tbuckley/cabot-search huggingface dataset:
AB0657 25 hydroxy D vitamin status in patients with primary sjÖgren’s disease
Authors: E. Kiss, A. Bazso, J. Meszaros, E. Nagy, G. Lelkes, G. Poor
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Primary Sjogren's syndrome (pSS) is characterised by diminished exocine glandular functions caused by autoimmune epithelitis due to dysregulated immune response. Low vitamin D level might be one of its etiologic factors. <h3>Objectives</h3> The aim of this cross-sectional study was to evaluate 25 hydroxy D vitamin status in a cohort of Hungarian patients with pSS. <h3>Methods</h3> European-American consensus criteria were used to identify pSS patients. 25-hydroxyvitamin D (25OH D) was measured by a direct competitive chemiluminescent immunoassay. Anti-SS-A, anti-SS-B and rheumatoid factor (RF) were assessed with routine laboratory methods. Appropriate statistical tests were used to analyse association between 25OH D level and clinical as well as laboratory parameters. <h3>Results</h3> The mean ages of the 54 pSS female patients was 58.6±13.92 years. Anti- SS-A, anti-SS-B and RF was present in 33, 26 and 17 patients. Arthritis, vasculitis, CNS or PNS manifestations and autoimmune thyreoiditis occurred in 37, 10, 8, 14 and 17 patients, respectively. The concentration of 25OH D (mean±SD) was 76.86±42.6 nmol/L. As much as 35.19% were vitamin D insufficient and 16.66% deficient. These groups were definied based on 25OH D concentration between 37.5 and 75L or &lt;37.5 nmol/L. There was a weak but significant correlation between vitaminD concentration and the age of patients (p=0.026, r=-0.303, Spearman correlation), but no correlation was found with other laboratory parameters. Chi2 test revealed association between vitamin D level groups and the presence of RF (p=0.047) as well as autoimmune thyreoiditis (p=0.009). <h3>Conclusions</h3> Reduced vitamin D level might contribute to the pathogenesis of primary Sjogren's disease, but until now only a few data are available. Further prospective studies are required in larger cohort of patients in comparison with other autoimmune diseases and healthy population. <h3>References</h3> CantornaMT: Vitamin D and autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence? Proc Soc Exp Biol Med 2000;223:230-3. Cutolo M: Vitamin D and autoimmune rheumatic diseases. Rheumatology (Oxford) 2009; 48: 210-212. Borba VZ, Vieira JGH, Kasamatsu T, et al. Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporosis 2009; 3: 427-433. Szodoray P, Tarr T, Bazso A, et al: The immunopathological role of vitamin D in patients with SLE: data from a single centre registry in Hungary. Scand J Rheumatol. 2011 Mar;40(2):122-6. Amital H, Szekanecz Z, Szücs G, et al: Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis. 2010 Jun;69(6):1155-7. <h3>Disclosure of Interest</h3> None Declared
P3-01-16: Expression of Basal Markers in Correlation with PTEN and BRCA 1 in Triple Negative Breast Carcinomas (TN) Treated with Chemotherapy Versus PARP Inhibitors.
Authors: M Chivukula, G Carter, S Puhalla
Journal: Cancer Research (2011)

