tbuckley/cabot-search huggingface dataset:
Abstract 1507: Aberrant oncolytic human adenovirus late mRNA translation causes failure of viral progeny production in murine cancer
Authors: Anna M. Young, Iain A. McNeish
Journal: Cancer Research (2010)

Abstract Introduction. Oncolytic viruses have therapeutic potential in cancer by selectively replicating within malignant cells, causing death. Adenovirus type 5(Ad5) mutant dl922-947 contains a 24 bp deletion in E1A-CR2 and selectively replicates in cells with an abnormal Rb pathway - a feature of 90% human malignancies. dl922-947 has activity in human ovarian cancer following intraperitoneal (ip) delivery. Immunocompetent models are essential to evaluate the host immunological response as adenoviruses induce robust immune responses and CD8+ T cell infiltration has prognostic importance in ovarian cancer. However, adenoviridae are species specific and Ad5 fails to produce infectious progeny in murine tissue, preventing development of such models. We have investigated why human adenovirus replication fails in murine cancer. Methods. dl922-947 lifecycle was examined in murine carcinoma cells CMT64 and MOVCAR7 and human epithelial ovarian cancer (EOC) cells OVCAR4. Results. Infectivity, qPCR and sub-fractionation assays demonstrated no deficit in virion internalisation, genome replication or mRNA nuclear export in murine cells. E1A transcription and expression were similar in murine and human cells. However, there was marked failure of late viral capsid protein expression on immunoblot, which was not reversed by proteasome inhibition. TCID50 assay confirmed minimal infectious progeny production in murine cells (0.005-0.25 pfu/cell at MOI 10 in murine cells vs 104 pfu/cell in OVCAR4 cells 48h pi). Temporal differences in late gene transcription were seen between OVCAR4 and MOVCAR7 but not CMT64 cells, whilst late mRNA processing was qualitatively normal in murine cells. dl922-947 infection failed to induce global shut-down of host protein translation in murine cells on Coomassie staining. Transcription of L4 100K, important for preferential viral mRNA translation, was 1 log lower in murine cells than human controls, which may contribute to decreased production of infectious virions. Interestingly, co-infection of MOVCAR7 cells with dl922-947 and murine adenovirus type 1 (MAV-1) partially rescued late viral protein expression and increased dl922-947 cytotoxicity by MTT assay (&amp;gt;50% reduction of EC50). Conclusions: Failure of late viral mRNA translation results in failure of dl922-947 replication in murine cells. Current work focuses on the importance of the 5’ UTR tripartite leader sequence (TPL) common to all adenoviral late mRNAs. Specifically, sequence differences between human Ad5 and MAV-1 TPL may prevent adequate translation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1507.
FDA halts sale of genetic test sold to consumers
Authors: M. McCarthy
Journal: BMJ (2013)

The US Food and Drug Administration has ordered 23andMe, which sells genetic testing directly to consumers, to stop marketing its popular $99 (£60; €73) home testing service.

For the test consumers provide a DNA sample by spitting into the company’s “DNA spit kit” and mail it for analysis.

The company claims that its Personal Genome Service (PGS) is capable of identifying more than 250 genetic risk markers for disease and adverse drug reactions. The company claims …
NT-PROBNP PREDICTS THE DEVELOPMENT OF ARTERIAL HYPERTENSION IN NORMOTENSIVE AND PREHYPERTENSIVE SUBJECTS: THE MULTIETHNIC STUDY OF ATHEROSCLEROSIS (MESA)
Authors: Daniel Duprez, David R. Jacobs, Hossein Bahrami, Joao Lima, Carmen A. Peralta, Lori Daniels, Alan Maisel
Journal: Journal of the American College of Cardiology (2012)
Lichen planus associated with hepatitis C
Authors: Betty Bellman, RajenderK. Reddy, Vincent Falanga
Journal: The Lancet (1995)

