tbuckley/cabot-search huggingface dataset:
<i>TP53</i> Genomic Status Regulates Sensitivity of Gastric Cancer Cells to the Histone Methylation Inhibitor 3-Deazaneplanocin A (DZNep)
Authors: Lai Ling Cheng, Yoko Itahana, Zheng Deng Lei, Na-Yu Chia, Yonghui Wu, Yingnan Yu, Shen Li Zhang, Aye Aye Thike, Anuradha Pandey, Steve Rozen, Pieter Mathijs Voorhoeve, Qiang Yu, Puay Hoon Tan, Boon Huat Bay, Koji Itahana, Patrick Tan
Journal: Clinical Cancer Research (2012)

Abstract Purpose: DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNep responsiveness in cancer cells remain largely unknown. We sought to determine molecular factors influencing DZNep response in gastric cancer. Experimental Design: Phenotypic effects of DZNep were evaluated in a panel of gastric cancer cell lines. Sensitive lines were molecularly interrogated to identify potential predictors of DZNep responsiveness. The functional importance of candidate predictors was evaluated using short hairpin RNA (shRNA) and siRNA technologies. Results: DZNep depleted PRC2 pathway components in almost all gastric cancer lines, however, only a subset of lines exhibited growth inhibition upon treatment. TP53 genomic status was significantly associated with DZNep cellular responsiveness, with TP53 wild-type (WT) lines being more sensitive (P &amp;lt; 0.001). In TP53-WT lines, DZNep stabilized p53 by reducing ubiquitin conjugation through USP10 upregulation, resulting in activation of canonical p53 target genes. TP53 knockdown in TP53-WT lines attenuated DZNep sensitivity and p53 target activation, showing the functional importance of an intact p53 pathway in regulating DZNep cellular sensitivity. In primary human gastric cancers, EZH2 expression was negatively correlated with p53 pathway activation, suggesting that higher levels of EZH2 may repress p53 activity. Conclusion: Our results highlight an important role for TP53 genomic status in influencing DZNep response in gastric cancer. Clinical trials evaluating EZH2-targeting agents such as DZNep should consider stratifying patients with gastric cancer by their TP53 genomic status. Clin Cancer Res; 18(15); 4201–12. ©2012 AACR.
Hydrazine sulfate protects D-galactosamine-sensitized mice against endotoxin and tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary.
Authors: R Silverstein, B R Turley, C A Christoffersen, D C Johnson, D C Morrison
Journal: The Journal of Experimental Medicine (1991)

In previously published studies, we had demonstrated that hydrazine sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same hydrazine sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of hydrazine sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of hydrazine sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of hydrazine sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after hydrazine sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by hydrazine sulfate. Although hydrazine sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by hydrazine sulfate. We conclude that hydrazine sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the hydrazine sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.
Characteristics of cholinergic neuroeffector transmission of ganglionic and aganglionic colon in Hirschsprung's disease.
Authors: E S Vizi, J Zseli, E Kontor, E Feher, T Verebelyi
Journal: Gut (1990)

Differences in the release and content of acetylcholine and the alpha 2 adrenoceptor mediated interaction between noradrenergic and cholinergic neurons were investigated by neurochemical and pharmacological methods in aganglionic and ganglionic segments of isolated human colon taken from children suffering from Hirschsprung's disease. Both at rest and during transmural stimulation the release of acetylcholine was significantly higher in the spastic (aganglionic) segment than in the proximal dilated bowel. Significant differences were found in the tissue concentration of acetylcholine between ganglionic and aganglionic specimens. The pattern of response to transmural stimulation was also different in the spastic and dilated bowel. Transmural stimulation induced relaxation and contraction in ganglionic specimens but only contractions in aganglionic specimens. The sensitivity of the smooth muscle in the aganglionic portion to exogenous acetylcholine and to field stimulation was found to be higher than in the ganglionic portion. While noradrenaline added to the organ bath reduced the stimulation-evoked release of acetylcholine from spastic segments, via an alpha 2 adrenoceptor mediated process, yohimbine did not enhance the release. It is suggested that in Hirschsprung's disease the increased acetylcholine release, the enhanced sensitivity of smooth muscle cells to acetylcholine, and the lack of alpha 2 adrenoceptor mediated noradrenergic modulation of acetylcholine release from cholinergic interneurons might be responsible for the spasm of aganglionic segments.
Use of forced vital capacity and forced expiratory volume in 1 second quality criteria for determining a valid test
Authors: John L. Hankinson, Bill Eschenbacher, Mary Townsend, Janet Stocks, Philip H. Quanjer
Journal: European Respiratory Journal (2014)

