bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Alterations Associated with Sulindac-Resistant Colon Tumors in ApcMin/+ Mice
Authors: Greenspan Emily J. , Nichols Frank C. , Rosenberg Daniel W. 
Published: August 2010

Abstract
Although nonsteroidal anti-inflammatory drugs (NSAID), including sulindac, have been used extensively as chemopreventive agents for colorectal cancer, results are not consistent. NSAIDs, most reportedly sulindac, often do not cause a complete regression of adenomas and some patients develop resistance to NSAID treatment. In this study, we evaluated the effect of sulindac on colon tumorigenesis in the ApcMin/+ mouse model. Sulindac (180 ppm) given in drinking water for 9 weeks to ApcMin/+ mice significantly reduced the size of colon tumors, but actually caused an increase in colon tumor multiplicity relative to untreated controls (average of 5.5 versus 1.6 tumors per mouse, respectively; P &lt; 0.0001). This indicated that the drug could inhibit colon tumor progression but not initiation. As expected, in the small intestine, sulindac significantly reduced tumor size and multiplicity relative to untreated controls (average of 2.3 versus 42.0 tumors per mouse, respectively; P &lt; 0.0001). Generation of a panel of prostanoids was comparably suppressed in the small intestine and colon by sulindac treatment. Sulindac is also known to exert its growth inhibitory effects through regulation of many noncyclooxygenase targets, including p21, β-catenin, E-cadherin, mitochondrial apoptotic proteins, and peroxisome proliferator–activated receptor-γ. We found that sulindac treatment protected against E-cadherin loss in colon tumors, with associated inhibition of nuclear β-catenin accumulation. Importantly, p21WAF1/cip1 and peroxisome proliferator–activated receptor-γ expression were absent in colon tumors from sulindac-treated mice, suggesting that loss of these proteins is necessary for drug resistance. Together, these observations may be translatable to designing novel clinical therapies using combinations of agents that target multiple molecular pathways to overcome sulindac resistance. Cancer Prev Res; 3(9); 1187–97. ©2010 AACR.
Low-Carbohydrate Diets and Prostate Cancer: How Low Is “Low Enough”?
Authors: Masko Elizabeth M. , Thomas Jean A. , Antonelli Jodi A. , Lloyd Jessica C. , Phillips Tameika E. , Poulton Susan H. , Dewhirst Mark W. , Pizzo Salvatore V. , Freedland Stephen J. 
Published: August 2010

AbstractPrevious studies indicate that carbohydrate intake influences prostate cancer biology, as mice fed a no-carbohydrate ketogenic diet (NCKD) had significantly smaller xenograft tumors and longer survival than mice fed a Western diet. As it is nearly impossible for humans to consume and maintain NCKD, we determined whether diets containing 10% or 20% carbohydrate kcal showed similar tumor growth as NCKD. A total of 150 male severe combined immunodeficient mice were fed a Western diet ad libitum, injected with the human prostate cancer cell line LAPC-4, and then randomized 2 weeks later to one of three arms: NCKD, 10% carbohydrate, or 20% carbohydrate diets. Ten mice not injected were fed an ad libitum low-fat diet (12% fat kcal) serving as the reference in a modified-paired feeding protocol. Mice were sacrificed when tumors reached 1,000 mm3. Despite consuming extra calories, all mice receiving low-carbohydrate diets were significantly lighter than those receiving a low-fat diet (P &lt; 0.04). Among the low-carbohydrate arms, NCKD-fed mice were significantly lighter than the 10% or 20% carbohydrate groups (P &lt; 0.05). Tumors were significantly larger in the 10% carbohydrate group on days 52 and 59 (P &lt; 0.05), but at no other point during the study. Diet did not affect survival (P = 0.34). There were no differences in serum insulin-like growth factor-I or insulin-like growth factor binding protein-3 at sacrifice among the low-carbohydrate arms (P = 0.07 and P = 0.55, respectively). Insulin was significantly lower in the 20% carbohydrate arm (P = 0.03). LAPC-4 xenograft mice fed a low-carbohydrate diet (10–20% carbohydrate kcal) had similar survival as mice consuming NCKD (0% carbohydrate kcal). Cancer Prev Res; 3(9); 1124–31. ©2010 AACR.
Automatic Remote Monitoring of Implantable Cardioverter-Defibrillator Lead and Generator Performance
Authors: Varma Niraj , Michalski Justin , Epstein Andrew E. , Schweikert Robert 
Published: August 2010

Background—
Monitoring performance of implantable cardioverter-defibrillator (ICD) generators and leads is important. Methods available are with in-person evaluations or by automatic remote home monitoring (HM). These were prospectively evaluated and compared in the TRUST trial. The HM technology tested performed daily self-checks and databasing with rapid event notifications for out-of-range (including asymptomatic) conditions.

