tbuckley/cabot-search huggingface dataset:
Abstract 4696: TRAF2 plays a critical role in maintaining lymphocyte homeostasis by regulating the basal activities of IKK and caspase-8
Authors: Laiqun Zhang, Ken Blackwell, Wen-Chen Yeh, Tak Wah Mak, Hasem Habelhah
Journal: Cancer Research (2011)

Abstract TRAF2 and TRAF5 are RING domain proteins, and their RING domain-mediated RIP1 ubiquitination is believed to be essential for NF-κB activation and inhibition of caspase-8-mediated cell death in response to TNFα stimulation. We have previously reported instead that TRAF2/5 double knockout (DKO) cells exhibit high basal IKK activity in unstimulated conditions, and that TNFα stimulation further increases IKK activity in the absence of RIP1 ubiquitination in TRAF2/5 DKO cells. These findings potentially revise the currently accepted model for the role of TRAF2/5 in TNFα signaling. However, most of the conclusions in the field regarding the role of TRAF2/5 in TNFα signaling are based on the studies performed in immortalized MEFs, as TRAF2 KO mice die within 10 days after birth. Notably, elimination of either TNFα or TNFR1 enhances the survival of TRAF2 KO mice. Thus, to examine the role of TRAF2 in NF-κB activation versus cell death in primary cells, we generated TRAF2 KO and TNF/TRAF2 DKO mice. Surprisingly, both IKK and caspase-8 are constitutively activated to a certain degree in thymus and spleen, but not in muscle and liver, of one week old TRAF2 KO mice. In TNF/TRAF2 DKO mice, on the other hand, the basal caspase-8 activity is completely suppressed in thymus and spleen, while the basal IKK activity still remained high compared to that in wild-type mice. In addition, caspase-8 substrates such as RIP1 and cFLIP are constitutively cleaved in thymus and spleen, but not in muscle and liver, of TRAF2 KO mice, and these cleavages were completely inhibited in TNF/TRAF2 DKO mice. Functional assays performed in primary MEFs, bone marrow macrophages and T-cells revealed that TRAF2 suppresses basal IKK activity and p100 processing through the NIK-dependent and -independent pathways. Moreover, both the basal and TNFα-induced expression of anti-apoptotic proteins are normal in these primary cells isolated from TNF/TRAF2 DKO embryos and adult mice, yet these cells remain sensitive to TNFα-induced cell death, due to the impaired recruitment of cIAP1/2 to the TNFR1 complex in the absence of TRAF2. Collectively, these data demonstrate that TRAF2 maintains lymphocyte homeostasis by negatively regulating the basal activities of IKK and caspase-8 in thymus and spleen, and that TRAF2 inhibits TNFα-induced cell death by recruiting anti-apoptotic proteins to the TNFR1 complex rather than by activating the NF-κB pathway. 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 4696. doi:10.1158/1538-7445.AM2011-4696
Measles outbreak in a refugee settlement in Calais, France: January to February 2016
Authors: G Jones, S Haeghebaert, B Merlin, D Antona, N Simon, M Elmouden, F Battist, M Janssens, K Wyndels, P Chaud
Journal: Eurosurveillance (2016)

