tbuckley/cabot-search huggingface dataset:
Hypomorphism of Fto and Rpgrip1l causes obesity in mice
Authors: George Stratigopoulos, Lisa Cole Burnett, Richard Rausch, Richard Gill, David Barth Penn, Alicja A. Skowronski, Charles A. LeDuc, Anthony J. Lanzano, Pumin Zhang, Daniel R. Storm, Dieter Egli, Rudolph L. Leibel
Journal: Journal of Clinical Investigation (2016)

Noncoding polymorphisms in the fat mass and obesity-associated (FTO) gene represent common alleles that are strongly associated with effects on food intake and adiposity in humans. Previous studies have suggested that the obesity-risk allele rs8050136 in the first intron of FTO alters a regulatory element recognized by the transcription factor CUX1, thereby leading to decreased expression of FTO and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Here, we evaluated the effects of rs8050136 and another potential CUX1 element in rs1421085 on expression of nearby genes in human induced pluripotent stem cell-derived (iPSC-derived) neurons. There were allele-dosage effects on FTO, RPGRIP1L, and AKT-interacting protein (AKTIP) expression, but expression of other vicinal genes, including IRX3, IRX5, and RBL2, which have been implicated in mediating functional effects, was not altered. In vivo manipulation of CUX1, Fto, and/or Rpgrip1l expression in mice affected adiposity in a manner that was consistent with CUX1 influence on adiposity via remote effects on Fto and Rpgrip1l expression. In support of a mechanism, mice hypomorphic for Rpgrip1l exhibited hyperphagic obesity, as the result of diminished leptin sensitivity in Leprb-expressing neurons. Together, the results of this study indicate that the effects of FTO-associated SNPs on energy homeostasis are due in part to the effects of these genetic variations on hypothalamic FTO, RPGRIP1L, and possibly other genes.
SAT0520 The Impact of Gout on Patient's Lives and Differences by Race and Gender: A Patient Perspective
Authors: J.A. Singh
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Little is known regarding the patient experience regarding the impact of gout on their lives, with most published qualitative studies assessing all aspects of gout, including treatment, knowledge, disease monitoring, outcomes and patient and clinician perspective, all in single studies. While these studies have provided important information, they have only scratched the issues related to impact of gout on quality of life (QOL). <h3>Objectives</h3> Our objective was to examine the impact of gout on quality of life and study differences by race and gender. <h3>Methods</h3> Ten race- and sex-stratified nominal groups were conducted, oversampling for African-Americans and women with gout. Patients presented, discussed, combined and rank ordered their concerns. <h3>Results</h3> 62 patients with mean age 65.1 years, 60% men, 64% African-American, participated in ten nominal groups: African-American men (n=23; 3 groups); African-American women (n=18; 3 groups); Caucasian men (n=15; 3 groups); and Caucasian women (n=6; 1 group). The most frequently cited highly-ranked concerns among the ten nominal groups were: (1) effect of gout flare on daily activities (n=10 groups); (2) work disability (n=8); (3) severe pain (n=8); (4) joint swelling and tenderness (n=6); (5) food restrictions (n=6); (6) medication related issues (n=6); (7) dependency on family and others (n=5); (8) emotional Impact (n=5); (9) interference with sexual function (n=4); (10) difficulty with shoes (n=4); and (11) sleep disruption (n=4). Compared to men, women ranked the following concerns high: problems with shoes (n=4 vs. 0 groups); dependency (n=3 vs. 2); and joint/limb deformity (n=2 vs. 1). Compared to Caucasians, African-Americans more often ranked the following concerns high: dietary restrictions (n=6 vs. 0 groups); severe pain (n=6 vs. 2); gout bringing the day to a “halt” (n=2 vs. 0); effect on emotional health (n=4 vs. 1); and the need for canes/crutches during flares (n=2 vs. 0). <h3>Conclusions</h3> Gout has significant impact on patient9s quality of life. There are differences in the impact of gout by race and gender. <h3>Acknowledgements</h3> This material is the result of work supported by a grant from the Division of Rheumatology at the University of Alabama at Birmingham and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute of Aging (NIA) and National Cancer Institute (NCI). <h3>Disclosure of Interest</h3> J. Singh Grant/research support: takeda, savient, Consultant for: Takeda, Savient, Regeneron, Allergan <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1147
AB0532 Diagnostic Performance of the American-European 2002 Criteria and the Preliminary 2012 American Criteria for Primary SjÖGren Syndrome
