tbuckley/cabot-search huggingface dataset:
Human Activin-A Is Expressed in the Atherosclerotic Lesion and Promotes the Contractile Phenotype of Smooth Muscle Cells
Authors: Marten A. Engelse, Jolanda M. Neele, Tanja A. E. van Achterberg, Benien E. van Aken, Ron H. N. van Schaik, Hans Pannekoek, Carlie J. M. de Vries
Journal: Circulation Research (1999)

Abstract —Activin is a member of the transforming growth factor-β superfamily, and it modulates the proliferation and differentiation of various target cells. In this study, we investigated the role of activin in the initiation and progression of human atherosclerosis. The expression of activin, its physiological inhibitor follistatin, and activin receptors were assayed in human vascular tissue specimens that represented various stages of atherogenesis. In situ hybridization experiments revealed activin mRNA in endothelial cells and macrophages and a strong induction of activin expression in neointimal smooth muscle cells from the early onset of atherogenesis. We developed an “in situ free-activin binding assay” by using biotinylated follistatin, which allowed us to detect bioactive activin at specific sites in atherosclerotic lesions. The mRNAs encoding the activin receptors are expressed similarly in normal and atherosclerotic tissue, which indicates that activin-A signaling in atherogenesis is most likely dependent on changes in growth factor concentrations rather than on receptor levels. In vitro, activin induces the contractile, nonproliferative phenotype in cultured smooth muscle cells, as is reflected by increased expression of smooth muscle-specific markers (SMα-actin and SM22α). Our data provide evidence that activin induces redifferentiation of neointimal smooth muscle cells, and we hypothesize that activin is involved in plaque stabilization.
Intravitreal Aflibercept for Diabetic Macular Edema
Authors: Jean-François Korobelnik, Diana V. Do, Ursula Schmidt-Erfurth, David S. Boyer, Frank G. Holz, Jeffrey S. Heier, Edoardo Midena, Peter K. Kaiser, Hiroko Terasaki, Dennis M. Marcus, Quan D. Nguyen, Glenn J. Jaffe, Jason S. Slakter, Christian Simader, Yuhwen Soo, Thomas Schmelter, George D. Yancopoulos, Neil Stahl, Robert Vitti, Alyson J. Berliner, Oliver Zeitz, Carola Metzig, David M. Brown
Journal: Ophthalmology (2014)
Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients With Atrial Fibrillation
Authors: Vivek Y. Reddy, Shephal K. Doshi, Horst Sievert, Maurice Buchbinder, Petr Neuzil, Kenneth Huber, Jonathan L. Halperin, David Holmes
Journal: Circulation (2013)

Background— The multicenter PROTECT AF study (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) was conducted to determine whether percutaneous left atrial appendage closure with a filter device (Watchman) was noninferior to warfarin for stroke prevention in atrial fibrillation. Methods and Results— Patients (n=707) with nonvalvular atrial fibrillation and at least 1 risk factor (age &gt;75 years, hypertension, heart failure, diabetes, or prior stroke/transient ischemic attack) were randomized to either the Watchman device (n=463) or continued warfarin (n=244) in a 2:1 ratio. After device implantation, warfarin was continued for ≈45 days, followed by clopidogrel for 4.5 months and lifelong aspirin. Study discontinuation rates were 15.3% (71/463) and 22.5% (55/244) for the Watchman and warfarin groups, respectively. The time in therapeutic range for the warfarin group was 66%. The composite primary efficacy end point included stroke, systemic embolism, and cardiovascular death, and the primary analysis was by intention to treat. After 1588 patient-years of follow-up (mean 2.3±1.1 years), the primary efficacy event rates were 3.0% and 4.3% (percent per 100 patient-years) in the Watchman and warfarin groups, respectively (relative risk, 0.71; 95% confidence interval, 0.44%–1.30% per year), which met the criteria for noninferiority (probability of noninferiority &gt;0.999). There were more primary safety events in the Watchman group (5.5% per year; 95% confidence interval, 4.2%–7.1% per year) than in the control group (3.6% per year; 95% confidence interval, 2.2%–5.3% per year; relative risk, 1.53; 95% confidence interval, 0.95–2.70). Conclusions— The “local” strategy of left atrial appendage closure is noninferior to “systemic” anticoagulation with warfarin. PROTECT AF has, for the first time, implicated the left atrial appendage in the pathogenesis of stroke in atrial fibrillation. Clinical Trial Registration:— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00129545.
Malnutrition and pulmonary function in children in a developing country
Authors: Michele Arigliani, Mattia Guerra, Michele Alltomare, Marco Driutti, Luca Varcasia, Gianluigi Mottini, Mario Canciano Canciani
Journal: European Respiratory Journal (2013)