Methods and Results—

Patients (n=1339) were randomly assigned after ICD implant 2:1 to HM or to conventional groups. Both groups underwent scheduled checks every 3 months and were followed for 15 months. In HM, in-person office visits were scheduled at 3 and 15 months. At 6, 9, and 12 months, HM only was used with subsequent office visits if necessary. Between these time points, ICDs triggered event notifications for system integrity problems. Patients randomly assigned to conventional follow-up were evaluated with office visits only. HM and conventional patients were similar (age, 63.3±12.8 versus 64.0±12.1 years; 72.0% versus 73.1% male; New York Heart Association II class, 55.9% versus 60.4%; left ventricular ejection fraction, 29.0±10.7% versus 28.5±9.8%; coronary artery disease, 64.8% versus 71.7%; primary prevention, 72.2% versus 73.8%; DDD devices, 57.8% versus 56.6%). Four patients crossed over from conventional to HM because of advisories. Scheduled checks were more successfully accomplished in HM (92.7% versus 89.2% in conventional,
P
<0.001). Sixty-two device-related events (53 in HM versus 9 in conventional) were observed in 46 patients (40 [4.4%] in HM versus 6 [1.39%] in conventional,
P
=0.004). Forty-seven percent were asymptomatic. HM detected generator and lead problems earlier (HM versus conventional: median, 1 versus 5 days;
P
=0.05). A total of 20 device problems (eg, lead fracture, elective replacement indicators) requiring surgical revision (0.012 per patient-year) were found, 15 in HM and 5 in the conventional groups. Other events were managed nonsurgically (eg, reprogramming, initiation of antiarrhythmics).

Conclusions—
ICD lead and generator malfunction was infrequent and often asymptomatic. Only a minority of detected events required surgical intervention. Automatic HM enhanced discovery, permitted prompt detection, and facilitated management decisions. Longitudinal parameter trending, with component function evaluated daily by remote monitoring, may enable long-term performance assessment.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00336284.
Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass
Authors: Gabet Yankel , Baniwal Sanjeev K. , Leclerc Nathalie , Shi Yunfan , Kohn-Gabet Alice E. , Cogan Jon , Dixon Alexis , Bachar Marilyn , Guo Lixin , Turman Jack E. , Frenkel Baruch 
Published: August 2010

AbstractKrox20/EGR2, one of the 4 early growth response genes, is a highly conserved transcription factor implicated in hindbrain development, peripheral nerve myelination, tumor suppression, and monocyte/macrophage cell fate determination. Here, we established a novel role for Krox20 in postnatal skeletal metabolism. Microcomputed tomographic analysis of 4- and 8-week-old mice revealed a low bone mass phenotype (LBM) in both the distal femur and the vertebra of Krox20+/− mice. This was attributable to accelerated bone resorption as demonstrated in vivo by increased osteoclast number and serum C-terminal telopeptides, a marker for collagen degradation. Krox20 haploinsufficiency did not reduce bone formation in vivo, nor did it compromise osteoblast differentiation in vitro. In contrast, growth and differentiation were significantly stimulated in preosteoclast cultures derived from Krox20+/− splenocytes, suggesting that the LBM is attributable to Krox20 haploinsufficiency in the monocytic lineage. Furthermore, Krox20 silencing in preosteoclasts increased cFms expression and response to macrophage colony-stimulating factor, leading to a cell-autonomous stimulation of cell-cycle progression. Our data indicate that the antimitogenic role of Krox20 in preosteoclasts is the predominant mechanism underlying the LBM phenotype of Krox20-deficient mice. Stimulation of Krox20 expression in preosteoclasts may present a viable therapeutic strategy for high-turnover osteoporosis.
Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques
Authors: Wang Xiaolei , Xu Huanbin , Pahar Bapi , Alvarez Xavier , Green Linda C. , Dufour Jason , Moroney-Rasmussen Terri , Lackner Andrew A. , Veazey Ronald S. 
Published: August 2010

Abstract
Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4+ and CD8+ T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)–infected neonates. The results demonstrate infant primates have much greater rates of CD4+ T-cell proliferation than adult macaques, and that these proliferating, recently “activated” CD4+ T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4+ T cells in acute infection. This depletion is accompanied by a marked increase in CD8+ T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4+ T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4+ T cells), which may explain the sustained “peak” viremia characteristic of pediatric HIV infection. Eventual failure of CD4+ T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants.
Coverage statistics for sequence census methods
Authors: Evans Steven N , Hower Valerie , Pachter Lior 
Published: August 2010

