tbuckley/cabot-search huggingface dataset:
Sirt1 regulates canonical TGF-β signalling to control fibroblast activation and tissue fibrosis
Authors: Pawel Zerr, Katrin Palumbo-Zerr, Jingang Huang, Michal Tomcik, Barbora Sumova, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Sirt1 is a member of the sirtuin family of proteins<i>.</i> Sirt1 is a class III histone deacetylase with important regulatory roles in transcription, cellular differentiation, proliferation and metabolism. As aberrant epigenetic modifications have been linked to the pathogenesis of systemic sclerosis (SSc), we aimed to investigate the role of Sirt1 in fibroblast activation. <h3>Methods</h3> Sirt1 expression was analysed by real-time PCR, western blot and immunohistochemistry. Sirt1 signalling was modulated with the Sirt1 agonist resveratrol and by fibroblast-specific knockout. The role of Sirt1 was evaluated in bleomycin-induced skin fibrosis and in mice overexpressing a constitutively active transforming growth fac­tor-β (TGF-β) receptor I (TBRIact). <h3>Results</h3> The expression of Sirt1 was decreased in patients with SSc and in experimental fibrosis in a TGF-β-dependent manner. Activation of Sirt1 potentiated the profibrotic effects of TGF-β with increased Smad reporter activity, elevated transcription of TGF-β target genes and enhanced release of collagen. In contrast, knockdown of Sirt1 inhibited TGF-β/SMAD signalling and reduced release of collagen in fibroblasts. Consistently, mice with fibroblast-specific knockdown of Sirt1 were less susceptible to bleomycin- or TBRIact-induced fibrosis. <h3>Conclusions</h3> We identified Sirt1 as a crucial regulator of TGF-β/Smad signalling in SSc. Although Sirt1 is downregulated, this decrease is not sufficient to counterbalance the excessive activation of TGF-β signalling in SSc. However, augmentation of this endogenous regulatory mechanism, for example, by knockdown of Sirt1, can effectively inhibit TGF-β signalling and exerts potent antifibrotic effects. Sirt1 may thus be a key regulator of fibroblast activation in SSc.
Transplantation of the Stomach.
Authors: R. C. Lillehei
Journal: Annals of Internal Medicine (1963)

s1 April 1963Transplantation of the Stomach.R. C. Lillehei, M.D., Ph.D., J. K. Longerbeam, M.D., J. Bloch, M.D.R. C. Lillehei, M.D., Ph.D.Search for more papers by this author, J. K. Longerbeam, M.D.Search for more papers by this author, J. Bloch, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-724_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPrevously we described techniques for making transplants of the entire small bowel. The success of this procedure depended upon the ability of the bowel to withstand up to 6 hours of total ischemiain vitrowhen cooled to 5 C. The stomach also tolerates a similar period of total ischemiain vitrowhen cooled. Accordingly, a technique was developed to remove the entire stomach so that a single arterial and venous anastomosis would revascularize the stomach when it was returned to its normal position as an autograft. Dogs with gastric autografts have now been studied for over 3 years and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: R. C. Lillehei, M.D., Ph.D.; J. K. Longerbeam, M.D.; J. Bloch, M.D.Affiliations: Minneapolis, Minn. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 724-725KeywordsIschemiaStomachTransplantation ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...
The “Dreamy State”: John Hughlings-Jackson’s Ideas of Epilepsy and Consciousness
Authors: R. Edward Hogan, Kitti Kaiboriboon
Journal: American Journal of Psychiatry (2003)

