bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection against Lethal Challenge withStreptococcus pneumoniaeIs Conferred by Aryl Hydrocarbon Receptor Activation but Is Not Associated with an Enhanced Inflammatory Response
Authors: Vorderstrasse Beth A. , Lawrence B. Paige 
Published: September 2006

ABSTRACTStreptococcus pneumoniaeis a common respiratory pathogen and a major cause of morbidity and mortality in humans, particularly in the elderly and young children. The pulmonary immune response toS. pneumoniaeis initiated very rapidly, and, ideally, innate immune responses are able to contain bacterial colonization. In the studies presented here, we sought to determine whether activation of the aryl hydrocarbon receptor (AhR) would protect mice from an otherwise lethal infection withS. pneumoniae. The rationale for this hypothesis is that, although most AhR agonists are potent immunosuppressants, AhR activation enhances the inflammatory response to pathogenic and nonpathogenic stimuli. Specifically, neutrophil numbers and levels of inflammatory cytokines are often increased in mice treated with the potent AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). To test the hypothesis, vehicle control- or TCDD-treated mice were intranasally infected withS. pneumoniae. Mortality, pulmonary bacterial burden, cytokine/chemokine levels, and influx of immune cells to the lung were analyzed at various times postinfection. As predicted, survival was substantially improved in the mice treated with TCDD, and the pulmonary bacterial burden was decreased. Surprisingly, however, there was no evidence suggesting that protection resulted from an enhanced inflammatory response. In fact, neutrophil numbers and inflammatory chemokines and cytokines were all decreased in the TCDD-treated mice relative to vehicle control-treated mice. This suggests that the protective effect of AhR activation is not the result of altered immune function but instead may reflect a direct effect on the response of lung cells to infection.
Non-random fluctuations in power output during self-paced exercise
Authors: Tucker R , Bester A , Lambert E V , Noakes T D , Vaughan C L , St Clair Gibson A 
Published: September 2006

Objectives:To analyse the power output measured during a self-paced 20-km cycling time trial, during which power output was free to vary, in order to assess the level and characteristics of the variability in power output that occurred during the exercise bout.Methods:Eleven well-trained cyclists performed a 20-km cycling time trial, during which power output was sampled every 200 m. Power spectrum analysis was performed on the power output data, and a fractal dimension was calculated for each trial using the Higuchi method.Results:In all subjects, power output was maintained throughout the trial until the final kilometre, when it increased significantly, indicating the presence of a global pacing strategy. The power spectrum revealed the presence of 1/f-like scaling of power output and multiple frequency peaks during each trial, with the values of the frequency peaks changing over the course of the trial. The fractal dimension (D-score) was similar for all subjects over the 20-km trial and ranged between 1.5 and 1.9.Conclusions:The presence of an end spurt in all subjects, 1/f-like scaling and multiple frequency peaks in the power output data indicate that the measured oscillations in power output during cycling exercise activity may not be system noise, but may rather be associated with system control mechanisms that are similar in different individuals.
A multidisciplinary selection model for youth soccer: the Ghent Youth Soccer Project
Authors: Vaeyens R , Malina R M , Janssens M , Van Renterghem B , Bourgois J , Vrijens J , Philippaerts R M 
Published: September 2006

Objectives:To determine the relationships between physical and performance characteristics and level of skill in youth soccer players aged 12–16 years.Methods:Anthropometry, maturity status, functional and sport-specific parameters were assessed in elite, sub-elite, and non-elite youth players in four age groups: U13 (n = 117), U14 (n = 136), U15 (n = 138) and U16 (n = 99).Results:Multivariate analyses of covariance by age group with maturity status as the covariate showed that elite players scored better than the non-elite players on strength, flexibility, speed, aerobic endurance, anaerobic capacity and several technical skills (p<0.05). Stepwise discriminant analyses showed that running speed and technical skills were the most important characteristics in U13 and U14 players, while cardiorespiratory endurance was more important in U15 and U16 players. The results suggest that discriminating characteristics change with competitive age levels.Conclusions:Characteristics that discriminate youth soccer players vary by age group. Talent identification models should thus be dynamic and provide opportunities for changing parameters in a long-term developmental context.
Use of the one-legged hyperextension test and magnetic resonance imaging in the diagnosis of active spondylolysis
Authors: Masci L , Pike J , Malara F , Phillips B , Bennell K , Brukner P 
Published: September 2006

