tbuckley/cabot-search huggingface dataset:
Cross-Sectional and Prospective Associations Between Proinsulin and Cardiovascular Disease Risk Factors in a Population Experiencing Rapid Cultural Transition
Authors: Anthony J.G. Hanley, Gail McKeown-Eyssen, Stewart B. Harris, Robert A. Hegele, Thomas M.S. Wolever, Jeremy Kwan, Philip W. Connelly, Bernard Zinman
Journal: Diabetes Care (2001)

OBJECTIVE—To examine cross-sectional and prospective associations between proinsulin and cardiovascular disease risk factors using data from a population-based study of type 2 diabetes among Native Canadians. RESEARCH DESIGN AND METHODS—Between 1993 and 1995, 72% of eligible members of a Native Canadian community participated in a baseline diabetes prevalence survey. Fasting samples were collected for glucose, C-peptide, proinsulin, lipids, and apolipoproteins. A 75-g oral glucose tolerance test was administered, and a second sample for glucose was drawn after 120 min. Blood pressure and waist circumference were determined. In the present study, subjects with normal glucose tolerance (NGT) (n = 505) and impaired glucose tolerance (IGT) (n = 74) were included in cross-sectional analyses. In 1998, 95 individuals who had IGT or NGT at baseline with an elevated 2-h glucose concentration (≥7.0 mmol/l) participated in a follow-up evaluation using the protocol used at baseline. Cross-sectional and prospective associations between proinsulin and cardiovascular risk factors were assessed using correlation and multiple linear regression analyses. RESULTS—After adjustment for covariates including age, sex, C-peptide, waist circumference, and glucose tolerance status, fasting proinsulin concentration was significantly associated with concurrently measured lipid and apolipoprotein concentrations (triglycerides: r = 0.18, P &amp;lt; 0.0001; total cholesterol: r = 0.10, P = 0.02; LDL cholesterol: r = 0.11, P = 0.01; HDL cholesterol: r = −0.16, P = 0.0002; apolipoprotein (apo) B: r = 0.17, P &amp;lt; 0.0001; apoAI: r = −0.11, P = 0.008). In the adjusted prospective analysis, baseline triglycerides, HDL cholesterol, and apoB were associated with changes over time in proinsulin (r = 0.23, P = 0.04; r = −0.30, P = 0.01; r = 0.23, P = 0.04; respectively). CONCLUSIONS—These results confirm previously reported cross-sectional associations between proinsulin and lipid concentrations. In addition, an unexpected association between baseline lipids and proinsulin change was documented.
Tin Mining and Silicosis in Cornwall
Authors: L. W. Hale
Journal: Thorax (1946)

In recent years pneumoconiosis among miners has increasingly attracted the attention of students of respiratory disease, and the urgent problem which it now presents in the South Wales coalfields, together with the importance of the industry involved, has produced a considerable literature dealing with pneumo- coniosis and the environmental considerations relative to it.It is thought that the practice of tin mining may be less well known to workers in this field, and it is the purpose of this communication to outline the processes involved, especially as they bear upon the production of silicosis, and to review briefly the features of this " classical " silicosis.
Graded functional diffusion map-defined characteristics of apparent diffusion coefficients predict overall survival in recurrent glioblastoma treated with bevacizumab
Authors: B. M. Ellingson, T. F. Cloughesy, A. Lai, P. S. Mischel, P. L. Nghiemphu, S. Lalezari, K. M. Schmainda, W. B. Pope
Journal: Neuro-Oncology (2011)

Diffusion imaging has shown promise as a predictive and prognostic biomarker in glioma. We assessed the ability of graded functional diffusion maps (fDMs) and apparent diffusion coefficient (ADC) characteristics to predict overall survival (OS) in recurrent glioblastoma multiforme (GBM) patients treated with bevacizumab. Seventy-seven patients with recurrent GBMs were retrospectively examined. MRI scans were obtained before and approximately 6 weeks after treatment with bevacizumab. Graded fDMs were created by registering datasets to each patient's pretreatment scan and then performing voxel-wise subtraction between post- and pretreatment ADC maps. Voxels were categorized according to the degree of change in ADC within pretreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions of interest (ROIs). We found that the volume of tissue showing decreased ADC within both FLAIR and contrast-enhancing regions stratified OS (log-rank, P < .05). fDMs applied to contrast-enhancing ROIs more accurately predicted OS compared with fDMs applied to FLAIR ROIs. Graded fDMs (showing voxels with decreased ADC between 0.25 and 0.4 µm2/ms) were more predictive of OS than traditional (single threshold) fDMs, and the predictive ability of graded fDMs could be enhanced even further by adding the ADC characteristics from the fDM-classified voxels to the analysis (log-rank, P < .001). These results demonstrate that spatially resolved diffusion-based tumor metrics are a powerful imaging biomarker of survival in patients with recurrent GBM treated with bevacizumab.
Unexpected Cardiac Masses
Authors: Talal Hilal, Lowell B. Anthony, Vincent L. Sorrell
Journal: JAMA Oncology (2015)

