bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in the proteome of the NHERF1 knockout mouse jejunal brush border membrane vesicles
Authors: Donowitz M. , Singh S. , Singh P. , Salahuddin F. F. , Chen Y. , Chakraborty M. , Murtazina R. , Gucek M. , Cole R. N. , Zachos N. C. , Kovbasnjuk O. , Broere N. , Smalley-Freed W. G. , Reynolds A. B. , Hubbard A. L. , Seidler U. , Weinman E. , de Jonge H. R. , Hogema B. M. , Li X.
Published: August 2010

Na/H exchanger regulatory factor 1 (NHERF1) is a scaffold protein made up of two PDZ domains and an ERM binding domain. It is in the brush border of multiple epithelial cells where it modulates 1) Na absorption by regulating NHE3 complexes and cytoskeletal association, 2) Cl secretion through trafficking of CFTR, and 3) Na-coupled phosphate absorption through membrane retention of NaPi2a. To further understand the role of NHERF1 in regulation of small intestinal Na absorptive cell function, with emphasis on apical membrane transport regulation, quantitative proteomic analysis was performed on brush border membrane vesicles (BBMV) prepared from wild-type (WT) and homozygous NHERF1 knockout mouse jejunal villus Na absorptive cells. Jejunal architecture appeared normal in NHERF1 null; however, there was increased proliferative activity, as indicated by increased crypt BrdU staining. LC-MS/MS analysis using iTRAQ to compare WT and NHERF1 null BBMV identified 463 proteins present in both WT and NHERF1 null BBMV of simultaneously prepared and studied samples. Seventeen proteins had an altered amount of expression between WT and NHERF1 null in two or more separate preparations, and 149 total proteins were altered in at least one BBMV preparation. The classes of the majority of proteins altered included transport proteins, signaling and trafficking proteins, and proteins involved in proliferation and cell division. Affected proteins also included tight junction and adherens junction proteins, cytoskeletal proteins, as well as metabolic and BB digestive enzymes. Changes in abundance of several proteins were confirmed by immunoblotting [increased CEACAM1, decreased ezrin (p-ezrin), NHERF3, PLCβ3, E-cadherin, p120, β-catenin]. The changes in the jejunal BBMV proteome of NHERF1 null mice are consistent with a more complex role of NHERF1 than just forming signaling complexes and anchoring proteins to the apical membrane and include at least alterations in proteins involved in transport, signaling, and proliferation.
A New System for Continuous Monitoring of Breathing and Kinetic Activity
Authors: Marani Roberto , Gelao Gennaro , Perri Anna Gina
Published: August 2010

We present a new system for acquiring simultaneously breathing rate and kinetic activity over a period of twenty-four hours. The system is based on a couple of sensors, which are very light, absolutely noninvasive, and compatible with everyday life. The proposed breathing sensor is cheap and uses a conductive rubber as active material. An analog signal representing the breathing rate is obtained from the sensor's signal, breath by breath, without any averaging or filtering. The kinetic activity sensor is based on a tiny accelerometer whose signal is averaged and filtered, so that both sensors have voltage compatible with a slow data logging.
Study of Possible Obstacles Preventing Obtaining a Tokomak Regime in the Egyptian Machine
Authors: Hegazy H. , Diab F. , Abd El-Aziz K. , Gott Yu. V. , Dremin M. M.
Published: August 2010

The main goal of this study is to clarify the possibility to obtain the plasma discharge and to prolong its duration as much as possible, and to analyze what are the preventing reasons of obtaining this goal. Possible reasons can be improper operation of the power supply system, a high level of stray magnetic fields, lack of equilibrium, influence of MHD instabilities, and a high level of impurities. We analyze experimentally these possibilities and discuss them in more details.
Actinomycin D Decreases Mcl-1 Expression and Acts Synergistically with ABT-737 against Small Cell Lung Cancer Cell Lines
Authors: Xu Haishan , Krystal Geoffrey W.
Published: August 2010

Purpose: ABT-737, which blocks the function of Bcl-2 and Bcl-XL but not Mcl-1, has shown single-agent activity in preclinical models of small cell lung cancer (SCLC). Elevated expression of Mcl-1 induces resistance to ABT-737 in SCLC. Based on the short half-life of Mcl-1 mRNA and protein, we hypothesized that the actinomycin D could reverse Mcl-1–induced resistance to ABT-737.

Experimental Design: The dose-response of multiple SCLC cell lines to actinomycin D in the absence and presence of ABT-737 was followed by the assessment of Bcl-2 family expression and poly ADP ribose polymerase cleavage by Western blot, viability by tetrazolium dye reduction and clonogenic assay, and cell cycle kinetics by flow cytometry.