Background:Active spondylolysis is an acquired lesion in the pars interarticularis and is a common cause of low back pain in the young athlete.Objectives:To evaluate whether the one-legged hyperextension test can assist in the clinical detection of active spondylolysis and to determine whether magnetic resonance imaging (MRI) is equivalent to the clinical gold standard of bone scintigraphy and computed tomography in the radiological diagnosis of this condition.Methods:A prospective cohort design was used. Young active subjects with low back pain were recruited. Outcome measures included clinical assessment (one-legged hyperextension test) and radiological investigations including bone scintigraphy (with single photon emission computed tomography (SPECT)) and MRI. Computed tomography was performed if bone scintigraphy was positive.Results:Seventy one subjects were recruited. Fifty pars interarticulares in 39 subjects (55%) had evidence of active spondylolysis as defined by bone scintigraphy (with SPECT). Of these, 19 pars interarticulares in 14 subjects showed a fracture on computed tomography. The one-legged hyperextension test was neither sensitive nor specific for the detection of active spondylolysis. MRI revealed bone stress in 40 of the 50 pars interarticulares in which it was detected by bone scintigraphy (with SPECT), indicating reduced sensitivity in detecting bone stress compared with bone scintigraphy (p  =  0.001). Conversely, MRI revealed 18 of the 19 pars interarticularis fractures detected by computed tomography, indicating concordance between imaging modalities (p  =  0.345). There was a significant difference between MRI and the combination of bone scintigraphy (with SPECT)/computed tomography in the radiological visualisation of active spondylolysis (p  =  0.002).Conclusions:These results suggest that there is a high rate of active spondylolysis in active athletes with low back pain. The one-legged hyperextension test is not useful in detecting active spondylolysis and should not be relied on to exclude the diagnosis. MRI is inferior to bone scintigraphy (with SPECT)/computed tomography. Bone scintigraphy (with SPECT) should remain the first-line investigation of active athletes with low back pain followed by limited computed tomography if bone scintigraphy is positive.
Results of arthroscopic debridement for osteochondritis dissecans of the elbow
Authors: Rahusen F Th G , Brinkman J-M , Eygendaal D 
Published: September 2006

Objective:To determine the clinical outcome of arthroscopic debridement for osteochondritis dissecans of the elbow.Methods:A prospective cohort study was started in 2000; between 2000 and 2005, 15 patients (six male, nine female, mean age 28 years (range 16–49)) were treated for osteochondritis dissecans of the elbow with arthroscopic debridement. The lesion was graded during surgery using the classification of Baumgarten. The dominant side was operated on in seven of 15 patients, and all patients were involved in a sport in which the elbow is used extensively. Elbow function was assessed before and after surgery using the modified Andrews elbow scoring system (MAESS); pain was scored on a visual analogue scale (0, no pain; 10, severe pain). Evaluation was performed an average of 45 (range 18–59) months after surgery. Statistical analysis (Student’s t test) was carried out using SPSS statistical software. p<0.005 was considered significant.Results:There were no complications. The range of motion did not improve significantly. The mean MAESS score improved from 65.5 (poor) before surgery to 90.8 (excellent) after (p<0.001). The mean level of pain at rest decreased from 3 to 1, and the level of pain after provocation decreased from 7 to 2 (p<0.001). All patients were able to return to work 3 months after surgery, and 80% were able to resume their pre-injury level of sport activity.Conclusion:The clinical outcome after arthroscopic debridement for osteochondritis dissecans of the elbow shows good results, with pain relief during activities of daily living and sport. The function of the elbow, as reflected by the MAESS score, improved from poor to excellent. All patients in this series will be reviewed after 5 years to determine long-term results.
The validation of a novel activity monitor in the measurement of posture and motion during everyday activities
Authors: Grant P M , Ryan C G , Tigbe W W , Granat M H 
Published: September 2006

