tbuckley/cabot-search huggingface dataset:
<i>Staphylococcus aureus</i> Sepsis and Mitochondrial Accrual of the 8-Oxoguanine DNA Glycosylase DNA Repair Enzyme in Mice
Authors: Raquel R. Bartz, Hagir B. Suliman, Ping Fu, Karen Welty-Wolf, Martha Sue Carraway, Nancy Chou MacGarvey, Crystal M. Withers, Timothy E. Sweeney, Claude A. Piantadosi
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Damage to mitochondrial DNA (mtDNA) by the production of reactive oxygen species during inflammatory states, such as sepsis, is repaired by poorly understood mechanisms.To test the hypothesis that the DNA repair enzyme, 8-oxoguanine DNA glycosylase (OGG1), contributes to mtDNA repair in sepsis.Using a well-characterized mouse model of Staphylococcus aureus sepsis, we analyzed molecular markers for mitochondrial biogenesis and OGG1 translocation into liver mitochondria as well as OGG1 mRNA expression at 0, 24, 48, and 72 hours after infection. The effects of OGG1 RNA silencing on mtDNA content were determined in control, tumor necrosis factor-α, and peptidoglycan-exposed rat hepatoma cells. Based on in situ analysis of the OGG1 promoter region, chromatin immunoprecipitation assays were performed for nuclear respiratory factor (NRF)-1 and NRF-2α GA-binding protein (GABP) binding to the promoter of OGG1.Mice infected with 10(7) cfu S. aureus intraperitoneally demonstrated hepatic oxidative mtDNA damage and significantly lower hepatic mtDNA content as well as increased mitochondrial OGG1 protein and enzyme activity compared with control mice. The infection also caused increases in hepatic OGG1 transcript levels and NRF-1 and NRF-2α transcript and protein levels. A bioinformatics analysis of the Ogg1 gene locus identified several promoter sites containing NRF-1 and NRF-2α DNA binding motifs, and chromatin immunoprecipitation assays confirmed in situ binding of both transcription factors to the Ogg1 promoter within 24 hours of infection.These studies identify OGG1 as an early mitochondrial response protein during sepsis under regulation by the NRF-1 and NRF-2α transcription factors that regulate mitochondrial biogenesis.
Electrical and mechanical alternans in canine myocardium in vivo. Dependence on intracellular calcium cycling.
Authors: Y Hirayama, H Saitoh, H Atarashi, H Hayakawa
Journal: Circulation (1993)

Electrical and mechanical alternans are thought to result from a common cellular mechanism. To confirm this phenomenon in vivo and extend our understanding, we investigated the effects of temperature, verapamil, and caffeine on alternans in intact beating hearts.We recorded surface ECG, monophasic action potential (MAP) using suction electrodes, and left ventricular pressure (LVP). Alternans of MAP configurations and of LVP were evaluated in 20 dogs. MAPs were recorded from the apex, base, and midportion of the left ventricle with LVP. The hearts were driven from the left ventricular apex at a basic cycle length of 1000 milliseconds, and alternans was induced with an abrupt shortening of the cycle length to 400 milliseconds. MAPD30/100, the ratio between the MAP durations (MAPD) at 30% and 100% repolarization levels, was measured as an index of MAP configuration. The magnitude of MAP or LVP alternans was defined as the difference in MAPD30/100 or in LVP between the fifth and sixth paced beats. The magnitude of MAP alternans differed by recording site but correlated with activation time. Lowering the temperature increased the magnitude. MAP alternans was always associated with LVP alternans under control conditions. Verapamil significantly attenuated the magnitude of MAP alternans but did not change that of LVP alternans. Caffeine attenuated the magnitude of both MAP and LVP alternans. T wave alternans was suppressed by verapamil or caffeine.Activation time is one of the factors modifying electrical alternans. Delayed intracellular Ca2+ cycling plays a role in the concomitant occurrence of electrical and mechanical alternans.
INTERLEUKIN-1 RECEPTOR ANTAGONIST: Role in Biology
Authors: William P. Arend, Mark Malyak, Carla J. Guthridge, Cem Gabay
Journal: Annual Review of Immunology (1998)

