tbuckley/cabot-search huggingface dataset:
P441Defective SR-mitochondria interaction and Ca2+ transfer in aged mouse cardiomyocytes
Authors: C Fernandez-Sanz, M Ruiz-Meana, E Miro-Casas, J Castellano, I Barba, E Nunez, J Vazquez, D Garcia-Dorado
Journal: Cardiovascular Research (2014)

Mitochondrial alterations are critically involved in the increased susceptibility to disease of the aging heart. We investigated the role of sarcoplasmic reticulum (SR)-mitochondria communication in myocardial calcium handling during aging. Methods and results: In subsarcolemmal and interfibrillar mitochondria isolated from old (>20 months) and young (<6 months) mouse hearts no differences in resting respiration through the different complexes were detected, but maximal ADP-stimulated O2 consumption was reduced in aged interfibrillar mitochondria. Accordingly, resting mitochondrial membrane potential in cardiomyocytes and ATP/phosphocreatine in intact myocardium (NMR spectroscopy) were preserved in old mice. Second generation proteomics disclosed an increase in mitochondrial protein oxidation during aging. Since mitochondrial Ca2+ regulates both energy production and oxidative status, we investigated whether aging affects mitochondrial Ca2+ uptake. No age-dependent differences were found in Ca2+ uptake kinetics in isolated mitochondria. By contrast, mitochondrial Ca2+ uptake resulting from SR transfer was significantly reduced in old cardiomyocytes, despite no changes in SR Ca2+ content. Immunocolocalization and proximity ligation assay identified defective communication between mitochondrial VDAC and SR ryanodine receptor (RyR) during aging, with adverse functional consequences on SR (Ca2+ transients and sparks). Age-dependent alterations in SR Ca2+ transfer to mitochondria could be reproduced in young cardiomyoctes after pharmacological disruption of the connection between both organelles, an intervention that had no effect in old cardiomyocytes or isolated mitochondria. Conclusion: Defective SR-mitochondria communication underlies inefficient Ca2+ exchange between both organelles that could be responsible, at least in part, for inadequate energy demand/supply matching in the aging heart.
BLOOD PRESSURE CONTROL AND ADHERENCE IN HYPERTENSIVE PATIENTS FOLLOWED THROUGHOUT A COMPREHENSIVE HYPERTENSION PROGRAM IN A DEVELOPING COUNTRY: INFLUENCE OF CLINICAL, SOCIO-ECONOMIC AND PSYCHOSOCIAL FACTORS
Authors: Daniela Sandoval, Javier Chacón, Ivonne Ahlers, Tomas Romero
Journal: Journal of the American College of Cardiology (2015)
PWE-066 Magnetic resonance enterography for the assessment of Crohn's disease: changing imaging paradigms?
Authors: K A Mcwhirter, J Limdi, R Filobbos
Journal: Gut (2012)

<h3>Introduction</h3> Recent advances in the immunopathogenesis and therapy of inflammatory bowel disease (IBD) coupled with bolder definitions of disease control have led to increasing reliance on imaging. Increased awareness of the potential downstream effects of ionising radiation has placed more emphasis on radiation-free imaging. We aimed to assess the role of magnetic resonance enterography (MRE) in assessing Crohn9s disease. <h3>Methods</h3> We conducted a retrospective review of 141 consecutive MRE studies performed between June 2009 and November 2010. Clinical data were obtained from electronic patient record review. Inflammatory markers, radiological investigations and ileocolonoscopy when performed within 90 days of MR enterography were recorded. MRE reports were recorded using accepted activity criteria- small bowel dilatation, stenosis, wall thickening, enhancement, mucosal irregularity, mesenteric inflammation, hypervascularity, lymph node enlargement, abscesses, fistulation and extraintestinal features. <h3>Results</h3> Of 67 patients with IBD, 60 had Crohn9s disease and 59 examinations were complete. Thirty- nine of 67 patients were female, mean age 34 (range 16–68) and median disease duration of 5 years (range 0–39). Abnormalities were noted in 47 MRE scans; 34 had active non-stricturing, 12 