tbuckley/cabot-search huggingface dataset:
Adherence to surveillance guidelines after removal of colorectal adenomas: a large, community-based study
Authors: Else-Mariëtte B van Heijningen, Iris Lansdorp-Vogelaar, Ewout W Steyerberg, S Lucas Goede, Evelien Dekker, Wilco Lesterhuis, Frank ter Borg, Juda Vecht, Pieter Spoelstra, Leopold Engels, Clemens J M Bolwerk, Robin Timmer, Jan H Kleibeuker, Jan J Koornstra, Harry J de Koning, Ernst J Kuipers, Marjolein van Ballegooijen
Journal: Gut (2015)

<h3>Objective</h3> To determine adherence to recommended surveillance intervals in clinical practice. <h3>Design</h3> 2997 successive patients with a first adenoma diagnosis (57% male, mean age 59 years) from 10 hospitals, who underwent colonoscopy between 1998 and 2002, were identified via Pathologisch Anatomisch Landelijk Geautomatiseerd Archief: Dutch Pathology Registry. Their medical records were reviewed until 1 December 2008. Time to and findings at first surveillance colonoscopy were assessed. A surveillance colonoscopy occurring within ±3 months of a 1-year recommended interval and ±6 months of a recommended interval of 2 years or longer was considered appropriate. The analysis was stratified by period per change in guideline (before 2002: 2–3 years for patients with 1 adenoma, annually otherwise; in 2002: 6 years for 1–2 adenomas, 3 years otherwise). We also assessed differences in adenoma and colorectal cancer recurrence rates by surveillance timing. <h3>Results</h3> Surveillance was inappropriate in 76% and 89% of patients diagnosed before 2002 and in 2002, respectively. Patients eligible under the pre-2002 guideline mainly received surveillance too late or were absent (57% of cases). For patients eligible under the 2002 guideline surveillance occurred mainly too early (48%). The rate of advanced neoplasia at surveillance was higher in patients with delayed surveillance compared with those with too early or appropriate timed surveillance (8% vs 4–5%, p&lt;0.01). <h3>Conclusions</h3> There is much room for improving surveillance practice. Less than 25% of patients with adenoma receive appropriate surveillance. Such practice seriously hampers the effectiveness and efficiency of surveillance, as too early surveillance poses a considerable burden on available resources while delayed surveillance is associated with an increased rate of advanced adenoma and especially colorectal cancer.
β-Arrestin1 Knockout Mice Appear Normal but Demonstrate Altered Cardiac Responses to β-Adrenergic Stimulation
Authors: David. A. Conner, Michael A. Mathier, Richard M. Mortensen, Michael Christe, Stephen F. Vatner, Christine E. Seidman, J. G. Seidman
Journal: Circulation Research (1997)

beta-Arrestin1 knockout mice were studied to define the physiological role of beta-arrestin1 in the regulation of G protein-coupled receptors. beta-Arrestin1 is thought to be involved in the desensitization of many G protein-associated cell surface receptors, particularly beta-adrenergic receptors. Homozygous knockout mice are overtly normal. Resting cardiovascular parameters modulated by beta-adrenergic receptors such as heart rate, blood pressure, and left ventricular ejection fraction are not changed. However, homozygous mutants are more sensitive to beta-receptor agonist-stimulated increases in ejection fraction, consistent with a role of beta-arrestin1 in beta-adrenergic receptor desensitization. We conclude that beta-arrestin1 is important for in vivo G protein-coupled receptor desensitization and that this aspect of desensitization represents a mechanism for fine-tuning responses. However, beta-arrestin1 does not appear to be required for development or for other essential biological functions.
Kidney Injury Accelerates Cystogenesis via Pathways Modulated by Heme Oxygenase and Complement
Authors: Juling Zhou, Xiaosen Ouyang, Trenton R. Schoeb, Subhashini Bolisetty, Xiangqin Cui, Sylvie Mrug, Bradley K. Yoder, Martin R. Johnson, Alexander J. Szalai, Michal Mrug
Journal: Journal of the American Society of Nephrology (2012)