A woman in her 50s with intermittent epigastric pain, palpitations, and hot flashes had multiple intramyocardial masses involving the left ventricle, aortopulmonary window lymphadenopathy, and moderate pericardial effusion. What is your diagnosis?
Epigenetic differences between Wilms' tumours in white and east-Asian children
Authors: Ryuji Fukuzawa, Norman E Breslow, Ian M Morison, Patrick Dwyer, Takeshi Kusafuka, Yasutsugu Kobayashi, David M Becroft, J Bruce Beckwith, Elizabeth J Perlman, Anthony E Reeve
Journal: The Lancet (2004)
Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids
Authors: G Jonasson, KH Carlsen, P Blomqvist
Journal: European Respiratory Journal (1998)

The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.
Cytolytic CD8+ T Cells Recognizing CFP10 Are Recruited to the Lung after <i>Mycobacterium tuberculosis</i> Infection
Authors: Arati B. Kamath, Joshua Woodworth, Xiaowei Xiong, Chad Taylor, Yu Weng, Samuel M. Behar
Journal: The Journal of Experimental Medicine (2004)

Optimum immunity against Mycobacterium tuberculosis requires both CD4+ and CD8+ T cells. In contrast with CD4+ T cells, few antigens are known that elicit CD8+ T cells during infection. CD8+ T cells specific for culture filtrate protein-10 (CFP10) are found in purified protein derivative positive donors, suggesting that CFP10 primes CD8+ T cells in vivo. Using T cells from M. tuberculosis–infected mice, we identified CFP10 epitopes recognized by CD8+ T cells and CD4+ T cells. CFP10-specific T cells were detected as early as week 3 after infection and at their peak accounted for up to 30% of CD8+ T cells in the lung. IFNγ-producing CD8+ and CD4+ T cells recognizing CFP10 epitopes were preferentially recruited to the lungs of M. tuberculosis–infected mice. In vivo cytolytic activity of CD8+ T cells specific for CFP10 and TB10.3/10.4 proteins was detected in the spleen, pulmonary lymph nodes, and lungs of infected mice. The cytolytic activity persisted long term and could be detected 260 d after infection. This paper highlights the cytolytic function of antigen-specific CD8+ T cells elicited by M. tuberculosis infection and demonstrates that large numbers of CFP10-specific cytolytic CD8+ T cells are recruited to the lung after M. tuberculosis infection.
Muscle mass and strength in obstructive lung disease: a smoking gun?
Authors: S. S. C. Kon, W. D.-C. Man
Journal: Thorax (2011)

Over the past 2 decades, there has been increasing interest in the extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). This is supported by the clinical observation that patients show significant improvements in functional performance and health-related quality of life with pulmonary rehabilitation in the absence of lung function changes.1 Furthermore, the forced expiratory volume in 1 s is an imperfect predictor of mortality in severe patients with COPD,2 and when forced expiratory volume in 1 s is corrected after double lung transplantation, peak exercise remains only approximately 50% of predicted up to 1–2 years after surgery.3 This limitation in exercise and functional capacity has led to a particular focus upon the skeletal muscle compartment. Certainly, a surprisingly high proportion of patients with COPD terminate exercise complaining of muscle effort.4 Cross-sectional studies have typically demonstrated muscle weakness5 and reduced endurance,6 particularly of the lower limbs, in COPD compared with age-matched controls. This is corroborated by biopsy findings of muscle fibre atrophy and muscle fibre shift from type I to type II fibres.7 Skeletal muscle dysfunction seems to be clinically relevant in COPD, as loss of skeletal muscle mass and strength are associated with poor health status,8 increased healthcare use9 and even mortality,2 10 independent of lung function parameters.

Debate continues as to the relative importance of systemic and local factors in the aetiology of …
Distribution of hobo transposable elements in natural populations of Drosophila melanogaster.
Authors: L Pascual, G Periquet
Journal: Molecular Biology and Evolution (1991)

Forty-six strains derived from American and French natural populations of Drosophila melanogaster were tested for the presence and activity of hobo elements by using Southern blotting and a gonadal dysgenesis assay. The oldest available strains exhibited weak detectable hybridization to the hobo-element probe and revealed neither hobo-activity potential nor hobo-repression potential. In contrast, all recently collected strains harbored hobo sequences and revealed a strong hobo-repression potential but no strong hobo-activity potential. On the basis of restriction-enzyme analysis, old strains appear to have numerous fragments hybridizable to hobo sequences, several probably conserved at the same locations in the genome of the tested strain and others dispersed. In recently isolated strains, and unlike the situation in the published sequence of the cloned hobo108 element, a PvuII site is present in the great majority of full-sized hobo elements and their deletion derivatives. When the genetic and molecular characteristics are considered together, the available evidence is consistent with the hypothesis of a worldwide hobo-element invasion of D. melanogaster during the past 50 years. Comparison of data from the I-R and P-M systems suggests that the putative invasion followed the introduction of the I element but preceded that of the P element. This hypothesis poses the problem of the plausibility of three virtually simultaneous element invasions in this species. Such a possibility might be due to a modification of the genetic structure of American populations of D. melanogaster during the first part of the 20th century.
Multiple prosthetic vascular implants into the acutely ischaemic myocardium
Authors: D. B. Clarke, M. C. J. A. Neligan
Journal: Thorax (1970)

