tbuckley/cabot-search huggingface dataset:
A3.6 Gene and micro-RNA expression of aggressive fibroblast-like synoviocytes from mice with chronic arthritis
Authors: F Madarena, M Böttcher, A Grützkau, JR Grün, A Jüngel, S Gay, T Kamradt
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Glucose-6-phosphate isomerase (G6PI) immunisation induces acute self-limiting arthritis in DBA/1 mice. Upon depletion of regulatory T cells (Treg<sub>s</sub>) it is possible to deliberately switch the outcome towards a chronic, destructive and non-remitting disease. Fibroblast-like synoviocytes (FLS) are important effector cells in rheumatoid arthritis (RA). The objective of this work is to unravel differences at the transcriptomic and miRNomic level between FLS from Treg-depleted mice (chronic) and FLS from not-depleted mice (acute). <h3>Materials and methods</h3> FLS were isolated from the small joints of G6PI immunised mice either Treg-depleted (chronic) or not-depleted (acute) at day 56 post-immunisation or from healthy mice as a baseline control. A transepitelial resistance assay (MATRIN) was used to test FLS collagen destructive potential, while apoptosis was assessed by serum starvation for 5 days followed by flow cytometry staining. Whole genome expression analysis was realised using mouse 430 2.0 array (Affymetrix). Whole microRNA expression was assessed using TaqMan<sup>®</sup> Rodent MicroRNA A Array v2.0 (Applied Biosystems). <h3>Results</h3> FLS from chronic mice at late stages of arthritis show an increased collagen destructive potential and their sensitivity to apoptosis is reduced. Transcriptomic analysis reveals a strong difference in gene expression between FLS from chronic mice and FLS from acute mice. Stimulation with pro-inflammatory cytokines at different time points modulates gene expression differently in cells from chronic mice, enhancing the expression of genes related to cell adhesion, regulation of apoptosis, cell motion and inflammatory response. Comprehensive miRNA analysis shows a panel of overexpressed and down regulated miRNAs that could have an important role in the regulation of arthritis chronicity. <h3>Conclusions</h3> FLS from chronic mice are more aggressive and less sensitive to cell death than FLS from acute mice. Whole genome expression analysis confirmed their profound differences at a molecular level. Moreover, stimulation with pro-inflammatory cytokines differentially activates gene expression in FLS from mice with chronic, destructive arthritis. Differences in microRNA expression also confirm these findings. G6PI-induced arthritis mouse model is a useful tool to unravel the role of differentially expressed genes and microRNAs in FLS from chronic mice, in order to discover potential candidates for therapeutic intervention in humans.
BRCA1 Discovery Aftermath: No Rush for Genetic Testing
Authors: B. Kuska
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article BRCA1 Discovery Aftermath: No Rush for Genetic Testing Get access Bob Kuska Bob Kuska Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 21, 1 November 1995, Pages 1578–1579, https://doi.org/10.1093/jnci/87.21.1578 Published: 01 November 1995
P343Effect of T3 on human induced pluripotent stem cell-derived cardiomyocyte maturation
Authors: N Hellen, JX Wheeler, C Pinto Ricardo, G Foldes, T Kodagoda, G Whiting, M Mioulane, C Terracciano, K Vauchez, SE Harding
Journal: Cardiovascular Research (2014)