The 2005 American Thoracic Society (ATS)/European Respiratory Society (ERS) spirometry guidelines define valid tests as having three acceptable blows and a repeatable forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The aim of this study was to determine how reviewer and computer-determined ATS/ERS quality could affect population reference values for FVC and FEV1. Spirometry results from 7777 normal subjects aged 8–80 years (NHANES (National Health and Nutrition Examination Survey) III) were assigned quality grades A to F for FVC and FEV1 by a computer and one reviewer (reviewer 1). Results from a subgroup of 1466 Caucasian adults (aged 19–80 years) were reviewed by two additional reviewers. Mean deviations from NHANES III predicted for FVC and FEV1 were examined by quality grade (A to F). Reviewer 1 rejected (D and F grade) 5.2% of the 7777 test sessions and the computer rejected ∼16%, primarily due to end-of-test (EOT) failures. Within the subgroup, the computer rejected 11.5% of the results and the three reviewers rejected 3.7–5.9%. Average FEV1 and FVC were minimally influenced by grades A to C allocated by reviewer 1. Quality assessment of individual blows including EOT assessments should primarily be used as an aid to good quality during testing rather than for subsequently disregarding data. Reconsideration of EOT criteria and its application, and improved grading standards and training in over-reading are required. Present EOT criteria results in the exclusion of too many subjects while having minimal impact on predicted values.
Submandibular Adenitis Due to Iodide Administration
Authors: R. McG. Harden
Journal: BMJ (1968)

Iodine is extensively used in expectorants and asthma prepara- tions, in the preoperative treatment of hyperthyroidism, and as a radio-opaque substance for diagnostic radiography.Toxic reactions may affect the thyroid, the skin, the eyes, the vascular system, and the salivary glands.Though " parotitis " is often referred to as a complication of iodide administration (Mato- vinovic and Ramalingaswami, 1960; Williams and Bakke, 1962 ; Meyler, 1963), few studies have been made of the salivary gland involvement.In this paper the relation between the
Dissociation of Intracellular Signaling Pathways in Response to Partial Agonist Ligands of the T Cell Receptor
Authors: Luan A. Chau, Jeffrey A. Bluestone, Joaquín Madrenas
Journal: The Journal of Experimental Medicine (1998)

The T cell receptor (TCR) is a versatile receptor able to generate different signals that result in distinct T cell responses. The pattern of early signals is determined by the TCR binding kinetics that control the ability of the ligand to coengage TCR and coreceptor. Coengagement of TCR and CD4 results in an agonist signaling pattern with complete tyrosine phosphorylation of TCR subunits, and recruitment and activation of ZAP-70. In contrast, TCR engagement without CD4 coengagement causes a partial agonist type of signaling, characterized by distinct phosphorylation of TCR subunits and recruitment but no activation of ZAP-70. The pathways triggered by partial agonist signaling are unknown. Here, we show that agonists cause association of active lck and active ZAP-70 with p120-GTPase–activating protein (p120-GAP). These associations follow engagement of CD4 or CD3, respectively. In contrast, partial agonists do not activate lck or ZAP-70, but induce association of p120-GAP with inactive ZAP-70. Despite these differences, both agonist and partial agonist signals activate the mitogen-activated protein kinase (MAPK) pathway. However, MAPK activation by partial agonists is transient, supporting a kinetic, CD4-dependent model for the mechanism of action of variant TCR ligands. Transient MAPK activation may explain some of the responses to TCR partial agonists and antagonists.
Evaluating the Relationship between Evolutionary Divergence and Phylogenetic Accuracy in AFLP Data Sets
Authors: María Jesús García-Pereira, Armando Caballero, Humberto Quesada
Journal: Molecular Biology and Evolution (2009)

