tbuckley/cabot-search huggingface dataset:
FRI0006 Mmp3 Predicts A Subgroup of Rheumatoid Patients with Structural Remission under Low-Dose Methotrexate (MTX) Monotherapy
Authors: K. Shiozawa, T. Yamane, M. Murata, C. Tanaka, N. Yo, R. Yoshihara, Y. Tanaka, K. Tsumiyama, S. Shiozawa
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Methotrexate (MTX) is still a mainstay in the therapy of rheumatoid arthritis (RA) in the era of biologics therapy, and some patients do respond well without radiographic progression to MTX monotherapy on individual basis. According to O9Dell et al., initial MTX monotherapy with the option step-up to combination therapy indicates that approximately 30% of patients fare well with MTX monotherapy (Ref 1). However, the discriminant identifying the subgroup with radiographic non-progression remains unclear and thus, predicting at the outset such patient subgroup would be highly rewarding clinically. <h3>Objectives</h3> To evaluate clinical efficacy of low-dose MTX monotherapy unique to Japan, and discover a predictor identifying a subgroup of RA patients with radiographic non-progression. <h3>Methods</h3> Clinical measure including disease activity score 28 (DAS28), modified health assessment of questionnaire (mHAQ) and others in rheumatoid patients continuously treated with MTX monotherapy (n=161) was compared with radiographic year-progression of van der Heijde modified total Sharp score (ΔTSS), by classifying the patients into subgroups with structural remission (REM; ΔTSS≤0.5), clinically relevant radiographic progression (CRRP; ΔTSS&gt;3) and rapid radiographic progression (RRP; ΔTSS&gt;5) prospectively for 3 yrs. <h3>Results</h3> Disease activity was improved yearly from baseline to 3yrs: DAS28-ESR (3) from 5.2±1.1 to 3.9±1.7, %DAS28 remission from 1% to 19%, mHAQ from 0.54±0.47 to 0.18±0.32, %mHAQ remission from 16% to 60%, and Boolean remission from 0.8% to 24.0%. As to radiographic progression, the patients classified to REM were increased from 62/161 (38.5%) to 69/137 (50.4%) (p=0.0466), as compared with 55/161 (34.2%) to 28/137 (20.4%) of CRRP (p=0.0095) and 35/161 (21.7%) to 15/137 (10.9%) of RRP (p=0.0019) patients. Receiver operating characteristic (ROC) analysis revealed lower baseline and annual serum MMP3 as a predictor identifying a subgroup of patients with radiographic non-progression: the patients containing baseline serum MMP3 levels below 103.7 ng/ml were classified to neither CRRP nor RRP, with negative predictive values (NPV) 88.7% and 96.8%, respectively (Fig.1). This baseline cut-off level was applicable to succeeding 1∼2 or 2∼3 yrs of MTX monotherapy, with NPV 88.1% or 87.9% (CRRP) and 87.8% or 91.0% (RRP), respectively, and also when male and female patients were studied separately. <h3>Conclusions</h3> Under low-dose MTX monotherapy, approximately half of Japanese rheumatoid patients maintained structural remission, and this radiographic non-progression was predictable by lower levels of serum MMP-3 at the outset. <h3>References</h3> JR O9Dell, et al. Arthritis Rheum 65:1985,2013. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3071
In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA
Authors: Dustin J Landau, Elizabeth Drake Brooks, Pablo Perez-Pinera, Hiruni Amarasekara, Adam Mefferd, Songtao Li, Andrew Bird, Charles A Gersbach, Dwight D Koeberl
Journal: Molecular Therapy (2016)

Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P < 0.04). Furthermore, transgene integration has been confirmed by sequencing in the majority of the mice treated with both vectors. Targeted alleles were 4.6-fold more common in livers of mice with GSD Ia, as compared with normal littermates, at 8 months following vector administration (P < 0.02). This suggests a selective advantage for vector-transduced hepatocytes following ZFN-mediated integration of the G6Pase vector. A short-term experiment also showed that 3-month-old mice receiving the ZFN had significantly-improved biochemical correction, in comparison with mice that received the donor vector alone. These data suggest that the use of ZFNs to drive integration of G6Pase at a safe harbor locus might improve vector persistence and efficacy, and lower mortality in GSD Ia.
A1.34 Telocytes in minor salivary glands of patients with primary Sjögren’s syndrome: association with the extent of inflammation and ectopic lymphoneogenesis
Authors: A Alunno, L Ibba-Manneschi, O Bistoni, I Rosa, S Caterbi, R Gerli, M Manetti
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> It has been recently reported that telocytes, a stromal cell subset involved in immune surveillance and tissue homeostasis, are hampered in the target organs of inflammatory/autoimmune disorders. Previous studies demonstrated a marked reduction in telocytes in the skin and in other organs targeted by the fibrotic process of systemic sclerosis patients and a disappearance of telocytes was observed in intestinal wall biopsies of patients with inflammatory bowel diseases. As far as salivary glands (SGs) are concerned, to date the only study available described telocyte distribution in normal parotid glands. Since no data concerning telocytes in minor SGs (MSGs) are currently available, aim of the study was to evaluate telocyte distribution in human MSGs with normal architecture, non-specific chronic sialadenitis (NSCS) and primary Sjögren's syndrome (pSS)-focal lymphocytic sialadenitis. <h3>Methods</h3> Twelve pSS patients and 16 sicca non-pSS subjects were enrolled and serial sections of MSGs were evaluated. Haematoxylin and eosin staining was employed to assess focus score and Tarpley biopsy score. Cellular infiltrate and lymphoid organisation were characterised by immunofluorescence with double staining for CD3 and CD20 (T/B cell segregation) and single staining for CD21 (germinal centre –(GC)-like structures). Telocytes were identified by CD34 immunohistochemistry and double immunofluorescence staining for CD34 and CD31 (CD34-positive/CD31-negative stromal cells). A double staining for CD34 and CD21 was also performed to co-localise telocytes and GC-like structures. <h3>Results</h3> In normal-MSGs telocytes were numerous and their long cytoplasmic processes surrounded vessels and formed an almost continuous layer encircling both the excretory ducts and the secretory units. In NSCS-MSGs, despite the presence of a certain degree of inflammation, telocytes were normally represented. Conversely, telocytes were markedly reduced in pSS-MSGs compared to normal- and NSCS-MSGs. Such a decrease was associated with both worsening of glandular inflammation and progression of ectopic lymphoneogenesis. In fact, telocyte reduction was more pronounced in severe FLS infiltrates with clear T/B cell segregation compared with milder FLS infiltrates without T/B cell segregation. In addition, no telocytes could be detected around ducts surrounded by inflammatory foci displaying GC-like structures. <h3>Conclusion</h3> Our findings suggest that telocytes may be involved in MSG homeostasis and therefore in the pathogenesis of pSS. The specific pro-inflammatory cytokine milieu of pSS-MSGs may be one of the causes of telocyte loss.
Prolonged endoscopic loop ligation for removal of gastrointestinal tumors
Authors: W. Chen, B. Weston, S. Krishna, G. Gomez, A. Rashid, M. Katz, J. Lee, G. Raju
Journal: Endoscopy (2013)

Endoscopic loop ligation has been shown to be successful in the removal of a variety of large mucosal and submucosal tumors of the gastrointestinal tract, such as lipomas, leiomyomas, lymphangiomas, carcinoid tumors, and Brunner's adenomas [1] [2] [3] [4]. However, immediate release of the endoscopic loop after ligation of the tumor may fail to eradicate the lesion in one session [1] [2]. We therefore evaluated the effect of holding on to the ligating loop for 15 minutes prior to its release on the rate of complete resection in one session, which therefore avoided a second session of loop ligation.
AB0522 Effect of first-line anti-tnf therapy on health related quality of life in patients with ankylosing spondylitis - results from the czech biologics registry attra
Authors: S. Forejtova, J. Závada, K. Jarosova, M. Uher, K. Hejduk, K. Pavelka, J. Vencovsky
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The aim of this study was to describe changes in the Medical Outcomes Study Short Form-36 (SF-36) physical (PCS) and mental (MCS) component summary and domain scores for ankylosing spondylitis (AS) patients enrolled in the ATTRA registry and completing one year of the first-line anti-TNF therapy., SF-36 domain scores of AS patients before and after one year of anti-TNF therapy were compared with age-standardized normative values of the general Czech population. <h3>Methods</h3> Only AS patients with available clinical (BASDAI, HAQ) and HRQOL (SF-36) data completing one year of anti-TNF treatment were included in the analyses. Paired Wilcoxon test was used to compare changes in continuous variables with baseline levels. One- sample T test was used to compare age-standardized mean domain scores of AS patients with reportedCzech normative values [1]. Numbers are median (5%&gt;95% percentile) if not stated otherwise <h3>Results</h3> 535 AS patients with available required data and completing one year of the first-line anti-TNF therapy were identified. In the analyzed sample there were 74% of males, with median age of 37 years (25-75) and median disease duration of 5 years (0-22) at the start of anti-TNF therapy. 23%, 35% and 43%of patients were treated with infliximab, adalimumab, and etanercept, respectively. PCS scores improved from 29 (11-62) to 58 (26-85) at W12 (p&lt;0.001) and to 64 (26-91) at W54 (p&lt;0.001). MCS scores improved from 43 (17-75) to 66 (31-87) at W12 (p&lt;0.001) and to 70 (31-91) at W54 (p&lt;0.001). <h3>Conclusions</h3> In this cohort of AS patients completing one year of the first-line anti-TNF therapy clinically meaningful and statistically significant improvements were observed in all SF-36 domains. In 4 domains (vitality, social functioning, role emotional, and mental health) the AS patients reached normative values of the Czech general population. . <h3>References: References</h3> Sobotník Z. [Experiences with the application of preliminary Czech version of the questionary SF36]. Zdravotnictví v ČR 1 – 2 / 1998, str. 50 – 54 <h3>Acknowledgements</h3> Supported by project 00023728 from Ministry of Health in the Czech Republic <h3>Disclosure of Interest</h3> None Declared
Correlation of serum CNTO 328-Anti IL-6 monoclonal antibody (MAb) concentrations and biomarker expression in renal cell carcinoma (RCC) patients
Authors: U. Prabhakar, H. Jang, Q. Jiao, J. Ford, B. E. Miller, M. A. Graham, H. M. Davis
Journal: Journal of Clinical Oncology (2004)