We report a measles outbreak in a refugee settlement in Calais, France, between 5 January and 11 February 2016. In total, 13 confirmed measles cases were identified among migrants, healthcare workers in hospital and volunteers working on site. A large scale vaccination campaign was carried out in the settlement within two weeks of outbreak notification. In total, 60% of the estimated target population of 3,500 refugees was vaccinated during the week-long campaign.
UNDERSTANDING OPTICAL COHERENCE TOMOGRAPHY: IMPORTANT SOURCES OF MISINTERPRETATION HIGHLIGHTED BY HISTOPATHOLOGY
Authors: Christoph Lutter, Tobias Koppara, Hiroyoshi Mori, Kazuyuki Yahagi, Robert Kutys, Elena Ladich, Maria Romero, Renu Virmani, Michael Joner
Journal: Journal of the American College of Cardiology (2016)
Abstract 18705: The miR-130/301 Family Exerts Systems-level Regulation of Proliferation, Vasoconstriction, and Extracellular Matrix Deposition to Control Pulmonary Hypertension
Authors: Thomas Bertero, Katherine A Cottrill, Yu Lu, Sofia Annis, Andrew Hale, Adrienn Krauszman, Balkrishen Bhat, Rajan Saggar, Rajeev Saggar, W. D Wallace, David J Ross, Sara O Vargas, Brian B Graham, Rahul Kumar, Stephen M Black, Sohrab Fratz, Jeffrey R Fineman, James D West, Kathleen J Haley, Aaron B Waxman, Wolfgang M Kuebler, B. N Chau, Stephen Y Chan
Journal: Circulation (2014)

Background: Pulmonary hypertension (PH) is a deadly vascular disease with enigmatic molecular origins. Facets of PH have been characterized in isolation, but many have yet to be unified by a common upstream regulator. Methods &amp; Results: We constructed a network in silico of 247 genes and 2,274 functional interactions involved in PH. Using this model and advanced network analysis, we predicted the miR-130/301 family to have the most diverse pool of PH-relevant target genes among conserved microRNAs (miRNAs). Guided by these predictions, we found that this family was up-regulated by hypoxia, inflammatory cytokines, and factors genetically linked to PH. MiR-130/301 family members were also up-regulated in remodeled pulmonary vessels in 7 animal models and 3 human subtypes of PH. Via gain- and loss-of-function experiments in vitro , we found that miR-130/301 suppressed a cohort of PPARgamma-related targets to regulate two pro-proliferative pathways (the apelin-miR-424/503-FGF2 axis in PAECs and the STAT3-miR-204-SRC axis in PASMCs); vasomotor tone ( e.g. , endothelin-1 and endothelial nitric oxide synthase); and extracellular matrix remodeling ( e.g. , the collagen crosslinking enzyme LOX). In turn, delivery of miR-130a mimic oligonucleotides in pulmonary vessels of mice altered expression of the predicted cohort of PPARgamma-related factors, leading to increased vascular remodeling (19.62±1.36 percent muscularized arterioles for miR-130a vs. 6.98±0.55 percent for scrambled control, p&lt;0.05, mean±SEM), pulmonary vascular resistance (791±124.5 [10 3 *dyn*s*cm -5 ] for miR-130a vs. 462±25.4 for control, p&lt;0.05), and perivascular collagen deposition and cross-linking (9.67±1.24 percent of perivascular area positive for Picrosirius Red stain vs 1.24±0.15 percent for scrambled control, p&lt;0.05). After PH initiation in mice (chronic hypoxia+SU5416), coordinated inhibition of these miRNAs in vivo via antisense oligonucleotides mitigated these effects. Conclusions: We used network modeling to identify miR-130/301 as a master regulator of PH and a novel potential therapeutic target. These findings provide critical support for the evolving application of network modeling to discover the hidden molecular origins of PH and other human diseases.
Abstract 690: Estrogen receptor beta (ERβ) enhances the chemosensitivity of breast cancer cells by altering DNA damage response signaling
Authors: Christoforos Thomas, Karolina Lindberg, Anders Strom, Tassos Damdimopoulos, Jan-Ake Gustafsson
Journal: Cancer Research (2010)