Using in silico amplified fragment length polymorphism (AFLP) fingerprints, we explore the relationship between sequence similarity and phylogeny accuracy to test when, in terms of genetic divergence, the quality of AFLP data becomes too low to be informative for a reliable phylogenetic reconstruction. We generated DNA sequences with known phylogenies using balanced and unbalanced trees with recent, uniform and ancient radiations, and average branch lengths (from the most internal node to the tip) ranging from 0.02 to 0.4 substitutions per site. The resulting sequences were used to emulate the AFLP procedure. Trees were estimated by maximum parsimony (MP), neighbor-joining (NJ), and minimum evolution (ME) methods from both DNA sequences and virtual AFLP fingerprints. The estimated trees were compared with the reference trees using a score that measures overall differences in both topology and relative branch length. As expected, the accuracy of AFLP-based phylogenies decreased dramatically in the more divergent data sets. Above a divergence of approximately 0.05, AFLP-based phylogenies were largely inaccurate irrespective of the distinct topology, radiation model, or phylogenetic method used. This value represents an upper bound of expected tree accuracy for data sets with a simple divergence history; AFLP data sets with a similar divergence but with unbalanced topologies and short ancestral branches produced much less accurate trees. The lack of homology of AFLP bands quickly increases with divergence and reaches its maximum value (100%) at a divergence of only 0.4. Low guanine-cytosine (GC) contents increase the number of nonhomologous bands in AFLP data sets and lead to less reliable trees. However, the effect of the lack of band homology on tree accuracy is surprisingly small relative to the negative impact due to the low information content of AFLP characters. Tree-building methods based on genetic distance displayed similar trends and outperformed parsimony at low but not at high divergences. However, the impact of using alternative phylogenetic methods on tree accuracy was generally small relative to the uncertainty arising from factors such as divergence, nonhomology of bands, or the low information content of AFLP characters. Nevertheless, our data suggest that under certain circumstances, AFLPs may be suitable to reconstruct deeper phylogenies than usually accepted.
Regulation of Intestinal Calcium Transport
Authors: Ramesh C. Khanal, Ilka Nemere
Journal: Annual Review of Nutrition (2008)

Calcium is an essential ion in all organisms and participates in a variety of structural and functional roles. Calcium (re)absorption occurs in epithelia, including the intestine, kidney, mammary glands, placenta, and gills of fish. Its transport is regulated by a complex array of processes that are mediated by hormonal, developmental, and physiological factors involving the gastrointestinal tract, bone, kidney, and the parathyroids. Here we review the calcium transport mechanisms-paracellular, which is energy independent, and transcellular, which is energy dependent-primarily focusing on the intestine. We provide a new perspective on the facilitated diffusion and vesicular transport models to account for the emerging concepts on transcellular calcium transport. Finally, we discuss how 1,25(OH)2D3 and parathyroid hormone regulate calcium transport.
Association Between Exclusive Pipe Smoking and Mortality From Cancer and Other Diseases
Authors: S. J. Henley, M. J. Thun, A. Chao, E. E. Calle
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Although many studies have examined the adverse health effects of pipe smoking combined with other forms of tobacco use, few have included large numbers of exclusive pipe smokers. The prevalence of pipe smoking has declined since the 1960s, yet usage is still common regionally, especially among older populations. Methods: Using Cox proportional hazards models, we examined the association between pipe smoking and mortality from tobacco-related cancers and other diseases in a cohort of U.S. men enrolled in the Cancer Prevention Study II, an American Cancer Society prospective study. The cohort of 138 307 men included those who reported, in their 1982 enrollment questionnaire, exclusive current or former use of pipes (n = 15 263 men) or never use of any tobacco product (n = 123 044 men). Analyses were based on 23 589 men who died during 18 years of follow-up. Results: Current pipe smoking, compared with never use of tobacco, was associated with an increased risk of death from cancers of the lung (relative risk [RR] = 5.00, 95% confidence interval [CI] = 4.16 to 6.01), oropharynx (RR = 3.90, 95% CI = 2.15 to 7.08), esophagus (RR = 2.44, 95% CI = 1.51 to 3.95), colorectum (RR = 1.41, 95% CI = 1.15 to 1.73), pancreas (RR = 1.61, 95% CI = 1.24 to 2.09), and larynx (RR = 13.1, 95% CI = 5.2 to 33.1), and from coronary heart disease (RR = 1.30, 95% CI = 1.18 to 1.43), cerebrovascular disease (RR = 1.27, 95% CI = 1.09 to 1.48), and chronic obstructive pulmonary disease (RR = 2.98, 95% CI = 2.17 to 4.11). These risks were generally smaller than those associated with cigarette smoking and similar to or larger than those associated with cigar smoking. Relative risks of lung cancer showed statistically significant increases with number of pipes smoked per day, years of smoking, and depth of inhalation and decreases with years since quitting. Conclusion: Results from this large prospective study suggest that pipe smoking confers a risk of tobacco-associated disease similar to cigar smoking.
Public Health Services and Cost-Effectiveness Analysis
Authors: H. David Banta, G. Ardine de Wit
Journal: Annual Review of Public Health (2008)

