Neuroendocrine differentiation and neuroendocrine morphology as two different patterns in large-cell bronchial carcinomas: outcome after complete resection

BACKGROUND: In 1999, large-cell neuroendocrine carcinoma of the lung was introduced by the World Health Organization (WHO) as a new tumor entity in the group of non-small cell, epithelial tumors, a differentiated classification of neuroendocrine tumors of the lung not existing until this time. Scientific knowledge on prognosis and therapy of these tumors, especially between those with neuroendocrine morphology only and those showing additional expression of neuroendocrine markers, is fragmentary. In this analysis, we studied the clinical behavior and the prognosis of these two rare tumor entities. PATIENTS AND METHODS: The analysis comprises 12 patients of a total of 2053, who underwent thoracotomy for non small-cell lung carcinoma between 1997 and 2005 in the Department of Thoracic Surgery at the University Hospital of Freiburg. Clinical data, pathological examinations as well as complete follow-up were reviewed from large-cell carcinoma with neuroendocrine morphology only (n=4) and from large-cell carcinoma expressing neuroendocrine markers (n=8). RESULTS: The median survival of patients with neuroendocrine morphology was 30 months (11–96 months). In the patient group showing the expression of neuroendocrine markers, the median survival time was 20 months (2–26 months). Tumor recurrences occurred in the group with neuroendocrine morphology, without exception, in the form of distant metastases and in the group with neuroendocrine markers as intrapulmonary metastases. CONCLUSION: Large-cell neuroendocrine carcinomas of the lung show aggressive behavior with a poor prognosis. Expression of neuroendocrine markers markedly reduce tumor-free interval as well as survival and might influence the site of metastases

Resonances in J/ψ→ϕπ+π−J/\psi \to \phi \pi ^+\pi ^- and ϕK+K−\phi K^+K^-

A partial wave analysis is presented of $J/\psi \to \phi \pi ^+\pi ^-$ and $\phi K^+K^-$ from a sample of 58M $J/\psi$ events in the BES II detector. The $f_0(980)$ is observed clearly in both sets of data, and parameters of the Flatt\' e formula are determined accurately: $M = 965 \pm 8$ (stat) $\pm 6$ (syst) MeV/c$^2$, $g_1 = 165 \pm 10 \pm 15$ MeV/c$^2$, $g_2/g_1 = 4.21 \pm 0.25 \pm 0.21$. The $\phi \pi \pi$ data also exhibit a strong $\pi \pi$ peak centred at $M = 1335$ MeV/c$^2$. It may be fitted with $f_2(1270)$ and a dominant $0^+$ signal made from $f_0(1370)$ interfering with a smaller $f_0(1500)$ component. There is evidence that the $f_0(1370)$ signal is resonant, from interference with $f_2(1270)$. There is also a state in $\pi \pi$ with $M = 1790 ^{+40}_{-30}$ MeV/c$^2$ and $\Gamma = 270 ^{+60}_{-30}$ MeV/c$^2$; spin 0 is preferred over spin 2. This state, $f_0(1790)$, is distinct from $f_0(1710)$. The $\phi K\bar K$ data contain a strong peak due to $f_2'(1525)$. A shoulder on its upper side may be fitted by interference between $f_0(1500)$ and $f_0(1710)$.Comment: 17 pages, 6 figures, 1 table. Submitted to Phys. Lett.

First Measurements of eta_c Decaying into K^+K^-2(pi^+pi^-) and 3(pi^+pi^-)

The decays of eta_c to K^+K^-2(pi^+pi^-) and 3(pi^+pi^-) are observed for the first time using a sample of 5.8X10^7 J/\psi events collected by the BESII detector. The product branching fractions are determined to be B(J/\psi-->gamma eta_c)*B(eta_c-->K^+K^-pi^+pi^-pi^+pi^-)=(1.21+-0.32+- 0.23)X10^{-4}$,B(J/\psi-->gamma eta_c)*B(eta_c-->K^{*0}\bar{K}^{*0}pi^+pi^-)= (1.29+-0.43+-0.32)X10^{-4}$, and (J/\psi-->gamma eta_c)* B(eta_c-->pi^+pi^-pi^+pi^-pi^+pi^-)= (2.59+-0.32+-0.48)X10^{-4}. The upper limit for eta_c-->phi pi^+pi^-pi^+pi^- is also obtained as B(J/\psi-->gamma eta_c)*B(eta_c--> phi pi^+pi^-pi^+pi^-)< 6.03 X10^{-5} at the 90% confidence level.Comment: 11 pages, 4 figure

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Face Coding Is Bilateral in the Female Brain

Background: It is currently believed that face processing predominantly activates the right hemisphere in humans, but available literature is very inconsistent. Methodology/Principal Findings: In this study, ERPs were recorded in 50 right-handed women and men in response to 390 faces (of different age and sex), and 130 technological objects. Results showed no sex difference in the amplitude of N170 to objects; a much larger face-specific response over the right hemisphere in men, and a bilateral response in women; a lack of face-age coding effect over the left hemisphere in men, with no differences in N170 to faces as a function of age; a significant bilateral face-age coding effect in women. Conclusions/Significance: LORETA reconstruction showed a significant left and right asymmetry in the activation of the fusiform gyrus (BA19), in women and men, respectively. The present data reveal a lesser degree of lateralization of brain functions related to face coding in women than men. In this light, they may provide an explanation of the inconsistencies in the available literature concerning the asymmetric activity of left and right occipito-temporal cortices devoted to fac

The Mast Cell Degranulator Compound 48/80 Directly Activates Neurons

Background Compound 48/80 is widely used in animal and tissue models as a “selective” mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. Methodology/Principal Findings We used in vivo recordings from extrinsic intestinal afferents together with Ca++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H1 and H2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca++ transients in mast cell-free enteric neuron cultures. Conclusions/Significance The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn

A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein

Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1–4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1–4, YFV, and WNV and confers protection from lethal challenge with DENV 1–4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans

Exact score distribution computation for ontological similarity searches

<p>Abstract</p> <p>Background</p> <p>Semantic similarity searches in ontologies are an important component of many bioinformatic algorithms, e.g., finding functionally related proteins with the Gene Ontology or phenotypically similar diseases with the Human Phenotype Ontology (HPO). We have recently shown that the performance of semantic similarity searches can be improved by ranking results according to the probability of obtaining a given score at random rather than by the scores themselves. However, to date, there are no algorithms for computing the exact distribution of semantic similarity scores, which is necessary for computing the exact <it>P</it>-value of a given score.</p> <p>Results</p> <p>In this paper we consider the exact computation of score distributions for similarity searches in ontologies, and introduce a simple null hypothesis which can be used to compute a <it>P</it>-value for the statistical significance of similarity scores. We concentrate on measures based on Resnik's definition of ontological similarity. A new algorithm is proposed that collapses subgraphs of the ontology graph and thereby allows fast score distribution computation. The new algorithm is several orders of magnitude faster than the naive approach, as we demonstrate by computing score distributions for similarity searches in the HPO. It is shown that exact <it>P</it>-value calculation improves clinical diagnosis using the HPO compared to approaches based on sampling.</p> <p>Conclusions</p> <p>The new algorithm enables for the first time exact <it>P</it>-value calculation via exact score distribution computation for ontology similarity searches. The approach is applicable to any ontology for which the annotation-propagation rule holds and can improve any bioinformatic method that makes only use of the raw similarity scores. The algorithm was implemented in Java, supports any ontology in OBO format, and is available for non-commercial and academic usage under: <url>https://compbio.charite.de/svn/hpo/trunk/src/tools/significance/</url></p