tbuckley/cabot-search huggingface dataset:
SP0105 Prevention of Collateral Damage by Immune Inhibitory Receptors
Authors: L. Meyaard
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The proper functioning of the immune system is based on a fine balance between activation and inhibition. Immune suppression leads to the threat of infection by pathogens and immunodeficiency, while insufficient inhibition can lead to damage to self or autoimmunity. Inhibitory immune receptors play a crucial role in this balance. Neutrophils are useful but also dangerous cells. They are essential to protect the host against invading pathogens and have the ability to quickly enter the tissues. However, their activity also causes collateral tissue damage that in ultimo can result in destruction of the tissue architecture and the formation of pus, also in non-infectious inflammatory conditions. Next to phagocytosis and degranulation, neutrophils fight bacteria through neutrophil extracellular traps (NETs), which arise from the release of the neutrophil9s nuclear content into the extracellular space and consist of decondensed DNA decorated with antimicrobial proteins. Despite the importance of NETs in host defense, NETs contribute to pathology by several mechanisms. It is suggested that the DNA and antimicrobial peptides of NETs can be recognized by B cells which leads to the production of auto-antibodies, such as in SLE. Furthermore, the antimicrobial peptides attached to the NETs have poor target specificity, which leads to the damage of the tissues surrounding the NET. Finally, NETs have recently been shown to form a platform for platelets and form a central role in thrombosis. Therefore, NET formation contributes to pathology in several diseases that involve tissue infiltration by neutrophils. We recently identified Signal Inhibitory Receptor on Leukocytes-1 (SIRL-1) as a negative regulator of human neutrophil function. SIRL-1 ligation inhibits the oxidative burst and prevents the pathogenic release of NETs in SLE. SIRL-1 engagement can dampen spontaneous and anti-neutrophil antibody-induced NET formation in SLE. This opens up the interesting therapeutic opportunity of inhibiting collateral damage by engagement of inhibitory receptors. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6265
Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas
Authors: Konstantinos Georgiou, Longyun Chen, Mattias Berglund, Weicheng Ren, Noel F. C. C. de Miranda, Susana Lisboa, Marco Fangazio, Shida Zhu, Yong Hou, Kui Wu, Wenfeng Fang, Xianhuo Wang, Bin Meng, Li Zhang, Yixin Zeng, Govind Bhagat, Magnus Nordenskjöld, Christer Sundström, Gunilla Enblad, Riccardo Dalla-Favera, Huilai Zhang, Manuel R. Teixeira, Laura Pasqualucci, Roujun Peng, Qiang Pan-Hammarström
Journal: Blood (2016)
Sarcoidosis of the Skull
Authors: Alvin S. Teirstein, Bernard S. Wolf, Louis E. Siltzbach
Journal: New England Journal of Medicine (1961)

OSSEOUS lesions occur in a minority of patients with sarcoidosis. When these lesions do occur, they are almost always limited to the bones of the hands and feet. Sarcoidosis of the skull is one of the rarest manifestations of this systemic disease. We could find only 2 other reported cases of skull localization confirmed by bone biopsy.1 , 2 This communication describes a patient under observation for chronic generalized sarcoidosis who exhibited two slowly growing, firm protuberances of the forehead, each attaining walnut size. When radiologic examination of the skull revealed punched-out areas in the frontal bone associated with the swellings, problems . . .
Abstract 589: NQO1-dependent anticancer action with combination β-lapachone and ionizing radiation in the head and neck cancer.
Authors: Long Shan Li, Srilakshmi Reddy, Jinming Gao, David A. Boothman, Baran Sumer, John S. Yordy
Journal: Cancer Research (2013)

