bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double‐blind randomized controlled trial study on post‐extraction immediately restored implants using the switching platform concept: soft tissue response. Preliminary report
Authors: Canullo Luigi , Iurlaro Giorgia , Iannello Giuliano 
Published: March 2009

AbstractAim: To evaluate the soft tissue response to immediately placed implants using the platform switching concept.Material and methods: In 22 patients, 22 implants of 5.5 mm platform diameter were placed immediately into fresh extraction sockets in maxillae without compromised bone tissue. Eventual post‐extraction bone defects were filled using bovine bone matrix mixed with collagen. Immediately after insertion, implants were randomly divided: 11 implants were connected with a 3.8 mm diameter abutment (test group) and 11 with a 5.5 mm diameter abutment (control group). A provisional crown was adapted and adjusted for non‐functional immediate positioning. Two months later, definitive prosthetic rehabilitation was performed. Periodontal parameter, buccal peri‐implant mucosal changes (REC), mesial and distal papilla height (PH) and vertical height of jumping distance (VHG) were measured at the time of implant placement, of definitive prosthesis insertion and every 6 months thereafter.Results: The mean follow‐up was 25 months. All implants were clinically osseointegrated.The test group showed a +0.18 mm REC gain. PH gain was +0.045 mm on average. The mean values were statistically significant (P≤0.005) compared with the control group (PH=−0.88 mm; REC=−0.45 mm). No difference between the two groups in periodontal parameters was found. The mean value of bone filling was 7.51 mm in the test group (97.4% of VHG) and 8.57 mm in the control group (95.2% of VHG). No statistically significant difference was found between the two groups.Conclusions: This study suggests that, in a limited time period of 2 years, immediately placed implants with subsequent platform switching can provide peri‐implant tissue stability.
Successful outcome of splinted implants supporting a ‘planned’ maxillary overdenture: a retrospective evaluation and comparison with fixed full dental prostheses
Authors: Sanna A. , Nuytens P. , Naert I. , Quirynen M. 
Published: March 2009

AbstractObjective: Whereas an overdenture concept is generally accepted for the mandible, the outcome of this therapy for the maxilla remains less documented. This retrospective analysis evaluated the peri‐implant parameters of implants supporting a ‘planned’ overdenture in the maxilla, and compared these data with those of an age‐matched control group, with a fixed full dental prosthesis.Material and methods: All patients with an implant‐supported overdenture in the maxilla from the Leuven University Hospital (at least 12 months in function) were recalled for a thorough examination. Forty‐four patients (162 implants, Brånemark type) could be enrolled.Results: The mean loading time was 9 years (range: >1 to >20 years). The cumulative survival rate after 10 years of function was 99.3% if four to six interconnected implants supported the overdenture, but only 85.7% in case two non‐connected implants were used as support. The marginal bone level in the former group remained stable, with changes comparable with those observed for implants supporting fixed full dental prostheses.Conclusions: These results fully support the overdenture treatment concept for the maxilla, at least when ≥4 splinted implants are used.
Vertical bone augmentation with fluvastatin in an injectable delivery system: a rat study
Authors: Jinno Yohei , Ayukawa Yasunori , Ogino Yoichiro , Atsuta Ikiru , Tsukiyama Yoshihiro , Koyano Kiyoshi 
Published: March 2009

