bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting p53-Null Neuroblastomas through RLIP76
Authors: Singhal Jyotsana , Yadav Sushma , Nagaprashantha Lokesh Dalasanur , Vatsyayan Rit , Singhal Sharad S. , Awasthi Sanjay
Published: March 2011

The search for p53-independent mechanism of cancer cell killing is highly relevant to pediatric neuroblastomas, where successful therapy is limited by its transformation into p53-mutant and a highly drug-resistant neoplasm. Our studies on the drug-resistant p53-mutant as compared with drug-resistant p53 wild-type neuroblastoma revealed a novel mechanism for resistance to apoptosis: a direct role of p53 in regulating the cellular concentration of proapoptotic alkenals by functioning as a specific and saturable allosteric inhibitor of the alkenal–glutathione conjugate transporter, RLIP76. The RLIP76-p53 complex was showed by both immunoprecipitation analyses of purified proteins and immunofluorescence analysis. Drug transport studies revealed that p53 inhibited both basal and PKCα-stimulated transport of glutathione conjugates of 4HNE (GSHNE) and doxorubicin. Drug resistance was significantly greater for p53-mutant as compared with p53 wild-type neuroblastoma cell lines, but both were susceptible to depletion of RLIP76 by antisense alone. In addition, inhibition of RLIP76 significantly enhanced the cytotoxicity of cisplatin. Taken together, these studies provide powerful evidence for a novel mechanism for drug and apoptosis resistance in p53-mutant neuroblastoma, based on a model of regulation of p53-induced apoptosis by RLIP76, where p53 is a saturable and specific allosteric inhibitor of RLIP76, and p53 loss results in overexpression of RLIP76; thus, in the absence of p53, the drug and glutathione-conjugate transport activities of RLIP76 are enhanced. Most importantly, our findings strongly indicate RLIP76 as a novel target for therapy of drug-resistant and p53-mutant neuroblastoma. Cancer Prev Res; 4(6); 879–89. ©2011 AACR.
What Is It like to Be a Person with Schizophrenia in the Social World? A First-Person Perspective Study on Schizophrenic Dissociality – Part 1: State of the Art
Authors: Stanghellini Giovanni , Ballerini Massimo
Published: March 2011

This is a critical review of research on the subjective experience of social dysfunction in persons with schizophrenia. Studies from the phenomenological and cognitive paradigms are examined, and significant outcomes and shortcomings are pointed out. Clinical phenomenologists have mainly interpreted schizophrenic dissociality as an anomaly of prereflexive attunement. The main shortcoming of phenomenological research is that it lacks adequate methodology to collect reliable data since most studies are based on the analysis of a few typical cases. Cognitivism has reliably documented disorders of social functioning in large-scale experimental studies. The main shortcoming of most cognitive paradigms is that they do not properly investigate the personal level of experience in real-world functioning. We conclude that there is a need to reliably collect data through quantitative as well as qualitative methodology as established and accepted by the scientific community in the area of schizophrenic dissociality, reflecting the subjective experiences of people with schizophrenia in the real world.
Expansion of CD56-Negative, CD16-Positive, KIR-Expressing Natural Killer Cells after T Cell-Depleted Haploidentical Hematopoietic Stem Cell Transplantation
Authors: De Angelis Claudia , Mancusi Antonella , Ruggeri Loredana , Capanni Marusca , Urbani Elena , Velardi Andrea , Stern Martin
Published: March 2011

The main functions of natural killer (NK) cells are early protection against viruses or tumor cells and production of cytokines that regulate immune functions. The present study assessed the role of different NK subsets in exerting graft-versus-leukemia effects in recipients of human leukocyte antigen (HLA) haploidentical hematopoietic transplants and monitored for the first time CD3–/CD56– lymphocyte expansion. CD3–/CD56– cells expressed NK cell-associated molecules, such as CD16, NKp46, NKp30, CD244 (2B4), CD161, and killer cell immunoglobulin-like receptors. CD3–/CD56– cells further exhibited the classical functional characteristics of NK cells: cytolysis of target cells lacking HLA class I, antibody-dependent cellular cytotoxicity and cytokine production. These results demonstrate that CD56– NK cells are functional, recognize missing self and, like their CD56+ counterparts, may contribute to graft-versus-leukemia reactions.
Expression of Genes Controlling Testicular Development in Adult Testis of the Seasonally Breeding Iberian Mole
Authors: Dadhich R.K. , Barrionuevo F.J. , Lupiañez D.G. , Real F.M. , Burgos M. , Jiménez R.
Published: March 2011

