tbuckley/cabot-search huggingface dataset:
Abstract 4853: Comparison of automated and a semi-automated methods for assessing Ki-67 staining.
Authors: Rochelle P. Ondracek, James Marshall, Karin Kasza, Christopher Morrison, Simoya Ghajar, Carl Morrison, Diana Mehedint, James L. Mohler
Journal: Cancer Research (2013)

Abstract Human evaluation of immuno-staining is limited by the subjectivity of the human evaluator, is time-consuming and is expensive. Semi-automated means of tissue evaluation have been proposed, but most of these have large subjective components. This study assesses semi-automated and newly-developed fully automated methods of evaluating Ki-67 staining of benign and malignant tissue from radical prostatectomy specimens. A research tissue microarray was constructed from 68 prostatectomy specimens and contained 3 core samples of benign and 3 of malignant tissue from each research subject. Tissue microarray sections were immune-stained for Ki-67. Two technicians (SG &amp; CM) evaluated each TMA core and labeled the nuclei positive for Ki-67 with a green dot, and negative with a red dot. Images were collected and Image-Pro software was used to count the number of green and red dots. In a separate procedure, Image-Pro (IP) software was used to identify nuclei, and grade each nucleus as positive or negative, and the percentage of positive nuclei was calculated. The semi-automated results correlated with each other (0.58, P&amp;lt;0.001). The semi-automated and fully automated results also correlated (0.8, P&amp;lt;0.001, CM vs. IP and 0.59, P&amp;lt;0.001, SG vs. IP). When stratified by tissue type (benign vs. malignant), the semi-automated results and the fully-automated results also correlated (benign tissue: 0.68, P&amp;lt;0.001, CM vs. IP, and 0.80, P&amp;lt;0.001, SG vs. IP; tumor tissue: 0.89, P&amp;lt;0.001, CM vs. IP and 0.47, P&amp;lt;0.001, SG vs. IP). These results suggest that semi-automated and automated analysis of Ki-67 staining of prostate tissue produces comparable results, and automated analysis can be used for prostate cancer research. Citation Format: Rochelle P. Ondracek, James Marshall, Karin Kasza, Christopher Morrison, Simoya Ghajar, Carl Morrison, Diana Mehedint, James L. Mohler. Comparison of automated and a semi-automated methods for assessing Ki-67 staining. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4853. doi:10.1158/1538-7445.AM2013-4853
Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase.
Authors: M Aviram, M Rosenblat, C L Bisgaier, R S Newton, S L Primo-Parmo, B N La Du
Journal: Journal of Clinical Investigation (1998)

HDL levels are inversely related to the risk of developing atherosclerosis. In serum, paraoxonase (PON) is associated with HDL, and was shown to inhibit LDL oxidation. Whether PON also protects HDL from oxidation is unknown, and was determined in the present study. In humans, we found serum HDL PON activity and HDL susceptibility to oxidation to be inversely correlated (r2 = 0.77, n = 15). Supplementing human HDL with purified PON inhibited copper-induced HDL oxidation in a concentration-dependent manner. Adding PON to HDL prolonged the oxidation lag phase and reduced HDL peroxide and aldehyde formation by up to 95%. This inhibitory effect was most pronounced when PON was added before oxidation initiation. When purified PON was added to whole serum, essentially all of it became HDL-associated. The PON-enriched HDL was more resistant to copper ion-induced oxidation than was control HDL. Compared with control HDL, HDL from PON-treated serum showed a 66% prolongation in the lag phase of its oxidation, and up to a 40% reduction in peroxide and aldehyde content. In contrast, in the presence of various PON inhibitors, HDL oxidation induced by either copper ions or by a free radical generating system was markedly enhanced. As PON inhibited HDL oxidation, two major functions of HDL were assessed: macrophage cholesterol efflux, and LDL protection from oxidation. Compared with oxidized untreated HDL, oxidized PON-treated HDL caused a 45% increase in cellular cholesterol efflux from J-774 A.1 macrophages. Both HDL-associated PON and purified PON were potent inhibitors of LDL oxidation. Searching for a possible mechanism for PON-induced inhibition of HDL oxidation revealed PON (2 paraoxonase U/ml)-mediated hydrolysis of lipid peroxides (by 19%) and of cholesteryl linoleate hydroperoxides (by 90%) in oxidized HDL. HDL-associated PON, as well as purified PON, were also able to substantially hydrolyze (up to 25%) hydrogen peroxide (H2O2), a major reactive oxygen species produced under oxidative stress during atherogenesis. Finally, we analyzed serum PON activity in the atherosclerotic apolipoprotein E-deficient mice during aging and development of atherosclerotic lesions. With age, serum lipid peroxidation and lesion size increased, whereas serum PON activity decreased. We thus conclude that HDL-associated PON possesses peroxidase-like activity that can contribute to the protective effect of PON against lipoprotein oxidation. The presence of PON in HDL may thus be a major contributor to the antiatherogenicity of this lipoprotein.
Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria
Authors: Matteo Bassetti, Jan J. De Waele, Philippe Eggimann, Josè Garnacho-Montero, Gunnar Kahlmeter, Francesco Menichetti, David P. Nicolau, Jose Arturo Paiva, Mario Tumbarello, Tobias Welte, Mark Wilcox, Jean Ralph Zahar, Garyphallia Poulakou
Journal: Intensive Care Medicine (2015)
Hypoxia-Regulated Expression of Attenuated Diphtheria Toxin A Fused with Hypoxia-Inducible Factor-1α Oxygen-Dependent Degradation Domain Preferentially Induces Apoptosis of Hypoxic Cells in Solid Tumor
Authors: Nobuko Koshikawa, Keizo Takenaga
Journal: Cancer Research (2005)

