tbuckley/cabot-search huggingface dataset:
Abstract 1167: The expression of urokinase plasminogen activator (uPA) system genes in prostate carcinoma is related to clinicopathological parameters
Authors: Omar Al-Janabi, Sven Wach, Elke Nolte Nolte, Bernd Wullich, Helge Taubert, Susanne Füssel, Andrea Lohse, Matthias Kotzsch, Wolf Wieland, Robert Stoehr, Arndt Hartmann
Journal: Cancer Research (2012)

Abstract Background: Prostate cancer (PCa) is a leading cause of tumor mortality. Members of the urokinase plasminogen activator (uPA) system play an important role in tumorigenesis in many human malignancies. We sought to characterize the mRNA expression of uPA members in primary PCa samples and to correlate this expression to clinicopathological parameters. Material and methods: We investigated the mRNA expression level of three members of the uPA system (uPA, PAI-1 and uPAR) using 26 paired samples of PCa and adjacent non-malignant tissue. Absolute quantification of gene expression was performed by quantitative PCR and subsequent standardization on the reference gene TBP. Gene expression measures were further correlated to clinicopathological characteristics as TNM classification, Gleason sum, and tumor grade. Results: Although we did not detect significant differences in expression of uPA system genes between tumor and matched nonmalingnant tissue in our patient cohort, we identified a positive correlation of all three uPA family members (p&amp;lt;0.01; bivariate correlation). When stratifying PAI-1 expression according to the median mRNA level we discovered correlations to defined tumor characteristics. Tumors with PAI-1 expression above median displayed a higher Gleason sum (8 or 9) than tumors expressing less-than-median PAI-1 (p=0.03, Fisher's exact test). Likewise, an elevated PAI-1 expression was correlated with higher tumor grade (p=0.01; Fisher exact test) and tumor stage (p=0.046; Fisher exact test). Conclusion: Our results demonstrate that mRNA expression of PAI-1 as a member of the uPA family correlates with characteristic pathological parameters of PCa. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1167. doi:1538-7445.AM2012-1167
Studies in the Ketosis of Fasting*
Authors: Daniel W. Foster
Journal: Journal of Clinical Investigation (1967)

A series of experiments was performed during the induction of starvation ketosis and in the acute reversal of the ketotic state. In contrast to the predictions of two widely held theories of ketogenesis, control of acetoacetate production by the liver appeared to be unrelated to changes in fatty acid mobilization from the periphery, fatty acid oxidation, fatty acid synthesis, or the acetyl coenzyme A concentration in the liver.Ketosis of fasting was shown to be reversible within 5 minutes by the injection of glucose or insulin. This effect was due to a prompt cessation of acetoacetate production by the liver. The possibility is raised that the ketosis of fasting is due to a direct activation of acetoacetate-synthesizing enzymes secondary to a starvation-induced depression of insulin secretion by the pancreas.
Biological role of interleukin 1 receptor antagonist isoforms
Authors: W. P Arend
Journal: Annals of the Rheumatic Diseases (2000)

The interleukin 1 receptor antagonist (IL1Ra) family of molecules now includes one secreted isoform (sIL1Ra) and three intracellular isoforms (icIL1Ra1, 2, and 3). Extensive evidence indicates that the sole biological function of sIL1Ra seems to be to competitively inhibit IL1 binding to cell-surface receptors. Although intracellular IL1Ra1 may be released from keratinocytes under some conditions, the intracellular isoforms of IL1Ra may carry out additional as yet poorly defined roles inside cells. Maintenance of a balance between IL1 and IL1Ra is important in preventing the development or progression of inflammatory disease in certain organs. Both the secreted and intracellular isoforms of IL1Ra contribute to maintenance of this balance. An allelic polymorphism in intron 2 of the IL1Ra gene (IL1RN*2) predisposes to the development or severity of a variety of human diseases largely of epithelial cell origin. Both the impaired production of IL1Ra and the overproduction of IL1β are related to the presence of this allele. Restoration of the balance between IL1Ra and IL1 through a variety of approaches is a therapeutic goal in specific chronic inflammatory diseases.
Alex's Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011
Authors: Quinn T. Ostrom, Peter M. de Blank, Carol Kruchko, Claire M. Petersen, Peter Liao, Jonathan L. Finlay, Duncan S. Stearns, Johannes E. Wolff, Yingli Wolinsky, John J. Letterio, Jill S. Barnholtz-Sloan
Journal: Neuro-Oncology (2014)

