tbuckley/cabot-search huggingface dataset:
AB0644 Scleroderma Cutaneous Form and Its Influence in Disorder Mood, Quality of Life and Disability Aspects
Authors: G.A.M.B. Bezerra, M.R. Costa, N.B.C. Lima, F.M.L. Pinheiro Júnior, S.M.A. Fontenele
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The modified Rodnan skin score (mRSS) analyzes the extent and severity of skin thickening of Systemic Sclerosis (SSc) by palpation in 17 anatomical sites. It is graded by a scale 0-3, where 0 = normal skin, 1 = mild skin thickening, 2 = moderate 3 = skin thickening and skin thickening with intense inability to pucker the skin.<sup>1</sup> Studies have shown that diffuse SSc have higher mRSS and this may compromise the rates of morbidity and mortality in these patients.<sup>2</sup> However, there is no consensus on a cutoff point that confirms mRSS as an independent marker of activity and severity disease; furthermore, the subjectivity in the evaluation and disease staging and therapeutic response-related variability impair its accuracy and reprodutibility.<sup>3</sup> <h3>Objectives</h3> To evaluate the correlation between skin thickening and disorders mood, quality of life and disability aspects in a group with diffuse and limited SSc patients. <h3>Methods</h3> Cross-sectional study with 59 SSc patients, followed-up at the Walter Cantidio University Hospital. The skin thickening was analyzed by mRSS; the disorders mood and quality of life by SRQ-20 and SF-36 questionnaires; and disability by HAQ. Mann-Whitney test was carried out to compare the scales of the diffuse and limited groups, and the Spearman test to correlate mRSS with the other scales. The significance level was stipulated in 5%. <h3>Results</h3> In that sample, 47 patients had the diffuse form (79%). The mean and standard deviation of mRSS was 20 (±8.7); of positives responses SRQ-20 8,9 (±4.9); of functional capacity, physical aspect and health general status, respectively, were 42.5 (±21.5), 26.5 (±35.9) and 38.3 (±20.1); of HAQ was 1.10 (±0.7). The mRSS correlated negatively with SRQ-20 (-0.2) and positively with HAQ (-0.2). When compared the diffuse and limited forms, the worse mRSS was the first one (21.9±8.5), P=0.00; in this group, mRSS correlated stronger negatively with SRQ-20 (-0.32; P=0.027) and positively with HAQ (-0.31; P=0.033). <h3>Conclusions</h3> It was confirmed that exist SSs related-disorders mood tendency, quality of life decrease and disability. The diffuse form showed the highest degree of skin thickening and that seemed to determine worsening of emotional and functional aspects. <h3>References</h3> Sampaio-Barros PD, Bortoluzzo AB, Marangoni RGJ, Rheumatol. Merkel PA, Silliman NP, Clements PJ, Arthritis Rheum Hasegawa M, Asano Y, Endo H, Rheumatology (Oxford) <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5829
Prime elements of subjectively experienced feelings and desires: Imaging the emotional cocktail
Authors: Ross W Buck
Journal: Behavioral and Brain Sciences (2012)

Abstract Primary affects exist at an ecological-communicative level of analysis, and therefore are not identifiable with specific brain regions. The constructionist view favored in the target article, that emotions emerge from “more basic psychological processes,” does not specify the nature of these processes. These more basic processes may actually involve specific neurochemical systems, that is, primary motivational-emotional systems (primes), associated with specific feelings and desires that combine to form the “cocktail” of experienced emotion.
Abstract 2738: c-Met antibody LY2875358 (LA480) has pre-clinical enhanced efficacy with gastric cancer standard-of-care <i>in vitro</i> and <i>in vivo</i>
Authors: Mark A. Wortinger, Victoria Peek, Wei Zeng, Lei Yan, Jonathan Tetreault, Jinqi Xia, Lu Jirong, Chi-Kin Chow, Jason R. Manro, Jennifer R. Stephens, Farhana Merzoug, Peter Vaillancourt, S. Betty Yan, Ling Liu
Journal: Cancer Research (2012)

