tbuckley/cabot-search huggingface dataset:
THE WHITE MAN IN THE ARCTIC
Authors: T. J. BOAG
Journal: American Journal of Psychiatry (1952)

Observations are reported on some of the psychological stresses of life in the Arctic, and reactions to them. The importance of distinguishing between situations involving direct exposure to climatic stress, and those in which such exposure is avoided, is pointed out. Some of the difficulties involved in the field work are described and suggestions are made as to the lines along which further study should proceed.
A condition of unknown significance: esophageal melanocytosis in a patient with celiac disease
Authors: Mevlut Hamamci, Fatih Karaahmet, Baris Yilmaz, Akif Altinbas, Sahin Coban
Journal: Endoscopy (2014)

A 74-year-old woman was admitted to our unit with complaints of abdominal discomfort and heartburn over 2 months. She had a history of hypertension and celiac disease, but admitted that she did not comply with a gluten-free diet. She had no history of any medication, smoking, or drinking alcohol, and her family history was unremarkable.
THU0040 Histology of nasal tissue destruction in GPA patients is reflected in human tissue transplants of GPA patients in immunodeficient mice
Authors: S. Ullrich, N. Kesel, U. Schumacher, W.L. Gross, M. Laudien, A. Müller, K. Holl-Ulrich
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tissue destruction of the upper respiratory tract related to Granulomatosis with Polyangiitis (Wegener’s) – (GPA) which may result in stigmatizing lesions of the face is still poorly understood. Nasal biopsies that contain cartilage and/or bone to study the destruction process are difficult to obtain. Recent findings in a xenograft model of GPA in immunodeficient mice suggest that fibroblasts mediate at least in part this destruction of cartilage. <h3>Objectives</h3> To compare morphological and immunohistochemical features of destruction in GPA patients and GPA tissues xenografted into immunodeficient mice. <h3>Methods</h3> Nasal biopsies from GPA patients containing cartilage and/or bone fragments were evaluated for destruction by conventional histology. Cellular components, markers of differentiation and proliferation were characterized by immunohistochemistry (vimentin, CD68, TRAP, MMP 1-3-13, ALP, Osteonectin, CD 31, Ki-67). Xenografts of nasal mucosa from GPA patients with active endonasal disease and from sinusitis control patients were co- transplanted with healthy human cartilage in immunodeficient pfp/rag2 -/- mice and were investigated in parallel. <h3>Results</h3> Samples of nasal biopsies from GPA patients as well as xenografted GPA tissues show GPA related cartilage/bone destruction mediated by invading cells, not by ischemic necrosis due to vasculitis or areactive geographical necrosis. Invading cells in xenografts were identified as predominantly human fibroblast, while human tissues showed a more complex and variable pattern of cartilage/bone destruction. However, the morphology of destruction was very similar in tissue samples from both sources. <h3>Conclusions</h3> Nasal cartilage/bone destruction in GPA is an active process related to a broad spectrum of cells. However, fibroblasts are the dominant cartilage destructing cells both in GPA patients and in GPA xenografts, thus validating the findings in xenografts to be relevant for the human pathophysiology. <h3>Disclosure of Interest</h3> None Declared
USEFULNESS OF MEAN PLATELET VOLUME AS A BIOMARKER FOR ANGIOGRAPHIC THROMBUS BURDEN AND SHORT-TERM MORTALITY IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Yi-Ning Yang, Hong-Mei Lai, Rui Xu, Yi Ma, Xiao-Mei Li, Qian Zhao, Qing-Jie Chen, Hui Zhai
Journal: Journal of the American College of Cardiology (2015)
Endoscopic aspiration mucosectomy using a novel vibration hood
Authors: K. Kume
Journal: Endoscopy (2009)

We recently reported the usefulness of three types of original prelooped caps: the irrigating prelooped cap [1], the two-channel prelooped hood [2], and the internally retained snare hood [3] for endoscopic aspiration mucosectomy (EAM). EAM is the simplest method of endoscopic mucosal resection (EMR) [1] [2] [3] [4] [5], but there is a risk of aspirating and perforating the full thickness of the gastric wall. To reduce the risk of such perforation, the resection is normally performed by strangulation with a snare using a light touch. Experience is needed to apply this light touch with just the right pressure, and it can be an uncertain process. In order to apply vibration during strangulation, a novel vibration hood has been developed that enables strangulation and resection of only the mucosal and submucosal layers, by vibrating the snare during strangulation to shake off the muscle layer and serous membrane ([Fig. 1]).
Detection of Subcentimeter Metastatic Cervical Lymph Node by 18F-FDG PET/CT in Patients With Well-Differentiated Thyroid Carcinoma and High Serum Thyroglobulin But Negative 131I Whole-Body Scan
Authors: Anchisa Kunawudhi, Rattaplee Pak-art, Somboon Keelawat, Supatporn Tepmongkol
Journal: Clinical Nuclear Medicine (2012)

