bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells
Authors: Ren Xi , Gomez Gustavo A. , Zhang Bo , Lin Shuo 
Published: February 2010

AbstractRecent lineage studies suggest that hematopoietic stem cells (HSCs) may be derived from endothelial cells. However, the genetic hierarchy governing the emergence of HSCs remains elusive. We report here that zebrafish ets1-related protein (etsrp), which is essential for vascular endothelial development, also plays a critical role in the initiation of definitive hematopoiesis by controlling the expression of 2 stem cell leukemia (scl) isoforms (scl-α and scl-β) in angioblasts. In etsrp morphants, which are deficient in endothelial and HSC development, scl-α alone partially rescues angioblast specification, arterial-venous differentiation, and the expression of HSC markers, runx1 and c-myb, whereas scl-β requires angioblast rescue by fli1a to restore runx1 expression. Interestingly, when vascular endothelial growth factor (Vegf) signaling is inhibited, HSC marker expression can still be restored by scl-α in etsrp morphants, whereas the rescue of arterial ephrinb2a expression is blocked. Furthermore, both scl isoforms partially rescue runx1 but not ephrinb2a expression in embryos deficient in Vegf signaling. Our data suggest that downstream of etsrp, scl-α and fli1a specify the angioblasts, whereas scl-β further initiates HSC specification from this angioblast population, and that Vegf signaling acts upstream of scl-β during definitive hematopoiesis.
Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell–lymphotoxin-dependent pathway
Authors: Kumar Varsha , Scandella Elke , Danuser Renzo , Onder Lucas , Nitschké Maximilian , Fukui Yoshinori , Halin Cornelia , Ludewig Burkhard , Stein Jens V. 
Published: February 2010

AbstractAdaptive immune responses are characterized by substantial restructuring of secondary lymphoid organs. The molecular and cellular factors responsible for virus-induced lymphoid remodeling are not well known to date. Here we applied optical projection tomography, a mesoscopic imaging technique, for a global analysis of the entire 3-dimensional structure of mouse peripheral lymph nodes (PLNs), focusing on B-cell areas and high endothelial venule (HEV) networks. Structural homeostasis of PLNs was characterized by a strict correlation between total PLN volume, B-cell volume, B-cell follicle number, and HEV length. After infection with lymphocytic choriomeningitis virus, we observed a substantial, lymphotoxin (LT) β-receptor–dependent reorganization of the PLN microarchitecture, in which an initial B-cell influx was followed by 3-fold increases in PLN volume and HEV network length on day 8 after infection. Adoptive transfer experiments revealed that virus-induced PLN and HEV network remodeling required LTα1β2-expressing B cells, whereas the inhibition of vascular endothelial growth factor-A signaling pathways had no significant effect on PLN expansion. In summary, lymphocytic choriomeningitis virus-induced PLN growth depends on a vascular endothelial growth factor-A–independent, LT- and B cell–dependent morphogenic pathway, as revealed by an in-depth mesoscopic analysis of the global PLN structure.
Extreme lymphoproliferative disease and fatal autoimmune thrombocytopenia in FasL and TRAIL double-deficient mice
Authors: Sedger Lisa M. , Katewa Arna , Pettersen Ann K. , Osvath Sarah R. , Farrell Geoff C. , Stewart Graeme J. , Bendall Linda J. , Alexander Stephen I. 
Published: February 2010

