bluuebunny/crossref_metadata_2025_split huggingface dataset:
Percutaneous sclerotherapy with ethanolamine oleate for venous malformations of the head and neck
Authors: Alexander Matthew David , McTaggart Ryan A , Choudhri Omar A , Marcellus Mary L , Do Huy M 
Published: November 2013

IntroductionVenous malformations frequently occur in the head and neck, and they can require treatment for a variety of reasons. Among multiple therapeutic approaches employed, percutaneous sclerotherapy has become one of the most commonly used treatments, with numerous sclerosants successfully utilized. Ethanolamine oleate has approval from the Food and Drug Administration for sclerosis of esophageal varices, and is used by some practitioners for the treatment of venous malformations. This study reports single center results of percutaneous sclerotherapy with ethanolamine oleate to treat venous malformations of the head and neck.Materials and methodsProspectively maintained procedural records were retrospectively reviewed to identify all patients with venous malformations who underwent percutaneous sclerotherapy. The Mulliken and Glowacki classification was used to diagnose venous malformations. Medical records and images were reviewed to record demographic information, lesion characteristics, treatment sessions, and clinical and imaging response. Quantitative volumetric analysis was conducted to augment commonly used poorly reproducible subjective outcome measures. Response was assessed after each session and completion of all percutaneous treatment. A χ2analysis was performed to evaluate the effects of the above described characteristics on outcomes.Results52 interventions were performed for lesions in 26 patients. No complications occurred following any procedures. Response to individual sessions was categorized as excellent following two (3.8%) sessions, good following 45 (86.5%), and fair following four (7.7%) session. No sessions resulted in poor responses. Final results were excellent in two patients (7.7%), good in 22 (84.6%), and fair in two (7.7%). Average lesion volume reduction was 39% following each session, and 61% after treatment completion. Periorbital lesions were significantly less likely than lesions located elsewhere to have good or excellent outcomes. No other lesion or demographic features affected outcomes.ConclusionsPercutaneous sclerotherapy with ethanolamine oleate appears to be safe and effective for the treatment of venous malformations and should be considered when treating these complex lesions. The efficacy of this agent appears to match or exceed that of other sclerosants used for such treatment, and further investigation in prospective controlled research is warranted.
Synergistic Activities of MET/RON Inhibitor BMS-777607 and mTOR Inhibitor AZD8055 to Polyploid Cells Derived from Pancreatic Cancer and Cancer Stem Cells
Authors: Zeng Jun-Ying , Sharma Sharad , Zhou Yong-Qing , Yao Hang-Ping , Hu Xing , Zhang Ruiwen , Wang Ming-Hai 
Published: November 2013

Abstract
Tyrosine kinase inhibitor BMS-777067 is an inhibitor of RON/MET receptor tyrosine kinases currently under clinical trials. Here, we report the synergistic activity of BMS-777607 in combination with mTOR inhibitor AZD8055 in killing chemoresistant pancreatic cancer and cancer stem cells. Treatment of pancreatic cancer L3.6pl cells with BMS-777607 alone inhibited clonogenic growth and moderately induced apoptotic death. However, BMS-777607 caused extensive polyploidy in L3.6pl cells through inhibition of aurora kinase B activity, independent of RON expression. In contrast, L3.6pl-derived cancer stem cells were highly resistant to BMS-777607–induced growth inhibition and apoptosis. The effect of BMS-777607 on induction of cancer stem cell polyploidy was also weak. BMS-777607–induced polyploidy features a predominant cell population with 8N chromosome content in both L3.6pl and cancer stem cells. These cells also showed decreased sensitivity toward chemotherapeutics by increased survival of IC50 values in response to doxorubicin, cisplatin, methotrexate, 5-fluorouracial, and gemcitabine. Among a panel of chemical inhibitors that target different signaling proteins, we found that BMS-777607 in combination with mTOR inhibitor AZD8055 exerted synergistic effects on L3.6pl and cancer stem cells. More than 70% of L3.6pl and cancer stem cells lost their viability when both inhibitors were used. Specifically, BMS-777607 in combination with inhibition of mTORC2, but not mTORC1, was responsible for the observed synergism. Our findings demonstrate that BMS-777607 at therapeutic doses exerts inhibitory activities on pancreatic cancer cells but also induces polyploidy insensitive to chemotherapeutics. Combination of BMS-777607 with AZD8055 achieves the maximal cytotoxic effect on pancreatic cancer and cancer stem cells. Mol Cancer Ther; 13(1); 37–48. ©2013 AACR.
Deficiency of NOX1/Nicotinamide Adenine Dinucleotide Phosphate, Reduced Form Oxidase Leads to Pulmonary Vascular Remodeling
Authors: Iwata Kazumi , Ikami Kanako , Matsuno Kuniharu , Yamashita Toshiharu , Shiba Dai , Ibi Masakazu , Matsumoto Misaki , Katsuyama Masato , Cui Wenhao , Zhang Jia , Zhu Kai , Takei Norio , Kokai Yasuo , Ohneda Osamu , Yokoyama Takahiko , Yabe-Nishimura Chihiro 
Published: November 2013