confirmed cases concentrated in western, south-central, and south Atlantic states of the USA between May and July and the unnamed agent of human granulocytic ehrlichiosis diagosed in 12 cases in Minnesota and Wisconsin.2Very few data are available from other countries: to our knowledge, in Europe, cases have only been reported from Portugal3 and Spain.Human ehrlichiosis appears to be a tick-borne zoonose transmitted in the US by Amblyoma americanum and perhaps Dermacentor variabili.The occurrence of additional vectors has been suggested since a few cases were observed in the US outside their distribution area as well as in Africa and in Europe.5The exceptionally warm weather observed in Western Europe this summer may have contributed to the occurrence of this case in Belgium.Serological tests for Ehrlichia should be performed in patients presenting with fever, leucopenia, thrombo-cytopenia, elevated serum transaminases and a history of recent tick bite or outdoor activities.
Glycosuria and Diabetes
Authors: A. GALAMBOS
Journal: Annals of Internal Medicine (1929)

Article1 June 1929Glycosuria and DiabetesA. GALAMBOS, M.D.A. GALAMBOS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-12-1328 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAt the February meeting of the Progressive Medical Society of New York Dr. Louis I. Harris, Health Commissioner of New York City, called our attention to the significance of the Periodic Health Examinations, emphasizing the importance of age. The usefulness of the periodic health examination can hardly be demonstrated in a more impressive way than in the practical case of glycosuria and diabetes. In this special instance the periodic health examination undoubtedly increases the number of the early diagnosed cases and consequently if there is any value in the early diagnosis, this swings the ratio between the mild and severe... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: A. GALAMBOS, M.D.Affiliations: New York City PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1929Volume 2, Issue 12Page: 1328-1340 ePublished: 1 December 2008 Issue Published: 1 June 1929 PDF downloadLoading ...
The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis
Authors: Janneke M. Stapelbroek, Casper W. Bollen, Johannes K. Ploos van Amstel, Karel J. van Erpecum, Jan van Hattum, Leonard H. van den Berg, Leo W.J. Klomp, Roderick H.J. Houwen
Journal: Journal of Hepatology (2004)
Coronary venous perfusion of the ischemic myocardium during acute coronary artery occlusion in isolated rat hearts.
Authors: Y Taira, H Kanaide, M Nakamura
Journal: Circulation Research (1985)

Effects of retrograde coronary venous perfusion on oxygen supply and energy metabolism of ischemic myocardium of the isolated perfused rat heart were examined by means of NADH fluorescence photography. Occlusion of the left coronary artery produced regional ischemia of the left ventricular free wall, as evidenced by the sharply demarcated increase in NADH fluorescence. During ischemia, a narrow area of minimal fluorescence (140 +/- 10 microns), indicating sufficient oxygenation for oxidative phosphorylation, was observed around the epicardial coronary veins in the ischemic lesion. Retrograde perfusion was introduced through the coronary vein (left cardiac vein) that drained off the ischemic area, which resulted in a marked reduction of the area of increased NADH fluorescence in the epicardial surface. In the cross-sectional view, although the myocardium of the entire ischemic area induced by left coronary artery occlusion could be perfused by venous retroperfusion, the effect on reduction of the area of increased NADH fluorescence was seen only in the epicardial half of the myocardium. Retrograde coronary venous perfusion also resulted in a small increase in tension development (P less than 0.05), a decrease in resting tension (P less than 0.01), and partial preservation of myocardial high energy phosphate content (P less than 0.01). We propose that coronary venous retroperfusion improves oxygenation, partially preserves oxidative phosphorylation in the epicardium, and improves contractile function in the ischemic region.
ARE TWO-DIMENSIONAL MEASURED SAGITTAL PLANE KINEMATICS RELATED TO THREE-DIMENSIONAL JOINT LOADING DURING THE DROP VERTICAL JUMP TEST?
Authors: B Dingenen, B Malfait, J Vanrenterghem, M Robinson, S Verschueren, F Staes
Journal: British Journal of Sports Medicine (2014)

