectively, whereas adefovir was administered in 79 patients with virological–biochemical breakthroughs or no response. Of the lamivudine-treated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event–free survival was 93%. The major event–free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event–free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96% or 98% vs. 88% or 90%, respectively).
In conclusion,
in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered. (Hepatology 2005;42:121–129.)
Male Cell Microchimerism in Normal and Diseased Female Livers From Fetal Life to Adulthood *
Authors: Guettier Catherine , Sebagh Mylène , Buard Jérôme , Feneux Danielle , Ortin-Serrano Monique , Gigou Michele , Tricottet Viviane , Reynès Michel , Samuel Didier , Féray Cyrille 
Published: June 2005

Abstract

Male microchimerism is frequent in the adult female liver and is attributed to fetal cells originating from previous male offspring. It has never been studied in pregnant women, female children, or fetuses. We examined its frequency and cellular nature in normal and diseased female livers from fetal life to adulthood. Forty-six liver samples from 29 women, 6 female children, and 11 female fetuses were screened for the Y chromosome via polymerase chain reaction (PCR) assay and fluorescent

in situ

hybridization (FISH). The X chromosome was used as an internal control. A third PCR assay was used for Y genotyping. The Y chromosome was detected in 5 of 6 children, 7 of 11 fetuses, 3 of 9 women with normal liver, 7 of 10 women with chronic hepatitis C, 5 of 6 women with acute liver disease during pregnancy with male offspring, and 2 of 4 nonpregnant women with fulminant hepatitis. In positive samples, the mean XY/XX ratio was 0.012 (±0.004). In women, male microchimerism was correlated with previous male offspring. Male hepatocytes, detected via FISH combined with anti-hepatocyte immunohistochemistry, were observed only in fetuses (4/9) and in postpartem women (4/6). Y genotypes were different from each other in 4 of 5 female livers.
In conclusion
, male liver microchimerism is frequent in normal and diseased female livers. The presence of male cells in the liver of female children and fetuses is probably due to the transplacental transmission of fetal cells preexisting in the mother and acquired either from previous pregnancy with male offspring or during the mother's own fetal life. (Hepatology 2005;42:35–43.)
Cytoplasmic Retention of Peroxide-Activated ERK Provides Survival in Primary Cultures of Rat Hepatocytes *
Authors: Rosseland Carola M. , Wierφd Lene , Oksvold Morten P. , Werner Heidi , ϕstvold Anne Carine , Thoresen Hege G. , Paulsen Ragnhild E. , Huitfeldt Henrik S. , Skarpen Ellen 
Published: June 2005

Abstract

Reactive oxygen species (ROS) are implicated in tissue damage causing primary hepatic dysfunction following ischemia/reperfusion injury and during inflammatory liver diseases. A potential role of extracellular signal-regulated kinase (ERK) as a mediator of survival signals during oxidative stress was investigated in primary cultures of hepatocytes exposed to ROS. Hydrogen peroxide (H2O2) induced a dose-dependent activation of ERK, which was dependent on MEK activation. The ERK activation pattern was transient compared with the ERK activation seen after stimulation with epidermal growth factor (EGF). Nuclear accumulation of ERK was found after EGF stimulation, but not after H2O2 exposure. A slow import/rapid export mechanism was excluded through the use of leptomycin B, an inhibitor of nuclear export sequence–dependent nuclear export. Reduced survival of hepatocytes during ROS exposure was observed when ERK activation was inhibited. Ribosomal S6 kinase (RSK), a cytoplasmic ERK substrate involved in cell survival, was activated and located in the nucleus of H2O2-exposed hepatocytes. The activation was abolished when ERK was inhibited with U0126.
In conclusion
, our results indicate that activity of ERK in the cytoplasm is important for survival during oxidative stress in hepatocytes and that RSK is activated downstream of ERK.