Results: Actinomycin D decreased Mcl-1 expression and resulted in a cell line–dependent increase in Noxa expression. Clinically relevant concentrations of actinomycin D from 0.4 to 4 ng/mL showed single-agent activity across a panel of SCLC cell lines. When combined with low micromolar doses of ABT-737, near complete loss of viability was seen with synergistic combination indices of 0.5 to 0.7. Exposure to 4 ng/mL actinomycin was only required for the first 24 hours of the combined incubation, mimicking a clinically achievable area under the curve, but the presence of ABT-737 was required for an additional 48 hours to obtain maximal effect.

Conclusions: Clinically relevant concentrations of actinomycin D act synergistically with ABT-737 to induce SCLC apoptosis, which can be at least partially attributed to the actinomycin D–induced decrease in Mcl-1 and increase in Noxa expression. Taken together, these data suggest the feasibility of combining actinomycin D with BH3-mimetic drugs in the clinical setting. Clin Cancer Res; 16(17); 4392–400. ©2010 AACR.
Ten-Year Follow-Up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II)
Authors: Hueb Whady , Lopes Neuza , Gersh Bernard J. , Soares Paulo R. , Ribeiro Expedito E. , Pereira Alexandre C. , Favarato Desiderio , Rocha Antonio Sérgio C. , Hueb Alexandre C. , Ramires Jose A.F.
Published: August 2010

Background—

This study compared the 10-year follow-up of percutaneous coronary intervention (PCI), coronary artery surgery (CABG), and medical treatment (MT) in patients with multivessel coronary artery disease, stable angina, and preserved ventricular function.

Methods and Results—

The primary end points were overall mortality, Q-wave myocardial infarction, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. At a single institution, 611 patients were randomly assigned to CABG (n=203), PCI (n=205), or MT (n=203). The 10-year survival rates were 74.9% with CABG, 75.1% with PCI, and 69% with MT (
P
=0.089). The 10-year rates of myocardial infarction were 10.3% with CABG, 13.3% with PCI, and 20.7% with MT (
P
<0.010). The 10-year rates of additional revascularizations were 7.4% with CABG, 41.9% with PCI, and 39.4% with MT (
P
<0.001). Relative to the composite end point, Cox regression analysis showed a higher incidence of primary events in MT than in CABG (hazard ratio 2.35, 95% confidence interval 1.78 to 3.11) and in PCI than in CABG (hazard ratio 1.85, 95% confidence interval 1.39 to 2.47). Furthermore, 10-year rates of freedom from angina were 64% with CABG, 59% with PCI, and 43% with MT (
P
<0.001).

Conclusions—

Compared with CABG, MT was associated with a significantly higher incidence of subsequent myocardial infarction, a higher rate of additional revascularization, a higher incidence of cardiac death, and consequently a 2.29-fold increased risk of combined events. PCI was associated with an increased need for further revascularization, a higher incidence of myocardial infarction, and a 1.46-fold increased risk of combined events compared with CABG. Additionally, CABG was better than MT at eliminating anginal symptoms.

Clinical Trial Registration Information—

URL: http://www.controlled-trials.com. Registration number: ISRCTN66068876.
On the Problem of “Reverse Perspective”: Definitions East and West
Authors: Antonova Clemena
Published: August 2010

The author considers the history of the theory of “reverse perspective” in the 20th century. She identifies six distinct views on reverse perspective, some of which are mutually exclusive. The first four definitions have circulated in both Western and Russian scholarship, while two further views proposed by Russian authors are little known in the West. The most useful contribution of Russian theory to the subject is the suggestion of a pictorial space fundamentally different from the three-dimensional space frequently taken for granted by Western viewers.
Enactive Dialectics
Authors: Dumitriu Anna , Holder John , Tikka Pia , Whitby Blay
Published: August 2010

Created as part of the experimental European/worldwide collaborative e-MobiLArt project—designed to encourage collaboration with scientists, and with artists from other cultural backgrounds and geographic locations. Enactive Dialectics converges both real and virtual emotional space into one digitally mediated experience and calls for reconsideration of the boundary between private and public self.
Sound-Lines
Authors: Walsh Lorraine
Published: August 2010

Sound-Lines is an interactive sound sculpture composed of sensors that trigger archived sounds and animated words. Our collaborative project, supported by e-MobiLArt (European Mobile Lab for Interactive Media Artists), invites the visitor to engage in a playful exploration of shifting perspectives and perceptual discovery. The collaborating artists are Cliona Harmey (IR), Christine Mackey (IR), Nita Tandon (AU), and Lorraine Walsh (US).
Crossings
Authors: Yankowitz Nina
Published: August 2010

Crossings is an interactive art installation that was part of the eMobilArt project. The game explores the relative perspectives of sacred texts. It emerged from believing the politics of world conflicts are fueled by religious intolerance and misunder-standing.
The Relationship between Flux Coefficient and Entrainment Ratio in Density Currents
Authors: Wells Mathew , Cenedese Claudia , Caulfield C. P.
Published: August 2010

