tbuckley/cabot-search huggingface dataset:
Diploid Cell Measles Vaccine
Authors: J. F. de Castro, J. L. V. Gomez, J. L. D. Ortega, Ma. L. Z. Aquino
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Dr Albert Sabin and one of us (J.F.D.)<sup>1,2</sup>recently reported seroconversion in infants administered measles vaccine of human diploid cells (HDCs) that contained the Ikić (Edmonston-Zagreb) strain and 1% human albumin, or chick embryo fibroblast (CEF) vaccine that contained the Edmonston-Schwartz strain by cutaneous or aerosol routes. In that study, we used enzyme-linked immunosorbent assay and plaque neutralization tests to demonstrate seroconversion. In this letter we report a further study inwhich antibody was measured using the more standard hemagglutination inhibition. This double-blind study was carried out in children aged 6 to 8 months residing in two poor urban areas of Mexico City between October 1983 and April 1984. <h3>Report of a Case.—</h3> One hundred seventy-two children received HDC vaccine manufactured in Mexico: 117 via aerosol (titer of virus, 10<sup>5.2</sup>50% tissue culture infective dose per milliliter), and 55 by injection (titer of virus, 10
Targeted Inactivation of Fh1 Causes Proliferative Renal Cyst Development and Activation of the Hypoxia Pathway
Authors: Patrick J. Pollard, Bradley Spencer-Dene, Deepa Shukla, Kimberley Howarth, Emma Nye, Mona El-Bahrawy, Maesha Deheragoda, Maria Joannou, Stuart McDonald, Alison Martin, Peter Igarashi, Sunita Varsani-Brown, Ian Rosewell, Richard Poulsom, Patrick Maxwell, Gordon W. Stamp, Ian P.M. Tomlinson
Journal: Cancer Cell (2007)
Prognostic and Predictive Value of Centrally Reviewed Expression of Estrogen and Progesterone Receptors in a Randomized Trial Comparing Letrozole and Tamoxifen Adjuvant Therapy for Postmenopausal Early Breast Cancer: BIG 1-98
Authors: Giuseppe Viale, Meredith M. Regan, Eugenio Maiorano, Mauro G. Mastropasqua, Patrizia Dell'Orto, Birgitte Bruun Rasmussen, Johnny Raffoul, Patrick Neven, Zsolt Orosz, Stephen Braye, Christian Öhlschlegel, Beat Thürlimann, Richard D. Gelber, Monica Castiglione-Gertsch, Karen N. Price, Aron Goldhirsch, Barry A. Gusterson, Alan S. Coates
Journal: Journal of Clinical Oncology (2007)

To evaluate locally versus centrally assessed estrogen (ER) and progesterone (PgR) receptor status and the impact of PgR on letrozole adjuvant therapy compared with tamoxifen in postmenopausal women with early breast cancer.Breast International Group (BIG) 1-98 randomly assigned 8,010 patients to four arms comparing letrozole and tamoxifen with sequences of each agent. The Central Pathology Office received material for 6,549 patients (82%), of which 79% were assessable (6,291 patients). Prognostic and predictive value of both local and central hormone receptor expression on disease-free survival (DFS) were evaluated among 3,650 assessable patients assigned to the monotherapy arms. Prognostic value and the treatment effect were estimated for centrally assessed ER and PgR expression levels using the Subpopulation Treatment Effect Pattern Plot.Central review confirmed 97% of tumors as hormone receptor-positive (ER and/or PgR > or =10%). Of 105 tumors locally ER-negative, 73 were found to have more than 10% positive cells, and eight had 1% to 9%. Of 6,100 tumors locally ER positive, 66 were found to have no staining, and 54 had only 1% to 9%. Discordance was more marked for PgR than ER. Patients with tumors reclassified centrally as ER-negative, or as hormone receptor-negative, had poor DFS. Centrally assessed ER and PgR showed prognostic value. Among patients with centrally assessed ER-expressing tumors, letrozole showed better DFS than tamoxifen, irrespective of PgR expression level.Central review changed the assessment of receptor status in a substantial proportion of patients, and should be performed whenever possible in similar trials. PgR expression did not affect the relative efficacy of letrozole over tamoxifen.
Population Approaches to Improve Diet, Physical Activity, and Smoking Habits
Authors: Dariush Mozaffarian, Ashkan Afshin, Neal L. Benowitz, Vera Bittner, Stephen R. Daniels, Harold A. Franch, David R. Jacobs, William E. Kraus, Penny M. Kris-Etherton, Debra A. Krummel, Barry M. Popkin, Laurie P. Whitsel, Neil A. Zakai
Journal: Circulation (2012)