AbstractObjectives: HMG‐CoA reductase inhibitors (statins) are widely used for hyperlipidemia. Previous studies demonstrate that statins stimulate bone morphogenetic protein‐2 (BMP‐2) expression and lead to bone formation. The aim of this study was to evaluate whether percutaneously injected statin with a novel statin delivery system achieved vertical bone augmentation.Material and methods: As experimental groups, atelocollagen‐α‐tricalcium phosphate (αTCP) composites containing 3.3 mg (low dose) or 6.7 mg (high dose) of fluvastatin were injected (one shot) subcutaneously over the calvarial periosteum of rats. The animals were then sacrificed 1, 2, and 4 weeks after injection. Vertically augmented bone was assessed by histomorphometric procedures, i.e., by measuring new bone thickness (NBT) and bone density (BD).Results: In control groups, no newly formed bone could be seen over the calvarial bone. In the experimental groups, in contrast, a large amount of newly formed bone could be seen over the preexisting calvarial bone. The newly formed bone was seen to be in direct contact with the preexisting bone. During the entire observation, significant NBT was observed in the experimental groups (P<0.05). At the final stage of observation (4 weeks), NBT was 66.7% (low‐dose group) and 59.7% (high‐dose group), while they were from 1% to 16.3% in the control groups. In the experimental groups, BD significantly increased in a time‐dependent manner.Conclusion: Percutaneously applied fluvastatin (one shot) with a composite of αTCP and collagen has great potential to augment the height of the bone.
Cadmium‐induced Cytosolic Ca2+ Elevation and Subsequent Apoptosis in Renal Tubular Cells
Authors: Yeh Jeng‐Hsien , Huang Chorng‐Chih , Yeh Mei‐Yin , Wang Jyh‐Seng , Lee Jenn‐Kuen , Jan Chung‐Ren 
Published: March 2009

Abstract: Cadmium (Cd2+) is an industrial and environmental metal. The effect of Cd2+ on intracellular free‐Ca2+ levels ([Ca2+]i) and viability in Madin Darby canine kidney cells was explored. Cd2+increased [Ca2+]i in a concentration‐dependent manner with an EC50 of 85 µM. Cd2+‐induced Mn2+ entry demonstrated Ca2+ influx. Removal of extracellular Ca2+ decreased the [Ca2+]i signal by 60%. The [Ca2+]i signal was inhibited by La3+ but not by L‐type Ca2+ channel blockers. In Ca2+‐free medium, Cd2+‐induced [Ca2+]i signal was abolished by pre‐treatment with 1 µM thapsigargin (an endoplasmic reticulum Ca2+pump inhibitor) and 2 µM carbonylcyanide m‐chlorophenylhydrazone (CCCP; a mitochondrial uncoupler). Cd2+‐induced Ca2+ release was not altered by inhibition of phospholipase C. At concentrations between 10 and 100 µM, Cd2+killed cells in a concentration‐dependent manner. The cytotoxic effect of 100 µM Cd2+was reversed by pre‐chelating cytosolic Ca2+with BAPTA. Cd2+‐induced apoptosis was demonstrated by propidium iodide. Collectively, this study shows that Cd2+ induced a [Ca2+]i increase in Madin Darby canine kidney cells via evoking Ca2+ entry through non‐selective Ca2+ channels, and releasing stored Ca2+ from endoplasmic reticulum and mitochondria in a phospholipase C‐independent manner.
POROSITY DEVELOPMENT AND ITS EFFECT ON OIL UPTAKE DURING FRYING PROCESS
Authors: ZIAIIFAR AMAN MOHAMMAD , COURTOIS FRANCIS , TRYSTRAM GILLES 
Published: March 2009

ABSTRACT The objective of this work was to study certain physical properties of French fries, such as density and porosity, and their relationship with oil absorption during the frying process. The effects of oil temperature and frying time on moisture loss, oil content and crust thickness were first studied. Changes in apparent density, absolute density as well as porosity during two successive periods of frying process (frying and cooling) were then investigated, and possible reasons for these changes were discussed. Finally, the porosity changes were related to oil uptake. Potatoes were cut into rectangular shapes and were fried at different oil temperatures (140, 155, 170 and 185C) for periods ranging from 60 to 240 s. Results showed that during frying, the porosity of the product increases, reaching a maximum at the end of frying, whereas during the cooling period, it decreases because of oil absorption and collapse phenomena. PRACTICAL APPLICATIONSThis study shows some physical changes that can be related to oil absorption during the frying process of French fries. Many food research projects attempt to understand oil uptake during the frying process in order to control and reduce the fat content of fried products. The results of this work may lead to finding the way(s) to produce less greasy fried products.
Public and User Participation in Public Service Delivery: Tensions in Policy and Practice
Authors: Martin Graham P. 
Published: March 2009