Abstract The number of new cases of oral cavity, pharynx and larynx cancers is estimated be 52,610 in 2012 with an expected 11,500 deaths. Despite progressive improvements in outcome, current treatment approaches still result in an overall survival rate of approximately 50% at five years for locally advanced head and neck cancer (HNC). Additional therapeutic approaches are needed to further enhance outcomes. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a two-electron oxidoreductase that reduces quinones to hydroquinones and has been shown to be overexpressed in a number of solid tumors. For the first time, our studies in 45 HNC cell lines identified NQO1 overexpression in more than 70% of HNC cell lines. Furthermore over-expression of NQO1 has been shown to be a critical determinant for tumor-selective therapy using β-lapachone (β-lap), a substrate of NQO1 that undergoes partial reduction and spontaneous reversion, creating a futile cycle that produces very high levels of reactive oxygen species. HNC cell lines that overexpress NQO1 are significantly killed by treatment with β-lap. The anti-cancer action of β-lap in HNC cells is initiated and processed through five essential downstream mediators: (i) reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2); (ii) DNA single strand breaks (SSBs) induced by ROS; (iii) hyperactivation of poly(ADP-ribose)polymerase-1 (PARP1) and accompanying poly(ADP-ribose)-PARP1 (PAR) formation; (iv) dramatic NAD+/ATP depletion; and (v) programmed necrosis (necroptosis). In combination with ionizing radiation (IR), β-Lap radiosensitized NQO1(+) HNC cells under conditions where nontoxic doses of either agent alone did not achieve threshold levels of DNA lesions and /or SSBs required for PARP-1 hyper-activation. Furthermore, combination therapy with β-lap and IR significantly enhanced γ-H2AX and 53BP1 foci formation and PARP-1 hyper-activation which was associated with ATP loss and induction of programmed cell death. Furthermore, the anticancer effects of combination β-Lap and IR were blocked by the NQO1 inhibitor dicoumarol. Our findings offer a strategy for the clinical utilization of β-lap as a radiosensitizer in HNC. Citation Format: Long Shan Li, Srilakshmi Reddy, Jinming Gao, David A. Boothman, Baran Sumer, John S. Yordy. NQO1-dependent anticancer action with combination β-lapachone and ionizing radiation in the head and neck cancer. [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 589. doi:10.1158/1538-7445.AM2013-589
The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease
Authors: Saulo Klahr, Andrew S. Levey, Gerald J. Beck, Arlene W. Caggiula, Lawrence Hunsicker, John W. Kusek, Gary Striker
Journal: New England Journal of Medicine (1994)

Restricting protein intake and controlling hypertension delay the progression of renal disease in animals. We tested these interventions in 840 patients with various chronic renal diseases.
Abstract 4189: Excess c-Myc loads tissue-specific enhancers in tumor cells
Authors: Charles Lin, Peter B. Rahl, Jakob Loven, Michael H. Kagey, Christopher B. Burge, Richard A. Young
Journal: Cancer Research (2012)

Abstract Excessive expression of c-Myc occurs frequently in human cancers, where high levels are associated with tumor aggression and poor clinical outcome. It is well established that the c-Myc protein forms a heterodimer with Max, binds to E-box sequences typically located near the core promoter elements of target genes involved in cellular proliferation, and alters expression of these genes. It is not yet clear, however, how altering the levels of c-Myc affects its activity across the genome to enhance the oncogenic state of cells. We show here that c-Myc occupies occupies enhancer elements only in tumor cells with elevated levels of c-Myc. The enhancers that are occupied are often tumor-specific and associated with the cell-of-origin of the tumor. These and additional results provide insights into a key mechanism by which c-Myc overexpression alters the transcriptional state of cancer cells to enforce their tumorigenic state and malignant potential. 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 4189. doi:1538-7445.AM2012-4189
TWO YEAR RESULTS OF THE STAND ALONE COX MAZE PROCEDURE FOR NONPAROXYSMAL ATRIAL FIBRILLATION: HIGH SUCCESS RATE AND IMPROVED QUALITY OF LIFE WITH A SINGLE PROCEDURE
Authors: Niv Ad, Sari Holmes, Graciela Pritchard, Deborah Lamont, Deborah Shuman
Journal: Journal of the American College of Cardiology (2016)
PTU-152 Pepsin In Saliva For The Diagnosis Of Gastro-esophageal Reflux Disease
Authors: JO Hayat, S Gabieta-Somnez, E Yazaki, J-Y Kang, A Woodcock, P Dettmar, J Mabary, C Knowles, D Sifrim
Journal: Gut (2014)

