tbuckley/cabot-search huggingface dataset:
RNA-Seq methods for imperfect samples: development, evaluation and applications
Authors: Xian Adiconis, Lin Fan, David DeLuca, Andrey Sivachenko, Nathalie Pochet, Aaron Berlin, Sarah Young, Gad Getz, Aviv Regev, Chad Nusbaum, Andreas Gnirke, Joshua Z Levin
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Is Plasma Oxidized Low-Density Lipoprotein, Measured With the Widely Used Antibody 4E6, an Independent Predictor of Coronary Heart Disease Among U.S. Men and Women?
Authors: Tianying Wu, Walter C. Willett, Nader Rifai, Iris Shai, JoAnn E. Manson, Eric B. Rimm
Journal: Journal of the American College of Cardiology (2006)
188. Transfer of DNA in Tissues Using Local Fast Injection
Authors: Franck M. Andre, Christel O. Cournil-Henrionnet, Paule Opolon, Lluis M. Mir
Journal: Molecular Therapy (2005)

Top of pageAbstract
The simple injection of naked DNA into skeletal muscle is known to result in the expression of the injected gene even though at very low and variable levels. We report here that, with respect to the local (intratissular) slow injection of the DNA (in about 25 seconds), the local fast injection in 1 to 2 seconds results in an increase in gene expression from 10 times in tumors and 100 times in liver, up to 500 times in the skeletal muscle. We also show that the fast liquid injection affects cell membrane and we demonstrate that the main mechanism of the increase in DNA uptake and gene expression is the enhancement of the receptor-mediated endocytosis of the injected DNA. However, at the highest speed of injection, there is not a complete inhibition of this receptor-mediated endocytosis process by means of a huge excess of a competitive inhibitor (heparin), suggesting the existence of another minor process for DNA uptake. Using a classical marker of membrane permeability (propidium iodide) we show that this small amount of non heparin-inhibitable DNA uptake could result from the direct permeabilisation of the cells by the high speed/high pressure DNA injection. This hydroporation could be similar to the permeabilisation found in the hydrodynamics method based upon the fast intravascular DNA injection. Neither the hydroporation nor the increase in DNA receptor-mediated endocytosis induce histologically detectable lesions, and the level of cell stress in the muscle, as measured by Hsp70 gene transcription induction, is similar whatever the injection speed. Thus the fast intratissular injection of DNA is a safe, easy and quick way to achieve local gene expression using naked DNA.
Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome
Authors: K. Kojima, Y. Inoue, Y. Katayama, M. Kataoka, K. Sunami, S. Fukuda, T. Sezaki, E. Omoto, M. Harada
Journal: Allergy (1998)

We report a case of hyperimmunoglobulin E syndrome (HIE) complicated by neutrophil deficiency which was successfully treated with oral administration of disodium cromoglycate. A 48‐year‐old Japanese man with HIE developed Streptococcus pneumoniae meningitis. Laboratory tests after the meningitis revealed persistent neutropenia (300‐800/mm 3 ) and defects of phagocytosis and bacterial killing by neutrophils. Administration of disodium cromoglycate was started, and neutrophil counts gradually increased to 1200‐1600/mm 3 TTie impaired neutrophil activities returned to normal. The patient improved clinically; during the 2‐year treatment, he had only two brief episodes of the common cold. Disodium cromoglycate may have potential clinical use in the treatment of cases of HIE even with neutrophil deficiency.
56 LONG-TERM EFFICACY OF ROSIGLITAZONE IN NONALCOHOLIC STEATOHEPATITIS (NASH): RESULTS OF THE EXTENSION PHASE OF THE FLIRT-2 TRIAL
Authors: V. Ratziu, F. Charlotte, C. Bernhardt, L. Serfaty, P. Podevin, J. Moussalli, T. Poynard
Journal: Journal of Hepatology (2009)
Antineutrophil cytoplasmic antibodies and their relevance to the dermatologist
Authors: N.P. BURROWS, C.M. LOCKWOOD
Journal: British Journal of Dermatology (2006)

