tbuckley/cabot-search huggingface dataset:
Government's "nudging" policies on behaviour are too weak on their own, report says
Authors: A. O'Dowd
Journal: BMJ (2011)

<b>Introduction:</b> Tuberculosis(TB) remains a leading cause of mortality worldwide.Drug resistant TB have increased need for developing novel antituberculosis agents,using medicinal plants. <b>Aims and objectives:</b> Study assessed antituberculosis and combined activity with Isoniazide(INH) of extracts of Cinnamomum verum &amp; Solanum surattense against <i>Mycobacterium tuberculosis</i> H37Rv strain. <b>Methods:</b> Aqueous &amp; methanolic extracts was prepared by soxhet extraction and their phytochemical screening was done. Median Cytotoxicity (CC50) was estimated by MTT assay using cell line. Antituberculosis activity of extracts was tested by agar dilution &amp; Microscopic Observation of Drug Susceptibility Assay (MODS).50% inhibition (IC50) was calculated by Resazurine Microtitre Assay (REMA).The combined effect of the extracts with INH was evaluated by checkerboard titrations. <b>Results:</b> Phytochemical analysis showed flavanoids, tannins,steroids &amp; essential-oils in both extracts. Minimum Inhibitory Concentration(MIC) of aqueous &amp; methanolic extracts of both plants showed 10 mcg/ml by agar dilution method.Acquous (CAS) &amp; methanolic(CMS) extracts of Cinnamomum showed MIC value of 0.5 &amp; 2 mcg/ ml respectively, while aqueous (KAS) &amp; methanolic (KMS) extracts of Solanum showed MIC value of 2 &amp; 1 mcg/ ml resp. by MODS. IC 50 of CAS &amp; CMS was 7.961 &amp; 4.016 mcg/ ml respectively while IC50 of KAS &amp; KMS was 11.27 &amp; 8.5 mcg/ ml resp. by REMA. Antagonistic activity was observed in both plant extracts with INH. <b>Conclusion:</b> Study demonstrated antituberculosis activity of plants,though antagonistic activity with INH.Active components in extracts need to be evaluated &amp; standard testing protocol to be developed.
cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells
Authors: Eun-Ah Cho, Eui-Jun Kim, Sahng-June Kwak, Yong-Sung Juhnn
Journal: Molecular Cancer (2014)

Abstract Background The ataxia–telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells. Methods Lung cancer cells were transfected with constitutively active stimulatory G protein (GαsQL), and irradiated with γ-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by western blotting, and apoptosis was assessed by western blotting, flow cytometry, and TUNNEL staining. The promoter activity of NF-κB was determined by dual luciferase reporter assay. BALB/c mice were treated with forskolin to assess the effect in the lung tissue. Results Transient expression of GαsQL significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung cancer cells. Treatment with okadaic acid or knock down of PP2A B56δ subunit abolished the inhibitory effect of Gαs on radiation-induced ATM phosphorylation. Expression of GαsQL increased phosphorylation of the B56δ and PP2A activity, and inhibition of PKA blocked Gαs-induced PP2A activation. GαsQL enhanced radiation-induced cleavage of caspase-3 and PARP and increased the number of early apoptotic cells. The radiation-induced apoptosis was increased by inhibition of NF-κB using PDTC or inhibition of ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with forskolin stimulated phosphorylation of PP2A B56δ, inhibited the activation of ATM and NF-κB, and augmented radiation-induced apoptosis in the lung tissue. GαsQL expression decreased the nuclear levels of the p50 and p65 subunits and NF-κB-dependent activity after γ-ray irradiation in H1299 cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56δ phosphorylation, decreased radiation-induced ATM phosphorylation and increased apoptosis. Conclusions cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-κB in lung cancer cells.
Acute infection with a single hepatitis C virus strain in dialysis patients: Analysis of adaptive immune response and viral variability
Authors: Lukas Weseslindtner, Christoph Neumann-Haefelin, Sergei Viazov, Anita Haberstroh, Josef Kletzmayr, Judith H. Aberle, Joerg Timm, Stefan R. Ross, Renate Klauser-Braun, Thomas F. Baumert, Michael Roggendorf, Robert Thimme, Heidemarie Holzmann
Journal: Journal of Hepatology (2009)
ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer
Authors: Changmeng Cai, Hongyun Wang, Housheng Hansen He, Sen Chen, Lingfeng He, Fen Ma, Lorelei Mucci, Qianben Wang, Christopher Fiore, Adam G. Sowalsky, Massimo Loda, X. Shirley Liu, Myles Brown, Steven P. Balk, Xin Yuan
Journal: Journal of Clinical Investigation (2013)

