bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bortezomib and Depsipeptide Sensitize Tumors to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand: A Novel Method to Potentiate Natural Killer Cell Tumor Cytotoxicity
Authors: Lundqvist Andreas , Abrams Scott I. , Schrump David S. , Alvarez Gauri , Suffredini Dante , Berg Maria , Childs Richard 
Published: July 2006

AbstractThe proteasome inhibitor, bortezomib, and the histone deacetylase inhibitor, depsipeptide (FK228), up-regulate tumor death receptors. Therefore, we investigated whether pretreatment of malignant cells with these agents would potentiate natural killer (NK)–mediated tumor killing. NK cells isolated from healthy donors and patients with cancer were expanded in vitro and then tested for cytotoxicity against tumor cell lines before and after exposure to bortezomib or depsipeptide. In 11 of 13 (85%) renal cell carcinoma cell lines and in 16 of 37 (43%) other cancer cell lines, exposure to these drugs significantly increased NK cell–mediated tumor lysis compared with untreated tumor controls (P &lt; 0.001). Furthermore, NK cells expanded from patients with metastatic renal cell carcinoma were significantly more cytotoxic against autologous tumor cells when pretreated with either bortezomib or depsipeptide compared with untreated tumors. Tumors sensitized to NK cell cytotoxicity showed a significant increase in surface expression of DR5 [tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)-R2; P &lt; 0.05]; in contrast, surface expression of MHC class I, MIC-A/B, DR4 (TRAIL-R1), and Fas (CD95) did not change. The enhanced susceptibility to NK cell killing was completely abolished by blocking TRAIL on NK cells, and partially abolished by blocking DR5 on tumor cells. These findings show that drug-induced sensitization to TRAIL could be used as a novel strategy to potentiate the anticancer effects of adoptively infused NK cells in patients with cancer. (Cancer Res 2006; 66(14): 7317-25)
The G-quadruplex Ligand Telomestatin Inhibits POT1 Binding to Telomeric Sequences In vitro and Induces GFP-POT1 Dissociation from Telomeres in Human Cells
Authors: Gomez Dennis , O'Donohue Marie-Françoise , Wenner Thomas , Douarre Céline , Macadré Jérome , Koebel Pascale , Giraud-Panis Marie-Josèphe , Kaplan Hervé , Kolkes Alain , Shin-ya Kazuo , Riou Jean-François 
Published: July 2006

Abstract
Telomestatin is a potent G-quadruplex ligand that specifically interacts with the 3′ telomeric overhang, leading to its degradation and that induces a delayed senescence and apoptosis of cancer cells. Protection of Telomere 1 (POT1) was recently identified as a specific single-stranded telomere-binding protein involved in telomere capping and T-loop maintenance. We showed here that a telomestatin treatment inhibits POT1 binding to the telomeric overhang in vitro. The treatment of human EcR293 cells by telomestatin induces a dramatic and rapid delocalization of POT1 from its normal telomere sites but does not affect the telomere localization of the double-stranded telomere-binding protein TRF2. Thus, we propose that G-quadruplex stabilization at telomeric G-overhang inactivates POT1 telomeric function, generating a telomere dysfunction in which chromosome ends are no longer properly protected. (Cancer Res 2006; 66(14): 6908-12)
Hypomethylated P4 Promoter Induces Expression of the Insulin-Like Growth Factor-II Gene in Hepatocellular Carcinoma in a Chinese Population
Authors: Tang Shao Hui , Yang Dong Hua , Huang Wei , Zhou Hong Ke , Lu Xiao Hua , Ye Gang 
Published: July 2006

