tbuckley/cabot-search huggingface dataset:
The long intergenic non-coding RNA, PVT1, regulates the TGF-β-induced proliferative response in airway smooth muscle cells from severe asthmatics
Authors: Mark Perry, Phillip Austin, Ian Adcock, Kian Fan Chung
Journal: European Respiratory Journal (2013)

Rationale

Only 2% of the nucleotides in the human genome code for protein. The overwhelming majority of the human genome is transcribed into non-coding RNA that are divided into house-keeping, short and long non-coding RNA (lncRNA), with the majority being lncRNAs (>200 nucleotides). lncRNAs are classified according to their function and/or their position relative to the transcription of protein-coding RNA and include the antisense, pseudogenes and long intergenic non-coding RNAs (lincRNAs).

Asthma is characterised by chronic airflow obstruction, chronic airway inflammation and remodelling. Airway smooth muscle (ASM) cells cultured from the biopsies of patients with asthma are of a hyperproliferative phenotype and release greater amounts of chemokines when compared to non-asthmatic subjects.

We have previously found that PVT1 was differentially expressed in asthmatic ASM by TGF-β. We hypothesise that by inhibiting this lincRNA in ASM cells from severe asthmatics, we may reverse the hyperproliferative phenotype.

Methods

Human ASM cells were transfected with a pool of siRNAs designed to target PVT1. Cells were then stimulated with TGF-β. Cellular proliferation and IL-6 release were measured by BrdU incorporation and ELISA, respectively.

Results

Inhibiting PVT1 in ASM cells from severe asthmatics reduced both the hyperproliferation and the increased IL-6 release.

Conclusions

This is the first time that the lincRNA, PVT1, has been demonstrated to be fundamental in controlling the hyperproliferative state of ASM cells from severe asthmatics. PVT1 may prove to be a novel target for treatment.
Prediction of survival for preterm births
Authors: T H H G Koh
Journal: BMJ (2000)

The sexual health of boys and men Commercial advertisements are needed to create a condom cultureEditor-Yamey highlighted the need for work on the sexual health of boys and men, and he identified education and service provision as the key factors in increasing condom use, among other outcomes. 1Both of these factors fail to address the underlying problem, that condoms are unpopularthey are far short of desired items among young men in particular.A major factor influencing cultural attitudes is not education or services but the media.Global marketing, vast advertising budgets, and sexual imagery are used to sell items as diverse as chocolate bars and sanitary products on television.However, noticeably absent in the United Kingdom is any commercial television advertisement promoting particular condom brands or targeted to the growing market for condoms.Consequently, the promotion of condom use falls largely on public sector bodies.Education and health bodies have already made condoms more available to young people and developed an understanding of their health benefits.However, without a cultural move making condom use popular, such efforts have limited success as health promotion fights to convince people to use unpopular products.Partly as a result, sexually transmitted infections in young people are increasing in England, 2 and there are 90 000 teenage conceptions a year. 3ondoms are produced commercially and lend themselves to many images that are used to market other products successfully, so you would predict a deluge of television adverts promoting one brand above another.Antiquated advertising rules may explain why this has not happened.Those governing condom advertisements on UK television expressly forbid companies from showing the product unwrapped, and consequently the image of an unwrapped condom cannot be normalised or promoted. 4Advertising limitations also dictate social responsibility in advertisements and prohibit anything promoting promiscuity.How far these other measures limit advertisers seems to be unknown, but such restrictions should be measured against the numerous television hours showing promiscuity without any reference to condoms.Furthermore, these considerable restrictions on condom advertising may prevent movement of new producers into markets and consequently stifle the competition necessary to refine marketing and product development.The government is pursuing strategies in communicable disease, sexual health, and HIV, as well as reductions in teenage pregnancy. 3Pragmatic revisions to existing rules on the commercial advertising of condoms may allow commercial interests to work with those of health to alter the image of condoms and increase markets (particularly among young people) in order to help reduce sexually transmitted infections and unwanted pregnancies.
MiR-145 and SMAD3 expression in patients with cystic fibrosis
Authors: Francesca Megiorni, Samantha Cialfi, Giuseppe Cimino, Riccardo Valerio De Biase, Daniela Savi, Carlo Dominici, Antonio Pizzuti, Serena Quattrucci
Journal: European Respiratory Journal (2013)