Background— Poor lifestyle behaviors, including suboptimal diet, physical inactivity, and tobacco use, are leading causes of preventable diseases globally. Although even modest population shifts in risk substantially alter health outcomes, the optimal population-level approaches to improve lifestyle are not well established. Methods and Results— For this American Heart Association scientific statement, the writing group systematically reviewed and graded the current scientific evidence for effective population approaches to improve dietary habits, increase physical activity, and reduce tobacco use. Strategies were considered in 6 broad domains: (1) Media and educational campaigns; (2) labeling and consumer information; (3) taxation, subsidies, and other economic incentives; (4) school and workplace approaches; (5) local environmental changes; and (6) direct restrictions and mandates. The writing group also reviewed the potential contributions of healthcare systems and surveillance systems to behavior change efforts. Several specific population interventions that achieved a Class I or IIa recommendation with grade A or B evidence were identified, providing a set of specific evidence-based strategies that deserve close attention and prioritization for wider implementation. Effective interventions included specific approaches in all 6 domains evaluated for improving diet, increasing activity, and reducing tobacco use. The writing group also identified several specific interventions in each of these domains for which current evidence was less robust, as well as other inconsistencies and evidence gaps, informing the need for further rigorous and interdisciplinary approaches to evaluate population programs and policies. Conclusions— This systematic review identified and graded the evidence for a range of population-based strategies to promote lifestyle change. The findings provide a framework for policy makers, advocacy groups, researchers, clinicians, communities, and other stakeholders to understand and implement the most effective approaches. New strategic initiatives and partnerships are needed to translate this evidence into action.
Genetic and Epigenetic <i>SLC18A2</i> Silencing in Prostate Cancer Is an Independent Adverse Predictor of Biochemical Recurrence after Radical Prostatectomy
Authors: Karina Dalsgaard Sørensen, Peter Johannes Wild, Ashkan Mortezavi, Katja Adolf, Niels Tørring, Sara Heebøll, Benedicte Parm Ulhøi, Peter Ottosen, Tullio Sulser, Thomas Hermanns, Holger Moch, Michael Borre, Torben Falck Ørntoft, Lars Dyrskjøt
Journal: Clinical Cancer Research (2009)

Abstract Purpose: This study investigates SLC18A2 (vesicular monoamine transporter 2) expression in prostate adenocarcinoma and examines its potential as a predictive marker for prostate cancer patient outcome after radical prostatectomy. Experimental Design: Expression and single nucleotide polymorphism microarray analyses identified SLC18A2 as both down-regulated and subject to common loss-of-heterozygosity in prostate cancer. Down-regulated SLC18A2 expression was validated on tissue microarrays containing benign and malignant prostate specimens from an independent patient group (n = 738). Furthermore, SLC18A2 immunoreactivity in radical prostatectomy tumor specimens (n = 506) was correlated to clinicopathologic characteristics and recurrence-free survival. The possibility of SLC18A2 silencing by aberrant DNA methylation in prostate cancer cells was investigated by bisulfite sequencing. Results: Tissue microarray analysis revealed markedly lower cytoplasmic SLC18A2 staining in cancer compared with nonmalignant prostate tissue samples, confirming RNA expression profiling results. Furthermore, multivariate analysis identified cytoplasmic SLC18A2 immunoreactivity as a novel predictor of biochemical recurrence following prostatectomy (hazard ratio, 0.485; 95% confidence interval, 0.333-0.709; P &amp;lt; 0.001) independent of prostate-specific antigen, Gleason score, tumor stage, and surgical margin status. SLC18A2 showed loss-of-heterozygosity in 23% of the tumors and was densely hypermethylated in 15 of 17 (88%) prostate cancer samples plus 6 of 6 prostate cancer cell lines. In contrast, SLC18A2 was unmethylated in 4 of 4 adjacent nonmalignant prostate and 3 of 5 benign prostatic hyperplasia tissue samples, whereas 2 of 5 benign prostatic hyperplasia samples had monoallelic hypermethylation. Methylation and histone deacetylase inhibitory agents rescued SLC18A2 expression in three prostate cancer cell lines. Conclusions: SLC18A2 silencing by DNA hypermethylation and/or allelic loss is a frequent event in prostate cancer and a novel independent predictor of biochemical recurrence after prostatectomy.
Hypoxia Inducible Factor-2α Stabilization and Maxi-K <sup>+</sup> Channel β <sub>1</sub> -Subunit Gene Repression by Hypoxia in Cardiac Myocytes
Authors: Lucía Bautista, María J. Castro, José López-Barneo, Antonio Castellano
Journal: Circulation Research (2009)