The term vasculitis embraces a heterogeneous group of conditions which may occur as primary phenomena or secondary to disorders such as rheumatoid arthritis or systemic lupus erythematosus. Classification of vasculitis is often difficult in the absence of identifiable aetiological factors or specific serological markers. However, the primary systemic vasculitides can be segregated morphologically, according to the size of blood vessels involved and the presence of granulomata (Table 1). Recently, the discovery of circulating antineutrophil cytoplasmic antibodies (ANCA) in many patients with these disorders, whose differing specificities substantiate the histological classification, has led to interest being focused on their relevance in the development of vasculitis. This paper reviews the historical aspects of the detection of ANCA, and the value of these antibodies in the diagnosis and management of the primary systemic vasculitides likely to be encountered by the dermatologist. The clinical features in patients with these vasculitides are also outlined.
Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas
Authors: Nathalie Théret, Orlando Musso, Bruno Turlin, Dominique Lotrian, Paulette Bioulac-Sage, Jean-Pierre Campion, Karim Boudjéma, Bruno Clément
Journal: Hepatology (2001)

Matrix metalloproteinase–2 (MMP2) is a key enzyme in the process of extracellular matrix remodeling involved in tumor invasion and metastasis. The activation of MMP2 involves interplay with the membrane type–matrix metalloproteinase–1 (MT1–MMP) and the tissue inhibitor of metalloproteinase–2 (TIMP2). In vitro, activated hepatic stellate cells are a main source of MMP2 and collagen I induces MMP2 activation. The steady–state mRNA levels of MMP2, MT1–MMP, TIMP2, collagen I, collagen IV, and laminin γ1 were compared with MMP2 activity in 55 hepatocellular carcinomas, 47 matching nontumor biopsies and 19 histologically normal livers. In hepatocellular carcinomas, increased collagen I mRNA levels were strongly associated with those of MMP2 (Spearman R = .74, P &lt; .001), MT1–MMP (R = .65, P &lt; .001) and TIMP2 (R = 0.61, P &lt; .001). MMP2 activity was correlated with the mRNA expression of collagen I (R = .45 P &lt; .01), collagen IV (R = .40, P &lt; .01) and laminin γ1 (R = .33, P &lt; .05). Unlike collagen IV and laminin γ1 mRNAs, MMP2, MT1–MMP, TIMP2, collagen I mRNA levels were increased in nonencapsulated compared with encapsulated tumors ( P &lt; .05). In addition, MMP2 activity was fourfold higher ( P &lt; .01) in tumors arising in cirrhotic livers than in those arising in noncirrhotic livers. Moreover, tumor recurrence was associated with 4.6– and 2.8–fold ( P &lt; .05) higher collagen I and MMP2 mRNA levels, respectively, in hepatocellular carcinomas arising in cirrhotic livers. Thus, a high extracellular matrix remodeling favors tumor progression in hepatocellular carcinomas.
Visceral and skin granuloma annulare, diabetes, and polyendocrine disease.
Authors: D J Thomas, M Rademaker, D D Munro, D A Levison, G M Besser
Journal: BMJ (1986)

A middle aged man suffered with insulin dependent diabetes, autoimmune Addison9s disease, myxoedema, and severe ulcerative colitis, for which he had undergone subtotal colectomy with formation of an ileostomy. Granuloma annulare confined to the anterior abdominal wall was diagnosed in 1981. In 1983 an episode of severe colicky pain and excessive working of the ileostomy occurred associated with severe hyperglycaemia and increased irritation of the granuloma annulare. Laparotomy disclosed adhesions and numerous white nodules over bowel, mesentery, and peritoneum histologically identical with the skin lesions. Two further episodes of subacute small bowel obstruction occurred, and a repeat laparotomy showed widespread intra-abdominal granuloma annulare. Visceral granuloma annulare appears not to have been reported before, and in this patient exacerbation of the skin lesion was associated with poor diabetic control.
Observations on Acute Renal Insufficiency Following Oral Cholecystography.
Authors: Ralph M. Myerson
Journal: Annals of Internal Medicine (1964)

