tbuckley/cabot-search huggingface dataset:
Clinical and Immunologic Investigations in Patients With Stiff-Person Spectrum Disorder
Authors: Eugenia Martinez-Hernandez, Helena Ariño, Andrew McKeon, Takahiro Iizuka, Maarten J. Titulaer, Mateus M. Simabukuro, Eric Lancaster, Mar Petit-Pedrol, Jesús Planagumà, Yolanda Blanco, Robert J. Harvey, Albert Saiz, Francesc Graus, Josep Dalmau
Journal: JAMA Neurology (2016)

Symptoms of stiff-person syndrome (SPS), stiff-limb syndrome (SLS), or progressive encephalomyelitis with rigidity, myoclonus, or other symptoms (SPS-plus) can occur with several autoantibodies, but the relative frequency of each antibody, syndrome specificity, and prognostic implications are unclear.To report the clinical and immunologic findings of a large cohort of patients with stiff-person spectrum disorder (SPSD), including SPS, SLS, and SPS-plus.This study retrospectively examined a case series (January 1, 1998, through December 31, 2014) of immunologic investigations performed in a neuroimmunology referral center. The study included 121 patients with clinical features of SPSD. Data analysis was performed from July 1, 2015, through November 1, 2015.Analysis of clinical-immunologic associations, including autoantibodies to 8 proteins expressed in inhibitory synapses.The median age of the patients was 51 years (interquartile range, 40-61 years), and 75 (62.0%) were female. Fifty (41.3%) had SPS, 37 (30.6%) had SPS-plus, 24 (19.8%) had SLS, and 10 (8.3%) had SPS or SLS overlapping with ataxia, epilepsy, or encephalitis. Fifty-two patients (43.0%) had glutamic acid decarboxylase (GAD65) antibodies (2 with γ-aminobutyric acid-A [GABA-A] receptor antibodies), 24 (19.8%) had α1-subunit of the glycine receptor (GlyR) antibodies (2 with GAD65 antibodies), 5 (4.1%) had other antibodies, and 40 (33.1%) tested negative for antibodies. None had gephyrin or glycine transporter antibodies. Among the main immunologic groups (GAD65 antibodies, GlyR antibodies, and antibody negative), those with GAD65 antibodies were more likely to be female (45 [86.5%] of 52, 8 [36.4%] of 22, and 18 [45.0%] of 40, respectively; P < .001), have systemic autoimmunity (34 [65.4%] of 52, 7 [31.8%] of 22, and 13 [32.5%] of 40, respectively; P = .004), and have longer delays in being tested for antibodies (median, 3 vs 0.5 and 1 year; P < .001). Patients with GAD65 antibodies were more likely to develop SPS (27 [51.9%] of 52) or overlapping syndromes (8 [15.4%] of 52) than patients with GlyR antibodies (5 [22.7%] and 0 [0%] of 22, respectively), who more often developed SPS-plus (12 [54.5%] of 22 vs 7 [13.5%] in those with GAD65 antibodies); antibody-negative patients had an intermediate syndrome distribution. In multivariable analysis, symptom severity (P = .001) and immunologic group (P = .01) were independently associated with outcome. Compared with patients with GlyR antibodies, those with GAD65 antibodies (odds ratio, 11.1, 95% CI, 2.3-53.7; P = .003) had worse outcome. Patients without antibodies had similar outcome than patients with GlyR antibodies (odds ratio, 4.2, 95% CI, 0.9-20.0; P = .07).In SPSD, symptom severity and presence and type of antibodies are predictors of outcome.
A4.14 Role of Different Adiponectin Receptors in Adiponectin Signaling In Rheumatoid Arthritis Synovial Fibroblasts
Authors: K Khawaja, KW Frommer, A Schäffler, C Büchler, S Rehart, A Lehr, U Müller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Adiponectin levels were found to be increased in the synovial fluid of rheumatoid arthritis (RA) patients suggesting a role in the pathophysiology of the disease. RA synovial fibroblasts (SF) are known to be a key cell in RA and to express adiponectin in vivo. Adiponectin exists in four isoforms, namely the globular, low molecular weight (LMW or trimer), middle molecular weight (MMW) and high molecular weight (HMW) form. These isoforms act by binding to its receptors AdipoR1, AdipoR2, PAQR3 and PAQR10, which are expressed by various cells. Subsequently, different intracellular signalling pathways are activated including AMPK, p38MAPK, and FAK. The purpose of the present study was to determine the adiponectin receptor expression and the specificity of the adiponectin receptors to the respective adiponectin isoforms mediating different signalling pathways in RASF. <h3>Methods</h3> AdipoR1, AdipoR2, PAQR3 and PAQR10 mRNA and protein expression were analysed in RASF by Real-time PCR, Western blotting, and immunocytochemistry. AdipoR1 and AdipoR2 down-regulation by siRNA via nucleofection technology and lentiviral transduction were performed followed by signalling analysis via Western blots. <h3>Results</h3> Real-time PCR and Western blotting results showed that cultured RASF express AdipoR1, AdipoR2, and PAQR3 but not PAQR10. This was further confirmed by immunocytochemical analysis. Transfection of siRNA specific for AdipoR1, AdipoR2 and PAQR3 via nucleofection showed successful receptor down-regulation at mRNA level but no effect was observed at protein level even after 10 days, most likely due to the long receptor half-life on the cell surface. However, lentiviral transduction showed successful down-regulation of AdipoR2 at mRNA as well as at protein level after 5 weeks (approx. 5 fold). AdipoR2 knockdown in RASF showed a reduction in adiponectin-induced p38MAPK signalling. <h3>Conclusions</h3> Our results show that RASF isolated from synovium of RA patients express the adiponectin receptors AdipoR1, AdipoR2 and PAQR3. Down-regulation of these adiponectin receptors by lentiviral transduction was found to be a more efficient technique as compared to siRNA transfection, which will facilitate to study their role in signalling. Moreover, the induction of the p38MAPK pathway by adiponectin seems to be dependent on AdipoR2. <h3>Funding</h3> This work was supported by the German research society (NE1174/8–1).
Abstract 646: Identification of FURIN as a tumor maintenance gene in solid tumors by in vivo Retroviral Mutagenesis and Directed Complementation
Authors: Lerner Lorena, Qing Liu, John Yang, Brian Krieger, Nianjun Tao, Jodi Zarycki, Fanglei You, Omar Kabbarah, Murray O. Robinson, M. Isabel Chiu
Journal: Cancer Research (2010)