AKI accelerates cystogenesis. Because cystogenic mutations induce strong transcriptional responses similar to those seen after AKI, these responses may accelerate the progression of cystic renal disease. Here, we modulated the severity of the AKI-like response in Cys1(cpk/cpk) mice, a model that mimics autosomal recessive polycystic kidney disease. Specifically, we induced or inhibited activity of the renoprotective enzyme heme oxygenase (HO) and determined the effects on renal cystogenesis. We found that induction of HO attenuated both renal injury and the rate of cystogenesis, whereas inhibition of HO promoted cystogenesis. HO activity mediated the response of NFκB, which is a hallmark transcriptional feature common to both cystogenesis and AKI. Among the HO-modulated effects we measured, expression of complement component 3 (C3) strongly correlated with cystogenesis, a functionally relevant association as suggested by Cys1(cpk/cpk) mice with genetically induced C3 deficiency. Because both C3 deficiency and HO induction reduce cyst number and cyst areas, these two factors define an injury-stimulated cystogenic pathway that may provide therapeutic targets to slow the formation of new renal cysts and the growth of existing cysts.
Effects of a Combined Aerobic and Resistance Exercise Program on C1q/TNF-Related Protein-3 (CTRP-3) and CTRP-5 Levels
Authors: Hae Yoon Choi, Ji Woo Park, Namseok Lee, Soon Young Hwang, Geum Ju Cho, Ho Cheol Hong, Hye Jin Yoo, Taek Geun Hwang, Seon Mi Kim, Sei Hyun Baik, Kyong Soo Park, Byung-Soo Youn, Kyung Mook Choi
Journal: Diabetes Care (2013)

To examine the effect of a combined exercise program on C1q/tumor necrosis factor-related protein (CTRP) 3 and CTRP-5 levels and novel adiponectin paralogs suggested to be links between metabolism and inflammation and to evaluate sex differences and association with cardiometabolic risk factors in humans with use of a newly developed ELISA.This cross-sectional study explored the implications of CTRP-3 and CTRP-5 on cardiometabolic parameters in 453 nondiabetic Korean adults. In addition, we evaluated the impact of a 3-month combined exercise program on CTRP-3 and CTRP-5 levels in 76 obese women. The exercise program consisted of 45 min of aerobic exercise at an intensity of 60-75% of the age-predicted maximum heart rate (300 kcal/session) and 20 min of resistance training (100 kcal/session) five times per week.Both CTRP-3 and CTRP-5 concentrations were significantly higher in women (P<0.001) than in men (P=0.030). In a multiple stepwise regression analysis, CTRP-3 levels were independently associated with age, sex, and triglyceride, LDL cholesterol, adiponectin, and retinol-binding protein 4 (RBP4) levels (R2=0.182). After 3 months of a combined exercise program, cardiometabolic risk factors, including components of metabolic syndrome, insulin resistance, and RBP4 levels, decreased significantly. In particular, CTRP-3 levels decreased significantly (median [interquartile range] 444.3 [373.8-535.0] to 374.4 [297.2-435.9], P<0.001), whereas CTRP-5 levels were slightly increased (34.1 [28.6-44.3] to 38.4 [29.8-55.1], P=0.048).A 3-month combined exercise program significantly decreased CTRP-3 levels and modestly increased CTRP-5 levels in obese Korean women.
SIRT1 deacetylates RORγt and enhances Th17 cell generation
Authors: Hyung W. Lim, Seung Goo Kang, Jae Kyu Ryu, Birgit Schilling, Mingjian Fei, Intelly S. Lee, Amanuel Kehasse, Kotaro Shirakawa, Masaru Yokoyama, Martina Schnölzer, Herbert G. Kasler, Hye-Sook Kwon, Bradford W. Gibson, Hironori Sato, Katerina Akassoglou, Changchun Xiao, Dan R. Littman, Melanie Ott, Eric Verdin
Journal: The Journal of Experimental Medicine (2015)