Abstract
Purpose: The expression of human insulin-like growth factor-II (IGF-II) is regulated by the activation of four promoters (P1-P4) acting in a development-dependent, tissue-specific manner. IGF-II overexpression associated with P3 and P4 activation is observed in animal and human hepatocarcinogenesis. We correlated P4 epigenetic alteration with P4 transcript activation and clinicopathologic features.
Experimental Design: We analyzed P4 epigenetic alteration using methylation-specific PCR in 34 hepatocellular carcinoma (HCC) specimens, 34 matched adjacent nontumor specimens, and 8 normal adult liver specimens. The data were correlated with activation of P4 transcription by using reverse transcription-PCR. Epigenetic alteration was compared with patients' clinicopathologic features.
Results: Compared with normal liver tissue, hypomethylation of P4 CpG islands was significantly more frequent in HCC (P = 0.03) and matched tissues (P = 0.047). P4 mRNA levels in HCC with unmethylated alleles were significantly higher than in HCC without unmethylated alleles (P = 0.001); P4 mRNA levels in matched nontumor tissues with unmethylated alleles were significantly higher than in matched nontumor tissues without unmethylated alleles (P = 0.005). P4 hypomethylation in HCC was associated with portal vein tumor embolus (P = 0.017) and poorer tumor differentiation (P = 0.025).
Conclusions: These findings suggest that IGF-II P4 hypomethylation may be an early and frequent event and that it may contribute to P4 transcription expression activation during the transformation of a premalignant liver lesion to HCC. Furthermore, aberrant hypomethylation of P4 CpG islands not only may play an important role during hepatocarcinogenesis but might also be a useful biomarker for poor prognosis of patients with HCC.
From Areopagus to Corinth (Acts 17:22–31; I Cor 2:1–5) A Study on the Transition from the Power of Knowledge to the Power of the Spirit
Authors: Pathrapankal Joseph 
Published: July 2006

AbstractHow are we to understand Christian mission in our time? Is it the obedient response to the commission of his disciples by Jesus after his resurrection (Mt 28:18–20)? What should be the motivating power behind the mission of the church? Is it patterned on the conquest expeditions of the people of Israel narrated in the Old Testament? The long history of the mission of the church, especially as organized by the West, would give us such an impression. This approach has more the nature of exercising power over the other, the power of knowledge and the power of self to win over the other. From the time of the Roman Emperor, Constantine, this had been the pattern in the history of the western church. But times have changed and there is a real shift in the understanding of Christian mission in the context of religious pluralism. The Bible itself seems to support and substantiate this change of perspective of understanding mission as the operation of the power of the Spirit of God. Taking two New Testament writings, the Acts of the Apostles and the first Letter to the Corinthians as paradigms, the author tries to see how Paul first of all attempted to preach the gospel in Athens with the eloquence and wisdom of the Greeks and then changed his approach in Corinth to give centrality to the power of the Spirit of God. Although we may not argue for a historical sequence for this change of attitude in the case of Paul, applying new developments in biblical interpretation, we can still propose it as a trans-textual approach with a message for our time. The Word of God has within itself a dynamism to take on new meanings and new horizons of ideas through its encounter with new contexts in a pluralistic world.
Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke
Authors: Machado Livia S , Kozak Anna , Ergul Adviye , Hess David C , Borlongan Cesario V , Fagan Susan C 
Published: July 2006

Abstract

Background
Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are increased in the brain after experimental ischemic stroke in rats. These two proteases are involved with the degradation of the basal lamina and loss of stability of the blood brain barrier that occurs after ischemia and that is associated with thrombolytic therapy in ischemic stroke. Minocycline is a lipophilic tetracycline and is neuroprotective in several models of brain injury. Minocycline inhibits inflammation, apoptosis and extracellular matrix degradation. In this study we investigated whether delayed minocycline inhibits brain MMPs activated by ischemia in a model of temporary occlusion in Wistar rats.

Results
Both MMP-2 and MMP-9 were elevated in the ischemic tissue as compared to the contra-lateral hemisphere after 3 hours occlusion and 21 hours survival (p < 0.0001 for MMP-9). Intraperitoneal minocycline at 45 mg/kg concentration twice a day (first dose immediately after the onset of reperfusion) significantly reduced gelatinolytic activity of ischemia-elevated MMP-2 and MMP-9 (p < 0.0003). Treatment also reduced protein concentration of both enzymes (p < 0.038 for MMP-9 and p < 0.018 for MMP-2). In vitro incubation of minocycline in concentrations as low as 0.1 μg/ml with recombinant MMP-2 and MMP-9 impaired enzymatic activity and MMP-9 was more sensitive at lower minocycline concentrations (p < 0.05).