Abstract The link between the BRCA1 tumour-suppressor gene and hereditary breast and ovarian cancer is established. The morphologic and immunohistochemical features of basal like phenotype carcinomas have shown to be correlated with the BRCA 1 expression. PTEN (phosphatase and Tensin Homolog) is a novel tumour suppressor gene located on chromosome 10. PTEN mutations are believed to exert their effects through the putative PI3K-AKT-mTOR signaling pathway. Lack of PTEN expression, suggests that PARP inhibitors may be therapeutically useful for a subset of invasive breast cancers. The data on PTEN status in breast carcinomas is emerging. The aim of our study is to assess the immunohistochemical expression of basal markers, PTEN and BRCA 1 in a subset of triple negative breast carcinomas with known BRCA status. Results: Results are shown in Table 1. Conclusions: 1. Initial results from our study indicate high expression of PTEN is seen in TN breast carcinomas. 2. There appears to be decreased BRCA 1 protein expression in TN patients who tested positive for BRCA mutations. 3. Given the loss of PTEN in a subset of TN Chemo group, PARP inhibitors may be suggested to be therapeutically useful and needs to be evaluated further. 4. The lack of CK 5 basal keratin in some patients needs to be addressed further. The study is on going with addition of new cases. The updated data and preliminary data with patient responses on PARP inhibitor will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-16.
Abstract 3106: Collagen-mediated chromatin remodeling promotes chemoresistance in pancreatic cancer
Authors: Surabhi Y. Dangi-Garimella, Hidayatullah G. Munshi
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer-related deaths in the US, is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. We have previously shown that PDAC cells grown in the collagen microenvironment are resistant to gemcitabine-induced proliferation- and checkpoint-arrest (Dangi-Garimella et al, Cancer Research 2011). The effects were mediated by ERK1/2-dependent expression of high mobility group A2 (HMGA2), a well-known chromatin remodeling protein. We have now found that relative to cells grown on tissue culture plastic, PDAC cells grown in 3D collagen display increased acetylation of lysines K9 and K27 on histone H3 along with a reduction in the levels of the heterochromatin binding protein HP1-α, suggesting that cells in collagen have a more open chromatin state. Decreasing HMGA2 expression or inhibiting ERK1/2 activity attenuates the effect of collagen on K9 and K27 acetylation. 3D collagen also promotes expression of the histone acetyl transferase (HAT) enzymes PCAF and GCN5 through increased HMGA2 expression and ERK1/2 activation. Additionally, human PDAC tumors display higher histone acetylation near fibrotic regions that also have increased HMGA2 expression. Finally, cells in 3D matrix demonstrate increased H2AX and a reduced tailing with the comet assay following gemcitabine treatment, suggesting that there is increased DNA repair associated with the more open chromatin state when cells are in the 3D collagen microenvironment. Downregulation of HATs along with inhibition of ERK1/2 phosphorylation attenuates gemcitabine-induced H2AX detected in 3D collagen. Overall, our results increase our understanding of how growth in 3D collagen contributes to chemo-resistance and identify potential therapeutic targets against this deadly 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 3106. doi:1538-7445.AM2012-3106
Insulin-Induced Lipohypertrophy
Authors: Stanley Landau
Journal: New England Journal of Medicine (2012)

A 55-year-old man with a 31-year history of type 1 diabetes mellitus presented for a routine clinical evaluation, his first in two decades. His insulin regimen consisted of a combination of neutral protamine Hagedorn (NPH) and rapid-acting insulin. In the many years since his diabetes diagnosis, he had habitually injected insulin into two locations in the periumbilical region. Two discrete subcutaneous masses were palpated. Both masses were firm and pendulous. A clinical diagnosis of insulin-induced lipohypertrophy was made. This condition has been documented with many insulin preparations. Careful attention should be paid to the teaching of correct methods of insulin . . .
Cost Effectiveness of Thrombolytic Therapy with Tissue Plasminogen Activator as Compared with Streptokinase for Acute Myocardial Infarction
Authors: Daniel B. Mark, Mark A. Hlatky, Robert M. Califf, C. David Naylor, Kerry L. Lee, Paul W. Armstrong, Gabriel Barbash, Harvey White, Maarten L. Simoons, Charlotte L. Nelson, Nancy Clapp-Channing, J. David Knight, Frank E. Harrell, John Simes, Eric J. Topol
Journal: New England Journal of Medicine (1995)

Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 11/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective.
Abstract A4: Hodgkin and Reed-Sternberg cells secrete soluble factors to modulate endothelial cell-T cell interactions in classical Hodgkin lymphoma
Authors: Chee Wai Fhu, Siew Meng Chong, Celestial Yap, Anne Graham, Yaw Chyn Lim
Journal: Cancer Research (2011)