The authors regret that the labels "Input" and "IP: a-Flag" were switched in the original publication of Fig. 2 (E andF).This has now been corrected in the HTML and PDF versions of the paper.The corrected image also appears below. Cor rectionFigure 2. SIRT1 interacts with RORt.(A) Flag-tagged WT or H363Y mutant SIRT1 was immunoprecipitated from transfected 293T cells and probed as indicated.(B) RORt was immunoprecipitated from thymocytes and Th17 cells, and probed with antibody against SIRT1.(C) Immunoprecipitation using lysates of 293T cells co-transfected with constructs encoding SIRT1 and various deletion mutants of RORt.Relative binding was calculated by normalizing the ratio of immunoprecipitated RORt/SIRT1 to the ratio of input RORt/SIRT1.(D) Acetylation of Flag-tagged RORt immunoprecipitated from 293T cells transfected with various acetyltransferases and Flag-RORt.(E and F) Acetylation of Flag-RORt co-transfected with p300 and WT or H363Y mutant SIRT1, in the absence (E) or in the presence (F) of nicotinamide and Ex-527.Equal amounts of Flag-RORt were loaded (D-F).Representative data are shown from four (A), three (B and E), and two (D) independent experiments, and combined data are shown from three (C and F) independent experiments with error bars representing ±SEM.
Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia
Authors: Xiaobo Xia, Andrew L Kung
Journal: Genome biology (2009)

Hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia. To better understand the determinants of HIF-1 binding and transactivation, we used ChIP-chip and gene expression profiling to define the relationship between the epigenetic landscape, sites of HIF-1 binding, and genes transactivated by hypoxia in two cell lines.We found that when cells were acutely subjected to hypoxia, HIF-1 preferentially bound to loci that were already transcriptionally active under normal growth conditions characterized by the presence of histone H3 lysine 4 methylation, the presence of RNA polymerase II, and basal production of mRNA. Cell type-specific differences in HIF-1 binding were largely attributable to differences in the basal gene expression patterns in the cells prior to the onset of hypoxia.These results suggest that the repertoire of genes active in a cell (for example, through lineage specific transcription factors) defines the subset of genes that are permissive for binding and transactivation by stimulus-responsive transcription factors.
Legal and Ethical Aspects of Psychiatric Research
Authors: HENRY A. DAVIDSON
Journal: American Journal of Psychiatry (1969)

The psychiatric investigator may face dilemmas arising from the ethical obligation to obtain a patient's "fully informed" consent for the use of an experimental drug, a placebo, or a form of therapy that may produce unwanted side effects. Research may also be complicated by the obligation to respect the confidentiality of physician-patient communications. Observing that there are no easy answers to the questions he raises, the author concludes that human responsibility is one of the most important elements in psychiatric research.
Reference values for peak flow and FEV1 variation in healthy schoolchildren using home spirometry
Authors: A. F. J. Brouwer, R. J. Roorda, E. J. Duiverman, P. L. P. Brand
Journal: European Respiratory Journal (2008)

Current reference values for diurnal peak flow variation in healthy children (median 8.2%; 95th percentile 31%) are so high that considerable overlap exists with those of asthmatic children. These values have been obtained using written peak flow diaries, which are unreliable. The aim of the present study was to obtain reliable reference values for the variation in peak flow and forced expiratory volume in one second (FEV 1 ) in healthy schoolchildren using home spirometry with electronic data storage. Healthy schoolchildren (n = 204; 100 males) aged 6–16 yrs measured their peak flow and FEV 1 twice daily for 2 weeks using an electronic home spirometer. The variation in peak flow and FEV 1 were calculated as a diurnal amplitude as a percentage of the day’s mean. The mean peak flow variation was 6.2% (95th percentile 12.3%) and the mean FEV 1 variation was 5.7% (95th percentile 11.8%). Using home spirometry with electronic data storage, healthy schoolchildren show considerably less peak flow and forced expiratory volume in one second variation than previously reported on the basis of written peak flow diaries. Being the 95th percentiles of the distributions in healthy children, a peak flow variation of 12.3% and an forced expiratory volume in one second variation of 11.8% are suggested as cut-off values for disease when using home spirometry.
Use of a Novel Double-Antibody Technique to Describe the Pharmacokinetics of Rapid-Acting Insulin Analogs
Authors: Torbjörn Lindström, Christina A. Hedman, Hans J. Arnqvist
Journal: Diabetes Care (2002)