Introduction Current diagnostic tests for GORD have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an “office-based” method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in a large cohort of healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus) from functional heartburn. Methods 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut off value for pepsin positivity was 16 ng/ml. Patients were divided into GORD (increased acid exposure time (AET) n = 58); Hypersensitive Oesophagus (HO) (normal AET and + SAP), n = 26) and Functional Heartburn (FH) (normal AET and – SAP, n = 27). Multiple group comparisons were performed using one-way ANOVA followed by with Tukey’s Test for Gaussian distributed data and the Kruskall-Wallis Test with Dunns comparison for non-Gaussian data. Receiver Operator Characteristic curves were constructed to determine and compare the sensitivity and specificity of different pepsin cut-off concentrations. Results 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0–59) ng/ml). Patients with reflux-related symptoms (GORD and HO) had higher prevalence (77–89%) and pepsin concentration than controls (HO, 237(52–311) ng/ml and GORD, 121(29–252) ng/ml) (p < 0.05). Patients with FH had low prevalence (33%) and concentration of pepsin in saliva (0(0–40) ng/ml). The area under the receiver operating characteristic curve had a value of 0.8034 +/-0.04 (95% confidence interval 0.719 to 0.8873, p < 0.0001). A positive test had 77.6% sensitivity and 63.2% specificity for diagnosis of GORD/HO. When all saliva samples were negative, there was 80% probability that symptoms were not due to reflux (FH). One positive sample with >210 ng/ml pepsin suggested the presence of GORD/HO with 95% probability. Conclusion In patients with symptoms suggestive of GORD, salivary pepsin can be used to confirm or reject the diagnosis before empirical PPI treatment. This may lessen the use of unnecessary anti-reflux therapy and the need for further invasive and expensive diagnostic methods. Disclosure of Interest J. Hayat: None Declared, S. Gabieta-Somnez: None Declared, E. Yazaki: None Declared, J.-Y. Kang: None Declared, A. Woodcock Employee of: RD Biomed Ltd, P. Dettmar Employee of: RD Biomed Ltd, J. Mabary Employee of: Sandhill Sci., C. Knowles: None Declared, D. Sifrim Grant/research support from: Sandhill Sci.
Abstract 4845: Reeducate the tumor microenvironment to improve the anticancer efficacy of adoptive T-cell therapy
Authors: Wei Liang, Ian Walters, Hua Yu, Richard Jove
Journal: Cancer Research (2012)

Abstract The hostile tumor microenvironment interferes with the function of efficient antitumor immune cells and constitutes a major obstacle for cancer immunotherapies. Here, we provide evidence that the immunosuppressive tumor microenvironment can be reeducated by an antiangiogenic agent to favor the development of adaptive antitumor immunity and to improve the efficacy of adoptive T cell therapy. Our results demonstrate that treatment with Brivanib, a novel small-molecule kinase inhibitor of VEGFRs and FGFRs, significantly enhanced the frequency and effector function of CD8+ cytotoxic T cells in tumor-bearing mice associated with significant reduction of tumor burden. Enhanced intratumoral infiltration of CD8+ T cells induced by Brivanib was associated with increased expression of chemokines (e.g., ccl3, ccl5, ccl11 and cxcl9) that regulates T cell trafficking and cell adhesion molecules (VCAM-1 and ICAM-1) on endothelial cells in the tumor microenvironment. Moreover, Brivanib treatment skewed the polarization of tumor-associated macrophages (TAM) away from the tumor-supporting M2 phenotype and restored the antigen presenting function of macrophages. Finally, Pretreatment of tumor-bearing animals with Brivanib prior to adoptive T cell transfer promotes in vivo proliferation, intratumoral infiltration and effector function of infused CD8+ T cells, resulting in better antitumor activity than either treatment alone. These findings indicate that Brivanib can be used to modulate the immunosuppressive microenvironment and as a potential adjuvant for enhancing the efficacy of cell-based cancer immunotherapy for cancer treatment. 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 4845. doi:1538-7445.AM2012-4845
P358Safety of intracoronary delivery of mesenchymal/stromal stem cells: insights from coronary microcirculation invasive assessment:
Authors: A Fiarresga, C Lobato Da Silva, S Cavaco-Goncalves, M Selas, I Simoes, E Oliveira, B Carrapico, N Cardim, J Sampaio Cabral, R Cruz Ferreira
Journal: Cardiovascular Research (2014)

