tbuckley/cabot-search huggingface dataset:
FRI0123 The Relationship between Ankylosing Spondylitis and Restless Leg Syndrome
Authors: O.N. Pamuk, A. Tekatas
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To assess the prevalence of restless leg syndrome (RLS) in patients with ankylosing spondylitis (AS) and to investigate factors potentially associated with RLS. <h3>Methods</h3> 130 patients diagnosed with AS (95M, 35F, mean age: 38.4) according to modified New York criteria and age-and-sex matched 91 healthy control subjects (66M, 25F, mean age: 37.6) were included in this study. The diagnosis of RLS was made according to the criteria of the International RLS Study Group. The factors associated with RLS were evaluated. Electrophysiological procedures were performed in a group of patients with RLS. <h3>Results</h3> The frequency of RLS was significantly higher in AS patients (30.8%) than in healthy subjects (13.2%) (p=0.002). When AS patients with RLS was compared with AS patients without RLS, it was seen that peripheral arthritis (60% vs 26.7%, p&lt;0.001), uveitis (25% vs 8.8%, p=0.016), iron deficiency anemia (62.5% vs 24.4%, p&lt;0.001) and smoking (60% vs 30%, p=0.001) were significantly higher in the former group. AS patients with RLS tended to be have a younger mean age than others (p=0.088). We also evaluated cutaneous silent period in a subgroup AS patients with and without RLS. The mean level of upper extremity (87.6+10.6 vs 76.8+10, p=0.004) and lower extremity latency (123.9+22.6 vs 105.9+18.7, p=0.017) were significantly higher in AS patients with RLS than in AS patients without RLS. The mean duration of upper extremity (31.3+10.5 vs 39.9+8.5, p=0.013) and lower extremity (29+9.5 vs 43.9+9.6, p&lt;0.001) were significantly shorter in AS patients with RLS than in AS patients without RLS. In multivariate regresssion analysis, it was seen that independent parameters associated with RLS in AS patients were the presence of iron deficiency anemia (OR: 4.3, 95%CI: 1.6-11.4, p=0.001) and smoking (OR: 5.2, 95%CI: 1.8-15.2, p=0.004). <h3>Conclusions</h3> Our findings indicate that RLS is commonly associated with AS. Possible causes include iron deficiency anemia, smoking and small fiber neuropathy. It is possible that many of AS patients with uncertain neurosensory symptoms and electrophysiologic abnormalities have previously unrecognized small fiber neuropathy. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4018
Abstract 1247: Transcriptional regulation of VEGF by WT1 and AR in prostate cancer
Authors: Kurtis Eisermann, Jennifer L. Reese, Carly J. Broderick, Gail C. Fraizer
Journal: Cancer Research (2010)

Abstract Identifying molecular mechanisms that influence prostate cancer progression is central to understanding how this disease develops. Angiogenesis is key for cancer development and growth as tumors require new blood vessels for nutrients and oxygen. Vascular endothelial growth factor (VEGF) is the most important signaling protein involved in angiogenesis and is up-regulated by oncogene expression among other things. Previous studies have shown that the zinc finger transcription factor WT1 (Wilms tumor 1) transcriptionally regulated VEGF in multiple cell lines. Additionally, WT1 activation of VEGF required an intact zinc finger domain and was mediated by DNA binding. Potential WT1 binding sites were identified in the VEGF promoter using in silico approaches and shown to bind WT1 protein using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Luciferase reporter assays showed increased activation of the VEGF promoter by over-expression of WT1. Additional factors known to induce VEGF expression are growth factors, hypoxia and hormones. How androgen regulates VEGF transcription is unknown, but we have identified two potential androgen receptor (AR) binding sites within 2kb of the transcriptional start site and demonstrated reporter activation by R1881 treatment of transfected LNCaP cells. This study examined the effect of mutating selected WT1 and AR binding sites in the VEGF promoter to determine whether they were responsible for activation of VEGF transcription. Mutating these binding sites by site-directed mutagenesis significantly decreased activation of the VEGF promoter by WT1 and the androgen analog R1881 in LNCaP cells. As predicted, treatment with the anti-androgen casodex similarly eliminated hormone response of the VEGF promoter, suggesting that androgens are functioning via androgen signaling. This was confirmed in vivo by both western blot analysis of VEGF protein and quantitative real-time PCR measurement of VEGF mRNA in cells treated with casodex. This is important because androgen signaling is vital to normal prostate development and malignant prostate growth. Overall these results show that both WT1 and AR transcriptionally regulate VEGF expression in prostate cancer cells and these factors directly bind and activate the promoter in vivo. Understanding how angiogenesis is regulated will lead to improved therapy and prevention of prostate cancer progression. This work was supported by NIHR15CA11360 (GF), Sigma Xi GIAR220034 (KE), and GSSKSU (KE) 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 1247.
VTE as a Quality Indicator
Authors: Myron Goldsmith, George Whitelaw, Denise A. Cannaday
Journal: Journal of the National Comprehensive Cancer Network (2008)