Abstract Introduction: Classical Hodgkin lymphoma (CHL) is characterized by the presence of a minority of malignant Hodgkin and Reed-Sternberg cells (H-RS cells) surrounded by an abundant mixed inflammatory infiltrate that includes CD4+ T helper 2 cells, regulatory T cells and CD8+ cytotoxic T cells. The mechanisms exploited by HRS cells to influence T cell recruitment into the involved lymph nodes are still unknown. Objective: The aim of this study is to elucidate whether H-RS cells can induce endothelial cell activation to modulate T cell recruitment in CHL. Procedures: Fresh cell culture supernatant (C/S) from the H-RS cell line, KM-H2, was used to stimulate endothelial cells (EC) in-vitro. Controls were EC incubated in medium alone; or with 10ng/ml TNF-α Up-regulation of adhesion molecule expression was assessed by ELISA and FACS. Using the transwell migration system and the parallel plate flow chamber apparatus respectivel, the ability of these stimulated EC to support T cell interactions in-vitro was assessed under static and defined flow conditions. Signaling pathways involved in C/S induced EC activation were examined by western blotting. Results: KM-H2 C/S-stimulated EC up-regulate ICAM-1, VCAM-1 and E-selectin to levels comparable to those of TNF-α-stimulated EC. Both C/S-stimulated EC and TNF-α stimulated-EC support naïve and memory T-cell interactions under defined flow conditions. Furthermore, both CD4+ naïve and memory T cell demonstrated enhanced transmigration across C/S-stimulated EC monolayers in response to SDF-1α, as compared to TNF-α-stimulated or unstimulated EC. The activation of EC by KM-H2 C/S is dependent on the NFkB pathway. Blocking of p65 nuclear translocation by the specific IκBα phosphorylation inhibitor (BAY11-8075) abrogated the stimulatory effect of C/S on EC. Phosphorylation of ERK, p38 and JNK were also detected in the KM-H2 C/S stimulated EC. Intracytoplasmic expression of TNF-α was detected in KM-H2 cells. The bioactivity assay showed that the TNF-α sensitive cell line, L929 is sensitive to KM-H2 C/S. However, treatment of cells with TNF-α neutralizing antibody did not effectively prevent L929 cell death, nor inhibit the stimulatory effect of KM-H2 C/S on EC. Conclusion: Our data suggest that the malignant Hodgkin and Reed-Sternberg cells secrete soluble mediators that modulate endothelial cell function and influence recruitment of T cells into the cHL lesion. While the C/S induced EC activation is dependent on the NFkB pathway, our data suggest that the dominant mediator involved is not TNF-α. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A4.
IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis
Authors: Katarzyna M. Luda, Thorsten Joeris, Emma K. Persson, Aymeric Rivollier, Mimoza Demiri, Katarzyna M. Sitnik, Lieneke Pool, Jacob B. Holm, Felipe Melo-Gonzalez, Lisa Richter, Bart N. Lambrecht, Karsten Kristiansen, Mark A. Travis, Marcus Svensson-Frej, Knut Kotarsky, William W. Agace
Journal: Immunity (2016)
PROSPECTIVE COMPARISON OF VENTRICULAR FUNCTION BY ECHOCARDIOGRAPHY AND MRI COMPARISON OF NORMAL TO ASYMPTOMATIC SINGLE RIGHT AND SINGLE LEFT VENTRICULAR MORPHOLOGY
Authors: Kristen Sexson, Cory Noel, Peng Chen, Ramkumar Krishnamurthy, Rajesh Krishnamurthy, Feagin Douglas, M. Regina Lantin-Hermoso, Ricardo Pignatelli
Journal: Journal of the American College of Cardiology (2015)
The Differentiation of Parenchymal Liver Disease and Mechanical Biliary Obstruction
Authors: Sherman M. Mellinkoff, Philip A. Tumulty, A. McGeHee Harvey
Journal: New England Journal of Medicine (1952)

IT IS frequently difficult to differentiate on-clinical grounds jaundice due to parenchymal liver disease and that secondary to extrahepatic biliary obstruction. This distinction is obviously essential for proper treatment. In this connection we have found that the determination of the cephalin flocculation, thymol turbidity and serum alkaline phosphatase are most helpful. In an effort to clarify the interpretation of these tests, we have reviewed their employment in the study of 127 jaundiced patients treated at the Johns Hopkins Hospital. In each case the cause of jaundice was clearly established by operation, autopsy or prolonged observation.Cephalin-Flocculation and Thymol-Turbidity TestsAlthough . . .
PTU-263 Is it time for gastroenterology and general medicine to go their separate ways?
Authors: V Sehgal, B Krishnan, G McCulloch, K Besherdas
Journal: Gut (2012)

