tbuckley/cabot-search huggingface dataset:
EBV Is Necessary for Proliferation of Dually Infected Primary Effusion Lymphoma Cells
Authors: Amanda A. Mack, Bill Sugden
Journal: Cancer Research (2008)

Abstract Epstein Barr virus (EBV) and Kaposi's sarcoma–associated herpesvirus (KSHV) are found together in ∼80% of primary effusion lymphomas (PEL), but their contribution to these cancers is unclear. We found that dominant-negative derivatives of EBNA1 inhibited EBV-positive PEL cells from forming colonies. Those rare PEL cells that proliferated after expression of the dominant-negative derivatives usually expressed these derivatives at low or undetectable levels and continued to maintain their EBV genomes. Those proliferating cells expressing higher levels of the derivatives expressed mutant derivatives that could not bind DNA. These findings indicate that EBV is required to sustain proliferation, as measured by colony formation of dually infected PEL cells. The dominant-negative derivatives of EBNA1 had no effect on the colony-forming ability of five EBV-negative, KSHV-negative hematopoietic cell lines. Surprisingly, they did inhibit the colony-forming ability of EBV-negative, KSHV-positive PEL cells. The small fraction of cells that continued to proliferate expressed only mutants of the EBNA1 derivatives that could no longer bind DNA. These findings indicate that the site-specific DNA-binding activity of EBNA1 or its derivatives when expressed efficiently in EBV-negative, KSHV-positive PEL cells inhibits their colony formation possibly through their binding to the KSHV genome. [Cancer Res 2008;68(17):6963–8]
CREB AND MEMORY
Authors: Alcino J. Silva, Jeffrey H. Kogan, Paul W. Frankland, Satoshi Kida
Journal: Annual Review of Neuroscience (1998)

▪ Abstract The cAMP responsive element binding protein (CREB) is a nuclear protein that modulates the transcription of genes with cAMP responsive elements in their promoters. Increases in the concentration of either calcium or cAMP can trigger the phosphorylation and activation of CREB. This transcription factor is a component of intracellular signaling events that regulate a wide range of biological functions, from spermatogenesis to circadian rhythms and memory. Here we review the key features of CREB-dependent transcription, as well as the involvement of CREB in memory formation. Evidence from Aplysia, Drosophila, mice, and rats shows that CREB-dependent transcription is required for the cellular events underlying long-term but not short-term memory. While the work in Aplysia and Drosophila only involved CREB function in very simple forms of conditioning, genetic and pharmacological studies in mice and rats demonstrate that CREB is required for a variety of complex forms of memory, including spatial and social learning, thus indicating that CREB may be a universal modulator of processes required for memory formation.
Timing and Consequences of Recurrent Polyploidy in Meadow-Rues (Thalictrum, Ranunculaceae)
Authors: Valerie L. Soza, Kendall L. Haworth, Verónica S. Di Stilio
Journal: Molecular Biology and Evolution (2013)

The discovery of ancient whole-genome duplications in eukaryotic lineages has renewed the interest in polyploidy and its effects on the diversification of organisms. Polyploidy has large-scale effects on both genotype and phenotype and has been linked to the evolution of genome size, dioecy, and changes in ecological interactions, such as pollinator visitation. Here, we take a molecular systematics approach to examine the evolution of polyploidy in the plant genus Thalictrum (Ranunculaceae) and test its correlation to changes in genome size, sexual system, and pollination mode. Thalictrum is an ideal study system due to its extensive ploidy range and floral diversity. Phylogenetic analyses were used for character reconstructions, correlation tests, and dating estimates. Our results suggest that polyploidization occurred frequently and recently in the evolution of Thalictrum, mostly within the last 10.6–5.8 My, coinciding with the diversification of particular clades. In spite of an overall trend of genomic downsizing accompanying polyploidy in angiosperms and proportional increases observed at finer scales, our genome size estimates for Thalictrum show no correlation with chromosome number. Instead, we observe genomic expansion in diploids and genomic contraction in polyploids with increased age. Additionally, polyploidy is not correlated with dioecy in Thalictrum; therefore, other factors must have influenced the evolution of separate sexes in this group. A novel finding from our study is the association of polyploidy with shifts to wind pollination, in particular, during a time period of global cooling and mountain uplift in the Americas.
PSYCHOSES IN THE COLORED RACE
Authors: MARY O'MALLEY
Journal: American Journal of Psychiatry (1914)

