tbuckley/cabot-search huggingface dataset:
SAT0176 Arthritis Might BE Useful in the Future to Select High Risk Patients for Systemic Inflammation and More Severe Disease- A Low Field MRI Study in Systemic Sclerosis
Authors: B.N. Stamenkovic, A.M. Stankovic, J.M. Nedovic, S.K. Stojanovic, D.B. Djordjevic, V. Zivkovic, S. Milenkovic
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Joint involvement is frequent finding and correlate with poor life quality in systemic sclerosis (SSc). MRI is a useful method for detection and quantification of inflammatory lesions of the hand (bone oedema, erosions, synovitis, tenosynovitis) in SSc patients. <h3>Objectives</h3> In order to clarify the reported association between joint involvement (synovitis, tendon friction rubs, joint contracture) and clinical and/or laboratory features, it was decided to evaluate a group of pts with SSc. <h3>Methods</h3> A total of 82 SSc pts (mean age 54y) were included in a study. All the patients were investigated for clinical and serological subset, disease duration, vascular, skin, joint, tendon, muscle, oesophagogastrointestinal, heart, lung and kidney involvement, diseaseactivity and HAQ-DI Index. MRI (contrast enhanced) low field MRI of the wrist the 2nd-5th metacarpophalangeal joints of the dominant hand were obtained. MRI were scored by 2 independent, blinded readers using the OMERACT RA scoring system for assessment bone marrow oedema, synovitis, bone erosions and tenosynovitis.Data were statistically analysed using Chi-square and the Students T test. A univariate step-wise logistic regression analysis was also performed for all variables identified with p&lt;0,01. p&lt;0,05 was considered statistically significant <h3>Results</h3> Of 82 SSc pts 17,1% had clinical arthritis (14/82). Inflammatory MR findings with synovitis we found in 64/82 (78%)pts, MRI erosions in 52 (62,4%) or tenosynovitis in 11/82 (14,1%). Synovitis was more frequently detected on MRI (78%) than clinically (17,1%, p&lt;0,001.We found that clinical arthritis of the hand was associated with joint contracture (probability for the occurrence of joint contractures was higher for the SSc pts with clinical arthritis- OR=4.64;95%CI 1,37-15,64; p&lt;0,01), with HAQ&gt;1,5 (OR=4.03;95%CI 1,14-14,21,p&lt;0,03), with elevated sPAP&gt;40mmHg (OR=8.62;95%CI 1,23-60,03;p&lt;0,04), muscle weakness (OR=9.00;95%CI 1,34-60,15, p&lt;0,03).It was also associated with elevated acute-phase reactants (OR=39,0;95%CI;474-320,62,p&lt;0,001). <h3>Conclusions</h3> Arthritis is a common finding in SSc even independent of clinical symptoms and signs. Our data show that arthritis is associated with a more severe disease and with systemic inflammation. This data support the use of MRI in clinical practice for early identification of SSc pts who will develop more severe disease with systemic inflammation <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5795
Abstract 5423: Effects of atorvastatin, celecoxib and tipifarnib alone or in combination on the growth of pancreatic cancer in Panc-1 cells cultured in vitro or Panc-1 tumors grown in immunodeficient mice
Authors: Xi Zheng, Xiao-Xing Cui, Zhi Gao, Yi Shi, Arnold Rabson, Allan H. Conney
Journal: Cancer Research (2010)

Abstract Ras mutation and overexpression of cyclooxygenase-2 (Cox-2) are present in the majority of pancreas cancer patients. An approach for inhibiting the progression and growth of pancreas cancer is the use of agents that inhibit the function of both Ras and COX-2. In the present study, we assessed the effects of atorvastatin, celecoxib and tipifarnib alone or in combination on the growth of human pancreatic cancer Panc-1 cells cultured in vitro or grown as xenograft tumors in severe combined immunodeficient (SCID) mice. In the in vitro studies, we found that treatment of Panc-1 cells with a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on proliferation and a stronger stimulatory effect on apoptosis than each drug alone or for any combination of two drugs. We also found that treatment of Panc-1 cells with a combination of the 3 drugs decreased the level of phosphorylated Erk1/2 and Atk to a much greater extent than the individual compounds alone or any combination of two compounds. In animal experiment, we found that daily i.p injections of a combination of atorvastatin, celecoxib and tipifarnib had a stronger inhibitory effect on the growth of Panc-1 tumors in SCID mice than each drug alone or for any combination of two drugs. The results from our study indicate that a combination of atorvastatin, celecoxib and tipifarnib may be an effective strategy for the treatment of pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5423.