Introduction: microRNAs (miRNAs) have recently been emerged as important regulatory molecules in Cystic Fibrosis (CF) disease in which airways tissues/organs are often characterized by severe inflammation and recurrent infections. Therefore, miRNA aberrant expression might explain the wide phenotypic variability observed in CF patients. Aims and Objectives: In order to comprehend the role of miRNAs in the CF pathogenesis, we analyzed the expression of specific miRNAs in nasal epithelia of CF patients and healthy controls. Methods: miRNA and mRNA levels were measured by quantitative real time PCR (Q-PCR) using the relative quantification 2−ΔΔCT method. Computational prediction algorithms and luciferase reporter assays were used to identify putative targets of miR-145. Results: miR-145 was significantly up-regulated in nasal epithelial tissues from CF patients compared with healthy subjects (p
Effects of Liposome-Entrapped Doxorubicin on Liver Metastases of Mouse Colon Carcinomas 26 and 38&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E G Mayhew, M H Goldrosen, J Vaage, Y M Rustum
Journal: JNCI Journal of the National Cancer Institute (1987)

The effects of doxorubicin (DOX) and DOX entrapped in standardized liposomes [mean diameter, 0.15 micron; (DOX-Lip)] on the survival of mice bearing liver metastases of mouse colon carcinoma CT38LD (C57BL/6J mice) or CT26 (BALB/c mice) were investigated. In vitro cultured CT38LD cells were more sensitive to DOX than CT26. In vivo DOX and DOX-Lip, administered iv 10 mg/kg weekly to a maximum of five injections, increased the life-spans of mice bearing CT38LD liver metastases 32% (P less than .05) and 64% (P less than .05), respectively. DOX-Lip was more effective than DOX in prolonging survival (P less than .05). Free DOX did not significantly increase the life-spans of mice bearing CT26 liver metastases (P greater than .5), whereas DOX-Lip increased the life-spans 35% (P less than .05). The results suggest that liposomal delivery of agents to the liver can enhance therapeutic activity and could be used as an arm of protocols for adjuvant therapy of liver metastases.
Fine Structural Organization of Human Lymphoblasts of a Tissue Culture Strain (EB1) From Burkitt's Lymphoma2
Authors: M. A. Epstein, B. G. Achong
Journal: JNCI Journal of the National Cancer Institute (1965)

Human lymphoblasts from an established tissue culture strain (EB1) derived from a Burkitt lymphoma were studied in thin sections with the electron microscope. The identification of the cells as lymphoblasts was confirmed at the fine structural level by their conformity to the usual morphological pattern of this type of cell. It was also observed that all the cultured cells were structurally uniform, irrespective of their shape or size, and that many possessed annulate lamellae such as are present in malignant cells. In addition, a peculiar cytoplasmic projection of the nuclear envelope was often observed, but its nature could not be determined.
Unusual Locations for Lymphomas
Authors: Steven J. Freedman, Liron Pantanowitz, Jeff T. Joseph, Julian Wu, Eric T. Wong, Bruce J. Dezube
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.11.2960 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11387370 Unusual Locations for Lymphomas Case 2. Pineal Lymphoma Steven J. FreedmanxSteven J. FreedmanSearch for articles by this author , Liron PantanowitzxLiron PantanowitzSearch for articles by this author , Jeff T. JosephxJeff T. JosephSearch for articles by this author , Julian WuxJulian WuSearch for articles by this author , Eric T. WongxEric T. WongSearch for articles by this author , Bruce J. DezubexBruce J. DezubeSearch for articles by this author Show More Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, Copyright © 2001 American Society of Clinical Oncology https://doi.org/10.1200/JCO.2001.19.11.2960 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Safety profile and pharmacokinetics of an inhaled GATA-3-specific DNAzyme in a phase Ib study in patients with stable allergic asthma
Authors: Jens Hohlfeld, Katrin Lüer, Norbert Krug, Agnieszka Turowska, Harald Renz, Holger Garn, Ursula Homburg
Journal: European Respiratory Journal (2013)