Venous thromboembolism (VTE) is still the most common preventable cause of hospital death, with cancer a known significant risk factor for its development. Prophylaxis to prevent VTE in hospitalized surgical and medical patients has been suboptimal, and efforts for improvement have been unsuccessful. Recent practice guidelines on VTE in oncology from the National Comprehensive Cancer Network and American Society of Clinical Oncologists have further highlighted this relationship and could bridge performance measures and outcomes that can affect the strategies for preventing deep venous thrombosis and pulmonary embolism in oncology patients. Hospitals and physicians with poor performance data will have problems with payment from the Centers for Medicare & Medicaid Services and contracting the best rates from other payors. Hospital accreditation from The Joint Commission could be an issue for poorly performing institutions, as could consumer acceptance. The authors believe that specific oncology VTE measures should be developed to help decrease the current poor rates of VTE prophylaxis and also improve hospital and physician compliance.
Evaluation of Ki-67 index in EUS–FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors
Authors: Toshiyuki Hasegawa, Kenji Yamao, Susumu Hijioka, Vikram Bhatia, Nobumasa Mizuno, Kazuo Hara, Hiroshi Imaoka, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Tutomu Tanaka, Yasuhiro Shimizu, Taira Kinoshita, Takuhiro Kohsaki, Isao Nishimori, Shinji Iwasaki, Toshiji Saibara, Waki Hosoda, Yasushi Yatabe
Journal: Endoscopy (2013)

