tbuckley/cabot-search huggingface dataset:
Albuterol Does Not Antagonize the Inhibitory Effect of Dexamethasone on Monocyte Cytokine Release
Authors: PAUL M. SELDON, DAVID A. STEVENS, IAN M. ADCOCK, BRIAN J. O'CONNOR, PETER J. BARNES, MARK A. GIEMBYCZ
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

β2-Adrenoceptor agonists given by the inhaled route are the most effective bronchodilators known, yet high doses of these drugs may be associated with an increase in asthma mortality and morbidity. One theory for this paradox is that chronic use of β2-adrenoceptor agonists compromises the anti- inflammatory action of glucocorticosteroids. This hypothesis derives from the ability of albuterol and fenoterol to inhibit the interaction of the glucocorticosteroid receptor (GR) with proinflammatory transcriptional activators acting on the promoter region of certain target genes that encode cytokines such as tumor necrosis factor- α (TNF α ) and granulocyte/macrophage colony-stimulating factor (GM-CSF). However, the functional relevance of these results has not been formally investigated. We have tested the hypothesis that albuterol reduces the ability of dexamethasone to inhibit the generation of TNF α and GM-CSF from lipopolysaccharide (LPS)-stimulated human monocytes. Pretreatment of human monocytes with albuterol (1 and 100 μ M) for 5 and for 180 min inhibited maximally TNF α generation by approximately 25%. However, regardless of the concentration of albuterol, or the time of preincubation, the inhibitory effect of dexamethasone was not significantly affected with respect to the EC50 or the maximal effect produced. Qualitatively identical data were obtained when GM-CSF release was used as an index of monocyte activation. We conclude that high concentrations of albuterol do not compromise the ability of dexamethasone to suppress the generation of TNF α and GM-CSF from LPS-stimulated human monocytes.
Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study
Authors: A.A. Brandes, U. Basso, F. Vastola, A. Tosoni, L.M. Pasetto, A. Jirillo, S. Lonardi, M.K. Paris, H. Koussis, S. Monfardini, M. Ermani
Journal: Annals of Oncology (2003)
Endophenotypes in Psychopathology Research: Where Do We Stand?
Authors: Gregory A. Miller, Brigitte Rockstroh
Journal: Annual Review of Clinical Psychology (2013)

Endophenotypes for psychopathology have been conceived as latent, unobserved, but measureable manifestations of phenomena that causally connect genetic liability to clinical disorder. Several decades of research have led to refinement of the construct and identification of some candidate endophenotypes, but rather limited progress on finding the genes involved or the mechanisms by which endophenotypes are driven by genetic and environmental factors and in turn drive psychopathology. Currently promising avenues for research involve development of transdiagnostic concepts not limited to traditional diagnostic categories, measures of endophenotypic and manifest psychopathology that have higher validity than those categories, and methods for modeling complex relationships among diverse contributors to etiology. With more grounding in animal neuroscience and other aspects of basic biological and psychological science, exemplified in the Research Domain Criteria initiative, there is every reason to anticipate that the endophenotype concept will grow more central in the psychopathology literature.
Improved Out-of-Hospital Cardiac Arrest Survival Through the Inexpensive Optimization of an Existing Defibrillation Program
Authors: Ian G. Stiell, George A. Wells, Brian J. Field III, Daniel W. Spaite, Valerie J. De Maio, Roxanne Ward, Douglas P. Munkley, Marion B. Lyver, Lorraine G. Luinstra, Tony Campeau, Justin Maloney, Eugene Dagnone, None for the OPALS Study Group
Journal: JAMA (1999)