The authors explore the theoretical and empirical relationship between the nonlocal quantities of the entrainment ratio E, the appropriately depth- and time-averaged flux coefficient Γ, and the bulk Froude number Fro in density currents. The main theoretical result is that E = 0.125 Γ Fro2(CU3/CL)/cosθ, where θ is the angle of the slope over which the density current flows, CL is the ratio the turbulent length scale to the depth of the density current, and CU is the ratio of the turbulent velocity scale to the mean velocity of the density current. In the case of high bulk Froude numbers Γ ∼ Fro−2 and (CU3/CL) = Cε ∼ 1, so E ∼ 0.1, consistent with observations of a constant entrainment ratio in unstratified jets and weakly stratified plumes. For bulk Froude numbers close to one, Γ is constant and has a value in the range of 0.1–0.3, which means that E ∼ Fro2, again in agreement with observations and previous experiments. For bulk Froude numbers less than one, Γ decreases rapidly with bulk Froude number, explaining the sudden decrease in entrainment ratios that has been observed in all field and experimental observations.
Interannual-to-Decadal Variability in the Bifurcation of the North Equatorial Current off the Philippines
Authors: Qiu Bo , Chen Shuiming
Published: August 2010

Satellite altimeter sea surface height (SSH) data from the past 17 yr are used to investigate the interannual-to-decadal changes in the bifurcation of the North Equatorial Current (NEC) along the Philippine coast. The NEC bifurcation latitude migrated quasi decadally between 10° and 15°N with northerly bifurcations observed in late 1992, 1997–98, and 2003–04 and southerly bifurcations in 1999–2000 and 2008–09. The observed NEC bifurcation latitude can be approximated well by the SSH anomalies in the 12°–14°N and 127°–130°E box east of the mean NEC bifurcation point. Using a 1 ½-layer reduced-gravity model forced by the ECMWF reanalysis wind stress data, the authors find that the SSH anomalies in this box can be simulated favorably to serve as a proxy for the observed NEC bifurcation. With the availability of the long-term reanalysis wind stress data, this helps to lengthen the NEC bifurcation time series back to 1962. Although quasi-decadal variability was prominent in the last two decades, the NEC bifurcation was dominated by changes with a 3–5-yr period during the 1980s and had low variance prior to the 1970s. These interdecadal modulations in the characteristics of the NEC bifurcation reflect similar interdecadal modulations in the wind forcing field over the western tropical North Pacific Ocean. Although the NEC bifurcation on interannual and longer time scales is generally related to the Niño-3.4 index with a positive (negative) index corresponding to a northerly (southerly) bifurcation, the exact location of bifurcation is determined by wind forcing in the 12°–14°N band that contains variability not fully representable by the Niño-3.4 index.
An Evaluation of Precipitation Forecasts from Operational Models and Reanalyses Including Precipitation Variations Associated with MJO Activity
Authors: Janowiak John E. , Bauer Peter , Wang Wanqiu , Arkin Phillip A. , Gottschalck Jon
Published: August 2010

In this paper, the results of an examination of precipitation forecasts for 1–30-day leads from global models run at the European Centre for Medium-Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction (NCEP) during November 2007–February 2008 are presented. The performance of the model precipitation forecasts are examined in global and regional contexts, and results of a case study of precipitation variations that are associated with a moderate to strong Madden–Julian oscillation (MJO) event are presented.

The precipitation forecasts from the ECMWF and NCEP operational prediction models have nearly identical temporal correlation with observed precipitation at forecast leads from 2 to 9 days over the Northern Hemisphere during the cool season, despite the higher resolution of the ECMWF operational model, while the ECMWF operational model forecasts are slightly better in the tropics and the Southern Hemisphere during the warm season. The ECMWF Re-Analysis Interim (ERA-Interim) precipitation forecasts perform only slightly worse than the NCEP operational model, while NCEP’s Climate Forecast System low-resolution coupled model forecasts perform the worst among the four models. In terms of bias, the ECMWF operational model performs the best among the four model forecasts that were examined, particularly with respect to the ITCZ regions in both the Atlantic and Pacific. Local temporal correlations that were computed on daily precipitation totals for day-2 forecasts against observations indicate that the operational models at ECMWF and NCEP perform the best during the 4-month study period, and that all of the models have low to insignificant correlations over land and over much of the tropics. They perform the best in subtropical and extratropical oceanic regions.