<b>Background and study aim:</b> Malignancy in pancreatic neuroendocrine tumors (PNETs) is graded by assessing the resected specimens according to the World Health Organization (WHO) 2010 criteria. The feasibility of such grading using endoscopic ultrasound-guided fine-needle aspiration (EUS–FNA) specimens remains unclear. The aim of this study was to ascertain the optimal method of measuring the Ki-67 index in EUS–FNA specimens, using resected specimens as the criterion standard. <b>Patients and methods</b>: A total of 58 consecutive patients diagnosed with PNETs between March 1998 and May 2011 were included. The study measured intratumoral Ki-67 index heterogeneity, concordance rates of PNET grading by EUS–FNA with grade of the resected tumor, optimal method of measuring the Ki-67 index in EUS–FNA specimens, and survival analysis based on EUS–FNA specimen grading. <b>Results: </b>Intratumoral dispersion of Ki-67 index in resected specimens was 0.033 for Grade 1 and 0.782 for Grade 2 tumors (<i>P</i> < 0.001). Concordance rates for WHO classification between EUS–FNA and resected specimens were 74.0 % using the mean Ki-67 index in EUS–FNA specimens and 77.8 % using the highest Ki-67 index. The concordance rate rose to 90 % when EUS–FNA samples with less than 2000 tumor cells were excluded (26 % of EUS–FNA cases). The Kaplan–Meier survival curves were significantly stratified by the EUS–FNA grading of PNETs with 5-year survival rates of 100 %, 58.3 %, and 0 %, for Grade 1, Grade 2, and neuroendocrine carcinoma (NEC) tumors, respectively. <b>Conclusions: </b>Grading of PNETs by the highest Ki-67 index in EUS–FNA specimens with adequate cellularity has a high concordance with grading of resected specimens, and can predict long term patient survival with high accuracy.
AB0023 In Vivo Effects of Epratuzumab, A Monoclonal Antibody Targeting Human CD22, on B Cell Function in Human CD22 Knock-In (HUKI) Mice
Authors: C. Brandl, L. Özgör, M. Wöhner, A. Shock, L. Nitschke
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Epratuzumab is a humanized monoclonal antibody that targets the B cell-specific protein CD22 and is currently in Phase 3 clinical trials in patients (pts) with systemic lupus erythematosus (SLE). Epratuzumab does not deplete B cells and appears to act in an immunomodulatory fashion, eg. by inhibiting activation through the B cell receptor (BCR).<sup>1</sup> It has also been shown to modulate adhesion molecule expression on B cells and their responsiveness to chemokines.<sup>2</sup> <h3>Objectives</h3> The present study aimed to understand the effect of epratuzumab on B cells <i>in vivo</i> using human CD22 knock-in (Huki) mice, in which the B cells express the human CD22 gene instead of the murine gene.<sup>3</sup> <h3>Methods</h3> Huki mice received a single intravenous injection (0.5mg) of epratuzumab and, at various time points up to Week (Wk) 12, B cell sub-populations in blood, spleen, bone marrow and lymph nodes were measured, along with B cell activation and homing markers. <i>Ex vivo</i> functional assays were also performed: Ca<sup>+</sup> flux, apoptosis and CD22 internalization on B cells were measured by flow cytometry and the proliferation of B cells was assessed after <i>in vivo</i> administration of BrdU. <h3>Results</h3> Epratuzumab-treated mice showed rapid and long-lasting human CD22 internalization on B cells from all organs up to Wk8 and an increase of B cell apoptosis (an increase of cells in sub G1 phase) <i>ex vivo</i>. Furthermore, decreased BCR-activated Ca<sup>+</sup>-flux was demonstrated after epratuzumab treatment <i>in vitro</i>. However, BrdU incorporation in several B cell subsets was unchanged at early time points and there were no consistent effects demonstrated on the numbers or proportions of such subsets in various organs at any time point up to Wk12. <h3>Conclusions</h3> Epratuzumab treatment of Huki mice induces functional effects on B cells assessed <i>ex vivo</i> but does not seem to strongly influence B cell development and B cell populations in various organs. These data have implications for understanding the effects of epratuzumab treatment on B cell function in SLE pts. <h3>References</h3> Sieger N. Arth Rheum 2013;65:770. Daridon C. Arth Res Ther 2010;12:R204. Wöhner M. Eur J Immunol 2012;42:3009. <h3>Acknowledgements</h3> C. Brandl and L. Özgör contributed equally to the work. The authors acknowledge Costello Medical Consulting for editorial assistance which was funded by UCB Pharma. <h3>Disclosure of Interest</h3> C. Brandl Grant/research support: UCB Pharma, L. Özgör Grant/research support: UCB Pharma, M. Wöhner: None declared, A. Shock Employee of: UCB Pharma, L. Nitschke Grant/research support: UCB Pharma <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1751
Case 27-2014
Authors: Inderneel Sahai, Ganeshwaran H. Mochida, Eric F. Grabowski, Paul A. Caruso
Journal: New England Journal of Medicine (2014)

A 10-month-old boy with microcephaly and developmental delay was admitted to the hospital because of episodes of respiratory distress and cyanosis. Microcephaly was present at birth, and hypotonia was noted at 5 months. On admission, brain MRI revealed decreased myelination.
A8.1 Tristetraprolin is a novel therapeutic target for rheumatoid arthritis
Authors: EA Ross, T Smallie, AJ Naylor, GE Desanti, J Crowe, JD O’Neil, JD Turner, A Yemm, LV Norling, H Perlman, NM Verrills, A Filer, JL Dean, CD Buckley, AR Clark
Journal: Annals of the Rheumatic Diseases (2015)

