tbuckley/cabot-search huggingface dataset:
Abstract 42: Differentiation of Human Multipotent Vascular Stem Cells Contributes to Vascular Diseases
Authors: Wen-Chin Huang, Aijun Wang, Song Li
Journal: Circulation Research (2015)

Vascular disease, such as neointimal hyperplasia and atherosclerosis, involves in migration and proliferation of vascular cells in blood vessel wall. It is generally accepted that the de-differentiation of vascular smooth muscle cells (SMCs) contributes to vascular diseases. However, previous studies suggest that resident multipotent vascular stem cells (MVSCs) are also involved in neointima formation. In this study, we isolated MVSCs from the medial layer of human carotid artery and thoracic aorta by explant cultures, characterized these cells, and identified the origin of these vascular cells populated in lesion areas. Human MVSCs could be isolated from healthy and diseased blood vessels, were cloneable, and were positive for stem cell markers SOX10 and SOX17 but not SMC markers α-actin and calponin-1. MVSCs were able to differentiate into neural cells, SMCs and other mesenchymal lineages in vitro. In addition, we examined the location of MVSCs in diseased vascular wall by immunohistochemistry. The majority of cells within tunica media were calponin-positive cells, whereas a small population of cells was proliferative and double positive for SOX10 and Ki67 in the border between tunica intima and media. The number of SOX10+ cells in atherosclerotic lesions was more than that in healthy blood vessels, and some of these cells were double positive for SOX10 and chondrogenic markers. Furthermore, we performed in situ PCR and proximity ligation assays to stain for the epigenetic markers of SMC lineage. The results suggested that SOX10+ cells in cell cultures and tissue sections were not derived from de-differentiated SMCs. In conclusion, these findings support that MVSCs contributes to human vascular diseases.
Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients
Authors: Paula Río, Susana Navarro, Guillermo Guenechea, Rebeca Sánchez-Domínguez, Maria Luisa Lamana, Rosa Yañez, Jose A. Casado, Parinda A. Mehta, Maria Roser Pujol, Jordi Surrallés, Sabine Charrier, Anne Galy, José C. Segovia, Cristina Díaz de Heredia, Julián Sevilla, Juan A. Bueren
Journal: Blood (2017)
06.09 Targeting therapeutic and regenerative biomedicine specifically to arthritic joints
Authors: Ahuva Nissim, Chris Hughes, Bjarne Faurholm, Ngee Han Lim, Chiara Vinchi, Louise Marry Topping
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic treatment with disease modifying anti-rheumatic drugs (DMARDs) is associated with side effects, since such treatment does not deliver pharmacologically active molecules solely to the site of disease activity in the joints We demonstrated that posttranslational modification of type II collagen (CII) by reactive oxygen species (ROS), which are known to be present in inflamed arthritic joints, can give rise to epitopes specific to damaged cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA). Our goal is to establish that antibodies specific to ROS-modified CII can be used to target therapeutics specifically to arthritic joints. <h3>Methods</h3> We raised antibodies specific to ROS-modified CII by phage display and validated the specificity by ELISA and immunostaining of articular cartilage from RA and OA patients. The <i>in vivo</i> targeting potential was tested by imaging using mice model with inflammatory arthritis and. The therapeutic effect of anti–ROS-CII was tested by fusing it to soluble murine tumour necrosis factor receptor II–Fc fusion protein (mTNFRII-Fc) and viral IL-10 (vIL-10). <h3>Results</h3> Anti-ROS-CII: i) binds specifically to arthritic cartilage from patients with RA and OA; ii) stains cartilage in murine models of inflammatory arthritis and OA; and iii) localises in the inflamed joint <i>in vivo</i> in a mouse model of antigen induced arthritis (AIA) following systemic administration of labelled anti-ROS-CII. Targeting mTNFR2-Fc or viral IL-10 significantly enhanced therapeutic effect on inflamed knee swelling in mouse model of inflammatory arthritis compared to un-targeted mTNFR2-Fc or viral IL-10 when they were fused to non-relevant antibody. We next developed a novel imaging platform whereby anti-ROS-CII labelled with Cy5.5 (a near-infrared (NIR) fluorescent probe) allowed us to successfully visualise development and progression of murine OA induced by destabilising of medial meniscus (DMM). Specific retention of Cy5.5-anti-ROS-CII scFv in the DMM joint was noted as early as 4 weeks post-surgery and before any evident cartilage damage. <h3>Conclusion</h3> The anti-ROS-CII antibodies have the potencial to become a very early diagnostic biomarker for OA as well as for targeting payload drug specifically to arthritic joints whether RA or OA.
