tbuckley/cabot-search huggingface dataset:
Chemosensitization of B-Cell Lymphomas by Methylseleninic Acid Involves Nuclear Factor-κB Inhibition and the Rapid Generation of Other Selenium Species
Authors: Simone Jüliger, Heidi Goenaga-Infante, T. Andrew Lister, Jude Fitzgibbon, Simon P. Joel
Journal: Cancer Research (2007)

Abstract Although recent reports suggest that selenium can modulate the activity of cytotoxic drugs, the mechanism underlying this activity remains unclear. This has been investigated using a panel of human B-cell lymphoma cell lines. The cytotoxic effects of chemotherapeutic agents (e.g., doxorubicin, etoposide, 4-hydroperoxycyclophosphamide, melphalan, and 1-β-d-arabinofuranosylcytosine) were increased by up to 2.5-fold when combined with minimally toxic concentrations (EC5-10) of the organic selenium compound, methylseleninic acid (MSA). DNA strand breaks were identified using comet assays, but the measured genotoxic activity of the combinations did not explain the observed synergistic effects in cell death. However, minimally toxic (EC10) concentrations of MSA induced a 50% decrease in nuclear factor-κB (NF-κB) activity after an exposure of 5 h, similar to that obtained with the specific NF-κB inhibitor, BAY 11-7082. Combinations of BAY 11-7082 with these cytotoxic drugs also resulted in synergism, suggesting that the chemosensitizing activity of MSA is mediated, at least in part, by its effects on NF-κB. Basal intracellular selenium concentration was higher in a MSA-sensitive cell line. After exposure to MSA, methylselenocysteine and selenomethionine were identified as the main intracellular species generated. Volatile selenium species, trapped using solid-phase microextraction fibers, were identified as dimethylselenide and dimethyldiselenide. These volatile species are thought to be the most biologically active forms of selenium. Taken together, these results show that the NF-κB pathway is one target for MSA underlying the interaction between MSA and chemotherapy. These data encourage the further clinical development of selenium as a potential modulator of cytotoxic drug activity in B-cell lymphomas. [Cancer Res 2007;67(22):10984–92]
A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination
Authors: Elin Enervald, Likun Du, Torkild Visnes, Andrea Björkman, Emma Lindgren, Josephine Wincent, Guntram Borck, Laurence Colleaux, Valerie Cormier-Daire, Dik C. van Gent, Juan Pie, Beatriz Puisac, Noel FCC de Miranda, Sven Kracker, Lennart Hammarström, Jean-Pierre de Villartay, Anne Durandy, Jacqueline Schoumans, Lena Ström, Qiang Pan-Hammarström
Journal: The Journal of Experimental Medicine (2013)

DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR.
TREATMENT OF THE SMALL INTESTINE IN OPERATIONS FOR INTESTINAL OBSTRUCTION
Authors: C. H. Whiteford
Journal: BMJ (1909)

<h3>Objective</h3> P-cadherin can act both as a tumour suppressor and an oncogene. The clinical prognostic value of P-cadherin overexpression in breast cancer (BC) remains unclear. We conducted a study-level meta-analysis to determine whether P-cadherin expression can help predict prognosis in BC. <h3>Methods</h3> A systematic literature search was performed to review eligible studies and clarify the relationship between P-cadherin overexpression and overall survival (OS), disease-free survival (DFS), pathological features, molecular subtypes and molecular phenotypes in BC. <h3>Results</h3> Thirty-one studies including 12 332 patients were included. P-cadherin overexpression was correlated with significantly worse OS (HR=1.77, p&lt;0.00001) and DFS (HR=1.96, p<i>&lt;</i>0.00001) than P-cadherin-negative. P-cadherin overexpression could lead to high histological grade (OR=3.33, p&lt;0.00001) and lymph node metastasis (OR=1.62, p&lt;0.00001). Moreover, P-cadherin overexpression was associated with low odds of the luminal A subtype and high odds of the human epidermal growth factor receptor-2 (HER2)-positive and triple-negative subtypes. P-cadherin expression led to low expression of oestrogen and progesterone receptor (OR=0.37 and OR=0.36, respectively, both p&lt;0.00001) and high expression of HER2 (OR=2.31, p&lt;0.00001), Ki-67 (OR=2.79, p&lt;0.00001), epidermal growth factor receptor (OR=5.85, p&lt;0.00001) and cytokeratin 5/6 (OR=6.79, p&lt;0.00001). <h3>Conclusions</h3> P-cadherin was found to be associated with invasiveness and metastasis. P-cadherin expression can probably be a useful biomarker for predicting poor survival and may act as an independent prognostic predictor.
Evaluation of plasma MMP-8, MMP-9 and TIMP-1 identifies candidate cardiometabolic risk marker in metabolic syndrome: results from double-blinded nested case–control study
Authors: Seyed Mehdi Hoseini, Ali Kalantari, Mohsen Afarideh, Sina Noshad, Aram Behdadnia, Manouchehr Nakhjavani, Alireza Esteghamati
Journal: Metabolism (2014)
Use of the General Practice Research Database (GPRD) for respiratory epidemiology: a comparison with the 4th Morbidity Survey in General Practice (MSGP4)
Authors: A. Hansell, J. Hollowell, T. Nichols, R. McNiece, D. Strachan
Journal: Thorax (1999)

