tbuckley/cabot-search huggingface dataset:
1133 A SEMI-MECHANISTIC MODEL OF FIBROSIS PROGRESSION USING COLLAGEN PROPORTIONATE AREA (CPA) IN POST LIVER TRANSPLANT (POLT) PATIENTS WITH CHRONIC HEPATITIS C (CHC)
Authors: G. Ma, A. Dhillon, A. Hall, A.K. Burroughs, M. Tsochatzis, G. Burgess, F. Guo
Journal: Journal of Hepatology (2012)
Abstract LB-430: Chemopreventive effect of beta-cryptoxanthin on smoke-induced lung inflammation and lesions in ferrets
Authors: Chun Liu, Roderick T. Bronson, Xiang-Dong Wang
Journal: Cancer Research (2010)

Abstract Background: High intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers in epidemiological studies. However, there are no available data from well-controlled animal studies to examine the effect of beta-cryptoxanthin on smoke-induced lung lesions and potential biological mechanisms by which beta-cryptoxanthin affects lung carcinogenesis. Using a ferret animal model, we evaluated the effect of beta-cryptoxanthin supplementation in both low-and high-dose (7.5 mcg/kg body weight per day vs. 37.5 mcg/kg body weight per day in ferrets which are equivalent to 104 mcg/day vs. 520 mcg/day, respectively, in the humans) on the cigarette smoke-induced pro-inflammatory cytokine TNF alpha, inflammation and squamous metaplasia in the lung. Methods: Thirty six male ferrets were assigned to one of six groups (n = 6 in each group) for 9 weeks as follows: 1) control; 2) cigarette smoke exposed; 3) low-dose beta-cryptoxanthin (7.5 mcg/kg body weight per day); 4) high-dose beta-cryptoxanthin (37.5 mcg/kg body weight per day); 5) cigarette smoke-exposed plus low-dose beta-cryptoxanthin; and 6) cigarette smoke-exposed plus high-dose beta-cryptoxanthin. Lung TNF alpha was measured by immunohistochemical staining. Lung inflammation and squamous metaplasia were quantified by histopathological evaluations. Results: Beta-cryptoxanthin supplementation dose-dependently increased plasma and lung beta-cryptoxanthin levels in ferrets. Cigarette smoke exposure lowered plasma and lung beta-cryptoxanthin levels. Treatment with beta-cryptoxanthin substantially reduced the cigarette smoke-elevated TNF alpha levels in bronchial/bronchiolar epithelial cells, alveolar epithelial cells, airway serous/mucous glands and lung macrophages. Beta-cryptoxanthin at both doses also significantly decreased the cigarette smoke-induced lung inflammation. In addition, both doses of beta-cryptoxanthin significantly lowered the incidence of lung squamous metaplasia induced by cigarette smoke exposure. There were no detectable squamous metaplasia in the groups treated with beta-cryptoxanthin alone and in the control group. Conclusions: Beta-cryptoxanthin may provide a beneficial effect against the smoke-induced lung inflammation and lung lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-430.
P572Pitx2 differently controls the expression of gene embedded microRNAs in cardiac and skeletal muscle cells.
Authors: F Hernandez-Torres, AE Aranega, D Franco
Journal: Cardiovascular Research (2014)

The Pitx2 gene is a member of the Bicoid-like homeobox family that plays an important role in embryonic left-right signalling and subsequently during cardiac and skeletal muscle organogenesis. Pitx2 misregulation has been as well associated with skeletal and cardiac muscle diseases. Although three Pitx2 isoforms are expressed in mice, Pitx2a, Pitx2b and Pitx2c, only Pitx2c plays a determinant role in left-right signalling and organogenesis. Over the last years we have gained insights into the transcriptional regulatory mechanisms driven by Pitx2 in both cardiac and skeletal muscle. Interestingly, besides playing a role in regulating a large number of protein-coding genes, microRNAs are also regulated by Pitx2. Whereas the functional role of distinct microRNAs in cardiac and skeletal muscle development and homeostasis is progressively emerging, their transcriptional control and the genetic networks in which they are involved remains largely unexplored. Among 34 differentially regulated microRNAs by Pitx2 in either skeletal or cardiac muscle cells, 10 (~30%) display putative Pitx2 binding sites in the -3000 bp proximal promoter sequence, among with other muscle-enriched transcription factor binding sites. Curiously, only two of these microRNAs were intergenic, supporting thus their own transcriptional regulatory mechanisms, while the majority of them were embedded into distinct host genes. Since transcriptional regulation of gene-embedded microRNAs seemed to be modulated in accordance with transcriptional regulation of the host gene, we evaluated the host gene/microRNA expression levels in Pitx2 gain-of-function experiments using Sol8 skeletal muscle and HL-1 atrial cardiomyocytes, respectively. Surprisingly, our data demonstrate that most of these microRNAs are independently regulated from its host gene, and moreover such transcriptional regulation is cell-type specific. We are now working to establish the mechanisms by with Pitx2 can exert this microRNAs transcriptional regulation.
