bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic mechanisms involved in differential MDR1mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy
Authors: Lee Tae-Bum , Park Jung-Hee , Min Young-Don , Kim Kyung-Jong , Choi Cheol-Hee 
Published: August 2008

Abstract

Background
The membrane transporters such as P-glycoprotein (Pgp), the MDR1 gene product, are one of causes of treatment failure in cancer patients. In this study, the epigenetic mechanisms involved in differential MDR1 mRNA expression were compared between 10 gastric and 9 colon cancer cell lines.

Methods
The MDR1 mRNA levels were determined using PCR and real-time PCR assays after reverse transcription. Cytotoxicity was performed using the MTT assay. Methylation status was explored by quantification PCR-based methylation and bisulfite DNA sequencing analyses.

Results
The MDR1 mRNA levels obtained by 35 cycles of RT-PCR in gastric cancer cells were just comparable to those obtained by 22 cycles of RT-PCR in colon cancer cells. Real-time RT-PCR analysis revealed that MDR1 mRNA was not detected in the 10 gastric cancer cell lines but variable MDR1 mRNA levels in 7 of 9 colon cancer cell lines except the SNU-C5 and HT-29 cells. MTT assay showed that Pgp inhibitors such as cyclosporine A, verapamil and PSC833 sensitized Colo320HSR (colon, highest MDR1 expression) but not SNU-668 (gastric, highest) and SNU-C5 (gastric, no expression) to paclitaxel. Quantification PCR-based methylation analysis revealed that 90% of gastric cancer cells, and 33% of colon cancer cells were methylated, which were completely matched with the results obtained by bisulfite DNA sequencing analysis. 5-aza-2'-deoxcytidine (5AC, a DNA methyltransferase inhibitor) increased the MDR1 mRNA levels in 60% of gastric cells, and in 11% of colon cancer cells. Trichostatin A (TSA, histone deacetylase inhibitor) increased the MDR1 mRNA levels in 70% of gastric cancer cells and 55% of colon cancer cells. The combined treatment of 5AC with TSA increased the MDR1 mRNA levels additively in 20% of gastric cancer cells, but synergistically in 40% of gastric and 11% of colon cancer cells.

Conclusion
These results indicate that the MDR1 mRNA levels in gastric cancer cells are significantly lower than those in colon cancer cells, which is at least in part due to different epigenetic regulations such as DNA methylation and/or histone deacetylation. These results can provide a better understanding of the efficacy of combined chemotherapy as well as their oral bioavailability.
Cytomegalovirus Infections among African-Americans
Authors: Wilms Isca R , Best Al M , Adler Stuart P 
Published: August 2008

Abstract

Background
Since African-Americans have twice the prevalence of cytomegalovirus (CMV) infections as age-matched Caucasians we sought to determine the ages and possible sources of infection of African-American children.

Methods
Subjects were 157 African-American healthy children and adolescents and their 113 household adults in Richmond VA. Families completed a questionnaire, provided saliva for antibody testing, and adolescents were interviewed regarding sexual activity.

Results
Regardless of age CMV seropositivity was not associated with gender, breast feeding, health insurance, sexual activity, or household income, education, or size. In the final regression model, prior CMV infection in adults was over two-fold higher than in children (chi-square = 18.8, p < 0.0001). At one year of age the CMV seropositivity rate was 11% (95%CI = 4% – 24%) and increased 1.8% each year until age 13 years. Between ages 13 and 20 years the CMV seropositivity rate remained between 22% and 33%. For adults, the CMV seropositivity rate was 84% in 21 year olds (95%CI = 69%–.92%). There was no association between CMV infections of the children and their mothers but CMV infections among siblings were associated.

Conclusion
We observed that African-American children had CMV seroprevalence rates by age 20 years at less than one-half of that of their adult mothers and caregivers. Sibling-to-sibling transmission was a likely source of CMV infections for the children. The next generation of African-American women may be highly susceptible to a primary CMV infection during pregnancy and may benefit from a CMV vaccine.
No effect of preterm birth on the risk of multiple sclerosis: a population based study
Authors: Ramagopalan Sreeram V , Valdar William , Dyment David A , DeLuca Gabriele C , Orton Sarah-Michelle , Yee Irene M , Criscuoli Maria , Ebers George C , Sadovnick A Dessa ,   for the Canadian Collaborative Study Group
Published: August 2008

Abstract

Background
Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. A clear parent of origin effect has been shown in several populations, perhaps resulting from factors operating during gestation. Preterm birth (birth at less than 37 weeks gestational age) has been shown to result in long-term health problems, including impaired neurological development. Here, in a population-based cohort, we investigate whether preterm birth increases the risk to subsequently develop MS.

