tbuckley/cabot-search huggingface dataset:
The purine nucleotide cycle. A pathway for ammonia production in the rat kidney.
Authors: R T Bogusky, L M Lowenstein, J M Lowenstein
Journal: Journal of Clinical Investigation (1976)

Particle-free extracts prepared from kidney cortex of rat catalyze the formation of ammonia via the purine nucleotide cycle. The cycle generates ammonia and fumarate from aspartate, using catalytic amounts of inosine monophosphate, adenylosuccinate, and adenosine monophosphate. The specific activities of the enzymes of the cycle are 1.27+/-0.27 nmol/mg protein per min (SE) for adenoylosuccinate synthetase, 1.38+/-0.16 for adenylosuccinase, and 44.0+/-3.3 for AMP deaminase. Compared with controls, extracts prepared from kidneys of rats fed ammonium chloride for 2 days show a 60% increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity, and a greater and more rapid synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate. Extracts prepared from kidneys of rats fed a potassium-deficient diet show a twofold increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity. In such extracts the rate of synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate is also increased. These results show that the reactions of the purine nucleotide cycle are present and can operate in extracts of kidney cortex. The operational capacity of the cycle is accelerated by ammonium chloride feeding and potassium depletion, conditions known to increase renal ammonia excretion. Extracts of kidney cortex convert inosine monophosphate to uric acid. This is prevented by addition of allopurinol of 1-pyrophosphoryl ribose 5-phosphate to the reaction mixture.
Bio‐Enabled Gold Superstructures with Built‐In and Accessible Electromagnetic Hotspots
Authors: Limei Tian, Max Fei, Sirimuvva Tadepalli, Jeremiah J. Morrissey, Evan D. Kharasch, Srikanth Singamaneni
Journal: Advanced Healthcare Materials (2015)

The bio-enabled synthesis of a novel class of surface enhanced Raman scattering probes is presented for functional imaging with built-in and accessible electromagnetic hotspots formed between densely packed satellites grown on a plasmonic core. The superstructures serve as nanoscale sensors to spatiotemporally map intravesicular pH changes along endocytic pathways inside live cells. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effects of diaspirin crosslinked haemoglobin during coronary angioplasty in the swine
Authors: J. E McKenzie, E. A Cost, D. M Scandling, N. W Ahle, R. W Savage
Journal: Cardiovascular Research (1994)

Journal Article Effects of diaspirin crosslinked haemoglobin during coronary angioplasty in the swine Get access Jack E McKenzie, Jack E McKenzie Department of Physiology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA: J E McKenzie, E A Cost, D M Scandling, N W Ahle; Department of Cardiology, National Naval Medical Center, Bethesda, Maryland, USA: R W Savage. Correspondence to Dr McKenzie. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth A Cost, Elizabeth A Cost Department of Physiology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA: J E McKenzie, E A Cost, D M Scandling, N W Ahle; Department of Cardiology, National Naval Medical Center, Bethesda, Maryland, USA: R W Savage. Search for other works by this author on: Oxford Academic PubMed Google Scholar Debbie M Scandling, Debbie M Scandling Department of Physiology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA: J E McKenzie, E A Cost, D M Scandling, N W Ahle; Department of Cardiology, National Naval Medical Center, Bethesda, Maryland, USA: R W Savage. Search for other works by this author on: Oxford Academic PubMed Google Scholar Neil W Ahle, Neil W Ahle Department of Physiology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA: J E McKenzie, E A Cost, D M Scandling, N W Ahle; Department of Cardiology, National Naval Medical Center, Bethesda, Maryland, USA: R W Savage. Search for other works by this author on: Oxford Academic PubMed Google Scholar Rodney W Savage Rodney W Savage Department of Physiology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA: J E McKenzie, E A Cost, D M Scandling, N W Ahle; Department of Cardiology, National Naval Medical Center, Bethesda, Maryland, USA: R W Savage. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 8, August 1994, Pages 1188–1192, https://doi.org/10.1093/cvr/28.8.1188 Published: 01 August 1994 Article history Received: 10 June 1993 Accepted: 16 March 1994 Published: 01 August 1994
The Anti-CD19 Antibody–Drug Conjugate SAR3419 Prevents Hematolymphoid Relapse Postinduction Therapy in Preclinical Models of Pediatric Acute Lymphoblastic Leukemia
Authors: Hernan Carol, Barbara Szymanska, Kathryn Evans, Ingrid Boehm, Peter J. Houghton, Malcolm A. Smith, Richard B. Lock
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Relapsed or refractory pediatric acute lymphoblastic leukemia (ALL) remains a major cause of death from cancer in children. In this study, we evaluated the efficacy of SAR3419, an antibody–drug conjugate of the maytansinoid DM4 and a humanized anti-CD19 antibody, against B-cell precursor (BCP)-ALL and infant mixed lineage leukemia (MLL) xenografts. Experimental Design: ALL xenografts were established as systemic disease in immunodeficient (NOD/SCID) mice from direct patient explants. SAR3419 was administered as a single agent and in combination with an induction-type regimen of vincristine/dexamethasone/l-asparaginase (VXL). Leukemia progression and response to treatment were assessed in real-time, and responses were evaluated using strict criteria modeled after the clinical setting. Results: SAR3419 significantly delayed the progression of 4 of 4 CD19+ BCP-ALL and 3 of 3 MLL-ALL xenografts, induced objective responses in all but one xenograft but was ineffective against T-lineage ALL xenografts. Relative surface CD19 expression across the xenograft panel significantly correlated with leukemia progression delay and objective response measure scores. SAR3419 also exerted significant efficacy against chemoresistant BCP-ALL xenografts over a large (10-fold) dose range and significantly enhanced VXL-induced leukemia progression delay in two highly chemoresistant xenografts by up to 82 days. When administered as protracted therapy following remission induction with VXL, SAR3419 prevented disease recurrence into hematolymphoid and other major organs with the notable exception of central nervous system involvement. Conclusion: These results suggest that incorporation of SAR3419 into remission induction protocols may improve the outcome for high-risk pediatric and adult CD19+ ALL. Clin Cancer Res; 19(7); 1795–805. ©2013 AACR.
Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis
Authors: Jesús Rivera-Nieves, Tracy L. Burcin, Timothy S. Olson, Margaret A. Morris, Marcia McDuffie, Fabio Cominelli, Klaus Ley
Journal: The Journal of Experimental Medicine (2006)