Abstract cMet is a member of the receptor tyrosine kinase family and is the receptor for hepatocyte growth factor (HGF). cMet has been implicated in the initiation and progression of cancer due to the range of activities that cMet stimulates including proliferation, migration, morphogenesis, and survival. Inappropriate activation of c-Met can be induced by ligand-independent mechanisms such as gene amplification, specific genetic mutations, and transcriptional upregulation, or by ligand-dependent autocrine or paracrine mechanisms. Indeed, amplification of the c-Met gene, with consequent protein overexpression and constitutive kinase activation, has been reported in a number of human cancers, including gastric, esophageal and non-small-cell lung carcinomas. It has been reported that ∼10-20% of gastric tumors have increased copy numbers of the MET gene and overexpression of c-Met significantly correlates with poor prognosis in gastric cancer. c-Met antibody LY2875358 treatment reduces proliferation of gastric cancer cell lines with ligand-independent activation of c-Met resulting from gene amplification. The ability of LY2875358 to internalize and deplete cell surface c-Met is implicated in its activity against ligand-independent driven gastric cell lines. Here, we demonstrate that the pre-clinical combination of c-Met antibody LY2875358 with gastric cancer standard-of-care treatment has better efficacy than either treatment alone, both in vitro and in vivo. These data suggest that LY2875358 in combination with standard-of-care may be a promising treatment for gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2738. doi:1538-7445.AM2012-2738
A NOVEL P53 BYSTANDER EFFECT INDUCES GLIOBLASTOMA CELL DEATH THROUGH A GLYCOSYLATION-DEPENDENT MECHANISM
Authors: E. G. Van Meir, S.-H. Lee, F. W. Khwaja, A. Zerrouqi, Z. Zhang, J. J. Olson, M. Kaluzova, C. G. Hadjipanayis, N. S. Devi
Journal: Neuro-Oncology (2014)

BACKGROUND: Mutations in the TP53 tumor suppressor gene are required for the development of many malignancies, including brain tumors. Yet, the molecular mechanisms underlying p53's anti-tumor effects remain incompletely understood. In the present study we demonstrate the existence of a novel cell-extrinsic mechanism whereby p53 can antagonize tumor growth. METHODS: To activate p53-dependent DNA damage, cells were either untreated (Ctrl) or treated with 25 µM etoposide (VP16), ultraviolet light (UV; 60 mJ per cm2) or γ-radiation (5 Gy). Gene and protein expression were analyzed by Northern Blot, Western blot and/or RT/PCR analyses. Standard apoptosis assays, crystal violet cytotoxicity assays, soft-agar colony formation assays and in vivo tumorigenicity experiments were used. RESULTS: We found that following DNA damage, cells with activated p53 can control the viability of adjacent tumor cells through secretion of galectin-3 (Gal-3), a β-galactoside-binding lectin. Gal-3 specifically induced the killing of bystander cancer cells but not normal cells by paracrine induction of caspase 9-mediated apoptosis. Induction of Gal3 secretion in tumor cells could also antagonize glioblastoma tumor growth in subcutaneous and intracranial models. Mechanistically, p53 indirectly induced Gal-3 export through transcriptional regulation of p53-tumor suppressor activated pathway-6 (TSAP6), a key component of the non-classical exosome-mediated secretory pathway. Investigation into the mechanism of tumor-specific killing by Gal-3 revealed preferential binding to β1 integrin on the surface of tumor cells due to differential post-translational N-glycosylation resulting from the coordinated upregulation of several glycosyltransferases in the tumor cells. CONCLUSIONS: The bystander apoptosis effect defined here is significant because it represents a novel paracrine tumor suppressive mechanism for p53, which increases our understanding of p53 function and has therapeutic implications. It is important for the optimization of chemo- and radiotherapies as well as reactivation of p53 through small molecule or gene therapies. These data also suggest that Gal-3 has potential as an anti-cancer therapeutic. This work was supported by NIH R01 CA163722. SECONDARY CATEGORY: n/a.
SAT0084 Chest Pain is not Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis
Authors: S. Rollefstad, I. C. Olsen, J. Hisdal, T. K. Kvien, A. S. Eirheim, T. R. Pedersen, A. G. Semb
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> During cardiovascular (CV) risk stratification in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), it can be difficult to distinguish between chest pain related to coronary atherosclerosis (CA), or to the rheumatic disease itself. <h3>Objectives</h3> The aim was to evaluate associations between chest pain, CV risk factors and CA in RA and AS patients without established CV disease. <h3>Methods</h3> Detailed information concerning chest pain and CV risk factors was obtained in 335 patients with RA and AS. In addition, 119 patients (RA n=86 and AS n=33) underwent multi detector computer tomography (MDCT) coronary angiography.<sup>1</sup> <h3>Results</h3> Thirty-one percent (104/335) reported chest pain. Only 6 patients (1.8%) had atypical angina pectoris (pricking pain at rest). In 50 patients with chest pain, 26 (52.0%) had CA, while in 69 patients without chest pain, 51 (73.9%) did have CA. In a logistic regression analysis with CA (by MDCT coronary angiography) as the dependent variable, chest pain was not associated with CA (p=0.28). About 30 % of CA was explained by any of the three following CV risk calculators: SCORE (systemic coronary risk evaluation), Framingham and Reynolds in these models (Table 1). <h3>Image/graph</h3> <h3>Conclusions</h3> Chest pain was surprisingly infrequently reported considering the underlying rheumatic joint disease, but when present, chest pain was of limited value in CV risk evaluation. <h3>References</h3> Hoffmann MH, Shi H, Schmitz BL, Schmid FT, Lieberknecht M, Schulze R et al. Noninvasive coronary angiography with multislice computed tomography. <i>JAMA</i> 2005; 293(20):2471-2478. <h3>Disclosure of Interest</h3> None Declared
ROLE OF KV1.3 CHANNEL IN VASCULAR SMOOTH MUSCLE CELLS PROLIFERATION IN A PORCINE MODEL OF RESTENOSIS
Authors: Mercè Roqué, Manel Garabito, Solanes Nuria, Montserrat Rigol, Pilar Cidad, M Teresa Perez-Garcia, Victor Ramos, Jose Ramon Lopez Lopez, Salvador Borros, Esperanza Alonso, Laura Jimenez Perez
Journal: Journal of the American College of Cardiology (2015)
Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells
Authors: Wilna Oosthuyzen, Kathleen M. Scullion, Jessica R. Ivy, Emma E. Morrison, Robert W. Hunter, Philip J. Starkey Lewis, Eoghan O'Duibhir, Jonathan M. Street, Andrea Caporali, Christopher D. Gregory, Stuart J. Forbes, David J. Webb, Matthew A. Bailey, James W. Dear
Journal: Journal of the American Society of Nephrology (2016)

Extracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Mechanistically, ECV entry into mCCDC11 cells required cAMP production, was reduced by inhibiting dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV deposition in kidney tissue. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs in vivo We conclude that ECV uptake is a specific and regulated process. Physiologically, ECVs are a new mechanism of intercellular communication; therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease.
P620 THE AMPK-RELATED KINASE, Nuak2 IS MODULATED BY THE ACTIVATION PROCESS AND REGULATES MOTILITY OF HEPATIC STELLATE CELLS (HSC)
Authors: C. Tosti-Guerra, A. Caligiuri, A. Provenzano, K. Rombouts, C. Bertolani, M. Pinzani, F. Marra
Journal: Journal of Hepatology (2014)
Ulcer in Barrett’s esophagus probably related to severe kyphosis
Authors: A. Oka, Y. Amano, T. Yuki, R. Kusunoki, N. Ishimura, S. Ishihara, Y. Kinoshita
Journal: Endoscopy (2010)

An 83-year-old man with severe kyphosis and parkinsonism caused by cerebral infarction was admitted to our hospital with a history of episodes of chest discomfort. Endoscopic study revealed a long segment of Barrett’s mucosa with large hiatal hernia and a deep ulcer in the Barrett’s mucosa ([Fig. 1]). No malignancy was proven by endoscopic biopsy of the ulcer. The patient was not receiving any drugs or chemicals. Thus, we diagnosed the ulcer as a ”Barrett“s ulcer” [1]. Computed tomography showed that the thoracic esophagus was dorsally displaced and the stomach ventrally displaced by kyphosis of the spine. Despite overnight fasting, fluid was retained in the mid-esophagus, which corresponded to the location of the Barrett’s ulcer ([Fig. 2 a]). A barium examination revealed reflux from the stomach to the mid-esophagus around the location of the ulcer when the patient was semi-upright and supine ([Fig. 2 b, c]). The patient had to sleep in the supine position during the night because his ability to turn over in bed was restricted by the parkinsonism. No evidence of Helicobacter pylori infection was found in the serological test. Evidently, highly acidic reflux fluid might be retained for a long time in the mid-esophagus, where the ulcer developed. The ulcer healed completely after treatment with omeprazole 20 mg/day for 2 months ([Fig. 3]).
P110 Exposure To Community Copd During Specialty Training
Authors: G. Jones, A. Collins, S. Sibley, D. Wat, M. Walshaw
Journal: Thorax (2014)