Abstract To identify tumor maintenance genes and pathways, we applied a genome-wide, large-scale functional screening approach using retrovirus-mediated mutagenesis on a number of inducible murine solid tumor models, including a HER2-driven breast tumor model and kRAS-driven breast and lung cancer models, in which viral integration could maintain established tumors in the absence of the initiating oncogene. We identified more than 3,000 recurrent viral integration sites in a collection of about 400 tumors. Whereas some genes were targeted by viral integration in specific tumor models, others were prominently hit in all the models. For example, insertions targeting the Furin locus were detected in tumors from all three models. In such tumors, viral integrations mapped to the Furin promoter consistent with the notion that activation of this gene and/or pathway may represent a common mechanism of tumor maintenance. Using our inducible directed complementation (DC) platform, we show that introduction of a wild type FURIN cDNA can maintain primary tumors in vivo in the absence of the initial driving oncogene. The FURIN DC tumors provide a useful pre-clinical model with which we can examine the effects of FURIN antagonists on tumor maintenance. Next, we sought to extend the utility of these validated DC tumor models to drug discovery by establishing FURIN-dependent cell lines for high-throughput screening. Here we describe detailed molecular characterization of the FURIN DC tumor models as well as from the cell lines derived from these tumor models. Furthermore, FURIN DC Tumor Models as wells as cell lines serve as a unique experimental tools, with which response to novel targeted therapies and other cancer agents can be studied. 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 646.
Internet images attract GP trainees to west Wales
Authors: R. Dobson
Journal: BMJ (1997)

Sun, sea, and surfing on the internet are being used to entice trainee GPs to Wales.