Impact of KIR-ligand mismatch on outcomes after peripheral blood haploidentical hematopoietic cell transplantation.
Authors: Michael Slade, Scott Ryan Goldsmith, Chang Liu, Rizwan Romee
Journal: Journal of Clinical Oncology (2016)

7051 Background: Historically, KIR-ligand mismatch (MM) has been associated with improved relapse free survival in AML patients after T-cell depleted haploidentical hematopoietic cell transplant (haplo-HCT) (Ruggeri et al, Science2002). However, there is a paucity of data regarding the impact of KIR-ligand MM on outcomes following T cell replete (TCR) haplo-HCT, especially in patients receiving peripheral blood (PB) grafts. Methods: We retrospectively identified all patients undergoing TCR PB haplo-HCT at Washington University School of Medicine between June 2009 and January 2016. The presence of ligands for KIR2DL1, KIR2DL2/3 and KIR3DL1 was determined using HLA typing and the Immuno Polymorphism Database. 6 patient-donor pairs without HLA-C typing were excluded. Engraftment delay was defined as no neutrophil recovery by day +28. Graft failure was defined as surviving to day +28 and never achieving neutrophil recovery. Results: 135 patients were included in the analysis. Incidence of KIR-ligand mismatch and impact on overall survival (OS), treatment-related mortality (TRM), relapse, neutrophil engraftment (NE) and platelet engraftment (PE) is summarized in table 1. HVG HLA-C was the only KIR-ligand MM to significantly impact outcomes and was associated with improved OS, TRM and NE. HLA-C KIR-ligand MM patients were also significantly less likely to experience engraftment delay (0% vs. 16%, p = 0.02) and no engraftment or mixed chimerism on 30 day marrow (0% vs. 19% p = 0.01), but not graft failure (0% vs. 4% p = 0.31). Conclusions: In our cohort, HVG HLA-C KIR-ligand MM was associated with significantly improved outcomes. Consequently, HLA-C KIR-ligand may be useful in donor selection. The underlying mechanism is unclear and requires further investigation. Impact of KIR-Ligand mismatch on outcomes. KIR-Ligand Mismatch Patients OS1 TRM1 Relapse1 NE1 PE1 Graft-versus-Host (GVH) Matched 92 - - - - - HLA-B and/or -C 43 NS NS NS NS NS HLA-B 14 NS NS NS NS NS HLA-C 23 NS NS NS NS NS Host-versus-Graft (HVG) Matched 96 - - - - - HLA-B and/or -C 39 NS NS NS <0.01 NS HLA-B 8 NS NS NS NS NS HLA-C 27 0.05 0.05 NS <0.01 NS 1Mantel-Cox test versus respective matched group.
Increasing Prevalence of Atrial Fibrillation and Permanent Atrial Arrhythmias in Congenital Heart Disease
Authors: Fabien Labombarda, Robert Hamilton, Azadeh Shohoudi, Jamil Aboulhosn, Craig S. Broberg, Marie A. Chaix, Scott Cohen, Stephen Cook, Annie Dore, Susan M. Fernandes, Anne Fournier, Joseph Kay, Laurent Macle, Blandine Mondésert, François-Pierre Mongeon, Alexander R. Opotowsky, Anna Proietti, Lena Rivard, Jennifer Ting, Bernard Thibault, Ali Zaidi, Paul Khairy
Journal: Journal of the American College of Cardiology (2017)
LEISURE CYCLISTS AT RISK OF MEDICAL COMPLICATIONS: OUTCOMES OF ONLINE PRE-PARTICIPATION SCREENING AMONG 22 650 ENDURANCE CYCLISTS, USING CURRENT EUROPEAN GUIDELINES - SAFER CYCLING
Authors: Jannelene Killops, Martin Schwellnus, Dina Christina Janse van Rensburg
Journal: British Journal of Sports Medicine (2017)

Background European guidelines have been introduced to screen masters and leisure athletes prior to participation in moderate- to high-intensity exercise, with the purpose of identifying the high risk athlete who should undergo a medical assessment. However, these guidelines have not been tested in large community based cycling races. Objective To determine the prevalence of cyclists who would require a full medical assessment before participating in a community based mass participation cycling race using current European guidelines. Design Cross-sectional study. Setting 2016 Cape Town Cycle Tour (109 km). Participants 22 650 cyclists. Assessment All 37 425 race entrants were