s1 April 1964Observations on Acute Renal Insufficiency Following Oral Cholecystography.Ralph M. Myerson, M.D., F.A.C.P., J. George Teplick, M.D., Frank J. Sanen, M.D.Ralph M. Myerson, M.D., F.A.C.P.Search for more papers by this author, J. George Teplick, M.D.Search for more papers by this author, Frank J. Sanen, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-724_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRecently there has been a number of reports of serious renal impairment after the use of oral cholecystographic media. Each of four opaque media was administered to patients without evidence of renal and hepatic disease and to known cirrhotic patients. In addition, one medium was administered to 18 patients with chronic renal insufficiency.Renal function was studied before and after the administration of the contrast media by determinations of blood urea nitrogen, blood creatinine, and creatinine clearance. Urinary output was followed and urinalyses were performed frequently. Blood pressures were determined hourly on the night of dye administration.No alteration in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Ralph M. Myerson, M.D., F.A.C.P.; J. George Teplick, M.D.; Frank J. Sanen, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1964Volume 60, Issue 4Page: 724-725KeywordsAcute renal failureBloodBlood pressureBlood urea nitrogenCreatinineRenal diseases ePublished: 1 December 2008 Issue Published: 1 April 1964 PDF downloadLoading ...
The private health sector in India
Authors: Amit Sengupta, Samiran Nundy
Journal: BMJ (2005)

Is burgeoning, but at the cost of public health care 

F oreigners in increasing numbers are now coming to India for private health care. They come from the Middle East, Africa, Pakistan, and Bangladesh, for complex paediatric cardiac surgery or liver transplants—procedures that are not done in their home countries. They also come from the United Kingdom, Europe, and North America for quick, efficient, and cheap coronary bypasses or orthopaedic procedures. A shoulder operation in the UK would cost £10 000 ($17 460; €14 560) done privately or entail several months' wait under the NHS. In India, the same operation can be done for £1700 and within 10 days of a first email contact.1

The recent remarkable growth of the private health sector in India has come at a time when public spending on health care at 0.9% of gross domestic product (GDP) is among the lowest in the world and ahead of only five countries—Burundi, Myanmar, Pakistan, Sudan, and Cambodia. This proportion has fallen from an already low 1.3% of GDP in 1991 when the neoliberal economic reforms began.2

Yet India ranks among the top 20 of the world's countries in its private spending, at 4.2% of GDP. Employers pay for 9% of spending on private care, health insurance …
Expression of hepatitis B virus proteins in transgenic mice alters lipid metabolism and induces oxidative stress in the liver
Authors: Fu Yang, Shikai Yan, Ying He, Fang Wang, Shuxia Song, Yingjun Guo, Qi Zhou, Yue Wang, Zhongying Lin, Yun Yang, Weidong Zhang, Shuhan Sun
Journal: Journal of Hepatology (2007)
Recent developments in anti‐inflammatory natural products
Authors: Raju Gautam, Sanjay M. Jachak
Journal: Medicinal Research Reviews (2009)

Abstract Many of the inflammatory diseases are becoming common in aging society throughout the world. The clinically used anti‐inflammatory drugs suffer from the disadvantage of side effects and high cost of treatment (in case of biologics). Alternative to these drugs are traditional medicines and natural products, which offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Since ancient times traditional medicines and phytopharmaceuticals are being used for the treatment of inflammatory and other disorders. The present review article describes anti‐inflammatory natural products derived from plants and marine sources reported during last decade. The compounds described belong to different chemical classes such as alkaloids, steroids, terpenoids, polyphenolics, phenylpropanoids, fatty acids and lipids, and various miscellaneous compounds. The attempt is also being made to enumerate the possible leads, e.g. curcumin, resveratrol, baicalein, boswellic acid, betulinic acid, ursolic acid, and oleanolic acid, for further development with the help of structure–activity relationship (SAR) studies and their current status. In addition SAR studies carried out on the anti‐inflammatory activity of flavonoid compounds and clinical studies performed on anti‐inflammatory natural products are also discussed. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 5, 767–820, 2009
Identifying familial myelodysplastic/acute leukemia predisposition syndromes through hematopoietic stem cell transplantation donors with thrombocytopenia
Authors: Jane E. Churpek, Eric Nickels, Rafael Marquez, Katarzyna Rojek, Bohao Liu, Rachelle Lorenz, Janet Lepore, Jozef Madzo, Amittha Wickrema, Andrew S. Artz, Koen van Besien, Lucy A. Godley
Journal: Blood (2012)
Abstract 1440: Pediatric pulmonary microenvironment differs from adults: Implications for pulmonary metastasis
Authors: Andrea Anita Hayes-Jordan, Yong Xin Wang
Journal: Cancer Research (2010)