The authors review John Hughlings-Jackson's writings on the "dreamy state" and his subsequent derivation of degrees of consciousness.They reviewed the publications of Hughlings-Jackson from his initial description of the "dreamy state" in 1876 until his writing about the "uncinate group of fits" in 1899. They then examined Hughlings-Jackson's use of the associated signs and symptoms of the "dreamy state" to formulate his ideas about human consciousness.Hughlings-Jackson defined the "dreamy state" as "over-consciousness," or a heightened intellectual state. He described associated symptoms of "crude sensations" of smell and taste, an unusual epigastric sensation, chewing and lip smacking, automatisms, postictal symptoms, and at least some degree of alteration of consciousness. Using his observations of the "dreamy state" as a model, Hughlings-Jackson proposed three degrees of consciousness, each with an object and subject component.Through his description of the "dreamy state," Hughlings-Jackson accurately characterized and localized medial temporal epilepsy. Correlating the ictal semiology of the "dreamy state" with consciousness, he developed a theory of consciousness that remains relevant to current understanding of the mind-brain relationship.
Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism
Authors: Jason R Clapper, Guillermo Moreno-Sanz, Roberto Russo, Ana Guijarro, Federica Vacondio, Andrea Duranti, Andrea Tontini, Silvano Sanchini, Natale R Sciolino, Jessica M Spradley, Andrea G Hohmann, Antonio Calignano, Marco Mor, Giorgio Tarzia, Daniele Piomelli
Journal: Nature Neuroscience (2010)
Epidemiological comparison of injuries in school and senior club rugby.
Authors: A J Lee, W M Garraway
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE: To determine the frequency, nature, circumstances, and outcome of schoolboy rugby injuries and to compare these injuries with those occurring in senior rugby clubs. METHODS: The study was a prospective cohort study, conducted on 1705 (98%) of 1736 eligible players from nine Edinburgh schools and 1169 (96%) of 1216 eligible players from all 26 senior Scottish Rugby Union clubs (South District) who provided personal details before the 1993-1994 rugby season. Adult linkpersons were appointed to notify the circumstances of all injury episodes occurring in matches or in rugby related training. RESULTS: 154 school players (9%) experienced 210 separate injuries in 186 injury episodes, 80% of which arose in matches. The prevalence rate of schoolboy match injuries was 86.8 (95% confidence interval 73.4 to 100.2) per 1000 player-seasons. Senior club match injury prevalence was much higher at 367.0 (339.4 to 394.6) per 1000 player-seasons. Club players had a higher rate of match injury than school-boys for all injury types. One third of schoolboy match injury episodes occurred in September and the majority of match injury episodes were associated with tackling (40%) or with being tackled (24%). Nine per cent of schoolboy match injury episodes were classified as severe, compared to 13% for clubs. Sixteen per cent (n = 23) of all schoolboy match injury episodes resulted in missed school attendance compared with 27% (n = 117) of all senior club match injury episodes which involved loss of employment or education. CONCLUSIONS: Schoolboy rugby is much safer than senior club rugby and the outcome of injuries that do occur is less disruptive. The relatively high rate of match injury in September migh be reduced by a more intensive period of preseason training.
Mechanisms of Mechanically Induced Spontaneous Arrhythmias in Acute Regional Ischemia
Authors: Xiao Jie, Viatcheslav Gurev, Natalia Trayanova
Journal: Circulation Research (2009)

Although ventricular premature beats (VPBs) during acute regional ischemia have been linked to mechanical stretch of ischemic tissue, whether and how ischemia-induced mechanical dysfunction can induce VPBs and facilitate their degradation into reentrant arrhythmias has not been yet addressed.This study used a novel multiscale electromechanical model of the rabbit ventricles to investigate the origin of and the substrate for spontaneous arrhythmias arising from ischemia-induced electrophysiological and mechanical changes.Two stages of ischemia were simulated. Dynamic mechanoelectrical feedback was modeled as spatially and temporally nonuniform membrane currents through mechanosensitive channels, the conductances of which depended on local strain rate. Our results reveal that both strains and strain rates were significantly larger in the central ischemic zone than in the border zone. However, in both ischemia stages, a VPB originated from the ischemic border in the left ventricular apical endocardium because of mechanically induced suprathreshold depolarizations. It then traveled fully intramurally until emerging from the ischemic border on the anterior epicardium. Reentry was formed only in the advanced ischemia stage as the result of a widened temporal excitable gap. Mechanically induced delayed afterdepolarization-like events contributed to the formation of reentry by further decreasing the already reduced-by-hyperkalemia local excitability, causing extended conduction block lines and slowed conduction in the ischemic region.Mechanically induced membrane depolarizations in the ischemic region are the mechanism by which mechanical activity contributes to both the origin of and substrate for spontaneous arrhythmias under the conditions of acute regional ischemia.
Long term monitoring in patients receiving treatment to lower blood pressure: analysis of data from placebo controlled randomised controlled trial
Authors: K. Keenan, A. Hayen, B. C Neal, L. Irwig
Journal: BMJ (2009)