<h3></h3> Chronic inflammatory conditions such as Rheumatoid Arthritis are characterised by over expression of pro-inflammatory factors resulting in prolonged and destructive inflammation. Dysregulation of endogenous anti-inflammatory control mechanisms contribute to this aetiology. The mRNA destabilising protein Tristetraprolin (TTP) targets pro-inflammatory transcripts for destruction, limiting the production of key inflammatory factors. Expression and activity of TTP are controlled via phosphorylation of serines 52 and 178. MAPK p38-dependent phosphorylation of these residues stabilises and inactivates TTP, promoting expression of inflammatory mediators and driving the on-phase of an inflammatory response. As MAPK p38 activity declines, accumulated TTP is activated by PP2A mediated dephosphorylation, driving the off-phase of the inflammatory response. We investigated the role of the TTP phosphorylation switch in inflammatory arthritis. Immuno-staining of human RA synovial biopsy tissue revealed abnormally high expression of TTP protein compared to control tissues, with highest expression in synovial macrophages. We hypothesise that TTP protein accumulates in a phosphorylated, inactive form, contributing to sustained expression of inflammatory mediators. To assess the therapeutic potential of targeting TTP we generated TTP<sup>aa/aa</sup> mice in which the two key serine residues in endogenous TTP are substituted. These mice produced significantly lower amounts of pro-inflammatory factors after systemic LPS challenge, due to constitutive mRNA destabilising activity of the mutant form of TTP, yet were still able to generate a protective immune response to bacterial infection. Intriguingly TTP<sup>aa/aa</sup> mice were protected from K/BxN induced inflammatory arthrtitis with no adverse histological pathology or bone remodelling compared to WT mice. Heterozygote mice, in which 20% of endogenous TTP is mutant, also demonstrated significant protection from inflammatory arthritis. Therefore, therapeutically altering the balance of activation in the total TTP pool could lead to a significant anti-inflammatory effect. An experimental reagent that activates TTP decreased clinical score, joint inflammation and bone erosions in K/BxN induced arthritis. Taken together, these data suggest that targeting of the equilibrium between phosphorylated (inactive) and dephosphorylated (active) TTP may exert therapeutic effects in arthritis without compromising immune function.
Authors' reply to Foley
Authors: D. Kaski, A. M. Bronstein
Journal: BMJ (2012)

We agree that the diagnosis of cerebellar stroke or vestibular neuritis cannot be made solely on the patient’s ability to stand.1 The presence of sudden onset severe disequilibrium in patients with posterior circulation infarcts adds weight to the diagnosis, but the clinical context must be taken into account. Indeed, we highlight that the diagnosis …
Virtue ethics – an old answer to a new dilemma? Part 1. Problems with contemporary medical ethics
Authors: David Misselbrook
Journal: Journal of the Royal Society of Medicine (2015)

The commonest practical model used in contemporary medical ethics is Principlism. Yet, while Principlism is a widely accepted consensus statement for ethics, the moral theory that underpins it faces serious challenges in its attempt to provide a coherent and accepted system of moral analysis. This inevitably challenges the stability of such a consensus statement and makes it vulnerable to attack by competitors such as preference consequentialism. This two-part paper proposes an inclusive version of virtue theory as a more grounded system of moral analysis.
67Ga SPECT/CT of Infected Bladder Stones and Pyelitis
Authors: Minkyung Lee, Jin Soo Lee, Ji-Hyeon Baek, In Young Hyun
Journal: Clinical Nuclear Medicine (2014)

A 64-year-old male patient diagnosed with amyotrophic lateral sclerosis 2 years ago was admitted with fever and chills. The patient had complex medical history and several indwelling catheters/tubes in his body. To identify the infection focus, 67Ga whole-body scintigraphy and SPECT/CT were obtained. 67Ga whole-body scintigraphy demonstrated focal 67Ga uptake in the lower pelvic cavity and the right kidney. Additional 67Ga SPECT/CT images were obtained, and it enabled characterization of these uptakes as infection of bladder stones that result in pyelitis.
Abstract 1231: Nuclear Factor I family members interact with FoxA1 to regulate androgen responsive promoters
Authors: Adu M. Boachie, David Degraff, Xiuping Yu, Qian Sun, David Friedman, Richard Gronostajski, Robert Matusik
Journal: Cancer Research (2010)

Abstract Forkhead (Fox) proteins are an important class of transcription factors (TFs) that act as molecular “pioneers” by increasing chromatin accessibility. The ability of FoxA1 to act in this manner allows for the subsequent nucleation of responsive promoters by additional, tissue specific TFs, allowing for gene regulation. Our laboratory has previously shown that FoxA1 interacts directly with the androgen receptor (AR), and that the expression of FoxA1 is essential for normal prostate maturation and differentiation. Thus, the ability of FoxA1 to enter a transcriptional complex with AR and other TFs contributes to tissue-specific gene expression in the prostate, and determining the components of FoxA1/AR TF complexes will identify additional targets for the treatment of castrate-resistant PCa. In order to identify additional proteins that interact with FoxA1, we ectopically expressed dual-affinity tagged FoxA1 in the human PCa cell line LNCaP. Following tandem purification and mass spectrometric analysis, we identified several FoxA1-interacting proteins, including Nuclear Factor I x (NFIx). NFIx is a member of the Nuclear Factor family of TFs, consisting of NFIa, NFIb, NFIc, and NFIx. Co-immunoprecipitation studies verify that NFI family members interact with FoxA1, and Chromatin immunoprecipitation (ChIP) experiments indicate NFI family members bind to androgen regulated, prostate-specific promoters. Finally, transient transfection experiments indicate that NFI family members modulate the androgenic stimulation of the Probasin and PSA promoters both in the presence and absence of FoxA1. In summary, we have identified NFIx as a novel FoxA1 interacting protein. NFI family members act to modulate the transcriptional activity of FoxA1 and AR on prostate-specific target promoters. 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 1231.
Staging accuracy of endoscopic ultrasonography in esophageal cancer, Jae Hoon Cheong, Pusan National University Hospital
Authors: Ryu Dong Yup
Journal: Endoscopy (2011)