Survival rates for out-of-hospital cardiac arrest are low; published survival rates in Ontario are only 2.5%. This study represents phase II of the Ontario Prehospital Advanced Life Support (OPALS) study, which is designed to systematically evaluate the effectiveness and efficiency of various prehospital interventions for patients with cardiac arrest, trauma, and critical illnesses.To assess the impact on out-of-hospital cardiac arrest survival of the implementation of a rapid defibrillation program in a large multicenter emergency medical services (EMS) system with existing basic life support and defibrillation (BLS-D) level of care.Controlled clinical trial comparing survival for 36 months before (phase I) and 12 months after (phase II) system optimization.Nineteen urban and suburban Ontario communities (populations ranging from 16 000 to 750 000 [total, 2.7 million]).All patients who had out-of-hospital cardiac arrest in the study communities for whom resuscitation was attempted by emergency responders.Study communities optimized their EMS systems to achieve the target response interval from when a call was received until a vehicle stopped with a defibrillator of 8 minutes or less for 90% of cardiac arrest cases. Working both locally and provincially, communities implemented multiple measures, including defibrillation by firefighters, base paging, tiered response agreements with fire departments, continuous quality improvement for response intervals, and province-wide revision and implementation of standard dispatch policies. All response times were obtained from a central dispatch system.Survival to hospital discharge.The 4690 cardiac arrest patients studied in phase I and the 1641 in phase II were similar for all clinical and demographic characteristics, including age, sex, witnessed status, rhythm, and receipt of bystander cardiopulmonary resuscitation. The proportion of cases meeting the 8-minute response criterion improved (76.7% vs 92.5%; P<.001) as did most median response intervals. Overall survival to hospital discharge for all rhythm groups combined improved from 3.9% to 5.2 % (P = .03). The 33% relative increase in survival represents an additional 21 lives saved each year in the study communities (approximately 1 life per 120000 residents). The charges were estimated to be US $46900 per life saved for establishing the rapid defibrillation program and US $2400 per life saved annually for maintaining the program.An inexpensive, multifaceted system optimization approach to rapid defibrillation can lead to significant improvements in survival after cardiac arrest in a large BLS-D EMS system.
A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphoma: a single-institution study
Authors: E. Nitta, K. Izutsu, T. Sato, Y. Ota, K. Takeuchi, A. Kamijo, K. Takahashi, K. Oshima, Y. Kanda, S. Chiba, T. Motokura, M. Kurokawa
Journal: Annals of Oncology (2006)
Proper experimental design and implementation are necessary conditions for a balanced social psychology
Authors: Andreas Ortmann, Michal Ostatnicky
Journal: Behavioral and Brain Sciences (2004)

We applaud the authors' basic message. We note that the negative research emphasis is not special solely to social psychology and judgment and decision-making. We argue that the proposed integration of null hypothesis significance testing (NHST) and Bayesian analysis is promising but will ultimately succeed only if more attention is paid to proper experimental design and implementation.
Relationship between Topoisomerase 2A RNA Expression and Recurrence after Adjuvant Chemotherapy for Breast Cancer
Authors: Joseph A. Sparano, Lori J. Goldstein, Barrett H. Childs, Steven Shak, Diana Brassard, Sunil Badve, Frederick L. Baehner, Roberto Bugarini, Steve Rowley, Edith Perez, Lawrence N. Shulman, Silvana Martino, Nancy E. Davidson, George W. Sledge, Robert Gray
Journal: Clinical Cancer Research (2009)

PURPOSE: To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. EXPERIMENTAL DESIGN: RNA was extracted from archived tumor samples derived from 378 patients with stage I to III HR-positive, HER2-normal breast cancer and analyzed by reverse transcription-PCR for a panel of 374 genes, including the 21-gene recurrence score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a nonrecurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. RESULTS: TOP2A expression exhibited the strongest association with increased recurrence risk (P = 0.01), and was significantly associated with recurrence (P = 0.008) in a multivariate analysis adjusted for clinicopathologic features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95% confidence interval, 1.3-5.2; P = 0.008) in risk of recurrence if the RS was <18, and a 2.0-fold increase (95% confidence interval, 1.2-3.2, P = 0.003) if there was an intermediate RS of 18 to 30. CONCLUSIONS: In patients with HR-positive, HER2-normal breast cancer, a population known to have a low incidence of TOP2A gene alterations thought to be predictive of anthracycline benefit, there is a range of TOP2A RNA expression that is strongly associated with recurrence after adjuvant anthracyclines, which provides information complementary to RS, indicating that it merits further evaluation as a prognostic and predictive marker. (Clin Cancer Res 2009;15(24):7693-700).
Serum anti-tumour antibodies and auto-antibodies in vitiligo
Authors: HAROLD WOOLFSON, OWEN A. FINN, RONA M. MACKIE, ALEX McQUEEN, RODERICK N.M. MacSWEEN
Journal: British Journal of Dermatology (1975)