Fusion of the androgen receptor-regulated (AR-regulated) TMPRSS2 gene with ERG in prostate cancer (PCa) causes androgen-stimulated overexpression of ERG, an ETS transcription factor, but critical downstream effectors of ERG-mediating PCa development remain to be established. Expression of the SOX9 transcription factor correlated with TMPRSS2:ERG fusion in 3 independent PCa cohorts, and ERG-dependent expression of SOX9 was confirmed by RNAi in the fusion-positive VCaP cell line. SOX9 has been shown to mediate ductal morphogenesis in fetal prostate and maintain stem/progenitor cell pools in multiple adult tissues, and has also been linked to PCa and other cancers. SOX9 overexpression resulted in neoplasia in murine prostate and stimulated tumor invasion, similarly to ERG. Moreover, SOX9 depletion in VCaP cells markedly impaired invasion and growth in vitro and in vivo, establishing SOX9 as a critical downstream effector of ERG. Finally, we found that ERG regulated SOX9 indirectly by opening a cryptic AR-regulated enhancer in the SOX9 gene. Together, these results demonstrate that ERG redirects AR to a set of genes including SOX9 that are not normally androgen stimulated, and identify SOX9 as a critical downstream effector of ERG in TMPRSS2:ERG fusion–positive PCa.
I<scp>nterleukin</scp>-10<scp>and</scp>R<scp>elated</scp>C<scp>ytokines and</scp>R<scp>eceptors</scp>
Authors: Sidney Pestka, Christopher D. Krause, Devanand Sarkar, Mark R. Walter, Yufang Shi, Paul B. Fisher
Journal: Annual Review of Immunology (2004)

The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29). The interaction of these cytokines with their specific receptor molecules initiates a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory responses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and affect many immune mechanisms. The information derived from crystal structures and molecular evolution has led to progress in the analysis of the molecular mechanisms initiating their biological activities. These cytokines have significant roles in a variety of pathophysiological processes as well as in regulation of the immune system. Further investigation of these critical intercellular signaling molecules will provide important information to enable these proteins to be used more extensively in therapy for a variety of diseases.
ACC/AHA 2004 Guideline Update for Coronary Artery Bypass Graft Surgery: Summary Article
Authors: Kim A. Eagle, Robert A. Guyton, Ravin Davidoff, Fred H. Edwards, Gordon A. Ewy, Timothy J. Gardner, James C. Hart, Howard C. Herrmann, L. David Hillis, Adolph M. Hutter, Bruce Whitney Lytle, Robert A. Marlow, William C. Nugent, Thomas A. Orszulak, Elliott M. Antman, Sidney C. Smith, Joseph S. Alpert, Jeffrey L. Anderson, David P. Faxon, Valentin Fuster, Raymond J. Gibbons, Gabriel Gregoratos, Jonathan L. Halperin, Loren F. Hiratzka, Sharon Ann Hunt, Alice K. Jacobs, Joseph P. Ornato
Journal: Circulation (2004)

The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid any actual or potential conflicts of interest that might arise as a result of an outside relationship or personal interest of a member of the writing panel.Specifically, all members of the writing panel are asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest.These statements are reviewed by the parent task force, reported orally to all members of the writing panel at the first meeting, and updated as changes occur.The
Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update
Authors: Shahid A Khan, Brian R Davidson, Robert D Goldin, Nigel Heaton, John Karani, Stephen P Pereira, William M C Rosenberg, Paul Tait, Simon D Taylor-Robinson, Andrew V Thillainayagam, Howard C Thomas, Harpreet Wasan
Journal: Gut (2012)

The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in 2002. This is the first update since then and is based on a comprehensive review of the recent literature, including data from randomised controlled trials, systematic reviews, meta-analyses, cohort, prospective and retrospective studies.
Molecular Mechanisms and Timing of Cortical Immune Activation in Schizophrenia
Authors: David W. Volk, Anjani Chitrapu, Jessica R. Edelson, Kaitlyn M. Roman, Annie E. Moroco, David A. Lewis
Journal: American Journal of Psychiatry (2015)

Immune-related abnormalities are commonly reported in schizophrenia, including higher mRNA levels for the viral restriction factor interferon-induced transmembrane protein (IFITM) in the prefrontal cortex. The authors sought to clarify whether higher IFITM mRNA levels and other immune-related disturbances in the prefrontal cortex are the consequence of an ongoing molecular cascade contributing to immune activation or the reflection of a long-lasting maladaptive response to an in utero immune-related insult.
A randomized double-blind comparison of PUVA-etretinate and PUVA-placebo in the treatment of chronic plaque psoriasis
Authors: S. PARKER, P. COBURN, C. L. AWRENCE, JANET MARKS, SAM SHUSTER
Journal: British Journal of Dermatology (1984)