Background and aim: Surgery is considered the treatment of choice for advanced esophageal cancers, but the 5-year survival rate in the resected group is still dismal. It is important to determine the depth of infiltration of the cancer into the esophageal wall and presence of lymph nodes or metastasis. Endoscopic ultrasonography (EUS) has been shown to provide accurate assessment of the depth of tumor invasion and regional lymph nodes. The purpose of this study was to analyze the staging accuracy of esophageal cancer by EUS.
Abstract 56: Differential expression of fatty-acid-binding proteins 3 and 5 among African American and Caucasian women with breast cancer
Authors: Teleka Calderon, Sharda Kalla Singh, Marino De Leon, Daisy De Leon
Journal: Cancer Research (2010)

Abstract Breast cancer is a major cause of mortality among middle-aged and elderly women. It is well documented that African-American (AA) patients tend to present with more advanced states of breast cancer and have lower survival rates than Caucasian-Americans (CA). Additionally, the age specific breast cancer incidence rate for AA women under age 35 is greater than twice the rate for CA of similar age, and the mortality rate is more than three times greater. Some of this disparity is due to socioeconomic factors; however, biological factors may also be involved. Altered expression of intracellular fatty-acid binding proteins (FABPs) has been implicated in the progression of breast cancer. FABP3 (heart/muscle type), also known as mammary-derived growth inhibitor (MDGI), is associated with differentiation of breast tissue, and is downregulated in breast cancer tissues. FABP5 (epidermal type) is upregulated in breast cancer tissues as a possible compensation for FABP3's decrease. Therefore, we hypothesized that AA malignant breast tissue samples would contain lower levels of FABP3, and higher levels of compensatory FABP5. We determined levels of the aforementioned proteins and the corresponding mRNA in paired breast tissue samples from AA and CA women by Western blot analysis and RT-PCR. Data was divided into three groups- ages 17-45, ages 45-65, and ages 66 and up. In ages 17-45, FABP3 protein levels were higher in AA malignant tissues relative to CA malignant, and FABP5 protein levels were similar between racial groups. Also, FABP3 levels were decreased in AA malignant tissues compared to AA normal. In ages 46-65, levels of FABP3 protein, and of FABP5 protein and mRNA, were higher in AA malignant tissues relative to CA malignant. Furthermore, FABP3 protein levels were increased in AA malignant tissues relative to AA normal tissues. In ages 66 and up, levels of both FABPs were similar between AA malignant and CA malignant tissues. However, mRNA levels of both FABPs were significantly increased in the CA malignant tissues compared to AA malignant. In addition, levels of FABP3 and FABP5 were increased in the AA malignant tissues relative to the AA normal tissues. Thus, it appears that the conventional knowledge regarding FABP3 downregulation in breast cancer may only apply to AA cancer patients below age 45. Furthermore, in ages above 66, AA breast cancer patients are at a significant disadvantage compared to their CA counterparts, as it relates to expression of FABPs 3 and 5. Further study is needed to elucidate the mechanisms involved in this differential FABP expression pattern between the racial groups, and its implication on the survival disparity. 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 56.
Anthracofibrosis Manifesting as False-Positive Iodine Accumulation in a Patient With Recent History of Thyroid Carcinoma
Authors: Katharina Licht, Claus Kroegel, Kathrin Katenkamp, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2015)

A 33-year-old Indonesian woman presented for follow-up after a recent history of papillary thyroid carcinoma treated with total thyroidectomy and radioiodine therapy. A 131I whole-body scintigraphy showed an elongated iodine accumulation in the right hemithorax. On suspicion of pulmonary metastasis, further diagnostics with 124I PET/CT showed thickening of the bronchial wall and retention of secretion in a middle lobe bronchus. Bronchoscopy and histology allowed a diagnosis of stenosing anthracofibrosis with chronic inflammatory changes.