Supplementary material for this article can be found on the Hepatology website

(
http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html
). (Hepatology 2005;42:200–207.)
Testing the purchasing power parity through I(2) cointegration techniques
Authors: Bacchiocchi Emanuele , Fanelli Luca 
Published: June 2005

AbstractThis paper contributes to the empirical literature on the purchasing power parity (PPP) over the post‐Bretton Woods period by providing a time‐series based interpretation of the controversial evidence characterizing the dynamics of real exchange rates. It is shown that the persistence of deviations from the PPP between a set of European countries and the United States may be empirically attributed to the presence of I(2) stochastic trends in prices using Consumer Price Indices. Interestingly, the slow adjustment towards the equilibrium can be modelled through ‘integral‐proportional’ equilibrium correction models and this evidence can be partly reconciled with theories where the inflation rate reduces the markup of profit‐maximizing firms acting on imperfectly competitive markets. Copyright © 2005 John Wiley & Sons, Ltd.
Radiation synthesis of poly(N‐vinyl‐2‐pyrrolidone)–κ‐carrageenan hydrogels and their use in wound dressing applications. I. Preliminary laboratory tests
Authors: Şen Murat , Avcı Esra Nazan 
Published: June 2005

AbstractPoly(N‐vinyl‐2‐pyrrolidone)–κ‐carrageenan hydrogels (PVP‐KC) were prepared by irradiating the mixtures of aqueous solutions of PVP, KC, potassium chloride, and poly(ethylene glycol) by γ‐rays at different doses. Their preliminary laboratory tests were evaluated to identify their usability in wound dressing applications. For investigation of the effect of components on the gelation of PVP, sol–gel analyses were made and gel fractions of the hydrogels were determined. Mechanical experiments were conducted for both unirradiated and irradiated samples. For investigation of the fluid uptake capacity of the hydrogels, swelling experiments were performed in pseudo‐extracellular fluid solution at various temperatures. Acidity/alkalinity (pH) and electrical conductivity tests were achieved from aqueous extracts of hydrogels, and bioadhesion strength of the hydrogels was investigated on human skin. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Improving the blood compatibility of polyurethane using carbon nanotubes as fillers and its implications to cardiovascular surgery
Authors: Meng J. , Kong H. , Xu H. Y. , Song L. , Wang C. Y. , Xie S. S. 
Published: June 2005

AbstractBlood compatibility has been an occlusion for biomaterials used in the cardiovascular system. In this work, a multiwalled carbon nanotubes‐polyurethane composite (MWNT‐PU) was prepared through a controlled co‐precipitation. The surface chemical composition of treated carbon nanotubes was analyzed with XPS and the thermal behaviors of composite were characterized by DSC. The platelet adhesion and activation caused by the composite were evaluated by using SEM and flow cytometric analysis, respectively, and the disruption of red blood cells was analyzed through measuring the absorbance of free hemoglobin. The experimental results demonstrated that: (1) Multiwalled carbon nanotubes (MWNTs) with oxygen‐containing functional groups could be well dispersed in polyurethane matrix through a controlled coprecipitation; (2) the composite surface displayed a significantly improved anticoagulant function, which can be indicative of the promising potentials of carbon nanotube‐based materials in the implants and medical devices applied in blood‐contacting environments. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Effects of nano HAP on biological and structural properties of glass bone cement
Authors: Fu Qiang , Zhou Nai , Huang Wenhai , Wang Deping , Zhang Liying , Li Haifeng 
Published: June 2005

AbstractA novel type of glass‐based nanoscale hydroxyapatite (HAP) bioactive bone cement (designed as GBNHAPC) was synthesized by adding nanoscale hydroxyapatite crystalline (20–40 nm), into the self‐setting glass‐based bone cement (GBC). The inhibition rate of nanoscale HAP and micron HAP on osteosarcoma U2‐OS cells was examined. The effects of nanoscale HAP on the crystal phase, microstructure and compressive strength of GBNHAPC were studied, respectively. It was concluded that nanoscale HAP could inhibit the cell proliferation, whereas micron HAP could not, and that nanoscale HAP could be dispersed in the cement evenly and the morphology did not change significantly after a longer immersion time. XRD and FTIR results show nanoscale HAP did not affect the setting reaction of the cement. Furthermore, GBNHAPC had a higher compressive strength (92.6 ± 3.8 MPa) than GBC (80.1 ± 3.0 MPa). It was believed that GBNHAPC might be a desirable biomaterial that could not only fill bone defects but also inhibit cancer cell growth. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
A novel osteotropic biomaterial OG‐PLG: In vitro efficacy
Authors: Whang Kyumin , Grageda Edgar , Khan Ambereen , McDonald Jonathan , Lawton Mark , Satsangi Neera 
Published: June 2005

