bluuebunny/crossref_metadata_2025 huggingface dataset:
Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease
Authors: Brodlie M. , McKean M.C. , Johnson G.E. , Anderson A.E. , Hilkens C.M.U. , Fisher A.J. , Corris P.A. , Lordan J.L. , Ward C.
Published: November 2010

Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells.

Immunohistochemistry was performed on explanted CF lungs and compared with the non-suppurative condition pulmonary hypertension (PH). Airway lavages and epithelial cultures were generated from explanted CF lungs.

Immunoreactivity for IL-17 was significantly increased in the lower airway epithelium in CF (median 14.1%) compared with PH (2.95%, p = 0.0001). The number of cells staining positive for IL-17 in the lower airway mucosa was also increased (64 cells·mm−1compared with 9 cells·mm−1basement membrane, p = 0.0005) and included both neutrophils in addition to mononuclear cells. IL-17 was detectable in airway lavages from explanted CF lungs. Treatment of epithelial cultures with IL-17 increased production of IL-8, IL-6 and granulocyte macrophage colony-stimulating factor.

In conclusion, immunoreactive IL-17 is raised in the lower airway of people with CF and localises to both neutrophils and mononuclear cells. IL-17 increases production of pro-neutrophilic mediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.
House dust mite extract downregulates C/EBPα in asthmatic bronchial smooth muscle cells
Authors: Miglino N. , Roth M. , Tamm M. , Borger P.
Published: November 2010

Reduced translation ofCEBPAmRNA has been associated with increased proliferation of bronchial smooth muscle (BSM) cells of asthma patients.

Here, we assessed the effect of house dust mite (HDM) extracts on the cell proliferation ([3H]-thymidine incorporation), inflammation (interleukin (IL)-6 release) and upstream translation regulatory proteins of CCAAT/enhancer-binding protein (C/EBP)α in human BSM cells of healthy controls and asthmatic patients.

HDM extract significantly increased IL-6 protein and proliferation of BSM cells of asthma patients only. HDM extract reduced the C/EBPα expression in BSM cells of asthma patients, which coincided with significantly increased levels of calreticulin (CRT) protein, an inhibitor ofCEBPAmRNA translation. HDM extract elicited both protease-dependent and -independent responses, which were mediatedviaprotease-activated receptor (PAR)2 and CRT, respectively.

In conclusion, HDM extract reducedCEBPAmRNA translation, specifically in asthmatic BSM cells, and 1) upregulated CRT, 2) activated PAR2, and increased 3) IL-6 expression and 4) the proliferation of asthmatic BSM cells. Hence, HDM exposure contributes to inflammation and remodelling by a nonimmune cell-mediated mechanismviaa direct interaction with BSM cells. These findings may potentially explain several pathological features of this disease, in particular BSM cell hyperplasia.
Childhood diet and asthma and atopy at 8 years of age: the PIAMA birth cohort study
Authors: Willers S.M. , Wijga A.H. , Brunekreef B. , Scholtens S. , Postma D.S. , Kerkhof M. , de Jongste J.C. , Smit H.A.
Published: November 2010

Diet may affect the development of asthma. We investigated whether asthma or atopy outcomes at 8 yrs of age were associated with long-term dietary exposure, and whether associations were different for consumption at early or later age.

The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort enrolled 4,146 participants at baseline, who were followed up to 8 yrs of age. Dietary intakes of interest were fruit, vegetables, brown/wholemeal bread, fish, milk, butter and margarine. Associations between food intake at early (2–3 yrs) and later (7–8 yrs) age, and long-term intake, asthma and atopy at 8 yrs of age were calculated by logistic regression.

Complete longitudinal dietary data for at least one of the food groups were available for 2,870 children. Fruit consumption at early age was associated with reduced asthma symptoms (OR per 1 consumption day per week increase 0.93, 95% CI 0.85–1.00). Long-term fruit intake was inversely associated with asthma symptoms (OR 0.90, 95% CI 0.82–0.99) and sensitisation to inhaled allergens (OR 0.90, 95% CI 0.82–0.99). We found no consistent associations between diet and outcomes for other foods.

This study indicates no consistent effects of increased early or late consumption, or long-term intake of certain foods on asthma and atopy in 8-yr-olds, with a possible exception for fruit.
Normative data for lung function and exhaled nitric oxide in unsedated healthy infants
Authors: Fuchs O. , Latzin P. , Thamrin C. , Stern G. , Frischknecht P. , Singer F. , Kieninger E. , Proietti E. , Riedel T. , Frey U.
Published: November 2010

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards.

Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean±sdage of 5.1±0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow–volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5–10 acceptable interruption resistance (Rint) measurements.