Authors: M.A. Gauna, A. Secco, M. Oliver, D. Puente, S. Scarafia, L. Carlevaris, G. Bennasar, L. Marino, S. Papasidero, J.C. Barreira, L. Encinas, F. Caeiro, F. Zazzetti, S. Velez, H. Laborde, A. catalan Pellet, O. Rillo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The diversity of classification criteria for Primary Sjögren9s Syndrome (pSS) makes it difficult to draw conclusions from clinical studies. The most commonly used are the 2002 American European criteria. Recently, the new 2012 preliminary criteria have been proposed. <h3>Objectives</h3> To assess the diagnostic value of both pSS classification criteria, the American-European 2002 and the preliminary 2012. <h3>Methods</h3> The medical expert opinion of rheumatologists from different reference centers in Argentina was considered as the Gold Standard. Sensitivity (S), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio (LR+) of both criteria was evaluated. <h3>Results</h3> 100 patients were diagnosed with pSS according to expert opinion and 83 with another rheumatic disease or Sicca symptoms (AR: 31 LES: 17, Scleroderma: 3, Dermatomyositis: 2, Rhupus: 2, Undifferentiated Arthritis: 2, Psoriatic Arthritis 1, PTI: 1, Sicca: 24). 93.1% were female, with a median current age of 54 years (IQR 45-65). <h3>For the 2002 criteria</h3> the overall sensitivity was 0.88 (0.81-0.94), the Sp: 0.89 (0.82 -0.96), the LR+: 8.07 (4.33 - 15.03), PPV 0.90 (0.83- 0.96), NPV 0.87 (0.80-0.94). <h3>For the 2012 criteria</h3> the overall results were: for sensitivity 0.92 (0.86-0.98), Sp: 0.96 (0.92- 1), LR+: 23.67 (7.79 - 71.9), PPV: 0.96 (0.91-1), NPV 0.93 (0.87- 0.98). <h3>Conclusions</h3> The 2012 preliminary criteria showed better performance than the American European 2002 Criteria. However, considering that most of confidence intervals overlap, these differences might not be relevant. <h3>References</h3> Shiboski et al. American College of Rheumatology Classification Criteria for Sjögren9s Syndrome: A Data-Driven, Expert Consensus Approach in the SICCA Cohort. Arthritis Care Res 2012. John P. Whitcher et al. A Simplified Quantitative Method for Assessing Kerato conjunctivitis Sicca from the Sjögren9s Syndrome International RegistryAm J Ophthalmol. 2010. C Vitali et al. Classification criteria for Sjögren9s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4418
AB0456 Granulomatosis with polyangiitis in tunisia. description of 21 cases.
Authors: I. Ben Ghorbel, N. Belfeki, N. Baouandi, A. Hamzaoui, T. Ben Salem, M. Khanfir-Smiti, M. Lamloum, M. Miled, M. H. Houman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Granulomatosis with Polyangiitis or Wegener's granulomatosis (WG) is a necrotizing vasculitis of unknown etiology that involves small and medium calibre vessels. It is associated to anti-neutrophil cytoplasm antibodies (ANCA). It most often affects the respiratory tract and the kidneys and its most important pathologic feature is the presence of necrotizing granulomas. <h3>Objectives</h3> To detail the features of 21 patients with WG diagnosed in a university department of Internal Medicine. <h3>Methods</h3> Retrospective study: between 2000 and 2012, 21 patients with WG were diagnosed in our centre. The WG diagnosis was retained according to ACR criteria (1990). Epidemiological, clinical, laboratory tests as well as pathologic studies and treatment were retrospectively analyzed. <h3>Results</h3> Twenty-one patients were diagnosed: 14 men and 7 women. Mean age at diagnosis: 45.5 years (16–70). Mean delay to diagnosis: 28 months. Fourteen patients had general symptoms (66%), 18 ear-nose-throat symptoms (85.7%), 16 pulmonary involvement (76%), 12 renal involvement (57%), 2 ureteral stenosis (9.5%), 11 neurological involvement (52.4%), 4 arthromyalgia (19%), 12 mucocutaneous manifestations (57%), 9 ocular involvement (43%), 5 cardiac involvement (24%), 4 vascular involvement (19%), 2 gastrointestinal involvement (9.5%). In one case, we report an association to a retroperitoneal fibrosis. ANCA were positive in 16 cases (76%), all had a cytoplasmic c-ANCA pattern. Anti-protease-3 specificity was detected in 5 cases and anti-myeloperoxydase in 3 cases. All patients received intravenous glucocorticoids and cyclophosphamide as induction therapy. During the disease progression 3 patients died, 9 patients progressed to chronic renal failure and hemodialysis. The remaining patients presented several relapses. <h3>Conclusions</h3> The clinical features of this series do not differ from those described by other authors, except the younger age at diagnosis. Frequently used drugs were glucocorticoids and cyclophosphamide. The course was usually unfavourable, with outbreaks or complications due to immunosuppression, except for those with limited forms. Immunosuppressive therapy should be maintained indefinitely in most cases. <h3>Disclosure of Interest</h3> None Declared
Bile Duct Stenosis Seemingly Caused by a Giant Pedunculated Hemangioma With Hypogastric Growth
Authors: ANABEL CORTÉS-BLANCO, RAÚL MARTÍNEZ-LÁZARO
Journal: Clinical Nuclear Medicine (2000)

In a 60-year-old woman with obstructive jaundice, an abdominal ultrasound showed compression of the common bile duct caused by two solid nodular masses in the liver and a giant mass situated in the epigastrium and right hypochondrium. Abdominal computed tomography revealed two intrahepatic lesions and a giant hepatic mass, with extrahepatic growth seemingly compressing the common bile duct. Labeled erythrocyte scintigraphy detected these lesions as hemangiomas. The scintigraphic peculiarities in this case were the size and location of the giant hemangioma. A giant hepatic hemangioma and a common bile duct stenosis caused by a pancreatic head adenocarcinoma were confirmed at surgery.