Most testicular features undergo major circannual variation in seasonal breeding species. Although the ultimate cause of these variations is known to be the photoperiod in most cases, very little is known about the genetic mechanisms by which these changes are modulated in the testis. Many genes involved in testis development are known to be expressed in the adult testis as well. Since these genes encode genetic regulatory factors, it is reasonable to suspect that they could play some role in the control of the adult testis function. Using immunological detection techniques and RT-Q-PCR, we have studied the spatio-temporal expression pattern of WT1, SF1, SOX9, AMH, and DMRT1 in 4 representative stages of the circannual cycle of the testes of Talpa occidentalis, a mole species with strict seasonal reproduction. AMH is not expressed at any stage of the cycle, showing that inactive adult testes are functionally different from pre-pubertal, juvenile ones. The continuous presence of primary spermatocytes may explain the permanent repression of AMH in the mole testis. WT1 and SF1 are down-regulated and SOX9 is up-regulated in regressed mole testes, suggesting that the modulation of the expression of these genes may be involved in the control of circannual gonad variation. Furthermore, SOX9 and DMRT1 show clear spermatogenic stage-dependent expression patterns. Both genes are expressed more intensely during the proliferative stages of spermatogonia, although SOX9 expression is limited to Sertoli cells, whereas DMRT1 is expressed in both Sertoli and spermatogonial cells. Available data suggest that intratesticular levels of testosterone could regulate circannual spermatogenic variations of seasonal breeders by modulating the expression of DMRT1 to control spermatogonial proliferation.
Impact of Acquired Enamel Pellicle Modification on Initial Dental Erosion
Authors: Cheaib Z. , Lussi A.
Published: March 2011

The acquired enamel pellicle that forms on the tooth surface serves as a natural protective barrier against dental erosion. Numerous proteins composing the pellicle serve different functions within this thin layer. Our study examined the effect of incorporated mucin and casein on the erosion-inhibiting potential of the acquired enamel pellicle. Cyclic acidic conditions were applied to mimic the erosive environment present at the human enamel interface during the consumption of soft drinks. One hundred enamel specimens were prepared for microhardness tests and distributed randomly into 5 groups (n = 20) that received the following treatment: deionized water, humidity chamber, mucin, casein, or a combination of mucin and casein. Each group was exposed to 3 cycles of a 2-hour incubation in human saliva, followed by a 2-hour treatment in the testing solution and a 1-min exposure to citric acid. The microhardness analysis demonstrated that the mixture of casein and mucin significantly improved the erosion-inhibiting properties of the human pellicle layer. The addition of individual proteins did not statistically impact the function of the pellicle. These data suggest that protein-protein interactions may play an important role in the effectiveness of the pellicle to prevent erosion.
Identifying Sarcomere Gene Mutations in Hypertrophic Cardiomyopathy
Authors: Seidman Christine E. , Seidman J.G.
Published: March 2011

This review provides an historical and personal perspective on the discovery of genetic causes for hypertrophic cardiomyopathy (HCM). Extraordinary insights by physicians who initially detailed remarkable and varied manifestations of the disorder, collaboration among multidisciplinary teams with skills in clinical diagnostics and molecular genetics, and hard work by scores of trainees solved the etiologic riddle of HCM and unexpectedly demonstrated mutations in sarcomere protein genes as the cause of disease. In addition to celebrating 20 years of genetic research in HCM, this article serves as an introductory overview to a thematic review series that will present contemporary advances in the field of hypertrophic heart disease. Through the continued application of advances in genetic methodologies, combined with biochemical and biophysical analyses of the consequences of human mutations, fundamental knowledge about HCM and sarcomere biology has emerged. Expanding research to elucidate the mechanisms by which subtle genetic variation in contractile proteins remodel the human heart remains an exciting opportunity, one with considerable promise to provide new strategies to limit or even prevent HCM pathogenesis.
A Terrain-Following Coordinate with Smoothed Coordinate Surfaces
Authors: Klemp J. B.
Published: March 2011

An alternative form for a height-based terrain-following coordinate is presented here that progressively smoothes the coordinate surfaces with height to remove smaller scale (steeper) terrain structure from the surfaces. Testing this approach in comparison with traditional and hybrid terrain-following formulations in resting-atmosphere simulations demonstrates that it can significantly reduce artificial circulations caused by inaccuracies in the horizontal pressure gradient term. The simulations also suggest that some further improvement in the accuracy of the horizontal pressure gradient terms can be achieved using a simplified version of Mahrer’s approach, which can be implemented with little increase in computational cost or complexity.
The NSSL Hydrometeor Classification Algorithm in Winter Surface Precipitation: Evaluation and Future Development
Authors: Elmore Kimberly L.
Published: March 2011

The National Severe Storms Laboratory (NSSL) has developed a hydrometeor classification algorithm (HCA) for use with the polarimetric upgrade of the current Weather Surveillance Radar-1988 Doppler (WSR-88D) network. The algorithm was developed specifically for warm-season convection, but it will run regardless of season, and so its performance on surface precipitation type during winter events is examined here. The HCA output is compared with collocated (in time and space) observations of precipitation type provided by the public. The Peirce skill score (PSS) shows that the NSSL HCA applied to winter surface precipitation displays little skill, with a PSS of only 0.115. Further analysis indicates that HCA failures are strongly linked to the inability of HCA to accommodate refreezing below the first freezing level and to errors in the melting-level detection algorithm. Entrants in the 2009 American Meteorological Society second annual artificial intelligence competition developed classification methods that yield a PSS of 0.35 using a subset of available radar data merged with limited environmental data. Thus, when polarimetric radar data and environmental data are appropriately combined, more information about winter surface precipitation type is available than from either data source alone.
Assessment of Forecasts during Persistent Valley Cold Pools in the Bonneville Basin by the North American Mesoscale Model
Authors: Reeves Heather Dawn , Elmore Kimberly L. , Manikin Geoffrey S. , Stensrud David J.
Published: March 2011