Also presented are results that show that striking improvements have been made over the past two decades in the ability of the models to represent precipitation variations that are associated with MJO. The model precipitation forecasts exhibit the ability to characterize the evolution of precipitation variations during a moderate–strong period of MJO conditions for forecast leads as long as 10 days.
Characteristics of Sonoran Desert Microbursts
Authors: Willingham Katherine M. , Thompson Elizabeth J. , Howard Kenneth W. , Dempsey Charles L.
Published: August 2010

During the 2008 North American monsoon season, 140 microburst events were identified in Phoenix, Arizona, and the surrounding Sonoran Desert. The Sonoran microbursts were studied and examined for their frequency and characteristics, as observed from data collected from three Doppler radars and electrical power infrastructure damage reports. Sonoran microburst events were wet microbursts and occurred most frequently in the evening hours (1900–2100 local time). Stronger maximum differential velocities (20–25 m s−1) were observed more frequently in Sonoran microbursts than in many previously documented microbursts. Alignment of Doppler radar data to reports of wind-related damage to electrical power infrastructure in Phoenix allowed a comparison of microburst wind damage versus gust-front wind damage. For these damage reports, microburst winds caused more significant damage than gust-front winds.
Advances in the 5q− syndrome
Authors: Boultwood Jacqueline , Pellagatti Andrea , McKenzie Andrew N. J. , Wainscoat James S.
Published: August 2010

The 5q− syndrome is the most distinct of all the myelodysplastic syndromes with a clear genotype/phenotype relationship. The significant progress made during recent years has been based on the determination of the commonly deleted region and the demonstration of haploinsufficiency for the ribosomal gene RPS14. The functional screening of all the genes in the commonly deleted region determined that RPS14 haploinsufficiency is the probable cause of the erythroid defect in the 5q− syndrome. A mouse model of the human 5q− syndrome has now been created by chromosomal engineering involving a large-scale deletion of the Cd74-Nid67 interval (containing RPS14). A variety of lines of evidence support the model of ribosomal deficiency causing p53 activation and defective erythropoiesis, including most notably the crossing of the “5q− mice” with p53-deficient mice, thereby ameliorating the erythroid progenitor defect. Emerging evidence supports the notion that the p53 activation observed in the mouse model may also apply to the human 5q− syndrome. Other mouse modeling data suggest that haploinsufficiency of the microRNA genes miR-145 and miR-146a may contribute to the thrombocytosis seen in the 5q− syndrome. Lenalidomide has become an established therapy for the 5q− syndrome, although its precise mode of action remains uncertain.
Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma
Authors: Moskowitz Alison J. , Yahalom Joachim , Kewalramani Tarun , Maragulia Jocelyn C. , Vanak Jill M. , Zelenetz Andrew D. , Moskowitz Craig H.
Published: August 2010

To identify prognostic factors for patients transplanted for relapsed or refractory Hodgkin lymphoma we carried out a combined analysis of patients followed prospectively on 3 consecutive protocols at Memorial Sloan-Kettering Cancer Center. One hundred fifty-three patients with chemosensitive disease after ICE (ifosfamide, carboplatin, and etoposide)–based salvage therapy (ST) proceeded to high-dose chemoradiotherapy followed by autologous stem cell transplantation (ASCT). Patients were evaluated with computed tomography and functional imaging (gallium or fluorodeoxyglucose-positron emission tomography) prior to ST and again before ASCT. Functional imaging status before ASCT was the only factor significant for event-free survival (EFS) and overall survival by multivariate analysis and clearly identifies poor risk patients (5-year EFS 31% and 75% for FI-positive and negative patients respectively). Administration of involved-field radiotherapy with ASCT was marginally significant for EFS (P = .055). Studies evaluating novel STs, conditioning regimens, post-ASCT maintenance, or allogeneic stem cell transplantation are warranted for patients who fail to normalize pre-ASCT functional imaging.
Taurine's health influence on Japanese high school girls
Authors: Ishikawa Megumi , Arai Shiho , Takano Mio , Hamada Atsumi , Kunimasa Kazuhiro , Mori Mari
Published: August 2010

Background

The prevalence of metabolic syndrome (MS) in children and adolescents has been increasing at an alarming rate. MS risks during childhood and adolescence adversely affect health conditions in later life. Thus, the characterization of their MS risks is a critical research field. The aims of this study are to survey the health status of Japanese adolescent females, a poorly characterized population, and to investigate the potential relationship between their MS risks and dietary factors like potassium (K) and taurine.

Methods

Anthropometric characteristics of 243 healthy school girls aged 13 to 18 years were measured. Serum levels of triglycerides, total cholesterol and high-density lipoprotein (HDL), and plasma levels of glucose and insulin were analyzed in fasting blood samples. We assessed overweight, disturbed lipid prolife, higher blood pressure (hBP) and higher plasma glucose (hGlc) levels as indicators of MS risks. The relationships between MS risks and urinary K or taurine excretion were investigated by dividing into higher and lower groups at medians of their urinary excretions.

Results

Half of junior high school (JHS) and one-quarter of senior high school (SHS) girls had at least one MS risk. The quite common risk was hGlc, the rates being 21% in JHS girls and 14% in SHS. The prevalence of being overweight and obesity were only small portions, the rate being 0% and 0% in JHS girls, and 10% and 1% in SHS, respectively. Substantial differences in the prevalence of hBP were observed between JHS (22%) and SHS (4%) girls. Furthermore, higher urinary K excretion group showed a significant decrease in triglyceride level (P = 0.03) and increase in HDL level (P = 0.003) compared with the lower. Also, the higher urinary taurine excretion group exhibited a significant reduction in triglyceride level (P = 0.04) compared with the lower.