In animal models perinatal nutritional deficiency profoundly disturbs lung development. It appears reasonable that a similar poor nutritional status in humans leads to reduced pulmonary function. To the best of our knowledge, few studies have been performed to assess the effects of malnutrition on pulmonary function tests (PFTs) in children.[1]  AIMS: to elucidate the relationship between nutritional status and pulmonary function in children living in a poor country  METHODS: in this cross-sectional study 163 children (5-11 y.) living in the northern of Madagascar (Human Development Index 0.480) underwent a clinical exam and PFTs. Children were grouped according to the presence (group 1) or absence (group 2) of malnutrition, defined as BMI z-score   RESULTS: among the whole cohort, 100 children (mean age 8.1±1.3; 42F) performed successfully PFTs according to ERS/ATS guidelines. Group 1 was constituted by 25 malnourished children (median BMI z-score -2.88), while the remaining 75 had an adequate nutritional status (group 2; median BMI z-score -0.63). Group 1 showed lower lung volumes, such as FVC (p  * % of predicted values  CONCLUSIONS: Our data highlight the close relationship between nutritional status and pulmonary function. Malnutrition has a negative effect on PFTs in Malgascian children. It might affect respiratory muscles strength and endurance and/or parenchymal structure of the lung.  [1] Ong TJ et al. Arch Dis Child 1998;79:18-21.
Serum-Soluble B7x Is Elevated in Renal Cell Carcinoma Patients and Is Associated with Advanced Stage
Authors: R. Houston Thompson, Xingxing Zang, Christine M. Lohse, Bradley C. Leibovich, Susan F. Slovin, Victor E. Reuter, John C. Cheville, Michael L. Blute, Paul Russo, Eugene D. Kwon, James P. Allison
Journal: Cancer Research (2008)

Abstract B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently described in renal cell carcinoma (RCC) and was associated with poor outcome. We developed an assay to detect serum-soluble B7x (sB7x) and investigated 101 patients with clear cell RCC who underwent nephrectomy between 2003 and 2007. For controls, we obtained serum from 101 sex-matched blood donors within the same age range. Following an ELISA for sB7x, detectable levels (&amp;gt;0.1 ng/mL) of sB7x were observed in 53 RCC patients compared with 18 controls (P &amp;lt; 0.001). Median (range) concentrations of sB7x for RCC patients and controls were 14.4 ng/mL (0.1–56.9) and 2.7 ng/mL (0.2–37.1), respectively. For RCC patients with detectable sB7x, median levels were significantly higher for patients with a tumor thrombus (19.2 versus 6.6 ng/mL; P = 0.007), positive lymph nodes (41.3 versus 10.3 ng/mL; P = 0.018), and distant metastases at nephrectomy (43.3 versus 8.5 ng/mL; P = 0.002) and tended to be higher in patients with high-grade tumors (18.8 versus 8.5; P = 0.090). Additionally, median sB7x levels for tumor-node-metastasis stage I to IV RCC were 6.6, 10.3, 14.5, and 43.3 ng/mL, respectively (P = 0.012). In this first evaluation of sB7x in RCC, we show that RCC patients are more likely to have detectable sB7x compared with controls and higher sB7x levels correlate with advanced tumor stage. These early results merit further investigation of this serum marker for potential diagnostic and prognostic purposes. [Cancer Res 2008;68(15):6054–8]
Neutrophils Exert Protection in the Early Tuberculous Granuloma by Oxidative Killing of Mycobacteria Phagocytosed from Infected Macrophages
Authors: Chao-Tsung Yang, C.J. Cambier, J. Muse Davis, Christopher J. Hall, Philip S. Crosier, Lalita Ramakrishnan
Journal: Cell Host & Microbe (2012)
Airway and systemic inflammation in obese children with asthma
Authors: Megan E. Jensen, Peter G. Gibson, Clare E. Collins, Lisa G. Wood
Journal: European Respiratory Journal (2013)