Mesenchymal/stromal stem cells (MSC) have unique properties favorable to their future use in clinical practice and have been studied for cardiac repair. MSC are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could compromise the intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status and could be applied for evaluation of the acute effects of MSC intracoronary infusion providing new insights for this open question. Our purpose was to examine heart microcirculation effects after MSC intracoronary injection with IMR. Methods and Results: Eighteen healthy swine were randomized to receive 30 x 106 MSC or saline by intracoronary infusion. In the heart catheterization laboratory hemodynamic, electrocardiographic and coronary flow parameters were monitored and there were no differences between groups. Thermodilution-derived coronary flow reserve (CFR) and IMR were assessed at baseline, 5 and 30 minutes post-delivery using a coronary pressure wire. CFR had a small although not significant decrease in animals receiving MSC. After cell infusion, IMR increased at 5 and 30 minutes with a significant difference from the control group at 30 minutes (Table). Conclusion: Intracoronary delivery of MSC is possible without a significant negative impact on hemodynamic parameters, electrical stability and epicardial coronary flow status. However, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of MSC, in a large animal model closely resembling human cardiac physiology, function and anatomy. CFR and IMR mean values Coronary flow reserve (CFR), index of microcirculatory resistance (IMR) CFR and IMR mean values Coronary flow reserve (CFR), index of microcirculatory resistance (IMR)
Monkey Diet May Hold Clues for Finding Anti-HIV Drugs
Authors: J. Randal
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Monkey Diet May Hold Clues for Finding Anti-HIV Drugs Get access Judy Randal Judy Randal Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 11, 7 June 1995, Pages 790–791, https://doi.org/10.1093/jnci/87.11.790-a Published: 07 June 1995
Serogroup C invasive meningococcal disease among men who have sex with men and in gay-oriented social venues in the Paris region: July 2013 to December 2014
Authors: L Aubert, M  K Taha, N Boo, Y Le Strat, A E Deghmane, A Sanna, A S Barret, D Lévy-Bruhl, S Vandentorren, I Parent du Châtelet
Journal: Eurosurveillance (2015)

In November 2014, French public health authorities renewed the recommendation to target for vaccination against invasive meningococcal disease men who have sex with men (MSM) and all individuals ≥25 years attending social venues associated with the gay community. This policy was extended beyond the Paris region as a reaction to the continuing spread of serogroup C isolates belonging to a new lineage within clonal complex cc11 since the recommendation was first issued in July 2013.
PTU-021 3D Reconstruction in Capsule Endoscopy; a Feasibility Study
Authors: A Koulaouzidis, A Karargyris, E Rondonotti, J N Plevris
Journal: Gut (2013)