Anti-tumour antibody was sought in the sera of three groups of patients; idiopathic vitiligo, malignant melanoma and miscellaneous skin disorders. No precipitating antibody to a series of prepared pigmented tumour antigens was demonstrated. All sera were tested for a number of auto-antibodies. No significant differences were detected between the groups. The evidence for an immunological factor in the causation of vitiligo remains circumstantial only.
p53 Is Preferentially Recruited to the Promoters of Growth Arrest Genes <i>p21</i> and <i>GADD45</i> during Replicative Senescence of Normal Human Fibroblasts
Authors: James G. Jackson, Olivia M. Pereira-Smith
Journal: Cancer Research (2006)

Abstract Replicative senescence is the terminal growth arrest that most normal human cells enter into after a fixed number of divisions in vitro, limiting the proliferative potential of a cell and preventing genomic instability caused by critically short telomeres. Thus, senescence presents a tumor-suppressive mechanism and a barrier to tumor formation. However, senescent cells are inherently resistant to apoptosis and, as they accumulate in aging tissues, may contribute to organ dysfunction and promote tumor progression as part of the stromal environment. Replicative life span in normal human cells can be extended by inactivation of the tumor suppressor gene p53 or its direct target, the cyclin-dependent kinase inhibitor p21, suggesting a direct role for this pathway in senescence. However, p53 recruitment to promoters of target genes during replicative senescence has not been shown in live cells. In this study, we used chromatin immunoprecipitation to determine that p53 preferentially occupied the promoters of growth arrest genes p21 and GADD45 in senescent normal human diploid fibroblasts but not the promoters of other target genes that recruited p53 following doxorubicin-induced DNA damage, such as apoptosis regulators TNFRSF10b, TNFRSF6, and PUMA. This differential recruitment of p53 in senescent versus doxorubicin-treated fibroblasts was accompanied by differences in post-translational modification of p53. These data provide mechanisms for both the growth arrest mediated by p53 and the resistant nature of senescent cells to apoptosis despite p53 activity. (Cancer Res 2006; 66(17): 8356-60)
2002 Update of Recommendations for the Use of Chemotherapy and Radiotherapy Protectants: Clinical Practice Guidelines of the American Society of Clinical Oncology
Authors: Lynn M. Schuchter, Martee L. Hensley, Neal J. Meropol, Eric P. Winer
Journal: Journal of Clinical Oncology (2002)

Article Tools ASCO SPECIAL ARTICLE Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.04.178 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065567 2002 Update of Recommendations for the Use of Chemotherapy and Radiotherapy Protectants: Clinical Practice Guidelines of the American Society of Clinical Oncology Lynn M. SchuchterxLynn M. SchuchterSearch for articles by this author , Martee L. HensleyxMartee L. HensleySearch for articles by this author , Neal J. MeropolxNeal J. MeropolSearch for articles by this author , Eric P. WinerxEric P. WinerSearch for articles by this author , Show More From the American Society of Clinical Oncology, Alexandria, VA. https://doi.org/10.1200/JCO.2002.04.178 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Stem cell transplantation: limits and hopes
Authors: K P MACHOLD
Journal: Annals of the Rheumatic Diseases (2001)

The clinical course and severity of inflammatory rheumatic diseases vary considerably. A large proportion of patients have mild to moderate activity of the inflammatory process which can be successfully controlled by conventional therapeutic measures: traditional disease modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA) and some other forms of chronic arthritides, intermediate steroid doses or mild immunomodulatory agents for systemic lupus erythematosus (SLE) and other connective tissue diseases. Also, control of more severe disease is often manageable by more aggressive, established means, such as high dose methotrexate and combination treatment for RA, or pulse cyclophosphamide treatment and steroids in SLE. For most of these therapeutic approaches significant evidence has accumulated in randomised controlled trials.1-3 