<h3>Introduction</h3> There has been an exponential growth in Community COPD care delivered by respiratory consultants in the last 5 years. Despite this rapid expansion, little is known about trainees’ exposure to these services even though a proportion of them will go on to work in or set up such posts after completing their training. <h3>Methods</h3> We conducted a national survey of respiratory trainees to assess their views and experience of Community COPD, including the commissioning process which forms an integral part of establishing such services. <h3>Results</h3> We obtained 59 responses from trainees in 12 different regions (including all four home nations): 17% less than full time (LTFT), 81% ST5+, and 53% female. Despite the majority (64%) being aware of an expansion in services locally over 86% had no experience of Community COPD and most (75%) had no direct involvement in the commissioning process. Unsurprisingly, over three quarters felt their exposure to Community COPD services during specialty training was inadequate. Of 8 who had attended Community COPD clinics, 7 had to organise ad hoc sessions themselves. Some trainees perceived a reluctance to facilitate formal training opportunities due to hospital service delivery requirements or a concern that community services were commissioned to be consultant-delivered. While over 22% of respondents stated that they would not apply for a consultant post that included any community COPD sessions, this did not include any LTFT trainees and this group were also more likely to consider a job wholly based in the community [50% vs. 27%]. <h3>Discussion</h3> This survey suggests that most respiratory trainees, especially those in LTFT, would be willing to work in Community COPD roles as consultants, but are struggling to obtain adequate experience during training. It is envisaged that there will be further expansion of community respiratory services to improve patient access and to facilitate integration between primary and secondary care in the future. We suggest that training programme directors consider making experience of Community COPD a formal requirement and that the curriculum is updated to better reflect the needs of trainees.
Abstract 942: Protein kinase CK2 contributes to 1, 25-dihydroxyvitamin D3-mediated CYP24A1 gene expression in prostate cancer cells
Authors: Wei Luo, Adam R. Karpf, Mikhail Chernov Chernov, Candace Johnson, Donald Trump
Journal: Cancer Research (2011)

Abstract The active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a major role in regulating calcium homeostasis and bone mineralization. 1,25(OH)2D3 also modulates cellular proliferation and differentiation in a variety of cell types through the activation of vitamin D receptor (VDR), by both genomic and nongenomic pathways. 1,25-(OH)2D3 has anti-tumor effects in several tumor models. 24-hydroxylase, encoded by the CYP24A1 gene, plays a key role in degrading 1,25(OH)2D3. Suppression of CYP24A1 function enhances the antitumor activity of vitamin D. In order to isolate regulators of CYP24A1 expression in prostate cancer cells, we established the prostate cancer cell line PC3 stably transfected with CYP24A1 promoter driving luciferase expression and used this cell line to screen for compounds that inhibit CYP24A1 promoter activity, using a drug library. From this screening, we identified, 4,5,6,7-tetrabromobenzimidazole (TBBz), a protein kinase CK2 selective inhibitor as a disruptor of CYP24A1 promoter activity. We show that TBBz specifically inhibits CYP24A1 promoter activity induced by 1,25(OH)2D3 in prostate cancer DU145 and PC3 cells. In addition, TBBz downregulates endogenous CYP24A1 mRNA level in TBBz treated PC3 cells. Furthermore, siRNA-mediated CK2 knockdown reduces 1,25(OH)2D3 induced CYP24A1 mRNA expression in PC3 cells. This inhibitory effect on CYP24A1 expression by CK2 siRNA is enhanced by the addition of TBBz. These results suggest that CK2 signaling contributes to 1,25(OH)2D3 mediated induction of CYP24A expression. This study provides among the first line of evidence that CK2 is linked to vitamin D metabolism. Future studies will elucidate the mechanism(s) underlying the mechanism by which CK2 regulates CYP24A1 expression. In summary, our findings reveal that protein kinase CK2 is involved in the regulation of CYP24A1 expression by 1,25(OH)2D3, and highlight a novel strategy to facilitate the optimization of antitumor therapy of vitamin D. This study was supported by NIH/NCI grants 5R01CA067267 and 5R01CA095045 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 942. doi:10.1158/1538-7445.AM2011-942
A Case of Chylothorax Diagnosed by Lymphoscintigraphy Using Tc-99m HSA-DTPA
Authors: SHIGEYUKI OGI, NOBUYOSHI FUKUMITSU, MAYUKI UCHIYAMA, YUTAKA MORI
Journal: Clinical Nuclear Medicine (2002)