The Ca 2+ - and voltage-dependent K + (maxi-K) channel β 1 -subunit mRNA is particularly abundant in cardiomyocytes but its functional role is unknown. This is intriguing because functional maxi-K channels are not found in cardiomyocyte plasmalemma, although they have been suggested to be in the inner mitochondrial membrane and participate in cardioprotection. We report here that β 1 protein may interact with mitochondrial proteins and that the β 1 -subunit gene (KCNMB1) is repressed by sustained hypoxia in dispersed cardiomyocytes as well as in heart intact tissue. The effect of hypoxia is time- and dose-dependent, is mimicked by addition of reactive oxygen species, and selectively requires hypoxia inducible factor-2α (Hif-2α) stabilization. We have observed that adaptation to hypoxia exerts a protective role on cardiomyocytes subjected to ischemia and that, unexpectedly, this form of preconditioning absolutely depends on Hif-2α. Interference of the β 1 -subunit mRNA increases cardiomyocyte resistance to ischemia. Therefore, Hif-2α–mediated β 1 -subunit gene repression is a previously unknown mechanism that could participate in the gene expression program triggered by sustained hypoxia to prevent deleterious mitochondrial depolarization and ATP deficiency in cardiac cells. Our work provides new perspectives for research on cardiac preconditioning.
Generation and decay of the immune response to a progressive fibrosarcoma. II. Failure to demonstrate postexcision immunity after the onset of T cell-mediated suppression of immunity.
Authors: I Bursuker, R J North
Journal: The Journal of Experimental Medicine (1984)

This study shows that surgical removal of the meth A fibrosarcoma from its semisyngeneic host fails to result in postexcision immunity to growth of a tumor implant unless the host already has acquired a mechanism of concomitant immunity to growth of an implant. Therefore, tumor excision does not cause immunity to be generated but preserves a mechanism of concomitant immunity that already exists and which otherwise would eventually undergo down-regulation under the influence of suppressor T cells. Removal of the tumor after it has grown large enough to cause the T cell-mediated suppression of concomitant immunity does not result in the reemergence of immunity. Instead, the host remains unable to generate concomitant immunity to a second tumor for a long period of time and retains, for at least 31 d, suppressor T cells able to passively transfer suppression to appropriate recipients. Like the suppressor T cells responsible for active suppression of concomitant immunity, the suppressor T cells responsible for "memory" suppression are of the Ly-1+2- phenotype. The results indicate that progressive tumor growth results in a state of immunological tolerance of tumor-specific, transplantation antigens that can persist in the apparent absence of tumor antigens.
A 75-year-old man with chest discomfort and a cough
Authors: J J Owen, L Perry, R Delaney, M Charig, M J Smith, L Hart
Journal: Thorax (2008)

A 75-year-old man was admitted with a non-productive cough and chest discomfort. He had been admitted 2 months previously with left lower lobe (LLL) consolidation for which he received intravenous antibiotics. He had no weight loss or constitutional symptoms. The chest radiograph (fig 1) revealed persistent consolidation and he was urgently referred to the chest clinic for review. …
Should imaging be a component of rheumatoid arthritis remission criteria? A comparison between traditional and modified composite remission scores and imaging assessments
Authors: B. Saleem, A. K. Brown, H. Keen, S. Nizam, J. Freeston, R. Wakefield, Z. Karim, M. Quinn, E. Hensor, P. G. Conaghan, P. Emery
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Patients can fulfil clinical criteria for remission, yet still have evidence of synovitis detectable clinically and by ultrasound, and this is associated with structural damage. Stricter remission criteria may more accurately reflect true remission (no synovitis). This hypothesis was examined by studying patients using more stringent thresholds for clinical remission and determining their levels of ultrasound synovitis. <h3>Methods</h3> Rheumatoid arthritis patients with a disease activity score in 28 joints (DAS28) ≤2.6 for at least 6 months were classified using standard and more stringent DAS28 and simplified disease activity index (SDAI) remission thresholds and the corresponding clinical and ultrasound imaging measures of synovitis recorded. <h3>Results</h3> 128 patients (all DAS28 &lt;2.6, median DAS28 1.70) receiving either disease-modifying antirheumatic drugs alone (n=66) or with a tumour necrosis factor blocker (n=62) were recruited. Of the 640 imaged joints, 5% had moderate or severe power Doppler (PD) activity, 8% were clinically swollen and 1% tender. In patients fulfilling DAS28, American College of Rheumatology or SDAI remission criteria, moderate or severe PD activity was present in 21%, 15% and 19%, respectively. More stringent DAS28 and SDAI criteria reduced the mean number of swollen and tender joints (p&lt;0.001) but not the percentage of patients with PD activity: 32 patients had a DAS28 &lt;1.17 but eight (25%) had significant PD activity. <h3>Conclusion</h3> Using more stringent remission criteria resulted in reduced signs and symptoms of inflammation, but the percentage of joints with PD activity was not reduced, even in those without signs or symptoms. These data suggest that clinical criteria are sufficiently insensitive to detect low but clinically relevant levels of inflammation accurately.
Hand-scoring of MESAM 4 recordings is more accurate than automatic analysis in screening for obstructive sleep apnoea
Authors: M Koziej, JK Cieslicki, K Gorzelak, P Sliwinski, J Zielinski
Journal: European Respiratory Journal (1994)

