tbuckley/cabot-search huggingface dataset:
A sensory neuron–expressed IL-31 receptor mediates T helper cell–dependent itch: Involvement of TRPV1 and TRPA1
Authors: Ferda Cevikbas, Xidao Wang, Tasuku Akiyama, Cordula Kempkes, Terhi Savinko, Attila Antal, Gabriela Kukova, Timo Buhl, Akihiko Ikoma, Joerg Buddenkotte, Vassili Soumelis, Micha Feld, Harri Alenius, Stacey R. Dillon, Earl Carstens, Bernhard Homey, Allan Basbaum, Martin Steinhoff
Journal: Journal of Allergy and Clinical Immunology (2013)
The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer
Authors: Lambert C. J. Dorssers, Nicolai Grebenchtchikov, Arend Brinkman, Maxime P. Look, Simone P. J. van Broekhoven, Danielle de Jong, Harry A. Peters, Henk Portengen, Marion E. Meijer-van Gelder, Jan G. M. Klijn, Doorlene T. H. van Tienoven, Anneke Geurts-Moespot, Paul N. Span, John A. Foekens, Fred C. G. J. Sweep
Journal: Clinical Cancer Research (2004)

Abstract Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large series of breast cancer specimens. Experimental Design: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1 were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1). Results: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both P &amp;lt; 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups stratified by nodal and menopausal status. Conclusions: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent of the traditional prognostic factors and the other novel marker PAI-1.
Regulation of blood ammonia.
Authors: A M Dawson
Journal: Gut (1978)

Disturbance of ammonia metabolism is an important but not the only factor in the genesis of hepatic coma. In this review mechanisms controlling the concentration of ammonia in the blood other than disturbed liver function have been discussed. The key function of ammonia in the pyridine nucleotide cyde has been outlined and it is suggested that the function of this cycle in patients with liver disease would repay further study.
Influence of intermittent anaerobic exercise on mouse physical endurance and antioxidant components
Authors: D Qiao, L Hou, X Liu
Journal: British Journal of Sports Medicine (2006)

To determine the effect of intermittent anaerobic exercise on physical endurance, antioxidant capacity, and lipid peroxidation of brain, heart, and skeletal muscles in mice.Mice were made to perform intermittent (with short or long rest intervals) anaerobic swimming on six consecutive days. Body weight was monitored. Tissue total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and thiobarbituric acid reaction substance (TBARS) were determined on the 2nd, 4th, and 6th day. Physical endurance was determined on day 7 by using an exhaustive swimming test and a static grasping test.The intermittent anaerobic exercise resulted in decreased growth rate and physical endurance capacity, as indicated by less weight gain and shorter time to exhaustion during the exhaustive swimming and static grasping test (p<0.05). It also led to a higher T-AOC in muscle, heart, and brain, higher SOD activity in muscle and heart, and higher TBARS content in muscle (p<0.05). This type of exercise had no effect on brain SOD and TBARS. The changes in T-AOC in brain, muscle, and heart were all more pronounced the longer the experiment continued (p<0.05).Intermittent anaerobic exercise reduced growth and physical endurance and increased tissue antioxidant capacity and lipid peroxidation.
ADVANCES IN CANCER EPIDEMIOLOGY: Understanding Causal Mechanisms and the Evidence for Implementing Interventions
Authors: David Schottenfeld, Jennifer L. Beebe-Dimmer
Journal: Annual Review of Public Health (2004)

▪ Abstract In a worldwide population of 6 billion, in the year 2000, approximately 10 million cancers were diagnosed, and there were an estimated 6.2 million cancer deaths. Whereas the universality of cancer incidence and mortality is established, the burden of cancer by type or organ site is distributed unequally between developing and industrialized nations. Populations in developing countries are disproportionately affected by cancers in which infectious agents are causal. Our review of advances in cancer epidemiology underscores the complexity of pathogenic mechanisms mediated by chronic inflammation, obesity, and gene-environment interactions as in tobacco and alcohol carcinogenesis. Ultimately, the implementation of effective cancer control interventions that will serve to alleviate the cancer burden must integrate basic and applied research in the behavioral, social, biomedical, and population sciences.
High energy phosphate stores and lactate levels in different layers of the canine left ventricle during reactive hyperemia.
Authors: R B Dunn, K M McDonough, D M Griggs
Journal: Circulation Research (1979)