FRI0058 Comorbidity Indexes/Scales in Rheumatoid Arthritis: A Systematic Literature Review:
Authors: J.A. Martínez-Lόpez, E. Loza, A. Ortiz, E. Toledano, V. Villaverde, C. Lajas, S. Castañeda
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In rheumatoid arthritis (RA), comorbidity might delay diagnosis and influence treatment decisions; it alters survival, outcomes and confounds analysis. Therefore, it is vital to measure it properly. The use of comorbidity indexes/scales could help in daily practice. <h3>Objectives</h3> To examine validity, reliability and feasibility of comorbidity indexes in daily practice in RA. <h3>Methods</h3> A systematic literature review was performed by 2 reviewers, a librarian and a methodologist. Studies were identified by sensitive search strategies in the main bibliographic databases (Medline, Embase and Cochrane Library) up to May 2013. Mesh terms and text word were used. We selected articles that analyzed comorbidity indexes/scales. Any type of study except case series or case reports was eligible. Two reviewers (JAML and EL) screened the titles and abstracts of the retrieved articles independently. JAML reviewed the selected articles in detail and collected the data from the studies included by using ad hoc standard forms. A hand search was completed by reviewing the references of the included studies. Validity process was evaluated, and study quality using the Newcastle-Ottawa scale. The level of evidence for each comorbidity index/scale was graded with the Oxford Centre for Evidence-based Medicine Levels of Evidence. <h3>Results</h3> We included 33 studies (moderate quality, 2 were systematic reviews) that described more than 40 comorbidity indexes, 1 specific for RA. We found a great variability regarding to type of measure of comorbidity, validation populations, number of items included, definitions, scoring method, etc. Content and face validity varied but tended to be high. Reliability was in general moderate-high, but feasibility in daily practice complicated mainly because of lack of time. The table summarizes the characteristics of some of the most popular comorbidity indexes. <h3>Conclusions</h3> There is not enough evidence to recommend an especific comorbidity index in RA patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5773
A Less Costly Regimen of Alglucerase to Treat Gaucher's Disease
Authors: Michael L. Figueroa, Barry E. Rosenbloom, Andrea C. Kay, Paul Garver, Dennis W. Thurston, James A. Koziol, Terri Gelbart, Ernest Beutler
Journal: New England Journal of Medicine (1992)

Alglucerase (Ceredase) provides effective enzyme-replacement treatment for patients with Gaucher's disease, but at the usually recommended dose of 60 U per kilogram of body weight every two weeks (130 U per kilogram per month), it costs $382,200 per year for a 70-kg patient. Theoretical considerations suggest that more frequent administration would be more efficient.
Abstract 3460: Genome-wide copy number analysis reveals novel somatic mutations associated with choroid plexus tumorigenesis
Authors: Diana M. Merino, Adam Shlien, Malgorzata Pienkowska, Uri Tabori, David Malkin
Journal: Cancer Research (2011)

Abstract Choroid plexus carcinomas (CPCs) are aggressive pediatric neoplasms accounting for less than 1% of brain tumors, but representing more than 10% of brain tumors in children under 1 year of age. CPCs are frequently observed in the context of the Li-Fraumeni Syndrome (LFS), yet this association has not been fully elucidated. The genetic mechanisms leading to this disease are poorly understood; however, we have recently demonstrated that TP53 status and total structural variation are correlated with tumor subtype and clinical outcome in choroid plexus tumor (CPT) patients, distinguishing between individuals with CPC and choroid plexus papilloma (CPP), a benign tumor with a more favorable prognosis. We set out to characterize genomic regions in which copy number variation and gene expression changes are uniquely associated with CPC tumors in order to identify genes that may serve as markers in tumor diagnosis and prognosis. DNA and RNA from 59 choroid plexus tumors (CPC, n=29 and CPP, n=30) and two samples of normal choroid plexus tissue were obtained from a multi-institutional tissue and clinical database. We conducted high-resolution copy number alteration (CNA) and gene expression