Abstract Estrogen Receptor beta (ERβ) is a mediator of estrogen signaling that regulates growth in mammary gland and is involved in breast cancer. In response to DNA damage most tumor cells due to disruptions in the p53 pathway and consequent loss of G1 cell cycle arrest are entirely dependent in S and G2/M checkpoints to maintain genomic integrity. Inhibition of these checkpoints following DNA damage induces selective killing of p53-defective tumor cells. We show that expression of ERβ caused abrogation of Cdc25C-mediated G2/M checkpoint following cisplatin and doxorubicin exposure selectively in p53-deficient cells, resulting in mitotic catastrophe and decreased cancer cell survival. The loss of G2/M checkpoint observed was due to ERβ-mediated inhibition of the DNA damage-induced expression of brca1. ERβ by modulating DNA damage response signaling seems to selectively enhance the chemosensitivity of tumor cells. This suggests that co-operation of compounds that specifically induce the ERβ signaling with DNA damaging chemotherapeutic drugs may represent an attractive new cancer therapeutic strategy. 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 690.
Do the Results of Randomized Clinical Trials of Cardiovascular Drugs Influence Medical Practice?
Authors: Gervasio A. Lamas, Marc A. Pfeffer, Peggy Hamm, John Wertheimer, Jean-Lucien Rouleau, Eugene Braunwald
Journal: New England Journal of Medicine (1992)

Medical practice patterns change in response to a variety of stimuli, one of which may be the publication of the results of randomized clinical trials. We assessed the temporal association between the publication of clinical trials on myocardial infarction and changes in treatment practices for this disorder.
AB0884 The Factors Affecting Bone Mineral Content in Patients with Juvenile Idiopathic Arthritis
Authors: A. Hari, S. Rostom, R. Lahlou, D. Khnaba, R. Bahiri, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To determine the factors influencing bone mineral content in patients with juvenile idiopathic arthritis. <h3>Methods</h3> A cross sectional studyin patientswith juvenile idiopathic arthritis (JIA) according to the International League of Association of Rheumatology criteria was conducted. Sociodemographic parameters and clinical data related to the disease were collected. Bone mineral content was measured by dual energy X-ray absorptiometry on Lunar Prodigy machine at the full body. Disease activity of the JIA was assessed by the number of painful joints (PJ), number of swollen joints (SJ), the visual analogic scale (VAS) pain assessed by patient (VASp) and physician (VASd), and biological parameters (ESR,CRP). Biochemical markers of bone turnover were represented by serum calcium, phosphorus and alkaline phosphatase. Normal serum calcium in children &lt;3 years is 88-110 mg/l and for children&gt;3 years: 90-105 mg/l. For phosphate: 40-60 mg/l. For alkaline phosphatase: 90-450 IU/l. The daily food intake was assessed by a questionnaire for 7 consecutive days. Two nutritionists analyzed the diet to identify its macronutrient and oligonutriments content. Food intake was analyzed by Bilnut Version 2.01 software 1991. <h3>Results</h3> Thirty-three patients with JIA were included. The mean age was10±4.35 years with amale predominance 54.5%. Twenty-four percent had a systemic form, 27% an oligoarticular and 48% a polyarticular form. The median disease duration was 2 years (1 - 4.5). The median duration of taking corticosteroids was 3 years (1-6). The median rate of vitamin D was 20ng/ml (13.85-31.5), for serum calcium 95 mg/l (93-97). The mean rate of phosphorus was 45mg/l ±7.36. The mean rate of alkaline phosphatase was 161UI/l ±52.The median of CMO, PJ, SJ, VASp, VAS d, ESR and CRP were respectively 1044.97g (630-1808), 3 (1-9), 1 (0 - 3), 20 (10-50) 35 (25-50.5) 20 (10.5-40). There was no correlation between bone mineral content and JIA disease activity parameters: PJ (r =0.06, p=0.77), SJ (r =0.25, p=0.23), VASp (r =0.16, p=0.46), VASd (r =0.02, p=0.91), ESR (r =0.13, p=0.54), CRP (r =0.10, p=0.64).There was no correlation between the bone mineral content and the cumulative duration and corticosteroid dose taken with respectively (r =0.15, p=0.61) (r =0.28, p=0.33).There was a positive correlation between the rate of phosphorus and bone mineral content as well as alkaline phosphatase with respectively (r =0.47, p=0.02) (r =0.41, p=0.04) while the CMO is not correlated with the rate of vitamin D (r =0.14, p=0.5) or the serum calcium levels (r =0.11, p=0.59). <h3>Conclusions</h3> This study suggests that bone mineral content was correlated with markers of bone turnover such as alkaline phosphatase and serum phosphate. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5295
Prolonged Transgene Expression Mediated by a Helper-Dependent Adenoviral Vector (hdAd) in the Central Nervous System
Authors: Linglong Zou, Heshan Zhou, Lucio Pastore, Keyi Yang
Journal: Molecular Therapy (2000)