Background Acute and overuse knee injuries are common in sports involving jump-landing movements, especially in female athletes. More erect sagittal plane movement patterns are believed to increase injury risk. Whilst three-dimensional (3D) measurements are considered to be the gold standard, they are complex and two-dimensional (2D) video analysis may be a valuable alternative to screen athletes in clinical practice. Objective The purpose of the present study was to investigate the relationship between 2D sagittal plane kinematics and 3D joint loading during the drop vertical jump (DVJ) test. Design Cross-sectional. Setting Controlled laboratory study. Participants Fifty injury-free elite female athletes were tested. Risk factor assessment Two-dimensional sagittal plane video analysis and 3D motion analysis were used during the DVJ test. Main outcome measurements Hip flexion, knee flexion and ankle dorsiflexion angles were measured at the deepest landing position (2D analysis). External hip flexion moments (HFM), knee flexion moments (KFM) and knee abduction moments (KAM) were measured across the entire support phase (3D analysis). One-dimensional statistical parametric mapping was used to examine the temporal relationship between 2D angles at the deepest landing position and 3D moments across the entire support phase. Significance was set at P&lt;.0055. Results The amount of hip flexion was significantly related to HFM, KFM and KAM during the time frames corresponding with highest 3D moments, while the amount of knee flexion was only significantly related to HFM during these time frames. No significant results were found for ankle dorsiflexion. Conclusions These results indicate that 2D measured sagittal plane hip and knee flexion angles at the deepest landing position are associated with sagittal plane peak joint loading during a DVJ. Furthermore, the significant association of hip flexion with frontal plane knee loading provides evidence that assessment of knee joint injury risk could benefit from measuring maximal hip flexion.
Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities.
Authors: J L Roberts, S O Sharrow, A Singer
Journal: The Journal of Experimental Medicine (1990)

The present study demonstrates that immune tolerance can be achieved in the thymus both by clonal deletion and by clonal inactivation, but that the two tolerant states are induced by cellular elements with different radiation sensitivities. TCR engagement of self antigens on bone marrow-derived, radiation-sensitive (presumably dendritic) cells induces clonal deletion of developing thymocytes, whereas TCR engagement of self antigens on radiation-resistant cellular elements, such as thymic epithelium, induces clonal anergy. The nondeleted, anergic thymocytes can express IL-2-Rs but are unable to proliferate in response to either specific antigen or anti-TCR antibodies, and do develop into phenotypically mature cells that emigrate out of the thymus and into the periphery.
THE EFFECT OF CEVITAMIC ACID INJECTIONS ON CAPILLARY RESISTANCE
Authors: GILBERT DALLDORF
Journal: JAMA (1935)

Relative fragility of skin capillaries is a common condition.<sup>1</sup>It may be found in individuals of all ages who are otherwise free of signs or symptoms of scurvy. Nevertheless, increase in the antiscorbutic value of the diet of such individuals increases their capillary resistance. This borderland nutritional disorder has been called subclinical scurvy, and a general experience with experimental nutritional diseases suggests that other slight deviations from health are probably present in such persons. The condition is therefore deserving of study. The influence of cevitamic acid on this condition forms the basis of the present report. <h3>METHOD</h3> The cevitamic acid used was Cebione, Merck &amp; Co. The product was assayed against a standard iodine solution by Harris's method<sup>2</sup>and found to be pure within the limits of error of the method. The acid was administered intravenously, 100 mg. being dissolved in at least 10 cc. of distilled water
MPs ridicule proposed UK partial smoking ban
Authors: Michael Day
Journal: BMJ (2006)

A Labour backbench rebellion may yet see smoking in public places fully banned in England, antismoking campaigners say. Their prediction follows an unprecedented savaging of the government's policy of a partial ban by the influential Commons health committee. The cross party group of MPs dismissed the current proposals, which would allow smoking to continue in all bars and clubs that do not serve food, as “unfair, unjust, inefficient, and unworkable.”