L-selectin ligands might be relevant for inflammatory cell trafficking into the small intestine in a spontaneous model of chronic ileitis (i.e., SAMP1/YitFc mice). Immunoblockade of peripheral node addressin or mucosal addressin cell adhesion molecule 1 failed to ameliorate ileitis, whereas P-selectin glycoprotein ligand 1 (PSGL-1) neutralization attenuated both the adoptively transferred and spontaneous disease. PSGL-1 was detected in venules of mesenteric lymph node and small intestine by immunohistochemistry and confirmed by real-time reverse transcription polymerase chain reaction and flow cytometry. In addition, reconstitution of wild-type mice with PSGL-1−/− bone marrow demonstrated that PSGL-1 messenger RNA and PSGL-1 protein expression remained on endothelium, localized within mesenteric lymph node and small intestine. Endothelial PSGL-1 bound P-selectin–IgG and its blockade or genetic deletion altered the recruitment of lymphocytes to the small intestine, as revealed by intravital microscopy and homing studies. Endothelial expression of PSGL-1 adds a new dimension to the various cellular interactions involved in small intestinal recruitment. Thus, the multiple roles of PSGL-1 may explain why targeting this single adhesion molecule results in attenuation of chronic murine ileitis, a disease previously resistant to antiadhesion molecule strategies.
Dexamethasone in Vietnamese Adolescents and Adults with Bacterial Meningitis
Authors: Nguyen Thi Hoang Mai, Tran Thi Hong Chau, Guy Thwaites, Ly Van Chuong, Dinh Xuan Sinh, Ho Dang Trung Nghia, Phung Quoc Tuan, Nguyen Duy Phong, Nguyen Hoan Phu, To Song Diep, Nguyen van Vinh Chau, Nguyen Minh Duong, James Campbell, Constance Schultsz, Chris Parry, M. Estee Torok, Nicholas White, Nguyen Tran Chinh, Tran Tinh Hien, Kasia Stepniewska, Jeremy J. Farrar
Journal: New England Journal of Medicine (2007)