CBTRUS contains incidence data from 51 independent central cancer registries (46 NPCR and 5 SEER registries) representing 99.8% of the US population for the time period examined in this report (for 1 of 51 registries, data were available only from 2007 -2010). 2 Please see The CBTRUS Statistical Report: Primary and Central Nervous System Tumors Diagnosed in the United States in 2007 -2011 for additional information about the way that these data are obtained and processed. 2ge-adjusted incidence rates per 100,000 for the entire US for selected other cancers were obtained from the United States Cancer Statistics (USCS), 3 produced by the CDC and the NCI, via # The Centers for Disease Control and Prevention.
Selective response to H-Y antigen by F1 female mice sensitized to F1 male cells.
Authors: R D Gordon, L E Samelson, E Simpson
Journal: The Journal of Experimental Medicine (1977)

T-cell mediated cytotoxic responses to H-Y antigen require co-recognition of H-Y and H-2 gene products. F1 mael stimulating cells and target cells express H-Y antigen in association with both parental H-2 haplotypes. However, F1 females primed in vivo and challenged in vitro with F1 male cells lyse male target cells of F1 and only one parental H-2 haplotype. Thus, (CBA X B10)F1 females sensitized to (CBA X B10)F1 male cells lyse (CBA X B10)F1 and CBA but not B10 male target cells, and (BALB/c X B10)F1 females sensitized to (BALB/c X B10)F1 male cells will lyse (BALB/c X B10)F1 and B10 but not BALB/c male target cells. It is suggested that this may represent an effect of immune response or suppressor genes mapping in the major histocompatibility gene complex which regulate responsiveness to H-Y antigen.
Myocyte hypertrophy and apoptosis: a balancing act
Authors: V VANEMPEL
Journal: Cardiovascular Research (2004)

In response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress the heart responds by enlarging the individual myofibers. Even though myocardial hypertrophy can normalize wall tension, it instigates an unfavorable outcome and threatens affected patients with sudden death or progression to overt heart failure, suggesting that in most instances hypertrophy is a maladaptive process. Increasing evidence suggests that several of the signaling cascades controlling myocyte growth in the adult heart also function to enhance survival of the myocyte population in response to pleiotropic death stimuli. In this review, we summarize recent insights into hypertrophic signaling pathways and their ability to control the balance between myocyte life and death. As modulation of myocardial growth by antagonizing intracellular signaling pathways is increasingly recognized as a potentially auspicious approach to prevent and treat heart failure, the design of such therapies should respect the dichotomous action of pathways that dictate a balance between myocyte hypertrophy, survival and death.
Estimation of Progression-Free Survival in the Randomized Discontinuation Trial Design
Authors: Theodore G. Karrison
Journal: Journal of Clinical Oncology (2013)

TO THE EDITOR: Nosov et al recently published an article reporting on a study with a randomized discontinuation trial (RDT) design. Inthisdesign,allpatients initially receivedtivozanib for16weeks.After16 weeks, patients who responded (response was considered as 25% tumor shrinkage) continued on tivozanib, those with progressive disease were removed from the study, and those with stable disease were randomly assigned to either continue tivozanib or to be given a placebo. In Figure 4 of the article, a Kaplan-Meier curve is presented as an estimate of the progression-free survival (PFS) rate of all patients who were treated with tivozanib, measured from the time of initial dosing. However, this estimate may be biased, given that the method described was to simply censor patients who were assigned to the placebo at the time of random assignment. The reason for the bias is that the censoring is selectively performed only in the stable disease subgroup. If these patients have subsequent survival rates that are lower than those with initial tumor shrinkage (a likely possibility), the estimate will be positively biased. The solution is to combine the PFS estimate for the first 16 weeks (based on all patients) with a weighted average of the PFS rates beyond 16 weeks intherespondingandstabledisease/continually treatedsubgroups, asdescribedinthearticlebyRatainetal (seealsothearticlebyKarrisonet al). In the study by Nosov et al, 78 patients had an initial response and 118 had stable disease. The extent of the bias would depend on the magnitude of the difference in subsequent PFS in these two subgroups.
Human Leukocyte Histamine Release Assays with Whole Ragweed and Alternaria Antigens Using Technicon Autoanalyzer II
Authors: Evan J. Reinders, Hui Chong Chiu, T. J. Yoo
Journal: Allergy (1980)

A simple and commercially available automated technique for fluorometric analysis of histamine is described. It is applicable to histamine release experiments utilizing washed leukocytes, and analyzes 15 samples/h at histamine concentrations between 1 and 1000 ng/ml with a mean variance between 0.5% and 18%. This technique is applied to a cross sectional study of leukocytes from 14 ragweed sensitive patients (7 on and 7 off immunotherapy) as well as five normals. It was also applied to 17 Alternaria-sensitive patients (4 on and 12 off immunotherapy) in addition to six normals. While antigen induced in histamine release clearly separated the sensitive group from the normals, it did not correlate with immunotherapy, and a considerable variation was seen in the sensitive patients of both the treated and untreated groups.
PREPARING FOOTBALL REFEREE TO MANAGE CONFLICT
Authors: C Dell, D Rhind, G Misia
Journal: British Journal of Sports Medicine (2014)