Purpose This study aimed to evaluate the diagnostic value of 18F-FDG PET/CT and identify the best parameter to detect subcentimeter cervical nodal metastasis in patients with a well-differentiated thyroid carcinoma (WDTC), elevated serum thyroglobulin (Tg) levels, but negative findings in the 131I whole-body scan (WBS). Materials and Methods We prospectively studied 30 consecutive patients with WDTC after standard surgery and radioiodine treatment. All patients had serum Tg greater than 10 ng/mL during thyroid hormone withdrawal but negative findings in the therapeutic 131I WBS. One whole-body CT scan and serial whole-body and neck PET scans were performed between 10 and 170 minutes after 18F-FDG injection. Parameters studied were SUVmax, percent change in SUVmax, SUV ratios of lesions to reference organs, and their percent change. Result in the PET/CT scan was correlated with histopathology and follow-up information. Patient-based and lesion-based (subcentimeter cervical lymph nodes) analyses were performed. Outcome of Tg level after lymph node resection was also analyzed. Results The overall sensitivity, specificity, accuracy, and positive and negative predictive values were 100%, 78%, 93%, 91%, and 100%, respectively. In lesion-based analysis, the differential SUVmax between 2 time points did not provide higher sensitivity than the individual SUVmax at the 60th or 90th minute. A combined SUVmax at the 90th minute greater than 2.75 and a percent change of SUVmax between the 60th and 90th minute greater than −1.1% provides the best diagnostic value with sensitivity, specificity, accuracy, and positive and negative predictive values of 81%, 90%, 83%, 97%, and 56%, respectively. After surgery, patients with completely resected PET-positive nodes without distant metastasis showed reduction of suppressed Tg to less than 2 ng/mL. Conclusions Combined SUVmax at the 90th minute and the percent change of SUVmax between the 60th and 90th minute provides the best diagnostic value to differentiate benign from malignant conditions in subcentimeter lymph nodes.
S37 Can the Lung Reverse Remodel? Gene Therapy For Cardiac Failure Alters Pulmonary Gene Expression
Authors: JES Park, AR Lyon, L Hector, MJD Griffiths
Journal: Thorax (2012)

<h3>Introduction</h3> Irreversible alveolar capillary membrane (ACM) remodelling accompanies chronic heart failure (CHF), contributing to dyspnoea, the predominant symptom that limits quality of life in CHF. Gene therapy is aimed at improving myocardial function in CHF. Restoration of Sarco-endoplasmic reticulum calcium ATPase (SERCA2a) gene expression in animal models of CHF restores haemodynamic parameters towards normal. The lungs are the direct upstream target of raised left atrial pressure and hence pulmonary venous hypertension. We hypothesised that mechanical strain at the pulmonary micro vasculature associated with PVH up-regulates mediators leading to pulmonary inflammation and ACM remodelling. We have previously shown that gene expression of monocyte chemoattractant protein (MCP)-1, interleukin(IL)-6, endothelin (ET)-1, endothelin receptors (ETR) A and B, and endothelial converting enzyme (ECE) are altered in the lungs of Sprague-Dawley rats at 16 weeks after left coronary artery ligation. We now sought to determine the effect of SERCA2a gene therapy on gene expression of these mediators in the lung. <h3>Methods</h3> Gene expression of components of the ET-1 pathway, MCP-1 and IL-6 were investigated in whole lungs of rats at 16 weeks after LCA, at 16 weeks post LCA with tail vein injection of adeno-associated viral (AAV) gene transfer of SERCA2a at 12 weeks post LCA, or sham procedure(n=5 in each group). Lungs were snap frozen in liquid nitrogen, RNA extracted using a modified Trizol and RN easy protocol and gene expression determined in reverse transcribed cDNA by qPCR. <h3>Results</h3> Expression of ET-1, ETAR, MCP-1 and IL-6 genes were elevated in heart failure animals and reduced to or towards normal in SERCA2a treated animals. In heart failure animals there was a trend towards reduced ETRB expression which was significantly improved by SERCA2a gene therapy (figure 1). ECE gene expression was not altered by LCA or gene therapy. <h3>Conclusion</h3> SERCA2a gene therapy directed at the myocardium in heart failure also affects gene expression in the lungs of CHF animals. This may provide therapeutic benefit to the lungs in addition, reducing inflammation and stimuli associated with structural and vascular remodelling.
HG-09 * INFANTILE GLIOBLASTOMA WITH SARCOMATOUS HISTOLOGY DRIVEN BY ETV6:NTRK3 FUSIONS ARE SENSITIVE TO TRK INHIBITION BY PHA-848125
Authors: D. Carvalho, K. Taylor, A. Burford, I. Nowak, A. Mackay, M. Vinci, L. Bjerke, V. Molinari, M. Nandhabalan, W. Ingram, A. Jury, R. Natrajan, D. Jones, S. Pfister, L. Shats, A. Moore, T. Jacques, S. Popov, C. Jones
Journal: Neuro-Oncology (2015)