A7.12 Identification of the Semaphorin Receptor Plexin-A2 as a Candidate Gene for Susceptibility to Ankylosing Spondylitis
Authors: A Chatzikyriakidou, PV Voulgari, AA Drosos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Semaphorins are a large family of secreted and membrane bound proteins linked to their receptors in a variety of cells and implicated with the development and function of many systems (nevrous, immune, vascular) and organs (bone, heart, lung, kidney). Plexins and neuropilins are the primary semaphorin receptors. The present study addresses Plexin-A2 (PLXNA2) Rs6656560 variant in rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) susceptibility. <h3>Materials and Methods</h3> One hundred thirty-six RA, 49 AS, 29 PsA patients and 147 controls were enrolled in the study. Polymerase chain reaction coupled with restriction fragment length polymorphism analysis was used in Rs6656560 genotyping. <h3>Results</h3> Statistical significant difference was observed in Rs6656560 genotypes' distribution between AS patients and controls (P = 0.041), but not between RA or PsA patients and controls (P = 0.183, P = 0.729; respectively). Similarly, significant difference was observed in Rs6656560 alleles' distribution between AS patients and controls (P = 0.013). Since AS and PsA both belong to spondyloarthropathies (SpAs), no statistical difference was observed in genotypes' distribution between these two groups (P = 0.178), while the statistical difference was significant between AS and RA patients (P = 0.035). <h3>Conclusions</h3> The positive association of PLXNA2 polymorphism with AS susceptibility seems to indicate its effect in cellular semaphorin signalling related to bone development and remodelling, both of which are implicated in AS features. Additional studies are needed to ensure the revealed genetic association with AS predisposition and the effect of this variant in semaphorin/plexin complex function in specific cell types.
Drug Development Link Between U.S. and Europe Yielding Results
Authors: Hugh McIntosh
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Drug Development Link Between U.S. and Europe Yielding Results Get access Hugh McIntosh Hugh McIntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 1, 1 January 1992, Pages 13–14, https://doi.org/10.1093/jnci/84.1.13 Published: 01 January 1992
AB0396 Plasma ghrelin levels in patients with systemic sclerosis
Authors: G. Keskin, E. D. Keskin, M. Yıldız, L. Özışık
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis (SSc) is a systemic connective tissue disease characterised by immune system changes, fibrosis of the skin and internal organs involvement and diffuse microangiopathy. Ghrelin, a 28 amino acid peptide, was found to be a potent releaser of growth hormone (GH) and actively participate in controlling energy balance and regulation of food intake. Ghrelin has reported to be synthesized by several immun system cells and can also modulate the inflammatory response. In literature, there are so many studies investigating possible role of ghrelin in many diseases. It was hypothesized that this peptide may exert immunoregulatory effects on immune system. There is currently no published evidence demonstrating a role for anti-inflammatory effects of ghrelin in SSc. <h3>Objectives</h3> For this reason, we investigated the role of plasma ghrelin levels in patients with SSc. <h3>Methods</h3> Plasma samples were obtained from 38 patients (22 ISSc, 16 DSSc) with SSc (26 female, 12 male, mean age; 29.2 ± 6.9 years, mean disease duration 8.3 ± 2.9 years) and from 16 healthy controls (10 female, 6 male; mean age 31.7 ± 7.2 years). We recorded clinical (ulcers, teleangectasias, calcinosis, skin score, heart and lung involvement) and immunological characteristics (ANA, scl 70) of patients. Plasma ghrelin levels were determined by EIA. <h3>Results</h3> The mean plasma ghrelin levels were 227.9 ± 45.1 pg/ml in patients with SSc and 69.2 ± 4.7 pg/ml in healthy controls. Plasma ghrelin levels were significantly high in patients with SSc compared to healthy controls (p&lt;0.001). Plasma ghrelin levels were significantly high in DSSc patients and Scl70 positive patients and correlated with skin score (p&lt;0.001, p&lt;0.01 and r=0.524, p&lt;0.001 respectively). <h3>Conclusions</h3> In this study, we demonstrated that plasma unacylated ghrelin levels were significantly elevated in patients with SSc. It is showed that ghrelin may play significant role of the pathogenesis of SSc, especially DSSc. The high levels of plasma ghrelin level might support a role of ghrelin and similar anti inflammatory proteins in SSc. <h3>References</h3> Gnanapavan, S.; Kola, P.; Bustin, S.A.; Morris, D.G.; McGee, P.; Fairclough, P.; Bhattacharya, S.; Carpenter, R.; Grossman, A.B.; Korbonits, M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R in humans. <i>J Clin Endocrinol Metab</i>, <b>2002</b>, <i>87</i>:2988. Dixit, V.D.; Schaffer, E.M.; Pyle, R.S.; Collins, G.D.; Sakthivel, S.K.; Palaniappan, R.; Lillard, Jr. J.W.; Taub, D.D. Ghrelin inhibits leptin and activation induced proinflammatory cytokine expression by human monocytes and T cells. <i>J Clin Invest</i>, <b>2004</b>, <i>114</i>;57-66. Kojima, M.; Kangawa, K. Ghrelin; struction and function. <i>Physiol Rev</i>, <b>2005</b>, <i>85</i>:495-522. <h3>Acknowledgements</h3> No disclosure of interest. <h3>Disclosure of Interest</h3> None Declared
SP0033 Osteoarthritis: Recent Advances
Authors: M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Osteoarthritis is a musculoskeletal disease affecting especially the knee, hip and hand joints. It is a prevalent disease with a high "global burden of disease" as estimated by the World Health Organization in 2010. OA is an important cause of years lived with disability worldwide. In the Western World, this impact is even higher. OA is affecting all compartments of the joint, and especially the involvement of other tissues than than articular cartilage is of interest. To understand the role of bone and synovium MR images have played an important role, however a recent study showed that also in knees of patients with normal knee radiographs many MRI abnormalities can be observed. What the meaning of these signs is has to been investigated. Currently OA is considered not as one disease but as a group of diseases with different phenotypes. Further insight in the risk factors for OA could increase insight in these phenotypes. Especially associations with genetic and metabolic risk factors have been investigated recently and increased our understanding about underlying biological mechanisms of OA. The current treatment of OA is directed at symptom relief. For this purpose both non-pharmacological and pharmacological treatments are used. Physical therapy can be effective in pain reduction, although not all interventions are, as shown in a recent systematic review. A recent randomized controlled trial comparing physical therapy with surgery for a meniscal tear in patients with signs of knee OA, suggested that no difference was seen on pain and functional outcome, although 30% of patients who were assigned to physical therapy alone underwent surgery. The ultimate goal is to develop disease-modifying treatments and these are actively sought for, especially for OA in the knee or hip. Recently, randomized controlled trials have been finalized on the effect of avocado- soybean unsaponifiable, strontium ranelate, selective iNOS inhibitor, vitamin D, etc. The results of these trials will be discussed. <h3>Disclosure of Interest</h3> M. Kloppenburg Grant/research support from: Pfizer, TI-Pharma, Servier, Speakers bureau: Bristol-Myers Squibb
1345 1H-NMR METABOLIC PROFILING IN GERM-FREE AND CONVENTIONALLY HOUSED MOUSE MODELS OF ACETAMINOPHEN-INDUCED HEPATOTOXICITY
Authors: L.A. Possamai, M. Harrison, R.D. Cox, R. Williams, Q.M. Anstee, M.R. Thursz, I.J. Cox
Journal: Journal of Hepatology (2012)
Effects of Citalopram on Neuropsychiatric Symptoms in Alzheimer’s Dementia: Evidence From the CitAD Study