required to complete an online pre-race medical questionnaire (containing all the elements in the screening guidelines), and 22 650 (60.3%) gave consent that the information could be used for research purposes. Main Outcome Measurements Prevalence (%) of risk factors that would require cyclists to undergo a full medical assessment before moderate- to high-intensity sports participation. Results More than 35% cyclists would require a full medical assessment prior to participation. Risk factors for cardiovascular disease (CVD) were present in 24% of cyclists and 4% reported existing cardiac disease. The prevalence of chronic diseases in other organ systems was as follows: respiratory (14%), gastrointestinal (6%), nervous system (4%), metabolic/hormonal (4%), and urinary tract (4%). The prevalence of other possible risk factors for medical complications were, allergies (17%), chronic prescription medication use (29%), and use of acute medication (including NSAID's) before or during races (10%). Conclusions These data show that &gt;35% of cyclists entering a community based mass participation cycling race would require a medical assessment prior to participation if current international guidelines are to be implemented. We suggest that further research is conducted to determine if screening guidelines predict medical complications. Once these data are available, pre-screening guidelines for medical assessments may have to be revised.
Efficacy of two ipilimumab (IPI) doses (10 vs. 3 mg/kg) in Alberta, Canada, tertiary cancer centers.
Authors: Richard M. Lee-Ying, Xiaolan Feng, Michael Smylie, Jose Gerard Monzon, Tina Cheng
Journal: Journal of Clinical Oncology (2014)

9090 Background: The efficacy of IPI for the treatment of metastatic melanoma (MM) has been demonstrated in randomized phase 3 trials. Response rates in the initial dose-finding phase 2 trial indicated the highest overall response rate (ORR) in the 10mg/kg group. Prior studies have identified that the degree of drug exposure during induction is statistically significant in predicting response. The optimal dosing is currently under investigation with a 10 vs. 3mg/kg trial (NCT01515189). Methods: Two cohorts were identified in the province of Alberta, one received 10mg/kg, while the second received 3mg/kg inductions. Treatment responses were determined by clinical immune-related response criteria. Fisher’s exact test was used to compare response rates. Results: A total of 97 patients were identified from 2006-2013, with 31 patients in the 10mg/kg group and 66 patients in the 3mg/kg group. The median follow-up was 15.7 vs. 11.7 months, respectively. The complete response (CR) rate is 19.4% (6/31) and 1.5% (1/66), which significantly favors the 10mg/kg group, p=0.006. The partial response (PR) rates are 19.4% (6/31) and 19.7% (13/66), p=0.97 and the stable disease (SD) rates are 22.6% (7/31) and 12.1% (8/66), p=0.09. Progressive disease (PD) rates are lower in the 10mg/kg group, 32.3% (10/31), vs. 63.6% (42/66) p=0.004. A trend towards improved response rate favored the 10 vs. 3mg/kg group (38.7%, 12/31 vs. 21.2%, 14/66) p=0.07, while the clinical benefit rate (CBR) (CR, PR and SD) was statistically significant, 61.3% (19/31) vs. 33.3% (22/66) p=0.01. An additional 3 patients in the 10mg/kg and 2 patients in the 3mg/kg group are alive with no evidence of disease after subsequent therapy. The frequency of immune-related side effects was not significantly different between groups, despite higher dosing in the 10 vs. 3mg/kg group, p=0.79. Conclusions: IPI used at 10mg/kg produces a better CBR than 3mg/kg in this study. This benefit is largely due to marked improvement in CR rates in the 10mg/kg group, and lower rates of PD. These findings are limited by the small sample size, retrospective nature and limited follow-up. Our results support the importance of dose exposure with IPI for MM, and will be explored further in a phase III trial.