Acceptable measurements were obtained in ≤285 infants with high variability. Mean values were 7.48 mL·kg−1(95% limits of agreement 4.95–10.0 mL·kg−1) for tidal volume, 14.3 ppb (2.6–26.1 ppb) for eNO, 23.9 mL·kg−1(16.0–31.8 mL·kg−1) for functional residual capacity, 6.75 (5.63–7.87) for lung clearance index and 3.78 kPa·s·L−1(1.14–6.42 kPa·s·L−1) forRint. In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section.

This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.
Improvements to previous algorithms to predict gene structure and isoform concentrations using Affymetrix Exon arrays
Authors: Anton Miguel A , Aramburu Ander , Rubio Angel
Published: November 2010

Background

Exon arrays provide a way to measure the expression of different isoforms of genes in an organism. Most of the procedures to deal with these arrays are focused on gene expression or on exon expression. Although the only biological analytes that can be properly assigned a concentration are transcripts, there are very few algorithms that focus on them. The reason is that previously developed summarization methods do not work well if applied to transcripts. In addition, gene structure prediction, i.e., the correspondence between probes and novel isoforms, is a field which is still unexplored.

Results

We have modified and adapted a previous algorithm to take advantage of the special characteristics of the Affymetrix exon arrays. The structure and concentration of transcripts -some of them possibly unknown- in microarray experiments were predicted using this algorithm. Simulations showed that the suggested modifications improved both specificity (SP) and sensitivity (ST) of the predictions. The algorithm was also applied to different real datasets showing its effectiveness and the concordance with PCR validated results.

Conclusions

The proposed algorithm shows a substantial improvement in the performance over the previous version. This improvement is mainly due to the exploitation of the redundancy of the Affymetrix exon arrays. An R-Package of SPACE with the updated algorithms have been developed and is freely available.
β-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis
Authors: Mirando Anthony J , Maruyama Takamitsu , Fu Jiang , Yu Hsiao-Man Ivy , Hsu Wei
Published: November 2010

Background

Mouse genetic study has demonstrated that Axin2 is essential for calvarial development and disease. Haploid deficiency of β-catenin alleviates the calvarial phenotype caused by Axin2 deficiency. This loss-of-function study provides evidence for the requirement of β-catenin in exerting the downstream effects of Axin2.

Results

Here we utilize a gain-of-function analysis to further assess the role of β-catenin. A transgenic expression system permitting conditional activation of β-catenin in a spatiotemporal specific manner has been developed. Aberrant stimulation of β-catenin leads to increases in expansion of skeletogenic precursors and the enhancement of bone ossification reminiscent to the loss of Axin2. The constitutively active signal promotes specification of osteoprogenitors, but prevents their maturation into terminally differentiated osteoblasts, along the osteoblast lineage. However, the prevention does not interfere with bone synthesis, suggesting that mineralization occurs without the presence of mature osteoblasts. β-catenin signaling apparently plays a key role in suture development through modulation of calvarial morphogenetic signaling pathways. Furthermore, genetic inactivation of the β-catenin transcriptional target, cyclin D1, impairs expansion of the skeletogenic precursors contributing to deficiencies in calvarial ossification. There is a specific requirement for cyclin D1 in populating osteoprogenitor cell types at various developmental stages.

Conclusion

These findings advance our knowledge base of Wnt signaling in calvarial morphogenesis, suggesting a key regulatory pathway of Axin2/β-catenin/cyclin D1 in development of the suture mesenchyme.
No evidence for increased extinction proneness with decreasing effective population size in a parasitoid with complementary sex determination and fertile diploid males
Authors: Elias Jan , Dorn Silvia , Mazzi Dominique
Published: November 2010

Background

In species with single locus complementary sex determination (sl-CSD), the sex of individuals depends on their genotype at one single locus with multiple alleles. Haploid individuals are always males. Diploid individuals are females when heterozygous, but males when homozygous at the sex-determining locus. Diploid males are typically unviable or effectively sterile, hence imposing a genetic load on populations. Diploid males are produced from matings of partners that share an allele at the sex-determining locus. The lower the allelic diversity at the sex-determining locus, the more diploid males are produced, ultimately impairing the growth of populations and jeopardizing their persistence. The gregarious endoparasitoid wasp Cotesia glomerata is one of only two known species with sl-CSD and fertile diploid males.

Results

By manipulating the relatedness of the founders, we established replicated experimental populations of the parasitoid C. glomerata differing in their genetic effective size, and thus in allelic richness at the sex-determining locus and in the expected magnitude of diploid male production. Our long-term survey of population welfare and persistence did not provide evidence for increased proneness to population extinction with decreasing initial genetic effective population size. Most recorded surrogates of fitness nevertheless decayed over time and most experimental populations eventually went extinct, suggesting that the negative effects of inbreeding outweighed any premium from the fertility of diploid males.