Abstract Tumor cells in hypoxic areas of solid tumors are resistant to conventional chemotherapy and radiotherapy and thus are obstacles of cancer therapy. We report here the feasibility of applying hypoxia-regulated expression of diphtheria toxin A (DT-A) for killing hypoxic tumor cells. The expression vector was constructed to express DT-A fused with hypoxia-inducible factor-1α (HIF-1α) oxygen-dependent degradation (ODD) domain under the control of vascular endothelial growth factor gene promoter and contain erythropoietin mRNA-binding protein (ERBP)–binding sequence downstream of the DT-A/ODD sequence. In vitro ubiquitination assay showed that DT-A/ODD, but not DT-A, was ubiquitinated as efficient as HIF-1α under normoxic conditions in a von Hippel-Lindau– and oxygen-dependent manner. DT-A/ODD exhibited a comparable translation inhibitory activity to DT-A. ERBP-binding sequence was effective in stabilizing mRNA under hypoxic conditions in various cell types. Transfection of the vector expressing DT-A/ODD into high-metastatic Lewis lung carcinoma (3LL) A11 cells resulted in induction of apoptosis independently of hypoxia, probably due to its extreme toxicity. However, transfection of the vector expressing attenuated DT-AW153F/ODD or DT-AH21A/ODD resulted in a hypoxia-dependent induction of apoptosis. Liposomal gene transfer of the vector encoding DT-AW153F/ODD induced apoptosis in hypoxic, but not in normoxic, areas of solid tumors established by A11 variant cells with higher resistance to hypoxia-induced apoptosis and inhibited the growth of hypoxic tumors established by 3LL-P29 cells. These results suggest that hypoxia-regulated expression of attenuated DT-AW153F/ODD fusion protein is potentially of use for killing hypoxic tumor cells with minimizing the damage to normoxic normal tissues. (Cancer Res 2005; 65(24): 11622-30)
Advances in mechanisms of activation and deactivation of environmental chemicals.
Authors: J A Goldstein, M B Faletto
Journal: Environmental Health Perspectives (1993)

Environmental chemicals are both activated and detoxified by phase I and phase II enzymes. The principal enzymes involved in phase I reactions are the cytochrome P-450s. The phase II enzymes include hydrolase and the conjugative enzymes such as glucuronyltransferases, glutathione transferases, N-acetyltransferase, and sulfotransferase. Although other phase I and phase II enzymes exist, the present review is limited to these enzymes. Once thought to be a single enzyme, multiple cytochrome P-450 enzymes have been purified and characterized from many different species across the evolutionary tree. The application of molecular biology techniques to this field has identified more than 150 cytochrome P-450 genes to date. At least 20-30 cytochrome P-450 enzymes appear to exist in each mammalian species, and many polymorphisms in these enzymes are being identified. The cytochrome P-450 enzymes can now be expressed in recombinant form using cDNA expression systems. The phase II conjugative enzymes add a hydrophilic moiety such as sulfate, glucuronide, or acetate to compounds, which increases their water solubility and facilitates their excretion. However, conjugates of a number of compounds also result in more reactive electrophilic species, which appear to be the ultimate carcinogens. Many of these phase II enzymes also represent families of enzymes, and polymorphisms can affect the ability of these enzymes to metabolize chemicals. Whenever possible, we have reviewed knowledge of the human enzymes involved in particular pathways.
Sulfate Metabolism in Human Chondrocyte Cultures
Authors: Edith R. Schwartz, P. Roger Kirkpatrick, Roby C. Thompson
Journal: Journal of Clinical Investigation (1974)