Those who tune into a new vocational training scheme web site will find pictures of doctors enjoying themselves on the beaches, in the sea, and on the cliffs of west Wales as part of a bid to sell the area to trainees. “On the site you will find the most glorious pictures of Wales. There are doctors windsurfing and rock …
The Major Urologic Considerations in Paraplegia
Authors: Herbert S. Talbot, Melvin K. Lyons, Arthur J. Bassell
Journal: New England Journal of Medicine (1949)

THE health of the upper urinary tract in paraplegia is, except for one hazard, dependent upon the health and function of the bladder. That exception is a tendency toward the formation of renal stones during prolonged recumbency or inactivity. But this tendency is itself greatly exaggerated by infection and stasis, both of which are sequelae of vesical dysfunction. From the hour of injury, therefore, there can be no temporizing with the care of the bladder if the dangerous consequences of the neurogenic disorder are to be averted or diminished.After any severe spinal-cord injury, there is often a period of . . .
Ambitious plan for "tobacco-free" Scotland by 2034
Authors: B. Christie
Journal: BMJ (2013)

The Scottish government has again positioned itself as the pacesetter in smoking cessation in the United Kingdom, launching a fresh attack on smoking with the aim of making the country virtually “smoke-free” by 2034.

Scotland has become only the third country in the world to set a timetable for reducing smoking to less than 5% of the population. New Zealand and Finland have set targets of 2025 and 2040.

To achieve its aim, Scotland has made a commitment to introduce plain packaging for cigarettes as part of a wider initiative to …
SAT0212 Pregnancy and fetal outcome in patients with an established diagnosis of primary sjögren’s syndrome
Authors: R. Priori, A. Gattamelata, M. Modesti, S. Colafrancesco, M. Maset, L. Quartuccio, S. De Vita, E. Bartoloni, A. Alunno, R. Gerli, F. Strigini, C. Baldini, C. Tani, M. Mosca, S. Bombardieri, G. Valesini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate pregnancy and fetal outcome in patients with an established diagnosis of primary Sjögren’s syndrome (pSS) <h3>Methods</h3> The clinical charts of 1073 women with pSS from four rheumatology centres were retrospectively evaluated. When a pregnancy has occurred after pSS diagnosis, the patient was personally interviewed to obtain more detailed information regarding obstetric history; obstetric clinical charts were reviewed as well. <h3>Results</h3> Patients’ mean age was 59 yr (17-89), mean age at diagnosis 51,4 yr; 138/1073 (12,8%) were diagnosed before 35 yr. Thirty-five women (31 with anti-SSA/Ro and/or anti-SSA/La antibodies) with an established diagnosis of pSS had 44 pregnancies which ended with the delivery of 39 newborns. Two miscarriages, 2 fetal death and one induced abortion were recorded. Mean age at the latest pregnancy was 34,6 yr (range 29-44), mean number of pregnancy 1,25 (1-3); 17/39 cesarean sections were performed, mean pregnancy length was 38,5 week (range 32-43) with 6 preterm delivery. The mean Apgar score at 5 minute was 8,9 (range 5-10), mean birth weight was 2934 mg (range 826-4060). Congenital heart block (CHB) occurred in 2 newborns of 31 mothers with anti-SSA and/or SSB antibodies (6,45%), with fatal outcome. Other 2 infants had cardial incontinence and a mild interatrial defect, respectively. During pregnancy one patient presented thrombocytopenia and another palpable purpura. In 4/39 pregnancies (10,2%) a flare of disease activity was observed (arthralgia/arthritis and central nervous system involvement) within a year from delivery. <h3>Conclusions</h3> Even if pSS generally starts after menopause, it can appear during the childbearing age. pSS can have successful pregnancies, which might be followed by a mild relapse. CHB is a fearful complication for women with anti-SSA/Ro and or anti-SSB/La antibodies. <h3>Disclosure of Interest</h3> None Declared
Immunoregulatory Protein B7-H3 Reprograms Glucose Metabolism in Cancer Cells by ROS-Mediated Stabilization of HIF1α
Authors: Sangbin Lim, Hao Liu, Luciana Madeira da Silva, Ritu Arora, Zixing Liu, Joshua B. Phillips, David C. Schmitt, Tung Vu, Steven McClellan, Yifeng Lin, Wensheng Lin, Gary A. Piazza, Oystein Fodstad, Ming Tan
Journal: Cancer Research (2016)