Methods
We identified 6585 MS index cases and 2509 spousal controls with preterm birth information from the Canadian Collaborative Project on Genetic Susceptibility to MS. Rates of individuals born preterm were compared for index cases and controls.

Results
There were no significant differences between cases and controls with respect to preterm births. 370 (5.6%) MS index cases and 130 (5.2%) spousal controls were born preterm, p = 0.41.

Conclusion
Preterm birth does not appear to contribute to MS aetiology. Other factors involved in foetal and early development need to be explored to elucidate the mechanism of the increased risk conferred by the apparent maternal effect.
Androgen regulation of the androgen receptor coregulators
Authors: Urbanucci Alfonso , Waltering Kati K , Suikki Hanna E , Helenius Merja A , Visakorpi Tapio 
Published: August 2008

Abstract

Background
The critical role of the androgen receptor (AR) in the development of prostate cancer is well recognized. The transcriptional activity of AR is partly regulated by coregulatory proteins. It has been suggested that these coregulators could also be important in the progression of prostate cancer. The aim of this study was to identify coregulators whose expression is regulated by either the androgens and/or by the expression level of AR.

Methods
We used empty vector and AR cDNA-transfected LNCaP cells (LNCaP-pcDNA3.1, and LNCaP-ARhi, respectively), and grew them for 4 and 24 hours in the presence of dihydrotestosterone (DHT) at various concentrations. The expression of 25 AR coregulators (SRC1, TIF2, PIAS1, PIASx, ARIP4, BRCA1, β-catenin, AIB3, AIB1, CBP, STAT1, NCoR1, AES, cyclin D1, p300, ARA24, LSD1, BAG1L, gelsolin, prohibitin, JMJD2C, JMJD1A, MAK, PAK6 and MAGE11) was then measured by using real-time quantitative RT-PCR (Q-RT-PCR).

Results
Five of the coregulators (AIB1, CBP, MAK, BRCA1 and β-catenin) showed more than 2-fold induction and 5 others (cyclin D1, gelsolin, prohibitin, JMJD1A, and JMJD2C) less than 2-fold induction. Overexpression of AR did not affect the expression of the coregulators alone. However, overexpression of AR enhanced the DHT-stimulated expression of MAK, BRCA1, AIB1 and CBP and reduced the level of expression of β-catenin, cyclinD1 and gelsolin.

Conclusion
In conclusion, we identified 5 coactivators whose expression was induced by androgens suggesting that they could potentiate AR signaling. Overexpression of AR seems to sensitize cells for low levels of androgens.
A quantitative risk assessment approach for mosquito-borne diseases: malaria re-emergence in southern France
Authors: Ponçon Nicolas , Tran Annelise , Toty Céline , Luty Adrian JF , Fontenille Didier 
Published: August 2008

Abstract

Background
The Camargue region is a former malaria endemic area, where potential Anopheles vectors are still abundant. Considering the importation of Plasmodium due to the high number of imported malaria cases in France, the aim of this article was to make some predictions regarding the risk of malaria re-emergence in the Camargue.

Methods
Receptivity (vectorial capacity) and infectivity (vector susceptibility) were inferred using an innovative probabilistic approach and considering both Plasmodium falciparum and Plasmodium vivax. Each parameter of receptivity (human biting rate, anthropophily, length of trophogonic cycle, survival rate, length of sporogonic cycle) and infectivity were estimated based on field survey, bibliographic data and expert knowledge and fitted with probability distributions taking into account the variability and the uncertainty of the estimation. Spatial and temporal variations of the parameters were determined using environmental factors derived from satellite imagery, meteorological data and entomological field data. The entomological risk (receptivity/infectivity) was calculated using 10,000 different randomly selected sets of values extracted from the probability distributions. The result was mapped in the Camargue area. Finally, vulnerability (number of malaria imported cases) was inferred using data collected in regional hospitals.

Results
The entomological risk presented large spatial, temporal and Plasmodium species-dependent variations. The sensitivity analysis showed that susceptibility, survival rate and human biting rate were the three most influential parameters for entomological risk. Assessment of vulnerability showed that among the imported cases in the region, only very few were imported in at-risk areas.