The depletion of articular cartilage in the afflicted joints is a primary clinical feature of osteoarthritis. This disorder has been linked to a disturbance in the metabolism of the extracellular matrix components of this tissue. The mechanisms involved in the regulation of sulfated proteoglycan metabolism in articular cartilage were therefore studied by measuring the biosynthesis and distribution of (35)S-labeled glycosaminoglycans in chondrocyte cultures derived from normal and osteoarthritic tissue. Incorporation experiments were carried out at pH 7.0 with [(35)S]Na(2)SO(4) in the presence of fetal calf serum, human serum from normal or arthritic individuals, or a combination of these. In the presence of heat-inactivated human sera, osteoarthritic chondrocytes incorporate about two times as much of the available sulfate into macromolecules as do normal chondrocytes. The deposition of newly synthesized sulfated macromolecules into the cell layer by these cells is lower, however, than that by normal cells. In cultures of normal human chondrocytes, noninactivated sera from individuals with osteoarthritis stimulate proteoglycan biosynthesis more than equal concentrations of normal sera. The fraction of the newly synthesized material deposited into the cell layer was found to decrease with increasing serum concentrations. In the absence of serum, a 5- to 10-fold increase in deposited sulfated macromolecules was found. The distribution within the cell layer between intra- and extracellular sites also was monitored by serum factors. Heat inactivation of the human serum component of the medium resulted in a 50% decrease in intracellular retention. These data suggest that biosynthesis of sulfated proteoglycans and their retention in the matrix are modulated by cell and serum factors. Despite and increased uptake of radioactively labeled inorganic sulfate by osteoarthritic chondrocytes in cell culture, a lower rate of deposition into the cell layer resulted in less matrix formation. This may be representative of the process leading to cartilage degradation in degenerative joint disease in vivo.
The Repair of Umbilical Hernia: Unvoiced Assumptions and Sex
Authors: Lydia A. Engelhardt
Journal: JAMA (1988)

<h3>To the Editor.</h3> —As obstetricians, we read Dr Falla's<sup>1</sup>recommendations on pediatric umbilical herniorrhaphy with great interest. However, we were horrified to read her closing statement about girls ("pregnancy") and boys ("highly competitive and active sports"). We can only hope that as a physician treating children and adolescents, she is providing a positive role model for the female patients she sees. We hope more adolescent females (especially from such socioeconomically deprived areas as rural South Carolina and Newark, NJ) will be pursuing "highly competitive and active sports" rather than adolescent pregnancies.
Watchdog approves embryo selection to treat 3 year old child
Authors: C. Dyer
Journal: BMJ (2002)

The Human Fertilisation and Embryology Authority last week gave the go-ahead for the first time in the United Kingdom for embryo selection to be used for the purpose of treating an existing sibling.

The authority agreed that Raj and Shahana Hashmi could use genetic tests, in conjunction with in vitro fertilisation, to have a child whose umbilical cord blood could save the life of their 3 year old son, Zain. The couple asked the authority for permission last year (6 October, p 767).

The couple's embryos will be screened for thalassaemia, the blood disorder that Zain has inherited, and then …
Mitral Incompetence after Repair of Ostium Primum Septal Defects
Authors: A. R. C. Dobell, D. R. Murphy, G. M. Karn, A. Martinez-Caro
Journal: Thorax (1965)