<h3>Background and objectives</h3> Sedentary behavior is associated with increased mortality in the general population. Whether replacing sedentary behavior with low- or light-intensity activities confers a survival benefit in the general or CKD populations is unknown. <h3>Design, setting, participants, &amp; measurements</h3> This observational analysis of the 2003–2004 National Health and Nutrition Examination Survey examined the associations of low- and light-intensity activities with mortality. On the basis of the number of counts/min recorded by an accelerometer, durations of sedentary (&lt;100/min), low (100–499/min), light (500–2019/min), and moderate/vigorous (≥2020/min) activity were defined and normalized to 60 minutes. The mortality associations of 2 min/hr less sedentary duration in conjunction with 2 min/hr more (tradeoff) spent in one of the low, light, or moderate/vigorous activity durations while controlling for the other two activity durations were examined in multivariable Cox regression models in the entire cohort and in the CKD subgroup. <h3>Results</h3> Of the 3626 participants included, 383 had CKD. The mean sedentary duration was 34.4±7.9 min/hr in the entire cohort and 40.8±6.8 in the CKD subgroup. Tradeoff of sedentary duration with low activity duration was not associated with mortality in the entire cohort or the CKD subgroup. Tradeoff of sedentary duration with light activity duration was associated with a lower hazard of death in the entire cohort (hazard ratio, 0.67; 95% confidence interval, 0.48 to 0.93) and CKD subgroup (hazard ratio, 0.59; 95% confidence interval, 0.35 to 0.98). Tradeoff of sedentary duration with moderate/vigorous activity duration had a nonsignificant lower hazard in the entire cohort and CKD subgroup. <h3>Conclusions</h3> Patients with CKD are sedentary nearly two thirds of the time. Interventions that replace sedentary duration with an increase in light activity duration might confer a survival benefit.
On a New Remedy in Certain Forms of Skin-Disease
Authors: J. I. Murray
Journal: BMJ (1877)

THE -BRITISH MEDICAL 7OURNAL.6o9the acid, fifteen minims of liquor potassae, and three ounces of water, allowed to digest during three days.Their action was so evident, that I found it impossible to use any more so large doses.I, therefore, made seven other observations on the effect of similar draughts con- taining only six grains, and I found them to take all the effect which a dose of fifteen grains given as powder takes.I made sixty observations with pills containing either the acid or the crude powder combined with confection of roses.I confine my remarks to those containing the acid, since I observe no essential difference in action between them.Each pill contained four grains of chrysophanic acid.I find the action of the drug in this form more uniform than in any other, except that of an alkaline draught.Eight grains are suffi- cient to take with effect in both kinds upon the majority of persons.Action is delayed almost invariably beyond two hours; often, if sleep intervene, the dose taken at night does not-operate until the next morn- ing.In that case, sickness, as always, is the first effect, but the
Myeloid-Derived Suppressor Cells Enhance Stemness of Cancer Cells by Inducing MicroRNA101 and Suppressing the Corepressor CtBP2
Authors: Tracy X. Cui, Ilona Kryczek, Lili Zhao, Ende Zhao, Rork Kuick, Michael H. Roh, Linda Vatan, Wojciech Szeliga, Yujun Mao, Dafydd G. Thomas, Jan Kotarski, Rafał Tarkowski, Max Wicha, Kathleen Cho, Thomas Giordano, Rebecca Liu, Weiping Zou
Journal: Immunity (2013)
Fast Measurement of Sarcomere Length and Cell Orientation in Langendorff-Perfused Hearts Using Remote Focusing Microscopy
Authors: Edward J. Botcherby, Alex Corbett, Rebecca A.B. Burton, Chris W. Smith, Christian Bollensdorff, Martin J. Booth, Peter Kohl, Tony Wilson, Gil Bub
Journal: Circulation Research (2013)

