tbuckley/cabot-search huggingface dataset:
A2.38 Role of podoplanin in the high IL-17 secretion resulting from interactions between activated lymphocytes and mesenchymal cells from different origins
Authors: M Noack, N Thiam, P Miossec
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> During chronic inflammation, immune cells, notably Th17 cells, infiltrate the inflammatory site and interact with local mesenchymal cells. Applied to rheumatoid arthritis (RA) and extended to psoriasis (Pso), the aim is to study the interactions between mesenchymal cells (MC) from different origins and peripheral blood mononuclear cells (PBMC) with a focus on the Th17 pathway and to identify a mechanism which leads to high IL-17 secretion. In this way, our interest is focussed on podoplanin, a transmembrane protein which is increased in inflammatory sites and known to modulate IL-8 secretion during synoviocyte-platelet interaction. <h3>Materials and methods</h3> A co-culture system with MC (RA synoviocytes or skin fibroblasts) and PBMC (healthy or autologous) was developed. MC were cultured overnight and PBMC were seeded at a 5:1 ratio for 48h, in the presence or not of TCR activation with PHA. Transwell system was used to study cell-cell contact. An antibody against podoplanin was pre-incubated 4h with PBMC before co-culture. Supernatants were collected at 48h and IL-6, IL-1β and IL-17 production measured by ELISA. Extracellular (CD3, CD4) and intracellular (IL-17) staining of PBMC was analysed by flow cytometry at 48h. <h3>Results</h3> In control conditions, IL-8, IL-6 and IL-1β production was increased in PBMC-MC co-culture compared to PBMC alone (<i>p ≤ </i>0.05). No additional effect was observed with PBMC activation. Flow cytometry showed no difference in the percentage of Th17 cells in activated-PBMC alone or co-cultured with MC (<i>p = </i>0.4). Conversely, IL-17 production was highly increased only in co-cultures with activated-PBMC (<i>p ≤ </i>0.02). Transwell experiments confirm that cell-cell contact was critical for IL-17 secretion. Addition of an anti-podoplanin antibody decreased significantly IL-17 secretion by 60%. Furthermore, all results were confirmed in autologous system. <h3>Conclusions</h3> The interactions between resting PBMC and MC alone is sufficient to induce pro-inflammatory cytokine production (IL-8, IL-6 and IL-1β). Both PBMC activation and cell interactions with MC are needed to induce a high IL-17 secretion. Podoplanin contributes largely to the massive IL-17 secretion and given its involvement in different diseases, it could be a potential therapeutic target to block Th17 cell activity during chronic inflammation.
Abstract 3466: Increased steady-state levels of microtubules in aberrant distributions in Ni+2 ion-/MCA-transformed C3H/10T1/2 mouse embryo cell lines
Authors: Aruni T. Pehl-De Silva, Preethi Samala, Hongkyu Lee, Joseph R. Landolph
Journal: Cancer Research (2010)