North American Mesoscale Model (NAM) forecasts of low-level temperature and dewpoint during persistent valley cold pools in the Bonneville Basin of Utah are assessed. Stations near the east sidewall have a daytime cold and nighttime warm bias. This is due to a poor representation of the steep slopes on this side of the basin. Basin stations where the terrain is better represented by the model have a distinct warm, moist bias at night. Stations in snow-covered areas have a cold bias for both day and night. Biases are not dependent on forecast lead or validation time. Several potential causes for the various errors are considered in a series of sensitivity experiments. An experiment with 4-km grid spacing, which better resolves the gradient of the slopes on the east side of the basin, yields smaller errors along the east corridor of the basin. The NAM assumes all soil water freezes at a temperature of 273 K. This is likely not representative of the freezing temperature in the salt flats in the western part of the basin, since salt reduces the freezing point of water. An experiment testing this hypothesis shows that reducing the freezing point of soil water in the salt flats leads to an average error reduction between 1.5 and 4 K, depending on the station and time of day. Using a planetary boundary layer scheme that has greater mixing alleviates the cold bias over snow somewhat, but the exact source of this bias could not be determined.
Extensionalism in Context
Authors: Bar-Am Nimrod
Published: March 2011

Quine’s philosophy comprises a bewildering set of views whose integrating principle is his “confirmed extensionalism”. The paper offers a historical as well as an intellectual reconstruction of extensionalism. Traditional extensionalism (Boole) freed logic from Aristotelian essentialism that had inhibited the development of logic. Quine’s confirmed extensionalism is the acceptance, as a matter of course, of the validity of Frege’s criticism of [Boole’s] extensionalism. His confirmed extensionalism is a generalized version of the philosophy of science known as conventionalism. As such, it places the advancement of science outside the province of science proper. It is, thus, at odds with Quine’s repeated expressions of alliance with the Popperian (hypothetico-deductive) model of science.
Validation of a Job Satisfaction Scale in the Australian Clinical Medical Workforce
Authors: Hills Danny , Joyce Catherine , Humphreys John
Published: March 2011

Job satisfaction has become an increasingly important topic of focus for the medical profession over the last 20 years. This report details the application of factor analysis to validate a widely used 10-item job satisfaction scale that has not previously been validated in a medical practitioner population. The study drew on data from 9,900 participants enrolled in the first wave of a longitudinal survey of Australian doctors. The instrument was found to possess a dominant single factor explaining 75% of the variance and internal reliability was high ( r = .86), enabling the determination of a composite job satisfaction score. Australian doctors experienced high levels of job satisfaction overall, but this varied with doctor subpopulation, age, geographic location, and hours worked per week. The validation of this brief scale in a large cohort of Australian doctors provides opportunities for undertaking further exploratory and comparative job satisfaction research in medical practitioner populations.
Toxicological Assessment of Dihydroergotamine after Chronic Inhalation in Dogs
Authors: Armer Thomas A. , Lynch MaryEllen , Moutvic Ronald , Singer Allen
Published: March 2011

The objective was to determine the respiratory toxicity of MAP0004, orally inhaled dihydroergotamine (DHE), via inhalation for six months. Forty beagle dogs (twenty females, twenty males) were treated by nose-only inhalation for 182 days. Groups 2 through 5 received MAP0004 (mean doses: 0.045, 0.154, 0.44, 0.825 mg/kg); Group 1 received vehicle only. Groups 1 through 4 received single thirty-minute exposures, whereas Group 5 was exposed twice daily for thirty minutes. Toxicity was assessed from clinical observations, objective evaluations, and clinical and anatomical pathology. Systemic effects were scabbing of ear tips in Groups 3, 4, and 5 and excessive salivation and emesis, observed in Group 5. No changes were observed in the lungs in any dose group. Minimal treatment-related microscopic changes were observed in the respiratory nasal epithelium only in Group 5. No plexiform, vascular media, or fibroproliferative changes in any heart valves were observed in any group. Expected systemic pharmacologic effects were observed only at MAP0004 target doses ≥ 0.224 mg/kg (achieved doses > 0.154 mg/kg), which was more than five times the maximum daily intravenous (IV) human clinical dose of DHE, and more than twenty times the systemic equivalent dose of MAP0004. The no-observed adverse effect level (NOAEL) was the achieved inhaled dose of 0.045 mg/kg, or four times the human clinical dose of MAP0004.
An exploration of musical communication through expressive use of timbre: The performer’s perspective
Authors: Holmes Patricia A.
Published: March 2011