active stricturing and one fibrostenotic disease. Within the active groups, there were four fistulae and three abscesses in four patients. Ileo-colonoscopy was performed in 14 of these patients with 12/14 showing active colitis and raised CRP in 11/16 within 90 days of MRE. Treatment was increased in 47% of the active non-stricturing group, 3/16 to azathioprine, 8/16 to infliximab, 4/16 to surgery with no change to treatment in the remaining 53%, of whom 4/8 had normal ileo-colonoscopy and 13/16 normal CRP. In 83% of active stricturing patient treatment was increased, one to azathioprine, six to biologics, three to surgery. Four of 12 patients in this group had an elevated CRP and 4/7 had active colitis at ileo-colonoscopy. Of 12 normal MRE, treatment was not increased in 92%. Of these, CRP was normal in 10/11 and ileo-colonoscopy normal in 4/7. Treatment was increased in one to biologics, with an elevated CRP and moderately severe colitis at colonoscopy. The fibrostenotic subject had normal CRP and mild colitis at colonoscopy, and proceeded to surgery. All the abscess/fistula subjects had raised inflammatory markers. Two were referred for surgery, one started biologics and one treated with antibiotics. <h3>Conclusion</h3> The small bowel remains difficult to assess endoscopically. MRE adds to the assessment of patients with Crohn9s disease, in addition to endoscopy and biological markers identifying patients with active disease where treatment escalation may result in meaningful benefit. <h3>Competing interests</h3> None declared.
Abstract PD07-06: Basal-Like Molecular Subtype Predicts Response to Neoadjuvant Chemotherapy with Epirubicine, Cyclophosphamide, and Docetaxel in Patients with Primary Breast Cancer
Authors: E Stickeler, M Klar, D Pils, M Orlowska-Volk, A zur Hausen, G Gitsch, C. Tempfer
Journal: Cancer Research (2010)

Abstract Background: Gene expression profiling provides an opportunity to predict response to specific regimens of neo-adjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: In a prospective cohort study of 32 women with primary invasive breast cancer with a measurable lesion, we obtained a tumor specimen by high speed core biopsy before and after 4 cycles of NAC with epirubicine 90mg/m2 and cyclophosphamide 600mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100mg/m2. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Agilent's 44K single color microarray interrogating 44000 unique human genes. Tumor lesions were ultrasonographically measured to assess response using Sinn criteria. Data analysis was performed by GeneSpring v11 and IBM SPSS v18. Results: Using three single sample predictors, 10 tumors were classified as basal-like and 22 tumors were classified as non basal-like. We found that gene expression-based molecular subtype (basal-like vs. non basal-like) (p=0.003), but not tumor grade (p=0.07), estrogen receptor (p=0.1), progesterone receptor (p=0.6), and HER2 status (p=0.4) predicted response to NAC. Specifically, 7/10 basal-like tumors responded to NAC, whereas 19/22 non basal-like tumors did not respond. Comparing gene expression signatures before and after 4 cycles of NAC, we found that all patients with an initial non basal-like tumor retained this tumor type, whereas 5/7 basal-like tumors, including all responders, lost this molecular subtype. Using regression models based on centroid predicition gene sets, complete prediction of response to NAC based on the initial tumor biopsy as well as on the change of gene expression between two tumor biopsies was achieved with a 21 gene list (p=0.000008) and a 23 gene list (p=0.000007), respectively. Of note, both the expression and upregulation of a single gene, ie HER4, predicted response to NAC in 26/32 (81%; p=0.002) and in 23/25 (92%; P&amp;lt;0.001) patients, respectively. Conclusions: Basal-like molecular subtype and therapy-induced HER4 gene upregulation predict response to NAC with epirubicine, cyclophosphamide, and docetaxel. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-06.