Background:Accurate measurement of physical activity patterns can be used to identify sedentary behaviour and may facilitate interventions aimed at reducing inactivity.Objective:To evaluate theactivPAL physical activity monitor as a measure of posture and motion in everyday activities using observational analysis as the criterion standard.Methods:Wearing threeactivPAL monitors, 10 healthy participants performed a range of randomly assigned everyday tasks incorporating walking, standing and sitting. Each trial was captured on a digital camera and the recordings were synchronised with theactivPAL. The time spent in different postures was visually classified and this was compared with theactivPAL output.Results:Intraclass correlation coefficients (ICC 2,1) for interdevice reliability ranged from 0.79 to 0.99. Using the Bland and Altman method, the mean percentage difference between theactivPAL monitor and observation for total time spent sitting was 0.19% (limits of agreement −0.68% to 1.06%) and for total time spent upright was −0.27% (limits of agreement −1.38% to 0.84%). The mean difference for total time spent standing was 1.4% (limits of agreement −6.2% to 9.1%) and for total time spent walking was −2.0% (limits of agreement −16.1% to 12.1%). A second-by-second analysis between observer and monitor found an overall agreement of 95.9%.Conclusion:TheactivPAL activity monitor is a valid and reliable measure of posture and motion during everyday physical activities.
Efficiency Considerations for Vertical kNN Text Categorisation
Authors: Rahal Imad , Najadat Hassan , Perrizo William 
Published: September 2006

The importance of text mining stems from the availability of huge volumes of text databases holding a wealth of valuable information that needs to be mined. Text mining is a coarse area encompassing many finer branches one of which is text categorisation or text classification. Text categorisation is the process of assigning class labels to documents based entirely on their textual contents where we are given a document d, and asked to find its subject matter or class label, Ci. In this paper, an optimised k-Nearest Neighbours classifier that uses discretisation, the P-tree technology, and dimensionality reduction to achieve a high degree of accuracy, space utilisation and time efficiency is proposed. One of the fundamental contributions of this work is that as new samples arrive, the proposed classifier can find the k nearest neighbours to the new sample from the training space without a single database scan.
Aberrant Expression of a Disintegrin and Metalloproteinase 17/Tumor Necrosis Factor-α Converting Enzyme Increases the Malignant Potential in Human Pancreatic Ductal Adenocarcinoma
Authors: Ringel Jörg , Jesnowski Ralf , Moniaux Nicolas , Lüttges Jutta , Ringel Jens , Choudhury Amit , Batra Surinder K. , Klöppel Günter , Löhr Matthias 
Published: September 2006

AbstractA disintegrin and metalloproteinase (ADAM) molecules are known for their unique potential to combine adhesion, proteolysis, and signaling. To understand the role of ADAM17/tumor necrosis factor-α (TNF-α) converting enzyme (TACE) in pancreatic ductal adenocarcinoma (PDAC), we investigated its expression, function, and in vitro regulation. ADAM17/TACE mRNA was expressed in 3 of 10 normal pancreatic tissues, 6 of 8 samples from patients with chronic pancreatitis, 10 of 10 PDAC tissues, and 9 of 9 pancreatic cancer cell lines, but it was absent in primary duct epithelial cells. Immunohistochemical staining revealed positive cancer cells in 8 of 10 PDACs but no staining of ducts in normal pancreas. ADAM17/TACE was found in 0 of 16 pancreatic intraepithelial neoplasia (PanIN)-1A lesions, 1 of 30 PanIN-1B lesions, 2 of 13 PanIN-2 lesions but, in 13 of 15 PanIN-3 lesions, associated with PDAC. Western blot, flow cytometry, and confocal microscopy analyses showed the aberrant expression of ADAM17/TACE protein in pancreatic cancer cell lines. The proteolytic activity of ADAM17/TACE, assessed by the release of TNF-α, was inhibited by TNF-α protease inhibitor. ADAM17/TACE gene silencing using small interfering RNA technique in vitro reduced invasion behavior dramatically, whereas proliferation was unaffected. Furthermore, ADAM17/TACE mRNA expression was down-regulated in pancreatic cancer cells arrested in G2-M phase as well as in a time-dependent manner after TNF-α and interleukin-6 incubation. In conclusion, our findings provide evidence of aberrant expression of the proteolytically active ADAM17/TACE in advanced precursor lesions (PanIN-3) and PDAC while identifying its critical involvement in the invasion process. (Cancer Res 2006; 66(18): 9045-53)
Role of p53 Up-regulated Modulator of Apoptosis and Phosphorylated Akt in Melanoma Cell Growth, Apoptosis, and Patient Survival
Authors: Karst Alison M. , Dai Derek L. , Cheng Jin Q. , Li Gang 
Published: September 2006

