tbuckley/cabot-search huggingface dataset:
IB-10 * A DUALITY OF ROLES FOR PERFORIN IN CD8+ T CELL- GLIOMA INTERACTIONS: CONTRIBUTIONS TO CYTOTOXICITY AND ALTERED VASCULAR PERMEABILITY
Authors: D. Renner, F. Jin, I. Parney, I. Pirko, K. Pavelko, A. Johnson
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is a highly aggressive malignancy of the central nervous system that exhibits extensive vascularization and a high degree of invasiveness into the surrounding brain parenchyma. Recent evidence in both animal model systems and clinical trials have demonstrated the viability of immunotherapeutic strategies at selectively targeting tumor cells, with the generation of tumor antigen-specific CD8+ T cells strongly correlating to reductions in tumor burden. We have utilized the GL261 glioma model in immune-competent C57BL/6 mice to demonstrate the efficacy of a novel picornavirus vaccination approach. Treatment of established gliomas with a picornavirus engineered to express tumor-specific antigens delayed tumor progression and extended survival, outcomes which were accompanied by increased tumor-specific CD8+ T cell responses in the brain. Importantly, both intracranial and peripheral vaccination routes were effective at promoting anti-tumor CD8+ T cell responses. Perforin, an immune effector molecule, is well characterized for its role in CD8+ T cell-mediated cytotoxicity. Our data demonstrate that, in addition to this role in direct tumor cell lysis, perforin also contributes to alterations in tumor vascular permeability. Untreated perforin deficient mice bearing GL261 gliomas demonstrated no difference in tumor burden compared to C57BL/6 controls. However, the heterogeneity of tumor vascular permeability in mice lacking perforin was significantly reduced. As such, we propose that perforin serves dual functions in CD8+ T cell-glioma interactions, contributing to both direct killing of tumor cells and immune-mediated alterations to tumor vasculature.
S120 IL-1 is a key epithelial alarmin which promotes fibroblast activation
Authors: M. I. Suwara, L. A. Borthwick, J. Mann, A. J. Fisher, D. A. Mann
Journal: Thorax (2010)

Background Alarmins are molecular ‘danger signals’ released by injured cells that can contribute to the innate immune response by activating immune cells via multiple receptors including Toll-like receptors (TLR), Nod-like receptors (NLR) and the receptor for advanced glycationend products (RAGE). Pulmonary fibrosis is associated with the upregulation of alarmins such as Interleukin 1 α (IL-1α) and High mobility group box 1 (HMGB1) in bronchoalveolar lavage fluid (BAL), however it remains unclear whether alarmins can contribute directly to the fibrogenic process by interacting with fibroblasts. We hypothesised that alarmins released from damaged epithelial cells act as damage associated molecular patterns (DAMPs) which are recognised by fibroblasts and lead to their activation. Methods The 16HBE14o- human bronchial epithelial cell line was damaged by hydrogen peroxide (H2O2) induced oxidative stress and alarmin release (Heat Shock Protein 60 (HSP-60), HMGB1, IL-1α) measured via ELISA. MRC5 human lung fibroblasts were treated with media from damaged lung epithelia and cell proliferation (XTT proliferation assay), phosphorylation of downstream TLR signalling molecules (interleukin 1 receptor associated kinase 1 (IRAK1), TGFβ associated kinase 1 (TAK1)—western blotting) and gene expression of proinflammatory cytokines (interleukin 6 (IL-6) and Interferon β (IFNβ)—qRT-PCR) assessed. Results Conditioned media from 16HBE14o- cells damaged with 200 μM H2O2 contained elevated concentrations of HSP-60 (16.7 vs 0.64 ng/ml; p<0.05, n=3), HMGB1 (71 vs 12 ng/ml; p<0.001, n=3) and IL-1α (434 vs 130 pg/ml; p<0.001, n=3) compared to untreated controls. Treatment of MRC5 cells with media from damaged lung epithelia enhanced cell proliferation by 29% (p<0.01, n=3), increased TAK1 and IRAK1 phosphorylation and increased IL-6 and IFNβ gene expression 2.7-fold (p<0.001, n=3) and threefold (p<0.001, n=3) respectively. Blocking IL-1R (500 ng/ml of IL-1R antagonist (IL-1Ra)) diminished IL-6 (85%; p<0.01, n=3) and IFNβ (34%; p<0.05, n=3) gene expression compared to treatment with conditioned media from damaged cells alone. Conclusions The results suggest that alarmins such as the intrerleukin-1 family, released by damaged human lung epithelia may be implicated in activation of fibroblasts and could contribute to fibrogenic responses in lung disease. However, further studies are required to confirm relative importance within the family and reveal mechanisms of action.
