tbuckley/cabot-search huggingface dataset:
Ca <sup>2+</sup> /Calmodulin-Dependent Protein Kinase II Phosphorylation of Ryanodine Receptor Does Affect Calcium Sparks in Mouse Ventricular Myocytes
Authors: Tao Guo, Tong Zhang, Ruben Mestril, Donald M. Bers
Journal: Circulation Research (2006)

Previous studies in transgenic mice and with isolated ryanodine receptors (RyR) have indicated that Ca2+-calmodulin-dependent protein kinase II (CaMKII) can phosphorylate RyR and activate local diastolic sarcoplasmic reticulum (SR) Ca2+ release events (Ca2+ sparks) and RyR channel opening. Here we use relatively controlled physiological conditions in saponin-permeabilized wild type (WT) and phospholamban knockout (PLB-KO) mouse ventricular myocytes to test whether exogenous preactivated CaMKII or endogenous CaMKII can enhance resting Ca2+ sparks. PLB-KO mice were used to preclude ancillary effects of CaMKII mediated by phospholamban phosphorylation. In both WT and PLB-KO myocytes, Ca2+ spark frequency was increased by both preactivated exogenous CaMKII and endogenous CaMKII. This effect was abolished by CaMKII inhibitor peptides. In contrast, protein kinase A catalytic subunit also enhanced Ca2+ spark frequency in WT, but had no effect in PLB-KO. Both endogenous and exogenous CaMKII increased SR Ca2+ content in WT (presumably via PLB phosphorylation), but not in PLB-KO. Exogenous calmodulin decreased Ca2+ spark frequency in both WT and PLB-KO (K0.5 approximately 100 nmol/L). Endogenous CaMKII (at 500 nmol/L [Ca2+]) phosphorylated RyR as completely in <4 minutes as the maximum achieved by preactivated exogenous CaMKII. After CaMKII activation Ca2+ sparks were longer in duration, and more frequent propagating SR Ca2+ release events were observed. We conclude that CaMKII-dependent phosphorylation of RyR by endogenous associated CaMKII (but not PKA-dependent phosphorylation) increases resting SR Ca2+ release or leak. Moreover, this may explain the enhanced SR diastolic Ca2+ leak and certain triggered arrhythmias seen in heart failure.
Nitroxyl Improves Cellular Heart Function by Directly Enhancing Cardiac Sarcoplasmic Reticulum Ca <sup>2+</sup> Cycling
Authors: Carlo G. Tocchetti, Wang Wang, Jeffrey P. Froehlich, Sabine Huke, Miguel A. Aon, Gerald M. Wilson, Giulietta Di Benedetto, Brian O’Rourke, Wei Dong Gao, David A. Wink, John P. Toscano, Manuela Zaccolo, Donald M. Bers, Hector H. Valdivia, Heping Cheng, David A. Kass, Nazareno Paolocci
Journal: Circulation Research (2006)

Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effective therapies to stimulate contraction has proven difficult. This is thought to be attributable to their frequent reliance on cAMP stimulation to increase activator Ca 2+ . A potential alternative is nitroxyl (HNO), the 1-electron reduction product of nitric oxide (NO) that improves contraction and relaxation in normal and failing hearts in vivo. The mechanism for myocyte effects remains unknown. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca 2+ pump and the ryanodine receptor 2, leading to increased Ca 2+ uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca 2+ -release channels and accelerates Ca 2+ reuptake into isolated sarcoplasmic reticulum by stimulating ATP-dependent Ca 2+ transport. Contraction improves with no net rise in diastolic calcium. These changes are not induced by NO, are fully reversible by addition of reducing agents (redox sensitive), and independent of both cAMP/protein kinase A and cGMP/protein kinase G signaling. Rather, the data support HNO/thiolate interactions that enhance the activity of intracellular Ca 2+ cycling proteins. These findings suggest HNO donors are attractive candidates for the pharmacological treatment of heart failure.
BORACIC ACID POISONING
Authors: J. H. Sanders
Journal: BMJ (1912)