Obese asthma presents via altered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls. In a cross-sectional study, children aged 8–17 years were assigned to one of four groups: obese asthma (OA, n=74); nonobese asthma (NOA, n=249); obese control (OC, n=9); nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured. Non-eosinophilic asthma was more prevalent among OA females (60.0%) versus OA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA, versus NOA and NOC, while adiponectin was reduced in OA versus NOC only. Expiratory reserve volume was reduced in OA, versus NOC. Residual volume (RV) and RV/total lung capacity were reduced in OC versus OA, and OC versus OA and NOA, respectively. Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation.
Reach Out to Enhance Wellness Home-Based Diet-Exercise Intervention Promotes Reproducible and Sustainable Long-Term Improvements in Health Behaviors, Body Weight, and Physical Functioning in Older, Overweight/Obese Cancer Survivors
Authors: Wendy Demark-Wahnefried, Miriam C. Morey, Richard Sloane, Denise C. Snyder, Paige E. Miller, Terryl J. Hartman, Harvey J. Cohen
Journal: Journal of Clinical Oncology (2012)

Diet and exercise interventions have been tested in cancer survivors as a means to reduce late effects and comorbidity, but few have assessed adherence and health outcomes long term.
p73 and p63 Sustain Cellular Growth by Transcriptional Activation of Cell Cycle Progression Genes
Authors: Konstantinos Lefkimmiatis, Mariano Francesco Caratozzolo, Paola Merlo, Anna Maria D'Erchia, Beatriz Navarro, Massimo Levrero, Elisabetta Sbisa', Apollonia Tullo
Journal: Cancer Research (2009)

Despite extensive studies on the role of tumor suppressor p53 protein and its homologues, p73 and p63, following their overexpression or cellular stress, very little is known about the regulation of the three proteins in cells during physiologic cell cycle progression. We report a role for p73 and p63 in supporting cellular proliferation through the transcriptional activation of the genes involved in G(1)-S and G(2)-M progression. We found that in MCF-7 cells, p73 and p63, but not p53, are modulated during the cell cycle with a peak in S phase, and their silencing determines a significant suppression of proliferation compared with the control. Chromatin immunoprecipitation analysis shows that in cycling cells, p73 and p63 are bound to the p53-responsive elements (RE) present in the regulatory region of cell cycle progression genes. On the contrary, when the cells are arrested in G(0)-G(1), p73 detaches from the REs and it is replaced by p53, which represses the expression of these genes. When the cells move in S phase, p73 is recruited again and p53 is displaced or is weakly bound to the REs. These data open new possibilities for understanding the involvement of p73 and p63 in cancer. The elevated concentrations of p73 and p63 found in many cancers could cause the aberrant activation of cell growth progression genes and therefore contribute to cancer initiation or progression under certain conditions.
Noninvasive Techniques for Prevention of Intradialytic Hypotension
Authors: L. Sornmo, F. Sandberg, E. Gil, K. Solem
Journal: IEEE Reviews in Biomedical Engineering (2012)

Episodes of hypotension during hemodialysis treatment constitutes an important clinical problem which has received considerable attention in recent years. Despite the fact that numerous approaches to reducing the frequency of intradialytic hypotension (IDH) have been proposed and evaluated, the problem has not yet found a definitive solution-an observation which, in particular, applies to episodes of acute, symptomatic hypotension. This overview covers recent advances in methodology for predicting and preventing IDH. Following a brief overview of well-established hypotension-related variables, including blood pressure, blood temperature, relative blood volume, and bioimpedance, special attention is given to electrocardiographic and photoplethysmographic (PPG) variables and their significance for IDH prediction. It is concluded that cardiovascular variables which reflect heart rate variability, heart rate turbulence, and baroreflex sensitivity are important to explore in feedback control hemodialysis systems so as to improve their performance. The analysis of hemodialysis-related changes in PPG pulse wave properties hold considerable promise for improving prediction.
Epidermal growth factor (EGF) and interleukin (IL)-1β synergistically promote ERK1/2-mediated invasive breast ductal cancer cell migration and invasion
Authors: Liqiang Ma, Fenghua Lan, Zhiyong Zheng, Feilai Xie, Lie Wang, Wei Liu, Junyong Han, Feng Zheng, Yanchuan Xie, Qiaojia Huang
Journal: Molecular Cancer (2012)