SB010 (a nebulization solution of the human GATA-3-specific DNAzyme hgd40) has been developed for treatment of Th2-driven asthma. DNAzymes are single-stranded catalytic DNA molecules that specifically bind and cleave target mRNAs. Single or multiple applications of SB010 were already proven to be safe in Phase Ia studies in healthy subjects. Aim of this study was to investigate safety, tolerability and pharmacokinetics of inhaled single ascending doses of SB010 in a Phase Ib clinical trial in male stable allergic asthma patients with airway hyperresponsiveness (PC 20  methacholine ≤ 4 mg/mL). The study was performed as a randomized, double-blind, placebo controlled, parallel group (per dose level) dose-escalation study in 24 patients (18-45 years). SB010 was applied as nebulized solution via a controlled breathing system (AKITA 2 APIXNEB®) in 3 dose levels (5, 10, 20 mg). Adverse events (AEs), vital signs, clinical chemistry, hematology, urinalysis, ECG, pulmonary function testing, body temperature, and overall tolerability were assessed. Generally, all dose levels were well tolerated. No clinically relevant influence on safety laboratory parameters, vital signs including lung function tests, differential blood count, or ECG measurements was observed. Plasma concentrations were analyzed using a hgd40-specific hybridization ELISA system. Maximum plasma concentrations of hgd40 were detected within the highest dose group at 1 hour after administration (13.51 ± 17.02 pg/mL); hgd40 was no longer detectable at 6 hours after administration. SB010 is now under evaluation in a phase IIa study.
Quadriceps muscle fibre type shift is more pronounced in sarcopenic patients with COPD
Authors: Coby van de Bool, Harry Gosker, Bram van den Borst, Celine Op den Kamp, Ilse Slot, Annemie Schols
Journal: European Respiratory Journal (2014)

Background   Quadriceps muscle in COPD is characterized by a loss of oxidative phenotype which adversely affects exercise performance. We recently showed in a large cohort of patients eligible for rehabilitation that sarcopenia in COPD not only is associated with muscle strength but also with cycle exercise endurance. We hypothesize that the loss of oxidative muscle fibres is more pronounced in COPD patients with sarcopenia, which in turn could accelerate muscle wasting.   Aim   To investigate quadriceps muscle fibre type composition in relation to sarcopenia in patients with COPD and in healthy controls.   Methods   Body composition was assessed by Dual-energy X-ray Absorptiometry in 49 COPD patients (FEV 1  52±17%, age 66±7y) and 53 healthy controls (FEV 1  112±17%, age 63±6y). Sarcopenia was defined as appendicular skeletal muscle mass-index (SMI) l7.23 kg/m 2  for males and l5.67 kg/m 2  for females. Muscle fibre type and cross sectional area (CSA) were assessed in quadriceps muscle biopsies.   Results   Sarcopenia was present in 6% of healthy controls  versus  31% of COPD patients (Pl0.001). COPD patients showed a 33% lower proportion of oxidative type I fibres (Pl0.001) and 10% lower CSA of type IIx fibre than healthy controls (Pl0.01). Sarcopenic patients showed a 33% lower proportion (Pl0.05) as well as a 27% lower CSA of type I fibres (Pl0.05) compared to non-sarcopenic patients.   Conclusion   The more pronounced decreased type I fibre proportion in sarcopenic COPD patients suggests a cross-talk between muscle mass and oxidative phenotype regulation.  This study was financially supported by the by the Lung Foundation Netherlands (grant number: 3.4.09.003).
Elevated serum iron as a marker for spirometric resistance to cigarette smoke: The Takahata study
Authors: Yoko Shibata, Sumito Inoue, Shuichi Abe, Akira Igarashi, Isao Kubota
Journal: European Respiratory Journal (2013)