Abstract B7-H3 is a member of B7 family of immunoregulatory transmembrane glycoproteins expressed by T cells. While B7-H3 overexpression is associated with poor outcomes in multiple cancers, it also has immune-independent roles outside T cells and its precise mechanistic contributions to cancer are unclear. In this study, we investigated the role of B7-H3 in metabolic reprogramming of cancer cells in vitro and in vivo. We found that B7-H3 promoted the Warburg effect, evidenced by increased glucose uptake and lactate production in B7-H3–expressing cells. B7-H3 also increased the protein levels of HIF1α and its downstream targets, LDHA and PDK1, key enzymes in the glycolytic pathway. Furthermore, B7-H3 promoted reactive oxygen species–dependent stabilization of HIF1α by suppressing the activity of the stress-activated transcription factor Nrf2 and its target genes, including the antioxidants SOD1, SOD2, and PRX3. Metabolic imaging of human breast cancer xenografts in mice confirmed that B7-H3 enhanced tumor glucose uptake and tumor growth. Together, our results illuminate the critical immune-independent contributions of B7-H3 to cancer metabolism, presenting a radically new perspective on B7 family immunoregulatory proteins in malignant progression. Cancer Res; 76(8); 2231–42. ©2016 AACR.
AB0669 The risk factor of perinatal complication in the connective tissue disease patients
Authors: H. Shimada, H. Dobashi, K. Kanenishi, K. Susaki, T. Kameda, Y. Takeuchi, M. Izumikawa, S. Nakashima, J. Danjo, T. Matsunaga
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pregnancies and deliveries are the most important life events for women. Many of connective tissue disease (CTD) patients occur in childbearing age. Once, CTD patients tended to give up pregnancy because of the high risk for preterm birth and abortion.Recently, CTD patients in hope of pregnancy were increased because of advanced examinations and therapies for CTD. However, CTD patients more often complicate preterm birth and abortion, light for dates (LFD) in perinatal period in spite of advanced examinations and therapies. There is no clear answer whether these problems are associated with activity of underlying disease or dose of corticosteroid during pregnancy. <h3>Objectives</h3> We reveal the relationship between perinatal complication and activity of underlying disease or dose of corticosteroid during pregnancy for pregnancy complicated with CTD (CTD-pregnancy) in our facility. <h3>Methods</h3> We investigated retrospectively as follow; underlying disease, anti SS-A antibody, complication with antiphospholipid syndrome (APS), the mode of delivery, the rate of preterm birth and abortion, perinatal complication, dose of corticosteroid during pregnancy and neonatal birth weight. <h3>Results</h3> Forty-three CTD-pregnancy patients were enrolled. Mean age was 30.5 years old, and mean CTD duration was 6.3 years on pregnancy. In this study, CTD-pregnancy patients had systemic lupus erythematosus (SLE), sjogren syndrome (SS), rheumatoid arthritis (RA), mixed connective tissue disease (MCTD), and so on. Six (17%) of all patients were exacerbated underlying disease during pregnancy. 3 cases of them needed corticosteroid pulse therapies because of their high disease activities. Positive anti SS-A antibody was found 16 cases (50%). However, there was no cardiac anomaly and arrythmia caused by anti SS-A antibody. Positive antiphospholipid antibody (aCL) revealed 14 cases (44%), and one of them had a preterm birth associated with APS. The rate of abortion was 9.3%, and the rate of preterm birth was 11.4%. The reason of abortion and preterm birth was high activity of underlying disease in all cases. There was no relationship between preterm birth, abortion, LFD or perinatal complication and dose of corticosteroid during pregnancy. <h3>Conclusions</h3> In CTD-pregnancy, preterm birth and abortion, LFD, perinatal complication is associated with the activity of underlying disease. We did not establish the relationship between dose of corticosteroid and these problems in our study. Therefore, it is important for safer pregnancy and delivery to treat underlying disease strictly with corticosteroid. <h3>Disclosure of Interest</h3> None Declared
TCT-151 Transcatheter Transplantation And In Vivo Tracking Of Human Stem Cell Based Three Dimensional Microtissues In A Porcine Model Of Myocardial Infarction
Authors: Maximilian Emmert, Petra Wolint, Volkmar Falk, Mariann Gyöngyösi, Simon P. Hoerstrup
Journal: Journal of the American College of Cardiology (2014)
THE ASSOCIATION OF ANTIDEPRESSANT AND STATIN USE TO FUTURE DEATH AND INCIDENT CARDIOVASCULAR DISEASE VARIES BY DEPRESSION SEVERITY
Authors: Heidi Thomas May, Tami Bair, Brenda Reiss-Brennan, Stacey Knight, Jeffrey Anderson, Benjamin Horne, Kimberly Brunisholz, J. Muhlestein
Journal: Journal of the American College of Cardiology (2015)
EG-09 * EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA
Authors: A. Olar, K. Wani, A. Mansouri, G. Zadeh, C. Wilson, F. DeMonte, G. Fuller, D. Jones, S. Pfister, A. von Deimling, E. Sulman, K. Aldape
Journal: Neuro-Oncology (2014)

