tbuckley/cabot-search huggingface dataset:
P775Molecular, label-free imaging for characterization of cardiomyopathy in mice
Authors: D M Poitz, N Steinbronn, P Barthel, E Koch, G Steiner, RH Strasser
Journal: Cardiovascular Research (2014)

Mice lacking Caveolin-1 (cav1ko) develop a severe hypertrophic cardiomyopathy (HCM). The HCM in this model is induced by an uncoupling of the endothelial NO-synthase, which leads to the enhanced production of radicals. The main characteristic of this form of cardiomyopathy is a thickened ventricle due to remodelling processes of the extracellular matrix composition mainly mediated by collagen deposition. However, the imaging of cardiomypathic tissue is still restricted to conventional histochemical analysis. Therefore, the aim of the present study was to characterize the myocardial tissue of cardiomyopathic cav1ko mice compared to wildtype C57BL6 mice (wt) by using Fourier Transformed Infrared (FT-IR) micro spectroscopic imaging. 15 weeks old wt or cav1ko mice were used to prepare thin cryosections of the hearts. Serial sections were prepared for spectroscopical analysis, hematoxylin-eosin staining and classical immunostaining of Collagene 1, 3 and 4. FT-IR micro spectroscopy was performed using the Bruker Hyperion system. Spectra were collected in transmission mode using a resolution of 6 cm-1 in a spectral range of 950–3800 cm-1. Approximately 25.000 individual spectra of each sample were acquired. IR spectra of cardiac samples show two strong bands namely the amide I (1650 cm-1) and amide II (1550 cm-1) modes. In addition, significant bands were observed around 1400 cm-1 (vibrations of fatty acids) and at 1460 cm-1 (CH2 bending vibrations). Absorption bands of nucleic acids were found between 1000 cm-1 and 1200 cm-1. Initially, the data set was evaluated by k-means clusters analysis. This analysis reveals that wt and cav1ko hearts significantly differ in their biochemical composition. To obtain detailed molecular information, a principal component analysis (PCA) was applied to the data. PCA shows, that cav-1 ko mice had a higher content of collagen within the ventricle. By comparison with the classical immunohistochemical stainings of the different collagen types in concert with the loading plots of the different principal components, the results of PCA allowed an identification of different collagen types and an objective quantification of the collagen content. In addition, the analysis of the bands representing nucleic acids revealed a lowered DNA content in cav-1 ko mice per area which is due to the hypertrophy of the ventricle. In conclusion, these results enlighten the capability of FT-IR micro spectroscopy for the label free and objective identification of cardiomyopathic heart failure by characterising the structural changes within the myocardial tissue.
FRI0051 Self-Reported Adherence to Cardiovascular Risk Reduction Intervention of Patients with Rheumatoid Arthritis: Results of the FRANCIS Study
Authors: D.F. Van Breukelen-van der Stoep, M. Castro Cabezas, J. Zijlmans, N. van der Meulen, B. Klop, M.A. de Vries, J. van der Arend, C. van Casteren-Messidoro, G.-J.M. van de Geijn, H.W. Janssen, E. Birnie, M.J. Hazes, D. van Zeben
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with Rheumatoid Arthritis (RA) have an elevated cardiovascular (CV) risk, comparable to the risk in type 2 diabetes mellitus. Recent guidelines suggest strict treatment of CV risk factors. It is well known that adherence to primary preventive interventions is frequently suboptimal (around 50%). <h3>Objectives</h3> To evaluate the self-reported adherence to CV prevention strategies by patients with RA participating in the FRANCIS study, a long term, randomized, single centre intervention study investigating the need for strict CV prevention strategies in RA. <h3>Methods</h3> Included RA patients who were randomized to strict CV risk prevention strategies received a validated questionnaire to evaluate adherence to therapy. All patients followed a structured CV risk management program with rheumatologists, vascular specialists, dieticians and specialized nurses for vascular and RA care. Strict treatment targets were defined and lifestyle recommendations, antihypertensive and lipid lowering drugs were prescribed following a pre-specified protocol. Questionnaires were sent to patients who had had at least two visits to our outpatient clinic and a minimum of 6 months follow up. CV risk was assessed using the SCORE algorithm <h3>Results</h3> Questionnaires were sent to 136 patients (response rate 111 (82%)). A high CV risk (≥20%) was found in 60 (53%) patients, but only 3 (3%) thought that they had an increased CV risk. In total, 65 (69%) patients followed the doctors9 suggestions exactly and 71 (75%) patients found it easy to follow their doctors suggestions exactly. From the 71 (66%) patients who were prescribed medication, 59 (83%) took all prescribed tablets. Dietary measures were advised to 46 (42%) patients and 30 (66%) said to adhere to the diet. Physical exercise was ad vised to 72 (66%) patients and 42 (58%) said to perform specific physical exercise ≥3 days/week. The adherence was not significantly different between patients with a CV risk &lt;10%, 10%&gt;20% and/or &gt;20%. <h3>Conclusions</h3> RA patients tend to underestimate their CV risk. Self-reported treatment adherence is 70%, being suboptimal. The adherence to recommendations is not associated to patients true CV risk. Better patient awareness of their CV risk is necessary to improve adherence. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1634
Abstract 2695: Osteopontin regulated epithelial-mesenchymal transition via PI3K/AKT signaling pathway in hepatocellular carcinoma.