Without the possibility of making individual predictions, there are many patients whose diseases are not sufficiently responsive to the traditional measures. At least for RA, the armamentarium has recently been significantly enriched by new means of intervention,4-6 among them biological agents which specifically target a key mediator of inflammation, tumour necrosis factor α (TNFα); more targets are currently being studied. The TNF blockers also appear to be quite efficient therapeutic agents for diseases which were often less easy to control, such as psoriatic arthritis,7 or ankylosing spondylitis, which was regarded as intractable when treated with traditional DMARDs.8 

However, despite some success of modern antirheumatic treatment, groups of patients exist, familiar to every rheumatologist, whose disease is resistant to therapeutic measures. This is still the case for a significant proportion of patients with RA whose continuing disease activity, refractory to traditional and new DMARDs, combination treatment, and biological agents, leads to a relentless progression of joint destruction; approximately 30–40% of patients with RA do not have clinical responses even when receiving the new agents. This is also the case for a significant number …
Dysglycemia and Heart Failure Hospitalization
Authors: Mark C. Petrie, John J.V. McMurray
Journal: Circulation (2007)

2][3][4][5][6][7][8][9] In diabetic individuals, the risk of developing heart failure is greatest in those with an elevated body mass index, poor glycemic control (as indicated by hemoglobin A 1c level), nephropathy, retinopathy, and coronary heart disease.
Phase 3 Study of Adjuvant Radiotherapy Versus Wait and See in pT3 Prostate Cancer: Impact of Pathology Review on Analysis
Authors: Dirk Bottke, Reinhard Golz, Stephan Störkel, Axel Hinke, Alessandra Siegmann, Lothar Hertle, Kurt Miller, Wolfgang Hinkelbein, Thomas Wiegel
Journal: European Urology (2013)
Kinetics of FKBP12.6 Binding to Ryanodine Receptors in Permeabilized Cardiac Myocytes and Effects on Ca Sparks
Authors: Tao Guo, Razvan L. Cornea, Sabine Huke, Emmanuel Camors, Yi Yang, Eckard Picht, Bradley R. Fruen, Donald M. Bers
Journal: Circulation Research (2010)

Rationale : FK506-binding proteins FKBP12.6 and FKBP12 are associated with cardiac ryanodine receptors (RyR2), and cAMP-dependent protein kinase A (PKA)-dependent phosphorylation of RyR2 was proposed to interrupt FKBP12.6-RyR2 association and activate RyR2. However, the function of FKBP12.6/12 and role of PKA phosphorylation in cardiac myocytes are controversial. Objective : To directly measure in situ binding of FKBP12.6/12 to RyR2 in ventricular myocytes, with simultaneous Ca sparks measurements as a RyR2 functional index. Methods and Results : We used permeabilized rat and mouse ventricular myocytes, and fluorescently-labeled FKBP12.6/12. Both FKBP12.6 and FKBP12 concentrate at Z-lines, consistent with RyR2 and Ca spark initiation sites. However, only FKBP12.6 inhibits resting RyR2 activity. Assessment of fluorescent FKBP binding in myocyte revealed a high FKBP12.6-RyR2 affinity ( K d =0.7±0.1 nmol/L) and much lower FKBP12-RyR2 affinity ( K d =206±70 nmol/L). Fluorescence recovery after photobleach confirmed this K d difference and showed that it is mediated by k off . RyR2 phosphorylation by PKA did not alter binding kinetics or affinity of FKBP12.6/12 for RyR2. Using quantitative immunoblots, we determined endogenous [FKBP12] in intact myocytes is ≈1 μmol/L (similar to [RyR]), whereas [FKBP12.6] is ≤150 nmol/L. Conclusions : Only 10% to 20% of endogenous myocyte RyR2s have FKBP12.6 associated, but virtually all myocyte FKBP12.6 is RyR2-bound (because of very high affinity). FKBP12.6 but not FKBP12 inhibits basal RyR2 activity. PKA-dependent RyR2 phosphorylation has no significant effect on binding of either FKBP12 or 12.6 to RyR2 in myocytes.
What makes species unique? The contribution of proteins with obscure features.
Authors: Martin Gollery, Jeff Harper, John Cushman, Taliah Mittler, Thomas Girke, Jian-Kang Zhu, Julia Bailey-Serres, Ron Mittler
Journal: Genome biology (2006)