To study postischemic recovery of myocardial energy metabolism in relation to the reactive hyperemic response, the tissue levels of creatine phosphate (CP), adenosine triphosphate (ATP), and lactate were estimated in the outer, middle, and inner layers of the left ventricle before, during, and at several times after a 20-second bilateral coronary arterial occlusion in the open-chest dog. The reactive hyperemic response was characterized by monitoring blood flow in the cannulated coronary sinus in a separate group of dogs. Substantial changes in myocardial CP and lactate, but not ATP, were produced by the occlusion and reciprocal transmural gradients in CP and lactate occurred such that CP was lowest and lactate was highest in the inner layer. Recovery of high energy phosphate stores (CP + ATP) occurred long before blood flow returned to the preocclusion level, this being achieved in two of the three layers after completion of only 29% of the reactive hyperemic response when the blood flow debt repayment was 151%. Lactate returned to control levels during the response, but recovery times in the different layers were delayed compared to those for the high energy phosphate stores. A transmural lactate gradient was maintained as the regional levels declined, and recovery times were different for each of the three layers, being longest in the inner layer. The results suggest that during the reactive hyperemic response (1) kinetically different processes are involved in the repletion of energy stores and the removal of anaerobically produced metabolites, and (2) metabolic vasodilation of coronary vessels probably is more pronounced and sustained longer in the inner than in the outer ventricular layer.
Catecholamines Regulate Tumor Angiogenesis
Authors: Debanjan Chakroborty, Chandrani Sarkar, Biswarup Basu, Partha Sarathi Dasgupta, Sujit Basu
Journal: Cancer Research (2009)

Among the regulators of angiogenesis, catecholamine neurotransmitters are of recent interest because of their opposite roles in the regulation of tumor neovascularization. Norepinephrine and epinephrine by acting through specific adrenoceptors increase the synthesis of proangiogenic factors, and thereby, promote tumor growth. In contrast, dopamine acting via its specific D(2) receptors inhibits tumor growth by suppressing the actions of vascular permeability factor/vascular endothelial growth factor-A on both tumor endothelial and bone marrow-derived endothelial progenitor cells. These reports identify novel endogenous regulators of tumor angiogenesis and also indicate a new and an inexpensive class of antiangiogenic drugs for the treatment of cancer.
Development changes in the human cardiac isomyosin distribution: an immunohistochemical study using monoclonal antibodies.
Authors: P Bouvagnet, S Neveu, M Montoya, J J Leger
Journal: Circulation Research (1987)

With monoclonal antibodies (Mab) specific for myosin heavy chain (MHC) isozymes, we have investigated the isomyosin content of atrial, ventricular and conductive fibers of 19 human fetuses (ranging from 14-36 weeks of gestation) and 3 newborns (2 days-2 weeks). In addition, the conduction system of 2 human adult hearts was studied. The fetal atrium is composed mostly of alpha-MHC during the first 23 weeks of gestation. beta-MHC is already expressed as traces at 14 weeks of gestation, and its expression increases progressively until birth, resulting in a great augmentation in beta-MHC. During this course, beta-MHC always predominates in certain areas (the crista terminalis and the interatrial septum) but not in other areas (the auricles). Preceding birth, the fetal ventricle is composed mostly of beta-MHC. From 14 weeks of gestation to birth, alpha-MHC is expressed in very rare fibers. Then, after birth, a large number of fibers simultaneously synthesize alpha-MHC. The AV node and His bundle system were labelled with anti-alpha and anti-beta Mab in fetal, newborn, and adult hearts with a double gradient of distribution: spatial (a higher proportion of alpha-containing fibers in the AV node than in the distal portion of the bundle of branches) and temporal (a higher proportion of alpha-containing fibers at a given point in fetal development than in the adult heart). One of the twenty-five hearts studied had an isomyosin distribution pattern not accorded to its age. Interestingly, it was clinically diagnosed as having idiopathic hypertrophic cardiomyopathy.
Efficacy of self monitoring of blood glucose in patients with newly diagnosed type 2 diabetes (ESMON study): randomised controlled trial
Authors: Maurice J O’Kane, Brendan Bunting, Margaret Copeland, Vivien E Coates
Journal: BMJ (2008)