AbstractBackgroundWe study the statistical properties of fragment coverage in genome sequencing experiments. In an extension of the classic Lander-Waterman model, we consider the effect of the length distribution of fragments. We also introduce a coding of theshapeof the coverage depth function as a tree and explain how this can be used to detect regions with anomalous coverage. This modeling perspective is especially germane to current high-throughput sequencing experiments, where both sample preparation protocols and sequencing technology particulars can affect fragment length distributions.ResultsUnder the mild assumptions that fragment start sites are Poisson distributed and successive fragment lengths are independent and identically distributed, we observe that, regardless of fragment length distribution, the fragments produced in a sequencing experiment can be viewed as resulting from a two-dimensional spatial Poisson process. We then study the successive jumps of the coverage function, and show that they can be encoded as a random tree that is approximately a Galton-Watson tree with generation-dependent geometric offspring distributions whose parameters can be computed.ConclusionsWe extend standard analyses of shotgun sequencing that focus on coverage statistics at individual sites, and provide a null model for detecting deviations from random coverage in high-throughput sequence census based experiments. Our approach leads to explicit determinations of the null distributions of certain test statistics, while for others it greatly simplifies the approximation of their null distributions by simulation. Our focus on fragments also leads to a new approach to visualizing sequencing data that is of independent interest.
Asymmetric localization of Arabidopsis SYP124 syntaxin at the pollen tube apical and sub-apical zones is involved in tip growth
Authors: Silva Pedro Ângelo , Ul-Rehman Reiaz , Rato Cláudia , Di Sansebastiano Gian-Pietro , Malhó Rui 
Published: August 2010

Abstract

Background
The continuous polarized vesicle secretion in pollen tubes is essential for tip growth but the location of endo- and exocytic sub-domains remains however controversial. In this report we aimed to show that Arabidopsis thaliana syntaxins are involved in this process and contribute to spatially define exocytosis and membrane recycling.

Results
Using GFP-fusion constructs, we imaged the distribution of pollen-specific (AtSYP124) and non-pollen syntaxins (AtSYP121 and AtSYP122) in transiently transformed Nicotiana tabacum pollen tubes. All three proteins associate with the plasma membrane and with apical vesicles indicating a conserved action mechanism for all SYPs. However, the GFP tagged SYP124 showed a specific distribution with a higher labelling at the plasma membrane flanks, 10-25 μm behind the apex. This distribution is affected by Ca2+ fluxes as revealed by treatment with Gd3+ (an inhibitor of extracellular Ca2+ influx) and TMB-8 (an inhibitor of intracellular Ca2+ release). Both inhibitors decreased growth rate but the distribution of SYP124 at the plasma membrane was more strongly affected by Gd3+. Competition with a related dominant negative mutant affected the specific distribution of SYP124 but not tip growth. In contrast, co-expression of the phosphatidylinositol-4-monophosphate 5-kinase 4 (PIP5K4) or of the small GTPase Rab11 perturbed polarity and the normal distribution of GFP-SYP but did not inhibit the accumulation in vesicles or at the plasma membrane.

Conclusions
The results presented suggest that in normal growing pollen tubes, a net exocytic flow occurs in the flanks of the tube apex mediated by SYP124. The specific distribution of SYP124 at the plasma membrane is affected by changes in Ca2+ levels in agreement with the importance of this ion for exocytosis. Apical growth and the specific localization of SYP124 were affected by regulators of membrane secretion (Ca2+, PIP5K4 and Rab11) but competition with a dominant negative mutant affected only SYP distribution. These data thus suggest that syntaxins alone do not provide the level of specificity that is required for apical growth and that additional signalling and functional mechanisms are required.
In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection
Authors: Constantoulakis Pantelis , Filiou Eftihia , Rovina Nikoletta , Chras George , Hamhougia Aggeliki , Karabela Simona , Sotiriou Adamandia , Roussos Charis , Poulakis Nikolaos 
Published: August 2010

Abstract

Background
Toll-like receptors (TLRs), Coronin-1 and Sp110 are essential factors for the containment of Mycobacterium tuberculosis infection. The purpose of this study was to investigate the in vivo expression of these molecules at different stages of the infection and uncover possible relationships between these markers and the state of the disease.