Objective—

Involvement of reactive oxygen species derived from nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase has been documented in the development of hypoxia-induced model of pulmonary arterial hypertension (PAH). Because the PAH-like phenotype was demonstrated in mice deficient in
Nox1
gene (Nox1
−/Y
) raised under normoxia, the aim of this study was to clarify how the lack of NOX1/NADPH oxidase could lead to pulmonary pathology.

Approach and Results—

Spontaneous enlargement and hypertrophy of the right ventricle, accompanied by hypertrophy of pulmonary vessels, were demonstrated in Nox1
−/Y
9 to 18 weeks old. Because an increased number of α-smooth muscle actin-positive vessels were observed in Nox1
−/Y
, pulmonary arterial smooth muscle cells (PASMCs) were isolated and characterized by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In Nox1
−/Y
PASMCs, the number of apoptotic cells was significantly reduced without any change in the expression of endothelin-1, and hypoxia-inducible factors HIF-1α and HIF-2α, factors implicated in the pathogenesis of PAH. A significant decrease in a voltage-dependent K
+
channel, Kv1.5 protein, and an increase in intracellular potassium levels were demonstrated in Nox1
−/Y
PASMCs. When a rescue study was performed in Nox1
−/Y
crossed with transgenic mice overexpressing rat
Nox1
gene, impaired apoptosis and the level of Kv1.5 protein in PASMCs were almost completely recovered in Nox1
−/Y
harboring the
Nox1
transgene.

Conclusions—
These findings suggest a critical role for NOX1 in cellular apoptosis by regulating Kv1.5 and intracellular potassium levels. Because dysfunction of Kv1.5 is among the features demonstrated in PAH, inactivation of NOX1/NADPH oxidase may be a causative factor for pulmonary vascular remodeling associated with PAH.
New Automated Assay of Small Dense Low-Density Lipoprotein Cholesterol Identifies Risk of Coronary Heart Disease
Authors: Tsai Michael Y. , Steffen Brian T. , Guan Weihua , McClelland Robyn L. , Warnick Russell , McConnell Joseph , Hoefner Daniel M. , Remaley Alan T. 
Published: November 2013

Objective—
Coronary heart disease (CHD) is the leading cause of death in the United States, yet assessing risk of its development remains challenging. The present study evaluates a new automated assay of small dense low-density lipoprotein cholesterol content (sdLDL-C) and whether sdLDL-C is a risk factor for CHD compared with LDL-C or small LDL particle concentrations derived from nuclear magnetic resonance spectroscopy.

Approach and Results—

sdLDL-C was measured using a new automated enzymatic method, and small LDL concentrations were obtained by nuclear magnetic resonance in 4387 Multi-Ethnic Study of Atherosclerosis participants. Cox regression analysis estimated hazard ratios for developing CHD for 8.5 years after adjustments for age, race, sex, systolic blood pressure, hypertension medication use, high-density lipoprotein cholesterol, and triglycerides. Elevated sdLDL-C was a risk factor for CHD in normoglycemic individuals. Those in the top sdLDL-C quartile showed higher risk of incident CHD (hazard ratio, 2.41;
P
=0.0037) compared with those in the bottom quartile and indicated greater CHD risk than the corresponding quartile of LDL-C (hazard ratio, 1.75;
P
=0.019). The association of sdLDL-C with CHD risk remained significant when LDL-C (<2.57 mmol/L) was included in a multivariate model (hazard ratio, 2.37;
P
=0.012). Nuclear magnetic resonance–derived small LDL concentrations did not convey a significant risk of CHD. Those with impaired fasting glucose or diabetes mellitus showed higher sdLDL-C and small LDL concentrations but neither was associated with higher CHD risk in these individuals.

