bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoskeleton rearrangement induced by tetraspanin engagement modulates the activation of T and NK cells
Authors: Crotta Stefania , Ronconi Vanessa , Ulivieri Cristina , Baldari Cosima T. , Valiente Nicholas M. , Abrignani Sergio , Wack Andreas 
Published: March 2006

AbstractThe hepatitis C virus (HCV) binds to human cells through the interaction of its envelope glycoprotein E2 with the tetraspanin CD81. We have previously reported that engagement of CD81 has opposite effects on T and NK cell function, as it enhances T cell receptor‐mediated T cell activation and inhibits CD16‐ or IL‐12‐mediated NK cell activation. We further investigated this dichotomy and found that another tetraspanin, CD82, induces the same opposing effects on human primary T and NK cells. Activation by other unrelated stimuli such as NKG2D‐ and beta‐1 integrin is also reduced by CD81 ligation on NK cells. CD81 engagement by monoclonal antibody or HCV‐E2 enhances zeta and Erk phosphorylation in T cells and reduces them in NK cells, reflecting the opposite functional outcomes. CD81 engagement induces dramatic morphological changes and local F‐actin accumulation in both NK and T cells, indicating rearrangement of the actin cytoskeleton. Pharmacological inhibition of actin polymerization reduces T cell activation, whereas it greatly enhances NK cell activation. Importantly, treatment with actin blockers abolishes the inhibitory effect of CD81 ligation on NK cells. We propose that tetraspanin engagement leads to comparable cytoskeleton reorganization in T and NK cells, which in turn results in opposite functional outcomes.
Expression of the class A macrophage scavenger receptor on specific subpopulations of murine dendritic cells limits their endotoxin response
Authors: Becker Mike , Cotena Alessia , Gordon Siamon , Platt Nick 
Published: March 2006

AbstractDendritic cells (DC) function at the interface of innate and acquired immunity and are uniquely sensitive to specific stimuli. Pattern recognition receptors (PRR) on these cells are critically important because of their ability to recognise and initiate responses to conserved microbial‐associated molecular signatures. With the exception of Toll‐like receptors (TLR), we know relatively little about the specific distribution of other PRR amongst populations of DC. Here, we describe the expression of the murine class A macrophage scavenger receptor (SR‐A) and show that it is restricted to specific subpopulations of bone marrow‐derived and splenic DC. Importantly, we demonstrate that the receptor significantly alters the response of DC to endotoxin. In contrast to the activities of other PRR that have so far been examined, uniquely SR‐A limits the maturation response; SR‐A–/– cells display enhanced CD40 expression and TNF‐α production. We discuss the potential contributions of SR‐A to DC biology in the context of the known multiple activities of this receptor.
Automatic CAD model topology generation
Authors: Patel Paresh S. , Marcum David L. , Remotigue Michael G. 
Published: March 2006

AbstractComputer aided design (CAD) models often need to be processed due to the data translation issues and requirements of the downstream applications like computational field simulation, rapid prototyping, computer graphics, computational manufacturing, and real‐time rendering before they can be used. Automatic CAD model processing tools can significantly reduce the amount of time and cost associated with the manual processing. The topology generation algorithm, commonly known as CAD repairing/healing, is presented to detect commonly found geometrical and topological issues like cracks, gaps, overlaps, intersections, T‐connections, and no/invalid topology in the model, process them and build correct topological information. The present algorithm is based on the iterative vertex pair contraction and expansion operations calledstitchingandfilling, respectively, to process the model accurately. Moreover, the topology generation algorithm can process manifold as well as non‐manifold models, which makes the procedure more general and flexible. In addition, a spatial data structure is used for searching and neighbour finding to process large models efficiently. In this way, the combination of generality, accuracy, and efficiency of this algorithm seems to be a significant improvement over existing techniques. Results are presented showing the effectiveness of the algorithm to process two‐ and three‐dimensional configurations. Copyright © 2006 John Wiley & Sons, Ltd.
Numerical analysis of mixed convection in three‐dimensional rectangular channel with flush‐mounted heat sources based on field synergy principle
Authors: Cheng Y. P. , Lee T. S. , Low H. T. 
Published: March 2006