AbstractSocial‐scientific analysis of public‐participation initiatives has proliferated in recent years. This review article discusses some key aspects of recent work. First, it analyses some of the justifications put forward for public participation, drawing attention to differences and overlaps between rationales premised on democratic representation/representativeness and those based on more technocratic ideas about the knowledge that the public can offer. Second, it considers certain tensions in policy discourses on participation, focusing in particular on policy relating to the National Health Service and other British public services. Third, it examines the challenges of putting a coherent vision for public participation into practice, noting the impediments that derive from the often‐competing ideas about the remit of participation held by different groups of stakeholders. Finally, it analyses the gap between policy and practice, and the consequences of this for the prospects for the enactment of active citizenship through participation initiatives.
Role of epidermal growth factor receptor (EGFR) in corneal remodelling in diabetes
Authors: Akhtar Saeed , Almubrad Turki , Bron Anthony J. , Yousif Mariam H. M. , Benter Ibrahim F. , Akhtar Saghir 
Published: March 2009

Abstract.Purpose:  This study examined the role of epidermal growth factor receptor (EGFR) signalling on the organization and remodelling of collagen fibrils (CFs) and proteoglycans (PGs) in the stroma of diabetic rat cornea.Methods:  Diabetes was induced in female Wistar rats (n = 5) by streptozotocin (STZ) injection (55 mg/kg). Treatment with a selective inhibitor of EGFR tyrosine kinase, AG1478, was started on the same day as the induction of diabetes and administered every other day for 4 weeks. Corneas were fixed in 4% paraformaldehyde at 4 ° to allow for analysis of CF diameters and in 2.5% glutaraldehyde in sodium acetate buffer containing cuprolinic blue to enable the study of PG distribution. AnalySIS soft imaging software was used to analyse CFs and PGs.Results:  Epithelial thickness, and median diameter and area fraction of CF in corneal stroma were decreased in diabetic rat cornea compared with normal cornea (p < 0.001), whereas the median PG area and area fractions were significantly increased (p < 0.001). Treatment with AG1478, although it had no action on normal cornea, prevented these diameter and area fraction changes in CFs and PGs. The cornea of AG1478‐treated diabetic rats showed a slight increase in CF diameter and area fraction and a decreased number density.Conclusions:  These data show that the distribution of corneal stroma CFs and PGs was altered after 4 weeks of diabetes and that, furthermore, treatment with an EGFR signalling inhibitor normalized these abnormalities. The data suggest that EGFR plays an important role in the development of diabetes‐induced corneal remodelling.
DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and in Cells Experiencing Replication Stress
Authors: Leung-Pineda Van , Huh Jiwon , Piwnica-Worms Helen 
Published: March 2009

Abstract
The Chk1 protein kinase preserves genome integrity in normal proliferating cells and in cells experiencing replicative and genotoxic stress. Chk1 is currently being targeted in anticancer regimens. Here, we identify damaged DNA-binding protein 1 (DDB1) as a novel Chk1-interacting protein. DDB1 is part of an E3 ligase complex that includes the cullin proteins Cul4A and Cul4B. We report that Cul4A/DDB1 negatively regulates Chk1 stability in vivo. Chk1 associates with Cul4A/DDB1 during an unperturbed cell division cycle and both Chk1 phosphorylation and replication stress enhanced these interactions. Cul4A/DDB1 regulates Chk1 ubiquitination in vivo and Chk1 is directly ubiquitinated in vitro in a Cul4A/DDB1–dependent manner. Furthermore, Chk1 is stabilized in cells deficient for Cul4A/DDB1. This study shows that Chk1 abundance is regulated by the Cul4A/DDB1 ubiquitin ligase during an unperturbed cell division cycle, in response to replicative stress and on heat shock protein 90 inhibition, and that deregulation of the Chk1/Cul4A/DDB1 pathway perturbs the ionizing radiation–induced G2 checkpoint. [Cancer Res 2009;69(6):2630–7]
Magnetovaccination as a Novel Method to Assess and Quantify Dendritic Cell Tumor Antigen Capture and Delivery to Lymph Nodes
Authors: Long Christopher M. , van Laarhoven Hanneke W.M. , Bulte Jeff W.M. , Levitsky Hyam I. 
Published: March 2009

Abstract
A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell–based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers. [Cancer Res 2009;69(7):3180–7]
E2F1 Induces Tumor Cell Survival via Nuclear Factor-κB–Dependent Induction of EGR1 Transcription in Prostate Cancer Cells
Authors: Zheng Chaogu , Ren Zijia , Wang Hetian , Zhang Weici , Kalvakolanu Dhananjaya V. , Tian Zhigang , Xiao Weihua 
Published: March 2009