It is uncertain whether all adults with bacterial meningitis benefit from treatment with adjunctive dexamethasone.We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone in 435 patients over the age of 14 years who had suspected bacterial meningitis. The goal was to determine whether dexamethasone reduced the risk of death at 1 month and the risk of death or disability at 6 months.A total of 217 patients were assigned to the dexamethasone group, and 218 to the placebo group. Bacterial meningitis was confirmed in 300 patients (69.0%), probable meningitis was diagnosed in 123 patients (28.3%), and an alternative diagnosis was made in 12 patients (2.8%). An intention-to-treat analysis of all the patients showed that dexamethasone was not associated with a significant reduction in the risk of death at 1 month (relative risk, 0.79; 95% confidence interval [CI], 0.45 to 1.39) or the risk of death or disability at 6 months (odds ratio, 0.74; 95% CI, 0.47 to 1.17). In patients with confirmed bacterial meningitis, however, there was a significant reduction in the risk of death at 1 month (relative risk, 0.43; 95% CI, 0.20 to 0.94) and in the risk of death or disability at 6 months (odds ratio, 0.56; 95% CI, 0.32 to 0.98). These effects were not found in patients with probable bacterial meningitis. Results of multivariate analysis indicated that dexamethasone treatment for patients with probable bacterial meningitis was significantly associated with an increased risk of death at 1 month, an observation that may be explained by cases of tuberculous meningitis in the treatment group.Dexamethasone does not improve the outcome in all adolescents and adults with suspected bacterial meningitis; a beneficial effect appears to be confined to patients with microbiologically proven disease, including those who have received prior treatment with antibiotics. (Current Controlled Trials number, ISRCTN42986828 [controlled-trials.com] .).
Juvenile idiopathic arthritis: state of the art and future perspectives
Authors: A. Martini, D. J. Lovell
Journal: Annals of the Rheumatic Diseases (2010)

Juvenile idiopathic arthritis (JIA) is not a disease but an exclusion diagnosis that includes all forms of chronic arthritis of unknown origin with onset before 16 years of age. The current classification identifies several different categories. While some of them appear to represent rather homogeneous entities others seem still to include heterogeneous conditions. The advent of the new biological treatments has dramatically changed both the observed responses to treatment and the expectations of treatments. International research networks of paediatric rheumatology have contributed to fostering the conduct of controlled clinical trials and also the development of validated outcome measures. However, despite a dramatic advance in the understanding of JIA categories, pathobiology and treatments, much remains to be done.
Vasculoprotective effect of insulin in the ischemic/reperfused canine heart: Role of Akt-stimulated NO production
Authors: H MA, H ZHANG, L YU, Q ZHANG, J LI, J HUO, X LI, W GUO, H WANG, F GAO
Journal: Cardiovascular Research (2005)

The objectives of this study were to investigate the vasculoprotective effects of glucose-insulin-potassium (GIK) on ischemia/reperfusion-induced coronary endothelial functional injury and to elucidate the mechanism involved.Dogs were subjected to 50 min of coronary occlusion and 4 h of reperfusion. Vehicle, GIK, or GK were intravenously infused 5 min before reperfusion, and the coronary vascular dysfunction and endothelial apoptosis were determined. In a separate study, cultured endothelial cells were subjected to simulated ischemia/reperfusion, and the signaling pathway involved in insulin's anti-apoptotic effect was investigated.In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium-dependent vasorelaxation, decreased nitric oxide (NO) production, and endothelial cell apoptosis as determined by caspase 3 activation and TUNEL staining. Treatment with GIK, but not GK, markedly improved the endothelium-dependent coronary vasorelaxation (P<0.01 versus vehicle), increased total NO production (P<0.01), and attenuated endothelial apoptosis. In cultured endothelial cells, treatment with insulin also markedly increased NO production and reduced simulated ischemia/reperfusion-induced apoptosis. Moreover, pre-treatment with either Akt inhibitor or NO synthase inhibitor almost abolished the anti-apoptotic effect exerted by insulin but not by SNAP, an NO donor.These results demonstrate that in vivo treatment with GIK at reperfusion attenuates ischemia/reperfusion-induced coronary endothelial dysfunction and endothelial apoptosis in an Akt-dependent and NO-mediated fashion. The coronary vasculoprotective effect elicited by insulin may contribute to the previously observed cardiac protective effect of GIK.
TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update
Authors: M. Rossle, A. L. Gerbes
Journal: Gut (2010)