<h2>Abstract</h2> Conventional adenoviral vectors such as E1-deleted first-generation adenovirus (fgAd) elicit striking host immune response, resulting in limited expression of the transgene. A recently described helper-dependent, or gutless, adenoviral vector (hdAd) can promote stable transgene expression in peripheral organs, including the liver. We therefore investigated the safety and durability of hdAd-mediated gene transfer to the central nervous system (CNS) of rats compared with gene delivery by fgAd. Equal amounts of either fgAd or hdAd carrying the βgeo transgene were stereotactically injected into the right hippocampus of adult rats. Transgene expression was assessed by histochemical staining, transgene stability by PCR analysis, and immune infiltration of T lymphocytes and macrophages by immunocytochemical methods. Strong transgene expression from either vector was detected in brain tissue examined on day 6 postinoculation. Thereafter, fgAd-mediated gene expression rapidly decreased, becoming undetectable by day 66, while expression from the hdAd vector persisted throughout the test period. PCR confirmed the presence of hdAd-associated DNA at 66 days postinoculation. The hdAd injection elicited apparently lower numbers of brain-infiltrating macrophages and T cells than did administration of fgAd. These results indicate improved transgene expression and reduced immunogenicity with use of hdAd to deliver genes to the CNS.
Abstract P2-14-06: A phase II trial of low dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to an aromatase inhibitor.
Authors: SJ Howell, MW Seif, AC Armstrong, J Cope, G Wilson, RS Welch, V Misra, D Ryder, E Blowers, C Palmieri, AM Wardley
Journal: Cancer Research (2012)

Abstract Background High dose estrogen (HDE) is an effective but toxic treatment for postmenopausal women with advanced breast cancer (ABC). In vitro, prolonged periods of estrogen deprivation (ED) sensitises cancers to the inhibitory effects of estrogen. We hypothesised that the profound ED seen with third generation aromatase inhibitor (AI) would sensitise cancers to LDE which would be better tolerated. Methods Single arm phase II study in postmenopausal women with measurable ER+ ABC and demonstrated clinical benefit (CB) with a third generation AI. Treatment: estradiol valerate 2mg daily. Primary endpoint: CB rate (CBR) was correlated with baseline and dynamic LH/FSH levels and on-treatment estradiol levels. Secondary endpoints included TTF, PFS, toxicity and QoL. If LDE was effective, retreatment with the AI on which the cancer had progressed prior to study entry was offered on progression. If LDE was ineffective HDE was offered. Results 21/50 patients were recruited before early closure due to slow accrual. 19 were assessable for efficacy and toxicity (1 ineligible; 1 no LDE). CBR was 5/19 (26%; 95%CI 9.1%,51.2%). Median TTF 2.8months (range 0.5–29.8). CBR durations were 11.1, 16.8, 17.3*, 19.8, 29.8 months (*censored). 4 stopped treatment early due to toxicity (G4 hypercalcaemia/ G2 vaginal bleeding (VB) plus G4 hyponatraemia/ G2 mucositis/ G2 headaches) 1 with SD at 3 months and 3 before response assessment. Other common toxicities were all G1/2 and mainly limitted to nausea (8/19), breast pain (7/19) and tumour flare (7/19). VB occurred in 8/11 without prior hysterectomy. Baseline LH correlated with CBR by logistic regression (p = 0.01). Of 3 retreated with the same AI post LDE; 1 had PR, 1 SD ≥6months and 1 PD. One woman received HDE after failure of LDE and achieved a PR. Conclusion LDE is an effective and largely well tolerated treatment in women with acquired resistance to AI. VB is common without prior hysterectomy. Rechallenge with the same AI post LDE seems effective and may offer an extra line of endocrine therapy. This should be tested in future trials. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-06.
A case of pyogenic granuloma of the cecum treated by endoscopic resection
Authors: Chang Shin, Seung Hong, Mahn Lee
Journal: Endoscopy (2014)