Journal Article A randomized double‐blind comparison of PUVA‐etretinate and PUVA‐placebo in the treatment of chronic plaque psoriasis Get access S. PARKER, S. PARKER Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, NEl4LP Search for other works by this author on: Oxford Academic Google Scholar P. COBURN, P. COBURN Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, NEl4LP Search for other works by this author on: Oxford Academic Google Scholar C. L. AWRENCE, C. L. AWRENCE Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, NEl4LP Search for other works by this author on: Oxford Academic Google Scholar JANET MARKS, JANET MARKS Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, NEl4LP Search for other works by this author on: Oxford Academic Google Scholar SAM SHUSTER SAM SHUSTER Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, NEl4LP Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 110, Issue 2, 1 February 1984, Pages 215–220, https://doi.org/10.1111/j.1365-2133.1984.tb07470.x Published: 01 February 1984 Article history Accepted: 12 July 1983 Published: 01 February 1984
Conditioning Effects of Chronic Infusions of Dobutamine
Authors: Chang-Seng Liang, Ronald R. Tuttle, William B. Hood, Haralambos Gavras
Journal: Journal of Clinical Investigation (1979)

We studied the conditioning effects of chronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 μg/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 10° incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning.
Functional amelioration of murine galactosialidosis by genetically modified bone marrow hematopoietic progenitor cells
Authors: Thasia Leimig, Linda Mann, Maria del Pilar Martin, Erik Bonten, Derek Persons, James Knowles, James A. Allay, John Cunningham, Arthur W. Nienhuis, Richard Smeyne, Alessandra d'Azzo
Journal: Blood (2002)
Placebos, Drug Effects, and Study Design: A Clinician’s Guide
Authors: Frederic M. Quitkin
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: This article examines the role of placebos in evaluating the efficacy of psychiatric drugs. Also addressed are the identification of placebo effects on drugs, the relevance of active placebo, the need for placebo groups in psychotherapy studies, and ethical issues concerning the use of placebo. METHOD: Psychiatric drug treatment trials were reviewed. RESULTS: Emphasis was placed on studies with ambiguous outcomes, studies using an active placebo, and studies attempting to understand the role of placebo effects on patients receiving a drug. The concept of pattern analysis for identifying true drug effect is reviewed. Evidence that placebos are required to prevent a false conclusion about drug efficacy is presented. The public health implications of concluding that an ineffective drug is beneficial are examined. Active placebos do not appear necessary, and there is some evidence that the odds of identifying a patient who has improved as a result of true drug effect (as opposed to placebo effect) exceed chance with pattern analysis. CONCLUSIONS: Psychiatric disorders have a fluctuating course, psychiatry's phenomenologically based nosological system is inexact, and the interaction between these two leads to a large proportion of patients experiencing a placebo effect. It may be possible to identify patients receiving an antidepressant who improved as a result of a placebo effect. This is an educated guess that may be helpful in planning the treatment of patients who have a contraindication to continuing a psychopharmacological regimen.
Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor blockers in ankylosing spondylitis
Authors: M Rudwaleit
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> TNFα blockers have been shown to be highly efficacious in patients with active ankylosing spondylitis (AS). <b>Objective:</b> To identify parameters predicting the clinical response to TNF blockers in AS. <b>Methods:</b> Patients with active AS participated in two placebo controlled, randomised trials conducted in Germany with infliximab (n = 69) and etanercept (n = 30), respectively. For inclusion in either trial patients had to have high disease activity (BASDAI ⩾4) and a spinal pain score (numerical rating scale 0–10) ⩾4 despite treatment with NSAIDs. A major clinical response was defined as a 50% improvement of the initial BASDAI (BASDAI 50) after 12 weeks' treatment with active drug. Logistic regression likelihood ratio tests (univariate and multivariate), Student's <i>t</i> test, and χ<sup>2</sup> tests were performed. <b>Results:</b> Univariate analysis showed the following to be predictors of a major response (BASDAI 50) to treatment: shorter disease duration (p = 0.003); lower BASFI (p = 0.007); younger age (p = 0.009); raised ESR (p = 0.033); raised CRP (p = 0.035). After adjustment for disease duration, BASFI, ESR, and CRP, but not age, remained significantly associated. After adjustment for disease duration and for BASFI, ESR, CRP, and in addition, a higher BASDAI were significantly associated with response. The best multivariate model built by stepwise regression contained the covariables disease duration, BASFI, BASDAI, and CRP. <b>Conclusion:</b> A shorter disease duration, younger age, and a lower BASFI are predictors of a major clinical response to TNF blockers in active AS. Raised CRP and a higher BASDAI may also be valuable predictors. These data need to be confirmed in further studies.
Combination DMARD therapy for rheumatoid arthritis. Full or low DMARD doses?
Authors: G F FERRACCIOLI, L CASATTA, E DI POI, R DAMATO, E BARTOLI;, J. R O'DELL
Journal: Annals of the Rheumatic Diseases (1997)