Experience inthesurgical treatment ofendocardial cushion defects hasbeenreported bya number ofauthors (Cooley, Kirklin, andHarshbarger, 1957;McGoon,DuShane, andKirklin, 1959; Crafoord and Senning, 1960;Dubostand Blondeau, 1960;Ellis, McGoon,andKirklin, 1960;Gerbode, Johnston, Robinson, Harkins, and Osborn, 1961;Maloney, Marable, andMulder, 1962;Scott, Hauck,Nadas, andGross, 1962). Thesepapershavefocused attention on the technical details ofsurgical repair, andforthe mostparttheyhavetakensurvival as their standard ofa successful operative repair. In evaluating theexperience at the Montreal Children's Hospital, webecameawarethatdegrees ofcorrection arepossible, andwiththis inmind theresults inthe27patients withendocardial cushion defects whohavebeensurgically treated werecritically reviewed. Eighteen ofthese hadan ostiumprimumatrial septal defect without an interventricular communication andthey formthe basis ofthis report. The18patients wereoperated uponfromfive years tofourmonths ago.Atthetimeofoperation there wasacomplete cleft oftheaortic leaflet of themitral valve in15patients, a partial cleft in onepatient, andintwopatients nocleft wasfound. Onepatient hadnoatrial septumwhatsoever, there being asingle commonatrial chamberintowhich drained twosuperior venaecavae, theinferior venacava,andthefourpulmonary veins. In another patient, themitral valve wasunusual in thatthere wascentral fusion between theaortic andthemuralleaflets, producing abridge ofvalve tissue extending between thetwoleaflets. These abnormalities areshowninFigure 1.Inthesurgicalrepair themitral valve cleft wasclosed with interrupted sutures. Themitral insufficiency was thentested and iffurther suturesappeared indicated, they wereadded.Abnormalchordae inserting directly intotheventricular septum were searched forbutwerenotrecognized despite our realization thattheyareoften present asreported by Edwards(1960). The upperpartof the ventricular septumimmediately belowtheatrioventricular valveswas probedin orderto determine whether asmall ventricular septal defect mightbepresent. Thelowatrial septal defect was closed inallbutoneofthepatients withapatch ofteflon felt sutured inplace withmultiple peripheral sutures. Inferiorly, thepatchwassutured tovalve tissue. All18patients survived operation. Withthe exception ofthelast patient, whowasoperated upontoorecently forevaluation, theyhavebeen evaluated uptofouryears post-operatively, with
A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease
Authors: Giovanni Musso, Roberto Gambino, Maurizio Cassader, Gianfranco Pagano
Journal: Hepatology (2010)

Nonalcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NAFLD carries a higher risk of cardio-metabolic and liver-related complications, the latter being confined to NASH and demanding specific treatment. We assessed the efficacy of proposed treatments for NAFLD/NASH by reviewing reports of randomized controlled trials (RCTs) on online databases and national and international meeting abstracts through January 2010. Primary outcome measure was histological improvement; secondary outcome was biochemical improvement; improvement in radiological steatosis was also evaluated. Two reviewers extracted articles using predefined quality indicators, independently and in duplicate. Main outcomes of randomized controlled trials (RCTs) were pooled using random-effects or fixed-effects models. Publication bias was assessed by funnel plots. Forty-nine RCTs (30 in NASH) were included: 23 RCTs (22 in NASH, 1 in NAFLD) had post-treatment histology. Most RCTs were small and did not exceed 1-year duration. Weight loss, thiazolidinediones (especially pioglitazone), and antioxidants were most extensively evaluated. Weight loss was safe and dose-dependently improved histological disease activity in NASH, but more than 50% of patients failed to achieve target weight loss. Thiazolidinediones improved steatosis and inflammation but yielded significant weight gain. RCTs with antioxidants yielded conflicting results and were heterogeneous with respect to type and dose of drug, duration, implementation of lifestyle intervention. Among the other agents, pentoxifylline, telmisartan and L-carnitine improved liver histology in at least 1 RCT in NASH; polyunsaturated fatty acid (PUFA) ameliorated biochemical and radiological markers of NAFLD. Other approaches yielded negative results. Conclusion: Well-designed RCTs of adequate size and duration, with histological endpoints, are needed to assess long-term safety and efficacy of proposed treatments on patient-oriented clinical outcomes. Hepatology 2010
On Professor Von Esmarch's Operation for Correcting Deformities of the Face by Transplanting Skinflaps from Distant Parts without Pedicles
Authors: J. R. Wolfe
Journal: BMJ (1889)

pliances that western science had armed them with for so beneficent an end.Surely it was no light thing to be privileged to take a part in this great work.While they ministered to the health of others, let them be reasonably careful of their own.Dr. Maclean then entered on the subject of a proposition made to the Secretary of State for India in Council, which was first started by a financial committee in India-namely, to send the young medical officers for that country there without the Netley training-and subjected it to exhaustive criticism.In concluding his address, he said the ques- tion had been sent back to the Viceroy of India in Council, with much evidence that was never presented to the Simla Commission, where the scheme of returning to what he had entitled " paper training" was believed to have originated.Let them hope that wiser counsels would prevail.Even should the decision go against them, he refused to despair.He believed that, when the matter came up at home once more for final settlement, it would be found that " the resources of civilisation" were not exhausted, and that, in the long run, the cause of common sense and sound education would prevail.
Postmenopausal Hormone Replacement
Authors: Salvatore Panico
Journal: Annals of Internal Medicine (1998)