Approximately 1% of all paediatric brain tumours occur at less than one year of age, and glioblastoma (GBM) account for only 2-9% of these. Their clinical presentation, location, histology, behaviour, response to therapy and outcome differ from GBMs of older children and adults, and they do not appear to be associated with known histone H3 or IDH1-driven subgroups. Recent genome and RNA sequencing data highlighted recurrent NTRK1-3 fusions in 4/10 non-brainstem GBM under the age of 3 years, including one case of ETV6-NTRK3 in a cerebral hemispheric tumour diagnosed at 1 month old. These fusions are usually associated with congenital mesoblastic nephroma and congenital infantile fibrosarcoma, and upon review of a series of cases diagnosed as glioblastoma under the age of 1yr, 6/14 were found to present with a predominant spindle cell morphology, a relatively circumscribed interface with adjacent brain, and without prominent infiltration. These tumours were positive for GFAP as well as desmin, CD56 and CD99. One case was diagnosed in utero by ultrasound, and at birth underwent surgical resection from which primary cell cultures were established under stem cell conditions on laminin-coated plates. Exome and RNA sequencing revealed the presence of the ETV6:NTRK3 fusion transcript as the sole somatic alteration, validated by RT-PCR, Sanger sequencing and FISH. 450K methylation profiling clustered the tumour with desmoplastic infantile ganglioglioma rather than subgroups of paediatric GBM. Primary cells treated with the CNS-penetrant small molecule Trk inhibitor PHA-848125, resulted in marked sensitivity (GI50 = 200nM) compared to cerebral hemispheric (H3 wild-type) and thalamic (H3.3K27M) paediatric GBM cells (GI50 = 1.8-4.6mM). A subset of infantile/congenital brain tumours classified as GBM appear to represent a distinct entity more closely related, biologically and histologically, to mesenchymal cancers. Agents targeting ETV:NTRK3 may be a useful novel treatment strategy in these children.
Abstract 3454: Molecular markers for breast carcinogenesis models induced by environmental substances and estrogen
Authors: Gloria M. Calaf, Adayabalam S. Balajee, Debasish Roy
Journal: Cancer Research (2010)

Abstract Breast cancer is the most common cancer in women throughout the world. Exogenous and endogenous agents such as environmental carcinogens and female hormones seem to be involved in the etiology of breast cancer. It is a multistage process involving a series of genetic alterations, identification of potential genes responsible for breast carcinogenesis is critical for timely diagnosis and prevention of breast cancer. To gain insights into the mechanisms for breast cancer initiation and development processes by exogenous environmental agents, we have developed many experimental breast cancer model systems: In vitro model with the immortalized human breast epithelial cell line, MCF-10F exposed to (I) low doses of high LET (linear energy transfer) alpha particles (150 keV/μm) (Carcinogenesis 21: 769, 2000) and b), (II) organophosphorous pesticides, either with Parathion (P) or Malathion (M) and (III) combination of either P or M in the presence of estrogen (E). Results showed that MCF-10F cells treated either with double dose of 60 cGy alpha particles in the presence of E or pesticides induced malignant transformation of MCF-10F. The malignant transformation was determined by multiple biological assays: increased cell proliferation, anchorage independency, invasive capabilities and tumor formation in nude mice, microsatellite instability and loss of heterozygosity in chromosomes 17, 11, 6, 8. Gene expression analysis using cancer pathway specific and affymetrix arrays detected alterations in the expression levels of p53, ErbB2, BRCA1, c-Ha-ras, Rho-A, PTEN, RB, c-Ha-ras, transforming protein Rho-A, F, GDP, TGF alpha, beta receptor, integrin B6, Notch3 and cathepsin. In addition to the in vitro human model, in vivo rat mammary gland model was also generated: (I) control (II) either P or M (III) E and (IV) P or M and E. Animals were treated for 5 days. These combined treatments induced significant progressive morphological and molecular changes. Alterations in the expression levels of RNA and protein were observed for c-fos, c-myc, mutant p53, ErbB2, BRCA1, c-Ha-ras, Rho-A, CYP1A1 gene and protein expression in the rat mammary gland after 240 days of treatment in comparison to control. Such stimulation led to mammary tumor formation. Collectively, our study shows the molecular signature of oncogenic deregulation in breast cancer progression induced by the combination of environmental substances and estrogen. Thus, aberrant expression of multiple genes involved in key signaling pathways renders these models as important tools for monitoring carcinogenic progression and chemo-intervention. Grant FONDECYT # 1080482 (GMC). 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 3454.
1247 HIGH CHOLESTEROL DIET INDUCES STEATOHEPATITIS IN RAT, AND IS ASSOCIATED WITH OXYSTEROL OVERPRODUCTION AND MITOCHONDRIAL-DEPENDENT UPREGULATED OXIDATIVE STRESS
Authors: F. Bellanti, L. Iuliano, M. Blonda, G. Iannelli, R. Tamborra, A. Petrella, G. Poli, G. Vendemiale, G. Serviddio
Journal: Journal of Hepatology (2013)
Abstract 1645: Characterization of a novel anti-insoluble-fibrin chimeric antibody (AFCA) for cancer stromal target (CAST) therapy and diagnosis.
Authors: Yohei Hisada, Masahiro Yasunaga, Yasuhiro Matsumura
Journal: Cancer Research (2013)