OBJECTIVE—To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 14 patients with type 1 diabetes, aged 35 ± 13 years (mean ± SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs. RESULTS—The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 ± 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 ± 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 ± 3 min and aspart at 55 ± 6 min after injection (P = 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs. CONCLUSIONS—The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediate-acting insulin given at bedtime.
Phoenix House
Authors: George De Leon
Journal: JAMA (1972)

Percentage of arrests was determined for a sample of 254 addicts who did not complete the Phoenix House Program (dropouts) and 104 who were in the last stages of the program. Results showed that the longer the residence the larger the postprogram reduction, eg, dropouts after 12 months' residence showed a 70% change in arrests in one year of followup. It was concluded that addicts with any residential experience in Phoenix, even those who failed to complete the program, showed sharp reductions in criminal activity during and after leaving the program. These changes relate to rehabilitative aspects of the program.
P-Glycoproteins and Multidrug Resistance
Authors: W T Bellamy
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Multidrug resistance represents a major obstacle in the successful therapy of neoplastic diseases. Studies have demonstrated that this form of drug resistance occurs both in cultured tumor cell lines as well as in human cancers. P-glycoprotein appears to play an important role in such cells by acting as an energy-dependent efflux pump to remove various natural product drugs from the cell before they have a chance to exert their cytotoxic effects. Expression of the MDR1 gene product has been associated with a poor prognosis in clinical studies. It has been demonstrated in the laboratory that resistance mediated by the P-glycoprotein may be modulated by a wide variety of compounds. These compounds, which include verapamil and cyclosporin, generally have little or no effect by themselves on the tumor cells, but when used in conjunction with antineoplastic agents, they decrease, and in some instances eliminate, drug resistance. Clinical trials to modulate P-glycoprotein activity are underway at the present time to determine if such strategies will be feasible. Although the P-glycoprotein is expressed in many cell lines and occurs in patient tumors, its expression is not a universal feature of multidrug resistance, suggesting that other mechanisms are operating.
Plasma Level of Transforming Growth Factor β1 Measured from the Azygos Vein Predicts Prognosis in Patients with Esophageal Cancer
Authors: Minoru Fukuchi, Tatsuya Miyazaki, Yasuyuki Fukai, Masanobu Nakajima, Makoto Sohda, Norihiro Masuda, Ryokuhei Manda, Katsuhiko Tsukada, Hiroyuki Kato, Hiroyuki Kuwano
Journal: Clinical Cancer Research (2004)