<h3>Introduction</h3> Three-dimensional (3D) imaging in small-bowel capsule endoscopy (SBCE) is not currently feasible due to hardware limitations. However, there has been increasing use of software algorithms to enable 3D reconstruction in this setting. The aim of this study was to explore a) whether innovative software offers accurate 3D reconstruction of monocular images and b) if its application leads to enhanced lesion visualisation in SBCE. <h3>Methods</h3> Feasibility study; first, a phantom was designed to test the accuracy of 3D reconstruction by comparing images of red, yellow and white phantom models to their 2D counterparts. Thereafter, a total of 192 SBCE images (84 PillCam®/108 MiroCam®; vascular: <i>n</i> = 50; inflammatory: <i>n</i> = 73; protruding structures/lesions: <i>n</i> = 69) were reviewed with the aid of a purpose-built 3D reconstruction software. Seven endoscopists rated visualisation improved or non-improved (compared to original 2D images) (Figure 1). Finally, the following sub-group analyses were performed: type of finding (vascular <i>vs</i> inflammatory <i>vs</i> protruding), colour of finding and SBCE equipment used (PillCam® <i>vs</i> Mirocam®). <h3>Results</h3> Overall, phantom experiments showed that the 3D reconstruction software was accurate in predicting the protruding or non-protruding nature for 90% of red, 70% of yellow and 45% of white phantom models. Furthermore, it offered enhanced visualisation for 56% of vascular, 23% of inflammatory and &lt; 10% of protruding structures/lesions (<i>P</i> = 0.007, 0.172 and 0.008, respectively). Lastly,when the images were categorised according to the predominant colour of the lesion, 3D software application enhanced 29/54 (53.7%) of red, 12/55 (21.8%) of white, 5/29 (17.3%) of red+white and 5/54 cases (9.2%) of lesions with colour similar to that of the surrounding mucosa, <i>P</i> &lt; 0.0001. <h3>Conclusion</h3> Application of a 3D reconstruction software in SBCE leads to image enhancement for a significant proportion (56%) of vascular, but less so for inflammatory and protruding lesions. Its integration, as adjunct tool, in CE reviewing software is desirable. <h3>Disclosure of Interest</h3> A. Koulaouzidis Grant/Research Support from: Research support from Given Imanging Ltd, A. Karargyris: None Declared, E. Rondonotti: None Declared, J. Plevris: None Declared
Abstract 1270: Elevated levels of poly(ADP-ribose) lead to novel apoptotic signaling and the induction of caspase-independent cell death
Authors: Xiaoxing Feng, Yiran Zhou, David W. Koh
Journal: Cancer Research (2010)

Abstract The metabolism of poly(ADP-ribose) (PAR) is activated by DNA damage, where PAR polymerase-1 (PARP-1) transfers ADP-ribose onto nuclear proteins to form PAR and PAR glycohydrolase (PARG) catalyzes its degradation. Previous findings show that high levels of PAR lead to its presence in the cytoplasm, where it signals the release of the proapoptotic protein, apoptosis inducing factor (AIF). Our studies suggest that inhibiting PAR glycohydrolase (PARG), and thus promoting increased levels of PAR, will increase the efficacy of anti-cancer agents by promoting this alternative cell death pathway mediated by AIF. The objective of this study is to elucidate the pathway of cytoplasm PAR cell death signaling in cancer cells. We utilized MDA-MB-231 breast cancer cells to reveal the ability of AIF to induce cancer cell death following caspase inhibition. In addition, PARG null embryonic trophoblast stem cells were utilized to determine the cytoplasmic PAR signaling pattern and to purify the PAR-modified nuclear proteins released in the cytoplasm. FACS analysis demonstrated equivalent levels of cell death with or without caspases and Western blot revealed a robust release of AIF from the mitochondria following DNA damage. Following low-dose DNA-damaging agent treatment in PARG null cells, cytoplasmic PAR was detected concurrently with AIF translocation to the nucleus, as shown by Western blot and confocal immunofluorescence. In PARG null cells in the absence of stress, cytoplasmic PAR levels were maximal after 3 days as shown by cell fractionations and Western blot. The cytoplasmic fraction containing PAR was then purified using dihydroxyboronyl Bio-Rex affinity chromatography. The purified PAR-modified proteins were treated with phosphodiesterase to remove all PAR and SDS-PAGE analysis demonstrated several proteins ranging from 20-50 kDa, which together serve as the cytoplasmic signal that causes AIF release from the mitochondria. These proteins potentially reveal novel nuclear-to-mitochondrial cell signaling ligands that are necessary for the induction of the AIF pathway of caspase-independent cell death. Taken together, the results demonstrate the importance of AIF in cancer cell death and novel insight into the cell death signaling by PAR that produces AIF-mediated cell death. Therefore, ability to increase PAR levels by inhibiting PARG is potentially a unique method to induce the death of cancer cells by an alternative cell death pathway. This research was supported by funding from the American Cancer Society and the Pharmaceutical Research Manufacturers of America. 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 1270.