Conclusions

The fertility of diploid males may have evolved as an adaptation prompted by the risk of extinction looming over small isolated populations of species with sl-CSD. However, fertility of diploid males does not negate the costs imposed by their production, and although it may temporarily stave off extinction, it is not sufficient to eradicate the negative effects of inbreeding.
The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa
Authors: Ioerger Thomas R , Feng Yicheng , Chen Xiaohua , Dobos Karen M , Victor Thomas C , Streicher Elizabeth M , Warren Robin M , Gey van Pittius Nicolaas C , Van Helden Paul D , Sacchettini James C
Published: November 2010

Background

The Beijing genotype ofM. tuberculosisis a virulent strain that is disseminating worldwide and has a strong association with drug resistance. In the Western Cape of South Africa, epidemiological studies have identified the R220 cluster of the Beijing genotype as a major contributor to a recent outbreak of drug-resistant tuberculosis. Although the outbreak is considered to be due to clonal transmission, the relationship among drug resistant isolates has not yet been established.

Results

To better understand the evolution of drug resistance among these strains, 14 drug-resistant clinical isolates of the Beijing genotype were sequenced by whole-genome sequencing, including eight from R220 and six from a more ancestral Beijing cluster, R86, for comparison. While each cluster shares a distinct resistance mutation for isoniazid, mapping of other drug-resistance mutations onto a phylogenetic tree constructed from single nucleotide polymorphisms shows that resistance mutations to many drugs have arisen multiple times independently within each cluster of isolates. Thus, drug resistance among these isolates appears to be acquired, not clonally derived. This observation suggests that, although the Beijing genotype as a whole might have selective advantages enabling its rapid dissemination, the XDR isolates are relatively less fit and do not propagate well. Although it has been hypothesized that the increased frequency of drug resistance in some Beijing lineages might be caused by a mutator phenotype, no significant shift in synonymous substitution patterns is observed in the genomes.

Conclusion

While MDR-TB is spreading by transmission in the Western Cape, our data suggests that further drug resistance (i.e. XDR-TB) at this stage is acquired.
Characterization of JG024, a pseudomonas aeruginosa PB1-like broad host range phage under simulated infection conditions
Authors: Garbe Julia , Wesche Andrea , Bunk Boyke , Kazmierczak Marlon , Selezska Katherina , Rohde Christine , Sikorski Johannes , Rohde Manfred , Jahn Dieter , Schobert Max
Published: November 2010

Background

Pseudomonas aeruginosa causes lung infections in patients suffering from the genetic disorder Cystic Fibrosis (CF). Once a chronic lung infection is established, P. aeruginosa cannot be eradicated by antibiotic treatment. Phage therapy is an alternative to treat these chronic P. aeruginosa infections. However, little is known about the factors which influence phage infection of P. aeruginosa under infection conditions and suitable broad host range phages.

Results

We isolated and characterized a phage, named JG024, which infects a broad range of clinical and environmental P. aeruginosa strains. Sequencing of the phage genome revealed that the phage JG024 is highly related to the ubiquitous and conserved PB1-like phages. The receptor of phage JG024 was determined as lipopolysaccharide. We used an artificial sputum medium to study phage infection under conditions similar to a chronic lung infection. Alginate production was identified as a factor reducing phage infectivity.

Conclusions

Phage JG024 is a suitable broad host range phage which could be used in phage therapy. Phage infection experiments under simulated chronic lung infection conditions showed that alginate production reduces phage infection efficiency.
Predominant porB1A and porB1B genotypes and correlation of gene mutations with drug resistance in Neisseria gonorrhoeae isolates in Eastern China
Authors: Sun Aihua , Fan Xingli , Gu Ye , Du Peng , Tang Renxian , Mao Yafei , Lin Xuai , Yan Jie
Published: November 2010

Background

Variations of porB1A and porB1B genes and their serotypes exist in Neisseria gonorrhoeae isolates from different geographical areas, and some site mutations in the porB1B gene correlate with drug resistance.

Methods

The β-lactamase production of N. gonorrhoeae isolates was determined by paper acidometric test and nitrocefin discs. The porB1A and porB1B genes of 315 non-penicillinase-producting N. gonorrhoeae (non-PPNG) strains were amplified by PCR for sequencing to determine serotypes and site mutations. A duplex PCR was designed to simultaneously detect both porB1A and porB1B genes. Penicillin and tetracycline resistance was assessed by an in vitro drug sensitivity test.