Conclusion
Minocycline inhibits enzymatic activity of gelatin proteases activated by ischemia after experimental stroke and is likely to be selective for MMP-9 at low doses. Minocycline is a potential new therapeutic agent to acute treatment of ischemic stroke.
The frequency of genes encoding three putative group B streptococcal virulence factors among invasive and colonizing isolates
Authors: Manning Shannon D , Ki Moran , Marrs Carl F , Kugeler Kiersten J , Borchardt Stephanie M , Baker Carol J , Foxman Betsy 
Published: July 2006

Abstract

Background
Group B Streptococcus (GBS) causes severe infections in very young infants and invasive disease in pregnant women and adults with underlying medical conditions. GBS pathogenicity varies between and within serotypes, with considerable variation in genetic content between strains. Three proteins, Rib encoded by rib, and alpha and beta C proteins encoded by bca and bac, respectively, have been suggested as potential vaccine candidates for GBS. It is not known, however, whether these genes occur more frequently in invasive versus colonizing GBS strains.

Methods
We screened 162 invasive and 338 colonizing GBS strains from different collections using dot blot hybridization to assess the frequency of bca, bac and rib. All strains were defined by serotyping for capsular type, and frequency differences were tested using the Chi square test.

Results
Genes encoding the beta C protein (bac) and Rib (rib) occurred at similar frequencies among invasive and colonizing isolates, bac (20% vs. 23%), and rib (28% vs. 20%), while the alpha (bca) C protein was more frequently found in colonizing strains (46%) vs, invasive (29%). Invasive strains were associated with specific serotype/gene combinations.

Conclusion
Novel virulence factors must be identified to better understand GBS disease.
An immune response in the bumblebee, Bombus terrestris leads to increased food consumption
Authors: Tyler Elizabeth R , Adams Sally , Mallon Eamonn B 
Published: July 2006

Abstract

Background
The concept of a costly immune system that must be traded off against other important physiological systems is fundamental to the burgeoning field of ecological immunity. Bumblebees have become one of the central models in this field. Although previous work has demonstrated costs of immunity in numerous life history traits, estimates of the more direct costs of bumblebee immunity have yet to be made.

Results
Here we show a 7.5% increase in energy consumption in response to non-pathogenic immune stimulation.

Conclusion
This increase in energy consumption along with other results suggests that immunity is one of the most important physiological systems, with other systems being sacrificed for its continuing efficiency. This increased consumption and maintained activity contrasts with the sickness-induced anorexia and reduced activity found in vertebrates.
A systematic review of complex system interventions designed to increase recovery from depression in primary care
Authors: Gunn Jane , Diggens Justine , Hegarty Kelsey , Blashki Grant 
Published: July 2006

AbstractBackgroundPrimary care is being encouraged to implement multiprofessional, system level, chronic illness management approaches to depression. We undertook this study to identify and assess the quality of RCTs testing system level depression management interventions in primary care and to determine whether these interventions improve recovery.MethodSearches of Medline and Cochrane Controlled Register of Trials. 'System level' interventions included: multi-professional approach, enhanced inter-professional communication, scheduled patient follow-up, structured management plan.Results11 trials met all inclusion criteria. 10 were undertaken in the USA. Most focussed on antidepressant compliance. Quality of reporting assessed using CONSORT criteria was poor. Eight trials reported an increase in the proportion of patients recovered in favour of the intervention group, yet did not account for attrition rates ranging from 5 to 50%.ConclusionSystem level interventions implemented in the USA with patients willing to take anti-depressant medication leads to a modest increase in recovery from depression. The relevance of these interventions to countries with strong primary care systems requires testing in a randomised controlled trial.
Implementation of a structured paediatric admission record for district hospitals in Kenya – results of a pilot study
Authors: Mwakyusa Sekela , Wamae Annah , Wasunna Aggrey , Were Fred , Esamai Fabian , Ogutu Bernhards , Muriithi Assumpta , Peshu Norbert , English Mike 
Published: July 2006