Conclusion
The current risk of malaria re-emergence seems negligible due to the very low number of imported Plasmodium. This model demonstrated its efficiency for mosquito-borne diseases risk assessment.
Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone
Authors: Gold Stefan M , Chalifoux Sara , Giesser Barbara S , Voskuhl Rhonda R 
Published: August 2008

AbstractBackgroundMultiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease. Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as a potential neuroprotective effect that could be beneficial in MS.MethodsTen male MS patients were treated with 10 g of gel containing 100 mg of testosterone in a cross-over design (6 month observation period followed by 12 months of treatment). Blood samples were obtained at three-month intervals during the observation and the treatment period. Isolated blood peripheral mononuclear cells (PBMCs) were used to examine lymphocyte subpopulation composition by flow cytometry andex vivoprotein production of cytokines (IL-2, IFNγ, TNFα, IL-17, IL-10, IL-12p40, TGFβ1) and growth factors (brain-derived neurotrophic factor BDNF, platelet-derived growth factor PDGF-BB, nerve growth factor NGF, and ciliary neurotrophic factor CNTF). Delayed type hypersensitivity (DTH) skin recall tests were obtained before and during treatment as anin vivofunctional immune measure.ResultsTestosterone treatment significantly reduced DTH recall responses and induced a shift in peripheral lymphocyte composition by decreasing CD4+ T cell percentage and increasing NK cells. In addition, PBMC production of IL-2 was significantly decreased while TGFβ1 production was increased. Furthermore, PBMCs obtained during the treatment period produced significantly more BDNF and PDGF-BB.ConclusionThese results are consistent with an immunomodulatory effect of testosterone treatment in MS. In addition, increased production of BDNF and PDGF-BB suggests a potential neuroprotective effect.Trial RegistrationNCT00405353http://www.clinicaltrials.gov
Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial
Authors: de Vos Alexander M , Rutten Annemarieke , van de Zaag-Loonen Hester J , Bots Michiel L , Dikkers Riksta , Buiskool Robert A , Mali Willem P , Lubbers Daniel D , Mosterd Arend , Prokop Mathias , Rensing Benno J , Cramer Maarten J , van Es H Wouter , Moll Frans L , van de Pavoordt Eric D , Doevendans Pieter A , Velthuis Birgitta K , Mackaay Albert J , Zijlstra Felix , Oudkerk Matthijs 
Published: August 2008

Abstract

Background
Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms.

Design
The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about 1200 patients are needed to detect a 24% reduction in primary outcome.

Implications
The GROUND study will provide insight into the question whether non-invasive cardiac imaging reduces the risk of cardiovascular events in patients with peripheral arterial disease, but without symptoms of coronary artery disease.

Trial registration
Clinicaltrials.gov NCT00189111
Urinary interleukin-18 does not predict acute kidney injury after adult cardiac surgery: a prospective observational cohort study
Authors: Haase Michael , Bellomo Rinaldo , Story David , Davenport Piers , Haase-Fielitz Anja 
Published: August 2008

Abstract
Introduction
Urinary interleukin-18 (IL-18) measured during the immediate postoperative period could be a promising predictor of acute kidney injury following adult cardiac surgery.

Methods
In a single-centre prospective observational cohort study, we enrolled 100 adult cardiac surgical patients undergoing cardiopulmonary bypass at a tertiary hospital. We measured the urinary concentration of IL-18 and creatinine preoperatively, on arrival in the intensive care unit, and 24 hours postoperatively. We assessed urinary IL-18 concentration and urinary IL-18/urinary creatinine ratio in relation to the postoperative development of acute kidney injury defined as an increase in serum creatinine of greater than 50% from preoperative to postoperative peak value within 48 hours after surgery.

Results
Twenty patients developed acute kidney injury. On arrival in the intensive care unit and at 24 hours postoperatively, urinary IL-18 (median [interquartile range]) was not different in patients who subsequently developed acute kidney injury compared with those who did not: on arrival in the intensive care unit (168 [717] versus 104 [256] pg/mL; P = 0.70) and at 24 hours (195 [483] versus 165 [246] pg/mL; P = 0.47). On arrival in the intensive care unit (area under the curve for the receiver operating characteristic curve [AUC-ROCC] 0.53, 95% confidence interval [CI] 0.38 to 0.68; P = 0.70) and at 24 hours postoperatively (AUC-ROCC 0.55, 95% CI 0.40 to 0.71; P = 0.48), urinary IL-18 was not better than chance in predicting acute kidney injury. All findings were confirmed when urinary IL-18 was adjusted for urinary creatinine. Urinary IL-18 correlated with duration of cardiopulmonary bypass (P < 0.001).