THE USE OF A GENE EXPRESSION SCORE WAS ASSOCIATED WITH IMPROVED MEDICAL DECISION MAKING IN THE EVALUATION OF WOMEN PRESENTING WITH SYMPTOMS SUGGESTIVE OF OBSTRUCTIVE CORONARY ARTERY DISEASE: SUMMARY RESULTS FROM TWO AMBULATORY CARE STUDIES IN PRIMARY CARE
Authors: Joseph Ladapo, Lee Herman, Bonnie H. Weiner, Brian Rhees, Lon Castle, John McPherson
Journal: Journal of the American College of Cardiology (2015)
AB0484 Analysis of factors predictive of survival based on 24 patients with systemic granulomatosis with polyangiitis in korea
Authors: Y. J. Kim, B. S. Koo, M.-W. So, W. J. Seo, Y.-G. Kim, C.-K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Granulomatosis with polyangiitis is a systemic necrotizing vasculitis of unknown origin with distinct racial, ethnic risk, and characteristics. <h3>Objectives</h3> Little is known about the features and prognostic factors in Korean patients with granulomatosis with polyangiitis. We retrospectively studied the risk factors predictive of long term survival in systemic granulomatosis with polyangiitis according to the ACR classification criteria<sup>1</sup>. <h3>Methods</h3> Twenty four cases of systemic granulomatosis with polyangiitis, diagnosed at a single tertiary hospital from 1996 to 2011, were identified. Univariate and Kaplan Meier analyses of survival were performed using the clinical, laboratory, and treatment parameters. <h3>Results</h3> The mean age was 48 ± 18 (18-75) years and C-antineutrophil cytoplasm antibodies (ANCA) and/or PR3 antibody were present in 15 of 24 patients (62.5%). Main clinical features were constitutional symptoms (96%) followed by lung (83%), ENT (83%), kidney (46%), nervous system (33%), skin (33%), and GI (21%) involvement. Two prognostic scoring systems, the Five Factor Score (FFS) and Birmingham Vasculitis Activity Score (BVAS) at diagnosis were 0 ± 0.8 (0-3) and 20 ± 9.4 (7-45), respectively. Twenty-three patients were treated with cyclophosphamide (CYC) plus corticosteroids and the outcomes were similar between oral (17/23) and intravenous (6/23) CYC regimen. The mortality rate was 8% during a mean follow-up duration of 3.8 years and was associated with the initial FFS (p = 0.01), BVAS (p = 0.03), vasculitis damage index (p = 0.04), and presence of major organ involvements (P &lt; 0.05) including GI and kidney. <h3>Conclusions</h3> Granulomatosis with polyangiitis is an uncommon, multi-organ disorder that relapses frequently (45%). Refractory cases (17%) need prolonged immunosuppressant. Although the outcome has been significantly improved, it still causes permanent organ damages and chronic disability. <h3>References</h3> The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis &amp; Rheumatism (1990). 33(8), 1101-7 An interdisciplinary approach to the care of patients with Wegener's granulomatosis long-term outcome in 155 patients. Arthritis &amp; Rheumatism (2000). 43(5), 1021–1032. Analysis of factors predictive of survival based on 49 patients with systemic Wegener's granulomatosis and prospective follow-up. Rheumatology, (2001). 492–498. <h3>Disclosure of Interest</h3> None Declared
Abstract P1-10-09: Access to HER2 Testing in Early Stage Breast Cancer (ESBC) in a Single Payor, Public Healthcare System — Ontario (ON), Canada
Authors: IL Ferrusi, M Trudeau, C Earle, NB Leighl, E Pullenayegum, P Cascagnette, DA. Marshall
Journal: Cancer Research (2010)