<h3>Introduction</h3> Currently most gastroenterologists within the UK are general physicians with a specialist interest in gastroenterology (85%) and most gastroenterology (GI) trainees train for dual accreditation in GI and general internal medicine (GIM). They therefore commit a major part of their time to the management of patients with GIM problems as part of their unselected acute medical take and ward work. With the development of “acute medicine” as a specialty in its own right and the formation of specialty-based wards to care for medical in-patients it has been questioned whether gastroenterologists should train to obtain dual accreditation in GI and GIM. The increasing demands for provision of GI services further support the conflict of whether training in GIM is required. With this in mind, we aimed to assess patients admitted with a primary GI complaint that should be triaged to a GI ward, the number of acute (active) non-GI diagnoses requiring acute treatment and whether these were managed by gastroenterology or whether referral to a specialist team was made. <h3>Methods</h3> A single centre, prospective analysis of all patients admitted with a primary GI diagnosis during the unselected general medical take over a 6-week period (November 2011–January 2012) was made. Chase Farm Hospital is a district general hospital that has a clinical decision unit, a short stay ward along with a speciality based ward triage for GIM patients. Data were obtained from medical notes and discharge summaries. <h3>Results</h3> 62 patients (29 male, 33 female), median age 72.5 years were admitted over the study period. 38 patients (61.3%) had no other acute non-GI diagnoses requiring prompt treatment. 24 patients (38.7%) had at least one other non-GI diagnosis (range 1–2): 16 patients (25.8%) had one and eight patients (12.9%) had two active non-GI diagnosis. The most common non-GI diagnosis was cardiovascular in origin (9, 37.5%). Other non-GI diagnoses were respiratory (6, 25%), renal (6, 25%), endocrine (6, 25%), or other (4, 16.6%). Of these patients, 5 (20.8%) required referral to a specialist team for further investigation and/or treatment of their condition. <h3>Conclusion</h3> A significant number of patients (∼39%) admitted as an acute medical emergency with a primary GI diagnosis have other active non-GI medical diagnoses. The majority of these were managed by gastroenterology and only in one in five patients was a specilaist opinion sort for further management. By training and maintaining skills in GIM, gastroenterologists are more able to independently manage acute medical patients admitted with a primary GI diagnosis and avoid inter-specialty referral in up to 25% of patients. From this study we support the dual accreditation sought by gastroenterology trainees in GIM. <h3>Competing interests</h3> None declared.
Abstract 34: Microenvironmental independence or co-option: How tumour-stromal interactions influence prostate cancer lethal outcomes
Authors: David Basanta, Arig Ibrahim Hashim, Robert J. Gillies, Robert A. Gatenby, Gustavo E. Ayala, Simon W. Hayward, Alexander RA Anderson
Journal: Cancer Research (2011)

Abstract The role of the tumour-microenvironment interactions in tumor progression has been the extensively studied in the last few years. Recently, the key role that stromal interactions in both cancer initiation and progression has become an important focus. Both of these interactions, cell-cell and cell-microenvironment, can fundamentally affect the outcome of tumour progression. In prostate cancer this is particularly true, with the tumour microenvironment being an independent predictor of patient prognosis. There are two main lethal outcomes for prostate cancer: (i) early in its genesis the tumour acquires a highly malignant lethal phenotype, growing rapidly and displacing the original stromal population. These less common aggressive tumours are independent of much of the local microenvironment. (ii) the tumour co-opts the local stroma taking on a classic stromagenic phenotype where the local microenvironment facilitates cancer growth. Using an integrated approach we have investigated the influence of tumour stroma interactions in driving these outcomes. With the help of a mathematical model based on evolutionary game theory, we considered three distinct cellular populations: stromal cells, tumour cells that are self-reliant in terms of microenvironmental factors and tumour cells that depend on the environment for resources (such as growth factors, nutrients and space) but can also co-opt stroma. The results from this mathematical model highlight the importance of carcinoma associated fibroblasts in stromagenic outcomes and that the resulting cooperation between certain stromal cells and the tumour could be disrupted as a result of changes in the microenvironment leading to a stromal independent outcome. Subsequently we have employed a biological model using TRAMP mice (TRansgenic Adenocarcinoma of the Mouse Prostate). TRAMP mice develop prostate cancer spontaneously after a few weeks and recapitulate many features of prostate cancer in humans. This mouse model allowed us to investigate the differences between the tumour populations driving the two distinct outcomes as well as the importance of microenvironmental changes in diverting this progression. 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 34. doi:10.1158/1538-7445.AM2011-34
In-111 Octreotide Uptake in the Thymus in a Patient with Cushing’s Syndrome
Authors: PAULO S. DUARTE, HONGMING ZHUANG, MARIA DE LOURDES GUSMÃO, BERNARDO LIBERMAN
Journal: Clinical Nuclear Medicine (2002)