Abstract
Malignant melanoma is an aggressive and chemoresistant form of skin cancer characterized by rapid metastasis and poor patient prognosis. The development of innovative therapies with improved efficacy is critical to treatment of this disease. Here, we show that aberrant expression of two proteins, p53 up-regulated modulator of apoptosis (PUMA) and phosphorylated Akt (p-Akt), is associated with poor patient survival. Using tissue microarray analysis, we found that patients exhibiting both weak PUMA expression and strong p-Akt expression in their melanoma tumor tissue had significantly worse 5-year survival than patients with either weak PUMA or strong p-Akt expression alone (P &lt; 0.001). Strikingly, no patients exhibiting strong PUMA expression and weak p-Akt expression in primary tumor tissue died within 5 years of diagnosis. We propose a two-pronged therapeutic strategy of (a) boosting PUMA expression and (b) inhibiting Akt phosphorylation in melanoma tumor tissue. Here, we report that a recombinant adenovirus containing human PUMA cDNA (ad-PUMA) efficiently inhibits human melanoma cell survival in vitro, rapidly induces apoptosis, and dramatically suppresses human melanoma tumor growth in a severe combined immunodeficient mouse xenograft model. In melanoma cells strongly expressing p-Akt, we show that Akt/protein kinase B signaling inhibitor-2 (API-2; a small-molecule Akt inhibitor) reduces cell survival in a dose- and time-dependent manner and enhances ad-PUMA-mediated growth inhibition of melanoma cells. Finally, we show that, by combining ad-PUMA and API-2 treatments, human melanoma tumor growth can be inhibited by &gt;80% in vivo compared with controls. Our results suggest that a strategy to correct dysregulated PUMA and p-Akt expression in malignant melanoma may be an effective therapeutic option. (Cancer Res 2006; 66(18): 9221-6)
Anticancer Activity of BIM-46174, a New Inhibitor of the Heterotrimeric Gα/Gβγ Protein Complex
Authors: Prévost Grégoire P. , Lonchampt Marie O. , Holbeck Susan , Attoub Samir , Zaharevitz Daniel , Alley Mike , Wright John , Brezak Marie C. , Coulomb Hélène , Savola Ann , Huchet Marion , Chaumeron Sophie , Nguyen Quang-Dé , Forgez Patricia , Bruyneel Erik , Bracke Mark , Ferrandis Eric , Roubert Pierre , Demarquay Danièle , Gespach Christian , Kasprzyk Philip G. 
Published: September 2006

Abstract
A large number of hormones and local agonists activating guanine-binding protein-coupled receptors (GPCR) play a major role in cancer progression. Here, we characterize the new imidazo-pyrazine derivative BIM-46174, which acts as a selective inhibitor of heterotrimeric G-protein complex. BIM-46174 prevents the heterotrimeric G-protein signaling linked to several GPCRs mediating (a) cyclic AMP generation (Gαs), (b) calcium release (Gαq), and (c) cancer cell invasion by Wnt-2 frizzled receptors and high-affinity neurotensin receptors (Gαo/i and Gαq). BIM-46174 inhibits the growth of a large panel of human cancer cell lines, including anticancer drug-resistant cells. Exposure of cancer cells to BIM-46174 leads to caspase-3-dependent apoptosis and poly(ADP-ribose) polymerase cleavage. National Cancer Institute COMPARE analysis for BIM-46174 supports its novel pharmacologic profile compared with 12,000 anticancer agents. The growth rate of human tumor xenografts in athymic mice is significantly reduced after administration of BIM-46174 combined with either cisplatin, farnesyltransferase inhibitor, or topoisomerase inhibitors. Our data validate the feasibility of targeting heterotrimeric G-protein functions downstream the GPCRs to improve anticancer chemotherapy. (Cancer Res 2006; 66(18): 9227-34)
Death Receptor-3, a New E-Selectin Counter-Receptor that Confers Migration and Survival Advantages to Colon Carcinoma Cells by Triggering p38 and ERK MAPK Activation
Authors: Gout Stéphanie , Morin Chantale , Houle François , Huot Jacques 
Published: September 2006