Sarcomere length (SL) is a key indicator of cardiac mechanical function, but current imaging technologies are limited in their ability to unambiguously measure and characterize SL at the cell level in intact, living tissue.We developed a method for measuring SL and regional cell orientation using remote focusing microscopy, an emerging imaging modality that can capture light from arbitrary oblique planes within a sample.We present a protocol that unambiguously and quickly determines cell orientation from user-selected areas in a field of view by imaging 2 oblique planes that share a common major axis with the cell. We demonstrate the effectiveness of the technique in establishing single-cell SL in Langendorff-perfused hearts loaded with the membrane dye di-4-ANEPPS.Remote focusing microscopy can measure cell orientation in complex 2-photon data sets without capturing full z stacks. The technique allows rapid assessment of SL in healthy and diseased heart experimental preparations.
IL6 and dendritic cells in allergic asthma
Authors: C E Fletcher
Journal: Thorax (2008)

Interleukin (IL)6 production by antigen-presenting dendritic cells (DCs) is integral to the differentiation of T helper cells into T helper type Th1, Th2 and Th17 subsets. However, molecular mechanisms that regulate IL6 production in DCs are yet to be elucidated. Stimulation of bone marrow-derived dendritic cells with the allergen house dust mite (HDM)—which causes asthma in humans—or the mucosal …
Stent Strut Thickness and Restenosis
Authors: John A. Ormiston, Mark W.I. Webster, Peter N. Ruygrok
Journal: Circulation (2002)

To the Editor:Kastrati et al recently reported 1 significantly less restenosis with lesions randomized to deployment of one stent design (ACS RX Multi-Link, [ML]) than with a related design (Multi-Link RX Duet, [DT]) from the same manufacturer (Guidant).They attributed the difference in restenosis to the difference in strut thickness.Although the two stent designs do differ significantly in strut thickness, there are other differences in design and mechanical properties that might impact on restenosis.The DT has greater radial strength: when tested in vitro in a pressure chamber, the DTs collapsed at a higher pressure (1.81Ϯ0.01atm) than the MLs (0.77Ϯ0.03 atm, PϽ0.05) (unpublished observations).Some experimental data suggest that greater stent hoop strength may cause increased neoimtimal proliferation. 2 The extent of metal coverage of vessel wall is greater for the ML (22.3%) than for the DT (16.5%).The gap size or uncovered area between the stent struts also differs.The ML has gaps of one size (area 3.3Ϯ0.1 mm 2 ) whereas the DT has gaps of two sizes, one similar in size (3.3Ϯ0.4 mm 2 ) to the ML and one bigger (4.9Ϯ0.4 mm 2 , Pϭ0.01) (unpublished observations).The larger-sized gaps may allow greater tissue prolapse and increased restenosis analogous to the original Palmaz-Schatz stent where restenosis occurred mostly at the articulation site. 3 On the other hand, we found no differences between the ML and the DT for expanded stent flexibility 4 or for acute recoil, so these do not explain the difference in restenosis rates.Besides strut thickness, there are other differences in mechanical and physical properties between the expanded ML and DT stents that are equally plausible explanations for the differences in restenosis rates between the two designs.These differences may have implications for the design of stents with low restenosis rates.
The Nuclear Receptor Interacting Factor-3 Transcriptional Coregulator Mediates Rapid Apoptosis in Breast Cancer Cells through Direct and Bystander-Mediated Events
Authors: Sharmistha Das, Jerome C. Nwachukwu, Dangsheng Li, Anthony I. Vulin, Sonia Martinez-Caballero, Kathleen W. Kinnally, Herbert H. Samuels
Journal: Cancer Research (2007)

