tbuckley/cabot-search huggingface dataset:
SAT0347 Cartilaginous Uric Acid Deposition in Advanced Osteoarthritis: Innocent Bystander or Promotor of Cartilage Destruction?
Authors: T. Bongartz, O. M. Andre, R. J. Sierra, H. D. Arlen, T. J. Michael
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Recent studies have suggested that synovial fluid uric acid could contribute to tissue inflammation, disease severity and progression of osteoarthritis (OA). Intraarticular uric acid has been associated with OA disease severity and may promote cartilage destruction through inflammasome activation (1). We aimed to explore if intraarticular uric acid deposition does indeed occur in patients with OA of the knee who have never experienced an episode of gout. <h3>Methods</h3> We recruited patients with advanced OA of the knee and no history of gout who were scheduled to undergo knee replacement surgery. All subjects underwent dual-energy computed tomography (DECT) scanning of the target joint. DECT images were screened for areas of monosodium urate (MSU) deposition. During knee replacement surgery, samples of tibial and femoral condyle cartilage, menisci and synovium were obtained. Areas of possible MSU deposition as identified through DECT were particularly targeted for sample collection. A musculoskeletal pathologist performed bright field (DeGalantha and H&amp;E stains) and polarizing microscopy and recorded the presence of MSU crystals in a descriptive manner. <h3>Results</h3> 5 patients with advanced OA of the knee underwent DECT. In all subjects, DECT indicated areas of MSU deposition within the joint cartilage and the menisci. In 4 of these 5 patients, histopathology examination confirmed presence of MSU crystal clusters in the cartilage and/or menisci. In 2 patients, MSU deposition also involved the synovium. Of note, synovial fluid in all patients was negative for MSU crystals as detected by polarizing microscopy. The mean serum uric acid level was 5.7mg/dl, range 5.0-6.4 mg/dl. <h3>Conclusions</h3> This small pilot study revealed evidence of cartilaginous uric acid deposition in the majority of patients with advanced osteoarthritis. Future studies will have to confirm this finding in a larger patient cohort and clarify if intracartilaginous urate crystals accelerate cartilage damage or are deposited simply a result of matrix exposure and subsequent monosodium urate crystallization without significant effects on disease progression. <h3>Disclosure of Interest</h3> None Declared
AB0862 Qt Dispersion and P Wave Dispersion in Fibromyalgia: Table 1.
Authors: S. Yolbas, A. Yildirim, D. Duzenci, B. Karakaya, M.N. Dagli, S.S. Koca
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Fibromyalgia syndrome is a chronic disease with unknown etiology, characterized by widespread pain. QT dispersion represents a general repolarization abnormality and autonomic dysfunction. Longer QT dispersion is associated with higher risk of ventricular arrhythmias, cardiac events and mortality. P wave dispersion is a simple and useful parameter for the prediction of atrial arrhythmias. QT and P wave dispersions were investigated in several chronic inflammatory disorders such as rheumatoid arthritis, systemic lupus erythematosus, Behçet9s disease, and ankylosing spondylitis. <h3>Objectives</h3> The aim of the present study was to evaluate QT dispersion and P wave dispersions in patients with fibromyalgia. <h3>Methods</h3> The study involved 48 fibromyalgia patients fulfilled the established criteria and 29 healthy controls (HC). Standard 12-lead electrocardiogram was performed on all participants. QT dispersion was defined as the difference between the longest and the shortest QT intervals. Similarly, the differences between the shortest and the longest P wave were defined as P wave dispersion. <h3>Results</h3> The QT dispersion was shorter in the fibromyalgia group, when compared with the HC group (p&lt;0.001, Table). In terms of P wave dispersion value, there was no significant difference between the fibromyalgia and HC groups (p=0.088, Table). <h3>Conclusions</h3> Longer QT and P wave dispersions could not be observed in patients with fibromyalgia in our study. Therefore, it may be concluded that fibromyalgia have not the increased risk of atrial and/or ventricular arrhythmias. <h3>References</h3> Campbell RW, et al. Eur Heart J 1985; 6 Suppl D:81. Okin PM, et al. Circulation 2000;101:61. Tukek T, et al. Clin Cardiol 2001;24:676-80. Pırıldar T, et al. Clin Rheumatol 2003;22:225-8. Cindas A, et al. Scand J Rheumatol 2002;31(1):22-6. Yavuz B, et al. Clin Rheumatol 2007;26:376-9. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4140
Antibodies to DNA
Authors: Bevra Hannahs Hahn
Journal: New England Journal of Medicine (1998)

Antibodies to DNA are of interest to a broad spectrum of physicians and other scientists. The presence of large amounts of serum antibodies to double-stranded DNA is specific for systemic lupus erythematosus, and some subgroups of these antibodies are pathogenic. It is likely that people are predisposed to have systemic lupus erythematosus if they can make pathogenic subgroups of antibodies to DNA and if they cannot down-regulate them appropriately. Studies of patients with systemic lupus erythematosus and of murine models of the disease have provided information regarding the different types of antibodies to DNA, their role in pathogenesis, and new . . .