Authors: Anne K. Leonpacher, Matthew E. Peters, Lea T. Drye, Kelly M. Makino, Jeffery A. Newell, D.P. Devanand, Constantine Frangakis, Cynthia A. Munro, Jacobo E. Mintzer, Bruce G. Pollock, Paul B. Rosenberg, Lon S. Schneider, David M. Shade, Daniel Weintraub, Jerome Yesavage, Constantine G. Lyketsos, Anton P. Porsteinsson
Journal: American Journal of Psychiatry (2016)

Objective: Citalopram has been shown to improve agitation in patients with Alzheimer’s disease. The authors evaluated whether other neuropsychiatric symptoms improve with citalopram treatment compared with placebo. Method: In this planned secondary analysis of the Citalopram for Agitation in Alzheimer’s Disease study, the authors evaluated the effect of citalopram on the 12 neuropsychiatric symptom domains assessed by the Neuropsychiatric Inventory (NPI). They compared caregiver-reported NPI scores at week 9 in patients receiving citalopram (30 mg/day) or placebo with regard to both the presence or absence of individual neuropsychiatric symptoms and individual domain scores (reflecting severity) in participants who had symptoms at week 9. Results: At week 9, participants treated with citalopram were significantly less likely to be reported as showing delusions (odds ratio=0.40), anxiety (odds ratio=0.43), and irritability/lability (odds ratio=0.38). A comparison of median scores of participants with symptoms present at week 9 showed significant differences favoring citalopram for hallucinations and favoring placebo for sleep/nighttime behavior disorders. Conclusions: While dosage constraints must be considered because of citalopram’s adverse effect profile, this agent’s overall therapeutic effects in patients with Alzheimer’s disease and agitation, in addition to efficacy for agitation/aggression, included reductions in the frequency of irritability, anxiety, and delusions; among patients who had these symptoms at week 9, they included a reduction in the severity of hallucinations but an increase in the severity of sleep/nighttime behavior disorders.
FRI0005 Signal transducer and activator of transcription 3 regulates synovial inflammation through notch/hif1a pathways
Authors: W. Gao, J. McCormick, M. Connolly, D. Veale, U. Fearon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Angiogenesis is one of the primary events in the pathogenesis of inflammatory arthritis. Notch/HIF signalling interactions regulate angiogenesis and endothelial cell (EC) fate in Rheumatoid Arthritis (RA), however the precise mechanisms involved remain to be elucidated. <h3>Objectives</h3> To examine the role of signal transducer and activator of transcription 3 (STAT3) in mediating hypoxia/Notch-induced interactions and downstream functional pathways in RA. <h3>Methods</h3> Phospho-STAT3 (p-STAT3) expression in RA synovial tissue was quantified by Immunohistology/Immunofluorescence and Western Blot. Notch-1 IC, HIF1α, p-STAT3 and total-STAT3 protein levels were assessed in RA synovial fibroblast cells (RASFC) and an immortalised synoviocyte cell line (K4IM) under normoxic and hypoxic (3%) conditions by Western Blot. Gene expression of the Notch-1 receptor, its ligand DLL-4 and downstream target genes (<i>hrt-1, hrt-2</i>) were quantified by Real-time PCR. Migration, invasion, matrigel network formation and MMP2/9 in-gel zymography were quantified under normoxic and hypoxic (3%) conditions in the presence of STAT3 siRNA or STAT3 inhibitor (WP1066). Using RA synovial explants <i>ex-vivo</i>, the effect of the STAT3 inhibitor (WP1066) on IL-6, IL-8 and IL-10 expression were assessed by ELISA. <h3>Results</h3> Nuclear expression of p-STAT3 was demonstrated in RA synovial tissue, localised to the sub-lining and lining layer regions. p-STAT3 expression was significantly higher in inflamed synovial tissue compared to normal synovial tissue. Hypoxia-induced p-STAT3, Notch-1 IC, HIF1α protein expression in RASFC and K4IM, an effect that was inhibited by the presence of STAT3 siRNA or WP1066. Similarly hypoxia-induced Notch-1 receptor, DLL-4 and <i>hrt-1, hrt-2</i> gene expression were inhibited in the presence of WP1066. Functionally hypoxia-induced RASFC/K4IM invasion, matrigel network formation, migration, and pro-MMP-2/-9 activities, were