Patients with invasive breast ductal carcinoma (IBDC) with metastasis have a very poor prognosis. Little is known about the synergistic action of growth and inflammatory factors in IBDC metastases.The expression of activated extracellular signal-regulated kinase1/2 (phosphorylated or p-ERK1/2) was analyzed by immunohistochemistry in IBDC tissue samples from 80 cases. BT474 IBDC cell migration and invasion were quantified using the Transwell assay. Matrix metalloproteinase (MMP)-9 expression and activity were analyzed by RT-PCR, Western blotting and zymography. Activator protein (AP)-1 activity was measured with a luciferase reporter gene assay. The Wilcoxon signed-rank test, Chi-square test, the partition of Chi-square test, independent t-test, and Spearman's method were used for the statistical analysis.Phosphorylated ERK1/2 was detected in 58/80 (72.5%) IBDC tissues, and was associated with higher TNM stage and lymph node metastasis, but not patient age or tumor size. Individually, epidermal growth factor (EGF), and interleukin (IL)-1β activated ERK1/2, increased cell migration and invasion, MMP-9 expression and activity, AP-1 activation in vitro and the expression of p-ERK1/2 was positively correlated with EGF expression levels, as well as IL-1β, MMP-9 and c-fos in IBDC tissue samples. Co-stimulation with EGF and IL-1β synergistically increased ERK1/2 and AP-1 activation, cell migration and invasion, and MMP-9 expression and activity. Inhibition of ERK1/2 using U0126 or siRNA abolished EGF and/or IL-1β-induced cell migration and invasion in a dose-dependent manner.Activated ERK1/2 was associated with higher TNM stage and lymph node metastasis in IBDC. Both in vitro and in vivo studies indicated that ERK-1/2 activation may increase the metastatic ability of IBDC cells. Growth and inflammatory factors synergistically induced IBDC cell migration and invasion via ERK1/2 signaling, AP-1 activation and MMP-9 upregulation.
Tophaceous gout of the pubic symphysis: an unusual cause of groin pain
Authors: H Gardner
Journal: Annals of the Rheumatic Diseases (2004)

A 73 year old Polynesian woman was admitted with a 5 day history of severe pain in the right groin, right hip, and lower back and was unable to weight bear. Past history included tophaceous gout of 10 years’ duration, which was poorly controlled despite daily colchicine. She had chronic lymphoedema of the right leg (Milroy’s disease). This was complicated by recurrent episodes of right lower leg cellulitis requiring previous amputation of one of her toes due to intractable infection. She had a longstanding monoclonal gammopathy of uncertain significance. Other problems included hypertension, congestive cardiac failure, obesity, and impaired renal function (creatinine clearance 30 ml/min). Her drugs on admission were quinapril, furosemide, calcium carbonate, and paracetamol.

On examination she weighed 120 kg. A gouty tophus was present at the right index finger proximal interphalangeal joint. She was afebrile and normotensive. There was diffuse tenderness in the right groin and she was unable to actively lift the right leg owing to pain. Significant blood results …
Potent Antitumor Activity in Experimental Hepatocellular Carcinoma by Adenovirus-Mediated Coexpression of <i>TRAIL</i> and shRNA against <i>COX-2</i>
Authors: Qing Chen, Wenjia Lou, Junjie Shen, Leina Ma, Zhi Yang, Li Liu, Jingjing Luo, Cheng Qian
Journal: Clinical Cancer Research (2010)