Abnormalities of Acid-Base Regulation in Chronic Pulmonary Disease, with Special Reference to Hypercapnia and Extracellular Alkalosis
Authors: Eugene D. Robin
Journal: New England Journal of Medicine (1963)

CARBON dioxide retention resulting in an elevation of carbon dioxide tension of body fluids occurs commonly in chronic obstructive pulmonary disease. The hydration of carbon dioxide to carbonic acid leads to an increased concentration of hydrogen ions in body fluids or acidosis. Excess hydrogen ions, so generated, are partially buffered in tissue cells (erythrocytes, bone, muscle and brain) and also result in increased renal hydrogen ion excretion. (It is not clearly established, at present, whether the renal response depends only on increased hydrogen ion excretion, per se, or whether there is enhanced independent tubular bicarbonate resorption, but for descriptive purposes . . .
AB0680 Depression, anxiety, anger and fatigue in systemic lupus erythematosus: Association with disease activity and damage
Authors: J.-S. Song, S.T. Choi, J.I. Kang, E.-J. Kang, Y.-J. Ha, K.-H. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Various psychological distresses in systemic lupus erythematosus (SLE) may be associated with systemic conditions. However, the influence of psychological distresses to the SLE disease activity still remains unclear. <h3>Objectives</h3> We evaluated the levels of depression, anxiety, anger and fatigue in patients with SLE, compared to those of healthy controls. We investigated the association between the psychological distresses and disease activity and damage in patients with SLE. <h3>Methods</h3> 105 patients with SLE and 51 healthy controls completed a psychological questionnaire. Psychological distresses were assessed as follows: depression, Center for Epidemiologic Studies Depression Scale (CES-D); anxiety, Hospital Anxiety and Depression Scale (HADS); anger, State Trait Anger Expression Inventory (STAXI); fatigue, the Profile of Mood States fatigue-inertia Scale (POMS-F). Disease activity and damage index were measured by the SLE Disease Activity Index (SLEDAI) and the SLE Collaborating Clinics/American College of Rheumatology (SLICC/ACR), respectively. <h3>Results</h3> Patients with SLE showed higher levels of depression (<i>p</i>=0.003), anxiety (<i>p</i>=0.049), anger (<i>p</i>=0.021) and fatigue (<i>p</i>=0.003) than healthy controls. In the patients with SLE, psychological distresses were well correlated with each other (depression and anxiety: γ=0.712, <i>p</i>&lt;0.001; depression and anger: γ=0.573, <i>p</i>&lt;0.001; depression and fatigue: γ=0.703, <i>p</i>&lt;0.001; anxiety and anger: γ=0.513, <i>p</i>&lt;0.001; anxiety and fatigue: γ=0.592, <i>p</i>&lt;0.001; anger and fatigue: γ=0.556, <i>p</i>&lt;0.001, respectively). The group using higher doses of glucocorticoids (prednisolone &gt;7.5 mg/day) had greater symptoms in all of the psychological distresses than the group with lower doses of glucocorticoids (prednisolone ≤7.5 mg/day) (depression, <i>p</i>=0.002; anxiety, <i>p</i>=0.027; anger, <i>p</i>=0.007; fatigue, <i>p</i> =0.016, respectively). However, none of the psychological distresses showed significant differences between higher disease activity and lower disease activity groups, and between higher damage and lower damage groups. In a multiple linear analysis, depression was affected by SLE disease activity (β=0.223, <i>p</i>=0.026) and daily prednisolone doses (β=0.228, <i>p</i>=0.029). However, SLE disease activity was not affected by the psychological distresses. <h3>Conclusions</h3> SLE patients had more psychological distresses, such as depression, anxiety, anger and fatigue than healthy controls. Higher levels of disease activity and higher use of glucocorticoids affect on depression, while the results do not support that psychological distress affects disease activity status. <h3>Disclosure of Interest</h3> None Declared
The Role of Flow Cytometry in Myelodysplastic Syndromes
Authors: Michael R. Loken, Denise A. Wells