Cost-effectiveness analysis as an aid to decision making has been increasingly publicized and discussed during the past two to three decades. However, the total body of cost-effectiveness analyses in health care is actually rather small, and high-quality studies are rather rare. Furthermore, the applications of economic analysis to health policy have been hampered by a number of problems, including those that are methodological and contextual. We consider a number of areas of public health policy but pay special attention to a growing area of inquiry and application: the overall coverage of health services. Cost-effectiveness analysis has played a relatively small role in general coverage decisions, but in recent years, it has been applied increasingly to decisions concerning pharmaceutical coverage. We speculate on concerning reasons for this particular focus in cost-effectiveness analysis. Future progress will depend heavily on discussion and consensus building.
The Evolutionary History of Plasmodium vivax as Inferred from Mitochondrial Genomes: Parasite Genetic Diversity in the Americas
Authors: Jesse E. Taylor, M. Andreína Pacheco, David J. Bacon, Mohammad A. Beg, Ricardo Luiz Machado, Rick M. Fairhurst, Socrates Herrera, Jung-Yeon Kim, Didier Menard, Marinete Marins Póvoa, Leopoldo Villegas, None Mulyanto, Georges Snounou, Liwang Cui, Fadile Yildiz Zeyrek, Ananias A. Escalante
Journal: Molecular Biology and Evolution (2013)

Plasmodium vivax is the most prevalent human malaria parasite in the Americas. Previous studies have contrasted the genetic diversity of parasite populations in the Americas with those in Asia and Oceania, concluding that New World populations exhibit low genetic diversity consistent with a recent introduction. Here we used an expanded sample of complete mitochondrial genome sequences to investigate the diversity of P. vivax in the Americas as well as in other continental populations. We show that the diversity of P. vivax in the Americas is comparable to that in Asia and Oceania, and we identify several divergent clades circulating in South America that may have resulted from independent introductions. In particular, we show that several haplotypes sampled in Venezuela and northeastern Brazil belong to a clade that diverged from the other P. vivax lineages at least 30,000 years ago, albeit not necessarily in the Americas. We propose that, unlike in Asia where human migration increases local genetic diversity, the combined effects of the geographical structure and the low incidence of vivax malaria in the Americas has resulted in patterns of low local but high regional genetic diversity. This could explain previous views that P. vivax in the Americas has low genetic diversity because these were based on studies carried out in limited areas. Further elucidation of the complex geographical pattern of P. vivax variation will be important both for diversity assessments of genes encoding candidate vaccine antigens and in the formulation of control and surveillance measures aimed at malaria elimination.
Soft Lithography in Biology and Biochemistry
Authors: George M. Whitesides, Emanuele Ostuni, Shuichi Takayama, Xingyu Jiang, Donald E. Ingber
Journal: Annual Review of Biomedical Engineering (2001)

▪ Abstract Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in bas-relief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (≥50 μm), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.
The frequency of clones of cytotoxic lymphocytes generated by H-2 antigens.
Authors: J Marbrook, Y Nawa, J F Miller
Journal: The Journal of Experimental Medicine (1978)

By using a culture system that allows the segregation of individual precursors of cytotoxic lymphocytes, the number of clones generated by cells from different combinations of congenic mice have been measured. It has been found that 0.3% of the total anti-H2d clones are generated by stimulators which differ predominantly at the H-2 locus. The contribution of non-H-2 antigens to anti-H-2 responses is discussed.