Abstract 4970: Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma
Authors: Todd D. Prickett, Xiaomu Wei, Cristina G. Viloria, Alfredo Molinolo, Jimmy C. Lin, Pedro Cruz, Steven A. Rosenberg, Michael A. Davies, Jeffrey E. Gershenwald, Carlos López-Otin, Yardena Samuels
Journal: Cancer Research (2011)

Abstract An important feature of cellular signaling and migration involves the proteolytic cleavage of extracellular matrix and/or pro-ligands involved in signal transduction. Proteins called proteases are responsible for this action and include the matrix-metalloproteinase family and the A Disintegrin and Metalloproteinases family to name a few. The A Disintegrin and Metalloproteinases with Thrombospondin domains (ADAMTS) have been suggested to function as tumor suppressors as several have been found to be epigenetically silenced in various cancers. Thus further analysis is warranted in determining if ADAMTS genes/proteins play a role in melanoma genesis. In the present study we performed a mutational analysis of 19 ADAMTS gene family members in human melanoma and identified a large fraction of melanomas to harbor somatic mutations. To evaluate the functional consequences of the most commonly mutated gene, ADAMTS18, six of its mutations were biologically examined. ADAMTS18 mutations had little effect on melanoma cell growth under standard conditions, but reduced cell dependence on growth factors. ADAMTS18 mutations also reduced adhesion to Laminin-I and increased migration in vitro and metastasis in vivo. Melanoma cells expressing mutant ADAMTS18 had reduced cell migration after shRNA-mediated knockdown of ADAMTS18, suggesting that ADAMTS18 mutations are growth-, migration- and metastasis- promoting in melanoma. These results demonstrate that the ADAMTS18 is a major target for mutational activation in melanoma and may be a useful diagnostic and/or therapeutic target. 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 4970. doi:10.1158/1538-7445.AM2011-4970
SAT0256 Analytical and Functional Assessments When Developing Biosimilar Candidates
Authors: T. Born, V. Fung
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biosimilar monoclonal antibodies (mAb) are expressed in unique host cell systems and without knowledge of specific process conditions, which are proprietary to the innovator. A biosimilar developer may choose to express a biosimilar mAb in a cell expression system of a similar lineage as the innovator, or one that is quite different. The choice of expression system can have an impact on many aspects of the molecule, including the N-linked glycosylation of the mAb, which may ultimately affect efficacy, safety or immunogenicity. Thus, multiple factors must be considered in choosing an appropriate expression system and process, with the ultimate goal of producing a mAb with highly similar analytical properties to the innovator mAb, and most importantly matching all functional aspects of the molecule, whether or not they are thought to be involved in the mechanisms of action. <h3>Objectives</h3> The studies were designed to characterize analytical similarities and differences in mAbs produced in differing cellular expression systems, and to identify the optimal expression system for achieving functional similarity of two mAbs. <h3>Methods</h3> Two case studies are presented, one examining the production of a proposed biosimilar mAb in a similar host expression system, and the other case examining production of a proposed biosimilar in a different host expression system. In the first case both mAbs are produced in cells of the CHO lineage, and in the second case a mAb produced in NS2/0 is compared to a mAb produced in CHO cells. The glycan profile of innovator and proposed biosimilar mAb are assessed, as well as resulting ADCC and CDC activity of the molecules. <h3>Results</h3> Characterization of mAb1 demonstrates that two mAbs of the same amino acid sequence and expressed in the same parental expression system can result in differences in glycan distribution. These differences in glycans could not be resolved with process development, and had significant impact on functional activity of mAb1. In contrast, characterization of mAb2 illustrates the ability to match functional activity between an innovator mAb and proposed biosimilar, even with differences in choice of cellular expression system and the expected underlying differences in glycan distribution. <h3>Conclusions</h3> Analytical differences, especially with respect to the N-linked glycan profile, should be expected between a biosimilar mAb and the innovator mAb, as well as between different biosimilar mAbs compared to each other. In a step-wise approach to biosimilar development, analytical differences between the proposed biosimilar mAb and the innovator should be carefully characterized, and functional similarity should be demonstrated, before proceeding with clinical studies. <h3>Disclosure of Interest</h3> T. Born Shareholder of: AMGEN, Employee of: AMGEN, V. Fung Shareholder of: AMGEN, Employee of: AMGEN <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5532
Regional Enteritis and Granulomatous Colitis Associated with Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency
Authors: Richard G. Sheehan, Thomas F. Necheles, Robert J. Lindeman, Heidi J. Meyer, James F. Patterson
Journal: New England Journal of Medicine (1967)

THE simultaneous occurrence of two uncommon diseases in several families originating from a relatively circumscribed geographical region suggests a relation. Erythrocyte glucose-6-phosphate dehydrogenase deficiency is due to a group of related mutations of enzyme structure or rate of synthesis, all inherited as sex-linked characteristics. The incidence varies from less than 0.5 per cent in males of northern European origin to over 20 per cent in certain oriental Jewish groups.1 Regional enteritis and granulomatous colitis appear to be closely related forms of chronic granulomatous disease of unknown origin, one affecting primarily the small intestine and the other, apparently the same process, . . .