This study explores the sound world of the performer, building on increasing evidence that timbre is the most salient variable performance parameter and can also be the primary source of inspiration and structure in composition. Psychological, psychoacoustic, musicological and aesthetic literature is reviewed, to establish the connection between existing (listener focused) research and potential performer motivation and affect. An interview study with one elite performer/composer (classical guitar) was undertaken to investigate timbre in live performance, specifically as part of the communication process. Results show that timbre salience varies according to style: in Baroque music it mainly enhances other performance parameters and in ‘contemporary’ music it is integral to composition and interpretation. Emotional affect in the performer appears to be related to inner drive towards optimal representation of musical understanding, which then generates the evolution of extended instrumental techniques, allowing ever more imaginative use of timbre. Parallels with aesthetic and philosophical theory are offered as explanation for some of the more intangible elements of performance, particularly in relation to the main priorities and motivations of the performer. Further research might synthesize psychological and philosophical reasoning in this respect and establish whether these findings are common to other instruments, performers and cultures.
Sound and Sight
Authors: Trinick Robyn Margaret
Published: March 2011

With the introduction of the New Zealand government’s National Standards, there are increasing demands on teachers to provide evidence of student achievement in the areas of numeracy and literacy. As a result, primary school teachers may perceive that there is neither time nor the need for music activities such as singing, which may be viewed purely as entertainment. This perspective may prevent teachers from realizing the potential of song as a valuable tool for literacy learning, particularly during a child’s first 4 years of school. This article explores whether purposeful application of song can add a new dimension to existing language programs, offering a meaningful and engaging context for learning. Through an analysis of a range of literature, key elements and principles relating to the affective, sociocultural, cognitive, and linguistic benefits and issues of song for language learning are identified and discussed. Potential ideas for establishing a singing environment are suggested.
Differences in Male Breast Cancer Stage, Tumor Size at Diagnosis, and Survival Rate Between Metropolitan and Nonmetropolitan Regions
Authors: Klein Judith , Ji Ming , Rea Nancy K. , Stoodt Georjean
Published: March 2011

Although the incidence for breast cancer in men is lower than for women, male breast cancer (MBC) patients are diagnosed at a later stage and have a higher mortality rate than women. This study examined male cases reported from 1988 through 2006 in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for differences in cancer stage, tumor size at diagnosis, and survival rate between metropolitan and nonmetropolitan regions. Pearson’s chi-square was used to evaluate differences in stage and tumor size at diagnosis. Cox proportional hazards regression was used to assess survival differences after adjusting for confounders (race, marital status, median family income, age, and education). Regional differences in tumor grade size and stage at diagnosis were not statistically significant; however, survival differences were observed between metropolitan and nonmetropolitan regions. An interaction between nonmetropolitan area and regional stage MBC was a significant predictor of poorer survival. Raising awareness of MBC in nonmetropolitan areas could save the lives of many men and action should be taken to improve health care access, treatment, and thus prognosis in this population.
Role of miR-1 and miR-133a in myocardial ischemic postconditioning
Authors: He Bin , Xiao Jian , Ren An-Jing , Zhang Yu-Feng , Zhang Hao , Chen Min , Xie Bing , Gao Xiao-Gang , Wang Ying-Wei
Published: March 2011

Background

Ischemic postconditioning (IPost) has aroused much attention since 2003 when it was firstly reported. The role of microRNAs (miRNAs or miRs) in IPost has rarely been reported. The present study was undertaken to investigate whether miRNAs were involved in the protective effect of IPost against myocardial ischemia-reperfusion (IR) injury and the probable mechanisms involved.

Methods

Thirty SD rats weighing 250-300 g were equally randomized to three groups: Control group, where the rats were treated with thoracotomy only; IR group, where the rats were treated with ischemia for 60 min and reperfusion for 180 min; and IPost group, where the rats were treated with 3 cycles of transient IR just before reperfusion. The extent of myocardial infarction, LDH and CK activities were measured immediately after treatment. Myocardial apoptosis was detected by TUNEL assay. The myocardial tissue was collected after IR or IPost stimulation to evaluate the miRNAs expression level by miRNA-microarray and quantitative real-time RT-PCR. Real-time PCR was conducted to identify changes in mRNA expression of apoptosis-related genes such as Bcl-2, Bax and Caspase-9 (CASP9), and Western blot was used to compare the protein expression level of CASP9 in the three groups. The miRNA mimics and anti-miRNA oligonucleotides (AMO) were transferred into the cultured neonatal cardiomyocytes and myocardium before they were treated with IR. The effect of miRNAs on apoptosis was determined by flow cytometry and TUNEL assay. CASP9, as one of the candidate target of miR-133a, was compared during IR after the miR-133a mimic or AMO-133a was transferred into the myocardium.