The MESAM 4 system, developed to monitor breathing sounds, heart rate, arterial oxygen saturation (Sao2) and body position, was proposed as a screening method for obstructive sleep apnoea (OSA). The aim of the study was to assess the accuracy of hand-scoring versus automatic-scoring in screening for obstructive sleep apnoea. The study population consisted of 56 patients, 51 males, and 5 females, mean age 47 +/- 10 yrs, suspected of having obstructive sleep apnoea. Full polysomnography and MESAM 4 recordings were performed simultaneously. The apnoea+hypopnoea index was hand-scored in polysomnography and in MESAM 4. The hand-scoring in MESAM 4 was based on analysis of breathing sounds, heart rate and Sao2 changes taken together. The automatic-scoring system of MESAM 4 calculated oxygen desaturation index, heart rate variation index and intermittent snoring index. The diagnosis of obstructive sleep apnoea (apnoea+hypopnoea index &gt; or = 10) was established by polysomnography in 37 patients. Sensitivity and specificity of hand-scored MESAM 4 diagnosis were 100 and 63%, respectively. Sensitivity and specificity of MESAM 4 diagnosis with automatic-scoring were: from oxygen desaturation index 100 and 27%; from heart rate variation index 81 and 74%; and from intermittent snoring index 92 and 16%, respectively. We suggest that hand-scoring of MESAM 4 is more accurate than automatic-scoring in screening for obstructive sleep apnoea.
Type 1 Diabetes and Hypoglycemia
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2008)

This is the first of a series of articles based on presentations at the American Diabetes Association Scientific Sessions held 6–10 June 2008 in San Francisco, California.

Matthias von Herrath (La Jolla, CA) received the American Diabetes Association (ADA) 2008 Outstanding Scientific Achievement Award for his research on approaches to β-cell–specific immune interventions for type 1 diabetes. He began with a discussion of the evidence of a role of viral infections in the development of type 1 diabetes. In experimental models, viral infection may either accelerate or retard the immunologic process leading to type 1 diabetes. He pointed out that although type 1 diabetes is clearly an autoimmune disease, because a pancreas transplanted from an unaffected to a type 1 diabetic identical twin is associated with an immune response and rejection, the cause of autoreactivity is uncertain. Environmental factors are likely implicated: viral and also nutritional. Furthermore, the degree of islet inflammation in type 1 diabetes is rather mild, which may shed light on how viral infections might contribute to the disease process because only 3–4% of islets in pre-diabetic patients—and not a great deal more at the time of diagnosis—are affected by insulitis. Approaches to prevention might include modification of genes that predispose to diabetes and their gene products or modification of environmental factors, but emerging evidence suggests that type 1 diabetes is polygenic, with protective as well as enhancing genes, not all of which can suitably be altered.

Curing type 1 diabetes might be accomplished with an unlimited β-cell source, perhaps from stem cells, to make islet transplantation more generally feasible. β-Cell augmentation may be an intermediate goal for which islet transplant protocols not flawed by loss of islets after 3–4 years must be developed, perhaps by eliminating preexisting autoaggressive T-cells. Ongoing trials to prevent and cure recent-onset …
Radiofrequency ablation of airway smooth muscle for sustained treatment of asthma: preliminary investigations
Authors: P.G. Cox, J. Miller, W. Mitzner, A.R. Leff
Journal: European Respiratory Journal (2004)