1. As to the facts brought out, the tables show the conclusion is warranted that in the colored race a large increase of mental disorder is obvious since their attainment of freedom, and that, too, in localities favorable to the race. 2. That the mental mechanism in the given psychoses does not essentially differ in the two races. 3. That the dementia precox type is the preponderant mental disease entity among the colored, but it is not excessively disproportionate to the same manifestations in the whites; that there is an excess of the hebephrenic type in both races; that the number of catatonics in the colored exceeds the number in the whites, and that there are more of the paranoid type in the whites than in the colored. 4. That manic-depressive psychosis is not as prevalent among the colored as in the whites, and that in the colored the excited phase of this psychosis is more frequently observed, while the depressive types are not so common. 5. That involutional melancholia and depressions of various forms are rare in the colored, as these individuals do not react to the graver emotions—grief, remorse, etc.—owing to the fact that they have no strict moral standard and no scrupulosity as to social conventions; the absence of self-depreciatory ideas of sin, etc., is most noticeable. 6. That the prevalence of syphilis in the colored race has had a marked influence on certain types of mental disorder, as general paresis, cerebral syphilis and other luetic infections, and that these are very much in excess of the same diseases in the whites. 7. That while the colored race indulge in and imbibe large quantities of alcohol, they are in a degree immune to its influence and the reaction to its toxic effects is less lasting. 8. That paranoid conditions are present, but that true paranoia is rare, especially among the colored women. 9. That hysteria is a disease which is rare in the colored.
Benefits at 3 yrs of an asthma education programme coupled with regular reinforcement
Authors: J-M. Ignacio-García, M. Pinto-Tenorio, M.J. Chocrón-Giraldez, F. Cabello-Rueda, A.I. López-Cozar Gil, J-M. Ignacio-García, E. de Ramón-Garrido
Journal: European Respiratory Journal (2002)

The benefits at 3 yrs of an asthma self-management education programme coupled with educational reinforcement were assessed at follow-up visits in 63 adults with chronic asthma. Changes in asthma-related morbidity parameters, lung function and use of different classes of drugs before intervention and after 1, 2 and 3 yrs of the asthma education programme were compared using Friedman one-way analysis of variance. Improvements in the number of days off work or school, general practitioner consultations, admissions to emergency services, hospital admissions and nocturnal awakenings, as well as increases in forced expiratory volume in one second (FEV 1 ), were significant. Comparison of data obtained at 1 yr and 2–3 yrs showed significant differences in the number of asthma-associated sleep disruptions, days off work or school and unscheduled visits to the general practitioner, as well as FEV 1 , but significant differences between the data obtained at 2 and 3 yrs were not observed. The percentage of patients using oral steroids had decreased significantly at 3 yrs. In adults with chronic asthma, an asthma self-management education programme coupled with educational reinforcement was effective at decreasing asthma morbidity, improving lung function and decreasing consumption of oral steroids.
Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells
Authors: Robert E. Hunger, Peter A. Sieling, Maria Teresa Ochoa, Makoto Sugaya, Anne E. Burdick, Thomas H. Rea, Patrick J. Brennan, John T. Belisle, Andrew Blauvelt, Steven A. Porcelli, Robert L. Modlin
Journal: Journal of Clinical Investigation (2004)