Abstract We previously found amplification of the Ect-2 proto-oncogene, and higher steady-state levels of ect-2 mRNA and protein, in Ni+2 ion- and MCA-transformed C3H/10T1/2 (10T1/2) mouse embryo fibroblast cell lines. Here, we tested the hypotheses that there were 1) increased steady-state levels of microtubules in Ni+2/MCA-transformed 10T1/2 cell lines, 2) aberrant distributions of microtubules in transformed cell lines, and 3) increases in cross sectional areas of transformed cell lines. Log phase Ni+2 ion- and MCA-transformed and non-transformed 10T1/2 mouse embryo cells were stained separately with fluorescent antibodies to alpha tubulin or beta tubulin, then visualized using confocal microscopy (n=8). The number of microtubules/cell and cross sectional areas of stained cells were quantified using the volocity image analysis program, and ratios of (microtubules in transformed cell lines/microtubules in non-transformed 10T1/2 cells) were determined. In non-transformed 10T1/2 cells, microtubules were distributed homogeneously. In transformed cells, microtubules were often present as large aggregates in cells, and shapes of transformed cells were aberrant compared to shapes of non-transformed 10T1/2 cells. Compared to non-transformed 10T1/2 cells, MCA Cl 16, NiS3A1, NiS7A1 and NiO2C3 cell lines had a 2.1 (p &amp;lt; 0.001), 1.5 (p &amp;gt; 0.05), 1.8 (p &amp;gt; 0.05) and 1.9 (p &amp;lt; 0.05) fold higher fluorescent intensity for alpha tubulin, respectively. Compared to non-transformed 10T1/2 cells, MCA Cl 16, NiS3A1, NiS7A1 and NiO2C3 had 2.5 (p &amp;lt; 0.05) 1.7 (p&amp;lt;0.05), 1.8 (p&amp;gt;0.05) and 1.1 (p&amp;lt;0.05) fold-higher beta tubulin fluorescence intensity relative to 10T1/2 cells. Transformed cell lines showed 1.9 - 2.5 significant (p&amp;lt;0.1) fold-increases in cross-sectional area compared to non-transformed 10T1/2 cells (n = 8). We concluded MCA-/Ni+2 ion-transformed 10T1/2 cells had higher steady-sate levels of microtubules, present in aberrant distributions, and transformed cells were larger than non-transformed cells. Supported by Grant ES03341 from U. S. N. I. H., funding from the M. S. Program in the Dept. of Molecular Microbiology/Immunology at USC, and discretionary funding, to JRL. 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 3466.
TRANSFEMORAL AORTIC VALVE REPLACEMENT WITH THE REPOSITIONABLE LOTUS VALVE COMPARED WITH THE BALLOON-EXPANDABLE EDWARDS SAPIEN 3 VALVE
Authors: Jochen Woehrle, Birgid Gonska, Christoph Rodewald, Dominik Scharnbeck, Julia Seeger, Sinisa Markovic, Wolfgang Rottbauer
Journal: Journal of the American College of Cardiology (2015)
SP0014 The Challenges of Undertaking Ultrasound - Framework for Practice. A European Perspective on Commpetencies for HPS
Authors: P. Cornell
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Musculoskeletal ultrasonography is probably considered one of the most important developments in rheumatology clinical practice in recent years. It offers the potential for health professionals to improve their diagnostic skills, manage clinical decisions regarding drug therapy and increase the standard of patient care. It is most often employed by Rheumatologists or sonographers but increasingly nurses, physiotherapists and podiatrists are starting to use ultrasound to monitor disease progression, check diagnosis and guide intra-articular injections. But what competencies do health professionals need to show before they are deemed proficient in ultrasonography? This session aims to provide an overview of the competencies employed within the european union that enable health professionals to safely and competently undertake ultrasonography for patients with inflammatory arthritis. <h3>Disclosure of Interest</h3> P. Cornell Employee of: Abbvie <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6321
Circular RNA enrichment in platelets is a signature of transcriptome degradation
Authors: Abd A. Alhasan, Osagie G. Izuogu, Haya H. Al-Balool, Jannetta S. Steyn, Amanda Evans, Maria Colzani, Cedric Ghevaert, Joanne C. Mountford, Lamin Marenah, David J. Elliott, Mauro Santibanez-Koref, Michael S. Jackson
Journal: Blood (2015)
Abstract B34: The impact of chromosome 17p loss on cancer
Authors: Yu Liu, Claudio Scuoppo, Scott Lowe
Journal: Cancer Research (2013)

Abstract Chromosome 17p deletions are associated with short survival and poor response to current chemotherapy treatment in non-Hodgkin's lymphomas. Although the prevailing view is that these deletions serve as a “second hit” event to inactivate p53, these deletions often hundreds of other genes. Using an in vivo RNAi screening approach for tumor suppressor genes, we identified and validated two additional tumor suppressors adjacent to p53 suggesting these deletions may do more than merely inactivate p53. To test this hypothesis, we constructed a new mouse model conditionally targeting a broad region of 17p and are intending to investigate whether and how genes co-deleted with well-known tumor suppressor p53 affect lymphoma development and chemotherapy responses. These results will elucidate the aggressive nature of tumors harboring 17p deletions and create the first mouse model that can be used to test strategies to overcome its deleterious effects. Citation Format: Yu Liu, Claudio Scuoppo, Scott Lowe. The impact of chromosome 17p loss on cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B34.
Comparison of Bone SPECT, Magnetic Resonance Imaging, and Computed Tomography in the Demonstration of Vertebral Metastases from Bronchogenic Carcinoma
Authors: W J Shih, V V Runge, B L Mitchell, C Pulmano
Journal: Clinical Nuclear Medicine (2000)

A patient with bone metastases from bronchogenic carcinoma was examined with radionuclide imaging, magnetic resonance imaging (MRI), and computed tomography (CT). SPECT showed a photon-deficient lesion in L-1 surrounded by increased activity; MRI showed lesions in T-12, L-2, and L-1; and CT did not show metastases. In this case, MRI was superior to the other methods.
Abstract 2848: SHLP6: A naturally occurring mitochondrial-derived peptide has therapeutic potential in prostate cancer
Authors: Laura J. Cobb, Hiromi Nakamura, Pinchas Cohen
Journal: Cancer Research (2011)