Results

Of the N. gonorrhoeae isolates, 31.1% tested positive for porB1A and 68.9% for porB1B genes. All the 98 porB1A
+ isolates belonging to IA6 serotype with either no mutation at the 120 and 121 sites (88.8%) or a D120G (11.2%) mutation and were no resistance to both penicillin and tetracycline. Among the 217 porB1B
+ isolates, 26.7%, 22.6% and 11.5% belonged to IB3, IB3/6 and IB4 serotypes, respectively. Particularly, two novel chimeric serotypes, IB3/6-IB2 and IB2-IB4-IB2, were found in 77 and 8 porB1B
+ isolates. Two hundred and twelve (97.7%) of the porB1B
+ isolates were presented G120 and/or A121 mutations with 163 (76.9%) at both sites. Interestingly, within the 77 porB1B
+ isolates belonging to IB3/6-IB2 serotype, 15 were discovered to possess novel deletions at both A121 and N122 sites. All the replacement mutations at these sites in PorB1B were correlated with resistance and the deletion mutation showed the highest resistance.

Conclusion

N. gonorrhoeae isolates circulating in Eastern China include a sole PorB1A serotype (IA6) and five PorB1B serotypes. Multiple mutations in porB1B genes, including novel A121 and N122 deletions, are correlated with high levels of penicillin and tetracycline resistance.
Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study
Authors: Zhang Donghong , Zhang Qingying , Zhou Li , Huo Leijun , Zhang Yi , Shen Zhongying , Zhu Yi
Published: November 2010

Background

Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain.

Methods

Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining.

Results

The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027).

Conclusions

High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC.
Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol
Authors: Habl Gregor , Jensen Alexandra D , Potthoff Karin , Uhl Matthias , Hof Holger , Hajda Jacek , Simon Christian , Debus Jürgen , Krempien Robert , Münter Marc W
Published: November 2010

Background

Primary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival), combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®). Radiation therapy (RT) is carried out as intensity-modulated RT (IMRT) to avoid higher grade acute and late toxicity by sparing of surrounding normal tissues.

Methods/Design

The REACH study is a prospective phase II study combining chemoradiotherapy with carboplatin/5-Fluorouracil (5-FU) and the monoclonal epidermal growth factor-receptor (EGFR) antibody cetuximab (Erbitux®) as intensity-modulated radiation therapy in patients with locally advanced squamous-cell carcinomas of oropharynx, hypopharynx or larynx.

Patients receive weekly chemotherapy infusions in the 1st and 5th week of RT. Additionally, cetuximab is administered weekly throughout the treatment course. IMRT is delivered as in a classical concomitant boost concept (bid from fraction 16) to a total dose of 69,9 Gy.

Discussion

Primary endpoint of the trial is local-regional control (LRC). Disease-free survival, progression-free survival, overall survival, toxicity, proteomic and genomic analyses are secondary endpoints. The aim is to explore the efficacy as well as the safety and feasibility of this combined radioimmunchemotherapy in order to improve the outcome of patients with advanced head and neck cancer.

Trial registration

ISRCTN87356938
THE VAXED PROJECT: An Assessment of Immunization Education in Canadian Health Professional Programs
Authors: Pelly Lorine P , Pierrynowski MacDougall Donna M , Halperin Beth A , Strang Robert A , Bowles Susan K , Baxendale Darlene M , McNeil Shelly A
Published: November 2010

Background

Knowledge & attitudes of healthcare providers (HCP) have significant impact on frequency with which vaccines are offered & accepted but many HCP are ill equipped to make informed recommendations about vaccine merits & risks. We performed an assessment of the educational needs of trainees regarding immunization and used the information thus ascertained to develop multi-faceted, evaluable, educational tools which can be integrated into formal education curricula.

Methods

(i) A questionnaire was sent to all Canadian nursing, medical & pharmacy schools to assess immunization-related curriculum content (ii) A 77-item web-based, validated questionnaire was emailed to final-year students in medicine, nursing, & pharmacy at two universities in Nova Scotia, Canada to assess knowledge, attitudes, & behaviors reflecting current immunization curriculum.

Results

The curriculum review yielded responses from 18%, 48%, & 56% of medical, nursing, & pharmacy schools, respectively. Time spent on immunization content varied substantially between & within disciplines from <1 to >50 hrs. Most schools reported some content regarding vaccine preventable diseases, immunization practice & clinical skills but there was considerable variability and fewer schools had learning objectives or formal evaluation in these areas. 74% of respondents didn't feel comfortable discussing vaccine side effects with parents/patients & only 21% felt they received adequate teaching regarding immunization during training.