Authors: Qiongzhu Dong, Xu-Chao Zhu, Chun Dai, Xiao-Fei Zhang, Hu-Liang Jia, Qing-Hai Ye, Lun-Xiu Qin
Journal: Cancer Research (2013)

Abstract Our previous studies demonstrated that osteopontin (OPN) plays a crucial role in hepatocellular carcinoma (HCC) metastasis. However, its function in epithelial-mesenchymal transition (EMT) remains obscure. In this study, we reported the critical role of OPN in EMT mediated HCC metastasis. Increased expression of OPN in human HCC predicts poor survival and disease recurrence after surgery. HCC tumors overexpressing OPN were featured by active EMT and motility/invasion of tumor cells both in vitro and in vivo, whereas silencing OPN expression attenuated EMT. OPN overexpression enhanced twist through activation of Akt, a critical EMT regulation of transcription factor. Suppression of the PI3K-AKT-Twist pathway interfered with OPN-mediated EMT and invasion. Consistently, we have observed a significant correlation between OPN expression and twist levels in a cohort of HCC patients, and found that combination of these two parameters is a more powerful predictor of poor prognosis. Conclusions: OPN plays a pivotal role in EMT mediated HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target. Citation Format: Qiongzhu Dong, Xu-Chao Zhu, Chun Dai, Xiao-Fei Zhang, Hu-Liang Jia, Qing-Hai Ye, Lun-Xiu Qin. Osteopontin regulated epithelial-mesenchymal transition via PI3K/AKT signaling pathway in hepatocellular carcinoma. [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 2695. doi:10.1158/1538-7445.AM2013-2695
AB1073 Analysis of survival and causes of death of patients with gout:
Authors: M.S. Eliseev, I.S. Denisov, V.G. Barskova, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gout - an independent risk factor of overall mortality and mortality from cardiovascular disease, serum uric acid levels have almost no effect on the risk of mortality [1]. <h3>Objectives</h3> To analyze survival and causes of death in patients with gout. <h3>Methods</h3> The study included 305 patients with cristal-verified gout. Patients (pts)were observed in the <i>Research Institute of Rheumatology</i> from 2002 to 2011, 38 patients (12.5%) were not available. Mean age at the beginning of the observation was 51,5±11,4, the monitoring period was 6,1±1,4 years or 1629 person-years. The examination included assessment of the indicators anthropometry, biochemical analysis (lipid and carbohydrate metabolism, renal function, uric acid, hs-CRP), diagnosis of comorbid diseases and metabolic syndrome (MS) (ATP III criteria). Survival was calculated using the Kaplan-Meier method, the odds ratio of death for metabolic syndrome (MS) and its components, chronic kidney disease (CKD), ischemic heart disease (IHD), chronic heart failure (CHF). <h3>Results</h3> Survivalof ptswas 95%in 3 years, 93%in 5 years,85% in 7 years from the beginning of the observation. 34 pts died (12.7%). The causes of death in pts were cardiovascular complications (22 pts(65%)), cancer pathology (7 pts(20%)), renal failure (2 pts (6%)), accident (2 pts (6%)), infection (1 patient (3%)). The odds ratio (OR) of death in patients with gout from any cause and cardiovascular accidents, was highfor IHD, CHF, CKD,MS and some of its components (table). In addition, 34 pts, who died during follow-up, showed highermedian serum hs-CRP: 20.8 [13.6-33.5] mg/l vs 12.5 [5.8-19.0] mg/l (p=0.0041) in the remaining 233 patients, while uric acid and lipid metabolism parameters were comparable. <h3>Conclusions</h3> The survival of pts with gout in thelast 7 years of the follow up was 85% and 2/3of those deaths were the complications of cardiovascular diseases. In addition to ischemic heart disease,chronic heart failureand chronic kidney disease, metabolic syndrome and some of its components (rise in blood pressure, hyperglycemia and low HDL-C) are associated with a high chance of total and cardiovascular death in pts with gout. Another adverse factor can be increased hs-CRP. <h3>References</h3> Kuo C.F., Yu K.H., See L.C., at al. Elevated risk of mortality among gout patients: a comparison with the national population in Taiwan. Joint Bone Spine. 2011 Dec; 78(6): 577-80. <h3>Disclosure of Interest</h3> None Declared