Abstract Mitochondrial DNA (mtDNA) mutations have been demonstrated in prostate cancer, particularly at the 16S rRNA region; and abnormal mRNA transcripts from that locus have been described. We and others showed that a novel open reading frame (ORF) within the mitochondrial 16S rRNA region, encoding for a 24 AA peptide called humanin, is a potent cell-survival and metabolic factor. Hypothesizing that additional bioactive peptides may be encoded from this region we identified an additional six ORFs that encode peptides transcribed from within the 16s rRNA gene in the mtDNA, which we have named small humanin-like peptides, or SHLPs. SHLP1-5 are functionally analogous to humanin, and act as potent survival factors. Intriguingly an additional peptide, SHLP6, functions in a completely opposing manner. We demonstrate that endogenous SHLP6 is expressed in serum and in multiple tissues, including the prostate, and that its expression declines with age. In addition, the addition of exogenous SHLP6 promotes apoptosis in prostate cancer cell lines including 22RV1, LNCaP and DU145. To assess the in vivo potency of SHLP6, we treated 22RV1 xenografts in SCID mice with SHLP6 for 1 week, and observed a potent inhibition of CaP xenograft growth and angiogenesis in vivo. In addition, we show that SHLP6 expression is decreased in preliminary staining of human prostate cancer, compared with normal prostate tissue. Analysis of gene and protein expression of SHLP6 treated cells reveals modulation of cell cycle and apoptosis genes and a dramatic inhibition of VEGF expression. Importantly, treatment of prostate cells with siRNA against SHLP6 leads to a dramatic increase in VEGF expression, suggesting that endogenous SHLP6 plays a role in the regulation of VEGF levels. We therefore propose the revolutionary concept that a previously unrecognized family of peptides is produced from the mitochondria and that one of these, SHLP6, plays a key role in regulating angiogenesis, is altered in prostate cancer, and may serve as a novel therapeutic and diagnostic agent in this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2848. doi:10.1158/1538-7445.AM2011-2848
P249 Could an Intronic SNP in the Alpha-1-Antitrypsin Gene Confer Protection to Chronic Obstructive Pulmonary Disease?
Authors: SA Fyyaz
Journal: Thorax (2012)

<h3></h3> Chronic obstructive pulmonary disease (COPD) results from complex interactions between both environmental and genetic factors. This is evidenced by the considerable variation found in the risk of developing COPD despite the established dose-response relationship from the biggest known risk factor, tobacco smoking. Thus, genetic susceptibility remains poorly understood given the best-characterised genetic determinant of COPD, severe alpha-1-antitrypsin (AAT) deficiency, only affects1–2% of all COPD patients. A genome-wide association study implicated an intronic single nucleotide polymorphism (SNP) rs3748312 within AAT gene as the strongest locus associated with lung function (a heritable surrogate predictor of COPD). Thus, this was investigated as part of a larger research project aimed at identifying rare sequence variants of the AAT gene that may be associated with COPD. A sample of 230 COPD patients of European descent either predicted to carry one of six haplotypes conferring COPD risk, or who presented with severe early-onset COPD were genotyped for SNP rs3748312 within the AAT gene utilising TaqMan® assay with &gt;5% of samples sequenced for concordance. The data was compared against control data of 60 patients of European ancestry from dbSNP. In examining the allelic distribution (<i>p</i>=0.049, OR 0.57 95% CI: 0.323–1.003) borderline significance was noted, however no significant difference between cases and controls was found in the genotype distribution (<i>p</i>=0.096OR 0.583, 95% CI 0.308–1.106). This preliminary study suggests the SNP merits further work in a more adequately powered investigation with adjustment for covariates such as age, smoking history and lung function given the borderline nature of the findings indicative of a protective effect for developing COPD with the minorallele (A). It is feasible that associated functional SNPs in linkage disequilibrium reflect the true association.
257 MOLECULAR CHARACTERISATION OF HEPATOCELLULAR ADENOMAS DEVELOPED IN PATIENTS WITH GLYCOGENOSIS TYPE I
Authors: J. Calderaro, P. Labrune, D. Franco, S. Prévot, A. Quaglia, P. Bedossa, L. Libbrecht, G.P.A. Smit, P. Bioulac-Sage, J. Zucman-Rossi
Journal: Journal of Hepatology (2012)
INVESTIGATION OF HEMODYNAMIC CHANGES DURING BALLOON OCCLUSION TEST FOR PERCUTANEOUS ATRIAL SEPTAL DEFECT CLOSURE
Authors: Hiroyuki Yamamoto, Toshiro Shinke, Hiromasa Otake, Tomofumi Takaya, Masaru Kuroda, Takayoshi Toba, Hachidai Takahashi, Daisuke Terashita, Kenzo Uzu, Koji Kuroda, Natsuko Tahara, Daiji Kashiwagi, Yoshinori Nagasawa, Yoshiro Tsukiyama, Kenichi Yanaka, Ken-Ichi Hirata
Journal: Journal of the American College of Cardiology (2016)
Dabigatran and Postmarketing Reports of Bleeding
Authors: Mary Ross Southworth, Marsha E. Reichman, Ellis F. Unger
Journal: New England Journal of Medicine (2013)