AbstractIn this paper the fluid flow and heat transfer characteristics of mixed convection in three‐dimensional rectangular channel with four heat sources are investigated numerically. The SIMPLEC algorithm is applied to deal with the coupling between pressure and velocity, and a new high‐order stability‐guaranteed second‐order difference (SGSD) scheme is adopted to discretize the convection term. The influence of four parameters is studied: Richardson number, heat source distribution, channel height and inclination angle. The numerical results are analysed from the viewpoint of the field synergy principle, which says that the enhanced convective heat transfer is related not only to the velocity field and temperature field, but also to the synergy between them. It is found that the effects of the four parameters on the thermal performance can all be explained with the field synergy principle. To obtain better electronic cooling, the synergy between the velocity and temperature gradient should be increased when other conditions are unchanged. Copyright © 2006 John Wiley & Sons, Ltd.
A fractional two‐step implicit algorithm using curvilinear collected grids
Authors: Ye Jian , McCorquodale J. A. , Peng Jian 
Published: March 2006

AbstractAn efficient fractional two‐step implicit algorithm is reported to simulate incompressible fluid flows in a boundary‐fitted curvilinear collocated grid system. Using the finite volume method, the convection terms are discretized by the high‐accuracy Roe's scheme to minimize numerical diffusion. An implicitness coefficient Π is introduced to accelerate the rate of convergence. It is demonstrated that the proposed algorithm links the fractional step method to the pressure correction procedure, and the SIMPLEC method could be considered as a special case of the fractional two‐step implicit algorithm (when Π=1). The proposed algorithm is applicable to unsteady flows and steady flows. Three benchmark two‐dimensional laminar flows are tested to evaluate the performance of the proposed algorithm. Performance is measured by sensitivity analyses of the efficiency, accuracy, grid density, grid skewness and Reynolds number on the solutions. Results show that the model is efficient and robust. Copyright © 2006 John Wiley & Sons, Ltd.
Effects of different phases of an invitational screening program on breast cancer incidence
Authors: Seppänen Johanna , Heinävaara Sirpa , Anttila Ahti , Sarkeala Tytti , Virkkunen Hanna , Hakulinen Timo 
Published: March 2006

AbstractThe aim of this study was to quantify the effects of separate phases of an invitational screening program on breast cancer incidence at different ages. Our database included detailed municipality‐specific information about invitations for mass‐screening for breast cancer in 267 Finnish municipalities from time period 1987–2001. The age range was 50–74. For this study, the program was divided into 7 separate phases, and those that had not been invited served as a baseline. The incidence rate was modeled using Poisson regression. To study the differences between age groups within each program phase, an interaction term between age group and phase of screening was included in the model. The modeling was done separately for localized breast cancers, nonlocalized breast cancers and all stages combined. For localized cancers, the risk compared to the noninvited increased during the first years of the 2‐year screening rounds in all age groups, and declined below the baseline during the second years. This effect was larger during the first round compared to the subsequent ones. In nonlocalized cancers, a clear incidence peak was detected only during the first year of the first round. A decreasing post screening effect was detected in nonlocalized cancers in women aged 60–69, but not in localized cancers. Cumulating over ages 50–74, extra incidence caused by regular screening in localized cancers was 5.2% if the program was continued up to age 59, and 28.0% if it continued up to age 69. Corresponding figures for nonlocalized cancers were decreases of 19.8% and 20.9%, respectively. © 2006 Wiley‐Liss, Inc.
Progressive increase of SCCA‐IgM immune complexes in cirrhotic patients is associated with development of hepatocellular carcinoma
Authors: Pontisso Patrizia , Quarta Santina , Caberlotto Cristina , Beneduce Luca , Marino Maria , Bernardinello Elisabetta , Tono Natascia , Fassina Giorgio , Cavalletto Luisa , Gatta Angelo , Chemello Liliana 
Published: March 2006

