bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced nicotinamide adenine dinucleotide phosphate oxidase mediates fibrotic and inflammatory effects of leptin on hepatic stellate cells
Authors: De Minicis Samuele , Seki Ekihiro , Oesterreicher Christoph , Schnabl Bernd , Schwabe Robert F. , Brenner David A. 
Published: November 2008

Abstract

Although leptin induces fibrotic activity in hepatic stellate cells (HSCs), the mechanisms are not entirely understood. To investigate the potential role of reduced nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and reactive oxygen species (ROS) in leptin signaling in HSCs, we analyzed leptin-induced intracellular signaling pathways in primary wild-type (WT), p47
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, and signal transducer and activator of transcription protein 3 (STAT3)-deleted HSCs. Leptin-stimulated ROS production was attenuated in human and mouse HSCs by the NADPH oxidase inhibitor diphenylene-iodonium (DPI) and in HSCs lacking the NADPH component p47phox. Leptin-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT, but not of STAT3, was blocked by NADPH oxidase inhibition. Moreover, leptin-induced ROS production was inhibited by the Janus kinase (JAK) inhibitor, AG490, but normal ROS production was observed in STAT3-deleted HSCs. Pharmacologic or genetic inhibition of NADPH in HSCs not only resulted in a reduction of leptin-mediated HSC proliferation but also reduced the leptin-mediated up-regulation of the fibrogenic markers collagen α1(I) and α-smooth muscle actin and of the inflammatory mediators monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein 1 (MIP-1), and macrophage inflammatory protein 2 (MIP-2).

In vivo

, leptin enhanced chemokine expression induced by chemokine (C-C motif) ligand 4 (CCl4) in WT mice, but a blunted response was observed in p47phox−/− mice. In conclusion, NADPH oxidase is a crucial mediator of proliferative, fibrogenic, and inflammatory actions of leptin. Leptin-induced NADPH oxidase acts downstream of JAK activation but is independent of STAT3. Our results, in conjunction with previous studies on angiotensin II and platelet-derived growth factor (PDGF), place NADPH in the center of the fibrogenic signaling response in HSCs and demonstrate its potential role as a pharmacological target for antifibrotic therapies. (Hepatology 2008;48:2016–2026.)
Human reach envelope and zone differentiation for ergonomic design
Authors: Yang Jingzhou (James) , Abdel‐Malek Karim 
Published: November 2008

AbstractIn human‐centric design, the human reach envelope is one of the most important components to help layout design for workstations, vehicles, and aircrafts. It also can help people to study the range of motion of different body segments. Various methods have been developed to determine human reach envelopes. This article presents different methods and common challenges. Human reach envelopes only give feedback concerning whether a point is reachable. This is not enough for the designers. The more important information the designers need to know is the zones with different discomfort levels. This capability is a powerful tool for ergonomic designers. In addition, a methodology for workspace solid zone differentiation or surface zone differentiation in the three‐dimensional space is presented. © 2008 Wiley Periodicals, Inc.
Potent antitumor effect of SN‐38‐incorporating polymeric micelle, NK012, against malignant glioma
Authors: Kuroda Jun‐ichiro , Kuratsu Jun‐ichi , Yasunaga Masahiro , Koga Yoshikatsu , Saito Yohei , Matsumura Yasuhiro 
Published: November 2008