Conclusions

Important gaps were identified in the knowledge of graduating nursing, medical, & pharmacy trainees regarding vaccine indications/contraindications, adverse events & safety. The national curriculum review revealed wide variability in immunization curriculum content & evaluation. There is clearly a need for educators to assess current curricula and adapt existing educational resources such as the Immunization Competencies for Health Professionals in Canada.
The complexity of premenstrual dysphoric disorder - risk factors in the population of Polish women
Authors: Skrzypulec-Plinta Violetta , Drosdzol Agnieszka , Nowosielski Krzysztof , Plinta Ryszard
Published: November 2010

Background

Premenstrual dysphoric disorder has multiple determinants in the biological, psychological and socio-cultural domains. The aim of the study was to evaluate the risk factors for premenstrual dysphoric disorder in Polish women, considering their reproductive history, socio-economic factors, as well as lifestyle and health-related factors.

Methods

2,500 females, aged 18 to 45, from the Upper Silesian region of Poland were eligible for the prospective population study. The final study sample was 1,540 individuals. The research was based on a questionnaire containing socio-economic status, general health, lifestyle, medical and reproductive history, premenstrual symptoms based on the American Psychiatric Association's criteria for diagnosing premenstrual dysphoric disorder, and patient prospective daily ratings of symptoms. The Statistica 8.0 computer software was used for statistical analysis. The value of p < 0.05 was adopted as the level of statistical significance.

Results

The mean age of the studied population was 31.9 +/- 7.3 years. The majority of the studied women were married (57.9%), lived in large cities (42.0%) and had tertiary education (43.2%). The results of the study indicated that the prevalence of premenstrual dysphoric disorder was 2.1%. The final statistical analysis revealed that only tertiary education decreased the risk of premenstrual dysphoric disorder (OR = 0.08; p < 0.05).

Conclusions

Our research showed that women with tertiary education are less vulnerable to premenstrual dysphoric disorder than women with a lower level of education. Reproductive and lifestyle factors seem to be play a lesser role.
Chungsim-Yeunja-Tang decreases the inflammatory response in peripheral blood mononuclear cells from patients with cerebral infarction through an NF-κB dependent mechanism
Authors: Jeong Hyun-Ja , Choi In-Young , Kim Min-Ho , Kim Hyung-Min , Moon Phil-Dong , Hong Jin-Woo , Kim Soo-Hyun
Published: November 2010

Background

Chungsim-Yeunja-Tang (CYT) has been used as a medicine for cerebral infarction (CI) patients in Korea. The objective of this study was to determine precisely the effect of CYT on CI patients using peripheral blood mononuclear cells (PBMCs).

Methods

For a clinical study, 47 CI patients were identified who had taken CYT (0.01 g/kg) 3 times a day after meals for 2 weeks by oral administration. For ex vivo experiments, peripheral blood mononuclear cells (PBMCs) were isolated from CI patients. We analyzed the effect of CYT and its main components on lipopolysaccharide (LPS)-induced cytokine production and mechanism on PBMCs of CI patients by using ELISA, western blot analysis, transcription factor enzyme-linked immunoassay, and caspase assay.

Results

Clinical signs of CI significantly disappeared about 2 weeks after oral administration of CYT to CI patients (P< 0.05). CYT and quercetin, an active compound of CYT, significantly inhibited LPS-induced interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production and expression in PBMCs. CYT and quercetin also inhibited LPS-induced nuclear translocation and DNA binding activities of nuclear factor-κB and degradation of IκBα. In addition, CYT and quercetin inhibited LPS-induced IL-32 expression and caspase-1 activation.

Conclusion

These results suggest a mechanism that might explain the beneficial effect of CYT in treating CI patients. Taken together, our findings indicate that inhibition of IL-32 expression and caspase-1 activation may be a novel biomarker and potential therapeutic target in CI.
A novel totivirus and piscine reovirus (PRV) in Atlantic salmon (Salmo salar) with cardiomyopathy syndrome (CMS)
Authors: Løvoll Marie , Wiik-Nielsen Jannicke , Grove Søren , Wiik-Nielsen Christer R , Kristoffersen Anja B , Faller Randi , Poppe Trygve , Jung Joonil , Pedamallu Chandra S , Nederbragt Alexander J , Meyerson Matthew , Rimstad Espen , Tengs Torstein
Published: November 2010

Background

Cardiomyopathy syndrome (CMS) is a severe disease affecting large farmed Atlantic salmon. Mortality often appears without prior clinical signs, typically shortly prior to slaughter. We recently reported the finding and the complete genomic sequence of a novel piscine reovirus (PRV), which is associated with another cardiac disease in Atlantic salmon; heart and skeletal muscle inflammation (HSMI). In the present work we have studied whether PRV or other infectious agents may be involved in the etiology of CMS.

Results

Using high throughput sequencing on heart samples from natural outbreaks of CMS and from fish experimentally challenged with material from fish diagnosed with CMS a high number of sequence reads identical to the PRV genome were identified. In addition, a sequence contig from a novel totivirus could also be constructed. Using RT-qPCR, levels of PRV in tissue samples were quantified and the totivirus was detected in all samples tested from CMS fish but not in controls. In situ hybridization supported this pattern indicating a possible association between CMS and the novel piscine totivirus.