SAT0200 Clinical Application of the Soluble Lectin-Like Oxidized LDL Receptor-1 (SLOX-1) in Rheumatoid Arthritis: from Bench to Bedside
Authors: M. Ishikawa, H. Ito, M. Furu, M. Hashimoto, T. Fuji, S. Matsuda, T. Mimori
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Previously, we have reported that levels of sLOX-1 (soluble Lectin-like oxidized LDL receptor 1) in the plasma of RA patients were significantly higher than those in healthy controls, and the anti-cytokine therapies decreased the sLOX-1 level in plasma. <h3>Objectives</h3> Then, we investigated whether sLOX-1 levels are associated with RA disease activity or remission using a cohort study <h3>Methods</h3> The study examined 278 RA patients (female 84.9%) in the cohort. Levels of sLOX-1 in plasma were measured by ELISA. To evaluate the correlation with sLOX-1, VAS, CRP, ESR, MMP-3, autoantibody status, the number of swollen and tender joints, DAS-ESR, SDAI, and Boolean-based remission were measured in all patients. <h3>Results</h3> The levels of sLOX-1 in RF-positive or ACPA-positive RA were significantly higher than that in RF-negative or ACPA-negative RA. Levels of sLOX-1 in the patients with remission significantly lower than those with moderate disease activity. In the subgroup of patients who were not achieving Boolean-based remission, sLOX-1 level in RF-positive or ACPA-positive RA were significantly higher than that in RF-negative or ACPA-negative RA. In contrast, in the subgroup of patients who were achieving Boolean-based remission, the levels of sLOX-1 in ACPA-positive RA were not significantly higher than that in ACPA-negative RA. <h3>Conclusions</h3> These results suggest that the levels of sLOX-1 in the patients who are not achieving remission, especially ACPA-positive RA, increase to reflect disease activity. Therefore, sLOX-1 levels may be useful to evaluate the therapeutic effects of the anti-cytokine therapies. <h3>References</h3> Sawarura T, et al. Nature 1997; 386 Nakagawa T, et al. Arthritis Rheum 2002; 46, 2486-94. Kakimuma T, et al. Arthritis Rheum 2004; 50, 3495-503. Ishikawa M, et al. Arthritis Rheum 2012; 64, 1024-34. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2628
Reply to Curcio et al.
Authors: Byung Kim, Jung Lee
Journal: Endoscopy (2013)

We appreciate the interest of Curcio et al. in our recent case series “Rescue endoscopic bleeding control for nonvariceal upper gastrointestinal hemorrhage using clipping and detachable snaring” [1]. Curcio et al. reported a case of refractory gastric ulcer bleeding treated with the endoloop/clips technique [2]. They applied clipping and detachable snaring (CDS) in a case of rebleeding that occurred 1 week after primary hemostasis with endoclip placement. The patient was pregnant and receiving extracorporeal membrane oxygenation treatment. Curcio et al. suggested that the endoscopic method with CDS would be helpful not only as the rescue bleeding control method but also as a useful first-line hemostatic method. We agree that the CDS method may be considered as first-line therapy when the endoscopist is limited in their use of standard hemostatic treatments and also in cases where there is a high probability of rebleeding. In our article, primary failure of endoscopic hemostasis was defined as uncontrolled bleeding despite attempts at control using all available endoscopic hemostatic methods except for the detachable snare. We performed successful CDS hemostatic treatment in three cases in which first-line hemostatic therapy had failed. Therefore, we consider that the CDS method would be feasible and useful as an endoscopic hemostatic method used as first-line therapy. In our study, rescue endoscopic hemostasis was defined as bleeding control treatment following failure of first-line therapy, and in cases of rebleeding second-line therapy was applied. Although our study was prospective in design, the CDS method is an unproven treatment modality that lacks scientific evidence, which is why we applied it only as the rescue therapy in the first instance. Large randomized controlled trials are required to determine the value of the CDS method.