Langerhans cells (LCs) constitute a subset of DCs that initiate immune responses in skin. Using leprosy as a model, we investigated whether expression of CD1a and langerin, an LC-specific C-type lectin, imparts a specific functional role to LCs. LC-like DCs and freshly isolated epidermal LCs presented nonpeptide antigens of Mycobacterium leprae to T cell clones derived from a leprosy patient in a CD1a-restricted and langerin-dependent manner. LC-like DCs were more efficient at CD1a-restricted antigen presentation than monocyte-derived DCs. LCs in leprosy lesions coexpress CD1a and langerin, placing LCs in position to efficiently present a subset of antigens to T cells as part of the host response to human infectious disease.
Phosphorylation of Estrogen Receptor α Blocks Its Acetylation and Regulates Estrogen Sensitivity
Authors: Yukun Cui, Mao Zhang, Richard Pestell, Edward M. Curran, Wade V. Welshons, Suzanne A. W. Fuqua
Journal: Cancer Research (2004)

Abstract Estrogen receptor (ER) α is mutated (lysine 303 to arginine, K303R) in approximately one third of premalignant breast hyperplasias, which renders breast cancer cells expressing the mutant receptor hypersensitive for proliferation in response to low doses of estrogen. It is known that ERα is posttranslationally modified by protein acetylation and phosphorylation by a number of secondary messenger signaling cascades. The K303R ERα mutation resides at a major protein acetylation site adjacent to a potential protein kinase A (PKA) phosphorylation site at residue 305 within the hinge domain of the receptor. Mutation of this phosphorylation site to aspartic acid to mimic constitutive phosphorylation blocks acetylation of the K303 ERα site and generates an enhanced transcriptional response similar to that seen with the naturally occurring K303R mutant receptor. Activation of PKA signaling by the cell-permeable cyclic AMP (cAMP) analog 8-bromo-cAMP further enhances estrogen sensitivity of the mutant receptor, whereas a specific PKA inhibitor antagonizes this increase. We propose that the hypersensitive ERα mutant breast cancer phenotype involves an integration of coupled acetylation and phosphorylation events by upstream signaling molecules.
A Specific CD36-Dependent Signaling Pathway Is Required for Platelet Activation by Oxidized Low-Density Lipoprotein
Authors: Kan Chen, Maria Febbraio, Wei Li, Roy L. Silverstein
Journal: Circulation Research (2008)

Platelet hyperactivity associated with hyperlipidemia may contribute to development of a prothrombotic state. We previously showed that oxidized low-density lipoprotein (oxLDL) formed in the setting of hyperlipidemia and atherosclerosis activated platelets in a CD36-dependent manner. We now show that mitogen-activated protein kinase c-Jun N-terminal kinase (JNK)2 and its upstream activator MKK4 were phosphorylated in platelets exposed to oxLDL. Using apoE(-/-) mice as a model of hyperlipidemia, we showed that JNK was constitutively phosphorylated in platelets in a CD36-dependent manner. Inhibition of src kinase activity reduced JNK phosphorylation by oxLDL. Immunoprecipitations revealed that active phosphorylated forms of src kinases Fyn and Lyn were recruited to CD36 in platelets exposed to oxLDL. Pharmacological inhibition of the mitogen-activated protein kinase JNK or src family kinases abolished platelet activation by oxLDL in vitro. Using a murine carotid artery thrombosis model we demonstrated CD36-dependent phosphorylation of platelet JNK within thrombi. Furthermore, pharmacological inhibition of JNK prolonged thrombosis times in wild-type but not cd36-null mice in vivo. These findings suggest that a specific CD36-dependent signaling pathway is required for platelet activation by oxLDL and may provide insights related to development of novel antiplatelet therapies more relevant to atherothrombosis than to normal hemostasis.
Immunology of Insulin-Dependent Diabetes Mellitus
Authors: Aldo A. Rossini, John P. Mordes, Arthur A. Like
Journal: Annual Review of Immunology (1985)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Effect of hydrostatic pressure on isolated cardiac nuclei: stimulation of RNA polymerase II activity
Authors: S. S. SCHREIBER, M. ORATZ, M. A. ROTHSCHILD, F. REFF
Journal: Cardiovascular Research (1978)