AbstractPreviously, a novel osteotropic biomaterial, OG‐PLG [simvastatin grafted to poly(lactide‐co‐glycolide), PLG], was synthesized and shown to have degradation‐controlled release kinetics. The objective here was to determine the effect of grafting statins to PLG on bone regeneration in vitro. Rat bone marrow cells were stimulated in vitro with simvastatin dissolved in media, saponified simvastatin dissolved in media, simvastatin released through diffusion from emulsion freeze‐dried scaffolds, and OG‐PLG. Unstimulated cultures and cultures stimulated with dexamethasone were used as negative and positive controls, respectively. In vitro bone formation was assessed using the alkaline phosphatase (ALP) and von Kossa assays at different times up to 16 days. ALP analysis revealed that saponified simvastatin at 10−7M and OG‐PLG significantly increased ALP expression at various time points. von Kossa assay showed that simvastatin, saponified simvastatin, and OG‐PLG significantly enhanced mineralization, with the effect from OG‐PLG being the most significant. In short, OG‐PLG significantly enhanced in vitro bone cell mineralization beyond the effect of simvastatin or saponified simvastatin dissolved in media and simvastatin released via diffusion from scaffolds. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells: Role of nuclear factor‐κB and reactive oxygen species
Authors: Park Myung‐Jin , Lee Jae‐Young , Kwak Hee‐Jin , Park Chang‐Min , Lee Hyung‐Chahn , Woo Sang Hyeok , Jin Hyun‐Ok , Han Chul‐Ju , An Sungkwan , Lee Seung‐Hoon , Chung Hee Yong , Park In‐Chul , Hong Seok‐Il , Rhee Chang Hun 
Published: June 2005

AbstractIn order to define the role of As2O3 in regulating the tumor cell invasiveness, the effects of As2O3 on secretion of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA), and in vitro invasion of HT1080 human fibrosarcoma cells were examined. As2O3 inhibited cell adhesion to the collagen matrix in a concentration dependent manner, whereas the same treatment enhanced cell to cell interaction. In addition, As2O3 inhibited migration and invasion of HT1080 cells stimulated with phorbol 12‐myristate 13‐aceate (PMA), and suppressed the expression of MMP‐2, ‐9, membrane type‐1 MMP, uPA, and uPA receptor (uPAR). In contrast, As2O3 increased the expression of tissue inhibitor of metalloproteinase (TIMP)‐1 and PA inhibitor (PAI)‐1, and reduced the MMP‐2, ‐9, and uPA promoter activity in the presence and absence of PMA. Furthermore, the promoter stimulating and DNA binding activity of nuclear factor‐κB (NF‐κB) was blocked by As2O3, whereas the activator protein‐1 activity was unchanged. Pretreatment of the cells with N‐acetyl‐L‐cysteine (NAC) significantly prevented suppression of MMPs and uPA secretion, DNA binding activity of NF‐κB, and in vitro invasion of HT1080 cells by As2O3, suggesting a role of reactive oxygen species (ROS) in this process. These results suggest that As2O3 inhibits tumor cell invasion by modulating the MMPs/TIMPs and uPA/uPAR/PAI systems of extracellular matrix (ECM) degradation. In addition, the generation of ROS and subsequent suppression of NF‐κB activity by As2O3 might partly be responsible for the phenomena. Overall, As2O3 shows potent activity controlling tumor cell invasiveness in vitro. © 2005 Wiley‐Liss, Inc.
Compartmentalization of hnRNP‐K during cell cycle progression and its interaction with calponin in the cytoplasm
Authors: Laury‐Kleintop Lisa D. , Tresini Maria , Hammond Olivia 
Published: June 2005