Refractory ascites is a frequent complication of advanced cirrhosis and is associated with hepatorenal syndrome and hepatic hydrothorax. Large volume paracentesis and pleurodesis are regarded as first-line treatments in patients who do not respond adequately to diuretics. These treatments, however, do not prevent recurrence and carry the risk of worsening of the circulatory dysfunction leading to hepatorenal syndrome. The transjugular intrahepatic portosystemic shunt (TIPS) has been proposed as an alternative to paracentesis. TIPS reduces the rate of ascites recurrence mainly due to the reduction in the filtration pressure. In addition, TIPS results in a positive effect on renal function, including hepatorenal syndrome, demonstrated by a rapid increase in urinary sodium excretion, urinary volume, and improvement in plasma creatinine concentration. Furthermore, plasma renin activity, aldosterone, and noradrenalin concentrations improve gradually after TIPS insertion suggesting a positive effect on systemic underfilling, the factor of hepatorenal syndrome. As demonstrated recently in two meta-analyses including five randomised studies, TIPS also improves survival when compared with paracentesis. However, the evidence is based on relatively few studies with only 305 patients included. The positive effects of the TIPS are opposed by an increased frequency and severity of episodes of hepatic encephalopathy which may be reduced by both patient selection and reduced shunt diameter. Based on the present knowledge the recommended hierarchy of treatments for refractory ascites may be reconsidered upgrading TIPS in suitable candidates.
Ebola 2014 — New Challenges, New Global Response and Responsibility
Authors: Thomas R. Frieden, Inger Damon, Beth P. Bell, Thomas Kenyon, Stuart Nichol
Journal: New England Journal of Medicine (2014)

Stopping the Ebola outbreak at its source will take many months. But three core interventions have stopped every previous outbreak and can stop this one: exhaustive case and contact finding, effective response to patients and the community, and preventive interventions.
Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjögren's syndrome.
Authors: D I Stott, F Hiepe, M Hummel, G Steinhauser, C Berek
Journal: Journal of Clinical Investigation (1998)

Structures resembling germinal centers are seen in the salivary glands of patients with Sjögren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sjögren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters. The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants. These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sjögren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune diseases, we propose that germinal center- type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases.
Development and use of a privacy-protecting total population record linkage system to support observational, interventional, and policy relevant research
Authors: Ronan A Lyons, Hayley Hutchings, Sarah E Rodgers, Melanie A Hyatt, Joanne Demmler, Belinda J Gabbe, Caroline J Brooks, Sinead Brophy, Kerina Jones, David V Ford, Shantini Paranjothy, David Fone, Frank D Dunstan, Annette Evans, Mark Kelly, William J Watkins, Alison Maddocks, Peter Barnes, Michelle James-Ellison, Gareth John, Sarah Lowe
Journal: The Lancet (2012)
miR-212 Increases Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Sensitivity in Non–Small Cell Lung Cancer by Targeting the Antiapoptotic Protein PED
Authors: Mariarosaria Incoronato, Michela Garofalo, Loredana Urso, Giulia Romano, Cristina Quintavalle, Ciro Zanca, Margherita Iaboni, Gerald Nuovo, Carlo Maria Croce, Gerolama Condorelli
Journal: Cancer Research (2010)

PED/PEA-15 (PED) is a death effector domain family member of 15 kDa with a broad antiapoptotic function found overexpressed in a number of different human tumors, including lung cancer. To date, the mechanisms that regulate PED expression are unknown. Therefore, we address this point by the identification of microRNAs that in non-small cell lung cancer (NSCLC) modulate PED levels. In this work, we identify miR-212 as a negative regulator of PED expression. We also show that ectopic expression of this miR increases tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death in NSCLC cells. In contrast, inhibition of endogenous miR-212 by use of antago-miR results in increase of PED protein expression and resistance to TRAIL treatment. Besides, in NSCLC, we show both in vitro and in vivo that PED and miR-212 expressions are inversely correlated, that is, PED is upregulated and miR-212 is rarely expressed. In conclusion, these findings suggest that miR-212 should be considered as a tumor suppressor because it negatively regulates the antiapoptotic protein PED and regulates TRAIL sensitivity.
How the Pioneer ACO Model Needs to Change
Authors: John Toussaint, Arnold Milstein, Stephen Shortell
Journal: JAMA (2013)

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Foundation trusts predict first ever drop in income
Authors: A. O'Dowd
Journal: BMJ (2010)

Foundation trusts are predicting that their income over the next three years will fall for the first time and that clinical targets could be affected, according to the independent regulatory body, Monitor.

Monitor’s yearly review of NHS foundation trusts’ annual plans (2010-1) warned that the economic recession has hit this part of the NHS. Fears have also arisen that around a quarter of foundation trusts will miss performance standard targets linked to cancer care and hospital infections.

Foundation trusts have greater clinical and financial freedom than traditional NHS trusts to earn income and reinvest …