tbuckley/cabot-search huggingface dataset:
Definition of the Landscape of Promoter DNA Hypomethylation in Liver Cancer
Authors: Barbara Stefanska, Jian Huang, Bishnu Bhattacharyya, Matthew Suderman, Michael Hallett, Ze-Guang Han, Moshe Szyf
Journal: Cancer Research (2011)

We use hepatic cellular carcinoma (HCC), one of the most common human cancers, as a model to delineate the landscape of promoter hypomethylation in cancer. Using a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays, we have identified approximately 3,700 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appeared in clusters across the genome suggesting that a high-level organization underlies the epigenomic changes in cancer. In normal liver, most hypomethylated promoters showed an intermediate level of methylation and expression, however, high-CpG dense promoters showed the most profound increase in gene expression. The demethylated genes are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility, and invasion; functions that are essential for cancer progression and metastasis. The DNA methylation inhibitor, 5-aza-2'-deoxycytidine, activated several of the genes that are demethylated and induced in tumors, supporting a causal role for demethylation in activation of these genes. Previous studies suggested that MBD2 was involved in demethylation of specific human breast and prostate cancer genes. Whereas MBD2 depletion in normal liver cells had little or no effect, we found that its depletion in human HCC and adenocarcinoma cells resulted in suppression of cell growth, anchorage-independent growth and invasiveness as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Taken together, the findings define the potential functional role of hypomethylation in cancer.
Serum Inflammatory Markers and Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases
Authors: Ashwin N. Ananthakrishnan, Su–Chun Cheng, Tianxi Cai, Andrew Cagan, Vivian S. Gainer, Peter Szolovits, Stanley Y. Shaw, Susanne Churchill, Elizabeth W. Karlson, Shawn N. Murphy, Isaac Kohane, Katherine P. Liao
Journal: Clinical Gastroenterology and Hepatology (2014)
Interaction of Isoniazid and Warfarin
Authors: Alan R. Rosenthal, Timothy H. Self, Elizabeth Diane Baker, Robert A. Linden
Journal: JAMA (1977)

ALTHOUGH isoniazid has been shown to enhance the activity of the coumarin anticoagulant bishydroxycoumarin in one animal study,<sup>1</sup>investigations and clinical case reports in humans are, to our knowledge, nonexistent. We recently observed hemorrhage associated with warfarin sodium therapy in a patient taking isoniazid. <h3>Report of a Case</h3> A 35-year-old man was admitted to the City of Memphis Hospital in August 1976, complaining of bleeding from the gums, bloody urine, and bilateral flank pain and tenderness. Approximately one month prior to admission, the patient had been hospitalized for a right middle cerebral artery embolus. He had been in his usual state of good health until three days prior to admission and was receiving no medication. Following several days of heparin sodium therapy, a warfarin regimen was started, and by the time of discharge, when the patient was receiving a maintenance dosage of 10 mg/day, the prothrombin time (PT) was
Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines
Authors: Jens Nolting, Carolin Daniel, Sabine Reuter, Christina Stuelten, Peng Li, Henry Sucov, Byung-Gyu Kim, John J. Letterio, Karsten Kretschmer, Hye-Jung Kim, Harald von Boehmer
Journal: The Journal of Experimental Medicine (2009)

It has been reported that retinoic acid (RA) enhances regulatory T (T reg) cell conversion by inhibiting the secretion of cytokines that interfere with conversion. This report shows that these conclusions provide a partial explanation at best. First, RA not only interfered with cytokine secretion but also with the ability of these cytokines to inhibit T reg cell conversion of naive T cells. Furthermore, RA enhanced conversion even in the absence of inhibitory cytokines. The latter effect depended on the RA receptor α (RARα) but did not require Smad3, despite the fact that RA enhanced Smad3 expression. The RARα1 isoform was not essential for RA-dependent enhancement of transforming growth factor β–driven conversion, suggesting that conversion can also be mediated by RARα2. Interleukin (IL)-6 strongly reduced RARα expression levels such that a deficiency of the predominant RARα1 isoform leaves too little RARα2 for RA to inhibit the generation of Th17 cells in the presence of IL-6.
Prediction of Cardiac Stability After Weaning From Left Ventricular Assist Devices in Patients With Idiopathic Dilated Cardiomyopathy
Authors: Michael Dandel, Yuguo Weng, Henryk Siniawski, Evgenij Potapov, Thorsten Drews, Hans B. Lehmkuhl, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2008)