Conclusions

These results indicate that control of plasma glucose level rather than body weight is a crucial task in Japanese pubertal girls, and that a dietary habit rich in K and taurine could improve their lipid profile. Nutritional education based on these findings would help to prevent the future development of MS in Japanese female adolescents.
Locally adapted fish populations maintain small-scale genetic differentiation despite perturbation by a catastrophic flood event
Authors: Plath Martin , Hermann Bernd , Schröder Christiane , Riesch Rüdiger , Tobler Michael , García de León Francisco J , Schlupp Ingo , Tiedemann Ralph
Published: August 2010

Background

Local adaptation to divergent environmental conditions can promote population genetic differentiation even in the absence of geographic barriers and hence, lead to speciation. Perturbations by catastrophic events, however, can distort such parapatric ecological speciation processes. Here, we asked whether an exceptionally strong flood led to homogenization of gene pools among locally adapted populations of the Atlantic molly (Poecilia mexicana, Poeciliidae) in the Cueva del Azufre system in southern Mexico, where two strong environmental selection factors (darkness within caves and/or presence of toxic H2S in sulfidic springs) drive the diversification ofP. mexicana. Nine nuclear microsatellites as well as heritable female life history traits (both as a proxy for quantitative genetics and for trait divergence) were used as markers to compare genetic differentiation, genetic diversity, and especially population mixing (immigration and emigration) before and after the flood.

Results

Habitat type (i.e., non-sulfidic surface, sulfidic surface, or sulfidic cave), but not geographic distance was the major predictor of genetic differentiation. Before and after the flood, each habitat type harbored a genetically distinct population. Only a weak signal of individual dislocation among ecologically divergent habitat types was uncovered (with the exception of slightly increased dislocation from the Cueva del Azufre into the sulfidic creek, El Azufre). By contrast, several lines of evidence are indicative of increased flood-induced dislocation within the same habitat type, e.g., between different cave chambers of the Cueva del Azufre.

Conclusions

The virtual absence of individual dislocation among ecologically different habitat types indicates strong natural selection against migrants. Thus, our current study exemplifies that ecological speciation in this and other systems, in which extreme environmental factors drive speciation, may be little affected by temporary perturbations, as adaptations to physico-chemical stressors may directly affect the survival probability in divergent habitat types.
Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese
Authors: Liu Jie , Song Bao , Bai Xueli , Liu Wenjian , Li Zengjun , Wang Jialin , Zheng Yan , Wang Zhehai
Published: August 2010

Background

Recent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population.

Methods

We genotyped three SNPs of the IL-10 promoter (-1082A/G, -819T/C and -592A/C) using polymerase chain reaction-restriction fragment length polymorphism analysis in 262 subjects with PCa and 270 age-matched healthy controls. Odds ratio and 95% confidence interval were determined by logistic regression for the associations between IL-10 genotypes and haplotypes with the risk of PCa and advanced PCa grade.

Results

No significant differences in allele frequency or genotype distribution were observed for any of the IL-10 SNPs between PCa patients and control subjects. Significantly higher frequencies of -1082G, -819C and -592C allele and GCC haplotype were observed, however, in early stage patients in comparison to advanced PCa patients (for -1082 G, 13.9% vs 6.1%, OR = 2.48, P = 0.005; for -819 C 40.3% vs 30.8%, OR = 1.51, P = 0.043; for -512C, 40.3% vs 30.8%, OR = 1.51, P = 0.043; and for haplotype GCC 11.1%vs 5.1%, OR = 2.66, P = 0.008, respectively).

Conclusions

Our results identify that IL-10 promoter polymorphisms might not be a risk factor for PCa in Chinese cohorts, but rather incidence of polymorphisms associates with PCa grade, suggesting that IL-10 expression may impact PCa progression.
Molecular alterations in key-regulator genes among patients with T4 breast carcinoma
Authors: Massidda Bruno , Sini MariaCristina , Budroni Mario , Atzori Francesco , Deidda MariaCristina , Pusceddu Valeria , Perra MariaTeresa , Sirigu Paola , Cossu Antonio , Palomba Grazia , Ionta MariaTeresa , Palmieri Giuseppe
Published: August 2010

Background

Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period.

Methods

A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months. Archival paraffin-embedded tissue sections were used for immunohistochemistry (IHC) and fluorescencein situhybridization (FISH) analyses, in order to assess alterations in expression levels of survivin, p53, and pERK1-2proteins as well as in amplification ofCyclinD1andh-prunegenes. The Kaplan-Meier and Cox regression methods were used for survival assessment and statistical analysis.