<b>Objective</b> To determine the value of monitoring blood pressure by quantifying the probability that observed changes in blood pressure reflect true changes. <b>Design</b> Analysis of blood pressure measurements of patients in the perindopril protection against recurrent stroke study (PROGRESS). <b>Setting</b> Randomised placebo controlled trial carried out in 172 centres in Asia, Australasia, and Europe. <b>Participants</b> 1709 patients with history of stroke or transient ischaemic attack randomised to fixed doses of perindopril and indapamide. <b>Measurements</b> Mean of two blood pressure measurements in patients receiving treatment recorded to the nearest 2 mm Hg with a standard mercury sphygmomanometer at baseline and then at three months, six months, nine months, and 15 months and then every six months to 33 months. <b>Results</b> There was no change in the mean blood pressure of the cohort during the 33 month follow-up. Six months after blood pressure was stabilised on treatment, if systolic blood pressure was measured as having increased by &gt;10 mm Hg, six of those measurements would be false positives for every true increase of ≥10 mm Hg. The corresponding value for an increase of 20 mm Hg was over 200. Values for 5 mm Hg and 10 mm Hg increases in diastolic blood pressure were 3.5 and 39, respectively. The likelihood that observed increases in blood pressure reflected true increases rose with the time between measurements such that the ratio of true positives to false positives reached parity at 21 months. <b>Conclusions</b> Usual clinical approaches to the monitoring of patients taking drugs to lower blood pressure have a low probability of yielding reliable information about true changes in blood pressure. Evidence based guidelines for monitoring treatment response are urgently required to guide clinical practice. <b>Trial registration</b> Australia and New Zealand Clinical Trial Registry.
Bone formers: osteophyte and enthesophyte formation are positively associated
Authors: J. Rogers, L. Shepstone, P. Dieppe
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To test the hypothesis that enthesophyte formation and osteophyte growth are positively associated and to look for associations between bone formation at different sites on the skeleton so that a simple measure of bone formation could be derived. <h3>METHODS</h3> Visual examination of 337 adult skeletons. All common sites of either enthesophyte or osteophyte formation were inspected by a single observer who graded bone formation at these sites on a 0-3 scale. The total score for each feature was divided by the number of sites examined to derive an enthesophyte and an osteophyte score. Cronbach's α and principal components analysis were used to identify groupings. <h3>RESULTS</h3> Enthesophyte formation was associated with gender (M&gt;F) and age. There was a positive correlation between enthesophytes and osteophytes (<i>r</i> = 0.65, 95% confidence interval, 0.58 to 0.71) which remained after correction for age and gender. Principal components analysis indicated four different groupings of enthesophyte formation. By choosing one site from each group a simple index of total skeletal bone formation could be derived. <h3>CONCLUSIONS</h3> Osteophytes and enthesophytes are associated, such that a proportion of the population can be classified as "bone formers". Enthesophyte groupings provide some clues to aetiopathogenesis. Bone formation should be investigated as a possible determinant of the heterogeneity of outcome and of treatment responses in common musculoskeletal disorders.
Efficacy of carboplatin–taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials
Authors: M.M. Regan, E.K. O'Donnell, W.K. Kelly, S. Halabi, W. Berry, S. Urakami, N. Kikuno, W.K. Oh
Journal: Annals of Oncology (2009)
Ascorbic Acid Prevents Contrast-Mediated Nephropathy in Patients With Renal Dysfunction Undergoing Coronary Angiography or Intervention
Authors: Konstantinos Spargias, Elias Alexopoulos, Stamatis Kyrzopoulos, Panayiotis Iacovis, Darren C. Greenwood, Athanassios Manginas, Vassilis Voudris, Gregory Pavlides, Christopher E. Buller, Dimitrios Kremastinos, Dennis V. Cokkinos
Journal: Circulation (2004)