Background— During ventricular assist device (VAD) unloading, cardiac recovery is possible even in patients with chronic heart failure (HF). We sought parameters predictive of cardiac stability after VAD removal. Methods and Results— Among 81 patients weaned since March 1995, a homogenous group of 35 with idiopathic dilated cardiomyopathy weaned from left VADs was selected. We evaluated echo data obtained before left VAD implantation and during “off-pump” trials before explantation, histological changes, and serum anti-β1-adrenoceptor-autoantibody disappearance during unloading, duration of unloading, and HF duration. Postweaning 10-year survival with native hearts reached 70.7±9.2%. During the first 5 years, HF recurred in 13 patients (37.1%). Only 6 (17.1%) died after HF recurrence or noncardiac complications related to left VAD explantation. Comparison of patients with and without long-term cardiac stability showed that stable patients were younger, HF history and recovery time during unloading shorter, and preweaning left ventricular assessment revealed higher left ventricular ejection fraction, lower short/long axis ratios, and higher end diastolic relative wall thicknesses. For left ventricular ejection fraction ≥45% at end diastolic diameter of ≤55 mm, predictive value for ≥5-year cardiac stability was 87.5%. Left ventricular ejection fraction time course during the first 6 postweaning months appeared predictive for long-term stability. HF history &gt;5 years and preweaning instability of cardiac improvement appeared predictive for HF recurrence. Conclusions— In idiopathic dilated cardiomyopathy, left VAD removal can be successful for &gt;12 years even with incomplete cardiac recovery. Pre-explantation left ventricular ejection fraction, left ventricular end diastolic diameter and relative wall thicknesses, stability of unloading-induced cardiac recovery, duration of left VAD support, and HF duration before left VAD insertion allow identification of patients able to remain stable for &gt;5 years. Time course of left ventricular ejection fraction during the first 6 postweaning months allows prognostic assessment.
GELS OF NORMAL AND SICKLED HEMOGLOBIN
Authors: James G. White, Beatrice Heagan
Journal: The Journal of Experimental Medicine (1970)

Electron microscopic studies of the sickling phenomenon have described at least three different structural arrangements of sickled hemoglobin, including empty hexagonal crystals, microtubules, and solid rods. It is unlikely that sickling results in several different polymers, and it is essential to determine the true structure of sickled hemoglobin in order to define the mechanism of molecular assembly. The present study has explored the fine structure of gels formed in cell-free solutions of normal and sickle reduced and oxyhemoglobin. Gels of reduced sickled hemoglobin consisted entirely of solid rods. The gels formed from sickle oxyhemoglobin, normal oxyhemoglobin, and normal reduced hemoglobin contained masses of hollow polymers essentially identical in appearance with microtubules. These findings indicate that solid rods are the characteristic polymers of sickled hemoglobin and tubular polymers represent aberrant structures which are not related to erythrocyte sickling.
Sputum induction to aid diagnosis of smear-negative or sputum-scarce tuberculosis in adults in HIV-endemic settings
Authors: J. G. Peter, G. Theron, N. Singh, A. Singh, K. Dheda
Journal: European Respiratory Journal (2013)