Abstract Background: A large body of clinicopathological evidence supports the conclusion that abnormal coagulation occurs in a variety of cancers. In the non-malignant condition, fibrin clots (insoluble fibrin) form only at the onset or active state of disease and subsequently disappear because of plasmin digestion or replacement with collagen within a few weeks. However, in cancer, fibrin clot formation and subsequent replacement with collagen continue for as long as cancer cells survive in the body. In this context we considered that the fibrin clot could be a pathophysiologically specific target in cancer and accordingly developed an anti-insoluble-fibrin chimeric antibody (AFCA). Here, we characterize AFCA and demonstrate its potential as a tool for drug delivery to the cancer stroma. Method: The specificity of AFCA was evaluated by ELISA using insoluble fibrin, fibrinogen (the precursor of fibrin), soluble fibrin, and D-dimer (the degradation product of insoluble fibrin) as antigens. To compare AFCA with commercially available anti-fibrin antibodies, we performed ELISA with insoluble fibrin, fibrinogen, and D-dimer as antigens. We also conducted western blotting with native fibrinogen and denatured fibrinogen. To evaluate the accumulation of AFCA in tumors, we gave fluorescence-labeled AFCA to transgenic mice with pancreatic cancer. Results: AFCA recognized only insoluble fibrin, not any fibrin-related proteins. AFCA had higher specificity against insoluble fibrin than did commercially available anti-fibrin antibodies. Western blotting analysis revealed that AFCA reacted with denatured fibrinogen but not native fibrinogen. AFCA, but not isotype control IgG, accumulated in the pancreatic cancer tissues. Conclusion: These findings imply that the epitope of AFCA is a distinctive sequence that is uncovered only on the fibrin clot. Because lasting asymptomatic fibrin clot formation is a cancer-specific phenomenon, AFCA should be a useful tool for drug delivery to insoluble fibrin present around cancers. Citation Format: Yohei Hisada, Masahiro Yasunaga, Yasuhiro Matsumura. Characterization of a novel anti-insoluble-fibrin chimeric antibody (AFCA) for cancer stromal target (CAST) therapy and diagnosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1645. doi:10.1158/1538-7445.AM2013-1645
Hepatic Uptake of Tc-99m MDP on Bone Scintigraphy From Intravenous Iron Therapy (Blutal)
Authors: CHAN H. PARK, HYUN S. KIM, HYE Y. SHIN, HUGH C. KIM
Journal: Clinical Nuclear Medicine (1997)