Contrast agents can cause a reduction in renal function that may be due to the generation of reactive oxygen species. Conflicting evidence suggests that administration of the antioxidant acetylcysteine prevents this renal impairment. The action of other antioxidant agents has not been investigated.We conducted a randomized, double-blind, placebo-controlled trial of ascorbic acid in 231 patients with a serum creatinine concentration > or =1.2 mg/dL who underwent coronary angiography and/or intervention. Ascorbic acid, 3 g at least 2 hours before the procedure and 2 g in the night and the morning after the procedure, or placebo was administered orally. Contrast-mediated nephropathy was defined by an absolute increase of serum creatinine > or =0.5 mg/dL or a relative increase of > or =25% measured 2 to 5 days after the procedure. Contrast-mediated nephropathy occurred in 11 of the 118 patients (9%) in the ascorbic acid group and in 23 of the 113 patients (20%) in the placebo group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17 to 0.85; P=0.02). The mean serum creatinine concentration increased significantly in the placebo group (from 1.36+/-0.50 to 1.50+/-0.54 mg/dL, P<0.001) and nonsignificantly in the ascorbic acid group (from 1.46+/-0.52 to 1.52+/-0.64 mg/dL, P=0.07). The mean increase in serum creatinine concentration was greater in the placebo group than in the ascorbic acid group (difference of 0.09 mg/dL; 95% CI, 0.00 to 0.17; P=0.049).Prophylactic oral administration of ascorbic acid may protect against contrast-mediated nephropathy in high-risk patients undergoing a coronary procedure.
Response to Letter Regarding Article, “Bleeding After Initiation of Multiple Antithrombotic Drugs, Including Triple Therapy, in Atrial Fibrillation Patients Following Myocardial Infarction and Coronary Intervention: A Nationwide Cohort Study”
Authors: Morten Lamberts, Jonas Bjerring Olesen, Martin Huth Ruwald, Carolina Malta Hansen, Deniz Karasoy, Søren Lund Kristensen, Lars Køber, Christian Torp-Pedersen, Gunnar Hilmar Gislason, Morten Lock Hansen
Journal: Circulation (2013)
A Multicenter, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates
Authors: Paolo Manzoni, Ilaria Stolfi, Lorenza Pugni, Lidia Decembrino, Cristiana Magnani, Gennaro Vetrano, Elisabetta Tridapalli, Giuseppina Corona, Chiara Giovannozzi, Daniele Farina, Riccardo Arisio, Franco Merletti, Milena Maule, Fabio Mosca, Roberto Pedicino, Mauro Stronati, Michael Mostert, Giovanna Gomirato
Journal: New England Journal of Medicine (2007)

Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates.
Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice
Authors: H MATSUSAKA, T IDE, S MATSUSHIMA, M IKEUCHI, T KUBOTA, K SUNAGAWA, S KINUGAWA, H TSUTSUI
Journal: Cardiovascular Research (2006)

Objective Apoptosis may play an important role in cardiac remodeling after myocardial infarction (MI). p53 is a well-known proapoptotic factor. However, its pathophysiological significance in these conditions remains unclear. We thus examined the effects of target deletion of the p53 gene on post-MI hearts.
Targeted Disruption of the Matrix Metalloproteinase-9 Gene Impairs Smooth Muscle Cell Migration and Geometrical Arterial Remodeling
Authors: Zorina S. Galis, Chad Johnson, Denis Godin, Richard Magid, J. Michael Shipley, Robert M. Senior, Eugen Ivan
Journal: Circulation Research (2002)

Matrix remodeling plays an important role in the physiological and pathological remodeling of blood vessels. We specifically investigated the role of matrix metalloproteinase (MMP)-9, an MMP induced during arterial remodeling, by assessing the effects of genetic MMP-9 deficiency on major parameters of arterial remodeling using the mouse carotid artery flow cessation model. Compared with remodeling of matched wild-type (WT) arteries, MMP-9 deficiency decreased intimal hyperplasia, reduced the late lumen loss, eliminated the correlation between intimal hyperplasia and geometric remodeling, and led to significant accumulation of interstitial collagen. Biochemical analysis of MMP-9 knockout (KO) arterial tissue and isolated smooth muscle cells (SMCs) confirmed the lack of MMP-9 expression or compensation by other gelatinases. To investigate potential mechanisms for the in vivo observations, we analyzed in vitro effects of MMP-9 deficiency on the migration, proliferation, and collagen gel contracting capacity of aortic SMCs isolated from MMP-9 KO and WT mice. Although proliferation was comparable, we found that MMP-9-deficient cells had not only decreased migratory activity, but they also had decreased capacity to contract collagen compared with WT cells. Thus, MMP-9 appears to be involved not only in degradation, but also in reorganization of a collagenous matrix, both facets being essential for the outcome of arterial remodeling. Our results also establish MMP-9 as an attractive therapeutic target for limiting the effects of pathological arterial remodeling in restenosis and atherosclerosis.
Clinical Impact of Immune Microenvironment in Stage I Lung Adenocarcinoma: Tumor Interleukin-12 Receptor β2 (IL-12Rβ2), IL-7R, and Stromal FoxP3/CD3 Ratio Are Independent Predictors of Recurrence
Authors: Kei Suzuki, Kyuichi Kadota, Camelia S. Sima, Jun-ichi Nitadori, Valerie W. Rusch, William D. Travis, Michel Sadelain, Prasad S. Adusumilli
Journal: Journal of Clinical Oncology (2012)