▪ Abstract The interleukin-1 receptor antagonist (IL-1Ra) is a member of the IL-1 family that binds to IL-1 receptors but does not induce any intracellular response. Two structural variants of IL-1Ra have previously been described: a 17-kDa form that is secreted from monocytes, macrophages, neutrophils, and other cells (sIL-1Ra) and an 18-kDa form that remains in the cytoplasm of keratinocytes and other epithelial cells, monocytes, and fibroblasts (icIL-1Ra). An additional 16-kDa intracellular isoform of IL-1Ra has recently been described in neutrophils, monocytes, and hepatic cells. Both of the major isoforms of IL-1Ra are transcribed from the same gene through the use of alternative first exons. The two promoters regulating transcription of the secreted and intracellular forms have been cloned, and some of the functional cis-acting DNA regions have been characterized. The production of IL-1Ra is stimulated by many substances including adherent IgG, other cytokines, and bacterial or viral components. The tissue distribution of IL-1Ra in mice indicates that sIL-1Ra is found predominantly in peripheral blood cells, lungs, spleen, and liver, while icIL-1Ra is found in large amounts in skin. Studies in transgenic and knockout mice indicate that IL-1Ra is important in host defense against endotoxin-induced injury. IL-1Ra is produced by hepatic cells with the characteristics of an acute phase protein. Endogenous IL-1Ra is produced in numerous experimental animal models of disease as well as in human autoimmune and chronic inflammatory diseases. The use of neutralizing anti-IL-1Ra antibodies has demonstrated that endogenous IL-1Ra is an important natural antiinflammatory protein in arthritis, colitis, and granulomatous pulmonary disease. Treatment of human diseases with recombinant human IL-1Ra showed an absence of benefit in sepsis syndrome. However, patients with rheumatoid arthritis treated with IL-1Ra for six months exhibited improvements in clinical parameters and in radiographic evidence of joint damage.
A Vaccinia Virus Armed with Interleukin-10 Is a Promising Therapeutic Agent for Treatment of Murine Pancreatic Cancer
Authors: Louisa S. Chard, Eleni Maniati, Pengju Wang, Zhongxian Zhang, Dongling Gao, Jiwei Wang, Fengyu Cao, Jahangir Ahmed, Margueritte El Khouri, Jonathan Hughes, Shengdian Wang, Xiaozhu Li, Bela Denes, Istvan Fodor, Thorsten Hagemann, Nicholas R. Lemoine, Yaohe Wang
Journal: Clinical Cancer Research (2014)

Vaccinia virus has strong potential as a novel therapeutic agent for treatment of pancreatic cancer. We investigated whether arming vaccinia virus with interleukin-10 (IL10) could enhance the antitumor efficacy with the view that IL10 might dampen the host immunity to the virus, increasing viral persistence, thus maximizing the oncolytic effect and antitumor immunity associated with vaccinia virus.The antitumor efficacy of IL10-armed vaccinia virus (VVLΔTK-IL10) and control VVΔTK was assessed in pancreatic cancer cell lines, mice bearing subcutaneous pancreatic cancer tumors and a pancreatic cancer transgenic mouse model. Viral persistence within the tumors was examined and immune depletion experiments as well as immunophenotyping of splenocytes were carried out to dissect the functional mechanisms associated with the viral efficacy.Compared with unarmed VVLΔTK, VVLΔTK-IL10 had a similar level of cytotoxicity and replication in vitro in murine pancreatic cancer cell lines, but rendered a superior antitumor efficacy in the subcutaneous pancreatic cancer model and a K-ras-p53 mutant-transgenic pancreatic cancer model after systemic delivery, with induction of long-term antitumor immunity. The antitumor efficacy of VVLΔTK-IL10 was dependent on CD4(+) and CD8(+), but not NK cells. Clearance of VVLΔTK-IL10 was reduced at early time points compared with the control virus. Treatment with VVLΔTK-IL10 resulted in a reduction in virus-specific, but not tumor-specific CD8(+) cells compared with VVLΔTK.These results suggest that VVLΔTK-IL10 has strong potential as an antitumor therapeutic for pancreatic cancer.
Phospholipid decoration of microcapsules containing perfluorooctyl bromide used as ultrasound contrast agents
Authors: Raquel Díaz-López, Nicolas Tsapis, Danielle Libong, Pierre Chaminade, Carole Connan, Mohamed M. Chehimi, Romain Berti, Nicolas Taulier, Wladimir Urbach, Valérie Nicolas, Elias Fattal
Journal: Biomaterials (2008)
DIETARY ANALYSIS OF REGIONAL AND NATIONAL LEVEL YOUTH SWIMMERS IN THE UNITED KINGDOM
Authors: M Russell, R Lali, E Cockburn, PLS Rumbold
Journal: British Journal of Sports Medicine (2013)