Conclusions—
This new automated method for sdLDL-C identifies risk for CHD that would remain undetected using standard lipid measures, but only in normoglycemic, nondiabetic individuals.
Cyclic Adenosine Monophosphate-Response Element–Binding Protein Mediates the Proangiogenic or Proinflammatory Activity of Gremlin
Authors: Corsini Michela , Moroni Emanuela , Ravelli Cosetta , Andrés Germán , Grillo Elisabetta , Ali Imran H. , Brazil Derek P. , Presta Marco , Mitola Stefania 
Published: November 2013

Objective—
Angiogenesis and inflammation are closely related processes. Gremlin is a novel noncanonical vascular endothelial growth factor receptor-2 (VEGFR2) ligand that induces a proangiogenic response in endothelial cells (ECs). Here, we investigated the role of the cyclic adenosine monophosphate-response element (CRE)–binding protein (CREB) in mediating the proinflammatory and proangiogenic responses of ECs to gremlin.

Approach and Results—

Gremlin induces a proinflammatory response in ECs, leading to reactive oxygen species and cyclic adenosine monophosphate production and the upregulation of proinflammatory molecules involved in leukocyte extravasation, including chemokine (C-C motif) ligand-2 (Ccl2) and Ccl7, chemokine (C-X-C motif) ligand-1 (Cxcl1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). Accordingly, gremlin induces the VEGFR2-dependent phosphorylation, nuclear translocation, and transactivating activity of CREB in ECs. CREB activation mediates the early phases of the angiogenic response to gremlin, including stimulation of EC motility and permeability, and leads to monocyte/macrophage adhesion to ECs and their extravasation. All these effects are inhibited by EC transfection with a dominant-negative CREB mutant or with a CREB-binding protein–CREB interaction inhibitor that competes for CREB/CRE binding. Also, both recombinant gremlin and gremlin-expressing tumor cells induce proinflammatory/proangiogenic responses in vivo that are suppressed by the anti-inflammatory drug hydrocortisone. Similar effects were induced by the canonical VEGFR2 ligand VEGF-A
165
.

Conclusions—
Together, the results underline the tight cross-talk between angiogenesis and inflammation and demonstrate a crucial role of CREB activation in the modulation of the VEGFR2-mediated proinflammatory/proangiogenic response of ECs to gremlin.
Translation of Human Tissue Factor Pathway Inhibitor-β mRNA Is Controlled by Alternative Splicing Within the 5′ Untranslated Region
Authors: Ellery Paul E.R. , Maroney Susan A. , Martinez Nicholas D. , Wickens Marvin P. , Mast Alan E. 
Published: November 2013

Objective—
Tissue factor pathway inhibitor (TFPI) blocks the initiation of coagulation by inhibiting TF-activated factor VII, activated factor X, and early prothrombinase. Humans produce two 3′ splice variants, TFPIα and TFPIβ, which are differentially expressed in endothelial cells and platelets and possess distinct structural features affecting their inhibitory function. TFPI also undergoes alternative splicing of exon 2 within its 5′ untranslated region. The role of exon 2 splicing in translational regulation of human TFPI isoform expression is investigated.

Approach and Results—
Exon 2 splicing occurs in TFPIα and TFPIβ transcripts. Human tissue mRNA analysis uncovered a wide variability of exon 2 expression. Polysome analysis revealed a repressive effect of exon 2 on TFPIβ translation but not on TFPIα. Luciferase reporter assays further exposed strong translational repression of TFPIβ (90%) but not TFPIα. Use of a Morpholino to remove exon 2 from TFPI mRNA increased cell surface expression of endogenous TFPIβ. Exon 2 also repressed luciferase production (80% to 90%) when paired with the β-actin 3′ untranslated region, suggesting that it is a general translational negative element whose effects are overcome by the TFPIα 3′ untranslated region.