Results

IPost reduced the IR-induced infarct size of the left ventricle, and decreased CK and LDH levels. TUNEL assay showed that myocardial apoptosis was attenuated by IPost compared with IR. MiRNA-microarray and RT-PCR showed that myocardial-specific miR-1 and miR-133a were down-regulated by IR, and up-regulated by IPost compared with IR. Furthermore, IPost up-regulated the mRNA expression of Bcl-2, down-regulated that of Bax and CASP9. Western blot showed that IPost also down-regulated the CASP9 protein expression compared with IR. The results of flow cytometry and TUNEL assay showed that up-regulation of miR-1 and miR-133a decreased apoptosis of cardiomyocytes. MiR-133a mimic down-regulated CASP9 protein expression and attenuated IR-induced apoptosis.

Conclusion

MiRNAs are associated with the protective effect of IPost against myocardial IR injury. IPost can up-regulate miR-1 and miR-133a, and decrease apoptosis of cardiomyocyte. Myocardial-specific miR-1 and miR-133a may play an important role in IPost protection by regulating apoptosis-related genes. MiR-133a may attenuate apoptosis of myocardiocytes by targeting CASP9.
AnyExpress: Integrated toolkit for analysis of cross-platform gene expression data using a fast interval matching algorithm
Authors: Kim Jihoon , Patel Kiltesh , Jung Hyunchul , Kuo Winston P , Ohno-Machado Lucila
Published: March 2011

Background

Cross-platform analysis of gene express data requires multiple, intricate processes at different layers with various platforms. However, existing tools handle only a single platform and are not flexible enough to support custom changes, which arise from the new statistical methods, updated versions of reference data, and better platforms released every month or year. Current tools are so tightly coupled with reference information, such as reference genome, transcriptome database, and SNP, which are often erroneous or outdated, that the output results are incorrect and misleading.

Results

We developed AnyExpress, a software package that combines cross-platform gene expression data using a fast interval-matching algorithm. Supported platforms include next-generation-sequencing technology, microarray, SAGE, MPSS, and more. Users can define custom target transcriptome database references for probe/read mapping in any species, as well as criteria to remove undesirable probes/reads.

AnyExpress offers scalable processing features such as binding, normalization, and summarization that are not present in existing software tools.

As a case study, we applied AnyExpress to published Affymetrix microarray and Illumina NGS RNA-Seq data from human kidney and liver. The mean of within-platform correlation coefficient was 0.98 for within-platform samples in kidney and liver, respectively. The mean of cross-platform correlation coefficients was 0.73. These results confirmed those of the original and secondary studies. Applying filtering produced higher agreement between microarray and NGS, according to an agreement index calculated from differentially expressed genes.

Conclusion

AnyExpress can combine cross-platform gene expression data, process data from both open- and closed-platforms, select a custom target reference, filter out undesirable probes or reads based on custom-defined biological features, and perform quantile-normalization with a large number of microarray samples. AnyExpress is fast, comprehensive, flexible, and freely available at http://anyexpress.sourceforge.net.
A proteomics approach to decipher the molecular nature of planarian stem cells
Authors: Fernández-Taboada Enrique , Rodríguez-Esteban Gustavo , Saló Emili , Abril Josep F
Published: March 2011

Background

In recent years, planaria have emerged as an important model system for research into stem cells and regeneration. Attention is focused on their unique stem cells, the neoblasts, which can differentiate into any cell type present in the adult organism. Sequencing of the Schmidtea mediterranea genome and some expressed sequence tag projects have generated extensive data on the genetic profile of these cells. However, little information is available on their protein dynamics.

Results

We developed a proteomic strategy to identify neoblast-specific proteins. Here we describe the method and discuss the results in comparison to the genomic high-throughput analyses carried out in planaria and to proteomic studies using other stem cell systems. We also show functional data for some of the candidate genes selected in our proteomic approach.

Conclusions

We have developed an accurate and reliable mass-spectra-based proteomics approach to complement previous genomic studies and to further achieve a more accurate understanding and description of the molecular and cellular processes related to the neoblasts.
Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites
Authors: Schmidt Søren F , Jørgensen Mette , Chen Yun , Nielsen Ronni , Sandelin Albin , Mandrup Susanne
Published: March 2011

Background

The transcription factors peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) are key transcriptional regulators of adipocyte differentiation and function. We and others have previously shown that binding sites of these two transcription factors show a high degree of overlap and are associated with the majority of genes upregulated during differentiation of murine 3T3-L1 adipocytes.

Results

Here we have mapped all binding sites of C/EBPα and PPARγ in human SGBS adipocytes and compared these with the genome-wide profiles from mouse adipocytes to systematically investigate what biological features correlate with retention of sites in orthologous regions between mouse and human. Despite a limited interspecies retention of binding sites, several biological features make sites more likely to be retained. First, co-binding of PPARγ and C/EBPα in mouse is the most powerful predictor of retention of the corresponding binding sites in human. Second, vicinity to genes highly upregulated during adipogenesis significantly increases retention. Third, the presence of C/EBPα consensus sites correlate with retention of both factors, indicating that C/EBPα facilitates recruitment of PPARγ. Fourth, retention correlates with overall sequence conservation within the binding regions independent of C/EBPα and PPARγ sequence patterns, indicating that other transcription factors work cooperatively with these two key transcription factors.