AbstractRecent published reports on clinical trials of CPT‐11 indicate the effectiveness of this compound, a prodrug of SN‐38, against malignant glioma in combination with anti‐vascular endothelial growth factor antibody. Here, we determined if NK012, and SN‐38 incorporating micelle, can be an appropriate formulation for glioblastoma treatment compared with CPT‐11.In vitrocytotoxicity was evaluated against several glioma lines with NK012, CPT‐11, SN‐38, ACNU, CDDP and etoposide. For thein vivotest, a human glioma line (U87MG) transfected with theluciferasegene was inoculated into nude mice brain for pharmacokinetic analysis by fluorescence microscopy and high‐performance liquid chromatography after intravenous injection of NK012 and CPT‐11.In vivoantitumor activity of NK012 and CPT‐11 was evaluated by bioluminescence image and Kaplan‐Meier analyses. The growth‐inhibitory effects of NK012 were 34‐ to 444‐fold more potent than those of CPT‐11. Markedly enhanced and prolonged distribution of free SN‐38 in the xenografts was observed after NK012 injection compared with CPT‐11. NK012 showed significantly potent antitumor activity against an orthotopic glioblastoma multiforme xenograft and significantly longer survival rate than CPT‐11 (p= 0.0014). This implies that NK012 can pass through the blood brain tumor barrier effectively. NK012, which combines enhanced distribution with prolonged sustained release, may be ideal for glioma treatment. Currently, a phase I study of NK012 is almost complete in Japan and the US. The present translational study warrants the clinical phase II study of NK012 in patients with malignant glioma. © 2008 Wiley‐Liss, Inc.
Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study
Authors: Wilson Kathryn M. , Bälter Katarina , Adami Hans‐Olov , Grönberg Henrik , Vikström Anna C. , Paulsson Birgit , Törnqvist Margareta , Mucci Lorelei A. 
Published: November 2008

AbstractAcrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these 2 exposure measures. We used data from the population‐based case‐control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1,499 cases and 1,118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non‐smokers was 0.25 (95% confidence interval: 0.14–0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21–0.48); among cases it was 0.15 (95% CI: 0.00–0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47–1.85, p‐value for trend = 0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75–1.27, p trend = 0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ‐measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure—hemoglobin adducts or FFQ—was associated with risk of prostate cancer. © 2008 Wiley‐Liss, Inc.
A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays
Authors: Charpin Colette , Secq Véronique , Giusiano Sophie , Carpentier Séverine , Andrac Lucile , Lavaut Marie‐Noëlle , Allasia Claude , Bonnier Pascal , Garcia Stéphane 
Published: November 2008

AbstractQuantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow‐up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c‐Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c‐erb B2), and 15 when ER, PgR and c‐erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost‐effective. Quantitative densitometric measurement of immunoprecipitates by computer‐assisted devices from digitized microscopic images allows standardized high‐throughput “in situ” molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. © 2008 Wiley‐Liss, Inc.
Recurrent chemical reactivations of EBV promotes genome instability and enhances tumor progression of nasopharyngeal carcinoma cells
Authors: Fang Chih‐Yeu , Lee Chia‐Huei , Wu Chung‐Chun , Chang Yu‐Ting , Yu Shu‐Ling , Chou Sheng‐Ping , Huang Ping‐Ting , Chen Chi‐Long , Hou Jia‐Woei , Chang Yao , Tsai Ching‐Hwa , Takada Kenzo , Chen Jen‐Yang 
Published: November 2008

AbstractNasopharyngeal carcinoma (NPC) is an endemic malignancy prevalent in South East Asia. Epidemiological studies have associated this disease closely with Epstein‐Barr virus (EBV) infection. Previous studies also showed that EBV reactivation is implicated in the progression of NPC. Thus, we proposed that recurrent reactivations of EBV may be important for its pathogenic role. In this study, NPC cell lines latently infected with EBV, NA and HA, and the corresponding EBV‐negative NPC cell lines, NPC‐TW01 (TW01) and HONE‐1, were treated with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and sodium n‐butyrate (SB) for lytic cycle induction. A single treatment with TPA/SB revealed that DNA double‐strand breaks and formation of micronuclei (a marker for genome instability) were associated with EBV reactivation in NA and HA cells. Examination of EBV early genes had identified several lytic proteins, particularly EBV DNase, as potent activators that induced DNA double‐strand breaks and contribute to genome instability. Recurrent reactivations of EBV in NA and HA cells resulted in a marked increase of genome instability. In addition, the degree of chromosomal aberrations, as shown by chromosome structural variants and DNA copy‐number alterations, is proportional to the frequency of TPA/SB‐induced EBV reactivation. Whereas these DNA abnormalities were limited in EBV‐negative TW01 cells with mock or TPA/SB treatment, and were few in mock‐treated NA cells. The invasiveness and tumorigenesis assays also revealed a profound increase in both characteristics of the repeatedly reactivated NA cells. These results suggest that recurrent EBV reactivations may result in accumulation of genome instability and promote the tumor progression of NPC. © 2008 Wiley‐Liss, Inc.
Minimizing misclassification of hormone users at mammography screening
Authors: Njor Sisse Helle , Pedersen Anette Tønnes , Schwartz Walter , Hallas Jesper , Lynge Elsebeth 
Published: November 2008