Conclusions

Although causality for CMS in Atlantic salmon could not be proven for either of the two viruses, our results are compatible with a hypothesis where, in the experimental challenge studied, PRV behaves as an opportunist whereas the totivirus might be more directly linked with the development of CMS.
Profiles of cytokine and chemokine gene expression in human pulmonary epithelial cells induced by human and avian influenza viruses
Authors: Lam WY , Yeung Apple CM , Chu Ida MT , Chan Paul KS
Published: November 2010

Influenza pandemic remains a serious threat to human health. In this study, the repertoire of host cellular cytokine and chemokine responses to infections with highly pathogenic avian influenza H5N1, low pathogenicity avian influenza H9N2 and seasonal human influenza H1N1 were compared using anin vitrosystem based on human pulmonary epithelial cells. The results showed that H5N1 was more potent than H9N2 and H1N1 in inducing CXCL-10/IP-10, TNF-alpha and CCL-5/RANTES. The cytokine/chemokine profiles for H9N2, in general, resembled those of H1N1. Of interest, only H1N1, but none of the avian subtypes examined could induce a persistent elevation of the immune-regulatory cytokine - TGF-β2. The differential expression of cytokines/chemokines following infection with different influenza viruses could be a key determinant for clinical outcome. The potential of using these cytokines/chemokines as prognostic markers or targets of therapy is worth exploring.
NO signaling and S-nitrosylation regulate PTEN inhibition in neurodegeneration
Authors: Kwak Young-Don , Ma Tao , Diao Shiyong , Zhang Xue , Chen Yaomin , Hsu Janet , Lipton Stuart A , Masliah Eliezer , Xu Huaxi , Liao Francesca-Fang
Published: November 2010

Background

The phosphatase PTEN governs the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway which is arguably the most important pro-survival pathway in neurons. Recently, PTEN has also been implicated in multiple important CNS functions such as neuronal differentiation, plasticity, injury and drug addiction. It has been reported that loss of PTEN protein, accompanied by Akt activation, occurs under excitotoxic conditions (stroke) as well as in Alzheimer's (AD) brains. However the molecular signals and mechanism underlying PTEN loss are unknown.

Results

In this study, we investigated redox regulation of PTEN, namely S-nitrosylation, a covalent modification of cysteine residues by nitric oxide (NO), and H2O2-mediated oxidation. We found that S-nitrosylation of PTEN was markedly elevated in brains in the early stages of AD (MCI). Surprisingly, there was no increase in the H2O2-mediated oxidation of PTEN, a modification common in cancer cell types, in the MCI/AD brains as compared to normal aged control. Using several cultured neuronal models, we further demonstrate that S-nitrosylation, in conjunction with NO-mediated enhanced ubiquitination, regulates both the lipid phosphatase activity and protein stability of PTEN. S-nitrosylation and oxidation occur on overlapping and distinct Cys residues of PTEN. The NO signal induces PTEN protein degradation via the ubiquitin-proteasome system (UPS) through NEDD4-1-mediated ubiquitination.

Conclusion

This study demonstrates for the first time that NO-mediated redox regulation is the mechanism of PTEN protein degradation, which is distinguished from the H2O2-mediated PTEN oxidation, known to only inactivate the enzyme. This novel regulatory mechanism likely accounts for the PTEN loss observed in neurodegeneration such as in AD, in which NO plays a critical pathophysiological role.
Evaluation of rK-39 strip test using urine for diagnosis of visceral leishmaniasis in an endemic area in Bangladesh
Authors: Khan Md Gulam Musawwir , Alam Mohammad Shafiul , Podder Milka Patracia , Itoh Makoto , Jamil Kazi M , Haque Rashidul , Wagatsuma Yukiko
Published: November 2010

Diagnosis of visceral leishmaniasis (VL) by demonstration of parasites in tissue smears obtained from bone marrow, spleen or lymph nodes is risky, painful, and difficult. The rK-39 strip test is widely used for the diagnosis of VL using blood/serum samples in endemic countries. The aim of the study was to evaluate the rK-39 strip test using urine sample as a non-invasive means for the diagnosis of VL. The rk-39 strip test was performed using urine from 100 suspected VL cases along with 25 disease control (malarial febrile cases) and 50 healthy control (from endemic and non-endemic areas). All the VL suspected cases were positive with the rK-39 strip test using serum. The sensitivity and specificity of the rK-39 strip test using urine samples was 95% and 93.3%, respectively, compared to serum based rK-39 test. The findings suggest that the urine based rK-39 test could be a practical and efficient tool for the diagnosis of VL patients in rural areas, particularly where resources are limited.
Analysis of the expression pattern of the BCL11B gene and its relatives in patients with T-cell acute lymphoblastic leukemia
Authors: Huang Xin , Chen Shaohua , Shen Qi , Yang Lijian , Li Bo , Zhong Liye , Geng Suxia , Du Xin , Li Yangqiu
Published: November 2010