AbstractTo delineate the relative roles of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand in lymphocyte biology and lymphoproliferative disease, we generated mice defective in both molecules. B6.GT mice develop severe polyclonal lymphoproliferative disease because of accumulating CD3+CD4−CD8−B220+ T cells, CD4+ and CD8+ T cells, and follicular B cells, and mice die prematurely from extreme lymphocytosis, thrombocytopenia, and hemorrhage. Accumulating lymphocytes resembled antigen-experienced lymphocytes, consistent with the maximal resistance of B6.GT CD4+ and CD8+ T cell to activation-induced cell death. More specifically, we show that TRAIL contributes to Fas ligand-mediated activation-induced cell death and controls lymphocyte apoptosis in the presence of interferon-γ once antigen stimulation is removed. Furthermore, dysregulated lymphocyte homeostasis results in the production of anti-DNA and rheumatoid factor autoantibodies, as well as antiplatelet IgM and IgG causing thrombocytopenia. Thus, B6.GT mice reveal new roles for TRAIL in lymphocyte homeostasis and autoimmune lymphoproliferative syndromes and are a model of spontaneous idiopathic thrombocytopenia purpura secondary to lymphoproliferative disease.
Treatment outcome of multidrug/extensively drug-resistant tuberculosis in Latvia, 2000–2004
Authors: Leimane V. , Dravniece G. , Riekstina V. , Sture I. , Kammerer S. , Chen M.P. , Skenders G. , Holtz T.H. 
Published: February 2010

In the present study, we characterised drug-resistance patterns, compared treatment outcome between extensively and nonextensively drug-resistant tuberculosis (non-XDR-TB) cases, and assessed risk factors for poor outcome in a high-prevalence country that screens all TB patients for first-line anti-TB drug resistance.We reviewed drug susceptibility test results among all pulmonary TB cases in Latvia diagnosed from 2000–2004, as well as demographic and clinical characteristics, drug-resistance patterns, and treatment outcomes.During the 5-yr period, 1,027 multidrug-resistant tuberculosis (MDR-TB) cases initiated treatment. Among all cases, the proportion that experienced an outcome of cure or completion increased from 66.2 to 70.2% (p = 0.06 for linear trend). Among the 48 (4.7%) XDR-TB cases, 18 (38%) were cured, four (8%) died, three (6%) defaulted, and treatment failed in 23 (48%). In proportional-hazards analysis, characteristics significantly associated with poor outcome included XDR-TB, being retired, presence of bilateral cavitation, and previous MDR-TB treatment history for those aged ≥55 yrs.Overall, treatment success among all MDR-TB cases increased over time. Strategies to prevent transmission of XDR-TB and to further improve treatment outcome are crucial for the future of TB control in Latvia.
Healthy hire effect, job selection and inhalation exposure among young adults with asthma
Authors: Olivieri M. , Mirabelli M.C. , Plana E. , Radon K. , Antó J.M. , Bakke P. , Benke G. , D’Errico A. , Henneberger P. , Kromhout H. , Norbäck D. , Torén K. , van Sprundel M. , Villani S. , Wieslander G. , Zock J-P. , Kogevinas M. 
Published: February 2010

The aim of the present study was to assess whether asthma onset prior to entering the workforce influences whether a person holds a subsequent job with asthma-related inhalation exposures.The data of 19,784 adults from the European Community Respiratory Health Survey were analysed. For each respondent, a current or previously held job was linked to a job exposure matrix assigning high, low or no exposure to dust, gases or fumes. Jobs were also categorised according to the risk of exposures related to occupational asthma. Associations between asthma and subsequent occupational exposures were assessed using logistic regression models, with a random intercept for study centre and fixed adjustment for age, sex, type of study sample and smoking status.Of the respondents, 8% (n = 1,619) reported asthma with onset before completion of full-time education. This population was at decreased risk of having a job with high (odds ratio 0.79; 95% confidence interval 0.68–0.92) or low (0.91; 0.80–1.03) exposure to dust, gases or fumes. The associations were consistent across exposure types (dusts, gases or fumes) and for jobs with a high risk of occupational asthma.Adults with asthma onset prior to entering the workforce may be less likely to hold jobs involving inhalation exposures.
Tiotropium as a first maintenance drug in COPD: secondary analysis of the UPLIFT® trial
Authors: Troosters T. , Celli B. , Lystig T. , Kesten S. , Mehra S. , Tashkin D.P. , Decramer M. 
Published: February 2010