Sputum induction can aid tuberculosis (TB) diagnosis, but adult data from HIV-endemic environments are limited, and it is unclear how performance varies depending on the clinical context (in-patient <i>versus</i> outpatient), HIV status and whether patients are smear-negative or sputum-scarce. 696 adults with suspected smear-negative or sputum-scarce TB from Cape Town (South Africa) were referred for routine sputum induction. Liquid culture for <i>Mycobacterium tuberculosis</i> served as the reference standard. 82% (573 out of 696) of patients provided a specimen ≥1 mL, 83% (231 out of 278) of which were of adequate quality. 15% (96 out of 652) of sputum induction specimens were culture-positive, and this yield was higher among inpatients <i>versus</i> outpatients (17% (71 out of 408) <i>versus</i> 10% (25 out of 244), p=0.01) and HIV-infected <i>versus</i> uninfected patients (17% (51 out of 294) <i>versus</i> 9% (16 out of 173), p=0.02), but similar for CD4 (&gt;200 <i>versus</i> ≤200 cells·μL<sup>−1</sup>) and patient (smear-negative <i>versus</i> sputum-scarce) subcategories. Overall sensitivity (95% CI) of smear-microscopy was 49% (39–59%), higher among in-patients <i>versus</i> outpatients (55% (43–67%) <i>versus</i> 32% (14–50%), p=0.05), but unaffected by HIV co-infection, CD4 count or patient type. 29% (203 out of 696) of patients commenced anti-TB treatment and sputum induction offered microbiological confirmation and susceptibility testing in only 47% (96 out of 203). Under programmatic conditions in an HIV-endemic environment although the yield of culture was approximately two-fold higher amongst HIV-infected patients and inpatients, a fifth of all patients were unable to provide a specimen following sputum induction. Same-day microbiological diagnosis was only possible in ∼50% of patients.
MIXED CONNECTIVE TISSUE DISEASE
Authors: Carol Black
Journal: British Journal of Dermatology (1981)

Journal Article MIXED CONNECTIVE TISSUE DISEASE Get access Carol Black Carol Black Royal Postgraduate Medical School, Hammersmith Hospital, Ducane Road London W12 oHS. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 6, 1 June 1981, Pages 713–719, https://doi.org/10.1111/j.1365-2133.1981.tb00762.x Published: 01 June 1981
Insulin resistance in uremia. Characterization of insulin action, binding, and processing in isolated hepatocytes from chronic uremic rats.
Authors: J M Kauffman, J F Caro
Journal: Journal of Clinical Investigation (1983)

We have developed a model in the rat that leads to a predictable degree of severe uremia to study the role of the liver in the insulin-resistant state of uremia. The uremic animals were euglycemic and had increased serum immunoreactive insulin when compared with their pair-fed controls. Insulin action, binding, internalization, and degradation were characterized in freshly isolated hepatocytes from uremic animals, sham-operated pair-fed, and ad lib.-fed controls. The basal rate of aminoisobutyric acid (AIB) uptake was increased in hepatocytes from both uremic and pair-fed control rats. However, while hepatocytes from uremic animals were refractory to insulin with regard to AIB uptake, there was no significant difference in the absolute increment above basal AIB uptake by hepatocytes from pair-fed and fed ad lib. animals at any insulin concentration studied. 125I-Insulin binding at 24 degrees C was higher in hepatocytes from uremic rats at every insulin concentration studied when compared with fed ad lib. controls. The time course of 125I-insulin binding to the cell and to the fractions that were membrane bound or internalized were studied at 37 degrees C. An increase in membrane-bound 125I-insulin at 37 degrees C was present also in hepatocytes from uremic animals. The same fraction of membrane-bound 125I-insulin was internalized in hepatocytes from all groups of animals. Extracellular and receptor-mediated 125I-insulin degradation at the plasma membrane and after internalization was studied at 37 degrees C by gel chromatography. There was a delayed and decreased rate of 125I-insulin degradation in hepatocytes from uremic rats in the three compartments. We conclude: (a) In chronic uremia the liver is refractory to insulin with regard to AIB uptake. (b) Insulin resistance in uremic rat liver is not due to defects in insulin binding or internalization. (c) Despite the high level of circulating immunoreactive insulin, hepatocytes from uremic rats did not show the expected "down regulation" of their insulin receptors or an increased rate of insulin degradation. These studies further emphasize the primary role of postbinding events in the regulation of insulin binding and degradation. The mechanism as to how the coordinated steps of insulin metabolism in the liver are disrupted in a pathological state is presently unknown.
Cyclophosphamide-methotrexate ‘metronomic’ chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation
Authors: G. Bocci, M. Tuccori, U. Emmenegger, V. Liguori, A. Falcone, R.S. Kerbel, M. Del Tacca
Journal: Annals of Oncology (2005)
Long-term low-dose erythromycin in patients with unexplained chronic cough: a double-blind placebo controlled trial
Authors: N. Yousaf, W. Monteiro, D. Parker, S. Matos, S. Birring, I. D. Pavord
Journal: Thorax (2010)