Background:  Many cigarette smokers develop COPD. However, pulmonary function is preserved in some elderly individuals despite smoking, and their characteristics have not been investigated. We aimed to identify a biomarker in individuals in whom lung health is maintained despite smoking.   Methods:  Blood sampling and spirometry were performed on 3,257 subjects who participated in a community-based annual health check in Takahata, Japan, from 2004 to 2006. We selected 119 elderly smokers (age ≥ 70, Brinkman index ≥ 600, smoking years ≥ 30). The ‘smoking resistant’ group met the following criteria: FEV 1 /FVC ≥ 0.7, and FEV 1  %predicted ≥ 80. Spirometry was re-evaluated in 147 male, current smokers in 2009.   Results:  Increased serum iron (sFe) levels were demonstrated in the smoke resistant group compared with the non-resistant group. In those with low sFe levels, FEV 1 /FVC was reduced in males, and FEV 1  %predicted was reduced in females. These spirometric measures were positively associated with sFe levels in men, but not in women. Multiple linear regression analysis revealed that sFe levels were predictive for spirometric values, independent of other clinical factors. In addition, sFe levels were predictive for a decline in FEV 1 .   Conclusion:  Serum iron levels may be a biomarker for the spirometric susceptibility of individuals to cigarette smoke.
Potentiation of Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene-Induced Liver Enzyme Activity in Sprague-Dawley Female Rats by Aqueous Extract of Cigarette-Smoke Condensate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Katherine L. Sydnor, Cheryl Allen, James W. Flesher
Journal: JNCI Journal of the National Cancer Institute (1972)

An aqueous extract of cigarette-smoke condensate [(AECSC), 0.25 mg/ml of 5% sugar solution] administered to Sprague-Dawley female rats as drinking fluid potentiated benzo[a]pyrene-induced liver aryl hydroxylase and menadione reductase activities. Without benzo[a]pyrene, liver aryl hydroxylase activity was slightly increased by AECSC, but menadione reductase activity was not affected.
<i>Carbonic anhydrase IV</i>inhibits colon cancer development by inhibiting the Wnt signalling pathway through targeting the WTAP–WT1–TBL1 axis
Authors: Jingwan Zhang, Ho Tsoi, Xiaoxing Li, Hua Wang, Jing Gao, Kunning Wang, Minnie YY Go, Siew C Ng, Francis KL Chan, Joseph JY Sung, Jun Yu
Journal: Gut (2015)

<h3>Objective</h3> We found that carbonic anhydrase IV (CA4), a member of the carbonic anhydrases, is silenced in colorectal cancer (CRC). We analysed its epigenetic inactivation, biological effects and prognostic significance in CRC. <h3>Design</h3> The biological functions of CA4 were determined by in vitro and in vivo tumorigenicity assays. The CA4 co-operator was identified by immunoprecipitation and mass spectrometry. CA4 downstream effectors and signalling pathways were elucidated by promoter luciferase assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. The clinical impact of CA4 was assessed in 115 patients with CRC. <h3>Results</h3> CA4 was silenced in all nine CRC cell lines and 92.6% of CRC tumours. The promoter hypermethylation contributed to the inactivation of <i>CA4</i>, and it was detected in 75.7% of the patients with CRC. After a median follow-up of 49.3 months, multivariate analysis showed that the patients with <i>CA4</i> hypermethylation had a recurrence of Stage II/III CRC. The re-expression of CA4 inhibited cell proliferation, induced apoptosis and cell cycle arrest in the G1 phase. CA4 inhibited the activity of the Wnt signalling pathway and mediated the degradation of β-catenin<i>.</i> CA4 interacted with Wilms’ tumour 1-associating protein (WTAP) and induced WTAP protein degradation through polyubiquitination. Moreover, CA4 promoted the transcriptional activity of Wilms’ tumour 1 (WT1), an antagonist of the Wnt pathway, which resulted in the induction of transducin β-like protein 1 (<i>TBL1</i>) <i>and</i> the degradation of β-catenin. <h3>Conclusions</h3> CA4 is a novel tumour suppressor in CRC through the inhibition of the Wnt signalling pathway by targeting the WTAP–WT1–TBL1 axis. CA4 methylation may serve as an independent biomarker for the recurrence of CRC.
Abstract 2751: Correlation of Left Atrial Voltage Maps with Cardiovascular MR Provides Evidence of Pre-existent Scar in Atrial Fibrillation Patients
Authors: Jeongjoo Woo, Dana C Peters, John V Wylie, Reza Nezafat, Thomas H Hauser, Mark E Josephson, Warren J Manning
Journal: Circulation (2008)