Results

Overall, patients carrying increased expression of pERK1-2(p = 0.027) and survivin (p = 0.008) proteins as well as amplification ofh-prunegene (p = 0.045) presented a statistically-significant poorer overall survival in comparison with cases found negative for such alterations. After multivariate analysis, the pathological response to primary chemotherapy and the survivin overexpression in primary carcinoma represented the main parameters with a role as independent prognostic factors in our series.

Conclusions

Although retrospective, our study identified some molecular parameters with a significant impact on prediction of the response to therapy or prognosis among T4 breast cancer patients. Further large prospective studies are needed in order to validate the use of such markers for the management of these patients.
Effects of mitochondrial dysfunction on the immunological properties of microglia
Authors: Ferger Annette I , Campanelli Loretta , Reimer Valentina , Muth Katharina N , Merdian Irma , Ludolph Albert C , Witting Anke
Published: August 2010

Background

Neurodegenerative diseases are characterized by both mitochondrial dysfunction and activation of microglia, the macrophages of the brain. Here, we investigate the effects of mitochondrial dysfunction on the activation profile of microglial cells.

Methods

We incubated primary mouse microglia with the mitochondrial toxins 3-nitropropionic acid (3-NP) or rotenone. These mitochondrial toxins are known to induce neurodegeneration in humans and in experimental animals. We characterized lipopolysaccharide- (LPS-) induced microglial activation and the alternative, interleukin-4- (IL-4-) induced microglial activation in these mitochondrial toxin-treated microglial cells.

Results

We found that, while mitochondrial toxins did not affect LPS-induced activation, as measured by release of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), they did inhibit part of the IL-4-induced alternative activation, as measured by arginase activity and expression, induction of insulin-like growth factor 1 (IGF-1) and the counteraction of the LPS induced cytokine release.

Conclusions

Mitochondrial dysfunction in microglial cells inhibits part of the IL-4-induced alternative response. Because this alternative activation is considered to be associated with wound healing and an attenuation of inflammation, mitochondrial dysfunction in microglial cells might contribute to the detrimental effects of neuroinflammation seen in neurodegenerative diseases.
Neurotensin is increased in serum of young children with autistic disorder
Authors: Angelidou Asimenia , Francis Konstantinos , Vasiadi Magdalini , Alysandratos Konstantinos-Dionysios , Zhang Bodi , Theoharides Athanasios , Lykouras Lefteris , Sideri Kyriaki , Kalogeromitros Dimitrios , Theoharides Theoharis C
Published: August 2010

Autism spectrum disorders (ASD) are a group of pervasive neurodevelopmental disorders diagnosed in early childhood. They are associated with a set of "core symptoms" that include disabilities in social interaction skills, verbal and non-verbal communication, as well as repetitive and stereotypic behaviors. There is no definite pathogenetic mechanism or diagnostic tests. Many children with ASD also have "allergic-like" symptoms, but test negative implying mast cell activation by non-allergic triggers. We measured by Milliplex arrays serum levels of 3 neuropeptides that could stimulate mast cells in children with autistic disorder (n = 19; 16 males and 3 females; mean age 3.0 ± 0.4 years) and healthy, unrelated controls (n = 16; 13 males and 3 females; mean age 3 ± 1.2 years). Only neurotensin (NT) was significantly increased from 60.5 ± 6.0 pg/ml in controls to 105.6 ± 12.4 pg/ml in autistic disorder (p = 0.004). There was no statistically significant difference in the serum levels of β-endorphin or substance P (SP). NT could stimulate immune cells, especially mast cells, and/or have direct effects on brain inflammation and ASD.
How many are affected? A real limit of epidemiology
Authors: Poole Charles
Published: August 2010

A person can experience an effect on the occurrence of an outcome in a defined follow-up period without experiencing an effect on the risk of that outcome over the same period. Sufficient causes are sometimes used to deepen potential-outcome explanations of this phenomenon. In doing so, care should be taken to avoid tipping the balance between simplification and realism too far toward simplification. Death and other competing risks should not be assumed away. The time scale should be explicit, with specific times for the occurrence of specified component causes and for the completion of each sufficient cause. Component causes that affect risk should occur no later than the start of the risk period. Sufficient causes should be allowed to have component causes in common. When individuals experience all components of two or more sufficient causes, the outcome must be recurrent. In addition to effects on rates and risks, effects on incidence time itself should be considered.
Perforated Meckel's diverticulum presenting with combined bowel and urinary obstruction and mimicking Crohn's disease: a case report
Authors: Wong Banny S , Larson David W , Smyrk Thomas C , Oxentenko Amy S
Published: August 2010

Introduction

Meckel's diverticulum is a common congenital anomaly of the gastrointestinal tract, but is an uncommon cause of serious complications in adults. Although cases of patients with hemorrhage, bowel obstruction or perforation associated with Meckel's diverticulum have been reported, there have been no prior reports of patients with combined urinary and bowel obstruction due to abscess formation.