AbstractThe aim of the study was to retrospectively determine the impact of comparing current mammograms with prior mammograms on risk of misclassification especially for hormone users. Data on mammography screening were retrieved for 1993–2005 from Fyn, Denmark. At first screen, two projections were made; at subsequent screens, one projection for fatty and two projections for mixed/dense breasts. Until June 3, 2002, 2‐year‐old mammograms were used for comparison, and later 4‐year‐old mammograms. Prescription drug data were used to identify hormone, hormone therapy (HT), use. False positive risk and interval cancer proportion dependency on age, hormone use, screen number, projection and prior mammogram were tested with logistic regression. Controlled for breast density, current HT‐users had a lower risk of a false positive test 0.69 (95%CI 0.55–0.86) and a lower interval cancer proportion 0.66 (95%CI 0.45–0.99) when 4‐year‐old instead of 2‐year‐old mammograms were used for comparison. The use of 4‐year‐old instead of 2‐year‐old mammograms for comparison lowered the risk of false positive test in never users, but otherwise age of comparison mammogram had no impact on classification of never and past users of HT. The study indicated that misclassification at screening mammography in current users of HT can be reduced considerably, when the screening mammograms are viewed with the mammograms taken 4 years earlier. It should be stressed that these results come from a single clinic, and replication in other observational and/or experimental studies is warranted. © 2008 Wiley‐Liss, Inc.
Inducible NO synthase confers chemoresistance in head and neck cancer by modulating survivin
Authors: Fetz Verena , Bier Carolin , Habtemichael Negusse , Schuon Robert , Schweitzer Andrea , Kunkel Martin , Engels Knut , Kovács Adorján F. , Schneider Sandra , Mann Wolf , Stauber Roland H. , Knauer Shirley K. 
Published: November 2008

AbstractThe dual role of the inducible NO synthase (iNOS) and NO signaling in head and neck squamous cell carcinoma (HNSCC) is a complex and can both promote or inhibit tumor progression. However, the underlying molecular mechanisms are not yet resolved in detail. We show for the first time that conditions, favoring low NO levels conferred resistance against cisplatin/taxol‐induced apoptosis in HNSCC cell lines. Cytoprotection was mediated by survivin, because we observed its upregulation subsequent to low doses of the NO donors S‐nitroso‐N‐acetyl‐penicillamine (SNAP) and sodium nitroprusside (SNP) or ectopic expression of physiologic amounts of iNOS. Also, RNAi‐mediated depletion of survivin blocked NOs anti‐apoptotic effects. Induction of survivin involves activation of the phosphatidylinositol‐3‐kinase/Akt (PI3K/Akt) pathway, which was antagonized by the PI3K‐inhibitor LY294002. Importantly, application of the iNOS‐specific inhibitor 1400W combined with RNAi‐mediated downregulation of survivin cooperatively enhanced drug‐induced cell death. The iNOS/survivin‐axis appears to be also of clinical relevance since immunohistochemistry revealed that iNOS expression correlated with enhanced survivin levels in HNSCC specimens. In contrast, high NO concentrations suppressed survivin levels in HNSCC but also in non‐malignant cells resulting in apoptosis. Cell death induced by high amounts of SNAP/SNP or by strong overexpression of iNOS involved activation of p38MAP‐kinase, which was counteracted by the p38MAP‐kinase inhibitor SB202190. Here, we provide evidence for a novel molecular mechanism how NO signaling may contribute to therapy resistance in HNSCC by modulating survivin expression. Our data further suggest pursuing pharmacogenetic iNOS/survivin‐targeting approaches as potential therapeutic strategies in head and neck cancer. © 2008 Wiley‐Liss, Inc.
Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano‐hydroxyapatite composite microsphere‐based scaffolds for bone tissue engineering in rotating bioreactors
Authors: Lv Qing , Nair Lakshmi , Laurencin Cato T. 
Published: November 2008