Abstract
Transcription factor E2F1 has been implicated in both apoptosis-promoting and apoptosis-suppressing effects. However, factors that mediate its antiapoptotic effects are still not identified. Using prostate tumor–derived cell lines, we showed here that E2F1 activated the expression of transcription factor EGR1 for promoting cell survival. E2F1 up-regulated the production of EGR1-induced growth factors, epidermal growth factor, platelet-derived growth factor, and insulin-like growth factor II, which in turn activated the phosphoinositide-3-kinase/Akt pathway to resist drug-induced apoptosis. Moreover, E2F1 directly induced the transcription of the Egr1 gene using the κB site located in its proximal promoter. E2F1 physically interacted with the RelA subunit of nuclear factor-κB and modulated its transactivity to fully activate EGR1 transcription. Together, these studies uncovered a novel mechanism for E2F1-induced suppression of apoptosis in prostate cancer. [Cancer Res 2009;69(6):2324–31]
Dose-Response Relationships forN7-(2-Hydroxyethyl)Guanine Induced by Low-Dose [14C]Ethylene Oxide: Evidence for a Novel Mechanism of Endogenous Adduct Formation
Authors: Marsden Debbie A. , Jones Donald J.L. , Britton Robert G. , Ognibene Ted , Ubick Esther , Johnson George E. , Farmer Peter B. , Brown Karen 
Published: March 2009

AbstractEthylene oxide (EO) is widely used in the chemical industry and is also formed in humans through the metabolic oxidation of ethylene, generated during physiologic processes. EO is classified as a human carcinogen and is a direct acting alkylating agent, primarily forming N7-(2-hydroxyethyl)guanine (N7-HEG). To conduct accurate human risk assessments, it is vital to ascertain the relative contribution of endogenously versus exogenously derived DNA damage and identify the sources of background lesions. We have therefore defined in vivo dose-response relationships over a concentration range relevant to human EO exposures using a dual-isotope approach. By combining liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography-accelerator mass spectrometry analysis, both the endogenous and exogenous N7-HEG adducts were quantified in tissues of [14C]EO-treated rats. Levels of [14C]N7-HEG induced in spleen, liver, and stomach DNA increased in a linear manner from 0.002 to 4 adducts/108 nucleotides. More importantly, the extent of damage arising through this route was insignificant compared with the background abundance of N7-HEG naturally present. However, at the two highest doses, [14C]EO exposure caused a significant increase in endogenous N7-HEG formation in liver and spleen, suggesting that EO can induce physiologic pathways responsible for ethylene generation in vivo and thereby indirectly promote N7-HEG production. We present evidence for a novel mechanism of adduct formation to explain this phenomenon, involving oxidative stress and 1-aminocyclopropane-1-carboxylic acid as a potential biosynthetic precursor to ethylene in mammalian cells. Based on the proposed pathway, N7-HEG may have potential as a biomarker of cellular oxidative stress. [Cancer Res 2009;69(7):3052–9]
Effective Incorporation of Biomarkers into Phase II Trials
Authors: McShane Lisa M. , Hunsberger Sally , Adjei Alex A. 
Published: March 2009

Abstract
The incorporation of biomarkers into the drug development process will improve understanding of how new therapeutics work and allow for more accurate identification of patients who will benefit from those therapies. Strategically planned biomarker evaluations in phase II studies may allow for the design of more efficient phase III trials and better screening of therapeutics for entry into phase III development, hopefully leading to increased chances of positive phase III trial results. Some examples of roles that a biomarker can play in a phase II trial include predictor of response or resistance to specific therapies, patient enrichment, correlative endpoint, or surrogate endpoint. Considerations for using biomarkers most effectively in these roles are discussed in the context of several examples. The substantial technical, logistic, and ethical challenges that can be faced when trying to incorporate biomarkers into phase II trials are also addressed. A rational and coordinated approach to the inclusion of biomarker studies throughout the drug development process will be the key to attaining the goal of personalized medicine.
Genomic Analysis Using High-Density Single Nucleotide Polymorphism-Based Oligonucleotide Arrays and Multiplex Ligation-Dependent Probe Amplification Provides a Comprehensive Analysis of INI1/SMARCB1 in Malignant Rhabdoid Tumors
Authors: Jackson Eric M. , Sievert Angela J. , Gai Xiaowu , Hakonarson Hakon , Judkins Alexander R. , Tooke Laura , Perin Juan Carlos , Xie Hongbo , Shaikh Tamim H. , Biegel Jaclyn A. 
Published: March 2009