<h3>Aims</h3> Unexplained chronic cough is a common condition with no satisfactory treatments. Previous work has suggested that cough may be linked to neutrophilic airway inflammation. This study tested the hypothesis that long-term low-dose erythromycin reduces the induced sputum neutrophil count and 24 h cough frequency in patients with unexplained chronic cough. <h3>Methods</h3> 30 patients with an unexplained chronic cough lasting more than 8 weeks were randomly assigned to take 250 mg erythromycin once daily (n=15) or placebo (n=15) for 12 weeks in a double-blind parallel group study. Cough frequency, cough reflex sensitivity and cough severity were assessed at baseline, 6, 12 and 24 weeks. The primary outcome measure was change in 24 h cough frequency at 12 weeks. <h3>Results</h3> There was no difference in the change in cough frequency between the erythromycin and placebo groups at 12 weeks (mean difference in fold change 1.1; 95% CI 0.7 to 1.5; p=0.585) or at other times. There was a statistically significant between-treatment difference in the change in sputum neutrophils at 12 weeks (−10.2% vs +6.6% with erythromycin and placebo; mean difference 16.8%; 95% CI 1.6 to 32.1; p=0.03) but not at other times. There was no difference in the change in other measures of cough between treatments. <h3>Conclusions</h3> Treatment with low-dose erythromycin for 12 weeks reduces the induced sputum neutrophil count but not cough frequency or severity in patients with unexplained chronic cough.
Estimation of HIV Incidence in the United States
Authors: H. Irene Hall, Ruiguang Song, Philip Rhodes, Joseph Prejean, Qian An, Lisa M. Lee, John Karon, Ron Brookmeyer, Edward H. Kaplan, Matthew T. McKenna, Robert S. Janssen
Journal: JAMA (2008)

<h3>Context</h3>Incidence of human immunodeficiency virus (HIV) in the United States has not been directly measured. New assays that differentiate recent vs long-standing HIV infections allow improved estimation of HIV incidence.<h3>Objective</h3>To estimate HIV incidence in the United States.<h3>Design, Setting, and Patients</h3>Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia.<h3>Main Outcome Measure</h3>Estimated HIV incidence.<h3>Results</h3>An estimated 39 400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56 300 (95% confidence interval [CI], 48 200-64 500); the estimated incidence rate was 22.8 per 100 000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55 400 (95% CI, 50 000-60 800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter.<h3>Conclusions</h3>This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals.
Giant Saphenous Vein Graft Aneurysm Compressing Right Ventricular Outflow Tract and Main Pulmonary Artery
Authors: Rodrigo Fernández-Jiménez, Aleksander Kempny, Matina Prapa, Mohamed Amrani, Richard Trimlett, Anselm Uebing, Gerhard-Paul Diller, Konstantinos Dimopoulos, Tarun Mittal, Lorna Swan, Michael A. Gatzoulis
Journal: Circulation (2013)
Aspirin Plus Coumarin Versus Aspirin Alone in the Prevention of Reocclusion After Fibrinolysis for Acute Myocardial Infarction
Authors: Marc A. Brouwer, Paul J.P.C. van den Bergh, Wim R.M. Aengevaeren, Gerrit Veen, Hans E. Luijten, Don P. Hertzberger, Ad J. van Boven, Ralf P.J.W. Vromans, Gérard J.H. Uijen, Freek W.A. Verheugt
Journal: Circulation (2002)

Background — Despite the use of aspirin, reocclusion of the infarct-related artery occurs in ≈30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction. Methods and Results — At coronary angiography &lt;48 hours after fibrinolytic therapy, 308 patients receiving aspirin and intravenous heparin had a patent infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow). They were randomly assigned to standard heparinization and continuation of aspirin alone or to a 3-month combination of aspirin with moderate-intensity coumarin, including continued heparinization until a target international normalized ratio (INR) of 2.0 to 3.0. Angiographic and clinical follow-up were assessed at 3 months. Median INR was 2.6 (25 to 75th percentiles 2.1 to 3.1). Reocclusion (≤TIMI grade 2 flow) was observed in 15% of patients receiving aspirin and coumarin compared with 28% in those receiving aspirin alone (relative risk [RR], 0.55; 95% CI 0.33 to 0.90; P &lt;0.02). TIMI grade 0 to 1 flow rates were 9% and 20%, respectively (RR, 0.46; 95% CI, 0.24 to 0.89; P &lt;0.02). Survival rates free from reinfarction and revascularization were 86% and 66%, respectively ( P &lt;0.01). Bleeding (TIMI major and minor) was infrequent: 5% versus 3% ( P =NS). Conclusions — As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.
Therapeutic Footwear Can Reduce Plantar Pressures in Patients With Diabetes and Transmetatarsal Amputation
Authors: Michael J Mueller, Michael J Strube, Brent T Allen
Journal: Diabetes Care (1997)