Abstract We previously reported that amino acids 20 to 50 of nuclear receptor interacting factor-3 mediates rapid apoptosis in breast cancer cell lines but not in cells derived from other tissues. We refer to this short region as death domain-1 (DD1). Small interfering RNA studies indicated that DD1-mediated apoptosis is caspase-2 dependent. In this study, we examined DD1-mediated apoptosis in more detail and generated stable caspase-2 knockdown breast cancer cells. These cells are resistant to DD1-mediated apoptosis. Time-lapse movies suggested that DD1-mediated apoptosis also leads to a “bystander effect.” We found that within 5 h of DD1 expression, breast cancer cells release a factor(s) into the medium that leads to apoptosis of naive breast cancer cells or DD1-resistant cells (e.g., HeLa). The DD1-expressing caspase-2 knockdown cells also release a factor(s) that kills other cells, indicating that this effect is not dependent on the apoptogenic process. The bystander effect seems dependent on the production of reactive oxygen species (ROS). These and other studies indicate that DD1 expression in breast cancer cells leads to at least two death signals: one involving the rapid production of ROS and/or other soluble factors that directly or indirectly leads to a bystander effect and a second caspase-2–dependent process that leads to apoptosis in cells in which DD1 is expressed. [Cancer Res 2007;67(4):1775–82]
Obesity resistance and enhanced glucose metabolismin mice transplanted with white adipose tissue lackingacyl CoA:diacylglycerol acyltransferase 1
Authors: Hubert C. Chen, Dalan R. Jensen, Heather M. Myers, Robert H. Eckel, Robert V. Farese
Journal: Journal of Clinical Investigation (2003)

Recent studies have identified the white adipose tissue (WAT) as an important endocrine organ that regulates energy and glucose metabolism via a number of secreted factors. Mice lacking acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in mammalian triglyceride synthesis, are protected against diet-induced obesity and glucose intolerance because of increased energy expenditure and enhanced insulin sensitivity. Because DGAT1 is highly expressed in WAT, we hypothesized that DGAT1 deficiency affects the expression of adipocyte-derived factors that regulate energy and glucose metabolism. Here we show that the transplantation of DGAT1-deficient WAT decreases adiposity and enhances glucose disposal in wild-type mice. Analysis of DGAT1-deficient WAT revealed a twofold increase in the expression of adiponectin, a molecule that enhances fatty acid oxidation and insulin sensitivity, and this increase may account in part for the transplantation-induced metabolic changes. Our results highlight the importance of the endocrine function of WAT and suggest that an alteration in this function contributes to the increased energy expenditure and insulin sensitivity in DGAT1-deficient mice.
Multiple large surface photodynamic therapy sessions with topical methylaminolaevulinate in <i>PTCH</i> heterozygous mice
Authors: V. Caty, Y. Liu, G. Viau, R. Bissonnette
Journal: British Journal of Dermatology (2005)

Background Photodynamic therapy (PDT) combines the administration of a photosensitizer with its subsequent activation by light of the appropriate wavelength. Methylaminolaevulinate (MAL) is a photosensitizer precursor, transformed by cells into protoporphyrin IX. The PTCH gene plays a central role in the genesis of basal cell carcinoma (BCC). The PTCH transgenic mouse develops microscopic BCCs when chronically exposed to ultraviolet (UV) or ionizing radiation. Objectives The aim of this study was to explore the ability of multiple large surface MAL-PDT to prevent BCC, using the PTCH heterozygous mouse as a model. Methods Thirty-five mice were exposed to UV radiation for a total of 20 weeks. Group 1 (20 mice) was exposed only to UV whereas group 2 (15 mice) was exposed to UV and weekly to MAL-PDT. At 28 weeks the mice were killed and the skin of the back processed for standard histopathology. Assessment was blind and any slide showing the presence of BCC was counted as a single BCC. The number of mice in groups 1 and 2 showing BCC were compared using Fisher's exact test. Results Nineteen BCCs in nine mice from group 1 were found, but no BCCs in mice from group 2. The difference was statistically significant (P = 0·001). Conclusions Weekly suberythematous PDT sessions with topical MAL were able to delay the development of microscopic BCCs in PTCH mice chronically exposed to UV radiation.
T cells of the human intestinal lamina propria are high producers of interleukin-10
Authors: J Braunstein, L Qiao, F Autschbach, G Schürmann, S Meuer
Journal: Gut (1997)