AbstractAbout 3–4% of cirrhotic patients develop primary liver cancer every year. Specific serologic markers have not yet been identified for screening of high risk patients. The serpin squamous cell carcinoma antigen (SCCA) is overexpressed in liver cancer and circulating SCCA‐IgM complexes have been described in patients with hepatocellular carcinoma (HCC). The aim of the present study was to assess the behavior of SCCA‐IgM in relation to HCC development in patients with cirrhosis. A retrospective, longitudinal study was conducted in a cohort of prospectively followed cirrhotic patients. Two groups with similar clinical profile at presentation were studied : group A included 16 patients who developed HCC during a median follow up of 4 years; group B included 17 patients who did not develop HCC during the same time interval. Circulating SCCA‐IgM immune complexes were determined using a recently standardized ELISA assay. At presentation similar levels of SCCA‐IgM complexes [mean ± SD: 267.40 ± 382.25 U/ml vs. 249.10 ± 446.90 U/ml, p = 0.9006] and of alpha‐fetoprotein [AFP; 24.11 ± 59.04 IU/ml vs. 10.91 ± 23.34 IU/ml, p = 0.3995] were detected in group A and in group B. The increase over time (ϕ) of SCCA‐IgM, assessed within at least one year before clinical diagnosis of HCC, was remarkably higher in group A than in group B (mean ± SD = 280.05 ± 606.71 (U/ml)/year vs. −37.92 ± 95.94 (U/ml)/year, p = 0.0408), while AFP increase was not significantly different (11.89 ± 23.27 (IU/ml)/year vs. 3.67 ± 11.46 (IU/ml)/year, p = 0.2179). Receiver operating characteristic (ROC) curves were plotted for the rate of change in the levels of both markers and the diagnostic accuracy measured as AUROC was higher for SCCA‐IgM ϕ (0.821) than for AFP ϕ (0.654). In conclusion, the progressive increase of SCCA‐IgM over time was associated with liver tumor development, suggesting that monitoring the behavior of SCCA‐IgM might become useful to identify cirrhotic patients at higher risk of HCC development. © 2006 Wiley‐Liss, Inc.
Prediction of treatment outcome by cisplatin‐DNA adduct formation in patients with stage III/IV head and neck squamous cell carcinoma, treated by concurrent cisplatin‐radiation (RADPLAT)
Authors: Hoebers Frank J.P. , Pluim Dick , Verheij Marcel , Balm Alfons J.M. , Bartelink Harry , Schellens Jan H.M. , Begg Adrian C. 
Published: March 2006

AbstractThe purpose of our study was to test the predictive value of cisplatin‐DNA adduct levels in head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin‐radiation. Patients with advanced‐stage HNSCC were treated within a randomized trial, investigating the optimal route of cisplatin administration, concurrently with radiation. Cisplatin was administered intra‐arterially (IA, 150 mg/m2, with systemic rescue by sodium thiosulfate) or intravenously (IV, 100 mg/m2). In a subgroup, adducts were quantified in normal tissue and tumor. 32P‐postlabeling was used to quantify intrastrand guanosine–guanosine adducts (GG‐adducts) and adenosine–guanosine adducts (AG‐adducts). Adduct levels were correlated with treatment outcome. Thirty‐five patients were included (21 IV and 14 IA). At median follow‐up of 27 months, locoregional (LR) control was 75% at 1 and 70% at 2 years. Adduct levels in tumor were 4–5‐fold higher than in white blood cells (WBC) for both IA and IV treatment (p = 0.01). Adduct formation in WBC and buccal cells was higher in IV treated patients compared with IA infusion (p = 0.049 and 0.005 for GG‐adducts in WBC and buccal cells, respectively). Adducts in tumors after IA infusion were not statistically different from those after IV. A strong correlation was observed between GG‐ and AG‐adduct formation (r = 0.86, p < 0.001). Patients with higher GG adduct levels (>median) in primary tumor had significantly better disease free survival (DFS) than patients with lower (≤ median) adduct levels (p = 0.02). For overall survival (OS), a nonsignificant trend was observed, again in favor of patients with higher adduct levels (p = 0.06). In conclusion, cisplatin‐DNA adduct formation in primary tumor appears to be predictive for DFS in HNSCC. No differences were observed in intratumoral adduct levels between IA and IV treatments, despite selective infusion of high‐dose cisplatin with the IA procedure. However, systemic adduct levels (WBC and buccal cells) from IV patients were higher than in IA patients, consistent with less systemic exposure after IA administration. © 2006 Wiley‐Liss, Inc.
Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long‐term survival in a randomized study
Authors: Roselli Mario , Mariotti Sabrina , Ferroni Patrizia , Laudisi Anastasia , Mineo Davide , Pompeo Eugenio , Ambrogi Vincenzo , Mineo Tommaso C. 
Published: March 2006