Postmenopausal Estrogen and Progestin Use and the Risk of Cardiovascular Disease
Authors: Francine Grodstein, Meir J. Stampfer, JoAnn E. Manson, Graham A. Colditz, Walter C. Willett, Bernard Rosner, Frank E. Speizer, Charles H. Hennekens
Journal: New England Journal of Medicine (1996)

Estrogen therapy in postmenopausal women has been associated with a decreased risk of heart disease. There is little information, however, about the effect of combined estrogen and progestin therapy on the risk of cardiovascular disease.
OP0218 Erosions and Sclerosis, but not Squaring Predict the Development of New Syndesmophytes: A 12-Year Longitudinal Analysis
Authors: S. Ramiro, A. van Tubergen, C. Stolwijk, D. van der Heijde, M. Dougados, F. van den Bosch, R. Landewé
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Erosions, sclerosis and squaring are included in the modified Stoke Ankylosing Spondylitis (AS) Spine Score (mSASSS). However, their value in predicting the development of new syndesmophytes has not been established, and their value in the mSASSS has been argued. <h3>Objectives</h3> To analyse the effect of erosions, sclerosis and squaring on the development of new syndesmophytes over 12 years. <h3>Methods</h3> Biannual radiographs from patients with AS (mNY criteria) followed in OASIS (up to 12 years) were included. Two readers (R1 and R2) independently scored the x-rays according to the mSASSS and separately registered all the items with a score of 1 (erosions, sclerosis and squaring, or any combination) per vertebral corner (VC). The progression from erosions, sclerosis and squaring to new (bridging) syndesmophytes (either score of 2 or 3 in the mSASSS) in a 2-year period and over the 12 years was investigated by means of a multilevel (adjusted for time, reader and cervical/lumbar spinal region) auto-regressive and time-lagged longitudinal model, using generalized estimating equations. Interactions with reader and spinal region were investigated. <h3>Results</h3> 211 patients were included in this analysis (mean age 43 (SD 13) years old, 71% male, 85% HLA-B27 positive, 11.5 (SD 9.1) years since diagnosis and 20.5 (SD 11.6) years since symptom onset, 4.4 (SD 1.8) radiographs per patient). A total of 921 radiographs were included in this analysis, with a total of 20509 VCs (R1) and 20568 VCs (R2) evaluable. Of these, erosions were scored in 1% for R1 (2.5% R2), sclerosis in 0.3% for R1 (1.7% R2), squaring in 6.5% for R1 (5.1% R2) and syndesmophytes in 25% for R1 (27% R2). The presence of erosions, sclerosis and squaring together had, compared with a normal VC, a risk for the development of new syndesmophytes over a 2-year period of 1.96 (Table). There was a significant interaction with ‘spinal region’ (OR cervical spine: 3.12; OR lumbar spine: 1.27). There was no significant difference between the readers. Separately, the presence of erosions or the presence of sclerosis, but not the presence of squaring, gave an increased risk for new syndesmophytes, Squaring was predictive of the development of new syndesmophytes in the cervical spine only (Table). Table – Longitudinal effect (GEE) of erosions, sclerosis and squaring on the development of new syndesmophytes over 12 years (adjusted for spinal region and reader) <h3>Conclusions</h3> Erosions and sclerosis occur rarely on X-rays, but if so, are predictive for the development of new syndesmophytes. Therefore, these lesions not only seem to precede the development of syndesmophytes, but are also correctly included in the mSASSS. The possibility of excluding squaring from the mSASSS in the lumbar spine may be considered. <h3>Disclosure of Interest</h3> None Declared
Cancer Issues Infiltrate the Underground Comics
Authors: J. McCann
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Cancer Issues Infiltrate the Underground Comics Get access Jean McCann Jean McCann Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 1, 4 January 1995, Pages 9–11, https://doi.org/10.1093/jnci/87.1.9 Published: 04 January 1995
Splenectomy in Blood Dyscrasias
Authors: C. Stuart Welch, William Dameshek
Journal: New England Journal of Medicine (1950)

THIS communication presents the results of splenectomy performed in patients with various blood dyscrasias who have been followed in the Blood Clinic of the New England Medical Center during the past ten years (July 1, 1939, through June 30, 1949). In the greater number of these patients, splenectomy was performed for congenital hemolytic anemia and primary thrombocytopenic purpura, and the results represent examples of the well established value of this operation. In some patients splenectomy was performed for other, less well defined conditions, and in others the indications for splenectomy might be called unusual or experimental. To determine the effect . . .