Optimised nutritional intake is well established as being one of a multiplicity of factors that contributes to the development of attaining peak sporting performance. Few studies have sought to investigate the dietary habits of adolescent, as opposed to adult, swimmers; especially those competing in the United Kingdom. Therefore the purpose of this study was to investigate the nutritional and activity habits of amateur swimmers (n=25; Age: 15±1 years; Stature: 1.67±0.02 m; Mass: 56.2±1.7 kg; BMI: 20.1±0.4 kg·m 2 ) who trained and competed on behalf of Regional and National Development Squads based in the UK. All participants recorded their 4 day dietary intake and activity habits during a typical week that included ∼9 h of training (consisting of 1 h land training with the remaining time dedicated to swim training with a speed emphasis). The intake of carbohydrates (6.2±0.4 g·kg −1 ·d −1 ), proteins (1.8±0.1 g·kg −1 ·d −1 ) and fats (1.9±0.1 g·kg −1 ·d −1 ) represented 52±1%, 15±1%, and 36±1% of the mean daily energy intake, respectively. Compared to Recommended Nutrient Intake values, micronutrient deficiencies were observed for fibre (45±4% of RNI), vitamin A (52±7% of RNI) and selenium (72±6% of RNI), whereas all other analysed micronutrients met or exceeded recommendations. A mean daily energy deficit of 956±135 KCal existed. These data suggest that the nutritional practices of a group of amateur swimmers were less than optimal when seeking to sustain peak performance throughout training. Consequently, based on current dietary recommendations, if complete recovery, delay of fatigue and a reduced susceptibility to illness is desired, adolescent swimmers should seek to ensure that their dietary intake contains an optimised proportion of energy derived from macronutrients while ensuring that enough foods containing fibre, vitamin A and selenium are consumed.
Scientific Advisory Committee on Nutrition replies to Mary Fewtrell and colleagues
Authors: A. F. Williams, A. Prentice
Journal: BMJ (2011)

Fewtrell and colleagues selectively reviewed evidence on the appropriate age at which to introduce complementary food into the diet of breastfed infants.1 We comment on several of their statements about the role of the Scientific Advisory Committee on Nutrition (SACN) in advising UK governments on this issue. SACN is a committee of independent experts appointed under Nolan principles to advise these governments.

It is incorrect that SACN “was not asked to formally consider the scientific evidence” supporting the World Health Organization’s revised recommendations on breast feeding in 2001. The issue was initially considered in 2000 at a meeting chaired by the inaugural chair of SACN. It concluded: “There is sufficient scientific evidence that exclusive breast feeding for six months is nutritionally adequate.” SACN endorsed …
S130 HIV-1 infection of macrophages dysregulates pro-inflammatory host responses to Mycobacterium tuberculosis through inhibition of interleukin 10
Authors: G. S. Tomlinson, P. T. G. Elkington, L. Bell, N. F. Walker, J. Tsang, J. Brown, R. Breen, M. Lipman, D. R. Katz, R. F. Miller, B. M. Chain, M. Noursadeghi
Journal: Thorax (2011)

<h3>Introduction</h3> Human immunodeficiency virus (HIV)-1 greatly increases the risk of active <i>Mycobacterium tuberculosis</i> (Mtb) infection. Both pathogens target macrophages by evading innate immune recognition or intracellular killing. Since macrophages play a key role in inflammatory responses and their resolution, we tested the hypothesis that HIV-1 infection of macrophages may modulate inflammatory responses to co-infection with Mtb contributing to the immunopathogenesis of active tuberculosis (TB). <h3>Methods</h3> Innate immune responses to Mtb were assessed in human macrophages with and without productive HIV-1 infection using genome-wide transcriptional profiling. Array data were validated by quantitative PCR and correlated with protein secretion in cell culture supernatants. The effects of Mtb co-infection on HIV replication were assessed by ELISA. The mechanisms underlying the observed phenotype were examined by Western immunoblotting and using selective inhibitors of innate immune signalling pathways. <h3>Results</h3> HIV-1 infection of monocyte-derived macrophages leads to sustained, exaggerated pro-inflammatory responses to Mtb co-infection, including cytokines and chemokines that may recruit and activate further inflammatory leucocytes, and matrix metalloproteinases which play a role in tissue destruction. This phenotype is associated with rescue of HIV-1 replication following early repression in response to Mtb. Our data suggest that augmented inflammatory responses to Mtb result from deficient induction of anti-inflammatory interleukin-10 in HIV-1 infected cells. None of these changes were evident in HIV-1 infected macrophages co-infected with <i>Streptococcus pneumoniae</i>, and the specificity of the effect in Mtb co-infection was mirrored by lower IL-10 and higher pro-inflammatory IL-1β in respiratory samples from HIV-1 infected patients with pulmonary TB compared to non-tuberculous respiratory infection. Complementation of deficient IL-10 responses to Mtb in HIV-1 infected macrophages reverses the exaggerated pro-inflammatory phenotype. HIV-1 infection attenuates phosphorylation of p38 and ERK1/2 in mitogen activated kinase pathways involved in IL-10 induction downstream of TLR2 and dectin-1 receptor stimulation. IL-10 production in HIV-1 infected cells is also inhibited in response to zymosan stimulation of these pathways. Inhibition of virus maturation with HIV-1 protease inhibitors, does not affect attenuation of IL-10 responses. <h3>Conclusions</h3> Deficient induction of homeostatic IL-10 and consequent augmentation of pro-inflammatory responses may contribute to the immunopathogenesis of active TB and propagation of virus infection in HIV-1/Mtb co-infection.
Global Variation in the Relative Burden of Stroke and Ischemic Heart Disease
Authors: Anthony S. Kim, S. Claiborne Johnston
Journal: Circulation (2011)