<b>Objectives</b> To assess the effect of self monitoring of blood glucose concentrations on glycaemic control and psychological indices in patients with newly diagnosed type 2 diabetes mellitus. <b>Design</b> Prospective randomised controlled trial of self monitoring versus no monitoring (control). <b>Setting</b> Hospital diabetes clinics. <b>Participants</b> 184 (111 men) people aged &lt;70 with newly diagnosed type 2 diabetes referred to the participating diabetes clinics. Major exclusion criteria were secondary diabetes, insulin treatment, previous self monitoring of blood glucose. <b>Interventions</b> Participants were randomised to self monitoring or no monitoring (control) groups for one year with follow-up at three monthly intervals. Both groups underwent an identical structured core education programme. The self monitoring group received additional education on monitoring. <b>Main outcome measures</b> Between group differences in HbA<sub>1c</sub>, psychological indices, use of oral hypoglycaemic drugs, body mass index (BMI), and reported hypoglycaemia rates. <b>Results</b> 96 patients (55 men) were randomised to monitoring and 88 (56 men) to control. There were no baseline differences in mean (SD) age (57.7 (11.0) in monitoring group <i>v</i> 60.9 (11.5) in control group) or HbA<sub>1c</sub> (8.8 (2.1)% <i>v</i> 8.6 (2.3)%, respectively). Those in the monitoring group had a higher baseline BMI (34 (7) <i>v</i> 32 (6.2)). There were no significant differences between groups at any time point (12 months values given) in HbA<sub>1c</sub> (6.9 (0.8)% <i>v</i> 6.9 (1.2)%, P=0.69; 95% confidence interval for difference −0.25% to 0.38%), BMI (33.1 (6.4) <i>v</i> 31.8 (6.0); adjusted for baseline BMI, P=0.32), use of oral hypoglycaemic drugs, or reported incidence of hypoglycaemia. Monitoring was associated with a 6% higher score on the depression subscale of the well-being questionnaire (P=0.01). <b>Conclusions</b> In patients with newly diagnosed type 2 diabetes self monitoring of blood glucose concentration has no effect on glycaemic control but is associated with higher scores on a depression subscale. <b>Trial registration</b> ISRCTN 49814766.
PEGylation Confers Greatly Extended Half-Life and Attenuated Immunogenicity to Recombinant Methioninase in Primates
Authors: Zhijian Yang, Junhua Wang, Quan Lu, Jinbao Xu, Yoshinao Kobayashi, Tomoaki Takakura, Akio Takimoto, Takayuji Yoshioka, Changgen Lian, Chunmei Chen, Dongdong Zhang, Ying Zhang, Shukuan Li, Xinghua Sun, Yuying Tan, Shigeo Yagi, Eugene P. Frenkel, Robert M. Hoffman
Journal: Cancer Research (2004)

Abstract Methionine depletion by recombinant methioninase (rMETase) has been demonstrated previously to be highly effective in tumor-bearing mouse models. However, the therapeutic potential of rMETase has been limited by its short plasma half-life and immunologic effects, including high antibody production in mice and monkeys and anaphylactic reactions in monkeys. To overcome these limits of rMETase, the enzyme has been coupled to methoxypolyethylene glycol succinimidyl glutarate (MEGC-PEG-5000). In this study, we evaluated the pharmacokinetics, antigenicity and toxicity of MEGC-PEG-rMETase in Macaca fascicularis monkeys using an escalating-dose strategy. Dose ranging studies at 1,000, 4,000, and 8,000 units/kg i.v. determined that a single dose of 4,000 units/kg was sufficient to reduce plasma methionine to &amp;lt;5 μmol/L for 12 hours. Pharmacokinetic analysis with the single 4,000 units/kg dose showed that MEGC-PEG-rMETase holoenzyme activity was eliminated with a biological half-life of 1.3 hours, and the MEGC-PEG-rMETase apoenzyme was eliminated with a biological half-life of 90 hours, an ∼36-fold increase compared with non-PEGylated rMETase. A single dose at 2,000 units/kg of MEGC-PEG-rMETase resulted in an apoenzyme half-life of 143 hours. A seven-day i.v. administration of 4,000 units/kg every 12 hours resulted in a steady-state depletion of plasma methionine to &amp;lt;5 μmol/L. The only manifest toxicity was decreased food intake and slight weight loss. Red cell values and hemoglobin declined transiently during treatment but recovered after cessation of treatment. Subsequent challenges on days 29, 50 and, 71 did not result in any immunologic reactions. This result is in contrast to non-PEGylated rMETase, which elicited anaphylactic reactions in monkeys. Anti-MEGC-PEG-rMETase antibodies (at 10−2) were found on day 29, and these increased to 10−3 to 104 on day 71, 100 to 1,000-fold less than antibodies elicited by naked rMETase. Although anti-MEGC-PEG-rMETase antibodies were produced, no neutralizing antibody was identified, and each challenge dose was effective in depleting plasma methionine levels. The results of the present study demonstrate that PEGylation greatly prolongs serum half-life of the rMETase apoenzyme and eliminated anaphylactic reactions. The results indicate a profile with respect to serum half-life, toxicity, and antigenicity that suggest clinical potential of MEGC-PEG-rMETase.
Dissociation of Angiogenesis and Tumorigenesis in Follistatin- and Activin-Expressing Tumors
Authors: Jelena Krneta, Jens Kroll, Frauke Alves, Claudia Prahst, Farahnaz Sananbenesi, Christian Dullin, Sarah Kimmina, David J. Phillips, Hellmut G. Augustin
Journal: Cancer Research (2006)