SP0230 The Co-Occurrence of Other Autoimmune Diseases within Patients with Systemic Sclerosis
Authors: Y. Allanore
Journal: Annals of the Rheumatic Diseases (2015)

The co-occurrence of other autoimmune diseases within patients with systemic sclerosis (SSc) is a frequent condition affecting about one quarter of SSc-patients according to a recent meta-analysis performed by our group. Polyautoimmunity as well as the familial aggregation of autoimmune diseases strengthen the concept of “shared autoimmunity”, suggested by recent genetic studies. Epidemiologic studies have reported wide ranges of prevalence of co-occurrence of other autoimmune diseases in SSc. In our meta-analysis, based on 6102 SSc patients, the most prevalent associated autoimmune diseases were autoimmune thyroiditis (10.4%) followed by Sjogren Syndrome (7.7%) and dermatomyositis/polymyositis (5.6%), whereas co-occurrence of primary biliary cirrhosis, rheumatoid arthritis and systemic lupus erythematosus was observed in less than 5% of the patients. Some reports have suggested that patients with SSc and polyautoimmunity might have a milder disease, could occur more frequently in women and would be associated with the limited cutaneous subtype of SSc and anticentromere positive autoantibodies. However, we will present in the session cases illustrating that some SSc-patients with polyautoimmunity may develop a more severe SSc with severe organ damages. Further studies are warranted to increase the knowledge about the mechanisms of autoimmunity and polyautoimmunity and the specificities of this SSc-phenotype, in order to raise potential new approaches for the management and the treatment of SSc-patients with polyautoimmunity. <h3>Disclosure of Interest</h3> Y. Allanore Grant/research support from: Actelion, Bristol-Meyers Squibb, Inventiva, Pfizer, Roche/Genentech, Servier., Consultant for: Actelion, Bayer, Biogen, Bristol-Meyers Squibb, Inventiva, Medac, Pfizer, Roche/Genentech, Sanofi-Aventis and Servier.
Bone Scintigraphy of Madura Foot
Authors: S. NIMU GANGULI, MARLON HERSHKOP
Journal: Clinical Nuclear Medicine (1999)

Three-phase Tc-99m MDP bone imaging of the feet was performed in a 69-year-old woman, a retired missionary who had worked in India and Africa. She was followed in the tropical disease clinic at our institution for a draining sinus from the dorsum of her right foot, which was cultured and found to be positive for Madurella mycetomatis. The three-phase bone scan, performed to assess disease activity and rule out underlying fractures before therapy was begun, showed marked hyperemia to the right forefoot on the anterior and plantar projections. Delayed images showed increased activity in the medial aspect of the right foot that corresponded to the destructive changes seen on the plain radiographs of the right foot. The scintigraphic appearance was more consistent with infection rather than an acute fracture.