Journal: Journal of the National Comprehensive Cancer Network (2008)

Flow cytometry quantifies the gene product expression on hematopoietic cells, permitting the identification of all cells within a bone marrow aspirate and classifying them according to lineage and maturational stage. The relationships in the expression of multiple markers on myeloblasts, maturing monocytes, and myeloid cells suggests that development of these cells is a stepwise process in which genes are not only turned on or off, but are up- and down-regulated at the junctions between stages. In neoplastic processes, a loss of coordination of these steps is seen, resulting in the abnormal relationships identified by flow cytometry. In myelodysplastic syndromes, the abnormal patterns can be identified on both the immature myeloblasts and maturing myeloid cells and monocytes. The detection of these abnormalities is useful in diagnosing myelodysplasia but requires a detailed understanding of the expression of these gene products to discriminate neoplastic transformation from a stressed marrow. Although the patterns of antigen expression for normal hematopoiesis are precisely defined, each patient with a neoplastic transformation has a unique repertoire of abnormalities that may evolve as the disease progresses. Therefore, scoring systems, in which the abnormalities are counted, provide a means for determining the extent of dysregulation at all the maturational steps, thereby determining a "distance from normal" for a patient at a specific time in the disease course. This is useful, not only to facilitate diagnosis, but to provide prognostic information that may be complementary to the conventional classification schemes and scoring systems.
Abstract 1088: HOXB13 inhibition of succinate dehydrogenase leads to epithelial-to-mesenchymal transition in mouse ovarian cancer cell lines.
Authors: Paul-Joseph Aspuria, Dong-Joo Cheon, Maricel Gozo, Brenda Salumbides, Laurent Vergnes, John Asara, Karen Reue, Elizabeth Kensicki, Beth Karlan, Sandra Orsulic
Journal: Cancer Research (2013)

Abstract HOXB13 is a homeobox gene whose dysregulation has been implicated in cancer. We have previously shown that HOXB13 plays an oncogenic role in ovarian cancer by driving epithelial-to-mesenchymal transition (EMT); however the mechanism by which this occurs has not been established. Global metabolomics profiling revealed that overexpression of HOXB13 in genetically defined mouse ovarian cancer cell lines inhibits succinate dehydrogenase (SDH) activity. Targeted-knockdown of the SDH subunit SdhB by shRNA results in mislocalization of E-cadherin and a spindle-shaped morphology suggestive of EMT. Metabolomics and real-time flux analysis showed that knockdown of SdhB results in elevated levels of succinate as well as defective mitochondrial respiration. Despite the mitochondrial respiration defect, SdhB knockdown cells display increased anchorage-independent growth in soft agar and enhanced xenograft tumor formation. Elevated levels of succinate have been shown to inhibit α-ketoglutarate requiring enzymes such as the Jumanji C (JmjC)-domain containing H3K27 demethylases, UTX and JMJD3. Indeed, knockdown of SdhB results in a hypermethylated epigenome as evidenced by increased levels of H3K27me2 and H3K27me3. Both the epigenetic and EMT phenotypes can be recapitulated by pharmacological inhibition of UTX and JMJD3 in control cells. These data point to a mechanism wherein modulation of oncometabolite levels can affect the epigenome, thereby influencing cancer cell morphology and tumorigenic properties. Citation Format: Paul-Joseph Aspuria, Dong-Joo Cheon, Maricel Gozo, Brenda Salumbides, Laurent Vergnes, John Asara, Karen Reue, Elizabeth Kensicki, Beth Karlan, Sandra Orsulic. HOXB13 inhibition of succinate dehydrogenase leads to epithelial-to-mesenchymal transition in mouse ovarian cancer cell lines. [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 1088. doi:10.1158/1538-7445.AM2013-1088