Journal Article Effect of hydrostatic pressure on isolated cardiac nuclei: stimulation of RNA polymerase II activity Get access SIDNEY S. SCHREIBER, SIDNEY S. SCHREIBER 1 From the Department of Nuclear Medicine, Veterans Administration Hospital, New York, Department of Medicine, New York University Medical Center, and Department of Biochemistry, New York University School of Dentistry 1Address for reprints: Dr Sidney S. Schreiber, Department of Nuclear Medicine, Veterans Administration Hospital, 24th Street and First Avenue, New York, NY 10010, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar MURRAY ORATZ, MURRAY ORATZ From the Department of Nuclear Medicine, Veterans Administration Hospital, New York, Department of Medicine, New York University Medical Center, and Department of Biochemistry, New York University School of Dentistry Search for other works by this author on: Oxford Academic PubMed Google Scholar MARCUS A. ROTHSCHILD, MARCUS A. ROTHSCHILD From the Department of Nuclear Medicine, Veterans Administration Hospital, New York, Department of Medicine, New York University Medical Center, and Department of Biochemistry, New York University School of Dentistry Search for other works by this author on: Oxford Academic PubMed Google Scholar FRANCINE REFF FRANCINE REFF From the Department of Nuclear Medicine, Veterans Administration Hospital, New York, Department of Medicine, New York University Medical Center, and Department of Biochemistry, New York University School of Dentistry Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 12, Issue 5, May 1978, Pages 265–268, https://doi.org/10.1093/cvr/12.5.265 Published: 01 May 1978
Effects of Dietary Cholesterol on Hepatic Production of Lipids and Lipoproteins in Isolated Hamster Liver
Authors: J Chen, W Song, R N Redinger
Journal: Hepatology (1996)

The effect of 2-week 2% cholesterol vs. chow feeding on regulation of hepatic lipoprotein, lipids and apoprotein (Apo), and biliary lipids production was evaluated by the isolated perfused hamster liver model. Cholesterol feeding did not change very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle size but significantly increased the hepatic production of VLDL-cholesterol fourfold, VLDL-triglyceride two and one-half-fold but not phospholipid in VLDL. It also increased LDL-cholesterol fourfold but not triglyceride or phospholipid in LDL, whereas lipids in HDL remained unchanged. Gradient sodium dodecyl sulfate-polyacrylamide gel electrophesis (SDS-PAGE) and Western blot analysis (density of apoprotein/density of albumin/g liver) indicated that cholesterol feeding enhanced Apo B tenfold, Apo A-I fivefold but not Apo E in VLDL. Apo E and Apo B did not change in LDL. Apo E but not Apo A-I increased (threefold) in HDL by cholesterol feeding. Cholesterol feeding decreased bile salt secretion 28% but increased cholesterol secretion 118% in bile, whereas phospholipid and bile volume remained unchanged. Increased Apo A-I in VLDL suggested that Apo A-I is involved in enhanced hepatic export of cholesterol and triglyceride. Different patterns of lipid and Apos in VLDL and LDL after cholesterol feeding also suggested separate VLDL and LDL export mechanisms. Elevated Apo E but not lipids in HDL after cholesterol feeding suggests that hepatic HDL may function as a carrier of newly synthesized hepatic Apo E into the circulation for transfer to other lipoproteins (chylomicron [CM], CMr) to facilitate hepatic cholesterol uptake and clearance.
Animal models of human cardiovascular disease, heart failure and hypertrophy
Authors: G Hasenfuss
Journal: Cardiovascular Research (1998)