Background and aim — Some of the recently observed functional features characteristic of immunocompetent cells residing in the human intestinal lamina propria could be mediated by interleukin- 10 (IL-10). To investigate the role of IL-10 in the human intestinal mucosa, the regulation of IL-10 production by lamina propria T lymphocytes (LPL-T) was determined and compared with that of peripheral blood T lymphocytes (PBL-T). Methods — Following activation by using different stimuli, IL-10 release by LPL-T and PBL-T into the supernatant was measured by enzyme linked immunosorbent assay (ELISA). In parallel, cell growth was determined by [ 3 H]-thymidine incorporation. Results — Neither LPL-T nor PBL-T release IL-10 constitutively. Triggering through CD2 or the T cell receptor (TCR)/CD3 complex in the presence of autologous monocytes induces significantly greater IL-10 secretion by LPL-T than by PBL-T. Engagement of the CD45 receptor enhances IL-10 release and proliferation of CD2 triggered CD45RO+ PBL-T. In contrast, it reduces CD2 induced IL-10 production by LPL-T without altering cell growth significantly . Conclusions —Activated LPL-T release relatively high amounts of IL-10. Enhanced IL-10 production by activated LPL-T, in comparison with activated PBL-T, is not only related to the presence of a higher proportion of CD45RO+ T cells in the intestinal lamina propria, but is also caused by increased sensitivity of LPL-T to CD2 co-stimulation. The differential responsiveness of LPL-T, compared with PBL-T, to CD45 engagement demonstrates that CD45 could be involved in the altered CD2 reactivity of LPL-T.
Monomeric Phospholamban Overexpression in Transgenic Mouse Hearts
Authors: Guoxiang Chu, Gerald W. Dorn, Wusheng Luo, Judy M. Harrer, Vivek J. Kadambi, Richard A. Walsh, Evangelia G. Kranias
Journal: Circulation Research (1997)

Abstract Phospholamban, a prominent modulator of the sarcoplasmic reticulum (SR) Ca 2+ -ATPase activity and basal contractility in the mammalian heart, has been proposed to form pentamers in native SR membranes. However, the monomeric form of phospholamban, which is associated with mutating Cys 41 to Phe 41 , was shown to be as effective as pentameric phospholamban in inhibiting Ca 2+ transport in expression systems. To determine whether this monomeric form of phospholamban is also functional in vivo, we generated transgenic mice with cardiac-specific overexpression of the mutant (Cys 41 →Phe 41 ) phospholamban. Quantitative immunoblotting indicated a 2-fold increase in the cardiac phospholamban protein levels compared with wild-type controls, with ≈50% of phospholamban migrating as monomers and ≈50% as pentamers upon SDS-PAGE. The mutant-phospholamban transgenic hearts were analyzed in parallel with transgenic hearts overexpressing (2-fold) wild-type phospholamban, which migrated as pentamers upon SDS-PAGE. SR Ca 2+ -uptake assays revealed that the EC 50 values for Ca 2+ were as follows: 0.32±0.01 μmol/L in hearts overexpressing monomeric phospholamban, 0.49±0.05 μmol/L in hearts overexpressing wild-type phospholamban, and 0.26±0.01 μmol/L in wild-type control mouse hearts. Analysis of cardiomyocyte mechanics and Ca 2+ kinetics indicated that the inhibitory effects of mutant-phospholamban overexpression (mt) were less pronounced than those of wild-type phospholamban overexpression (ov) as assessed by depression of the following: (1) shortening fraction (25% mt versus 45% ov), (2) rates of shortening (27% mt versus 48% ov), (3) rates of relengthening (25% mt versus 50% ov), (4) amplitude of the Ca 2+ signal (21% mt versus 40% ov), and (5) time for decay of the Ca 2+ signal (25% mt versus 106% ov) compared with control (100%) myocytes. The differences in basal cardiac myocyte mechanics and Ca 2+ transients among the animal groups overexpressing monomeric or wild-type phospholamban and wild-type control mice were abolished upon isoproterenol stimulation. These findings suggest that pentameric assembly of phospholamban is important for mediating its optimal regulatory effects on myocardial contractility in vivo.