FRI0488 Analysis of REAL Life Vasoactive Therapy in over 3000 Patients with Systemic Sclerosis (SSC) Reveals Considerable Undertreatment and Significant Changes of Treatment Practice since 2004
Authors: P. Moinzadeh, A. Elisabeth, N. Blank, J. Distler, G. Fierlbeck, E. Genth, C. Guenther, R. Hein, J. Henes, M. Hellmich, I. Herrgott, I. Koetter, A. Kreuter, T. Krieg, I. Melchers, H. Mensing, U. Mueller-Ladner, C. Pfeiffer, G. Riemekasten, M. Sárdy, L. Susok, M. Worm, G. Wozel, G. Zeidler, C. Sunderkoetter, N. Hunzelmann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Vasculopathy is a major pathophysiological problem in patients with systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcerations (DU), pulmonary arterial hypertension (PAH). It is not known, how SSc patients are treated with vasoactive agents in daily practice. <h3>Objectives</h3> To determine, to which extent SSc patients are treated with vasoactive drugs. <h3>Methods</h3> Data of 3248 patients of the registry of German Network for Systemic Scleroderma were analyzed. <h3>Results</h3> Patients were treated with vasoactive drugs in 54.9% (1784) cases. Of these, 53% received calcium channel inhibitors (CCI), followed by 23.5% treated with intravenous Prostanoids (Iloprost, Prostavasin), 11.8% with beta-blockers, 11.3% with Pentoxifylline, 9.7% with Endothelin 1 receptor antagonists (ETRA), 4.6% with PDE5 inhibitors, 2.7% with topical vasodilative agents and 3.2% with others. Patients with RP received vasoactive therapy in 47,4%, with DU in 66,8% and with PAH in 71,6% of cases. Logistic regression analysis revealed, that patients who suffered from PAH were significantly more often treated with PDE5 inhibitors (odds ratio (OR) 7.2; p&lt;0.0001) and ETRA (OR 6.9; p&lt;0.0001) and those with digital ulcers with ETRA (OR 2.8; p&lt;0.0001) and intravenous prostanoids (OR 1.7; p&lt;0.0001). Patients were more frequently treated with β-blockers, when they had arterial hypertension (OR 4.2; p&lt;0.0001) and were male (OR 1.9; p&lt;0.0001). In addition 25,6% (830) patients were treated with ACE-inhibitors or AT1-receptor antagonists. They were often male and suffered from the diffuse form of SSc (p&lt;0.001). Logistic regression analysis within this group clearly indicated that patients with hypertension (OR 4.9; p&lt;0.0001) and renal insufficiency (OR 3.0; p&lt;0.0001) were significantly more often treated with ACE inhibitors. When patients, registered after 2009, were compared to patients registered prior to 2004, it was found that after 2009 significantly more patients received ETRA (12% vs 5.5%; p&lt;0.0001), beta-blockers (14.1% vs 7.6%; p&lt;0.001), AT1R antagonists (12.5% vs 4.6%; p&lt;0.0001), intravenous prostanoids (26.6% vs 18.2%; p&lt;0.001) and ACE inhibitors (28.6% vs 23.1%; p&lt;0.008). <h3>Conclusions</h3> These data clearly indicate that many SSc patients with RP, DU, and PAH do not yet receive sufficient vasoactive therapy. Furthermore, in recent years a marked change of treatment regimens can be observed. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4946
A memorable patient: An escalating problem
Authors: P K Das-Purkayastha
Journal: BMJ (2002)

Mrs C, a 77 year old lady, was admitted to the Royal United Hospital Bath on 26 September after an usual sequence of events. Earlier that day she had been parking her automatic car, but when she stopped and got out to open her garage door she unfortunately failed to engage the handbrake. While she was opening the door, her car eased forward …
Stratified Radiotracer Activity in a Floppy Neobladder on Both 18F-FDG PET/CT and 99mTc-MDP Bone Scan
Authors: Hai-Jeon Yoon, Bom Sahn Kim
Journal: Clinical Nuclear Medicine (2014)

18F-FDG and 99mTc-MDP are excreted through the renal system. For the most part, radiotracers are uniformly distributed in the bladder; however, their distribution can exhibit unique patterns in certain situations. We present a case of stratified urine activity in a floppy neobladder on nuclear medicine imaging performed just after CT and MRI contrast studies, respectively.