AbstractAlthough surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer, long‐term survival is not satisfactory and recurrence rate is high. We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival. We extended size and observation period of the study sample and performed a separate analysis for minimally resected patients. The trial was designed as a randomized, 2‐armed study with postoperative adjuvant chemotherapyversussurgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure (defined as anatomical or minimal). Chemotherapy consisted of cisplatin (100 mg/m2day 1) and etoposide (120 mg/m2days 1–3) for 6 cycles. The primary endpoint was overall survival; secondary endpoint was disease‐free survival (DFS). One hundred and forty patients entered the study: 70 were assigned to the adjuvant chemotherapy group and 70 to the control group. Groups were homogeneous for conventional risk factors. There was no clinically significant morbidity associated to chemotherapy. Patients were followed for a mean period of 40.31 ± 30.86 months. A significant difference in overall (p= 0.02) and disease‐free (p= 0.0001) survival was observed between patients undergoing adjuvant chemotherapyvs.control group. Adjuvant chemotherapy significantly improved both overall (p= 0.02) and DFS (p= 0.003) of anatomically resected patients, but only the DFS (p= 0.02) of minimally resected patients. Our results confirm that adjuvant chemotherapy may have a real impact on long‐term survival in patients with stage IB nonsmall cell lung cancer being this effect especially evident for those anatomically resected. © 2006 Wiley‐Liss, Inc.
The histone deacetylase inhibitor, suberoylanilide hydroxamic acid, overcomes resistance of human breast cancer cells to Apo2L/TRAIL
Authors: Butler Lisa M. , Liapis Vasilios , Bouralexis Stelios , Welldon Katie , Hay Shelley , Thai Le M. , Labrinidis Agatha , Tilley Wayne D. , Findlay David M. , Evdokiou Andreas 
Published: March 2006

AbstractWhile the apoptosis‐inducing ligand Apo2L/TRAIL is a promising new agent for the treatment of cancer, the sensitivity of cancer cells for induction of apoptosis by Apo2L/TRAIL varies considerably. Identification of agents that can be used in combination with Apo2L/TRAIL to enhance apoptosis in breast cancer cells would increase the potential utility of this agent as a breast cancer therapeutic. Here, we show that the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), can sensitize Apo2L/TRAIL‐resistant breast cancer cells to Apo2L/TRAIL‐induced apoptosis. Importantly, neither Apo2L/TRAIL alone, nor in combination with SAHA, affected the viability of normal human cells in culture. Apo2L/TRAIL‐resistant MDA‐MB‐231 breast cancer cells, generated by long‐term culture in the continuous presence of Apo2L/TRAIL, were resensitized to Apo2L/TRAIL‐induced apoptosis by SAHA. The sensitization of these cells by SAHA was accompanied by activation of caspase 8, caspase 9 and caspase 3 and was concomitant with Bid and PARP cleavage. The expression of the proapoptotic protein, Bax, increased significantly with SAHA treatment and high levels of Bax were maintained in the combined treatment with Apo2L/TRAIL. Treatment with SAHA increased cell surface expression of DR5 but not DR4. Interestingly, SAHA treatment also resulted in a significant increase in cell surface expression of DcR1. Taken together, our findings indicate that the use of these 2 agents in combination may be effective for the treatment of breast cancer. © 2006 Wiley‐Liss, Inc.
Enhanced EGR1 activity promotes the growth of prostate cancer cells in an androgen‐depleted environment
Authors: Yang Shan‐Zhong , Eltoum Isam A. , Abdulkadir Sarki A. 
Published: March 2006

AbstractDuring anti‐hormonal therapy for prostate cancer, a major clinical problem is the development of androgen‐independent disease. The molecular mechanisms underlying the transition to androgen independence are the subject of intense investigation. In many prostate tumors, the activity of the transcription factor EGR1 (early growth response gene 1) is elevated due to overexpression of EGR1 and/or downregulation of the co‐repressor, NAB2. We have modeled these alterations by expressing active EGR1 that does not bind NAB co‐repressor proteins in human prostate carcinoma cells. We show here that active EGR1 expression enhances the androgen‐independent growth of prostate carcinoma cells in vitro and in vivo. Employing RNAi and expression analyses, we show that EGR1 mediates its effects, at least in part, through the AR signaling pathway. These findings support a role for enhanced EGR1 activity in regulating the transition from androgen‐dependent to androgen‐independent prostate cancer. J. Cell. Biochem. 97: 1292–1299, 2006. © 2005 Wiley‐Liss, Inc.
Ghrelin stimulates interleukin‐8 gene expression through protein kinase C‐mediated NF‐κB pathway in human colonic epithelial cells
Authors: Zhao Dezheng , Zhan Yanai , Zeng Huiyan , Moyer Mary P. , Mantzoros Christos S. , Pothoulakis Charalabos 
Published: March 2006