A 45-year-old man presented with hematochezia during the 3 days prior to his admission. His past history included hemophilia without any major bleeding events. His vital signs were stable and his physical examination was unremarkable. Initial laboratory findings revealed a hemoglobin of 8.6 g/dL, hematocrit of 40.3 %, platelet count of 336 × 109/L, prothrombin time of 11.9 seconds, and activated partial thromboplastin time (aPTT) of 49.4 seconds.
EFFICACY AND SAFETY OF 131-I-MIBG THERAPY FOR ADVANCED NEUROBLASTOMA.
Authors: B. L. Engelstad, J. P. Huberty, K. K. Matthay, K. A. Muetterties, C. J. Miller, R. S. Hattner
Journal: Clinical Nuclear Medicine (1987)

Engelstad, B. L.; Huberty, J. P.; Matthay, K. K.; Muetterties, K. A.; Miller, C. J.; Hattner, R. S. Author Information
Cholestyramine Treatment of Diarrhea Associated with Ileal Resection
Authors: Alan F. Hofmann, J. Rainer Poley
Journal: New England Journal of Medicine (1969)

The efficacy of cholestyramine as treatment for diarrhea in patients with ileal resection was examined by inpatient and outpatient trials. Ten of 12 patients having less than 100 cm of distal ileum resected and some remaining ascending colon responded to cholestyramine, 16 gm per day, by a significant decrease in fecal frequency or fecal weight or both. By contrast, none of eight patients having resections of more than 100 cm of ileum responded. The degree of steatorrhea was also of predictive value since all eight patients with fecal fat excretion less than 20 gm per day responded, whereas none of five patients with greater steatorrhea responded. Cholestyramine is useful symptomatic treatment for diarrhea in patients with small ileal resections and mild steatorrhea. The response may be further evidence that diarrhea in these patients is caused by bile acid malabsorption resulting in increased passage of bile acids into the colon, where they induce secretion of salt and water.
Individual Variation in the Production and Survival of F Cells in Sickle-Cell Disease
Authors: George J. Dover, Samuel H. Boyer, Samuel Charache, Kay Heintzelman
Journal: New England Journal of Medicine (1978)