Conclusions—
Exon 2 is a molecular switch that prevents translation of TFPIβ. This is the first demonstration of a 5′ untranslated region alternative splicing event that alters translation of isoforms produced via independent 3′ splicing events within the same gene. Therefore, it represents a previously unrecognized mechanism for translational control of protein expression. Differential expression of exon 2 denotes a mechanism to provide temporal and tissue-specific regulation of TFPIβ-mediated anticoagulant activity.
Development of novel polysaccharide derived hybrid microcellular biocomposite and evaluation of cytotoxicity
Authors: Ghosh Subrata B , Bandyopadhyay-Ghosh Sanchita , Sain Mohini M 
Published: November 2013

Polysaccharide has become one of the most promising resources to substitute synthetic plastics because of its wide abundance, renewability, low cost and near-zero carbon footprint. In this work, a novel polysaccharide-derived biopolymer has been investigated as a potential candidate in developing hybrid biocomposite foam. Through the study of microcellular morphology and thermal degradation behaviour, an optimised processing methodology was identified. A synergistic technique of ball milling of modified biopolymer granules and two-step foam processing resulted in achieving reduced particle sizes, narrower particle size distribution and improved dispersion of biopolymer, which in turn resulted in enhanced microcellular morphology within the hybrid biocomposite foam. Considering the renewed interest for such bio-based materials and their potential use as reinforcements and fillers, a much needed study was undertaken to assess its health safety in terms of in vitro biocompatibility and cytotoxicity. The results from the studies indicated that modified biopolymer did not pose any health safety risks and were non-cytotoxic.
Therapeutic Approaches to Skeletal Muscle Repair and Healing
Authors: Danna Natalie R. , Beutel Bryan G. , Campbell Kirk A. , Bosco Joseph A. 
Published: November 2013

Context: Skeletal muscle is comprised of a highly organized network of cells, neurovascular structures, and connective tissue. Muscle injury is typically followed by a well-orchestrated healing response that consists of the following phases: inflammation, regeneration, and fibrosis. This review presents the mechanisms of action and evidence supporting the effectiveness of various traditional and novel therapies at each phase of the skeletal muscle healing process. Evidence Acquisition: Relevant published articles were identified using MEDLINE (1978-2013). Study Design: Clinical review. Level of Evidence: Level 3. Results: To facilitate muscle healing, surgical techniques involving direct suture repair, as well as the implantation of innovative biologic scaffolds, have been developed. Nonsteroidal anti-inflammatory drugs may be potentially supplanted by nitric oxide and curcumin in modulating the inflammatory pathway. Studies in muscle regeneration have identified stem cells, myogenic factors, and β-agonists capable of enhancing the regenerative capabilities of injured tissue. Furthermore, transforming growth factor-β1 (TGF-β1) and, more recently, myostatin and the rennin-angiotensin system have been implicated in fibrous tissue formation; several antifibrotic agents have demonstrated the ability to disrupt these systems. Conclusion: Effective repair of skeletal muscle after severe injury is unlikely to be achieved with a single intervention. For full functional recovery of muscle there is a need to control inflammation, stimulate regeneration, and limit fibrosis. Strength-of-Recommendation Taxonomy (SORT): B
Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study
Authors: Chaudhry Imran B. , Husain Nusrat , Drake Richard , Dunn Graham , Husain M. Omair , Kazmi Ajmal , Hamirani Munir M. , Rahman Raza , Stirling John , Deakin William 
Published: November 2013

Objectives: There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology. Methods: This was a 12-week rater-blind placebo-controlled study. A total of 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) and Abnormal Involuntary Movement Scale (AIMS). Results: Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with treatment as usual (TAU) on PANSS total score, although this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS. Conclusions: Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with TAU. This study has led to a larger Stanley Medical Research Institute (SMRI)-funded, double-blind, randomized control trial.
Altered distribution and function of natural killer cells in murine and human Niemann-Pick disease type C1
Authors: Speak Anneliese O. , te Vruchte Danielle , Davis Lianne C. , Morgan Anthony J. , Smith David A. , Yanjanin Nicole M. , Simmons Louise , Hartung Ralf , Runz Heiko , Mengel Eugen , Beck Michael , Imrie Jackie , Jacklin Elizabeth , Wraith James E. , Hendriksz Christian , Lachmann Robin , Cognet Celine , Sidhu Rohini , Fujiwara Hideji , Ory Daniel S. , Galione Antony , Porter Forbes D. , Vivier Eric , Platt Frances M. 
Published: November 2013