BORACIC ACID POISONING.6o.5S that the secondary infections of the urethra and vagina may also cause arthritis.The case now to be described was a patient of Dr.. Coonder, and tlle only part I had in the case was the preparation of the vaccine employed.CASE VII.J. E., a man aged 65, had spent the last forty-five years of his life in India.For the past twenty-five years he had trouble in his right knee in the nature of attacks of acute pain and swelling.These attacks had become more frequent and more severe in the previous six montbs.He had at times also pains in the left knee, elbow, and wrist, and in the right shoulder, ankle, and great toe, but not recently.On April 29th, 1911, Dr. Conder fotnd the right knee to contain fluid and to be 11-in.larger in circumferencee than the other.With a syringe he removed 2 oz. of purulent fluid, the pus cells of which were almost entirely polymorphs.There were also presant in the fluid cocci in pairs and short chains.A culture showed a good growth of a Gram-positive diplococcus noncapsulated.On Mav 4th another ounce of fluid was removed from the same joint and yielded the same organiism.On May 2nd the patient's opsonic index to this coccus was 0.89; on the same day he was given 100 million of his autogenous vaccine.After this he felt better, and on May 14th his opsonic index was l.59 ; as there
Quality of life in patients with psoriasis: the contribution of clinical variables and psoriasis-specific stress
Authors: D.G. FORTUNE, C.J. MAIN, T.M. O'SULLIVAN, C.E.M. GRIFFITHS
Journal: British Journal of Dermatology (1997)

Journal Article Quality of life in patients with psoriasis: the contribution of clinical variables and psoriasis‐specific stress Get access D.G. FORTUNE, D.G. FORTUNE Section of Dermatology, Department of Medicine, University of Manchester, Clinical Sciences Building, Hope Hospital, Stott Lane, Salford M6 8HD, U.K.Department of Behavioural Medicine, Hope Hospital, Salford Royal Hospitals NHS Trust, Manchester, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.J. MAIN, C.J. MAIN Department of Behavioural Medicine, Hope Hospital, Salford Royal Hospitals NHS Trust, Manchester, U.K. Search for other works by this author on: Oxford Academic Google Scholar T.M. O'SULLIVAN, T.M. O'SULLIVAN Section of Dermatology, Department of Medicine, University of Manchester, Clinical Sciences Building, Hope Hospital, Stott Lane, Salford M6 8HD, U.K.Department of Behavioural Medicine, Hope Hospital, Salford Royal Hospitals NHS Trust, Manchester, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.E.M. GRIFFITHS C.E.M. GRIFFITHS Section of Dermatology, Department of Medicine, University of Manchester, Clinical Sciences Building, Hope Hospital, Stott Lane, Salford M6 8HD, U.K. Professor C.E.M. Griffiths. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 5, 1 November 1997, Pages 755–760, https://doi.org/10.1046/j.1365-2133.1997.19472062.x Published: 01 November 1997 Article history Accepted: 18 June 1997 Published: 01 November 1997
459 FREQUENCY AND PREDICTORS OF NO TREATMENT IN ANTI-HCV POSITIVE PATIENTS AT TERTIARY LIVER CENTERS
Authors: N. Papadopoulos, S. Manolakopoulos, M. Deutsch, M. Mela, A. Christidou, A. Katoglou, D. Tzourmakliotis, G.V. Papatheodoridis
Journal: Journal of Hepatology (2011)
Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis
Authors: Tullio Palmerini, Giuseppe Biondi-Zoccai, Diego Della Riva, Christoph Stettler, Diego Sangiorgi, Fabrizio D'Ascenzo, Takeshi Kimura, Carlo Briguori, Manel Sabatè, Hyo-Soo Kim, Antoinette De Waha, Elvin Kedhi, Pieter C Smits, Christoph Kaiser, Gennaro Sardella, Antonino Marullo, Ajay J Kirtane, Martin B Leon, Gregg W Stone
Journal: The Lancet (2012)
Dexamethasone inhibits human interleukin 2 but not interleukin 2 receptor gene expression in vitro at the level of nuclear transcription.
Authors: D T Boumpas, E D Anastassiou, S A Older, G C Tsokos, D L Nelson, J E Balow
Journal: Journal of Clinical Investigation (1991)