OBJECTIVE To compare how footwear (full-length shoe or short shoe), a total contact insert, a rigid rocker-bottom (RRB) sole, and an ankle-foot orthosis (AFO) affect peak plantar pressure (PPP) on the distal residuum and contralateral extremity of patients with diabetes and transmetatarsal amputation (TMA). RESEARCH DESIGN AND METHODS Thirty patients with diabetes and TMA participated (mean age 62 ± 4 years). In-shoe plantar pressures during walking were measured in six types of footwear. Each measurement occurred after a 1-month adjustment period. Repeated measure analysis of variance (ANOVA) was used to compare treatments. RESULTS All five types of therapeutic footwear reduced plantar pressures compared with regular shoes with a toe-filler (P &amp;lt; 0.05). A full-length shoe, total contact insert, and RRB sole resulted in lower pressures on the distal residuum (222 vs. 284 kPa) and forefoot of the contralateral extremity (197 vs. 239 kPa), compared with a regular shoe and toe-filler. Footwear with an AFO showed reduced PPP on the residuum, but most patients complained of reduced ankle motion during walking. A short shoe reduced pressures on the residuum, but not on the contralateral extremity, and many patients had complaints regarding cosmesis of the shoe. CONCLUSIONS The full-length shoe, total contact insert, and an RRB sole provided the best pressure reduction for the residuum and contralateral foot, with the optimal compromise for cosmetic acceptance and function.
Genetic Variation of DKK3 May Modify Renal Disease Severity in ADPKD
Authors: Michelle Liu, Sally Shi, Sean Senthilnathan, Julie Yu, Elliot Wu, Carsten Bergmann, Klaus Zerres, Nadja Bogdanova, Eliecer Coto, Constantinos Deltas, Alkis Pierides, Kyproula Demetriou, Olivier Devuyst, Berenice Gitomer, Marku Laakso, Anne Lumiaho, Klea Lamnissou, Riccardo Magistroni, Patrick Parfrey, Martijn Breuning, Dorien J.M. Peters, Roser Torra, Christopher G. Winearls, Vicente E. Torres, Peter C. Harris, Andrew D. Paterson, York Pei
Journal: Journal of the American Society of Nephrology (2010)

Significant variation in the course of autosomal dominant polycystic kidney disease ( ADPKD) within families suggests the presence of effect modifiers. Recent studies of the variation within families harboring PKD1 mutations indicate that genetic background may account for 32 to 42% of the variance in estimated GFR (eGFR) before ESRD and 43 to 78% of the variance in age at ESRD onset, but the genetic modifiers are unknown. Here, we conducted a high-throughput single-nucleotide polymorphism (SNP) genotyping association study of 173 biological candidate genes in 794 white patients from 227 families with PKD1. We analyzed two primary outcomes: (1) eGFR and (2) time to ESRD (renal survival). For both outcomes, we used multidimensional scaling to correct for population structure and generalized estimating equations to account for the relatedness among individuals within the same family. We found suggestive associations between each of 12 SNPs and at least one of the renal outcomes. We genotyped these SNPs in a second set of 472 white patients from 229 families with PKD1 and performed a joint analysis on both cohorts. Three SNPs continued to show suggestive/significant association with eGFR at the Dickkopf 3 (DKK3) gene locus; no SNPs significantly associated with renal survival. DKK3 antagonizes Wnt/β-catenin signaling, which may modulate renal cyst growth. Pending replication, our study suggests that genetic variation of DKK3 may modify severity of ADPKD resulting from PKD1 mutations.