DUARTE, PAULO S. M.D.; ZHUANG, HONGMING M.D., Ph.D.; DE LOURDES GUSMÃO, MARIA M.D.; LIBERMAN, BERNARDO M.D. Author Information
Abstract SY08-01: Large-scale screens for cancer genes in the mouse
Authors: Louise van der Weyden, Alistair Rust, Pedro Perez-Mancera, David Tuveson, Jos Jonkers, Charles Mullighan, Doug Winton, David Adams
Journal: Cancer Research (2012)

Abstract As efforts to sequence thousands of human cancer genomes gain momentum, the challenge of distinguishing driver cancer genes from passengers, and determining how these genes contribute to tumorigenesis remains a major challenge. Many key cancer pathways have been identified from large-scale screens in model organisms due to the fact that most cancer genes are highly conserved, and play roles in a range of critical biological processes. We have been using mouse models of bowel, breast, pancreatic cancer and leukemia, to identify novel candidate cancer genes using approaches including transposon-mediated mutagenesis coupled with high-throughput insertion site sequencing, and next-generation sequencing of mouse tumours. Using these approaches we have not only recovered known cancer genes but also a large number of new candidates, many of which appear to be disrupted in human tumours and represent potential diagnostic and therapeutic targets. I will discuss the results of the screens we have performed and give specific examples of some of the novel cancer genes discovered from this work. 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 SY08-01. doi:1538-7445.AM2012-SY08-01
P165 The reliability and performance of electronic monitors of inhaler use in a real world asthma clinical trial
Authors: M Patel, J Pilcher, D Shaw, M Weatherall, R Beasley
Journal: Thorax (2013)

<h3>Introduction</h3> Electronic monitoring is one method to measure the use of inhaled therapy in asthma patients in clinical trials, though the reliability of these devices has been variable. Implementation of trial quality control processes and reporting on the performance of electronic monitors during patient use may help to better understand their utility and limitations. The Smartinhaler Tracker is an electronic monitor for metered dose inhalers (MDIs) that records the date, time and number of actuations to the nearest second. <h3>Objectives</h3> In a recently completed 24-week real-world randomised controlled trial of 303 asthma patients at risk of severe exacerbations, Smartinhaler Tracker electronic monitors were used to measure actual use of budesonide/formoterol and salbutamol MDI therapy with two treatment regimens. Our aim is to report on the performance of these monitors, based on the implementation of extensive pre-trial and within-trial validation protocols for their use. <h3>Methods</h3> Pre-study use checks involved two actuations of the MDI, with a further two actuations performed at least two hours later. Within-study monitor checks, performed prior to dispensing at follow-up clinic visits, included a computerised check of monitor clock function, actuation accuracy and battery life. Within-study data checks, performed after use of MDIs by participants during the trial, involved computerised checks of monitor clock function prior to data upload. <h3>Results</h3> 2678/2728 (98.2%) monitors passed pre-study use checks; 46/50 monitors failed pre-study checks either because they did not record actuations that were performed, or erroneously recorded extra actuations. 76/2642 (2.9%) monitors dispensed to participants failed within-study monitor checks; 33/76 monitors failed because the battery was not fully charged. 51/2642 (1.9%) monitors failed data upload checks, mostly as a result of fluid immersion during participant use. 93/2642 (3.5%) monitors were lost or thrown away by participants. Complete data was available from 2498/2642 (94.5%) of dispensed monitors and 2498/2549 (98.0%) of returned monitors. <h3>Conclusions</h3> The Smartinhaler Tracker is a reliable monitor for measuring MDI use in a real-world asthma clinical trial. Implementation of extensive monitor and data-checking protocols reduces data loss. The use of validated and reliable electronic monitors is the optimal method to assess patterns of inhaled medication use.