Methods
Twenty-two patients with active tuberculosis, 15 close contacts of subjects with latent disease, 17 close contacts of subjects negative for mycobacterium antigens and 10 healthy, unrelated to patients, subjects were studied. Quantitative mRNA expression of Coronin-1, Sp110, TLRs-1,-2,-4 and -6 was analysed in total blood cells vs an endogenous house-keeping gene.

Results
The mRNA expression of Coronin-1, Sp110 and TLR-2 was significantly higher in patients with active tuberculosis and subjects with latent disease compared to the uninfected ones. Positive linear correlation for the expression of those factors was only found in the infected populations.

Conclusions
Our results suggest that the up-regulation of Coronin-1 and Sp110, through a pathway that also includes TLR-2 up-regulation may be involved in the process of tuberculous infection in humans. However, further studies are needed, in order to elucidate whether the selective upregulation of these factors in the infected patients could serve as a specific molecular marker of tuberculosis.
Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor
Authors: Hwang Jun-Eul , Yoon Ju-Young , Bae Woo-Kyun , Shim Hyun-Jeong , Cho Sang-Hee , Chung Ik-Joo 
Published: August 2010

Abstract

Background
Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST.

Case presentation
A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities.

Conclusion
The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug.
Asthma in changing environments - chances and challenges of international research collaborations between South America and Europe - study protocol and description of the data acquisition of a case-control-study
Authors: Boneberger Anja , Radon Katja , Baer Jennifer , Kausel Leonie , Kabesch Michael , Haider Daniel , Schierl Rudolf , von Kries Rüdiger , Calvo Mario 
Published: August 2010

Abstract

Background
Asthma in children is an emerging public health problem in South America. So far, research in this part of the world is limited. This paper presents the methodology and description of the data acquisition of an asthma case-control study conducted in the Central South of Chile.

Methods/Design
A hospital-based case-control study about asthma (188 cases, 294 controls) in children (6-15 years) was carried out in Valdivia, Chile between November 2008 and December 2009. Data on asthma risk factors were collected by computer-assisted personal interview using validated questions from e.g. ISAAC phase II. Data on household dust exposure (endotoxin, allergen analyses), skin prick tests to most common allergens, stool examinations for parasitic infection, and blood samples (total IgE, genetics) were collected. Additionally, 492 randomly chosen blood donors were recruited in order to assess allele frequencies in the population of Valdivia.

Discussion
Overall 1,173 participants were contacted. Response was 82% among cases and 65% among controls. Atopic sensitization was high (78% among cases, 47% among controls). Cases had a statistically significantly (p < .0001) increased self-reported 12-month prevalence of symptoms of rhinitis (82% vs. 51%) and wheeze (68% vs. 16%). The study is well placed to address current hypotheses about asthma and its correlates in the South American context. Results of this study might help develop novel, innovative and individualized prevention strategies in countries in transition with respect to the South American context.
Inhibition of allogeneic inflammatory responses by the Ribonucleotide Reductase Inhibitors, Didox and Trimidox
Authors: Inayat Mohammed S , El-Amouri Ismail S , Bani-Ahmad Mohammad , Elford Howard L , Gallicchio Vincent S , Oakley Oliver R 
Published: August 2010

AbstractBackgroundGraft-versus-host disease is the single most important obstacle facing successful allogeneic stem cell transplantation (SCT). Even with current immunosuppressive therapies, morbidity and mortality rates are high. Current therapies including cyclosporine A (CyA) and related compounds target IL-2 signaling. However, although these compounds offer great benefit, they are also associated with multiple toxicities. Therefore, new compounds with a greater efficacy and reduced toxicity are needed to enable us to overcome this hurdle.MethodsThe allogeneic mixed lymphocyte reaction (MLR) is a uniqueex vivomethod to study a drug's action on the initial events resulting in T-cell activation and proliferation, synonymous to the initial stages of tissue and organ destruction by T-cell responses in organ rejection and Graft-versus-host disease. Using this approach, we examined the effectiveness of two ribonucleotide reductase inhibitors (RRI), Didox and Trimidox, to inhibit T-cell activation and proliferation.ResultsThe compounds caused a marked reduction in the proliferative responses of T-cells, which is also accompanied by decreased secretion of cytokines IL-6, IFN-γ, TNF-α, IL-2, IL-13, IL-10 and IL-4.ConclusionsIn conclusion, these data provide critical information to justify further investigation into the potential use of these compounds post allogeneic bone marrow transplantation to alleviate graft-versus-host disease thereby achieving better outcomes.