Background The number of football referees in the United Kingdom has significantly declined over recent years (The F.A, 2011). Objective Previous research has indicate that conflict is an importnat factor in referees leaving the game and impact on their personal health and wellbeing (Dell, Rhind &amp; Gervis, 2013). This study evaluates a training programme which aims to develop referee's ability to manage conflict during matches. It is intended that this research will inform The F.A.'s drive to retain referees. Design Mixed methods design with two groups used. Setting The aims of the workshop were for the individuals to develop self-awareness of their own referee behaviour; to use conflict management stratergies to help them referee more effectively and to enhance their practical refereeing skills. Participants Trainee referees participated in this study; Group A (experimental) and Group B (control). Both genders were represented (Group A M=19 F=1/Group B M=18 F=2) aged from 14-&gt;55 years of age. Intervention Group A undertook a new specifically designed conflict managment and resolution workshop for referees as part of their basic referee training course. Group B completed the normal training programme. Main outcome measurements Both groups completed a pre-workshop questionaire based on their training and how they felt they had dealt with conflict during their 6 training games as a referee. The questionaire employed both likert-type scales and qualitative questions. Upon completion of the training programme both groups completed a post-workshop questionaire. Results Results from the post-workshop questionnaires for Group A indicate a significant imporvement in their ability to manage conflict relative to Group B. The significance for Group A in managing conflict was still present 3 months later. Conclusions This workshop has had a direct impact on how referees deal with and handle conflict.
Increased Expression of Histone Proteins during Estrogen-Mediated Cell Proliferation
Authors: Zheying Zhu, Robert J. Edwards, Alan R. Boobis
Journal: Environmental Health Perspectives (2009)

BackgroundThere is concern about the potential risk posed by compounds with estrogen-like activity present in the environment. As previous studies have shown that combined exposure to such compounds results in dose additivity, it should be possible to assess estrogen exposure with suitable biomarkers of effect.ObjectivesOur goal was to identify candidate protein biomarkers of effect for estrogenic compounds.MethodsIn the search for biomarkers, we assessed the effect of several estrogenic compounds on the expression profile of proteins in breast-derived cell lines varying in their estrogen receptor (ER) phenotype using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. We identified responsive proteins, after separating them by SDS-polyacrylamide gel electrophoresis, and analyzing the trypsin-digested proteins by tandem mass spectrometry.ResultsThe estrogenic compounds 17β-estradiol, genistein, bisphenol A, and endosulfan produced similar protein profile changes in MCF-7 cells (phenotype: ERα+/ERβ+), but had no effect on MDA-MB-231 (ERα−/ERβ+), MCF-10F (ERα−/ERβ+), or MCF-10A (ERα−/ERβ−) cells. The most responsive proteins in MCF-7 cells were identified as histones H2A, H2B, H3, and H4. Histone levels were not increased in cell lines that showed no proliferative response to estrogens despite their rapid intrinsic growth rate in culture.ConclusionOur results indicate that ER-mediated cell proliferation results in up-regulation of core histone proteins.
Successful and Safe Use Of Icatibant For Life-Threatening Angioedema Attack During Pregnancy In a Patient With Hereditary Angioedema Type I
Authors: Karine Boufleur, Luana Delcaro, Daniel L. Cordeiro, Priscila B. Botelho Palhas, Janaina Fernandes de Melo Sousa, Thaís Mendonça, Janaina Michele de Lima Melo, Gustavo Neppelenbroek, Wlly Sarti, Adriana S. Moreno, Luisa Karla P. Arruda
Journal: Journal of Allergy and Clinical Immunology (2014)
Hydrostatic pressure induces expression of interleukin 6 and tumour necrosis factor alpha mRNAs in a chondrocyte-like cell line
Authors: K. Takahashi, T. Kubo, Y. Arai, I. Kitajima, M. Takigawa, J. Imanishi, Y. Hirasawa
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To clarify the effect of pressure on the expressions of proteoglycan core protein and metabolism related cytokines in a chondrocyte-like cell line, HCS-2/8. <h3>METHODS</h3> HCS-2/8 cells were exposed to 1, 5, 10, or 50 MPa of hydrostatic pressure (HP) for two hours, and mRNA expressions of interleukin 6 (IL6) and tumour necrosis factor α (TNFα) were examined by using reverse transcription-polymerase chain reaction (RT-PCR) method with specific primer sets; and mRNA of proteoglycan core protein, stromelysin, and tissue inhibitor of metalloproteinase 1 (TIMP1) were measured with northern blotting. <h3>RESULTS</h3> HP exposure caused temporal morphological changes of the cells, but did not affect cellular viability. IL6 and TNFα mRNA expressions were not observed in the control cells under the atmospheric pressure, whereas in the cells treated with HP, pressure dependent enhancement of IL6 mRNA expression was observed between 30 minutes and four hours after the HP release. TNFα mRNA expression also increased 30 minutes after the exposure to 50 MPa of HP and disappeared four hours later. Proteoglycan core protein mRNA levels increased between 30 minutes and four hours after the exposure to 1 or 5 MPa of HP, whereas the levels decreased after 10 or 50 MPa of HP. Stromelysin and TIMP1 mRNA signals did not respond to HP. <h3>CONCLUSIONS</h3> HP at excessively high levels induced IL6 and TNFα expression and reduced the expression of proteoglycan core protein, while physiological levels of HP increased the expression of proteoglycan core protein. These findings are important when considering the pathology of osteoarthritis.
Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy
Authors: Judy Savige, Martin Gregory, Oliver Gross, Clifford Kashtan, Jie Ding, Frances Flinter
Journal: Journal of the American Society of Nephrology (2013)