AbstractCoronary artery blockage, due to cardiovascular disease, is routinely treated by either balloon‐angioplasty or bypass surgery. The limited success of these clinical interventions is due at least in part to smooth muscle cell (SMC) proliferation. Here we show that heterogeneous nuclear ribonucleoprotein complex K (hnRNP‐K) protein levels increase in SMC with response to serum stimulation in vitro, in the aortas from an animal model of atherosclerosis, and in occluded human vein segments. hnRNP‐K is a multi‐functional protein that has been studied primarily in cancer cells and has been suggested to play a role in cell cycle progression. We show that in untransformed, cultured SMC, hnRNP‐K protein sub‐cellular localization modulates through the cell cycle in both the cytoplasm and nucleus. Using cycloheximide, we observed that cytoplasmic accumulation of hnRNP‐K protein at later time points in the cell cycle occurred with a concomitant decrease in nuclear hnRNP‐K protein, suggesting a translocation of nuclear hnRNP‐K protein to the cytoplasm. Also, because we did not observe an increase in hnRNP‐K protein at early time points in the cell cycle in the presence of cycloheximide, we propose that the early increase in cytoplasmic hnRNP‐K protein following serum stimulation is due to new hnRNP‐K protein synthesis. When present in the cytoplasm, hnRNP‐K is part of a multi‐protein complex that consists of at least two other proteins, calponin and ERK1/2. Our findings from this study are intriguing because they suggest that cytoplasmic hnRNP‐K in SMC is part of a signaling complex that may be involved in growth‐stimulated post‐transcriptional regulation. © 2005 Wiley‐Liss, Inc.
Overexpression of regucalcin suppresses cell proliferation in cloned rat hepatoma H4‐II‐E cells: Involvement of intracellular signaling factors and cell cycle‐related genes
Authors: Yamaguchi Masayoshi , Daimon Yuko 
Published: June 2005

AbstractThe role of regucalcin, which is a regulatory protein in intracellular signaling pathway, in the regulation of cell proliferation was investigated by using the cloned rat hepatoma H4‐II‐E cells overexpressing regucalcin. The hepatoma cells (wild type) and stable regucalcin/pCXN2 transfectants were cultured for 72 h in a medium containing 10% fetal bovine serum (FBS) to obtain subconfluent monolayters. The proliferation of cells was significantly suppressed in transfectants cultured for 24–72 h. The proliferation of wild‐type cells was significantly inhibited when the cells were cultured for 72 h in a medium containing an inhibitor of transcriptional activity or protein synthesis. Such an effect was not seen in transfectants. The presence of various inhibitors of protein kinase including PD 98059 (10−7 or 10−6 M), dibucaine (10−6 M), wortmannin (10−8 or 10−6 M), or genistein (10−5 M) caused a significant inhibition of the proliferation of wild‐type cells. These inhibitory effects were not seen in transfectants. Staurosporine (10−8 − 10−7 M) significantly inhibited the proliferation of wild‐type cells and transfectants. Also, the effect of vanadate (10−5 M), an inhibitor of protein tyrosine phosphatase, or Bay K 8644 (10−6 M), an agonist of calcium entry into cells, in inhibiting the proliferation of wild‐type cells was not observed in transfectants. Moreover, the proliferation of wild‐type cells was significantly inhibited in the presence of roscovitine (10−7 or 10−6 M) or sulforaphane (10−7 M), which induces cell‐cycle arrest. Such effect was not seen in transfectants. The inhibitory effect of sodium butyrate (8.3 × 10−4 M) on proliferation of wild‐type cells was also induced in transfectants. Gene expression in hepatoma cells cultured for 72 h with 10% FBS was determined by using reverse transcription‐polymerase chain reaction (RT‐PCR). The expression of p21 mRNA was significantly enhanced in transfectants, while cdc2a and chk2 mRNA expression were not significantly changed. Insulin‐like growth factor‐I (IGF‐I) mRNA expression was significantly suppressed in transfectants. This study demonstrates that overexpression of regucalcin has a suppressive effect on cell proliferation that is partly mediated through various intracellular signaling‐related factors, and that the effect may be partly involved in the change in p21 or IGF‐I mRNA expression. The finding further supports that regucalcin plays an important role as a suppressor in the enhancement of cell proliferation. © 2005 Wiley‐Liss, Inc.
Methionine aminopeptidases type I and type II are essential to control cell proliferation
Authors: Bernier Sylvie G. , Taghizadeh Nazbeh , Thompson Charles D. , Westlin William F. , Hannig Gerhard 
Published: June 2005