2560 Background: RCC is the most common malignant tumor of the kidney and is associated with high expression of interleukin-6 (IL-6). IL-6 modulates the transcription of several liver-specific genes including C-reactive protein (CRP) and serum amyloid protein (SAA), both of which are prognostic markers in RCC. The goal of the present study was to assess the serum concentrations of an intravenously administered chimeric anti-IL-6 MAb (CNTO 328) in RCC patients and evaluate if the anti -L-6 MAb could inhibit the serum expression of IL-6, CRP, and SAA in these patients. Methods: Anti IL-6 MAb (1, 3, & 6 mg/kg) was administered by i.v. infusion to metastatic RCC patients on days 1, 29, 43, and 57. Blood samples were collected at various time points following treatment. MAb and biomarker concentrations in these samples were analyzed using validated ELISA methods. Results: Preliminary results following a single intravenous infusion of the anti-IL-6 MAb indicated that all patients exhibited significant serum exposure to the antibody. The serum concentrations of the anti-IL-6 MAb were proportional to the dose of the antibody administered. The half-life of the antibody ranged from 14.69 –17.54 days. Serum CRP and SAA levels, which have a strong correlation and mechanistic association with IL-6 activity, were both significantly inhibited in these patients. The degree of inhibition of the serum biomarkers was dependent on the dose of anti IL-6 MAb administered, serum anti-IL-6 concentrations and the baseline levels of these biomarkers. Conclusions: Collectively, these results indicate that the anti-IL-6 MAb used in this study is showing early promising changes in potentially predictive biomarkers of RCC and may have therapeutic impact in this disease. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor, Inc. Centocor Centocor
Abstract 5099: Adiponectin inhibits oxidative stress in prostate cancer cells
Authors: ZheFeng Hou, JianPing Lu, Jehonathan H. Pinthus
Journal: Cancer Research (2010)

Abstract INTRODUCTION AND OBJECTIVES: Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC) but the mechanisms underlying this relationship remain to be fully elucidated. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy human but its levels are reduced in obesity. Case control studies have documented an association between lower adiponectin blood levels and PC implying that obese individuals with low adiponectin levels are more susceptible in developing PC. In this study we examined the effect of adiponectin on the generation and reduction of oxidative stress (OS) in PC cells, a process that intimately relates to the initiation and development of PC. METHOD: As models we used two human PC cell lines (22rv1 and DU145) expressing the adiponectin receptors AdipoR1, AdipoR2 and T-cadherin. Cells were treated with increasing doses of human recombinant adiponectin (0-40μg/ml) and were subjected to the following tests: Quantification of cellular OS (NBT reduction assay), expression of catalase and MnSOD (Western blot analysis), comparison of transcript levels of NADPH oxidases (NOX) enzymes- a major source of reactive oxygen species in PC cells (RT-PCR) and determination of the global cellular anti-oxidative capacity and catalase activity (colorimetric assays). RESULT: Adiponectin significantly inhibited OS in both cell types in a dose dependent manner by inducing the expression of the two key anti-oxidative enzymes; catalase and MnSOD, leading to an increase in the anti-oxidative capacity of the cells. Treatment with adiponectin reduced Nox 2,4 mRNA expression in Du145 cells but increased it in 22RV1 cells. CONCLUSIONS: These results suggest a protective role for adiponectin against the initiation and development of PC, through OS inhibition. 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 5099.
Abstract 3400: A systems biology approach reveals common metastatic pathways in osteosarcoma
Authors: Ricardo J. Flores, Yiting Li, Marina Vanucci, Ching C. Lau, Tsz-Kwong Man, Serrine S. Lau
Journal: Cancer Research (2012)