The progress made in our understanding of the pathophysiology and treatment of congestive heart failure (CHF) would not have been possible without a number of animal models of heart failure and hypertrophy, each one having unique advantages as well as disadvantages. The species and interventions used to create CHF depends on the scientific question as well as on factors such as ethical and economical considerations, accessibility and reproducibility or the model. How closely the model should mimic the human syndrome of CHF depends on the scientific question under investigation. If the goal is to study pathophysiological processes like remodeling or the function of subcellular systems such as excitation contraction-coupling processes, contractile protein function or energetics, the model of heart failure should mimic the clinical setting as closely as possible. However, if defined causal connections are under investigation such as structure–function analyses or regulation of gene expression, exact reflection of the clinical setting by the animal model may be less important. In this review, animal models of heart failure are discussed with particular focus on similarities between the animal model and the failing human heart regarding myocardial function as well as molecular and subcellular mechanisms. In addition, new models of heart failure and hypertrophy, and finally some recent animal models of myocarditis are reviewed.
Common Genetic Variants Associate with Serum Phosphorus Concentration
Authors: Bryan Kestenbaum, Nicole L. Glazer, Anna Köttgen, Janine F. Felix, Shih-Jen Hwang, Yongmei Liu, Kurt Lohman, Stephen B. Kritchevsky, Dorothy B. Hausman, Ann-Kristin Petersen, Christian Gieger, Janina S. Ried, Thomas Meitinger, Tim M. Strom, H. Erich Wichmann, Harry Campbell, Caroline Hayward, Igor Rudan, Ian H. de Boer, Bruce M. Psaty, Kenneth M. Rice, Yii-Der Ida Chen, Man Li, Dan E. Arking, Eric Boerwinkle, Josef Coresh, Qiong Yang, Daniel Levy, Frank J.A. van Rooij, Abbas Dehghan, Fernando Rivadeneira, André G. Uitterlinden, Albert Hofman, Cornelia M. van Duijn, Michael G. Shlipak, W.H. Linda Kao, Jacqueline C.M. Witteman, David S. Siscovick, Caroline S. Fox
Journal: Journal of the American Society of Nephrology (2010)

Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.
Effects of Selective Checkpoint Kinase 1 Inhibition on Cytarabine Cytotoxicity in Acute Myelogenous Leukemia Cells <i>In Vitro</i>
Authors: Erin L. Schenk, Brian D. Koh, Karen S. Flatten, Kevin L. Peterson, David Parry, Allan D. Hess, B. Douglas Smith, Judith E. Karp, Larry M. Karnitz, Scott H. Kaufmann
Journal: Clinical Cancer Research (2012)

Previous studies have shown that the replication checkpoint, which involves the kinases ataxia telangiectasia mutated and Rad3 related (ATR) and Chk1, contributes to cytarabine resistance in cell lines. In the present study, we examined whether this checkpoint is activated in clinical acute myelogenous leukemia (AML) during cytarabine infusion in vivo and then assessed the impact of combining cytarabine with the recently described Chk1 inhibitor SCH 900776 in vitro.AML marrow aspirates harvested before and during cytarabine infusion were examined by immunoblotting. Human AML lines treated with cytarabine in the absence or presence of SCH 900776 were assayed for checkpoint activation by immunoblotting, nucleotide incorporation into DNA, and flow cytometry. Long-term effects in AML lines, clinical AML isolates, and normal myeloid progenitors were assayed using clonogenic assays.Immunoblotting revealed increased Chk1 phosphorylation, a marker of checkpoint activation, in more than half of Chk1-containing AMLs after 48 hours of cytarabine infusion. In human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation and S-phase arrest but also markedly increased cytarabine-induced apoptosis. Clonogenic assays demonstrated that SCH 900776 enhanced the antiproliferative effects of cytarabine in AML cell lines and clinical AML samples at concentrations that had negligible impact on normal myeloid progenitors.These results not only provide evidence for cytarabine-induced S-phase checkpoint activation in AML in the clinical setting, but also show that a selective Chk1 inhibitor can overcome the S-phase checkpoint and enhance the cytotoxicity of cytarabine. Accordingly, further investigation of the cytarabine/SCH 900776 combination in AML appears warranted.
Preoperative Biliary Drainage for Cancer of the Head of the Pancreas
Authors: Niels A. van der Gaag, Erik A.J. Rauws, Casper H.J. van Eijck, Marco J. Bruno, Erwin van der Harst, Frank J.G.M. Kubben, Josephus J.G.M. Gerritsen, Jan Willem Greve, Michael F. Gerhards, Ignace H.J.T. de Hingh, Jean H. Klinkenbijl, Chung Y. Nio, Steve M.M. de Castro, Olivier R.C. Busch, Thomas M. van Gulik, Patrick M.M. Bossuyt, Dirk J. Gouma
Journal: New England Journal of Medicine (2010)

The benefits of preoperative biliary drainage, which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head, are unclear.