analysis for each tumor sample using highly dense microarrays (Affymetrix SNP 6.0 and Exon 1.0 ST array, respectively). DNA microarray data was segmented using a Hidden Markov Model (HMM) approach. Statistical analysis was carried out using Partek Genomics Suite in which CNAs and gene expression changes between CPC, CPP, and normal choroid plexus samples were contrasted. We identified 14 CPC-unique loci harboring CNAs with corresponding gene expression changes (p&amp;gt;0.05). We observed that CNAs were found at loci where cancer genes with well-characterized oncogenic functions have been previously identified (1p13.2, 1p13.3, 1p21.3, 1p22.1 and 5q13.3). Furthermore, more than 90% of tumors with copy number alterations and expression changes at these five loci also harbored mutant TP53. These observations suggest involvement of several genes in the malignant progression of CPCs, which may help elucidate the aggressiveness and poor clinical outcome of this tumor subtype compared to the more favorable CPP. Further analysis of CNAs and expression at these loci in the context of TP53 mutations, will provide a more refined genetic profile that will facilitate diagnosis of CPTs and aid in predicting patient outcome. 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 3460. doi:10.1158/1538-7445.AM2011-3460
1160METFORMIN INCREASES THE RESPONSE TO INTERFERON ALPHA BY INHIBITING PROTEIN TYROSINE PHOSPHATASES IN INSULIN RESISTANT MICE
Authors: I. García-Ruiz, P. Solís-Muñoz, Á.M. Valverde, É. Gómez-Izquierdo, T. Munoz-Yagüe, J. Solís-Herruzo
Journal: Journal of Hepatology (2012)
Abstract 882: Functional investigation of a novel cancer specific organic anion transporting polypeptide 1B3 variant 1 (OATP1B3 V1) in colon and pancreatic cancer.
Authors: Nilay Thakkar, Kyungbo Kim, Eun Ryoung Jang, Songhee Han, Kyunghwa Kim, Donghern Kim, Nipun Merchant, A. Craig Lockhart, Wooin Lee
Journal: Cancer Research (2013)

Abstract OATP1B3 is a member of the Organic Anion Transporting Polypeptide (OATP) superfamily that mediates the uptake of numerous endogenous and xenobiotic compounds. Initially, OATP1B3 was reported to be expressed exclusively in the normal hepatocytes. Subsequent studies have reported that OATP1B3 is frequently expressed in multiple types of cancer tissues derived from gastrointestinal tract, pancreas, prostate, lung and breast. Some reports have also suggested that OATP1B3 may be associated with differing clinical outcomes. However, so far the biological functions of OATP1B3 in cancer have not been elucidated. In this study, we confirmed that colon and pancreatic cancer cells express variant forms of OATP1B3, different from OATP1B3 wildtype (WT) expressed in normal liver. OATP1B3 variant 1 (V1) is the most prevalent form among the variants containing the alternate exon 2a, instead of exons 1 and 2 as in OATP1B3 WT. The translated protein sequence of OATP1B3 V1 is similar to OATP1B3 WT except lacking the first 28 amino acids at the N-terminus. OATP1B3 V1 has a limited transport activity toward cholecystokin-8 (CCK-8, a prototype OATP1B3 substrate) in contrast to OATP1B3 WT which showed a markedly efficient uptake of CCK-8. Consistent with these results, OATP1B3 V1 was localized mainly in the cytoplasm with a much lower extent of trafficking to the surface membrane compared to OATP1B3 WT. In summary, our results demonstrate that colon and pancreatic cancer cells express variant forms of OATP1B3 with a limited transport activity and different subcellular localization compared to OATP1B3 WT. These observed differences at molecular and functional levels will be important considerations for further investigations of the biological and clinical significance of OATP1B3 expression in cancer. Citation Format: Nilay Thakkar, Kyungbo Kim, Eun Ryoung Jang, Songhee Han, Kyunghwa Kim, Donghern Kim, Nipun Merchant, A. Craig Lockhart, Wooin Lee. Functional investigation of a novel cancer specific organic anion transporting polypeptide 1B3 variant 1 (OATP1B3 V1) in colon and pancreatic cancer. [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 882. doi:10.1158/1538-7445.AM2013-882
AB1191 High Prevalence of Various Upper Limb Musculoskeletal Disorders in Korean Orchardists
Authors: Y.S. Suh, Y.-H. Cheon, H.-O. Kim, W.-S. Lee, W.-H. Yoo, H.S. Lim, S.-I. Lee