Abstract Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis will not likely identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the up-regulated genes and glycoproteins separately revealed pathways associated to metastasis including RAS-related G-proteins signaling, cell cycle regulation, epithelial-to-mesenchymal-transition, cell adhesion, and WNT signaling. However, no common significant pathway was found between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes that remained hidden from the independent transcriptomic and glycoproteomic analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified important common pathways, including “Cytoskeleton remodeling/TGF/WNT,” “Development/WNT signaling,” “Cytoskeleton remodeling/Cytoskeleton remodeling,” and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the two cell line models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using a Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological networks that are known to play critical roles in metastasis. Since WNT signaling has been previously implicated in OS and other tumors, further characterization of this common pathway and other topological pathways may lead to a novel therapeutic strategy for curing metastatic OS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3400. doi:1538-7445.AM2012-3400
ECHOCARDIOGRAPHIC ASSESSMENT OF CALCIFIC MITRAL STENOSIS OVERESTIMATES SEVERITY COMPARED TO RHEUMATIC MITRAL STENOSIS
Authors: Kenta Nakamura, Sammy Elmariah, Eugene Pomerantsev, Marcia Leavitt, Ignacio Inglessis, Igor Palacios, Jonathan Passeri
Journal: Journal of the American College of Cardiology (2016)
Patient Educators Hold First Meeting
Authors: M. Croci
Journal: JNCI Journal of the National Cancer Institute (1989)

Patient Educators Hold First Meeting Get access Michele Croci Michele Croci Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 7, 5 April 1989, Page 480, https://doi.org/10.1093/jnci/81.7.480 Published: 05 April 1989
Influence of meteorological data on sun tolerance in patients with erythropoietic protoporphyria in France
Authors: S. de Bataille, H. Dutartre, H. Puy, J.-C. Deybach, L. Gouya, E. Raffray, M. Pithon, J.-F. Stalder, J.-M. Nguyen, S. Barbarot
Journal: British Journal of Dermatology (2016)

Erythropoietic protoporphyria (EPP) is a rare metabolic disorder, characterized by photosensitivity, caused by errors of the haem biosynthetic pathway. Avoidance of sun exposure is recommended; however, some patients suggested a paradoxical improvement of symptoms when they move to sunny areas.In a national French study, we sought to investigate the influence of sun exposure on EPP symptoms.We used a national transversal observational study by questionnaire. Patients were selected from the national record of the Centre Français des Porphyries (French Porphyrias referral centre). Sun exposure level by geographic area was assessed using climate data provided by the French national meteorological service (Météo France).Eighty-nine patients were included. We notably observed that 40% of patients declared an improvement in their tolerance of sun exposure after repeated sun exposures. In the more sunny areas, the intensity of the pain was lower (r = -0·26) and the duration of the sun exposure responsible for flares was longer (r = 0·39) than in the areas that were less sunny (P < 0·05).This study proposes a benefit of natural progressive sun exposure for patients with EPP.
High resolution microendoscopy for classification of colorectal polyps
Authors: S. Chang, R. Shukla, A. Polydorides, P. Vila, M. Lee, H. Han, P. Kedia, J. Lewis, S. Gonzalez, M. Kim, N. Harpaz, J. Godbold, R. Richards-Kortum, S. Anandasabapathy
Journal: Endoscopy (2013)

<b>Background and study aims:</b> It can be difficult to distinguish adenomas from benign polyps during routine colonoscopy. High resolution microendoscopy (HRME) is a novel method for imaging colorectal mucosa with subcellular detail. HRME criteria for the classification of colorectal neoplasia have not been previously described. Study goals were to develop criteria to characterize HRME images of colorectal mucosa (normal, hyperplastic polyps, adenomas, cancer) and to determine the accuracy and interobserver variability for the discrimination of neoplastic from non-neoplastic polyps when these criteria were applied by novice and expert microendoscopists. <b>Methods: </b>Two expert pathologists created consensus HRME image criteria using images from 68 patients with polyps who had undergone colonoscopy plus HRME. Using these criteria, HRME expert and novice microendoscopists were shown a set of training images and then tested to determine accuracy and interobserver variability. <b>Results: </b>Expert microendoscopists identified neoplasia with sensitivity, specificity, and accuracy of 67 % (95 % confidence interval [CI] 58 % – 75 %), 97 % (94 % – 100 %), and 87 %, respectively. Nonexperts achieved sensitivity, specificity, and accuracy of 73 % (66 % – 80 %), 91 % (80 % – 100 %), and 85 %, respectively. Overall, neoplasia were identified with sensitivity 70 % (65 % – 76 %), specificity 94 % (87 % – 100 %), and accuracy 85 %. Kappa values were: experts 0.86; nonexperts 0.72; and overall 0.78. <b>Conclusions:</b> Using the new criteria, observers achieved high specificity and substantial interobserver agreement for distinguishing benign polyps from neoplasia. Increased expertise in HRME imaging improves accuracy. This low-cost microendoscopic platform may be an alternative to confocal microendoscopy in lower-resource or community-based settings. Clinical trial registration no. NCT01384240