P4-16-03: Proof of the Anti-Tumour Effect of Zoledronic Acid (ZA) in Naive Bone-Only Metastatic and Locally Advanced Breast Cancer: Results from the Biological Window Therapy.
Authors: C Foroni, D Andreis, M Maldotti, MR Cappelletti, DG Generali
Journal: Cancer Research (2011)

Abstract Background: Pre-clinical studies have demonstrated an anti-tumour activity of ZA in several cancers. However, the clinical evidence of the ZA anti-tumour effect is still uncertain. Our study aimed to prove that ZA has anti-tumour activity administered alone as a biological window of 14 days therapy on naïve bone-only metastatic and locally advanced breast cancer. Material and Methods: 27 patients with locally advanced breast cancer (Group 1) and 12 patients at their first relapse with bone metastasis only (Group 2) received 4 mg single dose of ZA before starting with any treatment. In Group 1, Ki67 expression was evaluated in tumour specimens obtained before and after ZA administration (basal, day 14). In Group 2, circulating tumour cells (CTCs) were evaluated at baseline, 48 hrs and day 14. In Group 1 and 2, the apoptosis and necrosis of tumour cells were tested on blood samples by M30 and M65 ELISA assay respectively. Parallel, the anti-antitumor activity of ZA, given at the dose of 250 mg/mouse every 4 days for 6 cycles, in MDA-Mb-231 bearing mice was evaluated. Results: A significant reduction of Ki67 expression after 14 days (mean, 25.33% to 21.78%; p=0.035) was observed in Group 1. In Group 2, we detected a significant reduction of CTC number after 48 hrs (median, 16 to 7; p=0.045), followed by a tendency to increase on day 14 (p=0.093). The M30/M65 analysis performed on paired blood samples in Group 2 showed after 14 days a significant increase in M65 (median, 97 to 112 U/L; p=0.018), more accentuated than the concomitant increase in M30 (p=0.308). In MDA-MB-231 bearing mice, ZA treatment caused a significant inhibition of tumor growth. Conclusions: These results are the first prospective clinical data showing a direct anti-tumour effect (either on the tumour or on CTCs) of ZA, confirming the in vitro data. By directly affecting the proliferation, ZA could have an anti-tumour effect via induction of necrosis, suggesting its possible use in combination with conventional oncologic treatments of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-03.
AB1241 Interstitial lung disease ultrasound evaluation in churg-strauss patients
Authors: A. Delle Sedie, C. Baldini, M. Latorre, P. Pepe, L. Riente, P.L. Paggiaro, S. Bombardieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Churg Strauss syndrome (CSS) is a systemic vasculitis characterized by asthma, eosinophilia and lung infiltrates. Ultrasound (US) has recently been used to study the lung and specific findings (called B-lines) have been related to the thicknening of the interlobular septa, making it possible to assess interstitial lung disease. The B-lines have also been related to a decrease of carbon monoxide diffusing capacity (DLCO) values[1]. <h3>Objectives</h3> The aim of the study was to assess the usefulness of US in the assessment of lung involvement in a group of CSS patients. <h3>Methods</h3> A group of consecutive outpatients affected by CSS (according to ACR criteria) were enrolled. Asthma severity was evaluated according to FEV1, FEV1/SVC, GINA guidelines, asthma control test. In all the cases, chest X-rays and DLCO were performed. Systemic clinical and serological disease manifestations, BVAS and VDI were assessed. Lung US was performed blindly by the same operator with a Toshiba Powervision 6000 machine and a 6 MHz linear probe, using a scanning protocol used in the previous studies [2]. Total score was given by the sum of the B-lines in each intercostal space. <h3>Results</h3> Ninenteen patients (mean age 55.3±14.5 years, F:M=7:12, mean disease duration 6.9±7.1 years, ANCA positivity 32%) were enrolled. At study entry, all the patients were in clinical remission; asthma was poorly or partially controlled in 4 and 8 patients, respectively. Two patients showed persistent interstitial involvement on X-ray, which was confirmed on HRCT scan. Inhaled glucocorticoid (GC) and long-acting beta2-agonist were taken by all the patients. Fifteen subjects were on maintenance therapy with low-doses oral GC associated with methotrexate in 6/15 cases. B-lines total score was negative (&lt;12) (2) in 15/19 patients (mean 4.1±3.4). A positive B-line total score was detected in 4/19 subjects (mean 38±32.3) including the 2 HRCT positive cases. <h3>Conclusions</h3> These preliminary results emphasise the role of US in the assessment of lung interstitial involvement in CSS patients with the advantages of having a good prediction of disease damage and of the use of a radiation-free bed-side imaging technique. <h3>References</h3> Gargani L, Doveri M, D'Errico L et al. Rheumatology (Oxford). 2009;48:1382-7 Delle Sedie A, Doveri M, Frassi F et al. Clin Exp Rheumatol 2010;28(5 Suppl 62):S54 <h3>Disclosure of Interest</h3> None Declared