Bioenhanced advanced third generation solid dispersion of tadalafil: Repurposing with improved therapy in pyelonephritis
Authors: Prashant P. Mande, Sagar S. Bachhav, Padma V. Devarajan
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Tadalafil (TDL) a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN). However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid Dispersion (SD) of TDL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC) to achieve high drug loading, improved stability and rapid dissolution of TDL for enhancing bioavailability and efficacy in PN. TDL-SMEC-SD was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release SD as a film. TDL-SMEC-SD was evaluated for in-vivo oral bioavailability and in-vivo efficacy in lipopolysaccharide-induced PN in rats. TDL exhibited high solubility (45.6 mg/ml) in the SMEC. TDL-SMEC-SD exhibited remarkably high TDL loading (45%w/w), exceptionally low contact angle (9°), rapid in-vitro release (t50 7.3 min), microemulsion formation (globule size ~100 nm) in aqueous dispersion, and stability as per ICH guidelines. SEM, DSC, and XRD confirmed high physical stability. A relative bioavailability of 350% and 150% compared to TDL and TDL-SD without SMEC respectively, established the superiority of TDL-SMEC-SD. A significant reduction in serum creatinine, blood urea nitrogen and nitric oxide levels in the lipopolysaccharide-induced PN confirmed the benefit of the TDL-SMEC-SD. The advanced third generation SMEC SDs presents the possibility of platform technology for bioenhancement of poorly water soluble drugs.
Abstract 2506: Effect of Extracorporeal CPR for Witnessed Out-of Hospital Cardiac Arrest of Presumed Cardiac Origin
Authors: Kunihiko Maekawa, Satoshi Nara, Katsutoshi Tanno, Mamoru Hase, Kazuhisa Mori, Yasufumi Asai
Journal: Circulation (2009)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to improve outcome of in-hospital cardiac arrest. Although there were uncontrolled studies regarding ECPR followed by ...
A Simple Score, Based on Geriatric Assessment, Predicts Survival in Elderly Newly Diagnosed Chronic Lymphocytic Leukemia Patients
Authors: Stefano Molica, Diana Giannarelli, Luciano Levato, Rosanna Mirabelli, Domenico Levato, Mirella Lentini, Eugenio Piro, Daniela Zappalà
Journal: Blood (2016)
カチオン性両親媒性共重合体/siRhoAポリプレックスによるRhoAノックダウンはラット脊髄損傷モデルにおける軸索再生を促進する【Powered by NICT】
Authors: Gwak So-Jung, Macks Christian, Jeong Da Un, Kindy Mark, Lynn Michael, Webb Ken, Lee Jeoung Soo
Journal: Biomaterials (2017)
優れた光力学/化学療法のためのlayer‐by‐layer集合によって構築されたメソ多孔性シリカベース汎用型医用ナノプラットフォーム【Powered by NICT】
Authors: Chen Wei-Hai, Luo Guo-Feng, Qiu Wen-Xiu, Lei Qi, Liu Li-Han, Wang Shi-Bo, Zhang Xian-Zheng
Journal: Biomaterials (2017)
A simple laboratory algorithm for diagnosis of melioidosis in resource-constrained areas: a study from north-central Vietnam
Authors: T.T. Trinh, T.S. Hoang, D.A. Tran, V.T. Trinh, A. Göhler, T.T. Nguyen, S.N. Hoang, R. Krumkamp, L.T.N. Nguyen, J. May, P.M. Doan, C.D. Do, T.A. Que, I. Steinmetz
Journal: Clinical Microbiology and Infection (2017)
Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling
Authors: Meng Michelle Xu, Yang Pu, Dali Han, Yaoyao Shi, Xuezhi Cao, Hua Liang, Xiang Chen, Xiao-Dong Li, Liufu Deng, Zhijian J. Chen, Ralph R. Weichselbaum, Yang-Xin Fu
Journal: Immunity (2017)
Adrenal haemorrhage in the newborn.
Journal: BMJ (1973)

Introduction   Adrenal hemorrhage (AH) is a relatively uncommon condition (0.55-1.9%) during the neonatal period [1]. The adrenal gland is vulnerable to haemorrhage because of its large size and high vascularity. Clinical features of AH are variable and nonspecific. AH in a newborn can present as anemia, hyperbilirubinemia, abdominal mass, painful swelling or hematoma of the scrotum, acute adrenal crisis or shock [2]. We report such a case of adrenal haemorrhage in a newborn.   Please download the full paper by clicking on the PDF file below...