The aim of the present study was investigate the long-term effect of tiotropium as first maintenance respiratory medication in chronic obstructive pulmonary disease (COPD).A 4-yr, randomised, multicentre, double-blind, parallel-group, placebo-controlled trial (Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®)) was conducted. Analysis focused on the effect of tiotropiumversusmatching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting β-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation. Spirometry, health-related quality of life (St George’s Respiratory Questionnaire (SGRQ) score), exacerbations of COPD and mortality were also analysed.403 patients (mean±sdage 63±8 yrs, post-bronchodilator forced expiratory volume in 1 s (FEV1) 53±12% predicted) received tiotropium and 407 (64±8 yrs of age, post-bronchodilator FEV151±12% pred) received placebo. Post-bronchodilator FEV1decline was 42±4 mL·yr−1in the tiotropium group and 53±4 mL·yr−1in the placebo group (p = 0.026). At 48 months, the morning pre-dose FEV1was 134 mL higher in the tiotropium group compared to the placebo group (p<0.001). SGRQ total score declined more slowly in the tiotropium group (difference of 1.05±0.34 units·yr−1; p = 0.002). This was particularly significant for the impact (difference of 1.08±0.37 units·yr−1; p = 0.004) and activity (1.44±0.40 units·yr−1; p<0.001) domains, but not for symptoms (0.26±0.50 units·yr−1; p = 0.6). At 48 months, the difference in total score was 4.6 units (p<0.001) with tiotropium compared to placebo.In patients with COPD who are not on maintenance therapy, tiotropium is associated with significant benefits in disease progression.
Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin
Authors: Glader P. , Smith M.E. , Malmhäll C. , Balder B. , Sjöstrand M. , Qvarfordt I. , Lindén A. 
Published: February 2010

Previous studies on mouse models have indicated that interleukin (IL)-17 and IL-17-producing T-helper (Th) cells are important for pulmonary host defence against Gram-negative bacteria. Human correlates to these findings have not yet been demonstrated. The aim of the present study was to determine whether or not IL-17-producing Th cells are present and whether IL-17 and other Th17-associated cytokines are involved in the immunological response to endotoxin in human airways.Segmental exposure to endotoxin and contralateral exposure to vehicle were performed in the lungs of healthy volunteers, with subsequent bronchoalveolar lavage 12 or 24 h after exposure to study local changes in cytokines and inflammatory cells.Endotoxin exposure increased concentrations of IL-17, IL-22 and their downstream effector molecules, human β-defensin-2 and IL-8/CXC chemokine ligand 8, in bronchoalveolar lavage fluid. Th cells with the capacity to produce IL-17 were found among the bronchoalveolar lavage cells, and expression of IL-17 mRNA correlated with expression of the transcription factor, retinoic-acid-receptor-related orphan receptor C variant 2. Moreover, endotoxin increased the numbers of neutrophils, macrophages and IL-17-producing T-cells, as well as the concentration of the Th17-regulating cytokines, IL-21 and IL-23.In conclusion, IL-17-producing Th cells are present, and IL-17, as well as other Th17-associated cytokines, is involved in the immunological response to endotoxin in human airways.
Plasma DNA level in predicting therapeutic efficacy in advanced nonsmall cell lung cancer
Authors: Kumar S. , Guleria R. , Singh V. , Bharti A.C. , Mohan A. , Das B.C. 
Published: February 2010

Assessment of total plasma DNA can be a promising noninvasive tool for monitoring the effect of cytotoxic therapies in order to predict therapeutic efficacy at an early stage.Cell-free plasma DNA levels were quantified before the first, second and third cycle of chemotherapy in 42 patients with advanced nonsmall cell lung cancer and correlated with response to therapy, as assessed by computed tomography following the third chemotherapy cycle.A significantly lower plasma DNA level, measured before various treatment cycles, was found in patients with remission or stable disease than in those with progression. Higher levels and insufficient decrease in plasma DNA levels during the course of chemotherapy indicated poor outcome. For predicting insufficient therapy response, a sensitivity of 26.9% was achieved at 100% specificity using plasma DNA levels before the first therapy cycle. Prediction of disease progression was achieved with a sensitivity of 35.7% at 100% specificity using plasma DNA levels before the first therapy cycle.Monitoring of plasma DNA levels during the course of chemotherapy could identify patients who are likely to exhibit an insufficient therapeutic response and disease progression at an early stage. This may help in individualising treatment, and could lead to better management of advanced-stage lung cancer.
Functional conservation between rodents and chicken of regulatory sequences driving skeletal muscle gene expression in transgenic chickens
Authors: McGrew Michael J , Sherman Adrian , Lillico Simon G , Taylor Lorna , Sang Helen 
Published: February 2010