By February, MPs will vote again on the Health Bill, which will introduce the partial ban, as it enters its final report stage in …
Growth Hormone Doping in Sports: A Critical Review of Use and Detection Strategies
Authors: Gerhard P. Baumann
Journal: Endocrine Reviews (2012)

GH is believed to be widely employed in sports as a performance-enhancing substance. Its use in athletic competition is banned by the World Anti-Doping Agency, and athletes are required to submit to testing for GH exposure. Detection of GH doping is challenging for several reasons including identity/similarity of exogenous to endogenous GH, short half-life, complex and fluctuating secretory dynamics of GH, and a very low urinary excretion rate. The detection test currently in use (GH isoform test) exploits the difference between recombinant GH (pure 22K-GH) and the heterogeneous nature of endogenous GH (several isoforms). Its main limitation is the short window of opportunity for detection (∼12–24 h after the last GH dose). A second test to be implemented soon (the biomarker test) is based on stimulation of IGF-I and collagen III synthesis by GH. It has a longer window of opportunity (1–2 wk) but is less specific and presents a variety of technical challenges. GH doping in a larger sense also includes doping with GH secretagogues and IGF-I and its analogs. The scientific evidence for the ergogenicity of GH is weak, a fact that is not widely appreciated in athletic circles or by the general public. Also insufficiently appreciated is the risk of serious health consequences associated with high-dose, prolonged GH use. This review discusses the GH biology relevant to GH doping; the virtues and limitations of detection tests in blood, urine, and saliva; secretagogue efficacy; IGF-I doping; and information about the effectiveness of GH as a performance-enhancing agent.
Recurrence of malignant tumours in the head and neck
Authors: G R Ogden
Journal: BMJ (1996)

Field cancerisation may hold the clue to who will develop another cancer

One of the greatest challenges in the treatment of cancers in the head and neck is the occurrence of further tumours.1 World wide, cancer of the head and neck is the sixth most common cancer, and its prevalence is increasing.2 Despite therapeutic advances over the past 20 years, survival rates remain poor.3 Why?

As treatment of local disease has improved, so the opportunity has arisen for further tumours to develop, which adversely affect survival. In 1953 Slaughter et al first proposed the concept of field cancerisation, based on finding satellites of dysplastic epithelium adjacent to the main lesion.4 Such a concept helps to explain why multiple primary cancers and recurrence can occur, particularly in patients who stop smoking and drinking alcohol. Although alcohol and tobacco are the most important aetiological factors, second malignant tumours can arise in those who have never drunk …
Short-term vasodilator effect of captopril in patients with severe mitral regurgitation is parasympathetically mediated.
Authors: T Wisenbaugh, R Essop, P Sareli
Journal: Circulation (1991)

BACKGROUND Few data exist regarding the effects of angiotensin converting enzyme inhibitors in patients with regurgitant valvular lesions. We postulated an immediate improvement in cardiac performance with captopril in mitral regurgitation, which, in a hemodynamically compensated group of patients, might be mediated through parasympathetic vasodilation rather than through blockade of angiotension converting enzyme. METHODS AND RESULTS Hemodynamics were examined before and 90 minutes after oral captopril (25-50 mg) in 18 patients (mean age, 31 years) with chronic, severe mitral regurgitation in New York Heart Association functional class II and III. One group of patients was given captopril alone (group 1, n = 9) and a second group was given captopril plus atropine 0.04 mg/kg i.v. (group 2, n = 9). Captopril alone (group 1) produced decreases in heart rate (90-81 beats/min, p less than 0.001), mean arterial pressure (90-73 mm Hg, p less than 0.001), systemic resistance (28-23 Wood units, p = 0.068), and pulmonary wedge pressure (19-14 mm Hg, p less than 0.001). There was no improvement in either arteriovenous oxygen difference or thermodilution cardiac output; in fact, the latter slightly declined (3.45-3.35 l/min, p = 0.002). Pretreatment with atropine (group 2) diminished the effects of captopril on heart rate (107-103 beats/min, p = 0.065 for atropine effect by two-way ANOVA), mean arterial pressure (88-82 mm Hg, p = 0.01 for atropine effect), and systemic resistance (26-27 Wood units, p = 0.04 for atropine effect). CONCLUSIONS In patients with chronic, severe mitral regurgitation, captopril reduced systemic arterial and left ventricular filling pressures but did not immediately augment cardiac output as expected. Furthermore, the modest systemic vasodilator effect of captopril was parasympathetically mediated.
Should we advise patients with sutures not to swim?
Authors: K. M. Browne, O. Murphy, A. J. P. Clover
Journal: BMJ (2014)