AbstractBackgroundThe structured admission form is an apparently simple measure to improve data quality. Poor motivation, lack of supervision, lack of resources and other factors are conceivably major barriers to their successful use in a Kenyan public hospital setting. Here we have examined the feasibility and acceptability of a structured paediatric admission record (PAR) for district hospitals as a means of improving documentation of illness.MethodsThe PAR was primarily based on symptoms and signs included in the Integrated Management of Childhood Illness (IMCI) diagnostic algorithms. It was introduced with a three-hour training session, repeated subsequently for those absent, aiming for complete coverage of admitting clinical staff. Data from consecutive records before (n = 163) and from a 60% random sample of dates after intervention (n = 705) were then collected to evaluate record quality. The post-intervention period was further divided into four 2-month blocks by open, feedback meetings for hospital staff on the uptake and completeness of the PAR.ResultsThe frequency of use of the PAR increased from 50% in the first 2 months to 84% in the final 2 months, although there was significant variation in use among clinicians. The quality of documentation also improved considerably over time. For example documentation of skin turgor in cases of diarrhoea improved from 2% pre-intervention to 83% in the final 2 months of observation. Even in the area of preventive care documentation of immunization status improved from 1% of children before intervention to 21% in the final 2 months.ConclusionThe PAR was well accepted by most clinicians and greatly improved documentation of features recommended by IMCI for identifying and classifying severity of common diseases. The PAR could provide a useful platform for implementing standard referral care treatment guidelines.
Prevalence of diabetes and other cardiovascular risk factors in an Iranian population with acute coronary syndrome
Authors: Esteghamati Alireza , Abbasi Mehrshad , Nakhjavani Manouchehr , Yousefizadeh Abbas , Basa Amelita P , Afshar Hamid 
Published: July 2006

Abstract

Background
Coronary artery disease is the leading cause of death in industrialized countries and most patients with diabetes die from complications of atherosclerosis. The objective of this study was to determine the presence of diabetes mellitus and other conventional coronary heart disease risk factors (cigarette smoking, hypertension and hyperlipidemia) in patients with acute coronary events in an Iranian population.

Methods
The study included 514 patients with unstable angina or myocardial infarction (MI) out of 720 patients admitted to CCU ward of a general hospital from March 2003 to March 2005. History of diabetes, hypertension and cigarette smoking, demographic indices, coronary heart disease and diabetes mellitus treatment, myocardial enzymes, serum triglycerides (TG) and cholesterol and fasting and non fasting blood glucose levels and HbA1C of diabetics were recorded of admission sheets. The data were structured to appropriate one way ANOVA, T tests, and chi square test with SPSS 13 product for windows.

Results
Out of all patients 35.8% were female, 30% were diabetics (Duration 13.4 ± 8.7 years), 42% were smoker and 91% were hypertensive. Twenty four percent had MI and 76% had unstable angina. MI was significantly higher in diabetic patients (36.4% vs. 19.2%, P < 0.001). Location and extension of MI and myocardial enzymes did not differ between diabetics and non-diabetic patients. Diabetic patients were older than non diabetics (65 ± 11.6 vs. 59.7 ± 12.5 years, p < 0.05). Five (66.7%) out of 9 patients with fatal MI were diabetics (Odds Ratio = 2.98). Age, duration of diabetes and HbA1c levels, did not differ between diabetic patients with or without MI. Hypertension and current smoking was significantly higher in patients with MI compared to patients with unstable angina (p < 0.05). Serum TG, HDL-C, LDL-C and total cholesterol level did not differ between patients with MI and unstable angina. Diabetic patients compare to non diabetic patients were more hypertensive (96% vs. 88.7%, p < 0.005) and had higher serum triglyceride (TG over 200 mg/dl, 35.1% vs. 26.4, p <0.05). Diabetes was more frequent among women than men (36.4% vs. 26.4%, p < 0.05). Women were older than men (65 ± 11.6 vs. 59.2 ± 13 years, p < 0.005) and had higher total serum cholesterol (200 ± 41.8 vs. 192 ± 42.5 mg/dl, p < 0.05) and HDL-C levels (49.7 ± 22 vs. 40 ± 13 mg/dl, p < 0.005). Ninety seven percent of all patients had at least one of cardiovascular risk factors (hypertension, smoking, diabetes, high cholesterol and low HDL-cholesterol levels).