Conclusions

This study provides a comprehensive and systematic analysis of what biological features impact on retention of binding sites between human and mouse. Specifically, we show that the binding of C/EBPα and PPARγ in adipocytes have evolved in a highly interdependent manner, indicating a significant cooperativity between these two transcription factors.
Distinct roles for nitric oxide in resistant C57BL/6 and susceptible BALB/c mice to control Burkholderia pseudomallei infection
Authors: Breitbach Katrin , Wongprompitak Patimaporn , Steinmetz Ivo
Published: March 2011

Background

Burkholderia pseudomalleiis the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. We recently showed that NADPH oxidase but not nitric oxide (NO) contributes to resistance in innately resistant C57BL/6 mice in aB. pseudomalleirespiratory infection model. However, the function of NO for resistance was shown to differ among distinct strains of mice and proved also to be stage dependent in various infection models. The present study therefore aimed to examine the role of NO in a systemic infection model of melioidosis and to test whether the function of NO differs among innately resistant C57BL/6 and susceptible BALB/c mice afterB. pseudomalleiinfection.

Results

C57BL/6iNOS-/-mice that were intravenously infected withB. pseudomalleisurvived several weeks, whereas most of the wild type animals succumbed during this period. The bacterial burden in liver and spleen was significantly higher in wild type animals compared toiNOS-/-mice 13 days after challenge. In contrast, BALB/c mice that were treated with amminoguanidine to inhibit NO expression in vivo showed significantly enhanced mortality rates and higher bacterial loads in liver and spleen compared to control animals. The bactericidal function of IFN-γ stimulated C57BL/6iNOS-/-macrophages were not altered afterB. pseudomalleiinfection, but BALB/c macrophages exhibited reduced killing activity against the pathogen when NO was inhibited.

Conclusion

Our present data indicate a dual role of NO among resistant and susceptible mouse strains afterB. pseudomalleiinfection. NO mediated mechanisms are an essential component to control the infection in susceptible BALB/c mice. In contrast, NO production inB. pseudomalleiinfected C57BL/6 mice rather harmed the host likely due to its detrimental effects.
Psychometric properties of two physical activity questionnaires, the AQuAA and the PASE, in cancer patients
Authors: Liu Roberto DK , Buffart Laurien M , Kersten Marie José , Spiering Marjolein , Brug Johannes , van Mechelen Willem , Chinapaw Mai JM
Published: March 2011

Background

This study aimed to evaluate the reliability and validity of two self-report physical activity (PA) questionnaires - the AQuAA (Activity Questionnaire for Adults and Adolescents) and PASE (Physical Activity Scale for the Elderly) - in cancer patients.

Methods

Test-retest reliability was determined by administering the questionnaires twice within 5 days. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and smallest detectable difference (SDD) were calculated. Construct validity was determined by comparing the questionnaire results with ActiGraph accelerometer scores using Spearman correlation coefficients (rs) and ICCs. Content validity was examined using the Three-Step Test-Interview (TSTI).

Results

Reliability for the AQuAA scores were fair to excellent (ICC = 0.57 to 0.78). Reliability for the PASE scores ranged from good to excellent (ICC = 0.67 to 0.90). Correlations between the ActiGraph and the AQuAA and the PASE were low (rs = 0.05 and 0.16 respectively, and ICC = -0.001 to 0.44). The TSTI showed that participants experienced difficulties with the examples provided with the questions, the perceptions of intensity level of PA, and with recalling the time spent on PA.

Conclusions

Both questionnaires showed good to excellent test-retest reliability for most scores. Construct validity of both questionnaires was low, as indicated by the low correlations with the ActiGraph. Except for a few difficulties that participants perceived when filling out the questionnaires, the content validity of both questionnaires was good.
Development and implementation of the quality control panel of RT-PCR and real-time RT-PCR for avian influenza A (H5N1) surveillance network in mainland China
Authors: Gao Rongbao , Gao Yan , Wen Leying , Shao Ming , Zou Shumei , Li Changgui , Yang Lei , Li Xiyan , Wang Wei , Shu Yuelong
Published: March 2011

Background

Reverse transcription PCR (RT-PCR) and real time RT-PCR (rRT-PCR) have been indispensable methods for influenza surveillance, especially for determination of avian influenza. The movement of testing beyond reference lab introduced the need of quality control, including the implementation of an evaluation system for validating personal training and sample proficiency testing.

Methods

We developed a panel with lysates of seasonal influenza virus (H1N1, H3N2 and B), serials of diluted H5N1 virus lysates, and in-vitro transcribed H5 hemaglutinin (HA) and an artificial gene RNAs for RT-PCR and rRT-PCR quality control assessment. The validations of stability and reproducibility were performed on the panel. Additionally, the panel was implemented to assess the detection capability of Chinese human avian influenza networks.

Results

The panel has relatively high stability and good reproducibility demonstrated by kappa's tests. In the implementation of panel on Chinese human avian influenza networks, the results suggested that there were a relatively low number of discrepancies for both concise and reproducibility in Chinese avian influenza virus net works.