Abstract The transforming growth factor-β superfamily member activin and its antagonist, follistatin, act as a pleiotropic growth factor system that controls cell proliferation, differentiation, and apoptosis. Activin inhibits fibroblast growth factor 2–induced sprouting angiogenesis in vitro (spheroidal angiogenesis assay) and in vivo (Matrigel assay). To further study the role of the activin/follistatin system during angiogenesis and tumor progression, activin- and follistatin-expressing R30C mammary carcinoma cells were studied in mouse tumor experiments. Surprisingly, activin-expressing tumors grew much faster than follistatin-expressing tumors although they failed to induce increased angiogenesis (as evidenced by low microvessel density counts). Conversely, follistatin-expressing tumors were much smaller but had a dense network of small-diameter capillaries. Qualitative angioarchitectural analyses (mural cell recruitment, perfusion) revealed no major functional differences of the tumor neovasculature. Analysis of activin- and follistatin-expressing R30C cells identified a cell autonomous role of this system in controlling tumor cell growth. Whereas proliferation of R30C cells was not altered, follistatin-expressing R30C cells had an enhanced susceptibility to undergo apoptosis. These findings in experimental tumors are complemented by an intriguing case report of a human renal cell carcinoma that similarly shows a dissociation of angiogenesis and tumorigenesis during tumor progression. Collectively, the data shed further light into the dichotomous stimulating and inhibiting roles that the activin/follistatin system can exert during angiogenesis and tumor progression. Furthermore, the experiments provide a critical proof-of-principle example for the dissociation of angiogenesis and tumorigenesis, supporting the concept that tumor growth may not be dependent on increased angiogenesis as long as a minimal intratumoral microvessel density is maintained. (Cancer Res 2006; 66(11): 5686-95)
Use of Continuous Quality Improvement to Increase Use of Process Measures in Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: T. Bruce Ferguson, Eric D. Peterson, Laura P. Coombs, Mary C. Eiken, Meghan L. Carey, Frederick L. Grover, Elizabeth R. DeLong
Journal: JAMA (2003)