Transforming growth factor (TGF)-beta regulates cell growth inhibition. When tumor cells lose their sensitivity to TGF-beta growth inhibition, the excess TGF-beta that results may act on tumor cells to facilitate tumor development. Previously, we have shown that an elevated systemic TGF-beta 1 level is not related to tumor progression in esophageal cancer (Y. Fukai et al., Int J Cancer 2003;104:161-6). We considered that systemic inflammation or chronic disease, in addition to the tumor, may influence the plasma TGF-beta level. Therefore, we examined the hypothesis that the plasma TGF-beta level measured from the azygos vein would independently predict tumor progression and prognosis in patients with esophageal cancer.Fifty-seven plasma samples were obtained intraoperatively from the azygos vein in patients with esophageal cancer. ELISA was used to quantify the plasma TGF-beta 1 levels, which were correlated with pathological features and patient survival.The mean plasma TGF-beta 1 level measured from the azygos vein of esophageal cancer patients was 5.09 +/- 0.48 ng/ml (mean +/- SE). The survival rates of patients with a high TGF-beta 1 level (defined as a level above the 4.6 ng/ml level of normal controls) in the azygos vein were significantly lower than those of patients with a low TGF-beta 1 level (P = 0.0317). Moreover, the TGF-beta 1 level in the azygos vein was an independent prognostic factor for overall survival (P = 0.0474).The level of plasma TGF-beta 1 measured from the azygos vein is an independent predictor in patients with esophageal cancer and may reflect tumor progression more specifically because the azygos vein is responsible for venous return from the esophagus.
Involvement of Hepcidin in the Anemia of Multiple Myeloma
Authors: Sanjai Sharma, Elizabeta Nemeth, Yi-Hsiang Chen, Julia Goodnough, Alissa Huston, G.D. Roodman, Tomas Ganz, Alan Lichtenstein
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Hepcidin is a liver-produced peptide implicated in the anemia of inflammation. Because interleukin (IL)-6 is a potent inducer of hepcidin expression and its levels are elevated in multiple myeloma, we studied the role of hepcidin in the anemia of multiple myeloma. Experimental Design: Urinary hepcidin and serum levels of IL-6, ferritin, C-reactive protein, tumor necrosis factor-α, and IL-1β were studied in newly diagnosed myeloma patients. In vitro hepcidin induction assay was assessed by real-time PCR assay. Results: Pretreatment urinary hepcidin levels in 44 patients with stage III multiple myeloma were 3-fold greater than normal controls. In the subset of multiple myeloma patients without renal insufficiency (n = 27), a marked inverse correlation was seen between hemoglobin at diagnosis and urinary hepcidin level (P = 0.014) strongly supporting a causal relationship between up-regulated hepcidin expression and anemia. The urinary hepcidin also significantly (P &amp;lt; 0.05) correlated with serum ferritin and C-reactive protein, whereas its correlation with serum IL-6 levels was of borderline significance (P = 0.06). Sera from 14 multiple myeloma patients, with known elevated urinary hepcidin, significantly induced hepcidin mRNA in the Hep3B cells, whereas normal sera had no effect. For 10 patients, the ability of anti-IL-6 and anti-IL-6 receptor antibodies to prevent the serum-induced hepcidin RNA was tested. In 6 of these patients, hepcidin induction was abrogated by the anti-IL-6 antibodies, but in the other 4 patients, the neutralizing antibodies had no effect. Conclusions: These results indicate hepcidin is up-regulated in multiple myeloma patients by both IL-6-dependent and IL-6-independent mechanisms and may play a role in the anemia of multiple myeloma.
Evolution of protein complexes by duplication of homomeric interactions
Authors: Jose B Pereira-Leal, Emmanuel D Levy, Christel Kamp, Sarah A Teichmann
Journal: Genome biology (2007)

Cellular functions are accomplished by the concerted actions of functional modules. The mechanisms driving the emergence and evolution of these modules are still unclear. Here we investigate the evolutionary origins of protein complexes, modules in physical protein-protein interaction networks.We studied protein complexes in Saccharomyces cerevisiae, complexes of known three-dimensional structure in the Protein Data Bank and clusters of pairwise protein interactions in the networks of several organisms. We found that duplication of homomeric interactions, a large class of protein interactions, frequently results in the formation of complexes of paralogous proteins. This route is a common mechanism for the evolution of complexes and clusters of protein interactions. Our conclusions are further confirmed by theoretical modelling of network evolution. We propose reasons for why this is favourable in terms of structure and function of protein complexes.Our study provides the first insight into the evolution of functional modularity in protein-protein interaction networks, and the origins of a large class of protein complexes.