AB0313 Rituximab changes psychological attitudes to rheumatoid arthritis
Authors: I. R. Gaisin, L. V. Ivanova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psychological types of attitude to disease, or inner picture of disease, carefully describe the individual features of psychic reacting to somatic illness.<sup>1</sup> Reports rarely reflect personality traits, to establish psychological response to rheumatoid arthritis (RA).<sup>2</sup> No data are available regarding the influence of biologic therapy for RA patients on their peculiar psychological attitudes. <h3>Objectives</h3> To assess psychological styles of reacting to RA in patients following B cell-directed therapy. <h3>Methods</h3> Biologics-naïve RA patients were followed up for 27 months after commencing and continuing rituximab therapy (1, 2, 3 standard courses). The inner picture of disease was studied at baseline, 3, 15 and 27 months using the Lichko's questionnaire.<sup>3</sup> <h3>Results</h3> 86 patients [mean (SD) age 49.2 (15.3) years, 76 women; median (IQR) DAS28 5.64 (3.92–8.42); median (IQR) HAQ 1.85 (1.0–3.5)] were enrolled. The initial prevalence of disadaptive diffuse psychological type was 24.4%; during the follow-up of 27 months it disappeared (p for trend = 0.003). The incidence rates of two harmonic set components, harmonic ('sober assessment of self-condition') and ergopathic styles ('move away from disease to work'), significantly increased over time. <h3>Conclusions</h3> This study provides the first evidence that rituximab improves patients' perception of rheumatoid arthritis. Within the limitations of a relatively small samples size and yet not controlled, the data suggest socio-psychological benefits from continued therapy with rituximab. <h3>References</h3> Gaisin IR. Hypertension in pregnant women: cardiorenal continuum and treatment. <i>Saarbrücken</i>: <i>LAP LAMBERT Academic Publishing,</i> 2011. Luna KS, Ortiz AM, Patiño E et al. Influence of the structure of mood in the assessment of rheumatoid arthritis through the visual analog scale for pain, HAQ and DAS28. <i>Reumatol Clin</i> 2012;8:328–333. Vasserman LI, Iovlev BV, Karpova EB, Vuks AYa. Method of psychological diagnosis of types of attitudes to disease. <i>Leningrad</i>, 1987. <h3>Disclosure of Interest</h3> None Declared
Abstract 3259: An efficient total synthesis of Tubulysin B
Authors: Iontcho R. Vlahov, Michael Groaning, Paul Kleindl, Hari Krishna R. Santhapuram, Fei You, Yu Wang, Lecun Xu, Katheryn Stanford, Allen Ritter, Christopher P. Leamon
Journal: Cancer Research (2011)

Abstract The tubulysins are members of a new class of natural products isolated from myxobacterial species.[1] As cytoskeleton interacting agents, the tubulysins are mitotic poisons that inhibit tubulin polymerization and lead to cell cycle arrest and apoptosis.[2-4] Tubulysins are extremely potent cytotoxic molecules, exceeding the cell growth inhibition of any clinicaly relevant traditional chemotherapeutic e.g. paclitaxel, vinblastine, and epothilones. Furthermore, they are potent against multidrug resistant cell lines.[5] Structurally, tubulysins are closely related linear tetrapeptides comprised of distinctive, unusual, or hydrophobic amino acid segments: D-N-methyl pipecolinic acid, L-isoleucine, the heterocyclic tubuvalin, and the γ-amino acid tubutyrosine/tubuphenylalanine. The most prominent feature in the molecular architecture of these natural occurring compounds is the acid and base sensitive N-acyloxymethyl substituent (or a N,O-acetal of formaldehyde). In this poster we present an efficient yet simplified synthesis of Tubulysin B. The optimized synthetic protocol relyes on chemical as well as enzymatic steps and is readily scalable to industrial meaningful quantities. All the synthesized intermediates and final compound are well charectreized by several analytical methods including HPLC, MS, 1H and 13C NMR, etc. Biological activty of synthetic tubulysin B is identical with natural tubulysin B. This synthetic protocol is amenable to all other natural tubulysins and analogs. [1] F. Sasse, H. Steinmetz, G. Höfle, H. Reichenbach, J. Antibiot. 2000, 53, 879-885. [2] H. Steinmetz, N. Glasser, E. Herdtweck, F. Sasse, H. Reichenbach, G. Höfle, Angew. Chem. Int. Ed. 2004, 43, 4888-4892. [3] M. Khalil, F. Sasse, H. Lünsdorf, Y. Elnakady, H. Reichenbach, ChemBioChem. 2006, 7, 678-683. [4] G. Kaur, M. Hollingshead, S. Holbeck, Schauer-Vikašinovic, R. Camalier, A. Dömling, S. Agarwal, Biochem. J. 2006, 396, 235-242. [5] For a review see: A. Dömling, W.Richter, Mol. Diversity 2005, 9, 141-147 and references therein. 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 3259. doi:10.1158/1538-7445.AM2011-3259
Edward Daniel Fox
Authors: T. Fincham
Journal: BMJ (2012)

Edward Daniel Fox, the son of Russian emigres, was a larger than life figure, always happy to flout convention; untroubled by other people’s rules. After wartime service in the Royal Air Force—from which he retained his pilot’s licence until late in life, flying his own light aircraft—he studied medicine at University College Hospital, London. After working as an assistant in general practice in …