Key PointsLysosomal storage affects NK-cell frequency, development, and function. Lysosomal calcium is important for NK-cell degranulation.
How I treat ALL in Down's syndrome: pathobiology and management
Authors: Izraeli Shai , Vora Ajay , Zwaan C. Michel , Whitlock James 
Published: November 2013

Abstract
Children with Down syndrome are at high risk for developing B-cell precursor acute lymphoblastic leukemia (DS-ALL) associated with poor outcome due to both a high relapse rate and increased treatment-related mortality (TRM) from infections. Biologically, these heterogeneous leukemias are characterized by under-representation of the common cytogenetic subgroups of childhood ALL and overrepresentation of CRLF2-IL7R-JAK-STAT activating genetic aberrations. Although relapse is the major determinant of poor outcomes in this population, de-escalation of chemotherapy intensity might be feasible in the 10% to 15% DS-ALL patients with ETV6-RUNX1 or high hyperdipoidy in whom TRM is the major limiting event. As infection-associated TRM occurs during all treatment phases, including the maintenance period, increased surveillance and supportive care is required throughout therapy. Improvement in outcome will require better understanding of the causes of treatment failure and TRM, incorporation of new therapies targeting the unique biological properties of DS-ALL, and enhanced supportive care measures to reduce the risk of infection-related TRM. To facilitate these goals, an international collaboration plans to establish a prospective DS-ALL registry and develop specific supportive care recommendations for this at-risk population.
Effects of weight loss on asthma control in obese patients with severe asthma
Authors: Dias-Júnior Sérvulo Azevedo , Reis Monica , de Carvalho-Pinto Regina Maria , Stelmach Rafael , Halpern Alfredo , Cukier Alberto 
Published: November 2013

Studies on the effects of weight loss in patients with asthma are scarce. No studies have been performed in patients with severe asthma. Therefore, the aim of the present study was to assess the impact of weight loss in patients with severe asthma associated with obesity.This was an open, prospective, randomised study of two parallel groups, in patients with severe uncontrolled asthma and moderate obesity. The primary outcome was the level of asthma control 6 months after initiation of the weight reduction programme, quantified using the Asthma Control Questionnaire (ACQ). We evaluated clinical parameters, lung function, markers of airway inflammation and circulating cytokines.22 patients were randomised to undergo treatment for obesity and 11 to the control group. The weight reduction programme was associated with significant improvements in asthma control (mean±seACQ score 3.02±0.19 to 2.25±0.28 in the treatment groupversus2.91±0.25 to 2.90±0.16 in the controls, p=0.001). This improvement was not accompanied by changes in markers of airway inflammation or bronchial reactivity, but by an increase in forced vital capacity.Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation.
Role of activin-A in cigarette smoke-induced inflammation and COPD
Authors: Verhamme Fien M. , Bracke Ken R. , Amatngalim Gimano D. , Verleden Geert M. , Van Pottelberge Geert R. , Hiemstra Pieter S. , Joos Guy F. , Brusselle Guy G. 
Published: November 2013

Activin-A is a pleiotropic cytokine belonging to the transforming growth factor-β superfamily and has been implicated in asthma and pulmonary fibrosis. However, the role of activin-A and its endogenous inhibitor, follistatin, in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown.We first quantified activin-A and follistatin in the lungs of air- or cigarette smoke-exposed mice and in the lungs of patients with COPD by immunohistochemistry, ELISA and quantitative real-time PCR. We subsequently studied the effect of cigarette smoke on primary human bronchial epithelial cellsin vitro. Next, activin-A signalling was antagonisedin vivoby administration of follistatin in mice exposed to air or cigarette smoke for 4 weeks.Protein levels of activin-A were increased in the airway epithelium of patients with COPD compared with never-smokers and smokers. Cigarette smoke-exposed human bronchial epithelial cells expressed higher levels of activin-A and lower levels of follistatin. Both mRNA and protein levels of activin-A were increased in the lungs of cigarette smoke-exposed mice, whereas follistatin levels were reduced upon cigarette smoke exposure. Importantly, administration of follistatin attenuated the cigarette smoke-induced increase of inflammatory cells and mediators in the bronchoalveolar lavage fluid in mice.These results suggest that an imbalance between activin-A and follistatin contributes to the pathogenesis of cigarette smoke-induced inflammation and COPD.