AbstractGhrelin, a newly identified gastric peptide, is known for its potent activity in growth hormone (GH) release and appetite. Although ghrelin is involved in several other responses such as stress and intestinal motility, its potential role in intestinal inflammation is not clear. Here, we show that expression of ghrelin and its receptor mRNA is significantly increased during acute experimental colitis in mice injected intracolonically with trinitrobenzene sulfate (TNBS). We found by PCR that ghrelin receptor mRNA is expressed in non‐transformed human colonic epithelial NCM460 cells. Exposure of NCM460 cells stably transfected with ghrelin receptor mRNA to ghrelin, increased IκBα phosphorylation and its subsequent degradation. In addition, ghrelin stimulated NF‐κB‐binding activity and NF‐κB p65 subunit phosphorylation, and induced IL‐8 promoter activity and IL‐8 protein secretion. Furthermore, our data show that ghrelin‐induced IκBα and p65 phosphorylation was markedly reduced by pharmacological inhibitors of intracellular calcium mobilization (BAPTA/AM) and protein kinase C (GF 109203X). Pretreatment with BAPTA/AM or GF109203X also significantly attenuated ghrelin‐induced IL‐8 production. Together, our results strongly suggest that ghrelin may be a proinflammatory peptide in the colon. Ghrelin may participate in the pathophysiology of colonic inflammation by inducing PKC‐dependent NF‐κB activation and IL‐8 production at the colonocyte level. J. Cell. Biochem. 97: 1317–1327, 2006. © 2005 Wiley‐Liss, Inc.
Comparative proteomic analysis of apoptosis induced by sodium selenite in human acute promyelocytic leukemia NB4 cells
Authors: Dong Hua , Ying Tianyi , Li Ting , Cao Tingming , Wang Junjun , Yuan Jing , Feng Erling , Han Bingshe , Hua Fangyuan , Yang Yang , Yuan Jiangang , Wang Hengliang , Xu Caimin 
Published: March 2006

AbstractSelenium (Se) is an essential trace element possessing anticarcinogenic properties. Sodium selenite (Na2SeO3) induced apoptosis in human acute promyelocytic leukemia (APL) cell line NB4 with dose and time dependency. In this study, proteomic techniques were used to study the apoptosis of NB4 cells induced by sodium selenite. Twenty‐six downregulated and four upregulated proteins were identified, which exhibited a 1.5‐fold change or greater. The identified proteins included key regulators of signal transduction such as Rho GDP dissociation inhibitor (Rho GDI) alpha and beta members of the MAPK family, and proteins involved in the regulation of c‐fos or c‐myc expression. Importantly, the identified proteins, hnRNP D0B and Rho GDI beta, which were related with the regulation of c‐myc, c‐fos, and c‐jun, were determined by reverse transcription‐polymerase chain reaction (RT‐PCR) to confirm their downregulation in proteomic study. Western blot analysis and RT‐PCR were then performed on three associated proteins: c‐Myc, c‐Fos, and c‐Jun, and their expression were observed to be significantly downregulated. Results showed that certain regulation involved in c‐myc, c‐fos, and c‐jun was present in the apoptosis, and the c‐Myc dependent‐on and Jun N‐terminal kinase (JNK) pathway also play roles. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Splice variant 3, but not 2 of receptor protein‐tyrosine phosphatase σ can mediate stimulation of insulin‐secretion by α‐latrotoxin
Authors: Lajus Sophie , Lang Jochen 
Published: March 2006

Abstractα‐latrotoxin (α‐LTX) binds to several cell surface receptors including receptor protein‐tyrosine phosphatase σ (RPTPσ). Here we demonstrate that transient overexpression of the short splice variant 3 conferred α‐LTX induced secretion to hamster insulinoma (HIT‐15) cells. In contrast, the long splice variant 2 containing four additional extracellular fibronectin‐III domains was inactive in secretion or in a single cell assay. Toxin‐sensitive (MIN6) and toxin‐insensitive (HIT‐T15) insulinoma cell lines as well as PC12 cells expressed similar amounts of endogenous short RPTPσ splice variant suggesting that this receptor does not play a role for toxin‐sensitivity. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.