Abstract Background: In ON, testing for HER2 overexpression in ESBC was approved, along with trastuzumab (T) treatment with chemotherapy for HER2 positive (IHC = 3 or FISH ≥2.0) tumors in 2005. Guidelines for testing and treatment must be met for provincial T reimbursement. To study adherence to HER2 testing and T utilization guidelines in ESBC, we first describe patient access to HER2 testing by age, tumor, stage, urbanicity and income. Methods: A population-based retrospective cohort of ESBC patients diagnosed in 2006 and 2007 was identified using the Ontario Cancer Registry and for whom ≥1 pathology report was available from Cancer Care Ontario (CCO). All BC-related pathology reports were individually reviewed to identify early stage, resected, primary BC. Information was collected on surgical procedure, TN stage, histologic grade, receptor status (ER/PR) and HER2 test provision. Linkage to other administrative databases provided income quintile, urban vs. rural residence and institution of diagnosis. Odds ratios were calculated to determine association of HER2 testing with any pathologic or socioeconomic factors. Results: The 2-year cohort contains 13,430 ESBC patients, 60% of which had breast conserving surgery. 29,746 (2.2/patient) pathology reports were reviewed. 13% of the cohort had rural residences, and 95% were alive at end of follow-up. Age at diagnosis was distributed as: 5% &amp;lt; 40 years, 18% 40-49 years, 25% 50-59 years, 24% 60- 69 years, 18% 70-79 years and 10% ≥80 years. Stage at diagnosis was: 35% stage I, 32% stage II, 10% stage III and 22% stage unknown after removing all stage IV. No differences in HER2 testing were observed for patients across income quintiles (P&amp;gt;0.3550). Patients ≥80 years (P&amp;lt;0.0001) and &amp;lt;40 years (p=0.0074) had significantly lower odds of receiving ≥1 HER2 test than patients 40-49 years. ESBC of higher histologic grade had significantly greater odds (P&amp;lt;0.0001) of ≥1 HER2 test compared to grade I ESBC. Patients from rural areas had lower odds of HER2 testing compared to urban patients (P&amp;lt;0.0001). Conclusions: For the 2 years 2006-2007: 13,430 ESBC patients were identified from the OCR for which ≥1 pathology report was available from CCO. Age, stage at diagnosis, and surgical procedure were representative of an ESBC population. HER2 testing was universally available per Ontario policy, but not all reports were submitted to CCO. The odds of having a documented HER2 test were not affected by income, but testing was more likely to be documented for high grade tumours and less likely to be documented for the youngest and oldest women and those with rural residence. Pathology reports missing from CCO are being sought. Adherence to guidelines for testing, treatment with T and cardiac monitoring during treatment will be assessed. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-09.
THU0227 Early Rheumatoid Arthritis is Associated with Periarticular Demineralisation of the Metcarpal Bones
Authors: A. Pfeil, H.E. Langer, L. Reinhardt, A. Langer, S.G. Werner, J. Boettcher, P. Oelzner, G. Wolf
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Digital X-ray radiogrammetry (DXR) is an established computer-based technique for the quantification of periarticular hand bone mineral density at the metacarpal bones. Metacarpal bone mineral density function as a surrogate marker of radiological progression. <h3>Objectives</h3> The aim of this study was to evaluate cortical hand bone mineral density at the metacarpal bones in patients with early rheumatoid arthritis (ERA) at the time point of diagnosis and follow up at 12 months. <h3>Methods</h3> The study included 170 patients with ERA (duration of symptoms 9.9±7.8 months). The prognosis of ERA was stratified by the Visser Score. Based on the Visser Score four risk groups concerning the development of erosion were defined: low risk (&lt;25%), moderate risk (25-50%), high risk (50-75%) and very high risk (&gt;75%). Additional the therapeutic modalities were adapted at the risk groups (low risk: NSAR, moderate risk: corticosteroids, high risk: conventional DMARD, very risk: biologic DMARD). X-rays of the