AbstractDynamic flow culture bioreactor systems have been shown to enhance in vitro bone tissue formation by facilitating mass transfer and providing mechanical stimulation. Our laboratory has developed a biodegradable poly (lactic acid glycolic acid) (PLAGA) mixed scaffold consisting of lighter‐than‐water (LTW) and heavier‐than‐water (HTW) microspheres as potential matrices for engineering tissue using a high aspect ratio vessel (HARV) rotating bioreactor system. We have demonstrated enhanced osteoblast differentiation and mineralization on PLAGA scaffolds in the HARV rotating bioreactor system when compared with static culture. The objective of the present study is to improve the mechanical properties and bioactivity of polymeric scaffolds by designing LTW polymer/ceramic composite scaffolds suitable for dynamic culture using a HARV bioreactor. We employed a microsphere sintering method to fabricate three‐dimensional PLAGA/nano‐hydroxyapatite (n‐HA) mixed scaffolds composed of LTW and HTW composite microspheres. The mechanical properties, pore size and porosity of the composite scaffolds were controlled by varying parameters, such as sintering temperature, sintering time, and PLAGA/n‐HA ratio. The PLAGA/n‐HA (4:1) scaffold sintered at 90°C for 3 h demonstrated the highest mechanical properties and an appropriate pore structure for bone tissue engineering applications. Furthermore, evaluation human mesenchymal stem cells (HMSCs) response to PLAGA/n‐HA scaffolds was performed. HMSCs on PLAGA/n‐HA scaffolds demonstrated enhanced proliferation, differentiation, and mineralization when compared with those on PLAGA scaffolds. Therefore, PLAGA/n‐HA mixed scaffolds are promising candidates for HARV bioreactor‐based bone tissue engineering applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Different hatching strategies in embryos of two species, pacific herring Clupea pallasii and Japanese anchovy Engraulis japonicus, that belong to the same order Clupeiformes, and their environmental adaptation
Authors: Kawaguchi Mari , Fujita Hideaki , Yoshizaki Norio , Hiroi Junya , Okouchi Hiroyuki , Nagakura Yoshitomo , Noda Tsutomu , Watanabe Satoshi , Katayama Satoshi , Iwamuro Shawichi , Nishida Mutsumi , Iuchi Ichiro , Yasumasu Shigeki 
Published: November 2008