A rigorous evaluation of continuous quality improvement (CQI) in medical practice has not been carried out on a national scale.To test whether low-intensity CQI interventions can be used to speed the national adoption of 2 coronary artery bypass graft (CABG) surgery process-of-care measures: preoperative beta-blockade therapy and internal mammary artery (IMA) grafting in patients 75 years or older.Three hundred fifty-nine academic and nonacademic hospitals (treating 267 917 patients using CABG surgery) participating in the Society of Thoracic Surgeons National Cardiac Database between January 2000 and July 2002 were randomized to a control arm or to 1 of 2 groups that used CQI interventions designed to increase use of the process-of-care measures.Each intervention group received measure-specific information, including a call to action to a physician leader; educational products; and periodic longitudinal, nationally benchmarked, site-specific feedback.Differential incorporation of the targeted care processes into practice at the intervention sites vs the control sites, assessed by measuring preintervention (January-December 2000)/postintervention (January 2001-July 2002) site differences and by using a hierarchical patient-level analysis.From January 2000 to July 2002, use of both process measures increased nationally (beta-blockade, 60.0%-65.6%; IMA grafting, 76.2%-82.8%). Use of beta-blockade increased significantly more at beta-blockade intervention sites (7.3% [SD, 12.8%]) vs control sites (3.6% [SD, 11.5%]) in the preintervention/postintervention (P =.04) and hierarchical analyses (P<.001). Use of IMA grafting also tended to increase at IMA intervention sites (8.7% [SD, 17.5%]) vs control sites (5.4% [SD,15.8%]) (P =.20 and P =.11 for preintervention/postintervention and hierarchical analyses, respectively). Both interventions tended to have more impact at lower-volume CABG sites (for interaction: P =.04 for beta-blockade; P =.02 for IMA grafting).A multifaceted, physician-led, low-intensity CQI effort can improve the adoption of care processes into national practice within the context of a medical specialty society infrastructure.
Regulation of Vascular Endothelial Growth Factor D by Orphan Receptors Hepatocyte Nuclear Factor-4α and Chicken Ovalbumin Upstream Promoter Transcription Factors 1 and 2
Authors: Georgia Schäfer, Christoph Wißmann, Johannes Hertel, Victoria Lunyak, Michael Höcker
Journal: Cancer Research (2008)

Vascular endothelial growth factor D has recently been linked to the control of lymphangiogenesis and lymphatic metastasis. The molecular determinants regulating vegf-D gene transcription, however, have not yet been identified. After isolation of 2 kb of 5'-flanking DNA of the human vegf-D gene, we identified a novel, atypical direct repeat (DR) element consisting of a consensus half-site (AGGTCA) at -125/-119 and a degenerated DR half-site (ATGTTA) at -99/-94 as sufficient and necessary for vegf-D transcription. The vegf-D DR element is bound and activated by the orphan receptors hepatocyte nuclear factor 4 alpha (HNF-4 alpha) and chicken ovalbumin upstream promoter transcription factor (COUP-TF)-1/COUP-TF2. Additionally, chromatin immunoprecipitation assays identified transcriptional coactivators cyclic AMP-responsive element binding protein-binding protein and glucocorticoid receptor interacting protein 1 at the vegf-D DR element and functional assays confirmed their stimulatory effect on the vegf-D promoter. Histone deacetylase inhibition by trichostatin A led to accumulation of acetylated histones H3/H4 at the vegf-D promoter, up-regulation of vegf-D mRNA levels, and transactivation of vegf-D promoter reporter gene constructs in cancer cell lines. This study for the first time describes the molecular determinants in cis and trans controlling vegf-D gene transcription and identifies interaction of HNF-4 alpha and COUP-TF1/COUP-TF2 with a proximal, atypical DR element as indispensable for vegf-D transcription. Moreover, our findings suggest that epigenetic control of histone acetylation represents an important determinant of vegf-D gene expression in cancer cells. These results provide novel insights into the molecular machinery controlling vegf-D gene expression and may add to a better understanding of the regulation of lymphangiogenesis in vascular development and cancer.
Tumor mRNA Expression Profiles Predict Responses to Chemotherapy
Authors: John D. Minna, Luc Girard, Yang Xie
Journal: Journal of Clinical Oncology (2007)

The development of prognostic and diagnostic markers suchastumorstagingandmorerecentlymolecularfactorshavegreatlycontributed to identifying lung cancer patients that can beneﬁtfrom adjuvant or neoadjuvant chemotherapy. However, the pre-dictingefﬁcienciesvaryconsiderably,andmanytherapiesfailwhilesurviving patients often experience severe toxicities. Moreover,patients displaying similar clinical characteristics often responddifferently to therapy, and this is likely a result of heterogeneity ofthe tumors’ genetic and epigenetic characteristics. The advent ofthe human genome sequencing project and the concurrent devel-opment of many genomic-based technologies, including expres-sion microarrays, have allowed scientists to explore the possibilityof using expression proﬁles to predict tumor drug sensitivity orresistance before treatment, and thereby select the best possibletherapies while decreasing the risk of toxicities for the patients.To this end, various gene signatures and sequence alterationintargetgeneshavebeenobtainedforpredictionofdrugresponsein patients. Examples include signatures for taxane/doxorubicinsensitivity in breast cancer,