Proteins with obscure features (POFs), which lack currently defined motifs or domains, represent between 18% and 38% of a typical eukaryotic proteome. To evaluate the contribution of this class of proteins to the diversity of eukaryotes, we performed a comparative analysis of the predicted proteomes derived from 10 different sequenced genomes, including budding and fission yeast, worm, fly, mosquito, Arabidopsis, rice, mouse, rat, and human. Only 1,650 protein groups were found to be conserved among these proteomes (BLAST E-value threshold of 10-6). Of these, only three were designated as POFs. Surprisingly, we found that, on average, 60% of the POFs identified in these 10 proteomes (44,236 in total) were species specific. In contrast, only 7.5% of the proteins with defined features (PDFs) were species specific (17,554 in total). As a group, POFs appear similar to PDFs in their relative contribution to biological functions, as indicated by their expression, participation in protein-protein interactions and association with mutant phenotypes. However, POF have more predicted disordered structure than PDFs, implying that they may exhibit preferential involvement in species-specific regulatory and signaling networks. Because the majority of eukaryotic POFs are not well conserved, and by definition do not have defined domains or motifs upon which to formulate a functional working hypothesis, understanding their biochemical and biological functions will require species-specific investigations.
Functional defects of dendritic cells in patients with CD40 deficiency
Authors: Stefania Fontana, Daniele Moratto, Surinder Mangal, Maria De Francesco, William Vermi, Simona Ferrari, Fabio Facchetti, Necil Kutukculer, Claudia Fiorini, Marzia Duse, Pranab K. Das, Luigi D. Notarangelo, Alessandro Plebani, Raffaele Badolato
Journal: Blood (2003)
Brown and Polar Bear Y Chromosomes Reveal Extensive Male-Biased Gene Flow within Brother Lineages
Authors: Tobias Bidon, Axel Janke, Steven R. Fain, Hans Geir Eiken, Snorre B. Hagen, Urmas Saarma, Björn M. Hallström, Nicolas Lecomte, Frank Hailer
Journal: Molecular Biology and Evolution (2014)

Brown and polar bears have become prominent examples in phylogeography, but previous phylogeographic studies relied largely on maternally inherited mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y chromosome, a natural counterpart to mtDNA, has remained underexplored. Although this paternally inherited chromosome is indispensable for comprehensive analyses of phylogeographic patterns, technical difficulties and low variability have hampered its application in most mammals. We developed 13 novel Y-chromosomal sequence and microsatellite markers from the polar bear genome and screened these in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390-kb-long Y-chromosomal scaffold using sequencing data from published male ursine genomes. Y chromosome evidence support the emerging understanding that brown and polar bears started to diverge no later than the Middle Pleistocene. Contrary to mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic sister (or rather brother) lineages, without signals of introgression, 2) male-biased gene flow across continents and on phylogeographic time scales, and 3) male dispersal that links the Alaskan ABC islands population to mainland brown bears. Due to female philopatry, mtDNA provides a highly structured estimate of population differentiation, while male-biased gene flow is a homogenizing force for nuclear genetic variation. Our findings highlight the importance of analyzing both maternally and paternally inherited loci for a comprehensive view of phylogeographic history, and that mtDNA-based phylogeographic studies of many mammals should be reevaluated. Recent advances in sequencing technology render the analysis of Y-chromosomal variation feasible, even in nonmodel organisms.
Thyronamines—Past, Present, and Future
Authors: S. Piehl, C. S. Hoefig, T. S. Scanlan, J. Köhrle
Journal: Endocrine Reviews (2011)

After their initial discovery in the early 1950's, thyronamines (TAM), a class of endogenous signalling compounds exhibiting structural similarity to the thyroid hormone L-thyroxine, are now back in the focus of basic and clinical research. Numerous prompt pharmacological effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria and reduction of fat mass as well as promising therapeutic potential in the experimental prophylaxis and treatment of stroke have already been demonstrated in rodent experimental models. This review article summarizes the currently still somewhat scattered data on TAM, trying to yield a complete and updated picture of the current state of TAM research, which addresses issues on TAM biosynthesis, receptors, signalling and therapeutically relevant targets such as energy metabolism and the cardiovascular system.