AbstractPacific herring Clupea pallasii and Japanese anchovy Engraulis japonicus, which belong to the same order Clupeiformes, spawn different types of eggs: demersal adherent eggs and pelagic eggs, respectively. We cloned three cDNAs for Pacific herring hatching enzyme and five for Japanese anchovy. Each of them was divided into two groups (group A and B) by phylogenetic analysis. They were expressed specifically in hatching gland cells (HGCs), which differentiated from the pillow and migrated to the edge of the head in both species. HGCs of Japanese anchovy stopped migration at that place, whereas those of Pacific herring continued to migrate dorsally and distributed widely all over the head region. During evolution, the program for the HGC migration would be varied to adapt to different hatching timing. Analysis of the gene expression revealed that Pacific herring embryos synthesized a large amount of hatching enzyme when compared with Japanese anchovy. Chorion of Pacific herring embryo was about 7.5 times thicker than that of Japanese anchovy embryo. Thus, the difference in their gene expression levels between two species is correlated with the difference in the thickness of chorion. These results suggest that the hatching system of each fish adapted to its respective hatching environment. Finally, hatching enzyme genes were cloned from each genomic DNA. The exon–intron structure of group B genes basically conserved that of the ancestral gene, whereas group A genes lost one intron. Several gene‐specific changes of the exon–intron structure owing to nucleotide insertion and/or duplication were found in Japanese anchovy genes. J. Exp. Zool. (Mol. Dev. Evol.) 312B:95–107, 2009. © 2008 Wiley‐Liss, Inc.
Potential of magnetization transfer MRI for target volume definition in patients with non‐small‐cell lung cancer
Authors: Arnold Johannes F.T. , Kotas Markus , Pyzalski Robert W. , Pracht Eberhard D. , Flentje Michael , Jakob Peter M. 
Published: November 2008

AbstractPurposeTo develop a magnetization transfer (MT) module in conjunction with a single‐shot MRI readout technique and to investigate the MT phenomenon in non‐small‐cell lung cancer (NSCLC) as an adjunct for radiation therapy planning.Materials and MethodsA total of 10 patients with inoperable NSCLC were investigated using a 1.5T MR scanner. MT ratio (MTR) maps of several slices throughout the tumor were assessed. Each MTR‐map was acquired within a short breathhold. Fluorodeoxyglucose positron emission tomography (FDG‐PET) investigations were performed in addition to the MRI protocol. A total of 60 structures appearing conspicuous in FDG‐PET were compared with structures appearing conspicuous in corresponding MTR maps. Quantification of similarity between both modalities was performed using similarity index calculation.ResultsMTR‐maps showed different contrast than FDG‐PET images. However, structures that appeared conspicuous in FDG‐PET images, either by a marked signal enhancement or signal decrease, were found to be similarly present in MTR maps. A mean similarity index of 0.65 was calculated. MTR values of suspected atelectasis were on average lower than MTR values of tumor tissue.ConclusionThe proposed MT‐MRI technique provides a high MT efficiency, while being robust and fast enough for breathhold acquisition. The results obtained encourage for further exploration of MT‐MRI as an adjunct for radiotherapy planning in NSCLC. J. Magn. Reson. Imaging 2008;28:1417–1424. © 2008 Wiley‐Liss, Inc.
Conjunction analysis and propositional logic in fMRI data analysis using Bayesian statistics
Authors: Rudert Thomas , Lohmann Gabriele 
Published: November 2008

AbstractPurposeTo evaluate logical expressions over different effects in data analyses using the general linear model (GLM) and to evaluate logical expressions over different posterior probability maps (PPMs).Materials and MethodsIn functional magnetic resonance imaging (fMRI) data analysis, the GLM was applied to estimate unknown regression parameters. Based on the GLM, Bayesian statistics can be used to determine the probability of conjunction, disjunction, implication, or any other arbitrary logical expression over different effects or contrast. For second‐level inferences, PPMs from individual sessions or subjects are utilized. These PPMs can be combined to a logical expression and its probability can be computed. The methods proposed in this article are applied to data from a STROOP experiment and the methods are compared to conjunction analysis approaches for test‐statistics.ResultsThe combination of Bayesian statistics with propositional logic provides a new approach for data analyses in fMRI. Two different methods are introduced for propositional logic: the first for analyses using the GLM and the second for common inferences about different probability maps.ConclusionThe methods introduced extend the idea of conjunction analysis to a full propositional logic and adapt it from test‐statistics to Bayesian statistics. The new approaches allow inferences that are not possible with known standard methods in fMRI. J. Magn. Reson. Imaging 2008;28:1533–1539. © 2008 Wiley‐Liss, Inc.