Purpose: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold great potential for regenerative medicine and in vitro screening. However, the phenotype is immature and more closely resembles foetal/neonatal cardiomyocytes. The aim of this study is to drive hiPSC-CM to a more mature state using thyroid hormone, triiodothyronine (T3), which has a role in cardiomyocyte maturation during development. Methods: hiPSC-CM (Cellular Dynamics) were treated with 30nM T3 for up to 4 weeks. Expression of β1 adrenergic receptor (β1AR) was assessed by qPCR (Taqman). Beating rates were determined using a Nikon Eclipse TE2000E microscope with Digital sight camera and NIS Elements3.2 software video tracking. Ca2+ dynamics were studied using Fluo-4AM loaded cells imaged with a Nikon Eclipse T6200 and Redshirt NeuroCMOS camera at 0.5KHz with 1Hz, 15V, 5ms field stimulation. Comparative proteomic analysis (4 week T3) was performed by mass spectrometry using isobaric tags. Data expressed as mean ±SEM; statistical significance determined by student's t-test (n=3). Results: 4 week T3 treatment resulted in a 1.5-fold increase in basal beating rate. T3 increased β1AR gene expression and remained stable for up to 2 weeks (p<0.05). CGP 20712A (10μM), a β1AR inverse agonist, decreased the beating rate of T3-treated cells (39.3±9.7bpm) to basal levels in untreated cells (25.7±9bpm). Ca2+ transient analysis revealed alterations in Ca2+ handling. 4 week T3 treatment resulted in decreased time to transient peak from 244±4.0 ms to 90.7±15 (p<0.0006). Time to 50% decay also decreased from 309.2±6.6ms to 287.3±2.3ms (p<0.05) and transient duration (start to 75% decay) decreased from 695.4±6.4ms to 537.9±21.3ms (p<0.002). Proteomic analysis revealed increases in proteins involved in regulating sarcoplasmic reticulum (SR) function including; phospholamban (17.2%), SERCA (27.6%) and calsequestrin2 (303.8%). In addition increases in mitochondrial enzymes, including ATP5B (32.7%), and α/βMHC ratio were detected along with decreases in slow skeletal troponin I (-43.7%) and C (-36.2%) isoforms. Conclusions: T3 treatment induced alterations in expression of proteins involved in SR function, mitochondrial metabolism and cytoskeletal composition. In addition, T3 treatment improved Ca2+ handling and increased β1AR function, with increases in beating rate possibly driven by constitutive β1AR activity. Collectively these data provide evidence for a shift towards a more mature phenotype and indicate that this may be an effective strategy to drive maturation of hiPSC-CM.
Individualized Pharmacokinetically-Guided Dosing of Pazopanib: a Feasibility Study in Cancer Patients
Authors: R. Verheijen, S. Bins, C.G. Gadellaa-van Hooijdonk, R.H.J. Mathijssen, M.P. Lolkema, L. van Doorn, K. Rotteveel-Buchholtz, J.H. Schellens, J.H. Beijnen, A.D.R. Huitema, N. Steeghs
Journal: Annals of Oncology (2014)
Differing Birth Weight among Infants of U.S.-Born Blacks, African-Born Blacks, and U.S.-Born Whites
Authors: Richard J. David, James W. Collins
Journal: New England Journal of Medicine (1997)

In the United States, the birth weights of infants of black women are lower than those of infants of white women. The extent to which the lower birth weights among blacks are related to social or genetic factors is unclear.
Risk Factors for Perinatal Transmission of Human Immunodeficiency Virus Type 1 in Women Treated with Zidovudine
Authors: Lynne M. Mofenson, John S. Lambert, E. Richard Stiehm, James Bethel, William A. Meyer, Jean Whitehouse, John Moye, Patricia Reichelderfer, D. Robert Harris, Mary Glenn Fowler, Bonnie J. Mathieson, George J. Nemo
Journal: New England Journal of Medicine (1999)

Maternal, obstetrical, and infant-related factors associated with the risk of perinatal transmission of human immunodeficiency virus type 1 (HIV-1) were identified before the widespread use of zidovudine therapy in pregnant women. The risk factors for transmission when women and infants receive zidovudine are not well characterized.
P05.06 * INTRACRANIAL GERMINOMA IN CHILDREN-SINGLE INSTITUTIONAL EXPERIENCE
Authors: L. M. Paripovic, J. Bokun, Z. Bekic, V. Ilic, M. P. Slovic, I. Tufegdzic, V. Vukovic, D. Grujicic, M. Nikitovic
Journal: Neuro-Oncology (2014)

PURPOSE: The aim of our study is to evaluate results of treatment and to develop optimized treatment in children with Germinoma of Central nervous system (CNS). METHOD: Between 2001 and 2013., in Institute for Oncology and Radiology of Serbia we treated 9 patients with CNS Germinoma. The patients median age was 13 years (range 8 -18 yrs), and the male to female ratio was 8:1. A solitary tumor was found in pineal region (3 pts), in region ventriculi III and region supraselaris (2 pts), in one patient in region thalami, in one patient in region mesencephalon and 1 patient has leptomeningeal dissemination. Two patients had elevated B_HCG level in cerebrospinal fluid. After surgery (6 biopsy and 3 gross total resection) all patients received the boost to the primary tumor bed with additional prophylactic therapy to the craniospinal axis. Three patients (33,3 %) were treated with radiotherapy only and six pts (66,7%) were treated by using multimodal therapeutic approach including chemotherapy and radiotherapy. Two patients were treated according to SIOP GSCT trial - both achieved complete response (CR) after neoadjuvant chemotherapy. After irradiation patient with disseminated disease had also no residual tumor and afterwards he received 4 cycles of PEI regimen. One patient received 4 cycles of PEI regimen, also with complete response, followed by irradiation; one patient received only 2 cycles of SIOP GSCT regimen after irradiation (because of hematological toxicity); one patient received 1 cycle of PEI regimen, followed by irradiation and due to chematological toxicity, 3 cycles of Carboplatinum, Etoposid. RESULTS: All patients, treated either with radiotherapy or with radio and chemotherapy, remained disease free during the 20 to 146 months follow-up period (Me= 50 months). CONCLUSION: Results indicate that intracranial germinoma are highly radio and chemosensitive tumors. These excellent results suggest that ongoing trials are needed so to optimize treatment strategy in an effort to minimize late effects of therapy.
The esophagus as a working channel: successful closure of a large Mallory–Weiss tear with clips and an endoloop
Authors: H. Ivekovic, N. Rustemovic, T. Brkic, M. Opacic, R. Pulanic, R. Ostojic, B. Vucelic
Journal: Endoscopy (2011)

A 56-year-old man with alcoholic liver disease presented to our unit with a 1-day history of hematemesis. On admission, his blood pressure was 100/60 mmHg and pulse rate 102 beats/minute. The initial hematocrit was 29 %. Urgent esophagogastroduodenoscopy (EGD) revealed a large esophageal tear at the cardia, measuring 15 × 10 mm ([Fig. 1]). A diagnosis of Mallory–Weiss tear was made.
THU0109 The PTPN22 C1858T Polymorphism and Rheumatoid Arthritis: A Meta-Analysis
Authors: Y. H. Lee, J.-H. Kim, S. J. Choi, J. D. Ji, G. G. Song
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene encodes a lymphoid-specific phosphatase (Lyp). Lyp is an intracellular PTP, and physically binds through its proline-rich motif to the SH3 domain of Csk kinase, which is an important suppressor of kinases that mediate T cell activation. The PTPN22 1858C-&gt;T SNP changes the amino acid at position 620 from an arginine (R) to a tryptophan (W) and disrupts the interaction between Lyp and Csk, and thus, inhibits complex formation and suppresses T cell activation. <h3>Objectives</h3> The aim of this study was to determine whether the PTPN22 C1858T polymorphism confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. <h3>Methods</h3> MEDLINE database and manual search were utilized to identify to identify articles in which the PTPN22 polymorphism was determined in RA patients and controls. A meta-analysis was conducted on the associations between the PTPN22 C1858T polymorphism and RA using; 1) allelic contrast, 2) dominant model. <h3>Results</h3> A total of 30 separate comparisons involving 17,961 RA patients and 18,611 controls were considered in this meta-analysis. Meta-analysis showed an association between the T allele and RA in all subjects (OR = 1.490, 95% CI = 1.332 – 1.668, <i>P</i> &lt; 1.0x10<sup>-9</sup>). After stratification by ethnicity, analysis indicated that the T allele was significantly associated with RA in Europeans and in Non-Europeans (OR = 1.423, 95% CI = 1.260 – 1.605, <i>P</i> = 1.0x10<sup>-8</sup>; OR = 1.902, 95% CI = 1.488 – 2.430, <i>P</i> = 2.8x10<sup>-8</sup>). Meta-analysis of the CT + TT genotype showed the same result patterns as that shown by the PTPN22 C1858T polymorphism T allele. Furthermore, a direct comparison between rheumatoid factor (RF)-positive and -negative subjects revealed a significant association with the T allele in RA patients with RF, but not in subjects without RF (OR = 1.561, 95% CI = 1.373 – 1.775, <i>P</i> &lt; 1.0x10<sup>-9</sup>). <h3>Conclusions</h3> This meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with RA susceptibility in different ethnic groups, especially in Europeans, and the PTPN22 C1858T polymorphism T allele is significantly more prevalent in RF-positive patents than in RF-negative patients <h3>References</h3> Siminovitch KA. PTPN22 and autoimmune disease. Nat Genet 2004;36(12):1248-9. Gregersen PK. Pathways to gene identification in rheumatoid arthritis: PTPN22 and beyond. Immunological reviews 2005;204:74-86. <h3>Disclosure of Interest</h3> None Declared
Abstract 795: Transcriptome instability as a common characteristic of solid cancers.
Authors: Anita Sveen, Bjarne Johannessen, Manuel R. Teixeira, Ragnhild A. Lothe, Rolf I. Skotheim
Journal: Cancer Research (2013)

Abstract Analogous to the genomic types of instability describing cancer genomes, we recently proposed transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of colorectal cancer (Sveen et al., Genome Medicine, 2011). Here, we explore transcriptome instability in several major solid cancer types. We have analyzed exon microarray data from ten cancer datasets (555 samples; seven cancer types) and four normal tissue types (93 samples; paired samples from colonic mucosa, lung, prostate and the stomach) for variation in relative amounts of aberrant exon usage, based on alternative splicing scores calculated by the FIRMA algorithm. Most major solid cancer types (breast, cervical, colorectal (two datasets), lung, and prostate (two datasets) cancer) showed large variations in aberrant exon usage amounts among the samples, and these amounts were strongly associated with splicing factor expression levels. Thus, we consider these cancer types to exhibit transcriptome instability. Non-random associations with splicing factor (n = 280) expression levels were shown by separation of samples according to aberrant exon usage amounts upon unsupervised hierarchical clustering analyses, and by stronger correlations between aberrant exon usage amounts and splicing factor expression levels than expected by chance (compared with random gene sets and permutations of the aberrant exon usage amounts; P &amp;lt; 0.001). In comparisons across healthy tissue types and paired cancer and normal datasets, we observed tissue- and cancer-specific patterns in splicing factor correlations. Interestingly, in comparisons across cancer types with transcriptome instability (but not across cancer datasets that did not show transcriptome instability; gastric cancer, a second lung cancer dataset, and neuroblastoma), the non-random associations between aberrant exon usage amounts and splicing factor expression remained intact, indicating a failure to adhere to tissue specificity. Thus, we consider transcriptome instability to be a common feature of most major solid cancer types, and this deviant splicing pattern is associated with splicing factor expression levels. Citation Format: Anita Sveen, Bjarne Johannessen, Manuel R. Teixeira, Ragnhild A. Lothe, Rolf I. Skotheim. Transcriptome instability as a common characteristic of solid cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 795. doi:10.1158/1538-7445.AM2013-795
Response to: ‘IL-23 expression and activation of autophagy in synovium and PBMCs of HLA-B27 positive patients with ankylosing spondylitis‘ by Neerinckx<i>et al.</i>
Authors: Francesco Ciccia, Riccardo Alessandro, Giovanni Triolo
Journal: Annals of the Rheumatic Diseases (2014)

We read with interest the study by Neerinckx et al 1 addressing the expression of interleukin (IL)-23p19 and of autophagy genes in the synovium and in the peripheral blood mononuclear cells of patients with ankylosing spondylitis (AS). Differently from our observation in the gut,2 the authors failed to demonstrate any significant increase by RT-PCR in the expression of synovium autophagy-related genes (ATG16L1, IRGM, MAP1LC3A, ATG5, HSPA8 and HSP90AA1) together with no significant overexpression of IL-23p19 compared with disease and healthy controls.