Background— Although stroke and ischemic heart disease (IHD) have several well-established risk factors in common, the extent of global variation in the relative burdens of these forms of vascular disease and reasons for any observed variation are poorly understood. Methods and Results— We analyzed mortality and disability-adjusted life-year loss rates from stroke and IHD, as well as national estimates of vascular risk factors that have been developed by the World Health Organization Burden of Disease Program. National income data were derived from World Bank estimates. We used linear regression for univariable analysis and the Cuzick test for trends. Among 192 World Health Organization member countries, stroke mortality rates exceeded IHD rates in 74 countries (39%), and stroke disability-adjusted life-year loss rates exceeded IHD rates in 62 countries (32%). Stroke mortality ranged from 12.7% higher to 27.2% lower than IHD, and stroke disability-adjusted life-year loss rates ranged from 6.2% higher to 10.2% lower than IHD. Stroke burden was disproportionately higher in China, Africa, and South America, whereas IHD burden was higher in the Middle East, North America, Australia, and much of Europe. Lower national income was associated with higher relative mortality ( P &lt;0.001) and burden of disease ( P =0.001) from stroke. Diabetes mellitus prevalence and mean serum cholesterol were each associated with greater relative burdens from IHD even after adjustment for national income. Conclusions— There is substantial global variation in the relative burden of stroke compared with IHD. The disproportionate burden from stroke for many lower-income countries suggests that distinct interventions may be required.
Saturated free fatty acids induce cholangiocyte lipoapoptosis
Authors: Sathish Kumar Natarajan, Sally A. Ingham, Ashley M. Mohr, Cody J. Wehrkamp, Anuttoma Ray, Sohini Roy, Sophie C. Cazanave, Mary Anne Phillippi, Justin L. Mott
Journal: Hepatology (2014)

Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increased circulating free fatty acids (FFAs) in NAFLD, we hypothesized the involvement of cholangiocyte lipoapoptosis as a mechanism of cellular injury. Here, we demonstrate that the saturated FFAs palmitate and stearate induced robust and rapid cell death in cholangiocytes. Palmitate and stearate induced cholangiocyte lipoapoptosis in a concentration-dependent manner in multiple cholangiocyte-derived cell lines. The mechanism of lipoapoptosis relied on the activation of caspase 3/7 activity. There was also a significant up-regulation of the proapoptotic BH3-containing protein, PUMA. In addition, palmitate-induced cholangiocyte lipoapoptosis involved a time-dependent increase in the nuclear localization of forkhead family of transcription factor 3 (FoxO3). We show evidence for posttranslational modification of FoxO3, including early (6 hours) deacetylation and dephosphorylation that coincide with localization of FoxO3 in the nuclear compartment. By 16 hours, nuclear FoxO3 is both phosphorylated and acetylated. Knockdown studies confirmed that FoxO3 and its downstream target, PUMA, were critical for palmitate- and stearate-induced cholangiocyte lipoapoptosis. Interestingly, cultured cholangiocyte-derived cells did not accumulate appreciable amounts of neutral lipid upon FFA treatment.Our data show that the saturated FFAs palmitate and stearate induced cholangiocyte lipoapoptosis by way of caspase activation, nuclear translocation of FoxO3, and increased proapoptotic PUMA expression. These results suggest that cholangiocyte injury may occur through lipoapoptosis in NAFLD and nonalcoholic steatohepatitis patients.
The COPD control panel: towards personalised medicine in COPD
Authors: Alvar Agusti, William MacNee
Journal: Thorax (2012)