Abstract
Background
Regulatory elements that control expression of specific genes during development have been shown in many cases to contain functionally-conserved modules that can be transferred between species and direct gene expression in a comparable developmental pattern. An example of such a module has been identified at the rat myosin light chain (MLC) 1/3 locus, which has been well characterised in transgenic mouse studies. This locus contains two promoters encoding two alternatively spliced isoforms of alkali myosin light chain. These promoters are differentially regulated during development through the activity of two enhancer elements. The MLC3 promoter alone has been shown to confer expression of a reporter gene in skeletal and cardiac muscle in transgenic mice and the addition of the downstream MLC enhancer increased expression levels in skeletal muscle. We asked whether this regulatory module, sufficient for striated muscle gene expression in the mouse, would drive expression in similar domains in the chicken.

Results
We have observed that a conserved downstream MLC enhancer is present in the chicken MLC locus. We found that the rat MLC1/3 regulatory elements were transcriptionally active in chick skeletal muscle primary cultures. We observed that a single copy lentiviral insert containing this regulatory cassette was able to drive expression of a lacZ reporter gene in the fast-fibres of skeletal muscle in chicken in three independent transgenic chicken lines in a pattern similar to the endogenous MLC locus. Reporter gene expression in cardiac muscle tissues was not observed for any of these lines.

Conclusions
From these results we conclude that skeletal expression from this regulatory module is conserved in a genomic context between rodents and chickens. This transgenic module will be useful in future investigations of muscle development in avian species.
Mutations in epidermal growth factor receptor and K-ras in Chinese patients with colorectal cancer
Authors: Yunxia Zuo , Jun Cao , Guanshan Zhu , Yachao Lu , Xueke Zhou , Jin Li 
Published: February 2010

Abstract

Background
Mutations of EGFR and K-ras are biomarkers for predicting the efficacy of targeting agents in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Data on the gene mutation status of EGFR and K-ras in Chinese patients with CRC are limited.

Methods
EGFR mutations in exon 18-21 and K-ras mutations in exon 1 and 2 were detected in tumor samples from 101 Chinese patients with CRC by polymerase chain reaction-single strand conformational polymorphism. The relationship between patients' characteristics and survival time and gene mutation status were analyzed using the Statistical Package for the Social Sciences.

Results
Only two samples (2.0%) had EGFR mutations in exon 18 or 21, and 33 of 101 samples (32.7%) had K-ras mutations in codon 12, 13, 45, 69, or 80. Univariate analysis suggested that differentiation might be correlated with K-ras mutations (p = 0.05), which was confirmed by a logistic regression model (p = 0.04). The median overall survival (OS) and median survival after metastasis were 44.0 and 18.0 months, respectively, in the mutant K-ras group, and 53.3 and 19.0 months, respectively, in the wild K-ras group. K-ras mutation was not an independent prognostic factor for OS or survival after metastasis (p = 0.79 and 0.78, respectively).

Conclusions
In Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans. New mutations in codons 45, 69, and 80 were found in the Chinese population. Poor differentiation was an independent factor related to K-ras mutations.
Association between gefitinib and hemorrhagic cystitis and severely contracted bladder: a case report
Authors: Arakawa Maki , Nakamura Kogenta , Yamada Yoshiaki , Rosser Charles J , Tobiume Motoi , Saito Hiroko , Hasegawa Takaaki , Honda Nobuaki 
Published: February 2010

Abstract

Background
Gefitinib remains an excellent treatment option for patients with a variety of cancers, including non small cell lung cancer (NSCLC). However, clinicians must be aware of the potential of gefitinib to cause an inflammatory reaction in the skin, lungs and bladder.