Abstract 4818: Validation and clinical utility of a human hepatocellular carcinoma metastasis signature as prognostic classifier
Authors: Stephanie K. Roessler, Hu-Liang Jia, Anuradha S. Budhu, Lun-Xiu Qin, Qing-Hai Ye, Snorri Thorgeirsson, Zhao-You Tang, Xin W. Wang
Journal: Cancer Research (2010)

Abstract Hepatocellular carcinoma (HCC) is the most frequent malignant tumor in the liver and the third leading cause of cancer death worldwide. The high mortality of HCC is mainly caused by intra-hepatic metastasis or the high rate of recurrence after surgery. Despite potentially curative surgical resection, eligibility is scarce and patients suffer from a high recurrence rate. Recently, we developed a tumor-based 153-gene signature that is predictive of HCC portal venous metastasis and survival in 40 HCC patients (Ye et al, Nat Med, 9: 416-23, 2003). This signature was based on cDNA microarray profiling of 20 well defined HCC cases, in which ten developed tumor thrombi in the major branch of portal vein and ten had no metastasis at one year follow-up. In this study, we sought to validate this signature for its utility in predicting HCC survival using two independent cohorts. The first cohort consisted of 247 predominantly HBV+ HCC cases analyzed by the Affymetrix U133A 2.0 platform. The second cohort included 139 cases with mixed etiology analyzed by the Human Array-Ready Oligo Set (version 2) array platform. We employed a survival risk prediction algorithm with 10-fold cross validation and 1000 random permutation to test whether the 153-gene signature is associated with survival. We found that this gene signature was able to predict prognosis in both independent HCC cohorts. Importantly, the risk prediction was independent of the microarray platform and etiology. In addition, survival prediction was successful in patients with small (&amp;lt;5 cm in diameter) and/or solitary tumor and the signature performed well on patients particularly with early recurrence (&amp;lt;2 years). Thus, the 153-gene signature was validated in three independent cohorts to be related to HCC patient survival. Furthermore, the risk prediction performed independently of clinical characteristics and microarray platform. We recommend that this signture may serve as a molecular diagnostic test useful to assess the risk that an HCC patient will recur within 2 years after resection, particularly for those with tumors &amp;lt;5cm and in a solitary presentation. Supported by NIH intramural research funds 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 4818.
The Contribution of Low Birth Weight to Infant Mortality and Childhood Morbidity
Authors: Marie C. McCormick
Journal: New England Journal of Medicine (1985)

The low-birth-weight infant remains at much higher risk of mortality than the infant with normal weight at birth. In the neonatal period, when most infant deaths occur, the proportion of low-birth-weight infants, especially those with very low weight, is the major determinant of the magnitude of the mortality rates. Furthermore, differences in low-birth-weight rates account for the higher neonatal mortality rates observed in some groups, particularly those characterized by socioeconomic disadvantages. Much of the recent decline in neonatal mortality can be attributed to increased survival among low-birth-weight infants, apparently as a result of hospital-based services. The application of these services is currently considered cost-effective, although whether this will continue to be true in the future is unclear because of the increased survival of very tiny infants. Although low-birth-weight infants remain at increased risk of both postneonatal mortality and morbidity in infancy and early childhood, the risk is substantially smaller than that of neonatal death. In addition, these adverse later outcomes have not offset the gains achieved in the neonatal period. Nonetheless, the increased survival of high-risk infants raises concern about their future requirements for special medical and educational services and about the stress on their families. Despite increased access to antenatal services, only moderate declines in the proportion of low-birth-weight infants has been observed, and almost no change has occurred in the proportion of those with very low weight at birth. In addition, in many areas of the country the birth-weight-specific neonatal mortality rates are similar for groups at high and low risk of neonatal death. In view of these findings, continuation of the current decline in neonatal mortality and reduction of the mortality differentials between high- and low-risk groups require the identification and more effective implementation of strategies for the prevention of low-weight births.