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease whose assessment and management have traditionally been based on the severity of airflow limitation (forced expiratory volume in 1 s (FEV<sub>1</sub>)). Yet, it is now clear that FEV<sub>1</sub> alone cannot describe the complexity of the disease. In fact, the recently released Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2011 revision has proposed a new combined assessment method using three variables (symptoms, airflow limitation and exacerbations). <h3>Methods</h3> Here, we go one step further and propose that in the near future physicians will need a ‘control panel’ for the assessment and optimal management of individual patients with complex diseases, including COPD, that provides a path towards personalised medicine. <h3>Results</h3> We propose that such a ‘COPD control panel’ should include at least three different domains of the disease: severity, activity and impact. Each of these domains presents information on different ‘elements’ of the disease with potential prognostic value and/or with specific therapeutic requirements. All this information can be easily incorporated into an ‘app’ for daily use in clinical practice. <h3>Conclusion</h3> We recognise that this preliminary proposal needs debate, validation and evolution (eg, including ‘omics’ and molecular imaging information in the future), but we hope that it may stimulate debate and research in the field.
Retinoblastoma-Related Protein pRb2/p130 and Suppression of Tumor Growth In Vivo
Authors: Candace M. Howard, Pier Paolo Claudio, Gary L. Gallia, Jennifer Gordon, Giovan Giacomo Giordano, Walter W. Hauck, Kamel Khalili, Antonio Giordano
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The RB/p105 and p107 genes of the retinoblastoma family are tumor suppressor genes whose proteins are inactivated by interaction with T-antigen proteins encoded by polyomaviruses (e.g., simian virus 40 and human JC virus), which have been found to be highly tumorigenic in animals. A variety of indirect evidence suggests that another member of the retinoblastoma gene family, RB2/p130, is also a tumor suppressor gene. To investigate the putative tumor suppressor activity of RB2/p130 more directly, we utilized a tetracycline-regulated gene expression system to control expression of the encoded protein pRb2/p130 in JC virusinduced hamster brain tumor cells and to study the effects of pRb2/p130 on the growth of such tumor cells in nude mice. The ability of pRb2/p130 to interact with JC virus T antigen was also studied. Methods: Northern blot hybridization analyses were performed on samples of total cellular RNA to measure RB2/p130 and b-actin messenger RNA levels. Immunoprecipitation and western blot analyses were used to determine T-antigen and pRb2/p130 protein levels and to assess the phosphorylation status of these proteins. Tumor cells were injected subcutaneously into nude mice, and tumor growth, with or without induced expression of pRb2/ p130, was monitored. Results: Induction of pRb2/p130 expression brought about a 3.2-fold, or 69% (95% confidence interval = 64%-73%), reduction in final tumor mass in nude mice. We also demonstrated that JC virus T antigen binds hypophosphorylated pRb2/p130 and that stimulation of pRb2/p130 expression overcomes cellular transformation mediated by this antigen. Conclusion: Our findings support the hypothesis that RB2/p130 is a tumor suppressor gene. [J Natl Cancer Inst 1998;90:1451-60]
Efficacy of borage oil in patients with atopic eczema - reply from author
Authors: B.M. Henz
Journal: British Journal of Dermatology (2000)

Journal Article Efficacy of borage oil in patients with atopic eczema – reply from author Get access B.M. Henz B.M. Henz Department of Dermatology, V irchow Clinic, Free University Berlin, Augustenburgerplatz 1, 13344 Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 1, 1 July 2000, Page 201, https://doi.org/10.1046/j.1365-2133.2000.03620.x Published: 01 July 2000
PATHOGENESIS AND MANAGEMENT OF ACUTE PROMYELOCYTIC LEUKEMIA
Authors: Raymond P. Warrell
Journal: Annual Review of Medicine (1996)

▪ Abstract Acute promyelocytic leukemia, formerly a highly lethal disease, was recently shown to be highly responsive to treatment with the natural retinoid, all-trans retinoic acid. This compound induces terminal differentiation of the malignant cells and produces complete remission in most patients with this disease. The clinical response is due in part to the presence of a chromosomal break that occurs in a gene that encodes a nuclear retinoic acid receptor.