Conclusions

A quality control panel of RT-PCR and real-time RT-PCR for avian influenza A (H5N1) surveillance network was developed. An availably statistical data, which are used to assess the detection capability of networks on avian influenza virus (H5N1), can be obtained relatively easily through implementation of the panel on networks.
Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer
Authors: Cellier Patrice , Leduc Bernard , Martin Laurent , Vié Brigitte , Chevelle Christian , Vendrely Véronique , Salemkour Augustin , Carrie Christian , Calais Gilles , Burtin Pascal , Campion Loïc , Boisdron-Celle Michèle , Morel Alain , Berger Virginie , Gamelin Erick
Published: March 2011

Background

Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.

Methods

This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/2/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.

Results

Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (DPYD) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).

Conclusion

Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.
The DUNDRUM-1 structured professional judgment for triage to appropriate levels of therapeutic security: retrospective-cohort validation study
Authors: Flynn Grainne , O'Neill Conor , McInerney Clare , Kennedy Harry G
Published: March 2011

Background

The assessment of those presenting to prison in-reach and court diversion services and those referred for admission to mental health services is a triage decision, allocating the patient to the appropriate level of therapeutic security. This is a critical clinical decision. We set out to improve on unstructured clinical judgement. We collated qualitative information and devised an 11 item structured professional judgment instrument for this purpose then tested for validity.

Methods

All those assessed following screening over a three month period at a busy remand committals prison (n = 246) were rated in a retrospective cohort design blind to outcome. Similarly, all those admitted to a mental health service from the same prison in-reach service over an overlapping two year period were rated blind to outcome (n = 100).

Results

The 11 item scale had good internal consistency (Cronbach's alpha = 0.95) and inter-rater reliability. The scale score did not correlate with the HCR-20 'historical' score. For the three month sample, the receiver operating characteristic area under the curve (AUC) for those admitted to hospital was 0.893 (95% confidence interval 0.843 to 0.943). For the two year sample, AUC distinguished at each level between those admitted to open wards, low secure units or a medium/high secure service. Open wards v low secure units AUC = 0.805 (95% CI 0.680 to 0.930); low secure v medium/high secure AUC = 0.866, (95% CI 0.784 to 0.949). Item to outcome correlations were significant for all 11 items.

Conclusions

The DUNDRUM-1 triage security scale and its items performed to criterion levels when tested against the real world outcome. This instrument can be used to ensure consistency in decision making when deciding who to admit to secure forensic hospitals. It can also be used to benchmark admission thresholds between services and jurisdictions. In this study we found some divergence between assessed need and actual placement. This provides fertile ground for future research as well as practical assistance in assessing unmet need, auditing case mix and planning care pathways.
Dichrostachys cinerea (L.) Wight et Arn (Mimosaceae) hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig
Authors: Aworet-Samseny Raissa RR , Souza Alain , Kpahé Fidele , Konaté Kiessoun , Datté Jacques Y
Published: March 2011

Background

Dichrostachys cinerea (L.) Wight et Arn. (Mimosaceae) is largely used in ethno-medically across Africa, and mainly employed for the treatment of asthma in Ivory Coast and Gabon. The paper analyses the relaxation induced by the methanolic extract of D. cinerea (Edici) in the guinea-pig trachea preparations (GPTPs). Purpose: This study aimed to bring out the scientific basis to the use of this plant leading to the validation of this phytomedicine.

Method

The aorta obtained from guinea-pigs was immediately placed in a Mac Ewen solution. Experiments were performed in preparations suspended between two L-shaped stainless steel hooks in a 10 ml organ bath containing Mac Ewen solution. The isometric contractile force of the aorta strips of guinea-pig were recorded by using a strain gauge. The different drugs were directly administered into the organ bath and the magnitude of GPTPs was evaluated.

Results

Phytochemical analysis of the methanolic extract of Dichrostachys cinerea (Edici) using chemical methods revealed the presence of flavenoids, tannins, sterols, triterpenes and polyphenols. Pharmacological studies performed in GPTPs show that of Dichrostachys cinerea (0.1 mg/ml - 2 mg/ml) evoked a broncho-constriction in GPTPs. Whereas, at concentration up to 2 mg/ml, Edici induced a significant dose-dependent relaxation in the GPTPs. KCl-, ACh- or histamine-evoked contractions of isolated trachea was significantly inhibited by increasing concentrations of Edici (3.5-10 mg/ml). Edici (10 mg/ml) as well as promethazine (0.25 mg/ml) significantly inhibited contractions induced by increasing concentrations of histamine (1×10-7-1×10-4mg/ml). In the presence of atropine at a concentration of 10-6mg/ml, contractile response curve (CRC) evoked by ACh (1×10-5-1×10-2 mg/ml) was significantly abolished in concentration-dependent manner. Edici did not significantly reduced ACh evoked contraction (10-5-10-2mg/ml).