Conclusion
In this study 19 out of 20 patients with acute coronary event have at least one of conventional cardiac risk factors. Diabetes and hypertension are leading risk factors, which may directly or indirectly interfere and predict more serious complications of coronary heart disease.
Non-differential measurement error does not always bias diagnostic likelihood ratios towards the null
Authors: Fosgate GT 
Published: July 2006

AbstractDiagnostic test evaluations are susceptible to random and systematic error. Simulated non-differential random error for six different error distributions was evaluated for its effect on measures of diagnostic accuracy for a brucellosis competitive ELISA. Test results were divided into four categories: <0.25, 0.25 – 0.349, 0.35 – 0.499, and ≥ 0.50 proportions inhibition for calculation of likelihood ratios and diagnostic odds ratios. Larger variance components of the error structure resulted in larger accuracy attenuations as measured by the area under the receiver-operating characteristic curve and systematic components appeared to cause little bias. Added error caused point estimates of likelihood ratios to be biased towards the null value (1.0) for all categories except 0.25 – 0.349. Results for the 0.35 – 0.499 category also extended beyond the null value for some error structures. Diagnostic odds ratios were consistently biased towards the null when the <0.25 category was considered the reference level. Non-differential measurement error can lead to biased results in the quantitative evaluation of ELISA and the direction is not always towards the null value.
A radial basis classifier for the automatic detection of aspiration in children with dysphagia
Authors: Lee Joon , Blain Stefanie , Casas Mike , Kenny Dave , Berall Glenn , Chau Tom 
Published: July 2006

AbstractBackgroundSilent aspiration or the inhalation of foodstuffs without overt physiological signs presents a serious health issue for children with dysphagia. To date, there are no reliable means of detecting aspiration in the home or community. An assistive technology that performs in these environments could inform caregivers of adverse events and potentially reduce the morbidity and anxiety of the feeding experience for the child and caregiver, respectively. This paper proposes a classifier for automatic classification of aspiration and swallow vibration signals non-invasively recorded on the neck of children with dysphagia.MethodsVibration signals associated with safe swallows and aspirations, both identified via videofluoroscopy, were collected from over 100 children with neurologically-based dysphagia using a single-axis accelerometer. Five potentially discriminatory mathematical features were extracted from the accelerometry signals. All possible combinations of the five features were investigated in the design of radial basis function classifiers. Performance of different classifiers was compared and the best feature sets were identified.ResultsOptimal feature combinations for two, three and four features resulted in statistically comparable adjusted accuracies with a radial basis classifier. In particular, the feature pairing of dispersion ratio and normality achieved an adjusted accuracy of 79.8 ± 7.3%, a sensitivity of 79.4 ± 11.7% and specificity of 80.3 ± 12.8% for aspiration detection. Addition of a third feature, namely energy, increased adjusted accuracy to 81.3 ± 8.5% but the change was not statistically significant. A closer look at normality and dispersion ratio features suggest leptokurticity and the frequency and magnitude of atypical values as distinguishing characteristics between swallows and aspirations. The achieved accuracies are 30% higher than those reported for bedside cervical auscultation.ConclusionThe proposed aspiration classification algorithm provides promising accuracy for aspiration detection in children. The classifier is conducive to hardware implementation as a non-invasive, portable "aspirometer". Future research should focus on further enhancement of accuracy rates by considering other signal features, classifier methods, or an augmented variety of training samples. The present study is an important first step towards the eventual development of wearable intelligent intervention systems for the diagnosis and management of aspiration.