Abstract Background: Ewing's sarcoma (ES) is the second most common bone tumor in children. Still, despite multimodal therapy, lung metastasis are the most common cause of demise. Older age has been found to portend a poorer survival in ES. Here we identify differences in the pulmonary micro-environment comparing pediatric to adult lung tissue. Purpose: To identify molecular differences in the pediatric and adult lung micro-environment. Methods: To evaluate whether adult lungs provide a more permissive metastatic environment compared to pediatric lungs, we measured the migration and invasion of ES cells in a modified Boyden chamber assay. ES TC-71 cells, know to have moderate metastatic potential and ES LM-7 cells which are highly metastatic, were compared normal lung epithelial cells (CRL2300). Lungs from 4 week old adolescent and 9 week old adult nude mice, were morselated and placed in a modified Boyden chamber. To compare expression of metastatic genes in pediatric compared to adult lung, RNA was extracted from 4 week and 9 week nude mouse lung and a focused microarray of 128 genes were evaluated for differential expression. Results: The TC-71 cell line and the CRL2300 cells had equal area of migration to adolescent and adult lung. Whereas, LM-7 had a significantly larger area of cell migration to the adult lung compared to the adolescent lung.(p=0.033) The focused gene expression profile demonstrated significant differential expression of 2 genes, Interleukin 1-beta (IL1-B), and Integrin beta-3 (ItgB3). IL1-B was significantly under-expressed and ItgB3 was significantly over-expressed in adolescent lung tissue compared to adult lung tissue. Conclusions: Highly metastatic ES LM-7 cells have a significantly decreased migration to the adolescent/pediatric lung compared to adult lung tissue. This implies a different microenvironment in adolescent lung which does not have the same affinity for metastatic Ewing's sarcoma cells as the adult lung. Furthermore, differential gene expression of IL1-B and ItgB3 and may contribute to the cause of this difference since ItgB3 regulates cell adhesion, invasion and low doses of IL1-B can cause tumor cell eradication. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1440.
Postpartum Hemolytic Uremic Syndrome
Authors: L. Weinstein
Journal: JAMA (1982)

<h3>To the Editor.—</h3> My compliments to Spencer et al for an excellent clinical outcome by the use of plasma exchange in a female patient thought to have postpartum hemolytic uremic syndrome (HUS) (1982;247:2808). Unfortunately, the authors have fallen into the clinical trap of describing the trees but missing the forest. The condition present in their patient is a variant of severe preeclampsia comprised of microangiopathic hemolytic anemia, which caused the hemolysis (H), elevated levels of liver enzymes (EL), and thrombocytopenia (LP indicates low platelet count).<sup>1</sup>The term<i>HELLP syndrome</i>has been given to this compilation of symptoms that may occur ante partum or post partum. The treatment described of plasma exchange has been used at the University of Arizona, Tucson, as well as by other investigators.<sup>2</sup> The various forms of preeclampsia are often misdiagnosed, resulting in excessive perinatal and maternal morbidity and mortality.<sup>3</sup>The clinician who is
Improved Pregnancy Outcome Following Successful Treatment of Chlamydial Infection
Authors: Ilan Cohen
Journal: JAMA (1990)