AbstractThe dependence of cell growth on methionine aminopeptidase (MetAP) function in bacteria and yeast is firmly established. Here we report experimental evidence that the control of cell proliferation in mammalian cells is directly linked and strictly dependent on the activity of both MetAP‐1 and MetAP‐2. The targeted downregulation of either methionine aminopeptidase MetAP‐1 or MetAP‐2 protein expression by small interfering RNA (siRNA) significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVEC) (70%–80%), while A549 human lung carcinoma cell proliferation was less inhibited (20%–30%). The cellular levels of MetAP‐2 enzyme were measured after MetAP‐2 siRNA treatment and found to decrease over time from 4 to 96 h, while rapid and complete depletion of MetAP‐2 enzyme activity was observed after 4 h treatment with two pharmacological inhibitors of MetAP‐2, PPI‐2458 and fumagillin. When HUVEC and A549 cells were treated simultaneously with MetAP‐2 siRNA and PPI‐2458, or fumagillin, which irreversibly inhibit MetAP‐2 enzyme activity, no additive effect on maximum growth inhibition was observed. This strongly suggests that MetAP‐2 is the single critical cellular enzyme affected by either MetAP‐2 targeting approach. Most strikingly, despite their significantly different sensitivity to growth inhibition after targeting of either MetAP‐1 or MetAP‐2, HUVEC, and A549 cells, which were made functionally deficient in both MetAP‐1 and MetAP‐2 were completely or almost completely inhibited in their growth, respectively. This closely resembled the observed growth inhibition in genetically double‐deficient map1map2 yeast strains. These results suggest that MetAP‐1 and MetAP‐2 have essential functions in the control of mammalian cell proliferation and that MetAP‐dependent growth control is evolutionarily highly conserved. © 2005 Wiley‐Liss, Inc.
Myosin light chain kinase and acto‐myosin contractility modulate activation of the ERK cascade downstream of oncogenic Ras
Authors: Helfman David M. , Pawlak Geraldine 
Published: June 2005

AbstractThe actin cytoskeleton is recognized as an important component of both adhesion‐ and growth factor‐dependent signaling, but its role in oncogene‐dependent signaling has received much less attention. In this study, we investigated the role played by the acto‐myosin cytoskeleton and its main regulators, i.e., myosin light chain kinase and Rho kinase, in oncogenic Ki‐Ras‐induced signaling. We found that activation of the ERK cascade by Ras is dependent on acto‐myosin contractility, under the regulation of myosin light chain kinase but not Rho kinase. Inhibition of myosin II or myosin light chain kinase caused a complete loss of ERK phosphorylation in a time‐ and dose‐dependent manner, but proved dispensable for activation of the PI3K pathway. We also provide evidence that the target of myosin light chain kinase lays at the level of Raf activation. Since myosin light chain kinase is a target of ERK, these results suggest a previously uncharacterized signaling pathway involving Ras‐mediated alterations of the actin cytoskeleton, which might play a critical role in ERK activation by the Ras oncogene and contribute to aberrant signaling and enhanced cell motility. In addition, restoration of stress fibers following ectopic expression of tropomyosin 2 resulted in reduced levels of ERK phosphorylation. Finally, these studies suggest that myosin light chain kinase but not Rho kinase plays an essential role in the generation of ERK signaling in transformed cells and indicate distinct cellular roles for Rho‐kinase and myosin light chain kinase‐dependent functions involving the regulation of acto‐myosin contractility. © 2005 Wiley‐Liss, Inc.