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Orchardists are expected to show high prevalence of upper limb musculoskeletal disorders (MSDs) due to their heavy works and working postures. However, there are no systematic studies relating upper limb MSDs in Korean orchardists. <h3>Objectives</h3> To evaluate the prevalence and characteristics of upper limb MSDs among orchardists in rural areas of Korea. <h3>Methods</h3> The study was carried out from June 2013 to May 2014 in a tertiary medical center. The physical examinations of upper extremities were performed by rheumatologists, orthopedists, and rehabilitation medicine specialists. The plain radiographs of shoulder, elbow, and hand, nerve conduction examination of upper extremities, and MRI of both shoulder were taken. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was used to assess symptoms and function of upper extremities. <h3>Results</h3> Five hundred and fifty orchardists were included. Participants comprised of 49.5% female and 50.5% male with mean age of 59.5±8.1 years. The mean farming duration was 31.3±13.2 years. A total of 34 different types of upper limb MSDs were detected. The most frequent disorder was myofascial pain syndrome (80.5%) followed by rotator cuff syndrome (58.9%), hand osteoarthritis (58.0%), carpal tunnel syndrome (42.9%), and lateral epicondylitis (39.5%). Prevalence of any form of MSD was 98.5% and of three and more of MSDs was 77.3%. Participants with longer duration of farming had higher numbers of MSDs. Almost part of pruning and harvesting postures in orchard farming were loaded works for musculoskeletal systems. Total DASH score was relatively high (14.9±14.4). <h3>Conclusions</h3> Almost orchardists have upper limb MSDs. Our results suggest the need to implement interventions in orchardists to prevent MSDs. <h3>References</h3> Gomez MI, Hwang S, Stark AD, May JJ, Hallman EM, Pantea CI. An analysis of self-reported joint pain among New York farmers. J Agric Saf Health. 2003;9:143–157. Holmberg S, Stiernstrom EL, Thelin A, Svardsudd K. Musculoskeletal symptoms among farmers and non-farmers: A population based study. Int J Occup Environ Health. 2002;8:339–345. Osborne A, Blake C, Fullen BM, Meredith D, Phelan J, McNamara J, Cunningham C. Prevalence of musculoskeletal disorders among farmers: A systematic review. Am J Ind Med. 2012;55(2):143-58. <h3>Acknowledgements</h3> This study was supported by a grant of the Center for Farmer9s Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. <h3>Disclosure of Interest</h3> None declared
Abstract 536: Insulin-like growth factor II (IGF-II) is a potential target for the treatment of triple negative breast cancers (TNBC).
Authors: Vinodh Kumar Radhakrishnan, Qianwei Tan, Marino A. De León, Daisy D. De León
Journal: Cancer Research (2013)

Abstract In the United States, African American (AA) women have a lower incidence of breast cancer compared to Caucasian (CA) women, but higher overall mortality. Our lab have demonstrated that Breast Cancer from AA patients express significantly higher levels of IGF-II and show a higher activation of the IGF signaling system in African American (AA) when compared to Caucasian (CA) women. We showed that IGF-II promotes breast cancer progression and metastasis by inhibiting tumor cell death and promoting resistance to chemotherapy, thus contributing to increased breast cancer (BC) mortality. This study was designed to determine how IGF-II contributes to the aggressiveness of TNBC, the most deadly of breast tumors, which is highly prevalent among AA. To analyze IGF-II in a TNBC cell model, we chose cell lines established from tumors of AA and CA breast cancer patients. Expression of IGF-II and IGF-II regulated proteins mRNA expression was probed using the CFX96 real time PCR system. Similarly, IGF-II and related proteins expression was analyzed by western blots and chemiluminescence. We also characterized the epigenetic activation of IGF-II in these cell lines since variation in the expression of IGF-II alleles regulates a signature of proteins associated with tumor aggressiveness. Our exciting results demonstrated that higher IGF-II levels in TNBC cells from AA was associated with distinct epigenetic changes that included different promoter activation and higher levels of IGF-II translation which are inheritable traits. In contrast, TNBC from CA had higher IGF-II levels due to different molecular IGF-II regulation. Thus, IGF-II is an important biomarker and can be used as therapeutic target for treatment of TNBC. Citation Format: Vinodh Kumar Radhakrishnan, Qianwei Tan, Marino A. De León, Daisy D. De León. Insulin-like growth factor II (IGF-II) is a potential target for the treatment of triple negative breast cancers (TNBC). [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 536. doi:10.1158/1538-7445.AM2013-536
Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection
Authors: Avraham Bayer, Nicholas J. Lennemann, Yingshi Ouyang, John C. Bramley, Stefanie Morosky, Ernesto Torres De Azeved Marques, Sara Cherry, Yoel Sadovsky, Carolyn B. Coyne
Journal: Cell Host & Microbe (2016)
Ellis Jacob Epstein
Authors: D. R. Ramsdale
Journal: BMJ (2013)

Ellis Jacob Epstein was born to Dora and Charles Epstein, who lived in Broughton, Salford. He had an older sister, Evelyn, and a younger brother, Bernard. He went to school locally and after attending Salford Grammar School gained a place at Manchester University Medical School. After his house jobs at Manchester Royal Infirmary and Crumpsall Hospital, he entered the Royal Navy as surgeon lieutenant between 1951 and 1953. On completion of his national service, Ellis continued his general medical training at the Royal Devon and Exeter Hospital and Manchester Royal Infirmary (1954-5) before gaining medical registrar posts in Withington Hospital, south Manchester, and the London Chest Hospital (1955-7), achieving his MRCP (Edinburgh and London) in 1956. In 1959 Ellis gained a senior registrar post at the Liverpool regional cardiac centre at Sefton General Hospital, where his career in cardiology really began. In 1962 he went to Victor McKusick’s unit at the Johns Hopkins University School of Medicine and the Johns Hopkins Hospital in Baltimore, Maryland, USA, where he was awarded their fellowship in medicine in 1963. Here he worked with J Michael Criley himself an expert in cardiac haemodynamics and cardiac auscultation, at a time when cineangiography was becoming the technique for studying and diagnosing cardiac disease.

In 1962, Ellis was awarded his MD from Manchester University. His thesis on aortic stenosis correlated the symptoms, physical signs, chest x-ray, and ECG findings with those from carotid pulse wave morphology, apex cardiography, phonocardiography, and ultimately cardiac catheterisation, aiming to provide a reliable, non-invasive assessment of the severity …
Gastric Adenocarcinoma in the Setting of X-Linked Agammaglobulinemia (XLA) and HIV
Authors: Sana Hasan, Vagish Hemmige, Lisa R. Forbes, Jordan S. Orange, Joud Hajjar
Journal: Journal of Allergy and Clinical Immunology (2015)

X-linked agammaglobulinemia is a primary immunodeficiency resulting in the absence of B-cells and increased susceptibility to infections. There are sixteen published reports of XLA linked to malignancy. Here we present an additional patient with XLA and HIV who was diagnosed with gastric adenocarcinoma. Quantitative immunoglobulins, T/B cell phenotyping, CDH1 gene testing, esophagogastroduodenoscopy (EGD), and biopsy of the antrum of the stomach. A 24-year-old male with XLA, diagnosed at the age of 2, was maintained on IVIG replacement. He contracted HIV at the age of 23 and was treated with HAART, which kept his CD4 count >1000 and viral load undetectable. He developed recurrent Campylobacter bacteremia and leg cellulitis, which was treated with IV antibiotics. He developed low IgG troughs, despite increasing IVIG dose and frequency. He then developed iron deficiency anemia so EGD was performed, which showed gastric inflammation with erosions and ulceration. Biopsy showed poorly differentiated gastric adenocarcinoma, her2/neu negative, positive for Helicobacter Pylori. Genetic testing for mutations in the CDH1 gene, which are associated with hereditary diffuse gastric cancer, was negative. He underwent subtotal gastrectomy, lymphadenectomy, Roux-en-Y gastrojejunostomy, and had negative lymph nodes and margins making his final diagnosis stage 1A gastric cancer. He was placed under surveillance with no evidence of recurrence of the disease. There are multiple case reports linking early onset GI malignancy to XLA with inflammation possibly due to chronic infection as a predisposing factor. Further studies are needed to validate the cost effectiveness of early screening for GI malignancy in patients with XLA.