Pigmented villonodular synovitisI write with regard to the paper by Zuber and colleagues that purports to demonstrate a case of pigmented villonodular synovitis (PVNS). 1 The pathology material presented by the authors, however, is not diagnostic of PVNS, in that the cellular infiltrate did not demonstrate the large polyhedral cellsusually dubbed histiocytes-that are requisite for the diagnosis of PVNS.Villi, nodules, giant cells, and haemosiderin are not specific, and may be seen in a variety of conditions other than PVNS.It is the histiocyte that renders the pathology of PVNS unique and diagnostic.Indeed, Lichtenstein has described PVNS as a 'histiocytosis' of the synovial membrane. 2n addition, the authors suggest that in their patient PVNS was found to aVect the second to fifth MCP joints.However, the diffuse form of PVNS is nearly always monarticular; documented cases of polyarticular (usually biarticular) involvement by PVNS are exceptionally rare, and probably number less than half a dozen in the medical literature.The patient under discussion-who presented with progressive, bilateral ulnar deviation at the MCPs-most probably had rheumatoid disease, not PVNS.If there is a 'lesson' to this case, it is that the correct diagnosis of an unusual condition such as PVNS requires awareness of the characteristic clinical presentation of the disease and attentiveness to its diagnostic histopathology.
Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study
Authors: S. N. Vigod, T. Gomes, A. S. Wilton, V. H. Taylor, J. G. Ray
Journal: BMJ (2015)

<b>Objective</b> To evaluate maternal medical and perinatal outcomes associated with antipsychotic drug use in pregnancy. <b>Design</b> High dimensional propensity score (HDPS) matched cohort study. <b>Setting</b> Multiple linked population health administrative databases in the entire province of Ontario, Canada. <b>Participants</b> Among women who delivered a singleton infant between 2003 and 2012, and who were eligible for provincially funded drug coverage, those with ≥2 consecutive prescriptions for an antipsychotic medication during pregnancy, at least one of which was filled in the first or second trimester, were selected. Of these antipsychotic drug users, 1021 were matched 1:1 with 1021 non-users by means of a HDPS algorithm. <b>Main outcome measures</b> The main maternal medical outcomes were gestational diabetes, hypertensive disorders of pregnancy, and venous thromboembolism. The main perinatal outcomes were preterm birth (&lt;37 weeks), and a birth weight &lt;3rd or &gt;97th centile. Conditional Poisson regression analysis was used to generate rate ratios and 95% confidence intervals, adjusting for additionally prescribed non-antipsychotic psychotropic medications. <b>Results</b> Compared with non-users, women prescribed an antipsychotic medication in pregnancy did not seem to be at higher risk of gestational diabetes (rate ratio 1.10 (95% CI 0.77 to 1.57)), hypertensive disorders of pregnancy (1.12 (0.70 to 1.78)), or venous thromboembolism (0.95 (0.40 to 2.27)). The preterm birth rate, though high among antipsychotic users (14.5%) and matched non-users (14.3%), was not relatively different (rate ratio 0.99 (0.78 to 1.26)). Neither birth weight &lt;3rd centile or &gt;97th centile was associated with antipsychotic drug use in pregnancy (rate ratios 1.21 (0.81 to 1.82) and 1.26 (0.69 to 2.29) respectively). <b>Conclusions</b> Antipsychotic drug use in pregnancy had minimal evident impact on important maternal medical and short term perinatal outcomes. However, the rate of adverse outcomes is high enough to warrant careful assessment of maternal and fetal wellbeing among women prescribed an antipsychotic drug in pregnancy.
Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial
Authors: D.C. Linch, A.H. Goldstone, A. McMillan, R. Chopra, G. Vaughan Hudson, D. Winfield, B. Hancock, D. Moir, D. Milligan
Journal: The Lancet (1993)
Nutraceuticals as potential therapeutic agents for colon cancer: a review
Authors: Palaniselvam Kuppusamy, Mashitah M. Yusoff, Gaanty Pragas Maniam, Solachuddin Jauhari Arief Ichwan, Ilavenil Soundharrajan, Natanamurugaraj Govindan
Journal: Acta Pharmaceutica Sinica B (2014)

Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.