Purpose Mounting evidence suggests that tumor-infiltrating immune cells have prognostic value for patients with solid organ malignancies. Our aim was to investigate the prognostic significance of the immune microenvironment in patients with stage I lung adenocarcinoma (ADC). Patients and Methods Using tissue microarray and immunohistochemistry, we investigated eight types of tumor-infiltrating immune cells in the tumor nest and tumor-associated stroma as well as tumor expression of five cytokines in a uniform cohort of 956 patients with stage I lung ADC (478 each in training and validation cohorts). Results Although a high density of stromal forkhead box P3 (FoxP3) –positive cells was associated with shorter recurrence-free probability (RFP; P = .043), the relative proportion of stromal FoxP3 to CD3 was a stronger predictor of recurrence (5-year RFP, 85% for high v 77% for low ratio; P = .004). High expression of tumor interleukin-12 receptor β2 (IL-12Rβ2) was associated with better outcome (5-year RFP, 90% for high v 80% for low expression; P = .026), whereas high expression of tumor IL-7R was associated with worse outcome (5-year RFP, 76% for high v 86% for low expression; P = .001). In multivariate analysis, these immune markers were independently associated with recurrence. Although IL-7R remained significant for poor overall survival, all the markers remained prognostic for recurrence in patients with stages IA and IB disease as well as for patients with tumors ≤ 2 cm. Conclusion Our investigation confirms the biologic and prognostic significance of the tumor immune microenvironment for patients with stage I lung ADC and provides support for its use to stratify clinical outcome and immunotherapeutic interventions.
Treatment of Helicobacter pylori infection
Authors: L. Gatta, F. Di Mario, D. Vaira
Journal: Gut (2010)

We read with great interest the article of Liou et al published in Gut ,1 and we would like to highlight some points.

First, the authors stated that patients were considered positive only if two out of three tests performed (ie, rapid urease test, histology and culture) were positive. However, due to its high specificity (almost 100%),2 a positive culture alone can be considered a marker of Helicobacter pylori infection, as stated by guidelines for clinical trials on …
Dual signals underlying diabetic lymphatic barrier dysregulation
Authors: J. S. Alexander, F. Becker
Journal: Cardiovascular Research (2015)

This editorial refers to ‘Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling’ by J.P. Scallan et al. , doi:10.1093/cvr/cvv117. 

Physiologically, lymph vessels limit tissue oedema and control inflammation by recirculating solutes, lipids, and leucocytes; deficient lymphatic transport of these mediators has been described in many pathological conditions including IBD,1 obesity,2 metabolic syndrome,3 and diabetes.4 Since lymphatics are also an important route for reverse cholesterol transport,5 lymphatic transport failure may also link lymphostasis and atherogenesis. Because fluid transport in lymphatics critically depends on the integrity of the endothelial barrier, increased solute permeability, especially within lymphatic collecting vessels, can impair transport and greatly intensify the extent and severity of inflammation. Currently, evaluation of lymphovascular permeability in mice has proved …
Drug addiction finds its own niche
Authors: Alastair Reid
Journal: Behavioral and Brain Sciences (2011)

Abstract The evolutionary framework suggested by Müller &amp; Schumann (M&amp;S) can be extended further by considering drug-taking in terms of Niche Construction Theory (NCT). It is suggested here that genetic and environmental components of addiction are modified by cultural acceptance of the advantages of non-addicted drug taking and the legitimate supply of performance-enhancing drugs. This may then reduce the prevalence of addiction.