Background

In a human T-cell acute lymphoblastic leukemia (T-ALL) cell line (Molt-4), siRNA-mediated suppression of BCL11B expression was shown to inhibit proliferation and induce apoptosis, functions which may be related to genes involved in apoptosis (such as TNFSF10 and BCL2L1) and TGF-β pathways (such as SPP1 and CREBBP).

Methods

The expression levels of the above mentioned genes and their correlation with the BCL11B gene were analyzed in patients with T-ALL using the TaqMan and SYBR Green I real-time polymerase chain reaction technique.

Results

Expression levels of BCL11B, BCL2L1, and CREBBP mRNA in T-ALL patients were significantly higher than those from healthy controls (P < 0.05). In T-ALL patients, the BCL11B expression level was negatively correlated with the BCL2L1 expression level (r
s = -0.700; P
< 0.05), and positively correlated with the SPP1 expression level (r
s = 0.683; P
< 0.05). In healthy controls, the BCL11B expression level did not correlate with the TNFSF10, BCL2L1, SPP1, or CREBBP expression levels.

Conclusions

Over-expression of BCL11B might play a role in anti-apoptosis in T-ALL cells through up-regulation of its downstream genes BCL2L1 and CREBBP.
First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib
Authors: Wei Guoqing , Rafiyath Shamudheen , Liu Delong
Published: November 2010

Imatinib, a tyrosine kinase inhibitor (TKI) of BCR-ABL, was the standard first-line therapy for chronic myeloid leukemia (CML) for almost 10 years. Dasatinib and nilotinib, two newer drugs with higher potency than imatinib against BCR-ABL and activity against most imatinib-resistant BCR-ABL mutations, have each shown superior efficacy compared with imatinib for first-line treatment of chronic-phase CML in randomized phase 3 trials. With 14 months follow-up time, available data suggest no obvious differences in efficacy between dasatinib and nilotinib. Compared with imatinib, dasatinib is associated with higher rates of pleural effusion and thrombocytopenia, but lower rates of edema, gastrointestinal AEs, musculoskeletal AEs, and rash. Nilotinib is associated with higher rates of dermatologic toxicity, headache, and biochemical abnormalities associated with hepatic and pancreatic toxicity compared with imatinib, but lower rates of edema, gastrointestinal AEs, muscle spasm, and neutropenia. Several studies have shown that poor adherence to imatinib detrimentally affects responses and should be considered in patients with a suboptimal response. The different dosing requirements of dasatinib (once daily with or without food) and nilotinib (twice daily with fasting) may be an additional factor in selecting frontline agents. This review compares and contrasts the three FDA approved first line TKI agents.
Single nucleotide polymorphisms in the mitochondrial displacement loop and outcome of esophageal squamous cell carcinoma
Authors: Zhang Ruixing , Wang Rui , Zhang Fengbin , Wu Chensi , Fan Haiyan , Li Yan , Wang Cuiju , Guo Zhanjun
Published: November 2010

Backgroud

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described for different types of cancers and might be associated with cancer risk and disease outcome. We used a population-based series of esophageal squamous cell carcinoma (ESCC) patients for investigating the prediction power of SNPs in mitochondrial D-loop.

Methods

The D-loop region of mtDNA was sequenced for 60 ESCC patients recorded in the Fourth Hospital of Hebei Medical University between 2003 and 2004. The 5 year survival curve were calculated with the Kaplan-Meier method and compared by the log-rank test at each SNP site, a multivariate survival analysis was also performed with the Cox proportional hazards method.

Results

The SNP sites of nucleotides 16274G/A, 16278C/T and 16399A/G were identified for prediction of post-operational survival by the log-rank test. In an overall multivariate analysis, the 16278 and 16399 alleles were identified as independent predictors of ESCC outcome. The length of survival of patients with the minor allele 16278T genotype was significantly shorter than that of patients with 16278C at the 16278 site (relative risk, 3.001; 95% CI, 1.029 - 8.756;p= 0.044). The length of survival of patients with the minor allele 16399G genotype was significantly shorter than that of patients with the more frequent allele 16399A at the 16399 site in ESCC patients (relative risk, 3.483; 95% CI, 1.068 - 11.359;p= 0.039).