Glucocorticosteroids have an inhibitory effect on the expression of interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R) genes. To determine the mechanisms of this inhibition, human T lymphocytes were stimulated with mitogens in the presence of dexamethasone. Nuclear transcription run-off assays showed that high doses of dexamethasone inhibited the transcription of the IL-2 gene but not that of the IL-2R gene. Post-transcriptionally, high doses of dexamethasone (10(-4) M) were required to inhibit IL-2R mRNA levels by 50%, whereas lower doses (10(-6) M) inhibited by greater than 70% the accumulation of IL-2 mRNA. IL-2 mRNA half-life decreased in the presence of dexamethasone (10(-6) M) by approximately 50%. At the protein product level, dexamethasone inhibited both IL-2 production, as well as cell surface and soluble forms of IL-2R. IL-2R gene expression was inhibited for at least 72 h after exposure of cells to dexamethasone. In the presence of exogenous IL-2, dexamethasone failed to exert a significant effect on the production of IL-2R protein. These data indicate that dexamethasone has a greater effect on the expression of the IL-2 gene than on the IL-2R gene. Dexamethasone both inhibits transcription of the IL-2 gene and decreases the stability of IL-2 mRNA. The effect of dexamethasone on the IL-2R gene is post-transcriptional and may result indirectly from decreased IL-2 production.
Treatment of stage I and II Hodgkin's lymphoma with ABVD chemotherapy: results after 7 years of a prospective study
Authors: A. Rueda Domínguez, A. Márquez, J. Gumá, M. Llanos, J. Herrero, M.A. de las Nieves, J. Miramón, E. Alba
Journal: Annals of Oncology (2004)
Quantitative determination of isradipine in dog plasma by an ultra performance liquid chromatography–tandem mass spectrometry method
Authors: Xiaojing Yang, Haiyan Xu, Jingjing Gan, Li Li, Jiayang Li, Yi Jin, Bo Yuan
Journal: Asian Journal of Pharmaceutical Sciences (2013)

A simple, sensitive and specific ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed for the analysis of isradipine in dog plasma. After extracted with organic solvent, dog plasma samples were analyzed on an Acquity UPLC BEH C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode. Acetonitrile:water:formic acid (80:20:0.3, v/v/v) was used as the mobile phase at a flow rate of 0.2 ml/min. The chromatographic run time of each sample was 1.4 min. The calibration curve in plasma was linear in the range of 0.1–40.0 ng/ml. The intra- and inter-day precision was within 13.5% in terms of relative standard deviation (RSD%) and the accuracy was required to be 96.5%–98.4%. The validated UPLC–MS/MS method was successfully applied in a pharmacokinetic study of controlled-release isradipine in dogs.
Relaxin-Expressing, Fiber Chimeric Oncolytic Adenovirus Prolongs Survival of Tumor-Bearing Mice
Authors: Shanthi Ganesh, Melissa Gonzalez Edick, Neeraja Idamakanti, Marina Abramova, Melinda VanRoey, Michael Robinson, Chae-Ok Yun, Karin Jooss
Journal: Cancer Research (2007)

Selective replication of oncolytic viruses in tumor cells provides a promising approach for the treatment of human cancers. One of the limitations observed with oncolytic viruses currently used in the treatment of solid tumors is the inefficient spread of virus throughout the tumor mass following intratumoral injection. Data are presented showing that oncolytic adenoviruses expressing the relaxin gene and containing an Ad5/Ad35 chimeric fiber showed significantly enhanced transduction and increased virus spread throughout the tumor when compared with non-relaxin-expressing, Ad5-based viruses. The increased spread of such viruses throughout tumors correlated well with improved antitumor efficacy and overall survival in two highly metastatic tumor models. Furthermore, nonreplicating viruses expressing relaxin did not increase metastases, suggesting that high level expression of relaxin will not enhance metastatic spread of tumors. In summary, the data show that relaxin may play a role in rearranging matrix components within tumors, which helps recombinant oncolytic adenoviruses to spread effectively throughout the tumor mass and thereby increase the extent of viral replication within the tumor. Expressing relaxin from Ad5/Ad35 fiber chimeric adenoviruses may prove a potent and novel approach to treating patients with cancer.
Organs By Firing Squad: The Medical and Moral Implausibility of Death Penalty Organ Procurement
Authors: Daniel Fu-Chang Tsai, Meng-Kung Tsai, Wen-Je Ko
Journal: The American Journal of Bioethics (2011)

Using executed prisoners’ organs for transplantation has been a debated ethical, legal, and human rights issue for some time. Opinions in favor of such practice are usually based on the idea that t...
Patupilone Induced Vascular Disruption in Orthotopic Rodent Tumor Models Detected by Magnetic Resonance Imaging and Interstitial Fluid Pressure
Authors: Stephane Ferretti, Peter R. Allegrini, Terence O'Reilly, Christian Schnell, Michael Stumm, Markus Wartmann, Jeanette Wood, Paul M.J. McSheehy
Journal: Clinical Cancer Research (2005)