Conclusion
In adults, early postoperative measurement of urinary IL-18 appears not to be valuable in identifying patients who develop acute kidney injury after cardiac surgery, but rather represents a nonspecific marker of cardiopulmonary bypass-associated systemic inflammation.
Minireview: How Peptide Hormone Vesicles Are Transported to the Secretion Site for Exocytosis
Authors: Park Joshua J. , Loh Y. Peng 
Published: August 2008

AbstractPost-Golgi transport of peptide hormone-containing vesicles from the site of genesis at the trans-Golgi network to the release site at the plasma membrane is essential for activity-dependent hormone secretion to mediate various endocrinological functions. It is known that these vesicles are transported on microtubules to the proximity of the release site, and they are then loaded onto an actin/myosin system for distal transport through the actin cortex to just below the plasma membrane. The vesicles are then tethered to the plasma membrane, and a subpopulation of them are docked and primed to become the readily releasable pool. Cytoplasmic tails of vesicular transmembrane proteins, as well as many cytosolic proteins including adaptor proteins, motor proteins, and guanosine triphosphatases, are involved in vesicle budding, the anchoring of the vesicles, and the facilitation of movement along the transport systems. In addition, a set of cytosolic proteins is also necessary for tethering/docking of the vesicles to the plasma membrane. Many of these proteins have been identified from different types of (neuro)endocrine cells. Here, we summarize the proteins known to be involved in the mechanisms of sorting various cargo proteins into regulated secretory pathway hormone-containing vesicles, movement of these vesicles along microtubules and actin filaments, and their eventual tethering/docking to the plasma membrane for hormone secretion.
Valuing Future Information Under Uncertainty Using Polynomial Chaos
Authors: Prange Michael , Bailey William J. , Couët Benoit , Djikpesse Hugues , Armstrong Margaret , Galli Alain , Wilkinson David 
Published: August 2008

This paper estimates the value of information for highly uncertain projects whose decisions have long-term impacts. We present a mathematically consistent framework using decision trees, Bayesian updating, and Monte Carlo simulation to value future information today, even when that future information is imperfect. One drawback of Monte Carlo methods in multivariate cases is the large number of samples required, which may result in prohibitive run times when considerable computer time is required to obtain each sample, as it is in our example. A polynomial chaos approach suitable for black-box functions is used to reduce these computations to manageable proportions. To our knowledge, this is the first exposition of polynomial chaos in the valuation literature. In our example it provides a speed-up of more than two orders of magnitude.We demonstrate the approach with an oilfield example involving a future decision on where to place a new injection well relative to a fault. The example considers the value to the asset holder of a measurement, to be made in the future, that reveals the degree of reservoir compartmentalization caused by this fault. In conditions of high demand for rigs and other scarce capital-intensive oilfield equipment, it may be appropriate for the asset holder to agree to a forward contract for this critical measurement to be taken at a future date at some specified price. The service provider would be contractually bound to provide this measurement at this pre-agreed price within a specified time window, regardless of the prevailing price and availability of rigs and equipment. Despite the presence of financial uncertainty on future oil price and private uncertainty on reservoir variables that are largely unresolved by the measurement, our methodology provides a computationally efficient valuation framework, possibly leading to novel ways of setting up contract terms.
A Price Discrimination Model of Trade Promotions
Authors: Cui Tony Haitao , Raju Jagmohan S. , Zhang Z. John 
Published: August 2008

Critics have long faulted the wide-spread practice of trade promotions as wasteful. It has been estimated that this practice adds up to $100 billion worth of inventory to the distribution system. Yet, the practice continues. In this paper, we propose a price discrimination model of trade promotions. We show that in a distribution channel characterized by a dominant retailer, a manufacturer has incentives to price discriminate between the dominant retailer and smaller independents. While offering all retailers the same pricing policy, price discrimination can be implemented through trade promotions because they induce different inventory-ordering behaviors on the part of retailers. Differences in inventory holding costs have been shown to be an important determinant of consumer promotions. Our analysis suggests that differences in holding costs are also potentially an important driver for the use of trade promotions. The implications from our model explain a number of anecdotal and/or empirically observed puzzles about how trade promotions are practiced. For example, our analysis explains why chain stores welcome trade promotions but independents do not. Our analysis outlines implications for managing trade promotions.