Case presentation

We describe the case of a 21-year-old man with a history of recurrent papillary thyroid cancer, but no prior abdominal surgeries, who presented with a one-month history of rectal pain and new-onset obstipation with urinary retention. He reported night sweats and weight loss, and had a second-degree relative with known Crohn's disease. A digital rectal examination was notable and revealed marked tenderness with proximal induration. A computed tomography scan of the patient's abdomen revealed a large, complex, circumferential perirectal abscess compressing the rectal lumen and base of the urinary bladder, associated with terminal ileal thickening and an ileocecal fistula. A flexible sigmoidoscopy with an endorectal ultrasound scan displayed a complex abscess with extensive mucosal and surrounding inflammation. An exploratory laparotomy revealed a Meckel's diverticulum with a large perforation at its base, positioned near the ileocecal fistula and immediately superior to the perirectal abscess. The section of small bowel containing the Meckel's diverticulum, the terminal ileum, and the cecum, were all resected, and the abscess was debrided.

Conclusions

Pre-operative diagnosis of Meckel's diverticulum can be difficult. If the nature of the complication makes ultimate surgical management likely, an early laparoscopic or open exploration should be performed to prevent the morbidity and mortality associated with late complications.
Giant liver hemangioma resected by trisectorectomy after efficient volume reduction by transcatheter arterial embolization: a case report
Authors: Akamatsu Nobuhisa , Sugawara Yasuhiko , Komagome Masahiko , Ishida Takashi , Shin Nobuhiro , Cho Narihiro , Ozawa Fumiaki , Hashimoto Daijo
Published: August 2010

Introduction

Liver hemangiomas are the most common benign liver tumors, usually small in size and requiring no treatment. Giant hemangiomas complicated with consumptive coagulopathy (Kasabach-Merritt syndrome) or causing severe incapacitating symptoms, however, are generally considered an absolute indication for surgical resection. Here, we present the case of a giant hemangioma, which was, to the best of our knowledge, one of the largest ever reported.

Case presentation

A 38-year-old Asian man was referred to our hospital with complaints of severe abdominal distension and pancytopenia. Examinations at the first visit revealed a right liver hemangioma occupying the abdominal cavity, protruding into the right diaphragm up to the right thoracic cavity and extending down to the pelvic cavity, with a maximum diameter of 43 cm, complicated with "asymptomatic" Kasabach-Merritt syndrome. Based on the tumor size and the anatomic relationship between the tumor and hepatic vena cava, primary resection seemed difficult and dangerous, leading us to first perform transcatheter arterial embolization to reduce the tumor volume and to ensure the safety of future resection. The tumor volume was significantly decreased by two successive transcatheter arterial embolizations, and a conventional right trisectorectomy was then performed without difficulty to resect the tumor.

Conclusions

To date, there have been several reports of aggressive surgical treatments, including extra-corporeal hepatic resection and liver transplantation, for huge hemangiomas like the present case, but because of its benign nature, every effort should be made to avoid life-threatening surgical stress for patients. Our experience demonstrates that a pre-operative arterial embolization may effectively enable the resection of large hemangiomas.
Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study
Authors: Wolfs Marcel GM , Rensen Sander S , Bruin-Van Dijk Elinda J , Verdam Froukje J , Greve Jan-Willem , Sanjabi Bahram , Bruinenberg Marcel , Wijmenga Cisca , van Haeften Timon W , Buurman Wim A , Franke Lude , Hofker Marten H
Published: August 2010

Background

Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear.

We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots.

Methods

Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m2. Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.

Results

Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 × 10-5). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 × 10-5). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified.

Conclusions

In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.
A process evaluation of the scale up of a youth‐friendly health services initiative in northern Tanzania
Authors: Renju Jenny , Andrew Bahati , Nyalali Kija , Kishamawe Coleman , Kato Charles , Changalucha John , Obasi Angela
Published: August 2010

Background

While there are a number of examples of successful small‐scale, youth‐friendly services interventions aimed at improving reproductive health service provision for young people, these projects are often short term and have low coverage. In order to have a significant, long‐term impact, these initiatives must be implemented over a sustained period and on a large scale. We conducted a process evaluation of the 10‐fold scale up of an evaluated youth‐friendly services intervention in Mwanza Region, Tanzania, in order to identify key facilitating and inhibitory factors from both user and provider perspectives.

Methods

The intervention was scaled up in two training rounds lasting six and 10 months. This process was evaluated through the triangulation of multiple methods: (i) a simulated patient study; (ii) focus group discussions and semi‐structured interviews with health workers and trainers; (iii) training observations; and (iv) pre‐ and post‐training questionnaires. These methods were used to compare pre‐ and post‐intervention groups and assess differences between the two training rounds.