Serious and fatal bleeding events associated with use of the anticoagulant dabigatran have been reported. The FDA used the Mini-Sentinel database to determine that the actual rates of bleeding events were not higher with dabigatran than with warfarin.
Lessons for social franchises from sustainability in business and public health studies: a systematic review
Authors: Amy Penn, Juan Carlos Negrette, Dale Huntington, Dominic Montagu
Journal: The Lancet Global Health (2016)

Background Social franchising programmes are financed mostly by international donor agencies; however, because such funding lacks certainty in the long term, social franchises need to think about how to continue provision of services for their targeted populations. Corporate management analysts argue that for-profit companies face a similar challenge of uncertain funds, causing us to examine whether social franchises can learn from the business literature. In this systematic review of studies of sustainability in organisations from the business and public health sector, we aim to find common themes and lessons that are applicable to social franchising.
Depression of Left Ventricular Function Due to Acute Myocardial Ischemia and Its Reversal after Aortocoronary Saphenous-Vein Bypass
Authors: Kanu Chatterjee, H. J. C. Swan, William W. Parmley, Hector Sustaita, Harold Marcus, Jack Matloff
Journal: New England Journal of Medicine (1972)

Abstract In six patients with the preinfarction syndrome due to high-grade proximal occlusion of the left (five cases) or right (one case) coronary arteries, left ventricular function was evaluat...
Abstract 940: AR overexpression confers resistance to an aromatase inhibitor in ERα-positive breast cancer cells
Authors: Yassine Rechoum, Domenico Iacopetta, Ines Barone, Sebastiano Ando’, Stephanie Morales, Nancy L. Weigel, Suzanne A W Fuqua
Journal: Cancer Research (2011)

Abstract Background: Aromatase inhibitors (AIs) have emerged as the therapy of choice for the treatment of estrogen receptor alpha (ERα)-positive breast cancer. However, many patients develop resistance to AI treatment. Although the involvement of the ERα in AI resistance is well established, the role of the androgen receptor (AR) is not known. It has been estimated that about 60%-70% of ERα-positive breast cancer co-express the AR, and we have previously shown a role for AR-overexpression in tamoxifen resistance in ERα-positive MCF-7 breast cancer cells. Thus we hypothesized that AR overexpression might similarly be involved in resistance to the AI anastrazole (Anas). Materials and Methods: Stable transfection of MCF-7 cells was performed to generate cell lines that express the aromatase gene (MCF-7 BK Arom) and then co-transfected with an AR expression vector (MCF-7 AR Arom). Aromatase and AR expression levels were evaluated by western blot analysis. Proliferation was tested using anchorage independent soft agar assays and MTT in the presence of the androgen substrate androstenedione (AD), or AD plus Anas. ERα and AR transcriptional activities were tested with ERE-luciferase reporter assays. Results: Several clones expressing aromatase alone or aromatase plus AR were generated. MCF-7 aromatase clones overexpressing AR were resistant to the growth inhibitory effects of Anas when stimulated with the androgen AD. As expected AD treatment stimulated ERα transcriptional activity, but Anas was unable to block AD-stimulated activity in AR Arom-overexpressing cells. In addition, the growth of several of the AR Arom-overexpressing cells was stimulated with treatment of Anas alone. Resistance was not associated with activation of known mechanisms of resistance, such as HER2, or Akt activation. Inhibitors of various signaling and receptor growth pathways are currently being tested for their effects on blocking Anas resistance. Conclusion: Using a model of ERα-positive breast cancer cells expressing endogenous aromatase and AR, we have demonstrated that AR overexpression confers resistance to the AI Anas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 940. doi:10.1158/1538-7445.AM2011-940
Reversal of skeletal effects of endocrine treatments in the intergroup exemestane study.
Authors: RE Coleman, LM Banks, S Girgis, E Vrdoljak, J Fox, S Cawthorn, A Patel, C Coombes, JM Bliss, LS Kilburn, on Behalf of the IES Group
Journal: Cancer Research (2009)