Evaluation of vascular disruptive activity in orthotopic models as potential surrogate biomarkers of tumor response to the microtubule-stabilizing agent patupilone.Mice bearing metastatic B16/BL6 melanoma and rats bearing mammary BN472 tumors received vehicle or efficacious patupilone doses (4 and 0.8-1.5 mg/kg i.v., respectively). Tumor vascularity assessment by dynamic contrast-enhanced or dynamic susceptibility contrast magnetic resonance imaging and interstitial fluid pressure (IFP) occurred at baseline, 2 days (mice and rats), and 6 days (rats) after treatment and were compared with histologic measurements and correlated with tumor response.In B16/BL6 metastases, patupilone (4 mg/kg) induced a 21 +/- 5% decrease (P < 0.001) in tumor blood volume and a 32 +/- 15% decrease (P = 0.02) in IFP after 2 days and reduced tumor growth and vessel density (>42%) after 2 weeks (P < or = 0.014). Patupilone dose-dependently inhibited BN472 tumor growth (day 6) and reduced IFP on days 2 and 6 (-21% to -70%), and the percentage change in IFP correlated (P < 0.01) with the change in tumor volume. In both models, histology and vascular casts confirmed decreases in tumor blood volume. One patupilone (0.8 mg/kg) administration decreased (P < 0.01) tumor IFP (54 +/- 4%), tumor blood volume (50 +/- 6%), and vessel diameter (40 +/- 11%) by day 6 but not the apparent diffusion coefficient, whereas histology showed that apoptosis was increased 2.4-fold and necrosis was unchanged. Apoptosis correlated negatively (P < 0.001) with IFP, tumor blood volume, and tumor volume, whereas tumor blood volume and IFP were correlated positively (P = 0.0005).Vascular disruptive effects of patupilone were detected in situ using dynamic contrast-enhanced or dynamic susceptibility contrast magnetic resonance imaging and IFP. Changes in IFP preceded and correlated with tumor response, suggesting that IFP may be a surrogate biomarker for patupilone efficacy.
Regulation of Inflammation and Angiogenesis in Giant Cell Arteritis by Acute‐Phase Serum Amyloid A
Authors: Lorraine O'Neill, Peadar Rooney, Danielle Molloy, Mary Connolly, Jennifer McCormick, Geraldine McCarthy, Douglas J. Veale, Conor C. Murphy, Ursula Fearon, Eamonn Molloy
Journal: Arthritis & Rheumatology (2015)

Objective Giant cell arteritis (GCA) is pathologically characterized by dysfunctional angiogenesis and inflammatory cell infiltration. Acute‐phase serum amyloid A (A‐SAA) is an acute‐phase reactant, but is also produced at sites of inflammation and may contribute to vascular inflammation in atherosclerosis. This study was undertaken to examine the effect of A‐SAA on proinflammatory pathways and angiogenesis in GCA, using a novel ex vivo temporal artery tissue explant model. Methods Serum A‐SAA levels were measured by enzyme‐linked immunosorbent assay (ELISA). Temporal artery explants and peripheral blood mononuclear cell (PBMC) cultures were established from patients with GCA. Temporal artery explant morphology, viability, and spontaneous release of proinflammatory mediators following 24‐hour culture were assessed by hematoxylin and eosin, calcein viability staining, and ELISA. Temporal artery explants and PBMC cultures were stimulated with A‐SAA (10 μg/ml), and interleukin‐6 (IL‐6), IL‐8, vascular endothelial growth factor, Ang2, and matrix metalloproteinase 2 (MMP‐2)/MMP‐9 were quantified by ELISA and gelatin zymography. The effect of conditioned medium from temporal artery explants on angiogenesis was assessed using endothelial cell Matrigel tube‐formation assays. Temporal artery explants were also embedded in Matrigel, and myofibroblast outgrowth was assessed. Results Serum A‐SAA levels were significantly higher in GCA patients versus healthy controls ( P &lt; 0.0001). Intact tissue morphology, cell viability, and spontaneous cytokine secretion were demonstrated in temporal artery explants. A‐SAA treatment induced a significant increase in the levels of IL‐6 and IL‐8 from temporal artery explants ( P &lt; 0.05) and IL‐8 from PBMCs ( P &lt; 0.05) compared to basal conditions. Conditioned medium from A‐SAA–treated explants significantly induced angiogenic tube formation ( P &lt; 0.05 versus basal controls). Finally, A‐SAA induced myofibroblast outgrowth and MMP‐9 activation. Conclusion Our findings demonstrate a functional role for A‐SAA in regulating temporal artery inflammation, angiogenesis, and invasion, all key processes in the pathogenesis of GCA.
Risk factors, testing and preventative strategies for non-contact injuries in professional football: current perceptions and practices of 44 teams from various premier leagues
Authors: Alan McCall, Chris Carling, Mathieu Nedelec, Michael Davison, Franck Le Gall, Serge Berthoin, Gregory Dupont
Journal: British Journal of Sports Medicine (2014)