We have previously demonstrated by immunohistochemistry that in the …
Abstract P2-04-02: Identification of genes associated with breast cancer micrometastatic disease in bone marrow using a human-in-mouse xenograft system
Authors: R Aft, S Li, C Mudalagiriyappa, N Dasgupta, M Watson, T Fleming, M Ellis, S Pillai
Journal: Cancer Research (2012)

Abstract Disseminated tumor cells (DTCs) found in the bone marrow (BM) of breast cancer patients portend a poor prognosis and are thought to be the intermediaries in the metastatic process. Study of these cells has been limited due to their scarcity. To develop a clinically relevant model to characterize hese cells, we have employed a human in mouse (HIM) xenograft model for propagating, isolating, and molecularly characterizing DTCs. Human breast adenocarcinomas were prospectively collected from 5 patients and implanted into humanized NOD/SCID mouse mammary fat pads. BM was collected from the long bones at varying passages of the tumors and analyzed for human-specific gene expression by qRT-PCR and gene expression microarray. Human-specific gene expression of SNAI1, GSC, FOXC2, KRT19, and STAM2, presumably originating from disseminated tumor cells, was detectable in the BM of all mice that had developed metastatic disease to other solid organs, but was not detectable in xenotransplanted mice that did not develop metastatic disease. Comparative gene expression microarray analysis of the HIM primary tumor, the corresponding BM from mice with metastatic disease, and BM from control mice identified additional patterns of gene expression enriched in BM-associated DTCs which included several genes associated with epithelial-mesenchymal transition, aggressive clinical phenotype, and metastatic disease development in primary human tumors. We have found that BM DTCs can be detected using the HIM xenograft model and have identified unique patterns of gene expression associated with BM DTCs, which may provide further insight into the biology and therapeutic vulnerability of metastatic tumor cell populations in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-02.
AB0397 GO.A.RE.L. (Golimumab in Apulian Real-Life Patients) Study. Preliminary Data from Golimumab Therapy in Patients Affected with Polyarthritis. A Multicentre Experience in Apulia (Southern Italy)
Authors: L. Santo, A. Semeraro, C. Zuccaro, M.G. Anelli, R. Bucci, G. D'Alessandro, O. Casilli, L. Quarta, G. Carlino, F. Cacciapaglia, P.C.F. Falappone, L. Serafino, F. Iannone
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Golimumab has proven to be effective and safe in randomized clinical trials Go-Forward, Go-After, Go-Before and Go-More for Rheumatoid Arthritis (RA), Go-Raise for Ankylosing Spondlylitis (AS), Go-Reveal for Psoriatic Arthritis (PsA) for which patients have been accurately selected. Instead, data from Golimumab therapy in patients from daily clinical practice, where comorbidities, poly-therapy, severe clinical manifestations, systemic extra-articular involvement may influence drug effectiveness or safety, are still lacking. <h3>Objectives</h3> The scope of this multicentric spontaneous observational study is to evaluate the effectiveness and safety of Golimumab – the newest anti-TNFa monoclonal antibody – in unselected patients who are affected with chronic polyarthritis – RA and Spondyloarthritis (SpA) - and undergoing the treatment with Golimumab in 11 rheumatologic clinical Units of Apulia (Southern Italy). <h3>Methods</h3> 211 patients (69 males and 142 females) affected with polyarthritis (44 RA, 167 SpA, including 91 PsA and 76 axial-SpA) have been enrolled. Mean age was 50.5 (21-86) in SpA and 56.1 (21-81) in RA, with mean disease duration of 7 years in SpA and 9.31 in RA, respectively. Safety and effectiveness were established as primary end-points following 12 months for RA and 24 months for SpA. Effectiveness was assessed by 28-joints disease activity (DAS28), clinical disease activity index (CDAI) and Health Assessment Questionnaire (HAQ) in RA patients, whereas Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive protein Ankylosing Spondylitis Disease Activity Score (ASDAS) and DAS28 were used in axial-SpA and PsA. ANOVA for repeated measures has been used for statistical intra-group comparisons between baseline and different follow-up points. <h3>Results</h3> 8 patients out of 211 were lost during follow-up; 34 patients (16,7%) out of 203 interrupted Golimumab treatment due to inefficacy; 13 (6,4%) presented major side effects causing drug interruption; 5 (2,4%) showed minor side effects that did not demand the treatment interruption. Table 1 and 2 show treatment effectiveness. <h3>Conclusions</h3> Preliminary results confirm a good effectiveness and safety of Golimumab in patients with RA or SpA in standard care settings. Further analysis to assess the influence of obesity and other comorbidities, or combination therapy with standard drugs are ongoing. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1923