The protective role and underlying sources of the elevated levels of fetal hemoglobin associated with sickle-cell anemia were reassessed by microscopical immunodiffusion assays. Three variables that contribute to levels of fetal hemoglobin were examined: the percentage of fetal-hemoglobin-containing reticulocytes produced; the quantity of fetal hemoglobin synthesized within such cells; and the extent to which the fraction of fetal-hemoglobin-bearing erythrocytes is enriched beyond the level produced. Four general findings emerged from analysis of 29 patients: each variable is separately regulated; the expression of each is often distinctly different between individual patients; contrary to prior speculation, production of fetal hemoglobin may be as great in the absence of heterocellular hereditary persistence of the hemoglobin as in its presence; and fetal hemoglobin does not, as often supposed, guarantee preferential cell survival. We conclude that the differences encountered among patients must reflect heterogeneity among factors that modify production and survival of cells bearing fetal hemoglobin.
A10.07 The kinetic cytokine/chemokine secretory profile in surgical models of osteoarthritis
Authors: AC Ortiz, L Dunning, C Huesa, WR Ferrell, IB McInnes, JC Lockhart, CS Goodyear, A Crilly
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background&nbsp;and&nbsp;objectives</h3> Destabilisation of the medial meniscus (DMM) and section of the anterior cruciate ligament (ACL) are commonly used <i>in vivo</i> models of osteoarthritis (OA). Using explant culture, the secretory profile of synovium and patellar ligament was evaluated in DMM and ACL models. <h3>Material and methods</h3> All murine procedures were Home Office (UK) approved. OA was induced in 10–12 week old C57BL/6 male mice by either DMM or ACL (1). SHAM and naïve animals were used as controls. Knee joint diameter (KJD) was assessed prior to induction of arthritis and every three days thereafter. At 4 and 12 weeks post-surgery, synovium and patellar ligament were harvested and used for explant culture. Supernatants were collected after 4 h and analysed by Luminex. In parallel experiments, joints were collected for histological analysis ofF4/80+, IL-33+ and CCR4+ cells in synovium and ligaments. Freund's complete adjuvant (FCA) monoarthritis model was used as a positive control of inflammatory joint disease. Data were expressed as mean values ±SEM (n = 6) and analysed using a 1 or 2 way ANOVA, with p &lt; 0.05 as the criterion of significance. <h3>Results</h3> At 4 weeks post-surgery no change in KJD was observed in either DMM or ACL. Nonetheless, secretion of MIP-1β/CCL4 was significantly increased in explant cultures from DMM and ACL compared to naïve controls (p &lt; 0.001). In comparison, IL-33 was only significantly elevated in ACL cultures (p &lt; 0.02). Histological evaluation of both OA models revealed the presence of F4/80<sup>+</sup> macrophage, IL-33 and CCR4 (receptor for CCL4) in the synovium but not in the patella ligament. At 12 weeks post-surgery, IL-33 and IL-6 were the only cytokines detected in OA explant cultures, however, IL-33 levels were significantly reduced compared to 4 weeks post-surgery (p &lt; 0.001). <h3>Conclusion</h3> This study characterised the secretory profile of DMM and ACL joint tissue at 4 and 12 weeks post-surgery. This profile alters with time, with reduced IL-33 and an absence of CCL4 at 12 weeks. The potential role of IL-33 and CCL4 in the early and late stage pathogenesis of these OA models merits further investigation. <h3>Reference</h3> Glasson SS,&nbsp;<i>et al</i>. The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Osteoarthritis Cartilage. 2007;15(9):1061–1069
AB0372 Is routine ankle-brachial pressure index evaluation useful in rheumatoid arthritis?:
Authors: D. Guellec, L. Bressollette, F. Gueguen, S. Jousse-Joulin, T. Marhadour, V. Devauchelle-Pensec, A. Saraux
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular mortality and may therefore benefit from early atherosclerosis detection. Ankle brachial pressure index (ABPI) measurement can detect asymptomatic peripheral atherosclerosis, and isolated ABPI abnormalities can warrant treatment changes according to French recommendations. <h3>Objectives</h3> To evlauate the prevalence of ABPI abnormalities in RA in routine pratice. <h3>Methods</h3> We studied consecutive 100 patients meeting 1987 American College of Rheumatology criteria for RA when evaluated as inpatients or outpatients in November 2010 at a single rheumatology department. ABPI was measured routinely by a vascular physician. Patients were separated into three groups based on whether the ABPI was &lt;0.9 [decreased arterial flow (DAF)], 0.9 to 1.3 (normal), or &gt;1.3 (arterial stiffness). The three groups were compared using chi-square and Mann-Whitney tests. <h3>Results</h3> Of the 100 patients, 85 had normal ABPI values, 10 had DAF, and 5 had stiff arteries. Patients with DAF were older (69.1±12.6 years, <i>P</i>=0.002) and more often had a history of coronary artery disease (40%, <i>P</i>=0.004) compared to patients with normal arteries. The group with incompressible arteries had a larger proportion of patients with diabetes (40%, <i>P</i>=0.034) compared to the group with normal ABPI values. <h3>Conclusions</h3> The prevalence of DAF is relatively high in RA, especially in older patients. DAF is strongly associated with coronary artery disease in RA patients. <h3>Disclosure of Interest</h3> None Declared