Little is known about injury prevention practices in professional football clubs. The purpose of this study was therefore to determine the current perceptions and practices of premier league football clubs internationally concerning risk factors, testing and preventative exercises for non-contact injuries.A survey was administered to 93 premier league football clubs internationally. The survey included four sections: (1) persons involved in the injury prevention programme: position, quantity, role, qualification; (2) perceptions regarding non-contact injury risk factors; (3) tests used to identify non-contact injury risk and (4) non-contact injury prevention exercises used, their perceived effectiveness and implementation strategies.44 surveys were successfully returned (47%). The position of physiotherapist was the most represented position in the injury prevention programme. The top five perceived risk factors in rank order were previous injury, fatigue, muscle imbalance, fitness and movement efficiency. The five most commonly used tests to identify injury risk (in rank order) were functional movement screen, questionnaire, isokinetic dynamometry, physical tests and flexibility. The top five exercises used by clubs were (also in rank order) eccentric exercise, balance/proprioception, hamstring eccentric, core stability and, sharing the fifth position, Nordic hamstring and gluteus activation.The survey revealed the most common perceptions and practices of premier league football clubs internationally regarding risk factors, testing and preventative exercises. The findings can enable reduction of the gap between research and practice.
Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation
Authors: Francesco Ciccia, Antonina Accardo-Palumbo, Aroldo Rizzo, Giuliana Guggino, Stefania Raimondo, AnnaRita Giardina, Alessandra Cannizzaro, Robert A Colbert, Riccardo Alessandro, Giovanni Triolo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Interleukin (IL)-23 has been implicated in the pathogenesis of ankylosing spondylitis (AS). The aim of the study was to clarify the mechanisms underlying the increased IL-23 expression in the gut of AS patients. <h3>Methods</h3> Consecutive gut biopsies from 30 HLA-B27<sup>+</sup> AS patients, 15 Crohn9s disease (CD) patients and 10 normal subjects were obtained. Evidence for HLA-B27 misfolding was studied. Unfolded protein response (UPR) and autophagy were assessed by RT-PCR and immunohistochemistry. The contribution of UPR and autophagy in the regulation of IL-23 expression was evaluated in in vitro experiments on isolated lamina propria mononuclear cells (LPMCs). <h3>Results</h3> Intracellular colocalisation of SYVN1 and FHCs but not a significant overexpression of UPR genes was observed in the gut of AS patients. Conversely, upregulation of the genes involved in the autophagy pathway was observed in the gut of AS and CD patients. Immunohistochemistry showed an increased expression of LC3II, ATG5 and ATG12 but not of SQSTM1 in the ileum of AS and CD patients. LC3II was expressed among infiltrating mononuclear cells and epithelial cells resembling Paneth cells (PC) and colocalised with ATG5 in AS and CD. Autophagy but not UPR was required to modulate the expression of IL-23 in isolated LPMCs of AS patients with chronic gut inflammation, CD patients and controls. <h3>Conclusions</h3> Our data suggest that HLA-B27 misfolding occurs in the gut of AS patients and is accompanied by activation of autophagy rather than a UPR. Autophagy appears to be associated with intestinal modulation of IL-23 in AS.
Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma
Authors: Hala Girgis, Olena Masui, Nicole MA White, Andreas Scorilas, Fabio Rotondo, Annetta Seivwright, Manal Gabril, Emily R Filter, Andrew HA Girgis, Georg A Bjarnason, Michael AS Jewett, Andrew Evans, Sahar Al-Haddad, KW Michael Siu, George M Yousef
Journal: Molecular Cancer (2014)

Over 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation to clinicopathological features and clinical outcome. We assessed the expression of LDHA at the protein level, by immunohistochemistry, and correlated its expression with multiple clinicopathological features including tumor size, clinical stage, histological grade, disease-free and overall survival in 385 patients with primary clear cell renal cell carcinoma. We also correlated the LDHA expression with overall survival, at mRNA level, in an independent data set of 170 clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases. Cox proportional hazards models adjusted for the potential clinicopathological factors were used to test for associations between the LDHA expression and both disease-free survival and overall survival. There is statistically significant positive correlation between LDHA level of expression and tumor size, clinical stage and histological grade. Moreover, LDHA expression shows significantly inverse correlation with both disease-free survival and overall survival in patients with clear cell renal cell carcinoma. Our results are validated by examining LDHA expression, at the mRNA level, in the independent data set of clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases which also shows that higher lactate dehydrogenase A expression is associated with significantly shorter overall survival. Our results indicate that LDHA up-regulation can be a predictor of poor prognosis in clear cell renal cell carcinoma. Thus, it represents a potential prognostic biomarker that can boost the accuracy of other prognostic models in patients with clear cell renal cell carcinoma.