Conclusion

Genetic polymorphisms in the D-loop are independent prognostic markers for patients with ESCC. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups at high risk of a poor disease outcome.
Combined magnetic resonance and optical imaging of head and neck tumor xenografts using Gadolinium-labelled phosphorescent polymeric nanomicelles
Authors: Kumar Rajiv , Ohulchanskyy Tymish Y , Turowski Steve G , Thompson Mark E , Seshadri Mukund , Prasad Paras N
Published: November 2010

Background

The overall objective of this study was to develop a nanoparticle formulation for dual modality imaging of head and neck cancer. Here, we report the synthesis and characterization of polymeric phospholipid-based nanomicelles encapsulating near-infrared (NIR) phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin [Pt(TPNP)] and surface functionalized with gadolinium [Pt(TPNP)-Gd] for combined magnetic resonance imaging (MRI) and NIR optical imaging applications.

Methods

Dynamic light scattering, electron microscopy, optical spectroscopy and MR relaxometric measurements were performed to characterize the optical and magnetic properties of nanoparticles in vitro. Subsequently, in vivo imaging experiments were carried out using nude mice bearing primary patient tumor-derived human head and neck squamous cell carcinoma xenografts.

Results

The nanomicelles were ~100 nm in size and stable in aqueous suspension. T1-weighted MRI and relaxation rate (R1 = 1/T1) measurements carried out at 4.7 T revealed enhancement in the tumor immediately post injection with nanomicelles, particularly in the tumor periphery which persisted up to 24 hours post administration. Maximum intensity projections (MIPs) generated from 3D T1-weighted images also demonstrated visible enhancement in contrast within the tumor, liver and blood vessels. NIR optical imaging performed (in vivo and ex vivo) following completion of MRI at the 24 h time point confirmed tumor localization of the nanoparticles. The large spectral separation between the Pt(TPNP) absorption (~700 nm) and phosphorescence emission (~900 nm) provided a dramatic decrease in the level of background, resulting in high contrast optical (NIR phosphorescence) imaging.

Conclusions

In conclusion, Pt(TPNP)-Gd nanomicelles exhibit a high degree of tumor-avidity and favorable imaging properties that allow for combined MR and optical imaging of head and neck tumors. Further investigation into the potential of Pt(TPNP)-Gd nanomicelles for combined imaging and therapy of cancer is currently underway.
Opening and closing mechanisms of the leatherback sea turtle larynx: a crucial role for the tongue
Authors: Fraher John , Davenport John , Fitzgerald Edward , McLaughlin Patrick , Doyle Tom , Harman Luke , Cuffe Tracy
Published: November 2010

A combination of dissection and computed tomography scanning has provided significant novel insights into the structure and function of the Dermochelys coriacea larynx and its associated muscles. Several previously unknown features of the laryngeal aditus (glottis) are described and their functional significance in its opening and closure are considered. The tongue plays an essential part in producing and maintaining closure during dives and feeding bouts. Closure is brought about by compression of the glottis under the action of the two hyoglossus muscles. The tongue thus plays the role of the epiglottis of mammals, sealing the entrance to the larynx. As is already clear, opening is brought about by abduction of the arytenoid cartilages. In addition, there is a powerful mechanism for maintaining the larynx in close apposition to the hyoid plate during feeding and neck flexion, thereby enhancing the efficiency of feeding.
Human walking isn't all hard work: evidence of soft tissue contributions to energy dissipation and return
Authors: Zelik Karl E. , Kuo Arthur D.
Published: November 2010

The muscles and tendons of the lower extremity are generally considered the dominant producers of positive and negative work during gait. However, soft-tissue deformations not captured by joint rotations might also dissipate, store and even return substantial energy to the body. A key locomotion event is the collision of the leg with the ground, which deforms soft tissues appreciably in running. Significant deformation might also result from the impulsive ground collision in walking. In a study of normal human walking (N=10; 0.7–2.0 m s–1 speeds), we show indirect evidence for both negative and positive work performed by soft tissue, consistent with a damped elastic collision and rebound. We used the difference between measured joint work and another quantity – the work performed on the body center of mass – to indicate possible work performed by soft tissue. At 1.25 m s–1, we estimated that soft tissue performs approximately 7.5 J of negative work per collision. This constitutes approximately 60% of the total negative collision work and 31% of the total negative work per stride. The amount of soft tissue work during collision increases sharply with speed. Each collision is followed by 4 J of soft tissue rebound that is also not captured by joint work measures. Soft tissue deformation may save muscles the effort of actively dissipating energy, and soft tissue elastic rebound could save up to 14% of the total positive work per stride. Soft tissues not only cushion impacts but also appear to perform substantial work.
Disrupting vagal feedback affects birdsong motor control
Authors: Méndez Jorge M. , Dall'Asén Analía G. , Goller Franz
Published: November 2010

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback.