bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonal Analysis of Colonizing Group B
Streptococcus
, Serotype IV, an Emerging Pathogen in the United States
Authors: Diedrick Michelle J. , Flores Aurea E. , Hillier Sharon L. , Creti Roberta , Ferrieri Patricia
Published: July 2010

Colonizing group B
Streptococcus
(GBS) capsular polysaccharide (CPS) type IV isolates were recovered from vaginal and rectal samples obtained from 97 (8.4%) nonpregnant women of 1,160 women enrolled in a U.S. multicenter GBS vaccine study from 2004 to 2008. Since this rate was much higher than the rate of prevalence of 0.4 to 0.6% that we found in previous studies, the isolates were analyzed by using surface protein profile identification, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) to characterize them and identify trends in DNA clonality and divergence. Of the 101 type IV isolates studied, 53 expressed α and group B protective surface (BPS) proteins, 27 expressed BPS only, 20 expressed α only, and 1 had no detectable surface proteins. The isolates spanned three PFGE macrorestriction profile groups, groups 37, 38, and 39, of which group 37 was predominant. The isolates in group 37 expressed the α and BPS proteins, while those in groups 38 and 39 expressed the α protein only, with two exceptions. MLST studies of selective isolates from the four protein profile groups showed that isolates expressing α,BPS or BPS only were of a new sequence type, sequence type 452, while those expressing α only or no proteins were mainly of a new sequence type, sequence type 459. Overall, our study revealed a limited diversity in surface proteins, MLST types, and DNA macrorestriction profiles for type IV GBS. There appeared to be an association between the MLST types and protein expression profiles. The increased prevalence of type IV GBS colonization suggested the possibility that this serotype may emerge as a GBS pathogen.
Clostridium sordellii
Brain Abscess Diagnosed by 16S rRNA Gene Sequencing
Authors: Valour F. , Boisset S. , Lebras L. , Martha B. , Boibieux A. , Perpoint T. , Chidiac C. , Ferry T. , Peyramond D.
Published: July 2010

Clostridium sordellii
is usually associated with skin and soft tissue infections. We describe the first case to our knowledge of a
Clostridium sordellii
-associated brain abscess, diagnosed by 16S rRNA gene sequencing, expanding the microbiological spectrum of brain abscesses, with emphasis on the role of 16S rRNA gene PCR in their etiologic diagnosis.
Multicentric Comparative Analytical Performance Study for Molecular Detection of Low Amounts of
Toxoplasma gondii
from Simulated Specimens
Authors: Sterkers Yvon , Varlet-Marie Emmanuelle , Cassaing Sophie , Brenier-Pinchart Marie-Pierre , Brun Sophie , Dalle Frédéric , Delhaes Laurence , Filisetti Denis , Pelloux Hervé , Yera Hélène , Bastien Patrick
Published: July 2010

Although screening for maternal toxoplasmic seroconversion during pregnancy is based on immunodiagnostic assays, the diagnosis of clinically relevant toxoplasmosis greatly relies upon molecular methods. A problem is that this molecular diagnosis is subject to variation of performances, mainly due to a large diversity of PCR methods and primers and the lack of standardization. The present multicentric prospective study, involving eight laboratories proficient in the molecular prenatal diagnosis of toxoplasmosis, was a first step toward the harmonization of this diagnosis among university hospitals in France. Its aim was to compare the analytical performances of different PCR protocols used for
Toxoplasma
detection. Each center extracted the same concentrated
Toxoplasma gondii
suspension and tested serial dilutions of the DNA using its own assays. Differences in analytical sensitivities were observed between assays, particularly at low parasite concentrations (≤2
T. gondii
genomes per reaction tube), with “performance scores” differing by a 20-fold factor among laboratories. Our data stress the fact that differences do exist in the performances of molecular assays in spite of expertise in the matter; we propose that laboratories work toward a detection threshold defined for a best sensitivity of this diagnosis. Moreover, on the one hand, intralaboratory comparisons confirmed previous studies showing that rep529 is a more adequate DNA target for this diagnosis than the widely used B1 gene. But, on the other hand, interlaboratory comparisons showed differences that appear independent of the target, primers, or technology and that hence rely essentially on proficiency and care in the optimization of PCR conditions.
Long-Lasting Protective Antiviral Immunity Induced by Passive Immunotherapies Requires both Neutralizing and Effector Functions of the Administered Monoclonal Antibody
Authors: Nasser Roudaina , Pelegrin Mireia , Michaud Henri-Alexandre , Plays Marc , Piechaczyk Marc , Gros Laurent
Published: July 2010

Using FrCasEretrovirus-infected newborn mice as a model system, we have shown recently that a long-lasting antiviral immune response essential for healthy survival emerges after a short treatment with a neutralizing (667) IgG2a isotype monoclonal antibody (MAb). This suggested that the mobilization of adaptive immunity by administered MAbs is key for the success in the long term for the MAb-based passive immunotherapy of chronic viral infections. We have addressed here whether the anti-FrCasEprotective endogenous immunity is the mere consequence of viral propagation blunting, which would simply give time to the immune system to react, and/or to actual immunomodulation by the MAb during the treatment. To this aim, we have compared viral replication, disease progression, and antiviral immune responses between different groups of infected mice: (i) mice treated with either the 667 MAb, its F(ab′)2fragment, or an IgM (672) with epitopic specificity similar to that of 667 but displaying different effector functions, and (ii) mice receiving no treatment but infected with a low viral inoculum reproducing the initial viral expansion observed in their infected/667 MAb-treated counterparts. Our data show that the reduction of FrCasEpropagation is insufficient on its own to induce protective immunity and support a direct immunomodulatory action of the 667 MAb. Interestingly, they also point to sequential actions of the administered MAb. In a first step, viral propagation is exclusively controlled by 667 neutralizing activity, and in a second one, this action is complemented by FcγR-binding-dependent mechanisms, which most likely combine infected cell cytolysis and the modulation of the antiviral endogenous immune response. Such complementary effects of administered MAbs must be taken into consideration for the improvement of future antiviral MAb-based immunotherapies.
Binding of the Human Cytomegalovirus (HCMV) Tegument Protein UL69 to UAP56/URH49 Is Not Required for Efficient Replication of HCMV
Authors: Kronemann Daniel , Hagemeier Stacy R. , Cygnar Dan , Phillips Stacia , Bresnahan Wade A.
Published: July 2010

The human cytomegalovirus (HCMV) tegument protein UL69 is important for efficient viral replication at low multiplicities of infection. Several molecular mechanisms by which UL69 contributes to HCMV replication have been proposed, including UL69's ability to interact with the mRNA export factors UAP56 and URH49 to facilitate the shuttling of viral mRNAs from the nuclei of infected cells. Using a UL69 viral mutant that is unable to bind UAP56 and URH49, we demonstrated that UL69's interaction with UAP56 or URH49 does not contribute to the growth phenotype associated with the UL69 deletion mutant.
Application of Broad-Spectrum Resequencing Microarray for Genotyping Rhabdoviruses
Authors: Dacheux Laurent , Berthet Nicolas , Dissard Gabriel , Holmes Edward C. , Delmas Olivier , Larrous Florence , Guigon Ghislaine , Dickinson Philip , Faye Ousmane , Sall Amadou A. , Old Iain G. , Kong Katherine , Kennedy Giulia C. , Manuguerra Jean-Claude , Cole Stewart T. , Caro Valérie , Gessain Antoine , Bourhy Hervé
Published: July 2010

The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using database similarity searching. We focused on one of the largest and most diverse viral families described to date, the family
Rhabdoviridae
. We demonstrate that this approach has the potential to identify both known and related viruses for which precise sequence information is unavailable. In particular, we demonstrate that a strategy based on consensus sequence determination for analysis of RMA output data enabled successful detection of viruses exhibiting up to 26% nucleotide divergence with the closest sequence tiled on the array. Using clinical specimens obtained from rabid patients and animals, this method also shows a high species level concordance with standard reference assays, indicating that it is amenable for the development of diagnostic assays. Finally, 12 animal rhabdoviruses which were currently unclassified, unassigned, or assigned as tentative species within the family
Rhabdoviridae
were successfully detected. These new data allowed an unprecedented phylogenetic analysis of 106 rhabdoviruses and further suggest that the principles and methodology developed here may be used for the broad-spectrum surveillance and the broader-scale investigation of biodiversity in the viral world.
Fundamental Difference in the Content of High-Mannose Carbohydrate in the HIV-1 and HIV-2 Lineages
Authors: Stansell Elizabeth , Desrosiers Ronald C.
Published: July 2010

The virus-encoded envelope proteins of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) typically contain 26 to 30 sites for N-linked carbohydrate attachment. N-linked carbohydrate can be of three major types: high mannose, complex, or hybrid. The lectin proteins from
Galanthus nivalis
(GNA) and
Hippeastrum
hybrid (HHA), which specifically bind high-mannose carbohydrate, were found to potently inhibit the replication of a pathogenic cloned SIV from rhesus macaques, SIVmac239. Passage of SIVmac239 in the presence of escalating concentrations of GNA and HHA yielded a lectin-resistant virus population that uniformly eliminated three sites (of 26 total) for N-linked carbohydrate attachment (Asn-X-Ser or Asn-X-Thr) in the envelope protein. Two of these sites were in the gp120 surface subunit of the envelope protein (Asn244 and Asn460), and one site was in the envelope gp41 transmembrane protein (Asn625). Maximal resistance to GNA and HHA in a spreading infection was conferred to cloned variants that lacked all three sites in combination. Variant SIV gp120s exhibited dramatically decreased capacity for binding GNA compared to SIVmac239 gp120 in an enzyme-linked immunosorbent assay (ELISA). Purified gp120s from six independent HIV type 1 (HIV-1) isolates and two SIV isolates from chimpanzees (SIVcpz) consistently bound GNA in ELISA at 3- to 10-fold-higher levels than gp120s from five SIV isolates from rhesus macaques or sooty mangabeys (SIVmac/sm) and four HIV-2 isolates. Thus, our data indicate that characteristic high-mannose carbohydrate contents have been retained in the cross-species transmission lineages for SIVcpz-HIV-1 (high), SIVsm-SIVmac (low), and SIVsm-HIV-2 (low).
Thermostability of Subpopulations of H2N3 Influenza Virus Isolates from Mallard Ducks
Authors: Negovetich Nicholas J. , Webster Robert G.
Published: July 2010

Maintenance of avian influenza virus in waterfowl populations requires that virions remain infectious while in the environment. Temperature has been shown to negatively correlate with persistence time, which is the duration for which virions are infectious. However, thermostability can vary between isolates regardless of subtype, and it is not known whether this variation occurs when host and geographic location of isolation are controlled. In this study, we analyzed the thermostabilities of 7 H2N3 viruses isolated from mallard ducks in Alberta, Canada. Virus samples were incubated at 37°C and 55°C, and infectivity titers were calculated at different time points. Based on the rate of infectivity inactivation at 37°C, isolates could be grouped into either a thermosensitive or thermostable fraction for both egg- and MDCK-grown virus populations. Titers decreased more rapidly for isolates incubated at 55°C, and this loss of infectivity occurred in a nonlinear, 2-step process, which is in contrast with the consensus on thermostability. This suggests that stock samples contain a mixture of subpopulations with different thermostabilities. The rate of decrease for the sensitive fraction was approximately 14 times higher than that for the stable fraction. The presence of subpopulations is further supported by selection experiments and plaque purification, both of which result in homogenous populations that exhibit linear decreases of infectivity titer. Therefore, variation of thermostability of influenza virus isolates begins at the level of the population. The presence of subpopulations with high thermostability suggests that avian viruses can persist in water longer than previously estimated, thus increasing the probability of transmission to susceptible hosts.
Use of a membraneless extraction module for the voltammetric determination of total sulfites in wine
Authors: Gonçalves Luís Moreira , da Anunciação Miriam Franco , Valente Inês Maria , Pacheco João Grosso , Rodrigues José António , Barros Aquiles Araújo
Published: July 2010

A recently developed membraneless extraction module (MLEM) for sample preparation aiming the analysis of volatile and semi-volatile compounds is applied in the voltammetric analysis of total sulfites in wine. Square-wave voltammetry (SWV) is very advantageous in this case because sulfur dioxide (SO2) is instrumentally directly detected. The developed method shows good repeatability (RSD lower than 5%) and linearity (between 20 to 220 mg l–1) as well as suitable limits of detection (6 mg l–1) and quantification (19 mg l–1). The proposed method was also compared with the reference methodology (an iodimetry, the Ripper method) showing no significant differences in the obtained results.
DIRICHLET FORMS ON HYPERFINITE II1FACTOR
Authors: ZHAO BO
Published: July 2010

Based on the structure of hyperfinite II1factor, we study its Dirichlet forms which can be constructed from Dirichlet forms on M2n(ℂ).
THE CURVE OF LINES ON A PRIME FANO THREE-FOLD OF GENUS 8
Authors: FLAMINI F. , SERNESI E.
Published: July 2010

We show that a general prime Fano three-fold X of genus 8 can be reconstructed from the pair (Γ, L), where Γ is its Fano curve of lines and L = OΓ(1) is the theta-characteristic which gives a natural embedding Γ ⊂ ℙ5.
A CHARACTERIZATION OF THE REAL PROJECTIVE PLANE
Authors: ROUYER JOËL
Published: July 2010

It is proved in this article, that in the framework of Riemannian geometry, the existence of large sets of antipodes (i.e. farthest points) for diametral points of a smooth surface has very strong consequences on the topology and the metric of this surface. Roughly speaking, if the sets of antipodes of diametral points are closed curves, then the surface is nothing but the real projective plane.
F-TERM BRANEWORLD INFLATION IN LIGHT OF FIVE-YEAR WMAP OBSERVATIONS
Authors: BOUAOUDA A. , ZARROUKI R. , CHAKIR H. , BENNAI M.
Published: July 2010

We consider a supersymmetric hybrid inflation in the framework of the Randall–Sundrum type II braneworld model. We derive an analytical expression for the scalar potential and find that the F-term dominates the hybrid inflation process. We show that, for some value of brane tension, we can eliminate the fine-tuning problem related to coupling constant κ of the potential. We also calculate all known spectrum inflation parameters and show that observational bounds from WMAP5, BAO and SN observations are satisfied.
CURVATURE AND TOPOLOGICAL EFFECTS ON DYNAMICAL SYMMETRY BREAKING IN A FOUR- AND EIGHT-FERMION INTERACTION MODEL
Authors: HAYASHI MASAKO , INAGAKI TOMOHIRO
Published: July 2010

A dynamical mechanism for symmetry breaking is investigated under the circumstances with the finite curvature, finite size and nontrivial topology. A four- and eight-fermion interaction model is considered as a prototype model which induces symmetry breaking at GUT era. Evaluating the effective potential in the leading order of the 1/N-expansion by using the dimensional regularization, we explicitly calculate the phase boundary which divides the symmetric and the broken phase in a weakly curved space–time and a flat space–time with nontrivial topology, RD-1 ⊗ S1.
EXPANSION FORMULAS FOR EUROPEAN OPTIONS IN A LOCAL VOLATILITY MODEL
Authors: BENHAMOU E. , GOBET E. , MIRI M.
Published: July 2010

Because of its very general formulation, the local volatility model does not have an analytical solution for European options. In this article, we present a new methodology to derive closed form solutions for the price of any European options. The formula results from an asymptotic expansion, terms of which are Black-Scholes price and related Greeks. The accuracy of the formula depends on the payoff smoothness and it converges with very few terms.
AN APPLICATION OF THE SEGAL–BARGMANN TRANSFORM TO THE CHARACTERIZATION OF LÉVY WHITE NOISE MEASURES
Authors: LEE YUH-JIA , SHIH HSIN-HUNG
Published: July 2010

Being inspired by the observation that the Stein's identity is closely connected to the quantum decomposition of probability measures and the Segal–Bargmann transform, we are able to characterize the Lévy white noise measures on the space [Formula: see text] of tempered distributions associated with a Lévy spectrum having finite second moment. The results not only extends the Stein and Chen's lemma for Gaussian and Poisson distributions to infinite dimensions but also to many other infinitely divisible distributions such as Gamma and Pascal distributions and corresponding Lévy white noise measures on [Formula: see text].
DERIVATIONS ON ALGEBRAS OF MEASURABLE OPERATORS
Authors: AYUPOV SH. A. , KUDAYBERGENOV K. K.
Published: July 2010

The present paper is a survey of recent results concerning derivations on various algebras of measurable operators affiliated with von Neumann algebras. A complete description of derivation is obtained in the case of type I von Neumann algebras. A special section is devoted to the Abelian case, namely to the existence of nontrivial derivations on algebras of measurable function. Local derivations on the above algebras are also considered.
OPENNESS LEADS TO OPINION STABILITY AND NARROWNESS TO VOLATILITY
Authors: HUET SYLVIE , DEFFUANT GUILLAUME
Published: July 2010

We propose a new opinion dynamic model based on the experiments and results of Wood et al. (1996). We consider pairs of individuals discussing on two attitudinal dimensions, and we suppose that one dimension is important, the other secondary. The dynamics are mainly ruled by the level of agreement on the main dimension. If two individuals are close on the main dimension, then they attract each other on the main and on the secondary dimensions, whatever their disagreement on the secondary dimension. If they are far from each other on the main dimension, then too much proximity on the secondary dimension is uncomfortable, and generates rejection on this dimension. The proximity is defined by comparing the opinion distance with a threshold called attraction threshold on the main dimension and rejection threshold on the secondary dimension. With such dynamics, a population with opinions initially uniformly drawn evolves to a set of clusters, inside which secondary opinions fluctuate more or less depending on threshold values. We observe that a low attraction threshold favors fluctuations on the secondary dimension, especially when the rejection threshold is high. The opinion evolutions of the model can be related to some stylized facts.
THE RIEMANN–HILBERT APPROACH TO GLOBAL ASYMPTOTICS OF DISCRETE ORTHOGONAL POLYNOMIALS WITH INFINITE NODES
Authors: OU CHUNHUA , WONG R.
Published: July 2010

In this paper, we develop the Riemann–Hilbert approach to study the global asymptotics of discrete orthogonal polynomials with infinite nodes. We illustrate our method by concentrating on the Charlier polynomials [Formula: see text]. We first construct a Riemann–Hilbert problem Y associated with these polynomials and then establish some technical results to transform Y into a continuous Riemann–Hilbert problem so that the steepest descent method of Deift and Zhou ([8]) can be applied. Finally, we produce three Airy-type asymptotic expansions for [Formula: see text] in three different but overlapping regions whose union is the entire complex z-plane. When z is real, our results agree with the ones given in the literature. Although our approach is similar to that used by Baik, Kriecherbauer, McLaughlin and Miller ([3]), there are crucial differences in the details. For instance, our expansions hold in much bigger regions. Our results are completely new, and one of them answers a question raised in Bo and Wong ([4]). Asymptotic formulas are also derived for large and small zeros of the Charlier polynomials.
EIGENVALUE PROBLEMS WITH WEIGHT AND VARIABLE EXPONENT FOR THE LAPLACE OPERATOR
Authors: MIHĂILESCU MIHAI , RĂDULESCU VICENŢIU
Published: July 2010

This paper deals with an eigenvalue problem for the Laplace operator on a bounded domain with smooth boundary in ℝN(N ≥ 3). We establish that there exist two positive constants λ*and λ* with λ*≤ λ* such that any λ ∈ (0, λ*) is not an eigenvalue of the problem while any λ ∈ [λ*, ∞) is an eigenvalue of the problem.
Partiality of Memberships in Categories and Audiences
Authors: Hannan Michael T.
Published: July 2010

Recent theory and research have reconceptualized categories in markets and in other settings as part of the languages developed to characterize roles in a producer-audience interface. An important development in this work is the characterization of memberships in producer categories and in audiences as potentially partial. Producers often are regarded as members in a category to varying degrees, and audience members share to varying degrees in consensus about the applicability and meanings of category labels. Such partiality gives rise to fuzziness in boundaries, which has implications for the emergence and persistence of categories. A fast-developing literature has explored these implications empirically.
Incarceration and Stratification
Authors: Wakefield Sara , Uggen Christopher
Published: July 2010

In the past three decades, incarceration has become an increasingly powerful force for reproducing and reinforcing social inequalities. A new wave of sociological research details the contemporary experiment with mass incarceration in the United States and its attendant effects on social stratification. This review first describes the scope of imprisonment and the process of selection into prison. It then considers the implications of the prison boom for understanding inequalities in the labor market, educational attainment, health, families, and the intergenerational transmission of inequality. Social researchers have long understood selection into prison as a reflection of existing stratification processes. Today, research attention has shifted to the role of punishment in generating these inequalities.
A World of Standards but not a Standard World: Toward a Sociology of Standards and Standardization
Authors: Timmermans Stefan , Epstein Steven
Published: July 2010

Standards and standardization aim to render the world equivalent across cultures, time, and geography. Standards are ubiquitous but underappreciated tools for regulating and organizing social life in modernity, and they lurk in the background of many sociological works. Reviewing the relevance of standards and standardization in diverse theoretical traditions and sociological subfields, we point to the emergence and institutionalization of standards, the difficulties of making standards work, resistance to standardization, and the multiple outcomes of standards. Rather than associating standardization with totalizing narratives of globalization or dehumanization, we call for careful empirical analysis of the specific and unintended consequences of different sorts of standards operating in distinct social domains.
Historical Studies of Social Mobility and Stratification
Authors: van Leeuwen Marco H.D. , Maas Ineke
Published: July 2010

This review discusses historical studies of social mobility and stratification. The focus is on changes in social inequality and mobility in past societies and their determinants. It discusses major historical sources, approaches, and results in the fields of social stratification (ranks and classes in the past), marriage patterns by social class or social endogamy, intergenerational social mobility, and historical studies of the career.
Dynamics of the Green and Red Upconversion Emissions in Yb3+‐Er3+‐Codoped Y2O3 Nanorods
Authors: Meza O. , Diaz-Torres L. A. , Salas P. , Angeles-Chavez C. , Martínez A. , Morales J. , Oliva J.
Published: July 2010

Efficient green and red upconversion emission in Y2O3:Yb3+, Er3+ nanorods under 978 nm radiation excitation is achieved. Experimental effective lifetimes, luminescent emissions, and nanorod sizes depend strongly on the solvent ratios used during the synthesis. A microscopic nonradiative energy transfer model is used to approach the dynamics of the green, red, and infrared emissions. The excellent agreement between simulated and experimental decay suggests that the energy transfer mechanisms responsible of the visible emission depend on the solvent ratio.
Simulation of 802.21 Handovers Using ns-2
Authors: Marques Hugo , Ribeiro José , Marques Paulo , Rodriguez Jonathan
Published: July 2010

The new IEEE 802.21 standard specifies link layer intelligence and other related network information to upper layers in order to optimize handovers between networks of different types, such as WiMAX, Wi-Fi, and 3GPP. This paper makes a short description of 802.21 standard, how it is implemented in ns-2, and the signaling used in a handover between WiMAX and Wi-Fi. The paper also proposes a novel and very simple approach to determine the expected number of handovers in an ns-2 simulation and also evaluates the reliability and scalability of ns-2 when simulating 802.21 scenarios with multiple nodes.
The South Carolina Digital Watershed: End-to-End Support for Real-Time Management of Water Resources
Authors: Eidson G. W. , Esswein S. T. , Gemmill J. B. , Hallstrom J. O. , Howard T. R. , Lawrence J. K. , Post C. J. , Sawyer C. B. , Wang K.-C. , White D. L.
Published: July 2010

Water resources are under unprecedented strain. The combined effects of population growth, climate change, and rural industrialization have led to greater demand for an increasingly scarce resource. Ensuring that communities have adequate access to water—an essential requirement for community health and prosperity—requires finegrained management policies based on real-time in situ data, both environmental and hydrological. To address this requirement at the state level, we have developed the South Carolina Digital Watershed, an end-to-end system for monitoring water resources. In this paper, we describe the design and implementation of the core system components: (i) in situ sensing hardware, (ii) collection and uplink facilities, (iii) data streaming middleware, and (iv) back-end repository and presentation services. We conclude by discussing key organizational and technical challenges encountered during the development process.
A Useful Approach to Identify Novel Small-Molecule Inhibitors of Wnt-Dependent Transcription
Authors: Ewan Kenneth , Pająk Bożena , Stubbs Mark , Todd Helen , Barbeau Olivier , Quevedo Camilo , Botfield Hannah , Young Rodrigo , Ruddle Ruth , Samuel Lee , Battersby Alysia , Raynaud Florence , Allen Nicholas , Wilson Stephen , Latinkic Branko , Workman Paul , McDonald Edward , Blagg Julian , Aherne Wynne , Dale Trevor
Published: July 2010

The Wnt signaling pathway is frequently deregulated in cancer due to mutations in genes encoding APC, β-catenin, and axin. To identify small-molecule inhibitors of Wnt signaling as potential therapeutics, a diverse chemical library was screened using a transcription factor reporter cell line in which the activity of the pathway was induced at the level of Disheveled protein. A series of deconvolution studies was used to focus on three compound series that selectively killed cancer cell lines with constitutive Wnt signaling. Activities of the compounds included the ability to induce degradation of β-catenin that had been stabilized by a glycogen synthase kinase-3 (GSK-3) inhibitor. This screen illustrates a practical approach to identify small-molecule inhibitors of Wnt signaling that can seed the development of agents suitable to treat patients with Wnt-dependent tumors. Cancer Res; 70(14); 5963–73. ©2010 AACR.
Intake of Cruciferous Vegetables Modifies Bladder Cancer Survival
Authors: Tang Li , Zirpoli Gary R. , Guru Khurshid , Moysich Kirsten B. , Zhang Yuesheng , Ambrosone Christine B. , McCann Susan E.
Published: July 2010

Background: Intake of cruciferous vegetables, a rich source of dietary isothiocyanates, has been inversely associated with risk of bladder cancer. Due to the potent antiproliferative effects of dietary isothiocyanates on bladder cancer in in vitro and in vivo models, cruciferous vegetable intake may also play a role in survival among patients with bladder cancer.

Methods: Using information obtained from the Roswell Park Cancer Institute Tumor Registry, patient medical records, and routinely collected questionnaire data, we examined potential associations between intake of cruciferous vegetables and survival among bladder cancer patients. As cooking can substantially reduce or destroy isothiocyanates, consumption of raw versus cooked cruciferous vegetables was examined separately. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models.

Results: A total of 239 bladder cancer patients were included in the study. After an average of 8 years of follow-up, 179 deaths occurred, with 101 deaths attributable to bladder cancer. After adjustment for other prognostic factors, a strong and significant inverse association was observed between bladder cancer mortality and broccoli intake, in particular raw broccoli intake (≥1 versus <1 serving per month; HR for overall death, 0.57; 95% CI, 0.39-0.83; HR for disease-specific death, 0.43; 95% CI, 0.25-0.74). There were no significant associations for total vegetables, total fruits, or other individual cruciferous vegetables.

Conclusions: Considering the strong preclinical evidence, intake of broccoli may improve bladder cancer survival.

Impact: Further prospective investigation is warranted to confirm the potential role of cruciferous vegetables in bladder cancer prognosis. Cancer Epidemiol Biomarkers Prev; 19(7); 1806–11. ©2010 AACR.
Randomized Controlled Trial of Mammography Intervention in Insured Very Low–Income Women
Authors: Ahmed Nasar U. , Haber Gillian , Semenya Kofi A. , Hargreaves Margaret K.
Published: July 2010

Background: The expectation that insurance coverage mitigates health disparities and equalizes use of healthcare assumes that services are equally accessed; however, the insured low-income target population in this research had a mammography rate of 23.4%, well below the general population. Our objective was to determine the most effective intervention to improve mammography use in low-income women insured by a managed care organization (MCO).

Methods: The study was a randomized controlled trial. Participants were 2,357 women noncompliant with screening mammography randomly assigned to one of three groups: control (n = 786) received usual care; simple intervention (n = 785) received prompt letter from the MCO medical director; and stepwise intervention (n = 786) received the same prompt letter from the MCO; if noncompliant, a second prompt letter from their primary care physician and, if still noncompliant, counseling from lay health workers. Outcome was completion of screening mammography extracted from medical records.

Results: Screening rates were 13.4% for the control, 16.1% for the simple intervention, and 27.1% for the stepwise intervention. Compared with the control, the primary care physician letter in the stepwise intervention increased the likelihood of screening by 80% [Relative Risk (RR) = 1.80; P < 0.001], and counseling tripled the likelihood of screening (RR = 3.11; P < 0.001).

Conclusions: Compared with the control and simple intervention, a stepwise intervention to increase mammography is effective in a target population of hard-to-reach, low-income, insured women.

Impact: The research provides evidence for the impact of stepwise interventions to improve cancer screening in low-income insured populations, although the screening rates remain well below those of the general population. Cancer Epidemiol Biomarkers Prev; 19(7); 1790–8. ©2010 AACR.
Lack of Association between Human Papillomavirus Type 16 and 18 Infections and Female Lung Cancer
Authors: Simen-Kapeu Aline , Surcel Heljä-Marja , Koskela Pentti , Pukkala Eero , Lehtinen Matti
Published: July 2010

Background: A carcinogenic role of human papillomavirus (HPV) in lung cancer development has been suggested through both clinical and laboratory research during the last two decades.

Methods: We did a population-based case-control study nested within the Finnish Maternity Cohort to assess the role of HPV16/18 infections in female lung carcinogenesis. The Finnish Maternity Cohort containing samples from more than 600,000 subjects were linked with nationwide cancer registries (1973-2006). Serum samples were retrieved from 311 women who developed lung cancer and 930 matched controls. The samples were analyzed for antibodies to HPV types 16 and 18 and cotinine (a biomarker of tobacco exposure). Conditional logistic regression-based estimates of odds ratios and 95% confidence intervals adjusted for cotinine levels were calculated.

Results: Overall, there was no evidence of increased risk of lung cancer associated with HPV 16 and 18 type–specific infections among nonsmokers and smokers, assessed via cotinine levels.

Conclusions: The question of HPV etiologic effect on lung carcinoma deserves further longitudinal studies using different HPV detection methods.

Impact: Our results bring new insights into female HPV lung cancer research. Cancer Epidemiol Biomarkers Prev; 19(7); 1879–81. ©2010 AACR.
Does Sustained Lung Inflation at Birth Improve Outcome of Preterm Infants at Risk for Respiratory Distress Syndrome?
Authors: Lista Gianluca , Fontana Paola , Castoldi Francesca , Cavigioli Francesco , Dani Carlo
Published: July 2010

Background: Sustained lung inflation (SLI) applied at birth has been demonstrated to lead to clearance of lung fluid and achievement of a precocious functional residual capacity in animal studies. Objectives: To verify if the application of SLI in preterm infants at birth may reduce the need for mechanical ventilation and improve their respiratory outcome. Methods: We prospectively studied 89 infants with respiratory distress (gestational age (GA) 28.1 ± 2.2 weeks) treated at birth with a SLI (25 cm H2O, sustained for 15 s) in addition to AAP recommendations versus a historical control group (n = 119; GA 28.1 ± 2.0 weeks) treated without SLI with the same device (controlled positive end-expiratory pressure of 5 cm H2O). Results: The SLI group had less need for (51 vs. 76%, p < 0.0001) and shorter duration of mechanical ventilation (5 ± 11 vs. 11 ± 19 days, p = 0.008), a more frequent occurrence of exclusive nasal continuous airway pressure support (49 vs. 24%, p < 0.0001) and INtubation-SURfactant-Extubation (INSURE) treatment (16 vs. 3%, p = 0.01), less need for surfactant (45 vs. 61%, p = 0.027) and postnatal steroids (10 vs. 25%, p = 0.01), a shorter duration of oxygen therapy (21 ± 27 vs. 31 ± 31 days, p = 0.016), and, finally, a lower occurrence of bronchopulmonary dysplasia in survivors (7 vs. 25%, p = 0.004). Multiple regression analysis showed that 23–27 weeks of GA and birth weight <750 g increased the risk of mechanical ventilation, while a clinical risk index for babies (CRIB) score <3 as well as INSURE strategy and SLI treatment in the delivery room decreased it. Conclusions: The application of a SLI at birth in preterm infants with respiratory distress may decrease the need for mechanical ventilation without inducing evident adverse effects.
Epstein-Barr Virus-Related Atypical Lymphoproliferative Disorders in Waldeyer’s Ring: A Clinicopathological Study of 9 Cases
Authors: Kojima Masaru , Nakamura Naoya , Itoh Hideaki , Shimizu Ken , Shimizu Kazuhiko , Matsuda Hazuki , Tamaki Yoshio , Masawa Nobuhide , Nakamura Shigeo
Published: July 2010

Background and Study Aim: Because of the small biopsy specimens in the Waldeyer’s ring (WR) the differential diagnosis between Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) and malignant lymphoma is occasionally difficult. We report here clinicopathological, immunohistochemical and genotypic findings of 9 cases of EBV-associated LPDs in WR. Patients and Methods: Using formalin-fixed paraffin-embedded sections, histological analyses, immunohistochemistry, in situ hybridization and polymerase chain reaction were performed. Results: Clinically, all 9 cases showed more than one atypical clinical finding of infectious mononucleosis including absence of systemic symptoms, absence of atypical lymphocytosis and age over 30 years. Histologically, 3 types were delineated: (1) Hodgkin lymphoma-like (n = 1), (2) T cell/histiocyte-rich large B cell lymphoma-like (n = 4), and (3) marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT)-like (n = 4). The in situ hybridization study demonstrated EBV-encoded small RNA (EBER)+ cells in all 9 lesions. The immunohistochemical and flow cytometry study demonstrated the reactive nature of the B cells in all 9 lesions. However, 3 of our 7 cases examined demonstrated immunoglobulin heavy chain gene rearrangement on PCR study. There was no development of B cell lymphoma in any of the 3 lesions demonstrating IgH rearrangement. Conclusion: EBV-associated LPDs of the WR showed marked histological diversity. Among these, a MALT-like pattern was frequently seen. Marginal zone B cell lymphoma frequently affects WR. We emphasized that EBV-associated LPD should be added to the differential diagnosis of primary tonsillar MALT-type lymphoma.
Alterations of the LKB1 Gene in Lung Adenocarcinomas Induced by N-Nitrosobis(2-Hydroxypropyl)amine in Rats
Authors: Tajiri Masaki , Wakabayashi Naoko , Tsujino Megumu , Fujii Minako , Okabe Kyoko , Honoki Kanya , Tsujiuchi Toshifumi
Published: July 2010

Objective: Germ line mutations of the LKB1 gene cause the autosomal dominant Peutz-Jeghers syndrome (PJS), and PJS has also been associated with an increased risk of developing cancers, suggesting LKB1 may act as a tumor suppressor in PJS. By contrast, LKB1 mutations are rare events in most sporadic tumors in non-PJS patients, except for lung cancers. To better understand the involvement of LKB1 gene alterations during lung carcinogenesis, we investigated the LKB1 gene mutations and expressions in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Methods: Male Wistar rats, 6 weeks old, were given 2,000 ppm BHP in their drinking water for 12 weeks and maintained without further treatment until they were sacrificed at 25 weeks. A total of 15 lung adenocarcinomas were obtained, and genomic DNA was extracted for the search of mutations using polymerase chain reaction (PCR)-single strand conformation polymorphism analysis. To assess altered expressions of the LKB1 gene, reverse transcription-PCR analysis was also performed. Results: No mutations were found throughout exons 1–9 in any of the tumors. Aberrant transcripts bearing deletions of nucleotides 216–1459, 289–1302, 268–1261, or 257–1378 were detected in 5 of 15 adenocarcinomas (33.3%). Conclusion: These results suggest that alterations of the LKB1 gene might be involved in the development of lung adenocarcinomas induced by BHP in rats.
Effect of Diet Intervention and Oral Zinc Supplementation on Metabolic Control in Berardinelli-Seip Syndrome
Authors: Dantas de Medeiros Rocha Érika , Dantas Leite Lúcia , de Fátima Paiva Baracho Maria , Goretti do Nascimento Santos Maria , de Araújo Dina Maria , Cavalcante França Mardone , da Silva Carlos Antônio Bruno , das Graças Almeida Maria , Rezende Adriana Augusto , Marchini Júlio Sérgio , Brandão-Neto José
Published: July 2010

Background/Aims: Berardinelli-Seip syndrome (BSS), also termed congenital generalized lipodystrophy or congenital generalized lipoatropic diabetes, is a rare autosomal recessive disease characterized by the nearly complete absence of metabolically active adipose tissue from birth, extreme insulin resistance, diabetes mellitus, and hepatomegaly. The aim of this study was to evaluate the effect of diet intervention and oral zinc supplementation on the metabolic control of BSS patients. Methods: During a 3-month period, 10 BSS patients received individualized diets and oral zinc supplementation. Food intake, clinical laboratory parameters, serum zinc and leptin, and plasma C-peptide concentrations were evaluated at the beginning of the study and after 3 months. Results: At the beginning of the study, all patients had elevated energy, protein, total fat, carbohydrate, calcium, iron, and zinc intakes. After 3 months, all of these parameters had decreased. Total fiber intakes remained low before and after diet intervention and oral zinc supplementation, and plasma levels of fasting glucose remained high. In contrast, glycated hemoglobin decreased significantly. Plasma leptin, C-peptide, and serum zinc levels increased during venous zinc tolerance testing, but there were no significant differences between the 2 curves obtained before and after diet intervention and oral zinc supplementation. Conclusions: Diet intervention and oral zinc supplementation were effective at controlling energy consumption, macronutrients, and glycated hemoglobin. Zinc likely acts as an adjunct therapy, thereby improving the effectiveness of leptin.
Management of Hepatocellular Carcinoma: From Prevention to Molecular Targeted Therapy
Authors: Kudo Masatoshi
Published: July 2010

Hepatocellular carcinoma is a malignant tumor responsible for approximately 600,000–700,000 deaths worldwide, and is becoming more prevalent not only in South-East Asia and Africa, but also in Western countries; therefore, interest in hepatocellular carcinoma has mounted in recent years in the West, where little or no interest was evident 10–20 years ago.
Impact of Peginterferon Maintenance Therapy on the Risk of Developing Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Virus
Authors: Shiffman Mitchell L.
Published: July 2010

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. This is largely to do with the epidemic of chronic hepatitis C virus (HCV) in the USA and other developed countries and an increasing prevalence of cirrhosis. The current treatment for chronic HCV is peginterferon (Peg-IFN) and ribavirin. Unfortunately, response rates are limited especially in patients with cirrhosis. Several observations have led to the hypothesis that continuing Peg-IFN as maintenance therapy in patients with chronic HCV and cirrhosis could reduce the risk of developing complications including HCC. However, three large prospective controlled trials of maintenance therapy have now failed to demonstrate that Peg-IFN maintenance therapy reduces complications of cirrhosis, HCC and liver-related mortality. In the HALT-C trial, the only one of these three studies for which HCV RNA data is available during maintenance therapy, only a minimal reduction in serum HCV RNA level was observed during maintenance therapy. It therefore remains uncertain if profound and persistent virologic suppression to undetectable levels of HCV RNA impacts the risk of developing HCC in patients with chronic HCV and advanced fibrosis or cirrhosis. Based upon the available data, there appears to be no rationale for utilizing Peg-IFN maintenance therapy in patients with cirrhosis and this approach does not reduce the risk of HCC.
Will Gd-EOB-MRI Change the Diagnostic Algorithm in Hepatocellular Carcinoma?
Authors: Kudo Masatoshi
Published: July 2010

A hepatocyte-specific contrast agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), was approved in Japan in 2008. This contrast agent enhances the blood pool and also is hepatocyte specific: it is taken up by hepatocytes and excreted into the biliary tract. Approximately 50% of the administered dose of Gd-EOB-DTPA is taken up by normal hepatocytes and subsequently excreted into the biliary tract, while the remaining 50% is excreted via the kidney. Hepatocellular uptake is considered to represent passive diffusion mediated by organic anion transporter polypeptide 1 (OATP1), which is expressed on the hepatocyte membrane. Gd-EOB-DTPA-enhanced MRI may offer a breakthrough for the diagnosis of liver tumors, particularly early hepatocellular carcinoma (HCC). The differentiation of dysplastic nodules from early HCC has remained difficult, even for pathologists specialized in liver tumors, but Gd-EOB-DTPA MRI facilitates an objective diagnosis with accuracy close to that of HCC-specialized pathologists. In conclusion, Gd-EOB-DTPA MRI facilitates the diagnosis of hypervascular advanced HCC and the differentiation of early HCC and dysplastic nodules, which used to be difficult, even with CT during arterial portography, and offers a high accuracy rate. Thus, Gd-EOB-DTPA MRI will have a significant impact on diagnostic algorithm for HCC.
Local Ablation for Hepatocellular Carcinoma in Taiwan: Different Points between Japan, Asia and West
Authors: Lin Shi-Ming
Published: July 2010

Objectives: To illustrate the situation of radiofrequency ablation (RFA) and percutaneous ethanol injection for early-stage hepatocellular carcinoma (HCC) in Taiwan. Methods: LeVeen, RITA, Medsphere and internally cooled electrodes are currently available in Taiwan. Only LeVeen and Medsphere impedance-control RF electrodes are reimbursed. Results: When using the LeVeen electrode, we experienced that an interactive algorithm could enhance necrosis better than in those treated by standard algorithm. We reported that RFA was superior to ethanol or acetic acid injection in terms of lower local tumor progression and higher overall survival for HCC no larger than 3 or 4 cm. For high-risk located HCC, we found that combined ethanol injection and RFA tended to have a higher rate of complete ablation than RFA monotherapy. Since 2006, we have also employed a creation of artificial ascites or pleural effusion for HCC contiguous with vital structure. We found a lower major complication and higher survival rate compared to the era without artificial ascites or pleural effusion creation. Conclusions: RFA is the first option of local ablation for HCC in Taiwan due to its effective result. Refined algorithms of RFA could improve its effect.
A Preliminary Study of Biological Characteristics of Streptococcus oligofermentans in Oral Microecology
Authors: Zhang J. , Tong H.C. , Dong X.Z. , Yue L. , Gao X.J.
Published: July 2010

This study was designed to explore the biological characteristics of a new oral streptococcus species Streptococcus oligofermentans. Plaque samples were collected from caries-free and caries-active subjects. S. oligofermentans was selectively grown on Mitis salivarius agar plates and identified by using 2-step PCR and was isolated from 38% of 18 subjects. Isolates were found mostly on healthy tooth surfaces. S. oligofermentans had weaker abilities in acid production and demineralizing hydroxyapatite. When Streptococcus mutans was coincubated with S. oligofermentans, total number, acid production and calcium release were significantly inhibited. In conclusion, inhibition of S. mutans could be a beneficial biological characteristic of S. oligofermentans in oral microecology.