OGI, SHIGEYUKI M.D.; FUKUMITSU, NOBUYOSHI M.D.; UCHIYAMA, MAYUKI M.D.; MORI, YUTAKA M.D. Author Information
Outbreak of Salmonella enterica Goldcoast infection associated with whelk consumption, England, June to October 2013
Authors: T Inns, G Beasley, C Lane, V Hopps, T Peters, K Pathak, R Perez-Moreno, G  K Adak, A G Shankar, None on behalf of the Outbreak Control Team
Journal: Eurosurveillance (2013)

An increase in the number of cases of Salmonella enterica serotype Goldcoast infection was observed in England during September 2013. A total of 38 cases were reported, with symptom onset dates between 21 June and 6 October 2013. Epidemiological, environmental, microbiological and food chain evidence all support the conclusion that this outbreak was associated with eating whelks processed by the same factory. Whelks are a novel vehicle of Salmonella infection and should be considered when investigating future outbreaks.
THU0067 The Incidence of New Onset and Recurrent Uveitis in Ankylosing Spondylitis Patients during TNF Inhibitor Therapy in Korean
Authors: B.S. Koo, S. Hong, Y.J. Kim, J.S. Oh, W.J. Seo, Y.-G. Kim, C.-K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In ankylosing spondylitis (AS), uveitis is one of serious extra-articular manifestation and the recurrence has known to be reduced by treatment with TNF inhibitor (TNFi). However, new onset or recurrent episode of uveitis has been developed under TNFi in our clinical experience. <h3>Objectives</h3> The aim of this study was to find cases of new onset and recurrent of uveitis during TNFi therapy and compare incidence rate of uveitis among three TNFi agents in Korean. <h3>Methods</h3> A retrospective evaluation was performed in 316 AS patients who were treated with TNFi therapy in a tertiary care center from June 2003 to June 2011. Among them, patients who documented uveitis were reviewed during follow up and analyzed the incidence rates of uveitis among infliximab, adalimumab, and etanercept. We also analyzed patients who were developed first episode of uveitis after starting TNFi therapy. <h3>Results</h3> Among 316 AS patients treated with TNFi, we found 42 (13%) patients of uveitis. The mean age of starting TNFi (35.5±10.3 years), male predominance (86%), and the mean duration of TNFi therapy (31.2±18.3) were not different to non-uveitis patients. Of the 42 patients, fifteen, eight, and three had been treated with etanercept, adalimumb, and infliximab, respectively. Overall incidence rate of uveitis in all TNFi was 45.6 per 1,000 person-years (py) (95% CI: 31.6 – 63.8). The incidence rate for etanercept was 53.7/1,000 py (95% CI: 33.6-81.2); adalimumab, 45.7/1,000 py (95% CI: 20.9-86.7); and infliximab, 21.7/1,000 py (95% CI: 4.5-63.5). Among 42 patients, new onset of uveitis patients during TNFi therapy was 10 (7, etanercept; 2, adalimumab; and 1, infliximab). The incidence rate of new onset-uveitis during all TNF inhibitor agents was 15.2 per 1,000 py (95% CI: 7.3-28.0). The incidence rate for etanercept was 17.9 py (95% CI: 7.2-36.8); adalimumab, 13.9 py (95% CI: 1.7-50.2); and infliximab 8.1 py (95% CI: 2.1-45.7). <h3>Conclusions</h3> In Korean, development of uveitis under TNFi treatment was found in 13% and new onset of uveitis during TNFi therapy was 3% of our cohort. Among three TNFi, the new onset and recurrence of uveitis was low relatively in infliximab group. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2802
Updated results from CHAMPION-1, a phase I/II study investigating weekly carfilzomib with dexamethasone for patients (Pts) with relapsed or refractory multiple myeloma (RRMM).
Authors: James R. Berenson, Alan Cartmell, Alberto Bessudo, Roger M. Lyons, Wael A. Harb, Dimitrios Tzachanis, Morton Coleman, Ralph V. Boccia, Robert M. Rifkin, Priti Patel, Sandra Dixon, Jesus G. Berdeja
Journal: Journal of Clinical Oncology (2015)

8527 Background: Carfilzomib (K) is a selective proteasome inhibitor that is approved for the treatment of relapsed and refractory multiple myeloma in the US. CHAMPION-1 (NCT01677858) is a multicen...