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant methylation subtype in meningioma. CIMP-positivity with aberrant methylation in recurrent/malignant meningioma suggests a potential therapeutic target for clinically aggressive cases.
Role of PET/CT in Gynecological Tumors Based on the Revised FIGO Staging Classification
Authors: Tetsuya Tsujikawa, Tatsuro Tsuchida, Yoshio Yoshida, Tetsuji Kurokawa, Yasushi Kiyono, Hidehiko Okazawa, Hirohiko Kimura
Journal: Clinical Nuclear Medicine (2011)

FDG PET/CT imaging offers important information for the pre-, intra-, and postoperative management of gynecologic tumors. A review of FDG PET/CT imaging for the diagnosis of gynecologic tumors based on the revised International Federation of Gynecology and Obstetrics staging classification is presented.
Bilateral Lower Palpebral MALT Lymphoma
Authors: Issam Lalya, Hamid Mansouri
Journal: New England Journal of Medicine (2015)

A 65-year-old man presented with a 2-month history of painless swelling of the lower eyelids bilaterally. Excision biopsy of the palpebral tumor revealed mucosa-associated lymphoid tissue (MALT) lymphoma. Comprehensive physical examination revealed no other lesions.
THU0033 Overactive Bladder Symptom Bother is Increased in Patients with Systemic Lupus Erythematosus and SjÖGren's Syndrome: Table 1.
Authors: V. Romao, R. Pereira e Silva, T. Rodrigues, S. Oliveira, J. Brites, M. Neves, R. Garcia, F. Ramos, J. Palma dos Reis, J. Pereira da Silva, T. Lopes
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Interstitial Cystitis (IC) has been suggested to have an underlying autoimmune mechanism and to be associated with Systemic Lupus Erythematosus (SLE) and Sjögren9s syndrome (SS). In these conditions, lower urinary tract symptoms (LUTS) associated with overactive bladder (OAB) may be present since early stages of disease and be interpreted by patients as normal. <h3>Objectives</h3> To compare OAB symptom bother (SB) and health-related quality of life (HRQL) between healthy controls and patients with SLE and SS. <h3>Methods</h3> In a cross-sectional cohort study, we applied a validated questionnaire assessing LUTS and HRQL, the OAB questionnaire short form (OABq-SF, range 0-100), to SLE/SS patients followed in a hospital outpatient clinic and to patients from a primary health care centre that had none of the diseases. We further collected information on possible confounding variables. Group comparisons by Mann-Whitney and chi-square test and multiple regression analyses were conducted. Based on literature findings, we defined a SB score greater than 20/100 and a HRQL score lower than 90/100, as clinically meaningful. <h3>Results</h3> We included 203 controls and 93 rheumatic patients (64 SLE, 29 SS). Both groups had similar characteristics except for gender distribution, anti-depressant and corticosteroid consumption (Table 1). OABq-SF SB scores were greater and HRQL scores were lower in the SLE/SS group, compared to controls (p&lt;0.0001 and p=0.0002, respectively). SLE/SS patients had higher proportions of SB score ≥20 (OR 3.1, 1.9-5.2) and HQRL≤90 (OR 2.4, 1.4-4.2). The same differences were seen for the SLE/SS subgroups separately. Multivariate logistic regression revealed that SLE/SS patients were more likely to have a SB score greater than 20/100 (OR 2.72, 1.55-4.79) and a HRQL score lower than 90/100 (OR 1.90, 1.01-3.56), adjusting for age, sex, diuretics, recent urinary infection (≤3 months) and antidepressants. <h3>Conclusions</h3> Patients with SLE/SS had higher OAB symptom scores and lower HRQL scores compared to controls, using a validated questionnaire. They were also more likely to have a clinically meaningful score, suggesting that OAB and IC might be, indeed, more frequent in these patients. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4745