Case Presentation
We present a case on hemorrhagic cystitis and severaly contracted bladder in a patient with NSCLC on gefitinib.

Conclusions
Further studies are needed to substantiate the association of gefitinib therapy with hemorrhagic cystitis and contracted bladder.
A novel method for sample preparation of fresh lung cancer tissue for proteomics analysis by tumor cell enrichment and removal of blood contaminants
Authors: De Petris Luigi , Pernemalm Maria , Elmberger Göran , Bergman Per , Orre Lotta , Lewensohn Rolf , Lehtiö Janne 
Published: February 2010

Abstract

Background
In-depth proteomics analyses of tumors are frequently biased by the presence of blood components and stromal contamination, which leads to large experimental variation and decreases the proteome coverage. We have established a reproducible method to prepare freshly collected lung tumors for proteomics analysis, aiming at tumor cell enrichment and reduction of plasma protein contamination. We obtained enriched tumor-cell suspensions (ETS) from six lung cancer cases (two adenocarcinomas, two squamous-cell carcinomas, two large-cell carcinomas) and from two normal lung samples. The cell content of resulting ETS was evaluated with immunocytological stainings and compared with the histologic pattern of the original specimens. By means of a quantitative mass spectrometry-based method we evaluated the reproducibility of the sample preparation protocol and we assessed the proteome coverage by comparing lysates from ETS samples with the direct lysate of corresponding fresh-frozen samples.

Results
Cytological analyses on cytospin specimens showed that the percentage of tumoral cells in the ETS samples ranged from 20% to 70%. In the normal lung samples the percentage of epithelial cells was less then 10%. The reproducibility of the sample preparation protocol was very good, with coefficient of variation at the peptide level and at the protein level of 13% and 7%, respectively. Proteomics analysis led to the identification of a significantly higher number of proteins in the ETS samples than in the FF samples (244 vs 109, respectively). Albumin and hemoglobin were among the top 5 most abundant proteins identified in the FF samples, showing a high contamination with blood and plasma proteins, whereas ubiquitin and the mitochondrial ATP synthase 5A1 where among the top 5 most abundant proteins in the ETS samples.

Conclusion
The method is feasible and reproducible. We could obtain a fair enrichment of cells but the major benefit of the method was an effective removal of contaminants from red blood cells and plasma proteins resulting in larger proteome coverage compared to the direct lysis of frozen samples. This sample preparation method may be successfully implemented for the discovery of lung cancer biomarkers on tissue samples using mass spectrometry-based proteomics.
Species-independent bioassay for sensitive quantification of antiviral type I interferons
Authors: Kuri Thomas , Habjan Matthias , Penski Nicola , Weber Friedemann 
Published: February 2010

Abstract

Background
Studies of the host response to infection often require quantitative measurement of the antiviral type I interferons (IFN-α/β) in biological samples. The amount of IFN is either determined via its ability to suppress a sensitive indicator virus, by an IFN-responding reporter cell line, or by ELISA. These assays however are either time-consuming and lack convenient readouts, or they are rather insensitive and restricted to IFN from a particular host species.

Results
An IFN-sensitive, Renilla luciferase-expressing Rift Valley fever virus (RVFV-Ren) was generated using reverse genetics. Human, murine and avian cells were tested for their susceptibility to RVFV-Ren after treatment with species-specific IFNs. RVFV-Ren was able to infect cells of all three species, and IFN-mediated inhibition of viral reporter activity occurred in a dose-dependent manner. The sensitivity limit was found to be 1 U/ml IFN, and comparison with a standard curve allowed to determine the activity of an unknown sample.

Conclusions
RVFV-Ren replicates in cells of several species and is highly sensitive to pre-treatment with IFN. These properties allowed the development of a rapid, sensitive, and species-independent antiviral assay with a convenient luciferase-based readout.