Bronchial thermoplasty is a procedure now being tested in humans for the treatment of asthma. Current studies focusing on safety are encouraging. The procedure, which causes extensive ablation of airway smooth muscle (ASM), is well tolerated, and there is a sustained reduction in airway responsiveness to methacholine. Two assumptions underlie the development of this procedure: 1) ASM is a vestigial tissue; and 2) that treatment directed at ASM alone will provide sustained symptomatic and physiological improvement in asthmatic humans. Even if this procedure is efficacious, it must be safe in the long-term. Current studies in animals and humans suggest that this is very likely to be the case. While bronchial thermoplasty may have a broad application, especially for patients who wish for a permanent amelioration of their symptoms or have difficulty adhering to medical regimens, the compelling use of this procedure is for patients who are inadequately controlled on current drug therapy or who cannot adhere to therapeutic regimens. The application of this procedure for the treatment of asthma is currently being considered by regulatory agencies, and study centres are currently disseminated throughout North America and Europe. Within the next 1–2 yrs, a profile of the potential role of this therapy in human asthma should be developed fully.
Factors correlating with risk of mortality after transmyocardial revascularization
Authors: Daniel Burkhoff, Margaret N Wesley, Jon R Resar, Allan M Lansing
Journal: Journal of the American College of Cardiology (1999)

OBJECTIVES The purpose of this study was to determine factors correlating with the risk of postoperative mortality after transmyocardial laser revascularization (TMR). BACKGROUND Clinical studies have indicated that TMR reduces angina by an average of two classes in patients with medically refractory symptoms not treatable by coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty. Factors which correlate with mortality after TMR, however, have not been extensively investigated. METHODS One hundred thirty-two patients with severe angina underwent TMR as sole therapy with a CO2laser. Age, gender, ejection fraction, prior CABG, unstable angina and the severity of coronary artery disease (graded on the basis of a newly proposed Anatomic Myocardial Perfusion index, AMP) were each determined. Each vascular territory (left anterior descending artery [LAD] left circumflex artery and posterior descending artery [PDA]) was graded as either having (AMP = 1) or not having (AMP = 0) blood flow through an unobstructed major vessel in the territory. Univariate and multivariate analysis determined which factors correlated with mortality. RESULTS Patients with at least one AMP = 1 vascular territory (overall AMP = 1) had a 5% (4/82) postoperative mortality rate (POM), compared with 25% (12/49) with overall AMP 0 (p = 0.002). Left anterior descending artery AMP (p = 0.03) and previous CABG (p = 0.04) each correlated with the risk of POM. However, multivariate analysis indicated that no factor improved the correlation obtained with overall AMP by itself. With regard to overall mortality (Kaplan-Meier curves), univariate analysis also revealed correlations with overall AMP (p < 0.001), LAD AMP (p = 0.005), previous CABG (p = 0.003) and PDA AMP (p = 0.05) each individually correlated with mortality. Multivariate analysis indicated that overall AMP = 1, female gender and previous CABG together correlated best with lower postoperative mortality. CONCLUSIONS Patients with good blood flow to at least one region of the heart through a native artery or a patent vascular graft have a markedly reduced risk of perioperative and longer term mortality.
Platelet-activating factor impairs mucociliary transport and increases plasma leukotriene B4 in man
Authors: MM Nieminen, EK Moilanen, J-E Nyholm, MO Koskinen, JI Karvonen, TJ Metsa-Ketela, H Vapaatalo
Journal: European Respiratory Journal (1991)

We assessed the effect of inhaled platelet-activating factor (PAF) on tracheobronchial clearance, pulmonary function and blood pressure in seven healthy volunteers. After inhalation of 500 micrograms of PAF, retention of radioaerosol in ciliated airways measured at 4 h was 80% higher than in the control recording, and the clearance was reduced by 33% (p less than 0.005). Acetylsalicylic acid (ASA) did not abolish the phenomenon. PAF also decreased forced expiratory volume in one second (FEV1) by 16% (p less than 0.01), which was markedly attenuated by acetylsalicylic acid. The decrease in blood pressure after PAF (p less than 0.01) was not influenced by acetylsalicylic acid. Plasma leukotriene B4 (LTB4) was increased at 20 min after PAF inhalation (without and with ASA: mean 240 and 299 pg.ml.1, respectively) as compared to the baseline (144 and 166 pg.ml.1) and the values at 60 min after the challenge (133 and 178 pg.ml.1; p less than 0.05 and p less than 0.01, respectively). Only three out of seven subjects showed a bronchial hyperresponsiveness to methacholine measured 24 h after PAF. The PAF-induced reduction of mucociliary transport seems to be independent of cyclo-oxygenase products of arachidonic acid metabolism. These autacoids are, however, believed to contribute to the acute bronchial obstruction after PAF inhalation. In addition, inhaled PAF causes a transient increase in plasma LTB4.