Abstract
E-selectin-mediated adhesion of colon cancer cells to endothelial cells is a key event in metastasis. However, the signaling mechanisms that confer metastatic advantages to cancer cells adhering to E-selectin are ill defined. By using affinity column chromatography and pull-down assays on purified membrane extracts of HT29 and LoVo cells coupled to mass spectrometry analysis, we obtained the first evidence indicating that E-selectin binds to death receptor-3 (DR3) expressed by the cancer cells. Thereafter, we accumulated several results, suggesting that DR3 is an E-selectin receptor on colon cancer cells and that its activation by E-selectin triggers the activation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) and confers migration and survival advantages. First, by Western blotting, we found that the E-selectin-binding protein, identified as DR3, is recognized by two anti-DR3 antibodies. Second, the neutralization of DR3 with an antibody and its knockdown by small interfering RNA decrease the adhesion of colon cancer cells to E-selectin and E-selectin-expressing human umbilical vein endothelial cells. Third, inhibiting DR3 and knocking down its expression impair transendothelial migration of HT29 cells and block the activation of p38 and ERK by E-selectin. Fourth, high molecular weight isoforms of DR3 are expressed in samples of primary human colon carcinoma but not in samples from normal colon tissue. Intriguingly, DR3 is a death receptor but its activation by E-selectin does not induce apoptosis in colon cancer cells, except when ERK is inhibited. Our findings identify novel signaling and functional roles of DR3 activated in response to E-selectin and highlight the potential link between DR3 and metastasis. (Cancer Res 2006; 66(18): 9117-24)
HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker
Authors: Ogino Takeshi , Shigyo Hiroshi , Ishii Hideyuki , Katayama Akihiro , Miyokawa Naoyuki , Harabuchi Yasuaki , Ferrone Soldano 
Published: September 2006

AbstractWe have investigated the role of antigen-processing machinery (APM) component defects in HLA class I antigen down-regulation in laryngeal squamous cell carcinoma (SCC) lesions and assessed the clinical significance of these defects. To this end, 63 formalin-fixed, paraffin-embedded tumor lesions were examined for APM component and HLA class I antigen expression by immunohistochemistry. Calnexin, calreticulin, and ERp57 were down-regulated in ∼25% of the lesions tested, whereas LMP2, TAP1, tapasin, and HLA class I antigens were down-regulated in at least 70% of the lesions tested. LMP2 and tapasin expression was significantly correlated with HLA class I antigen expression suggesting APM component defects as a mechanism underlying HLA class I antigen down-regulation in laryngeal SCC lesions. The expression of most APM components and HLA class I antigens was correlated with the extent of CD8+ T cell infiltration into tumor lesions. Furthermore, LMP2 and HLA class I antigen down-regulation and low CD8+ T cell infiltration were significantly associated with reduced patients' survival. Multivariate analysis identified HLA class I antigen down-regulation as an independent unfavorable prognostic marker. This association is likely to reflect the reduction in the extent of CD8+ T cell infiltration in laryngeal SCC lesions. (Cancer Res 2006; 66(18): 9281-9)
A Mouse Model for the Molecular Characterization of Brca1-Associated Ovarian Carcinoma
Authors: Xing Deyin , Orsulic Sandra 
Published: September 2006

Abstract
Little is known about the mechanisms that underlie Brca1-associated ovarian tumorigenesis, mainly due to the lack of an appropriate experimental model. We developed genetically defined primary mouse ovarian surface epithelial (OSE) cell lines in which the loss of functional Brca1 and p53 recapitulates the events that are thought to occur in early ovarian cancer development in patients with Brca1 mutations. This system allows for the introduction of additional oncogenes that are thought to cooperate with the loss of Brca1 and p53 to induce tumorigenesis. We showed that Myc is sufficient to induce transformation of ovarian cells that are deficient for both Brca1 and p53 but not sufficient for the transformation of cells that are deficient for either Brca1 or p53. The transformed Brca1-deficient OSE cells display an increased number of centrosomes, acquire complex chromosome aberrations, and lack Rad51 nuclear foci in the presence of DNA-damaging agents, such as mitomycin C and cisplatin. Immunocompetent mice injected with transformed OSE cells develop tumors that resemble human metastatic serous ovarian carcinoma, the most common type of ovarian cancer in women. Consistent with the reported platinum chemosensitivity in patients with Brca1-associated ovarian cancer, the Brca1-deficient OSE cells have increased sensitivity to the DNA-damaging agent cisplatin, whereas sensitivity to the microtubule poison paclitaxel is similar between Brca1 wild-type and Brca1-deficient cells. The Brca1 wild-type and Brca1-deficient mouse ovarian tumors and cell lines provide a new experimental system for the evaluation of therapies that target the Brca1 pathway. (Cancer Res 2006; 66(18): 8949-53)