Salmonellosis Associated with Marijuana
Authors: David N. Taylor, I. Kaye Wachsmuth, Yung-hui Shangkuan, Emmett V. Schmidt, Timothy J. Barrett, Janice S. Schrader, Charlene S. Scherach, Harry B. McGee, Roger A. Feldman, Don J. Brenner
Journal: New England Journal of Medicine (1982)

In January and February of 1981, 85 cases of enteritis caused by Salmonella muenchen were reported from Ohio, Michigan, Georgia, and Alabama. Initial investigation failed to implicate a food source as a common vehicle, but in Michigan 76 per cent of the patients, in contrast to 21 per cent of the control subjects, admitted personal or household exposure to marijuana (P less than 0.001, relative risk = 20). Marijuana samples obtained from patients' households contained as many as 10(7) S. muenchen per gram. The outbreak-related isolates of S. muenchen were sensitive to all antibiotics and were phenotypically indistinguishable from other S. muenchen. Plasmid fingerprinting, however, revealed that all isolates related to marijuana exposure contained two low-molecular-weight plasmids (3.1 and 7.4 megadaltons), which were absent in control strains. Plasmid analysis of the isolates showed that the outbreaks in Ohio, Michigan, Georgia, and Alabama were related, and analysis of isolates submitted from various other states demonstrated that cases associated with marijuana may have been dispersed as far as California and Massachusetts.
PRESSURE-OVERLOAD INDUCED LV HYPERTROPHY AND DYSFUNCTION: CRITICAL ROLES OF CAMKII AND P38 MAP KINASE IN ER STRESS SIGNALING PATHWAY
Authors: Xing Chen, Guangming Cheng, Shiming Liu, Sheng Ye, Lin Zhao, Anweshan Samanta, Anja Browning, Robert Vincent, Yanjuan Yang, Jeryl Hauptman, Buddhadeb Dawn
Journal: Journal of the American College of Cardiology (2016)
Abstract 4984: Association of <i>PTEN</i> and <i>p16</i> mutational status with <i>MITF</i> expression may provide a novel context for a phenotype switch in melanoma
Authors: Bradford R. Brooks, Holly Yin, Donald Chow, Chris Sereduk, Julie Koeman, Chaonan Qian, Jeffrey P. MacKeigan, Sungwon Jung, Seungchan Kim, Mai Xu, Ashani Weeraratna, Kevin M. Brown, Jeffrey Trent
Journal: Cancer Research (2011)

Abstract For the last decade, array-based genomic screening has significantly advanced our understanding of genes involved in cancer development and progression. Moreover, genes identified in those screenings have subsequently been the focus of drug development efforts, ultimately leading to clinical trials. However, the efficient translation of cancer genomics results into the development of more effective therapeutics has been limited in part by the need for robust, high-throughput, functional validation of genes and pathways of interest in well-defined model systems. In order to identify new therapeutic targets in melanoma genomes, we have applied high-throughput RNA interference (RNAi) screening to well-characterized melanoma cell lines. We characterized a panel of 65 melanoma cell lines for genome-wide copy number changes and gene expression, as well as the mutation status of known melanoma genes (BRAF, HRAS, NRAS, KRAS, PTEN, CDKN2A, and TP53). From this panel, 18 cell lines were screened against some 1,250 genes (696 kinases, 550 supplemental; 4 siRNAs per gene) to identify modifiers of melanoma cell survival. A striking finding from our data is that MITF expression appears to be a determinant of invasive context and, furthermore, is associated with changes in both p16 and PTEN status. In the cell lines we examined, high MITF expression correlated with wild-type PTEN status, whereas PTEN was deleted or mutated in 30-35% of cell lines having low MITF expression. Similarly, p16 was unaltered in 40-45% of the cell lines that had high MITF expression but remained unaltered in only 20-25% of low MITF-expressing cell lines. The loss of p16 and PTEN are correlated with an aggressive phenotype in melanoma, and we confirmed by Western analysis that in cell lines with high MITF, p16 is present, but in cell lines with low MITF, p16 expression is absent. In agreement with the current literature, no association could be found with BRAF mutational status. Moreover, these data confirm that MITF is associated with the switch in phenotype from a proliferative to an invasive state in melanoma in a BRAF-independent manner, which in turn is associated with an increase in WNT5A expression, a change we previously have suggested is a critical determinant of melanoma metastasis. Results to be presented, aligned with new studies of sequence variants of MITF (Brown et al., unpublished), may help define a novel context for invasive potential of the important 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 4984. doi:10.1158/1538-7445.AM2011-4984