Few prospective, randomized controlled clinical trials address the diagnosis and management of patients with Alport syndrome or thin basement membrane nephropathy. Adult and pediatric nephrologists and geneticists from four continents whose clinical practice focuses on these conditions have developed the following guidelines. The 18 recommendations are based on Level D (Expert opinion without explicit critical appraisal, or based on physiology, bench research, or first principles—National Health Service category) or Level III (Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees—U.S. Preventive Services Task Force) evidence. The recommendations include the use of genetic testing as the gold standard for the diagnosis of Alport syndrome and the demonstration of its mode of inheritance; the need to identify and follow all affected members of a family with X-linked Alport syndrome, including most mothers of affected males; the treatment of males with X-linked Alport syndrome and individuals with autosomal recessive disease with renin-angiotensin system blockade, possibly even before the onset of proteinuria; discouraging the affected mothers of males with X-linked Alport syndrome from renal donation because of their own risk of kidney failure; and consideration of genetic testing to exclude X-linked Alport syndrome in some individuals with thin basement membrane nephropathy. The authors recognize that as evidence emerges, including data from patient registries, these guidelines will evolve further.
Varespladib and Cardiovascular Events in Patients With an Acute Coronary Syndrome
Authors: Stephen J. Nicholls, John J. P. Kastelein, Gregory G. Schwartz, Dianna Bash, Robert S. Rosenson, Matthew A. Cavender, Danielle M. Brennan, Wolfgang Koenig, J. Wouter Jukema, Vijay Nambi, R. Scott Wright, Venu Menon, A. Michael Lincoff, Steven E. Nissen
Journal: JAMA (2014)

<h3>Importance</h3> Secretory phospholipase A<sub>2</sub>(sPLA<sub>2</sub>) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA<sub>2</sub>inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. <h3>Objective</h3> To determine the effects of sPLA<sub>2</sub>inhibition with varespladib on cardiovascular outcomes. <h3>Design, Setting, and Participants</h3> A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). <h3>Interventions</h3> Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. <h3>Main Outcomes and Measures</h3> The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. <h3>Results</h3> At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank<i>P</i> = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank<i>P</i> = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA<sub>2</sub>inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01130246
ANCA associated glomerulonephritis in a patient with mixed connective tissue disease
Authors: G Hernandez-Molina
Journal: Annals of the Rheumatic Diseases (2006)

We report the case of a 47 year old woman with a 19 year history of mixed connective tissue disease (MCTD) diagnosed according to Alarcon-Segovia classification criteria.1 She had Raynaud’s phenomenon, arthritis, swollen hands, and anti-ribonucleoprotein antibodies (anti-RNP 1/1280). She received low doses of prednisone and her clinical course was uneventful, except for sporadic Raynaud’s phenomenon. Her drug treatment was stopped 10 years ago, but medical supervision continued without evidence of pulmonary, gastrointestinal or renal disease during her follow up.

In 2003, she sought medical attention complaining of malaise during the past 3 months. Physical examination disclosed paleness, facial telangiectases, and hypertension (160/100). Laboratory findings were high—erythrocyte sedimentation rate (102 mm/1st h), normocytic/normochromic anaemia (haemoglobin 90 g/l), severely decreased renal function (creatinine …