Letters15 July 1998Postmenopausal Hormone ReplacementSalvatore Panico, MD, MSc, Rocco Galasso, MD, and Franco Berrino, MDSalvatore Panico, MD, MScUniversity of Federico II; Naples, ItalyRegional Oncological Hospital; Potenza, ItalyNational Cancer Institute; Milan, ItalySearch for more papers by this author, Rocco Galasso, MDUniversity of Federico II; Naples, ItalyRegional Oncological Hospital; Potenza, ItalyNational Cancer Institute; Milan, ItalySearch for more papers by this author, and Franco Berrino, MDUniversity of Federico II; Naples, ItalyRegional Oncological Hospital; Potenza, ItalyNational Cancer Institute; Milan, ItalySearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-2-199807150-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The recent paper by McNagny and colleagues [1] stimulates discussion about two issues related to the potential primary prevention of ischemic heart disease on a large-scale basis by use of hormone replacement therapy (HRT).First, data on the personal characteristics of the U.S. women physicians who were using HRT indicate that these women were healthier than those who were not using HRT. Contrary to what one might expect, they were characterized by lower prevalences of high cholesterol levels and diabetes mellitus and by a personal or family history of a lower prevalence of coronary heart disease. We ...References1. McNagny SE, Wenger NK, Frank E. Personal use of postmenopausal hormone replacement therapy by women physicians in the United States. Ann Intern Med. 1997; 127:1093-6. Google Scholar2. Panico S, Galasso R, Celentano E, Ciardullo AV, Frova L, Capocaccia R, et al. Large-scale hormone replacement therapy and life expectancy: results from an international comparison among European and North American populations [Abstract]. Can J Cardiol. 1997; 13(Suppl B):187S. Google Scholar Author, Article, and Disclosure InformationAuthors: Salvatore Panico, MD, MSc; Rocco Galasso, MD; Franco Berrino, MDAffiliations: University of Federico II; Naples, ItalyRegional Oncological Hospital; Potenza, ItalyNational Cancer Institute; Milan, Italy PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1998Volume 129, Issue 2Page: 160-161KeywordsBreast cancerCardiovascular therapyDeath ratesEstrogen replacement therapyForecastingHeart diseasesHormone replacement therapyHypercholesterolemiaMortalityPrevention, policy, and public health ePublished: 15 August 2000 Issue Published: 15 July 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period
Authors: Arnaldo L. Colombo, Thais Guimarães, Teresa Sukienik, Alessandro C. Pasqualotto, Ricardo Andreotti, Flavio Queiroz-Telles, Simone A. Nouér, Marcio Nucci
Journal: Intensive Care Medicine (2014)

To describe temporal trends in the epidemiology, clinical management and outcome of candidemia in intensive care unit (ICU) patients.This study was a retrospective analysis of 1,392 episodes of candidemia in 647 adult ICU patients from 22 Brazilian hospitals. The characteristics of candidemia in these ICU patients were compared in two periods (2003-2007, period 1; 2008-2012, period 2), and the predictors of 30-day mortality were assessed.The proportion of patients who developed candidemia while in the ICU increased from 44 % in period 1 to 50.9 % in period 2 (p = 0.01). Prior exposure to fluconazole before candidemia (22.3 vs. 11.6 %, p < 0.001) and fungemia due to Candida glabrata (13.1 vs. 7.8 %, p = 0.03) were more frequent in period 2, as was the proportion of patients receiving an echinocandin as primary therapy (18.0 vs. 5.9 %, p < 0.001). The 30-day mortality rate decreased from 76.4 % in period 1 to 60.8 % in period 2 (p < 0.001). Predictors of 30-day mortality by multivariate analysis were older age, period 1, treatment with corticosteroids and higher APACHE II score, while treatment with an echinocandin were associated with a higher probability of survival.We found a clear change in the epidemiology and clinical management of candidemia in ICU patients over the 9-year period of the study. The use of echinocandins as primary therapy for candidemia appears to be associated with better outcomes.