Abstract Abstract #1128 The Intergroup Exemestane Study (IES) has demonstrated significantly improved disease related outcomes for post-menopausal women with ER+/unknown early breast cancer who switch to exemestane (E) after 2-3 years pre-treatment with tamoxifen (T). In comparison to 5 years T, a switch to E is associated with a favorable adverse event profile other than an increase in musculoskeletal side effects, accelerated bone loss &amp; increased fracture incidence. Here we report effects of endocrine treatment withdrawal on bone mineral density (BMD) at lumbar spine (LS) &amp; total hip (TH), bone turnover markers (BTM) &amp; fracture rates.&amp;#x2028; Of the 4724 patients (pts) who took part in IES, 206pts (101E, 105T) at selected centres with no evidence of osteoporosis or osteoporotic fracture were included in a bone health substudy. BMD &amp; BTM were assessed pre-randomization, after 6, 12, &amp; 24 months (m) treatment, end of treatment (EOT), 12 &amp; 24m post EOT. BTM were also assessed after 3, 9, 18, 30 &amp; 3m post EOT. To evaluate treatment withdrawal effects, 12 &amp; 24m post EOT BMD results are available for 160 (76E, 84T) &amp; 159 (75E, 84T) pts respectively. Similar pt numbers also had BTM (urinary NTX &amp; DPD, serum CTX, bone ALP, osteocalcin &amp; PICP) measured post EOT.&amp;#x2028; At EOT an ITT analysis showed that the switch to E was associated with a -3.9% &amp; -3.0% reduction since randomization in LS &amp; TH BMD respectively, compared with -1.2% &amp;-1.6% for continuing on T, resulting in an EOT difference between mean E &amp; T BMD of 2.8% (p=&amp;lt;.0001) &amp; 1.4% (p=.002). Following treatment withdrawal this difference was partially reversed. LS &amp; TH BMD increased after E by 1.7% &amp; 0.3% &amp; fell by 2.2% &amp; 2.8% with T at 24m from EOT. At 2 years post EOT there were no significant differences in BMD between treatment strategies.&amp;#x2028; &amp;#x2028; Corresponding changes in BTM were seen with an increase following T withdrawal &amp; a reduction in previously E induced acceleration of bone turnover. In IES main study a higher number of fractures were seen in E pts after a median follow-up of 74m; further analyses will describe changing pattern of events over time. The adverse effects of E on bone are partially reversed on treatment withdrawal while beneficial effects of T are lost during the 2 years after EOT. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1128.
SOX9 drives WNT pathway activation in prostate cancer
Authors: Fen Ma, Huihui Ye, Housheng Hansen He, Sean J. Gerrin, Sen Chen, Benjamin A. Tanenbaum, Changmeng Cai, Adam G. Sowalsky, Lingfeng He, Hongyun Wang, Steven P. Balk, Xin Yuan
Journal: Journal of Clinical Investigation (2016)

The transcription factor SOX9 is critical for prostate development, and dysregulation of SOX9 is implicated in prostate cancer (PCa). However, the SOX9-dependent genes and pathways involved in both normal and neoplastic prostate epithelium are largely unknown. Here, we performed SOX9 ChIP sequencing analysis and transcriptome profiling of PCa cells and determined that SOX9 positively regulates multiple WNT pathway genes, including those encoding WNT receptors (frizzled [FZD] and lipoprotein receptor-related protein [LRP] family members) and the downstream β-catenin effector TCF4. Analyses of PCa xenografts and clinical samples both revealed an association between the expression of SOX9 and WNT pathway components in PCa. Finally, treatment of SOX9-expressing PCa cells with a WNT synthesis inhibitor (LGK974) reduced WNT pathway signaling in vitro and tumor growth in murine xenograft models. Together, our data indicate that SOX9 expression drives PCa by reactivating the WNT/β−catenin signaling that mediates ductal morphogenesis in fetal prostate and define a subgroup of patients who would benefit from WNT-targeted therapy.
Transatlantic Spread of the USA300 Clone of MRSA
Authors: Andreas Tietz, Reno Frei, Andreas F. Widmer
Journal: New England Journal of Medicine (2005)

To the Editor: The emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is of great concern.1,2 USA300, the predominant epidemic clone in numerous outbreaks in closed communities in the United States,2 is also increasingly seen in Europe.3 International travel and the increasing trend of training or working abroad among health care workers probably contribute to its global spread. We describe the transfer of community-acquired MRSA from the United States to Europe and its successful eradication. A 41-year-old healthy Swiss physician performed a clinical fellowship in the United States from July 2001 to June 2003. Three months before his departure, nasal . . .