hand were acquired at baseline and after 12 months. Metacarpal Bone Mineral Density (DXR-BMD), Metacarpal Index (DXR-MCI), Cortical Index (DXR-CT) and Metacarpal Bone Width (DXR-W) was measured by DXR (Version 2, Sectra, Sweden). The T-Score as an age and gender independent parameter of DXR-BMD was calculated to compare DXR-BMD in ERA to DXR-BMD in healthy subjects. <h3>Results</h3> At baseline in all 170 patients the T-Score (-0.591 SD) of DXR-BMD was significantly reduced. No change of DXR-BMD (-0.9%; p = not significant) from 0.548 g/cm<sup>2</sup>(baseline) to 0.543 g/cm<sup>2</sup> (month 12) was revealed. A minimal reduction from 0.176 cm (baseline) to 0.174 (month 12) was verified for DXR-CT (-1.1%; p = not significant). No change was observed for DXR-MCI. <h3>Conclusions</h3> Patients with ERA present at the time point of diagnosis a reduced periarticular mineralisation of the metacarpal bones as quantified by the T-Score. With a risk stratified treatment in ERA no change of metacarpal bone mineral density was observed by DXR. The results highlights the usefulness of the DXR-parameters as radiological surrogate marker in ERA. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3678
P16.01 * MAGNETIC RESONANCE SPECTROSCOPY AT 3 T FOR IN VIVO DETECTION OF 2-HYDROXYGLUTARATE IN LOWER GRADE GLIOMAS
Authors: E. Anghileri, N. Bertolino, V. Cuccarini, I. Zucca, G. Finocchiaro, M. Bruzzone
Journal: Neuro-Oncology (2014)

Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are detected in up to 75% grade II-III (lower grade) gliomas. IDH1/2 mutations result in the neomorphic synthesis of the oncometabolite 2-hydroxyglutarate (2HG). The detection of 2HG could help for a non-invasive diagnosis, the clinical follow-up, and possibly the screening of patients for targeted, anti IDH1-mutated therapy. 2HG screening is a useful marker to detect the presence of IDH1/2 mutations. A magnetic resonance spectroscopy (MRS) study of 2HG on phantoms has been already performed by our group. AIM: To investigate methods for in vivo detection by MRS of 2HG on glioma patients. METHODS: Spectra from 12 patients with lower grade gliomas were acquired with a 1H-MRS single-voxel PRESS sequence with TE = 30 ms. The subsequent patients were acquired using a tailored PRESS sequence with TE = 97 ms (TE1 = 32 ms, TE2 = 65 ms). Both groups were studied using a clinical MR 3T scanner (Philips Achieva) with a 32 channel head coil. The MR protocol included two MRS acquisition for each subject: a voxel within the tumor and one contralateral. The voxel size was 2x1.5x1.5 cm3 for all the acquisitions for both sequences. Metabolite concentrations were estimated by linear combination analysis and a simulated basis set using LCModel software (version 6.3). After histopathological diagnosis IDH1/2 analysis were performed by immunochemistry and/or PCR. Results from 1H-MRS and immunochemistry or PCR were compared. RESULTS: Our data showed that spectra at TE = 30 ms are not specific: 4 patient carrying wild type gliomas and 8 carrying IDH mutated gliomas resulted in 2 false positive and 5 false negative respectively. The sequence at 97 ms resulted more specific: 4 patient carrying wild type glioma and 2 carrying IDH mutated glioma were correctly identified (0 false positive and 0 false negative, respectively). Moreover the sequence with short TE detected 2HG in the contralateral region in 5 cases, while the sequence with longer TE did not dectect 2HG in contralateral region. DISCUSSION: Our preliminary data suggest that MRS TE =97 ms is specific for 2HG detection. A larger number of samples will be required to confirm the accuracy of the technique.We will also pair the ex vivo detection by MRS with 2HG quantification by HPLC on tumoral samples and other biological fluids.