Abstract
Purpose: A high-resolution genomic profiling and comprehensive targeted analysis of INI1/SMARCB1 of a large series of pediatric rhabdoid tumors was done. The aim was to identify regions of copy number change and loss of heterozygosity (LOH) that might pinpoint additional loci involved in the development or progression of rhabdoid tumors and define the spectrum of genomic alterations of INI1 in this malignancy.
Experimental Design: A multiplatform approach using Illumina single nucleotide polymorphism-based oligonucleotide arrays, multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, and coding sequence analysis was used to characterize genome-wide copy number changes, LOH, and genomic alterations of INI1/SMARCB1 in a series of pediatric rhabdoid tumors.
Results: The biallelic alterations of INI1 that led to inactivation were elucidated in 50 of 51 tumors. INI1 inactivation was shown by a variety of mechanisms, including deletions, mutations, and LOH. The results from the array studies highlighted the complexity of rearrangements of chromosome 22 compared with the low frequency of alterations involving the other chromosomes.
Conclusions: The results from the genome-wide single nucleotide polymorphism array analysis suggest that INI1 is the primary tumor suppressor gene involved in the development of rhabdoid tumors with no second locus identified. In addition, we did not identify hotspots for the breakpoints in sporadic tumors with deletions of chromosome 22q11.2. By employing a multimodality approach, the wide spectrum of alterations of INI1 can be identified in the majority of patients, which increases the clinical utility of molecular diagnostic testing.
Regulatory T-Cell–Mediated Attenuation of T-Cell Responses to the NY-ESO-1 ISCOMATRIX Vaccine in Patients with Advanced Malignant Melanoma
Authors: Nicholaou Theo , Ebert Lisa M. , Davis Ian D. , McArthur Grant A. , Jackson Heather , Dimopoulos Nektaria , Tan Bee , Maraskovsky Eugene , Miloradovic Lena , Hopkins Wendie , Pan Linda , Venhaus Ralph , Hoffman Eric W. , Chen Weisan , Cebon Jonathan 
Published: March 2009

Abstract
Purpose: NY-ESO-1 is a highly immunogenic antigen expressed in a variety of malignancies, making it an excellent target for cancer vaccination. We recently developed a vaccine consisting of full-length recombinant NY-ESO-1 protein formulated with ISCOMATRIX adjuvant, which generated strong humoral and T-cell–mediated immune responses and seemed to reduce the risk of disease relapse in patients with fully resected melanoma. This study examines the clinical and immunologic efficacy of the same vaccine in patients with advanced metastatic melanoma.
Experimental Design: Delayed-type hypersensitivity responses, circulating NY-ESO-1–specific CD4+ and CD8+ T cells, and proportions of regulatory T cells (Treg) were assessed in patients.
Results: In contrast to patients with minimal residual disease, advanced melanoma patients showed no clinical responses to vaccination. Although strong antibody responses were mounted, the generation of delayed-type hypersensitivity responses was significantly impaired. The proportion of patients with circulating NY-ESO-1–specific CD4+ T cells was also reduced, and although many patients had CD8+ T cells specific to a broad range of NY-ESO-1 epitopes, the majority of these responses were preexisting. Tregs were enumerated in the blood by flow cytometric detection of cells with a CD4+CD25+FoxP3+ and CD4+CD25+CD127− phenotype. Patients with advanced melanoma had a significantly higher proportion of circulating Treg compared with those with minimal residual disease.
Conclusions: Our results point to a tumor-induced systemic immune suppression, showing a clear association between the stage of melanoma progression, the number of Treg in the blood, and the clinical and immunologic efficacy of the NY-ESO-1 ISCOMATRIX cancer vaccine.