Pregnancy outcomes of 244 women, successfully treated with erythromycin ethylsuccinate for cervical chlamydial infection, were compared with those of 79 chlamydia-positive pregnant women, who failed to respond to treatment, and 244 chlamydia-free control women, who were not treated. The three groups were at high risk for infection with Chlamydia trachomatis. The frequencies of premature rupture of the membranes, premature contractions, and small-for-gestational-age infants were significantly lower in the successfully treated patients when compared with those of the chlamydia-positive patients, but were not significantly different when compared with those of the control patients. These data indicate that in a pregnant population at high risk for infection with C trachomatis, repeated prenatal chlamydial testing, plus successful erythromycin treatment, can significantly reduce certain adverse effects on pregnancy outcome.
Immunocytochemical Localization of rH1 Sodium Channel in Adult Rat Heart Atria and Ventricle
Authors: Sidney A. Cohen
Journal: Circulation (1996)

Background Of the five sodium channel subtypes expressed in cardiac tissues, the rat (rH1) and human (hH1) isoforms are thought to be the predominant subtypes on the basis of heterologous expression studies. In this study, subtype-specific antibodies and immunocytochemistry were used to confirm protein expression and to localize rH1 protein in cardiac tissues. Methods and Results Subtype-specific antibodies immunolabeled adult rat heart tissue in a manner identical to that obtained with subtype-nonselective antibodies. All antibodies specifically bound to the surface and t-tubular systems of atrial and ventricular muscle cells. Cytoplasmic labeling, reflecting nascent sodium channels or cytoplasmic stores of sodium channel protein, was apparent. Most notably, all antibodies also specifically labeled the subset of intercalated disks located at the ends but not the sides of adjacent ventricular muscle cells. Conclusions rH1 is the predominant subtype expressed on rat atrial and ventricular muscle cells. rH1 protein localization in surface and t-tubular membranes is consistent with its proposed role in coordinating membrane depolarization along the length and deep within cardiac muscle cells. rH1 protein localization in terminal intercalated disks suggests that sodium channels may also act as a localized voltage-dependent current amplifier, raising the safety margin for conduction; they also may contribute to anisotropic or saltatory conduction in cardiac tissues. These electrophysiological properties would be particularly important under conditions of altered channel function resulting from ion channel gene defects (eg, long QT syndrome), antiarrhythmic drug therapy, ischemia, or other heart diseases by influencing the electrophysiological substrate for ventricular tachyarrhythmias. (Circulation. 1996;94:3083-3086.)
A Risk Model for Prediction of Lung Cancer
Authors: M. R. Spitz, W. K. Hong, C. I. Amos, X. Wu, M. B. Schabath, Q. Dong, S. Shete, C. J. Etzel
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundReliable risk prediction tools for estimating individual probability of lung cancer have important public health implications. We constructed and validated a comprehensive clinical tool for lung cancer risk prediction by smoking status.
The role of the bronchial vasculature in soluble particle clearance.
Authors: E M Wagner, W M Foster
Journal: Environmental Health Perspectives (2001)

Although a role for the airway circulation in the clearance of inhaled particles is generally assumed, there is little information to confirm its importance. We studied the effects of decreased bronchial blood flow on the uptake of the soluble tracer technetium=99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from subcarinal airways in sheep (n = 7). The bronchial artery was cannulated and perfused with autologous blood at a control flow (0.6 mL/min/kg) or when the perfusion pump was stopped (no flow). (99m)Tc-DTPA (6-10 microL) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both during control blood flow conditions and no-flow conditions. Airway retention (by scintigraphy) and blood uptake were monitored for 30 min after the local deposition of (99m(Tc-DTPA. During control flow conditions, 30 min after the delivery of the radiolabel, 21% of the tracer remained at the deposition site. Of the total delivered tracer, maximum blood uptake was 18% (n) = 3). When bronchial perfusion was stopped, airway retention 30 min after deposition increased to 43%, and maximum blood uptake decreased to 7% of the total delivered tracer. Although mucociliary clearance was not directly measured, radiolabel tracer was observed to move progressively from the deposition site up to larger airways and contributed to the overall removal of tracer from the site of deposition during both flow conditions. However, these results demonstrate that decreased bronchial perfusion increases airway retention by limiting vascular uptake of the soluble tracer. These results emphasize the importance of normal perfusion of the airway vasculature for uptake of therapeutic agents delivered specifically to the conducting airways.