PLASMA LEVELS OF NITRIC OXIDE METABOLITES ARE LOWER IN HFPEF SUBJECTS COMPARED TO HFREF AND HYPERTENSIVES
Authors: Lien Trieu, Payman Zamani, Paschalis-Thomas Doulias, Deepa Rawat, Prithvi Shiva Kumar, Rushik Bhuva, Neetha Vadde, Anjaneyulu Dunde, Haideliza Soto-Calderon, Ali Tariq, Ali Javaheri, Philip Haines, Harry Ischiropoulos, Scott Akers, Julio Chirinos Medina
Journal: Journal of the American College of Cardiology (2015)
Abstract 5285: miRNA expression pattern for predicting prognosis of ovarian serous carcinoma.
Authors: Shiying Cui, Xinchen Zhang, Xiaotang Yu, Yanfang Ding, Jinyao Zhao, Henan Zhao, Chang Wang
Journal: Cancer Research (2013)

Abstract Objective: One of the best prognosis predictors for patients with epithelial ovarian cancer is clinic pathological stage at diagnosis. The goal of this study is to develop and validate a gene expression profile that can predict prognosis to ovarian serous carcinoma (OSC) at early and advanced stages. Methods/materials: To identify a unique miRNAs pattern that involved in the progression of OSC at earlier and later stages, miRNA microarray was performed by using 38 China tumor-bank specimens with OSC at stage I and III in a retrospective analysis. The expression of dysregulated miRNAs were validated using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in external cohort OSC at stage I and stage III. Kaplan-Meier analysis was further performed to analysis the correlation between the expression of key microRNAs and prognosis. Results: Of the 768 miRNAs analyzed from microarray, 26 miRNAs were significantly either up or down-regulated with 2 fold difference at least in OSC at stage I compared to III. qRT-PCR results confirmed that 19 miRNAs were significantly down-regulated and 7 was up-regulated in OSC at stage III compared to stage I, which is consistent with the results of microarray. Downregulation of 5 miRNAs was significantly associated with poor disease-specific survival (P&amp;lt;0.05). The patient survival rate of miRNAs high-expression group was 77.8% higher than the low-expression group 33.3%. The different expression patterns of key miRNAs in OSC at stage I versus III were further validated by in situ hybridization. Conclusions: Our results suggest that miRNA plays an important role in the progression of OSC and 5 miRNAs may be considered as the novel candidates of clinic biomarkers for predicting OSC outcome. Citation Format: Shiying Cui, Xinchen Zhang, Xiaotang Yu, Yanfang Ding, Jinyao Zhao, Henan Zhao, Chang Wang. miRNA expression pattern for predicting prognosis of ovarian serous 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 5285. doi:10.1158/1538-7445.AM2013-5285
PWE-158 Thymosin Beta 4 as a Putative Marker in Neuroendocrine Tumours
Authors: D Mandair, D Marotta, J Ho, M Waugh, R Srirajaskanthan, G Woffendin, M Caplin, J Hsuan, N Beaumont
Journal: Gut (2013)

Introduction Neuroendocrine tumours (NETS) arise from the diffuse endocrine system which produce biogenic amines and peptides that could be potential biomarkers. We previously analysed proteomes secreted by NET cell lines and identified mac2BP as putative marker which was also elevated in patients compared to healthy controls Methods 3 Cell Lines BON-1, NCI-H727, and SHP-77 cells were grown in serum-free media overnight, which was then fractionated and the secreted 3–10kDa polypeptides were identified using Tandem Mass spectrometry. One of the small proteins, Thymosin β4 was measured in serum samples of patients and controls using ELISA. Mac2BP & chromogranin A was also measured Results 70 proteins were secreted by all three lines, including 20 small proteins of which 3 were thymosins α1, β4 & β10. Serum samples were analysed in 34 patients and 24 healthy controls. Thymosin β4 was elevated in the serum of NET patients compared with healthy controls (p < 0.002). The area under the curve was 0.84 following ROC analysis. Conclusion Mass spectrometry of the secretomes of 3 NET cell lines offers a novel way of identifying potential biomarkers. Thymosin β4 could be such a biomarker but further examination of tissue and other cell lines is necessary. A further analysis of serum from larger groups of patients both pre and post therapy is needed. Disclosure of Interest None Declared.