Two patients with hypochromic microcystic anemia received intravenous iron therapy (Blutal, Yuham Co., An Yang, Korea). These patients demonstrated diffuse hepatic uptake of Tc-99m MDP on bone scintigraphy, which was performed for evaluation of lower back pain in one patient and to rule out skeletal metastases from gastric cancer in the other patient. Blutal is an iron colloid chondroitin sulfate complex and is used to treat iron deficiency anemia in Korea. Phagocytized iron colloid within the hepatic reticuloendothelial system is responsible for the hepatic uptake of Tc-99m phosphate in the two presented cases.
FRI0263 Country of Residence and Its Wealth Determine Disease Activity Levels in RA: Results from Multi-National Study in 17 Countries (COMORA): Table 1.
Authors: P. Putrik, S. Ramiro, A.P. Keszei, I. Hmamouchi, M. Dougados, T. Uhlig, T.K. Kvien, A. Boonen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Socio-economic (SE) inequalities in health persist both between and within countries and even increased in the recent years. Therefore, it is important to explore whether country level factors may contribute to health inequities in patients with RA. <h3>Objectives</h3> The objectives of this study were to (1) investigate whether country level factors contribute to explain Disease Activity Score (DAS28) (2) explore whether uptake of biologic disease modifying anti-rheumatic drugs (bDMARDs) mediates the relationship between country welfare and DAS28. <h3>Methods</h3> Data from a cross-sectional multinational (17 countries) study (COMORA) was used. The outcome was DAS28. Contribution of country to DAS28 was explored in multivariable linear regression models, adjusting for potential confounders, using forward selection and accounting for multiple testing. The Netherlands (NL) with lowest DAS28 was used as reference. Next, the country of residence was replaced by GDP (in tertiles), to investigate the contribution of socio-economic welfare. Improvement in R<sup>2</sup> (model fit) of the two models that included either country or GPD was compared. Finally, the mediating role of uptake of bDMARDs in the relationship between GDP and DAS28 was explored by testing indirect effects. <h3>Results</h3> A total of 3920 RA patients from 17 countries (range 30-411) were included in the COMORA dataset. Mean age was 56 y.o. (SD13), 82% females. Mean DAS28 was 3.7 (range 2.6 (NL) – 5.2 (Morocco)), and 32% of patients were currently treated with bDMARDs (range 3% (Uruguay) – 74% (UK)). Country differences in DAS28 varied from 0.2 (France) to 2.3 (Morocco) compared to NL, after adjustment for individual factors. Additional contribution of country to R<sup>2</sup> was 0.15 and of GDP 0.08. Fifty and 13% of the relationship between DAS28 and medium and low GDP (vs. high GDP), respectively, was mediated by uptake of bDMARDs (total and indirect effect 0.06 and 0.03 (95% CI [0.02;0.04]) and 0.31 and 0.04 (95% CI [0.02;0.05]) for medium and low GDP, respectively, vs high GDP). Final model with countries classified into GDP groups is presented in Table 1. <h3>Conclusions</h3> Substantial differences in DAS28 between countries were observed after adjusting for individual factors. In societies with GDP in the two lowest tertiles disease activity was on average 1.2 and 0.2 units higher compared to high GDP countries. While total effect for medium GDP was negligibly small, 13% of the differences in DAS28 between low and high GDP countries was mediated by (lower) uptake of bDMARDs. Inequities across countries should come at focus of international societies of rheumatology and policy-makers. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3650
A7.19 Positive Association of TAGAP Rs212389 Polymorphism with Rheumatoid Arthritis Susceptibility
Authors: A Chatzikyriakidou, PV Voulgari, AA Drosos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> T-cell activation RhoGTPase activating protein (TAGAP) has recently been reported among genetic factors implicated in rheumatoid arthritis (RA) susceptibility. Up today, three polymorphisms at 6q25 locus, where TAGAP gene is mapped, have been associated with RA liability in patients of European descent: Rs394581, Rs212389, and Rs182429. According to a recent study, in which a comprehensive imputation of CEU HapMap single-nucleotide polymorphisms was conducted in a genome-wide association study, the polymorphism Rs212389 is the best predictor of TAGAP locus in RA predisposition at least in patients of European descent. In the present study, this polymorphism was genotyped, for first time, in RA samples as to validate the suggested association, while the genotypic analysis was extended to polymorphisms Rs394581 and Rs182429 in order to refine again the causative RA risk variant. <h3>Materials and Methods</h3> One hundred thirty five patients and 147 controls subjects were enrolled in the study. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) coupled with sequencing analysis was used as the screening method for TAGAP variants. <h3>Results</h3> Statistical significant difference was observed in Rs212389 alleles' distribution between RA patients and controls (p = 0.018, OR = 0.646, 95%CI: 0.449–0.930). No statistical significant difference was revealed in distribution of variants Rs394581 and Rs182429 between the studied groups. <h3>Conclusions</h3> Our results confirm that the polymorphism Rs212389 confers the risk to RA liability in Europeans. However, more studies in larger groups of patients and controls and of multiple origins are needed as to confirm and increase the power of the suggested association.