Results

Between 2004 and 2007, local government officials trained 429 health workers. The training was well implemented and over time, trainers' confidence and ability to lead sessions improved. The district‐led training significantly improved knowledge relating to HIV/AIDS and puberty (RR ranged from 1.06 to 2.0), attitudes towards condoms, confidentiality and young people's right to treatment (RR range: 1.23‐1.36). Intervention health units scored higher in the family planning and condom request simulated patient scenarios, but lower in the sexually transmitted infection scenario than the control health units. The scale up faced challenges in the selection and retention of trained health workers and was limited by various contextual factors and structural constraints.

Conclusions

Youth‐friendly services interventions can remain well delivered, even after expansion through existing systems. The scaling‐up process did affect some aspects of intervention quality, and our research supports others in emphasizing the need to train more staff (both clinical and non‐clinical) per facility in order to ensure youth‐friendly services delivery. Further research is needed to identify effective strategies to address structural constraints and broader social norms that hampered the scale up.
Plasma concentrations of Gas6 (growth arrest specific protein 6) and its soluble tyrosine kinase receptor sAxl in sepsis and systemic inflammatory response syndromes
Authors: Ekman Carl , Linder Adam , Åkesson Per , Dahlbäck Björn
Published: August 2010

Introduction

Gas6, the protein product of the growth arrest specific gene 6, is present in human circulation at subnanomolar concentrations. It is secreted by endothelial cells and is important for the activation of endothelium during inflammation. Axl, the tyrosine kinase receptor for Gas6, is also present in endothelium and can be cleaved and released into the circulation. The soluble of form Axl (sAxl), which is present in plasma, can bind Gas6 and inhibit Axl-mediated cell signalling.

Methods

We have developed reproducible and accurate enzyme-linked immunosorbent assays for both Gas6 and sAxl and used them to investigate plasma samples from 70 patients with severe sepsis, 99 patients with sepsis, 42 patients with various infections causing fever but no systemic inflammatory response syndrome (SIRS), 20 patients with SIRS without verified infection, and 100 blood donors that served as controls. Correlations between Gas6 and sAxl concentrations and other commonly used analytes were investigated.

Results

The patients with severe sepsis, sepsis, infection or SIRS had all increased concentrations of Gas6, approximately double compared to what was found in the controls. The concentrations of sAxl were also increased in the patient groups compared to the controls. Gas6 correlated with C-reactive protein, procalcitonin and interleukin 6, whereas sAxl correlated to bilirubin and procalcitonin.

Conclusions

We can confirm results of earlier studies showing that circulating Gas6 is increased in sepsis and related syndromes. sAxl is increased, but less pronounced than Gas6. The concentrations of Gas6 and sAxl correlate with a number of inflammatory markers, suggesting a role in systemic inflammation.
Phase III Trial of Carboplatin Plus Paclitaxel With or Without Gemcitabine in First-Line Treatment of Epithelial Ovarian Cancer
Authors: du Bois Andreas , Herrstedt Jørn , Hardy-Bessard Anne-Claire , Müller Hans-Helge , Harter Philipp , Kristensen Gunnar , Joly Florence , Huober Jens , Åvall-Lundqvist Elisabeth , Weber Béatrice , Kurzeder Christian , Jelic Svetislav , Pujade-Lauraine Eric , Burges Alexander , Pfisterer Jacobus , Gropp Martina , Staehle Anne , Wimberger Pauline , Jackisch Christian , Sehouli Jalid
Published: August 2010

Purpose

One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non–cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.

Patients and Methods

We performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m2, respectively) with the same combination and additional gemcitabine 800 mg/m2 on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.

Results

Between 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).

Conclusion

The addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.
The EGR family gene egrh-1 functions non-autonomously in the control of oocyte meiotic maturation and ovulation in C. elegans
Authors: Clary Lynn M. , Okkema Peter G.
Published: August 2010

Oocyte production, maturation and ovulation must be coordinated with sperm availability for successful fertilization. In C. elegans this coordination involves signals from the sperm to the oocyte and somatic gonad, which stimulate maturation and ovulation. We have found that the C. elegans early growth response factor family member EGRH-1 inhibits oocyte maturation and ovulation until sperm are available. In the absence of sperm, egrh-1 mutants exhibit derepressed oocyte maturation marked by MAPK activation and ovulation. egrh-1 mutants exhibit ectopic oocyte differentiation in the distal gonadal arm and accumulate abnormal and degraded oocytes proximally. These defects result in reduced brood size and partially penetrant embryonic lethality. We have found that endogenous EGRH-1 protein and an egrh-1::gfp reporter gene are expressed in the sheath and distal tip cells of the somatic gonad, the gut and other non-gonadal tissues, as well as in sperm, but expression is not observed in oocytes. Results of tissue-specific egrh-1(RNAi) experiments and genetic mosaic analyses revealed that EGRH-1 function is necessary in the soma and, surprisingly, this function is required in both the gut and the somatic gonad. Based on transformation rescue experiments we hypothesize that EGRH-1 in the somatic gonad inhibits oocyte maturation and ovulation.