Conclusion

These observations suggest that Edici could act through two mechanisms: firstly by activation of β-adrenergic or histaminergic receptors; and secondly muscarinic receptors may not be greatly involved, that justifying the use of the extract in traditional Medicine in Africa.
Preparation of stable magnetic nanofluids containing Fe3O4@PPy nanoparticles by a novel one-pot route
Authors: Zhao Baobao , Nan Zhaodong
Published: March 2011

Stable magnetic nanofluids containing Fe3O4@Polypyrrole (PPy) nanoparticles (NPs) were prepared by using a facile and novel method, in which one-pot route was used. FeCl3·6H2O was applied as the iron source, and the oxidizing agent to produce PPy. Trisodium citrate (Na3cit) was used as the reducing reagent to form Fe3O4 NPs. The as-prepared nanofluid can keep long-term stability. The Fe3O4@PPy NPs can still keep dispersing well after the nanofluid has been standing for 1 month and no sedimentation is found. The polymerization reaction of the pyrrole monomers took place with Fe3+ ions as the initiator, in which these Fe3+ ions remained in the solution adsorbed on the surface of the Fe3O4 NPs. Thus, the core-shell NPs of Fe3O4@PPy were obtained. The particle size of the as-prepared Fe3O4@PPy can be easily controlled from 7 to 30 nm by the polymerization reaction of the pyrrole monomers. The steric stabilization and weight of the NPs affect the stability of the nanofluids. The as-prepared Fe3O4@PPy NPs exhibit superparamagnetic behavior.
Infrared thermometry study of nanofluid pool boiling phenomena
Authors: Gerardi Craig , Buongiorno Jacopo , Hu Lin-wen , McKrell Thomas
Published: March 2011

Infrared thermometry was used to obtain first-of-a-kind, time- and space-resolved data for pool boiling phenomena in water-based nanofluids with diamond and silica nanoparticles at low concentration (<0.1 vol.%). In addition to macroscopic parameters like the average heat transfer coefficient and critical heat flux [CHF] value, more fundamental parameters such as the bubble departure diameter and frequency, growth and wait times, and nucleation site density [NSD] were directly measured for a thin, resistively heated, indium-tin-oxide surface deposited onto a sapphire substrate. Consistent with other nanofluid studies, the nanoparticles caused deterioration in the nucleate boiling heat transfer (by as much as 50%) and an increase in the CHF (by as much as 100%). The bubble departure frequency and NSD were found to be lower in nanofluids compared with water for the same wall superheat. Furthermore, it was found that a porous layer of nanoparticles built up on the heater surface during nucleate boiling, which improved surface wettability compared with the water-boiled surfaces. Using the prevalent nucleate boiling models, it was possible to correlate this improved surface wettability to the experimentally observed reductions in the bubble departure frequency, NSD, and ultimately to the deterioration in the nucleate boiling heat transfer and the CHF enhancement.
Acute toxicity of second generation HIV protease-inhibitors in combination with radiotherapy: a retrospective case series
Authors: See Alfred P , Zeng Jing , Tran Phuoc T , Lim Michael
Published: March 2011

Background

There is little data on the safety of combining radiation therapy and human immunodeficiency virus (HIV) protease inhibitors to treat cancers in HIV-positive patients. We describe acute toxicities observed in a series of HIV-positive patients receiving modern radiation treatments, and compare patients receiving HIV protease inhibitors (PI) with patients not receiving HIV PIs.

Methods

By reviewing the clinical records beginning January 1, 2009 from the radiation oncology department, we identified 29 HIV-positive patients who received radiation therapy to 34 body sites. Baseline information, treatment regimen, and toxicities were documented by review of medical records: patient age, histology and source of the primary tumor, HIV medication regimen, pre-radiation CD4 count, systemic chemotherapy, radiation therapy dose and fractionation, irradiated body region, toxicities, and duration of follow-up. Patients were grouped according to whether they received concurrent HIV PIs and compared using Pearson's chi-square test.

Results

At baseline, the patients in the two groups were similar with the exception of HIV medication regimens, CD4 count and presence of AIDS-defining malignancy. Patients taking concurrent PIs were more likely to be taking other HIV medications (p = 0.001) and have CD4 count >500 (p = 0.006). Patients taking PIs were borderline less likely to have an AIDS-defining malignancy (p = 0.06). After radiation treatment, 100 acute toxicities were observed and were equally common in both groups (64 [median 3 per patient, IQR 1-7] with PIs; 36 [median 3 per patient, IQR 2-3] without PIs). The observed toxicities were also equally severe in the two groups (Grades I, II, III respectively: 30, 30, 4 with PIs; 23, 13, 0 without PIs: p = 0.38). There were two cases that were stopped early, one in each group; these were not attributable to toxicity.

Conclusions

In this study of recent radiotherapy in HIV-positive patients taking second generation PIs, no difference in toxicities was observed in patients taking PIs compared to patients not taking PIs during radiation therapy. This suggests that it is safe to use unmodified doses of PIs and radiation therapy in HIV cancer patients, and that it is feasible to use PIs as a radiosensitizer in cancer therapy, as has been suggested by pre-clinical results.