inhibited in the presence of STAT3 siRNA and the STAT3 inhibitor. Finally we demonstrated in RA synovial explants <i>ex-vivo</i> that WP1066 significantly decreased IL-6, IL-8 expression and significantly increased anti-inflammatory cytokine IL-10 expression. <h3>Conclusions</h3> This study demonstrates regulatory mechanisms between p-STAT3, HIF1α and Notch-1 signaling in RA. STAT3 blockade by siRNA or WP1066 inhibits pro-inflammatory pathways in RA, suggesting that STAT3 may be a potential therapeutic agent for the treatment of RA. <h3>Disclosure of Interest</h3> W. Gao: None Declared, J. McCormick: None Declared, M. Connolly: None Declared, D. Veale Grant/research support from: Abbott, Opsona, Pfizer, Roche, Consultant for: MSD, Pfizer, Roche, Speakers bureau: Janssen, MSD, Pfizer, UCB, U. Fearon: None Declared
Scientists Press To Develop Potential of Biological Therapy
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Scientists Press To Develop Potential of Biological Therapy Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 1, 6 January 1993, Pages 9–10, https://doi.org/10.1093/jnci/85.1.9 Published: 06 January 1993
Harnessing apoptosis to kill breast cancer cells.
Authors: A Letai
Journal: Cancer Research (2009)

Abstract Abstract #ES-2 Most of the therapies that are used to treat breast cancer induce programmed cell death via the intrinsic apoptosis pathway. The key step in commiting to cell death via this pathway is permeabilization of the mitochondrion with subsequent release of proapoptotic factors. Control over permeabilization is mainly exerted by the BCL-2 family of proteins which consists of both pro- and anti- apoptotic proteins. However, it is generally poorly understood how the targeting of intracellular niches by both conventional and targeted therapies ultimately signals to the BCL-2 family. I will discuss how conventional chemotherapy as well as more modern targeted therapies enlist pro-apoptotic BCL-2 family proteins to induce apoptosis. Furthermore, I will discuss the potential role of novel drugs that specifically target the apoptotic pathway in the treatment of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr ES-2.
AB0678 Enuresis in moroccan children with juvenile idiopathic arthritis
Authors: D. El Badri, B. Amine, S. Rostom, M. Ezzahri, N. Mawani, F. Moussa, S. Gueddari, S. Shyen, W. Moujibou, I. Bouaddi, B. Chkirate, N. H. Hajjaj
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Enuresis is a health problem frequently encountered in childhood. This condition is most likely a symptom of psychological stress, although physiological causes, should not be ruled out. In general, the causes of bedwetting are related to anxiety, life stress, and possibly trauma (chronic illness), both inside and outside the home. <h3>Objectives</h3> The aim of our study was to evaluate the prevalence of nocturnal enuresis in children with juvenile idiopathic arthritis. <h3>Methods</h3> Forty seven children with juvenile idiopathic arthritis (JIA) and 47 healthy controls were included in a cross-sectional study. The diagnosis of JIA was made according to the criteria of the International League of Association of Rheumatology (ILAR). Data was collected with a questionnaire created by the researchers. Diagnosis of enuresis considered nocturnal voiding twice a week for at least three consecutive months. <h3>Results</h3> Forty seven children with JIA were included (28 male, 19 female); the median of age of the patients was 12 [5-16] years. The prevalence of the children having a diagnosis of enuresis was of 8 (17%) versus 2(4.3%) in healthy controls (p=0.04). This enuresis was primary in 62.5% of cases and 50% of the cases occurred after the installation of the JIA. Indifference was the majority reaction of parents. There was no significant association in our study between the enuresis and parameters of JIA. <h3>Conclusions</h3> This study suggests that bedwetting is common in children with JIA compared to controls, although it is related to the parameters of the disease. <h3>Disclosure of Interest</h3> None Declared