Patients often ask when they can swim after a wound has been sutured. Despite such an apparently simple query, evidence supporting any answer seems to be lacking. Many patient information sites advise against swimming after the suturing of wounds1 but fail to provide evidence to support this recommendation. Advice is broad ranging and inconsistent.1 Current information ranges from waiting until the sutures are removed and the wound has healed1 to abstaining from swimming for six weeks postoperatively.2 Patients with external frame fixators are advised that it is permissible to swim in a chlorinated pool or clean sea water, although in practice this is difficult to ascertain and is far from an objective measure, once the pin sites have healed.3 Evidence to back up the advice is scarce.

Concerns about the risks of swimming with a sutured wound primarily centre on the potential for infection,4 5 as opposed to impaired wound healing. The risk of infection depends on the type of wound (for example, an open wound might be said to be at higher risk than an epithelialised wound), comorbidities, the type and quality of water in which patients plan to swim, and the relative risks of complications should the wound become infected. Wound infections can result from exposure to aquatic microbes in treated swimming pools and fresh or marine water.4 5 6 The infective organisms vary accordingly.

It is, however, difficult to quantify the risk of infection in sutured wounds and hence giving an evidence based answer when patients ask about swimming is problematic.

To tackle our dilemma on how to advise patients on swimming with sutures, we searched PubMed, Embase, and Cochrane databases for articles on swimming related wound infections using combinations of the key words “swimming”, “infection”, “wound management”, “water”, “sutures”, …
THE IMPACT OF CYP2C19 POLYMORPHISM ON CORONARY ARTERY SPASM IN PATIENTS WITH VASOSPASTIC ANGINA
Authors: Michio Mizobe, Seiji Hokimoto, Tadasuke Chitose, Naoko Takaoka, Kenichi Tsujita, Koichi Kaikita, Nakagawa Kazuko, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2012)
Acute Ozone-Induced Differential Gene Expression Profiles in Rat Lung
Authors: Srikanth S. Nadadur, Daniel L. Costa, Ralph Slade, Robert Silbjoris, Gary E. Hatch
Journal: Environmental Health Perspectives (2005)

Ozone is an oxidant gas that can directly induce lung injury. Knowledge of the initial molecular events of the acute O3 response would be useful in developing biomarkers of exposure or response. Toward this goal, we exposed rats to toxic concentrations of O3 (2 and 5 ppm) for 2 hr and the molecular changes were assessed in lung tissue 2 hr postexposure using a rat cDNA expression array containing 588 characterized genes. Gene array analysis indicated differential expression in almost equal numbers of genes for the two exposure groups: 62 at 2 ppm and 57 at 5 ppm. Most of these genes were common to both exposure groups, suggesting common roles in the initial toxicity response. However, we also identified the induction of nine genes specific to 2-ppm (thyroid hormone-beta receptor c-erb-A-beta; and glutathione reductase) or 5-ppm exposure groups (c-jun, induced nitric oxide synthase, macrophage inflammatory protein-2, and heat shock protein 27). Injury markers in bronchoalveolar lavage fluid (BALF) were used to assess immediate toxicity and inflammation in rats similarly exposed. At 2 ppm, injury was marked by significant increases in BALF total protein, N-acetylglucosaminidase, and lavageable ciliated cells. Because infiltration of neutrophils was observed only at the higher 5 ppm concentration, the distinctive genes suggested a potential amplification role for inflammation in the gene profile. Although the specific gene interactions remain unclear, this is the first report indicating a dose-dependent direct and immediate induction of gene expression that may be separate from those genes involved in inflammation after acute O3 exposure.