Recent studies have indicated that short hairpin RNA (shRNA) driven by RNA polymerase (Pol) II promoters can be transcribed into precursor mRNAs together with transgenes. It remains unclear, however, whether coexpression of shRNA and transgene from a single promoter is feasible for cancer therapy.In this study, we generated novel adenoviral vectors that permitted coexpression of shRNA against cyclooxygenase-2 (COX-2) and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapeutic gene from a cytomegalovirus promoter to evaluate whether silencing of COX-2 could increase the sensitivity of hepatocellular carcinoma to TRAIL.Our data showed that adenovirus vector Ad-TM, in which the shRNA was inserted into the 3' untranslated region of the TRAIL gene, not only significantly suppressed COX-2 expression, but also expressed a high level of TRAIL. Moreover, infection with Ad-TM resulted in significant cytotoxicity in hepatocellular carcinoma cell lines. In contrast, it had no effect on normal liver cell line. Impressively, treatment of the established hepatocellular carcinoma tumors with Ad-TM resulted in complete tumor regression. This potent antitumor activity induced by Ad-TM was due to strong inhibition of COX-2 and high expression of TRAIL. Furthermore, using the shRNA and transgene coexpression adenovirus system, we showed that silencing of COX-2 increased the sensitivity of hepatocellular carcinoma to TRAIL through inhibition of Bcl-2 and Bcl-w.This study indicated that adenovirus carrying shRNA and transgene expressed from a single promoter represented a potent approach for cancer therapy.
Prevalence of smoking among patients treated in NHS hospitals in England in 2010/2011: a national audit: Table 1
Authors: L Szatkowski, R Murray, R Hubbard, S Agrawal, Y Huang, J Britton
Journal: Thorax (2014)

Using data from The Health Improvement Network and Hospital Episode Statistics, we investigate smoking prevalence, number of smokers treated and opportunities for cessation intervention among patients treated in National Health Service (NHS) hospitals in England from April 2010 to March 2011. Our results show that approximately 1.1 million smokers are treated in English hospitals each year, receiving a total of 2.6 million episodes of care. These findings suggest that delivering smoking cessation as a routine component of hospital care, as recommended by recent National Institute for Health and Care Excellence guidance, could achieve marked reductions in the prevalence of smoking and improve the cost-effectiveness of NHS hospitals.
Breast Cancer Risk for Noncarriers of Family-Specific <i>BRCA1</i> and <i>BRCA2</i> Mutations: Findings From the Breast Cancer Family Registry
Authors: Allison W. Kurian, Gail D. Gong, Esther M. John, David A. Johnston, Anna Felberg, Dee W. West, Alexander Miron, Irene L. Andrulis, John L. Hopper, Julia A. Knight, Hilmi Ozcelik, Gillian S. Dite, Carmel Apicella, Melissa C. Southey, Alice S. Whittemore
Journal: Journal of Clinical Oncology (2011)

Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs).Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors.We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases.These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.
Dissolution of peripheral arterial thrombi by ultrasound.
Authors: M Ariani, M C Fishbein, J S Chae, H Sadeghi, A D Michael, S B Dubin, R J Siegel
Journal: Circulation (1991)

BACKGROUND We have previously shown that continuous-wave ultrasound can rapidly dissolve human thrombi in vitro, with 99% of all residual particles measuring less than 10 microns in diameter. To assess the effects of pulsed-wave ultrasound energy on whole blood clots, 1) in vitro studies were preformed to assess precisely the rates of clot disruption and to quantify particulate size, and 2) in vivo studies were performed to assess the efficacy and safety of catheter-delivered ultrasound for intra-arterial thrombus dissolution. METHODS AND RESULTS In vitro, we studied 50 samples of human whole blood clots and using an 89-cm-long wire probe, applied pulse-wave energies from 8 to 23 W. The corresponding peak-to-peak tip displacement range was 63.5 - 102 microns. We studied arterial thrombosis in vivo in 21 canine superficial femoral arteries. To produce an acute thrombosis, 200 units of thrombin followed by 2 ml of 72-hour-old autologous clot were injected into a 5-7-cm segment of femoral artery and left to coagulate for 2 hours. Ultrasound energy was intermittently applied at a frequency of 20 kHz with a prototype ultrasound wire ensheathed in a catheter and directed to clots by fluoroscopy. In nine cases, angioscopic guidance was used to put the probe into direct contact with the intra-arterial thromboses. In vitro clot dissolution times were inversely related to the ultrasound power output (r = 0.95). All in vivo canine thromboses were disrupted in 4 minutes or less. All successful recanalizations were confirmed by angiography and in nine cases by angioscopy as well. Angioscopy demonstrated that probe activation caused rapid clot disruption. Histological studies of the vessels showed no evidence of thermal or cavitation injury, occlusive distal embolization, or perforation. CONCLUSIONS Our findings in this experimental canine model suggest that ultrasound clot dissolution has the potential to be an effective and safe alternative to current treatment modalities for peripheral arterial thrombosis.