Introduction: There is increasing evidence for and interest in detecting electrically silent left atrial (LA) myocardium which may be the substrate of atrial fibrillation (AF). Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) might detect these areas of pre-existent scar as high signal in the LA wall. We sought to correlate the extent low-voltage areas in AF patients with clinical parameters of LA volume and type of AF, and to correlate areas of low voltage with areas of high signal on LGE CMR, indicating areas of scarred tissue. Methods: Twenty-two patients with AF underwent high resolution atrial LGE CMR on a 1.5 T CMR scanner and bipolar voltage electroanatomic mapping (Carto, Biosense Webster). The number of the LA mapping points with low (&lt; 0.1mV) voltage was calculated for each patient. LA systolic volume was measured, indexed to BSA. Using the voltage maps, blood-LA contrast to noise ratio (CNR) was measured on the LGE CMR images in two areas, low and high voltage areas (N=10). Hypothesis testing used t-tests and p&lt;0.05. Results: The average extent of LA low voltage was 8 % of the LA. Four (18%) patients had no low voltage regions. The extent of low voltage for patients with non-paroxysmal vs. paroxysmal AF was 11 ± 13% vs. 4 % ± 5 % (p=0.08). The extent of low voltage for patients with larger than median LA volumes vs. smaller LA volumes was 12 ± 13% vs. 1 ± 1 % (p=0.027). In 10 patients in which LGE was measured in low and high voltage regions, the CNR was 10 vs. 6 (p=0.016). Conclusions: Patients with extensive low voltage regions in the LA have larger LA volumes. The CNR is higher in low-voltage regions, suggesting that such regions of possible scar can be identified by LGE CMR. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Relationship between quality of life and multidimensional assessment indices in patients with COPD
Authors: Eylem Sercan Özgür, Cengiz Özge, Ahmet Ilvan, Sibel Atis Nayci
Journal: European Respiratory Journal (2012)

Aim: Combining other health measures with FEV1 provides a more complete view of COPD patients' clinical situation. Although some multidimensional assessment indices have been developed recently, there are a few data on their relation with quality of life (QoL). This study was carried out to assess the relationship between QoL and multidimensional assessment indices in COPD patients.

Methods: We recruited 69 stable COPD patients. Quality of life was evaluated using the SGRQ questionnaire. The BODE (Body mass index, airway Obstruction, Dyspnea, Exercise capacity), DOSE (Dyspnea, airway Obstruction, Smoking status, Exacerbations) and ADO (Age, Dyspnea, airway Obstruction) index calculations were performed. The relation of quality of life with BODE, DOSE and ADO were assessed with Pearson correlation analysis.

Results: The mean age was 58.8±9.1 years and the postbronchodilator FEV1 was 61.1±13.5% predicted. Total SGRQ scores were positively correlated with BODE index (r = 0.559, p=0.0001), DOSE index (r=0.516, p<0.0001) and ADO index (r = 0.438, p=0.0001). The strongest correlation was evident in activity domain of SGRQ (r = 0.631, p=0.0001 for BODE; r = 0.566, p=0.0001 for DOSE; and r= 0.557, p=0.0001 for ADO).

Conclusion: This study showed a close correlation between quality of life (SGRQ) total and activity scores and multidimensional assesment indices in stable COPD. These scoring systems are useful tools for the assessment of quality of life in COPD, especially predicting in activity status of the patients.
Inhalation Bioassay Chemistry—Walton Horizontal Smoking Machine for Inhalation Exposure of Rodents to Cigarette Smoke&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M R Guerin, J R Stokely, C E Higgins, J H Moneyhun, R W Holmberg
Journal: JNCI Journal of the National Cancer Institute (1979)

Studies of experimental tobacco smoke carcinogenesis have suffered from the lack of a conveniently available and well-characterized device for exposing animals to tobacco smoke for inhalation. The Walton Horizontal Smoking Machine, a commercially available system designed to expose up to 20 mice to the smoke of a single cigarette, may fulfill this need. This system produced a uniform smoke aerosol of predictable concentration and appropriate composition for cigarettes with high delivery of nicotine (40 mg total particulate matter, 2.6 mg nicotine, and 17 cm3 carbon monoxide per cigarette) and with low delivery of nicotine (30 mg total particulate matter, 0.3 mg nicotine, and 17 cm3 carbon monoxide). In this experiment C57BL and DBA/2Bd strains of mice were used. Limitations of the concept of exposing animals to standing smoke were defined.