Stanford Battered On Indirect Costs; Other Schools Will Be Examined
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Stanford Battered On Indirect Costs; Other Schools Will Be Examined Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 8, 17 April 1991, Pages 533–534, https://doi.org/10.1093/jnci/83.8.533 Published: 17 April 1991
TCTAP C-142 Successful Percutaneous Coronary Intervention in the Old Patient with Severe Ischemic Heart Failure with 3 Vessel Disease Including 2 Chronic Total Occlusion
Authors: Yamamoto Kei, Yusuke Tamanaha, Naoyuki Akashi, Tatsuro Ibe, Tomohiro Nakamura
Journal: Journal of the American College of Cardiology (2015)
CHRONIC OPIOID USE IS ASSOCIATED WITH SIGNIFICANT HIGHER 12-MONTH ALL-CAUSE READMISSION AND ALL-CAUSE MORTALITY BUT NOT ASSOCIATED WITH 30-DAY ALL-CAUSE READMISSION OR ALL-CAUSE MORTALITY IN OLDER MEDICARE BENEFICIARIES HOSPITALIZED FOR HEART FAILURE
Authors: Raymond K. Young, Sarah Goodlin, Wen-Chih Wu, Charity Morgan, Sijian Zhang, Donna Bearden, Marc Blackman, Ross Fletcher, Cynthia Brown, Gregg Fonarow, Prakash Deedwania, Wilbert Aronow, Ioannis Kanonidis, Richard Allman, Ali Ahmed
Journal: Journal of the American College of Cardiology (2016)
598 SELECTED DOMAINS BUT NOT SUMMARY SCORE OF MINI-MENTAL STATE EXAMINATION CORRELATE WITH HEPATIC ENCEPHALOPATHY IN PATIENTS WITH LIVER CIRRHOSIS. A PROSPECTIVE, QUANTIFIED ELECTROENCEPHALOGRAPHY STUDY
Authors: D. Koziarska, E. Wunsch, M. Milkiewicz, J. Mieżńska-Kurtycz, P. Nowacki, P. Milkiewicz
Journal: Journal of Hepatology (2012)
A SINE that acquired a role in signal transduction during evolution
Authors: M. Shimamura, M. Nikaido, K. Ohshima, N. Okada
Journal: Molecular Biology and Evolution (1998)

We have discovered a new SINE that appears to have acquired a novel role in signal transduction in the lineage of a group of artiodactyls. SINEs are a group of retroposons which have been amplified and integrated into genomes by retroposition (Okada and Ohshima 1995) The majority of SINEs are believed to be parasitic and to represent junk DNA in host organisms. However, in certain cases, SINEs appear to have gained novel functions and to have become involved in biological processes. More than 10 such examples have been recorded, in which sequences of SINEs have become promoters that modify the expression of preexisting functional genes or provide a new polyadenylation signal (Britten 1996; Makalowski 1995). In other cases, SINEs have been integrated into the coding region and are translated into peptides, with resulting generation of protein variability. In fact, more than 30 SINEs have been found in the coding regions of mRNAs (Makalowski 1995). However, no examples of such messages playing an explicit role in an important biological process have yet been reported (Makalowski 1995). We recently characterized the CHR-1 SINEs, which are distributed exclusively among whales, cows, and hippopotamuses (Shimamura et al. 1997). In a BLASTN search (Altschul et al. 1990), we found an example of a CHR-1 SINE that was inserted into the coding region of mRNA for the EP3 subtype of receptor for bovine prostaglandin (PG) E2. It appears that this message with an integrated SINE plays a key role in the signal transduction that is mediated by the bovine EP3 