AB0675 First episode of chronic anterior uveitis in patients with juvenile idiopathic arthritis and relationship with administered treatments
Authors: A. L. Boteanu, M. A. Blazquez Cañamero, C. Velazquez Arce, C. Guillen Astete, M. L. Gamir Gamir
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chronic anterior uveitis is one of the most serious complications of juvenile idiopathic arthritis (JIA), showing an increased incidence in patients with early-onset disease, oligoarticualar, positive ANA. Biologic therapy used in the handling of JIA in the last years has greatly improved the articular prognosis; however their effectiveness in handling uveitis is still not well established, having reported new cases of uveitis during treatment with anti -TNF, especially during treatment with etanercept (ETN). <h3>Objectives</h3> The aim of this work is to report the incidence of new cases of chronic anterior uveitis in patients who were treated with methotrexate (MTX), adalimumab (ADM) or Etanercept (ETN) for JIA. <h3>Methods</h3> We performed a retrospective observational study of 70 patients with diagnosis of early-onset JIA with high risk of developing chronic anterior uveitis. There were recorded the new episodes of uveitis per patient. Incidence was calculated as the number of new episodes per 100 patients per year of follow-up according to the ILAR category and treatment and based exclusively on the treatment. Comparisons were made using T Student test. <h3>Results</h3> Fifty-six (80.0%) patients were female and 14 (20.0%) males. The categories ILAR were: 42 (60.0%) Oligoarticular, 10 (14.3%) extended Oligoarticular, 15 (21.4%) poliarticular and 3 (4.3%) associated with psoriasis. The average age at diagnosis was 3.5 SD 1.6 years (median 3 years). ANA positive were found in 41 (58.6%) patients. The mean follow-up of patients was 4.44 SD 3.65 years. There were 5 new cases of uveitis during treatment (3 MTX, 2 MTX-ETN or ETN and 0 with ADM only) and 10 cases presented to debut or before starting DMARDs or biologic therapy. The incidence was 0.15 and 0.14 cases per 100 patient / year, respectively (p&gt; 0.05, t Student test). <h3>Conclusions</h3> The incidence of occurrence of uveitis in our series of JIA patients at high risk of uveitis is comparable to that described in the literature (22.8%) and similar between patients who received MTX as monotherapy and those who received MTX and ETN or ETN. We reported no new cases of uveitis in patients treated with ADM, although in 85% of cases ADA was recommended in patients diagnosed with uveitis, with studies that have shown that it is more effective than treating this complication with ETN. The number of cases that occurred during treatment with ETN in our series of cases is too small to infer a causal relationship, the stratification by immunological profile, time of disease, age or baseline severity of thesymptomscould influence the development of this complication. Prospective comparative studies of biological and non-biological DMARDs are needed to assess the increase or decrease in the risk of uveitis associated with JIA. <h3>Disclosure of Interest</h3> None Declared
Hodgkin's Disease and Epstein-Barr Virus
Authors: N Mueller, A Evans, N L Harris, G W Comstock, E Jellum, K Magnus, N Orentreich, B F Polk, J Vogelman
Journal: New England Journal of Medicine (1989)

In patients with Hodgkin's disease, titers of IgG antibody against viral capsid antigen of Epstein-Barr virus and the prevalence of antibodies against early antigen are higher than expected. To evaluate whether this condition antedates diagnosis, we identified 43 persons with Hodgkin's disease, from whom blood had been drawn and stored for an average of 50.5 months before diagnosis, and 96 controls from the same populations, from whom blood had been drawn at the same time. The relative risks of Hodgkin's disease associated with elevated levels of IgG and IgA antibodies against capsid antigen were 2.6 (90 percent confidence interval, 1.1 to 6.1) and 3.7 (1.4 to 9.3), respectively. For Epstein-Barr nuclear antigen, the relative risk was 4.0 (1.4 to 11.4), and for early antigen D it was 2.6 (1.1 to 6.1). However, the prevalence of IgM antibody against capsid antigen was substantially lower in patients with Hodgkin's disease (0.22 [0.04 to 1.3]). These associations were stronger in serum samples obtained at least three years before diagnosis than in serum samples obtained closer to diagnosis. We conclude that the development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein-Barr virus. Whether Epstein-Barr virus has a direct role in the pathogenesis of the disease or is simply a marker for a more fundamental factor affecting the immune control of latent infections is unknown.