音楽療法は高齢認知症患者における行動と認知機能を強化する系統的レビューとメタ分析【Powered by NICT】
Authors: Zhang Yingshi, Cai Jiayi, An Li, Hui Fuhai, Ren Tianshu, Ma Hongda, Zhao Qingchun
Journal: Ageing Research Reviews (2017)
Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study
Authors: Insa Korten, Elisabeth Kieninger, Shkipe Klenja, Ines Mack, Njima Schläpfer, Maria Teresa Barbani, Nicolas Regamey, Claudia E Kuehni, Markus Hilty, Urs Frey, Meri Gorgievski, Carmen Casaulta, Philipp Latzin
Journal: Thorax (2017)

Rationale Acute viral respiratory tract infections in children with cystic fibrosis (CF) are known causes of disease exacerbation. The role of viral infections during infancy is, however, less known, although early infancy is thought to be a crucial period for CF disease development. We prospectively assessed symptomatic and asymptomatic viral detection in the first year of life in infants with CF and healthy controls. Methods In a prospective cohort study, we included 31 infants with CF from the Swiss Cystic Fibrosis Infant Lung Development Cohort and 32 unselected, healthy infants from the Basel Bern Infant Lung Development Cohort and followed them throughout the first year of life. Respiratory symptoms were assessed by weekly telephone interviews. Biweekly nasal swabs were analysed for 10 different viruses and two atypical bacteria with real-time seven duplex PCR (CF=561, controls=712). Measurements and results Infants with CF and healthy controls showed similar numbers of swabs positive for virus (mean 42% vs 44%; OR 0.91, 95% CI 0.66 to 1.26, p=0.6). Virus-positive swabs were less often accompanied by respiratory symptoms in infants with CF (17% vs 23%; OR 0.64, 95% CI 0.43 to 0.95, p=0.026). This finding was pronounced for symptomatic human rhinovirus detection (7% vs 11%; OR 0.52, 95% CI 0.31 to 0.9, p=0.02). Conclusions Viral detection is not more frequent in infants with CF and respiratory symptoms during viral detection occur even less often than in healthy controls. It is likely an interplay of different factors such as local epithelial properties and immunological mechanisms that contribute to our findings.
Diarylsulfonylureas and Radiotherapy I. <i>In Vitro</i> Studies with N-(5-Indanylsulfonyl)-N′-(4-chlorophenyl)-urea (Sulofenur)
Authors: Sara Rockwell, Gerald B. Grindey
Journal: Cancer Communications (1991)

The effects of proliferative state and environmental factors on the cytotoxicity of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea (Sulofenur) were examined using EMT6 mouse mammary tumor cells in monolayer cultures. The toxicity of Sulofenur was at least as great in quiescent, plateau phase cultures as in exponentially growing cultures. Acute hypoxia during treatment did not alter the efficacy of the drug. The pH of the culture medium was a critical determinant of cytotoxicity; survival decreased progressively as the pH of the culture medium decreased from 7.0 to 6.0. High concentrations of Sulofenur appeared to potentiate the cytotoxic effects of x-rays. The cytotoxicity of Sulofenur to quiescent cells, the enhanced cytotoxicity at acutely lowered pH, and the interactions between the drug and radiation all suggest that Sulofenur and other diarylsulfonylureas warrant further examination as agents for use in combination with radiotherapy for the treatment of solid tumors.
Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex
Authors: Alison Lee, Hsiao-Hsien Leon Hsu, Yueh-Hsiu Mathilda Chiu, Sonali Bose, Maria José Rosa, Itai Kloog, Ander Wilson, Joel Schwartz, Sheldon Cohen, Brent A. Coull, Robert O. Wright, Rosalind J. Wright
Journal: Journal of Allergy and Clinical Immunology (2017)
Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues
Authors: Michael Delacher, Charles D Imbusch, Dieter Weichenhan, Achim Breiling, Agnes Hotz-Wagenblatt, Ulrike Träger, Ann-Cathrin Hofer, Danny Kägebein, Qi Wang, Felix Frauhammer, Jan-Philipp Mallm, Katharina Bauer, Carl Herrmann, Philipp A Lang, Benedikt Brors, Christoph Plass, Markus Feuerer
Journal: Nature Immunology (2017)
AGMA1ポリ(アミドアミン)は細胞系での,ヒト頚膣組織培養での,そして膣に感染したマウスでの,単純ヘルペスウイルスの感染力を阻害する
Authors: Donalisio Manuela, Quaranta Paola, Chiuppesi Flavia, Pistello Mauro, Cagno Valeria, Cavalli Roberta, Volante Marco, Bugatti Antonella, Rusnati Marco, Ranucci Elisabetta, Ferruti Paolo, Lembo David
Journal: Biomaterials (2016)