receptor for PGE2. Prostaglandin E2 has a broad range of biological effects in diverse tissues that are mediated through its binding to specific receptors on plasma membranes. Four subtypes of receptors (EP1, EP2, EP3, and EP4) for PGE2 have been recognized on the basis of their respective responses to agonists and antagonists (Coleman et al. 1989). It has been proposed that the EP3 receptor mediates various very different effects of PGE2, such as inhibition of neurotransmitter release (Ohia and Jumblatt 1990), contraction of the uterus (Krall et al. 1984), inhibition of the reabsorption of sodium ions and water in kidney tubules (Nakao et al. 1989), and stimulation of catecholamine release from adrenal chromaffin cells (Tanaka et al. 1990). The EP3 receptor is a protein with seven transmembrane domains. The bovine EP3 receptor exists as
OC-030 Benefits of introduction of a symptom triggered regimen for management of alcohol withdrawal in a large teaching hospital trust: reduced admission duration and cost savings
Authors: T J W Lee, M Samuel, L Bewick, H Rutherford, P Perez, E Gilvarry, M Cunningham, C Dipper, S Masson
Journal: Gut (2012)

<h3>Introduction</h3> Acute alcohol withdrawal (AAW) is an increasingly frequent cause for hospital admission in the UK. NICE guidance (2010) recommends the use of a symptom triggered regimen (STR) rather than a fixed-dose regimen of benzodiazepines for the management of AAW. The aim of this study is to observe the effects of the introduction of a STR protocol as part of the introduction of a specialist Alcohol Liaison Team (ALT) in a large teaching hospital trust. <h3>Methods</h3> Data were collected prospectively on all patients admitted for management of AAW during two 3-month periods; before and after the introduction of a symptom triggered regimen. The Clinical institute for Withdrawal Assessment for alcohol scale (CIWA-Ar) was used to assess AAW objectively. The introduction of the STR was overseen by an ALT consisting of a specialist nurse and a consultant at both hospital sites in the trust. <h3>Results</h3> In the initial period, 102 patients were managed using a fixed-dose regime. Median length of stay (LoS) was 4.0 days (IQR 2–6 days). Median total chlordiazepoxide dose was 260 mg (IQR 120–490 mg). After introduction of STR, 119 patients were included. Median length of stay was 3.0 days (IQR 1.5-5.0 days). Median total chlordiazepoxide dose was 200 mg (IQR 55–450 mg). Age, gender and comorbidities in the before and after groups were comparable. The reduction in length of stay and total chlordiazepoxide dosage following introduction of the STR protocol were statistically significant (p&lt;0.001). <h3>Conclusion</h3> Introduction of a STR protocol for management of acute alcohol withdrawal was associated with a reduction in the length of stay and total benzodiazepine dose required. A specialist ALT facilitated the introduction of the STR at two hospital sites in a large teaching hospital trust. The reduction in length of stay alone could contribute to potential cost savings to the trust of around £280 000 per annum. This justifies the presence of an alcohol liaison team in the trust and supports the recommendations of the NICE guidelines. <h3>Competing interests</h3> None declared.