In nine dogs submitted to a severe myocardial ischaemic challenge, multiple prosthetic implants running from the descending aorta to myocardial tunnels were successful in sustaining effective ventricular contraction for a mean period of 27 minutes. A control series of five dogs and five animals, in which the prostheses clotted, developed ventricular fibrillation within six minutes of the ligation of either the left or both coronary arteries. It is suggested that these findings, although not applicable to clinical practice, should stimulate further investigation into the surgical support of the acutely ischaemic myocardium.
Effect of Chromium Supplementation on Glucose Metabolism and Lipids
Authors: Ethan M. Balk, Athina Tatsioni, Alice H. Lichtenstein, Joseph Lau, Anastassios G. Pittas
Journal: Diabetes Care (2007)

A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels.A literature search was conducted in MEDLINE and the Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium supplement intake > or = 3 weeks, with > or = 10 participants receiving chromium. All trials with glucose metabolism outcomes and trials of individuals with diabetes or glucose intolerance for lipid outcomes were included. Meta-analyses were performed as appropriate.Forty-one studies met criteria, almost half of which were of poor quality. Among participants with type 2 diabetes, chromium supplementation improved glycosylated hemoglobin levels by -0.6% (95% CI -0.9 to -0.2) and fasting glucose by -1.0 mmol/l (-1.4 to -0.5) but not lipids. There was no benefit in individuals without diabetes. There were some indications of dose effect and differences among chromium formulations. Larger effects were more commonly observed in poor-quality studies. The evidence was limited by poor study quality, heterogeneity in methodology and results, and a lack of consensus on assessment of chromium status.No significant effect of chromium on lipid or glucose metabolism was found in people without diabetes. Chromium supplementation significantly improved glycemia among patients with diabetes. However, future studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation.
The MicroRNA-Processing Enzyme Dicer Maintains Juxtaglomerular Cells
Authors: Maria Luisa S. Sequeira-Lopez, Eric T. Weatherford, Giulianna R. Borges, Maria C. Monteagudo, Ellen S. Pentz, Brian D. Harfe, Oscar Carretero, Curt D. Sigmund, R. Ariel Gomez
Journal: Journal of the American Society of Nephrology (2010)

Juxtaglomerular cells are highly specialized myoepithelioid granulated cells located in the glomerular afferent arterioles. These cells synthesize and release renin, which distinguishes them from other cells. How these cells maintain their identity, restricted localization, and fate is unknown and is fundamental to the control of BP and homeostasis of fluid and electrolytes. Because microRNAs may control cell fate via temporal and spatial gene regulation, we generated mice with a conditional deletion of Dicer, the RNase III endonuclease that produces mature microRNAs in cells of the renin lineage. Deletion of Dicer severely reduced the number of juxtaglomerular cells, decreased expression of the renin genes (Ren1 and Ren2), lowered plasma renin concentration, and decreased BP. As a consequence of the disappearance of renin-producing cells, the kidneys developed striking vascular abnormalities and prominent striped fibrosis. We conclude that microRNAs maintain the renin-producing juxtaglomerular cells and the morphologic integrity and function of the kidney.
Las noticias de Madrid (News from Madrid).
Authors: Suzanne Wahrle
Journal: Molecular Neurodegeneration (2006)

Over 5,000 participants attended the 10th International Conference on Alzheimer's Disease (ICAD) and Related Disorders in Madrid, Spain from July 15–20, 2006. Highlights of the conference included reports on brain imaging, the discovery of mutations in the progranulin gene that cause frontotemporal dementia, the finding that neuregulin-1 is a substrate for BACE1 and new interest in the connection between Alzheimer's disease and metabolic syndromes.
Infliximab Therapy in Patients with Chronic Sarcoidosis and Pulmonary Involvement
Authors: Robert P. Baughman, Marjolein Drent, Mani Kavuru, Marc A. Judson, Ulrich Costabel, Roland du Bois, Carlo Albera, Martin Brutsche, Gerald Davis, James F. Donohue, Joachim Müller-Quernheim, Rozsa Schlenker-Herceg, Susan Flavin, Kim Hung Lo, Barry Oemar, Elliot S. Barnathan
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Evidence suggests that tumor necrosis factor (TNF)-α plays an important role in the pathophysiology of sarcoidosis.Objectives: To assess the efficacy of infliximab in sarcoidosis.Methods: A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52.Measurements and Main Results: The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment.Conclusions: Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti–TNF-α therapy in severe, chronic, symptomatic sarcoidosis.
Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial
Authors: David N Krag, Stewart J Anderson, Thomas B Julian, Ann M Brown, Seth P Harlow, Joseph P Costantino, Takamaru Ashikaga, Donald L Weaver, Eleftherios P Mamounas, Lynne M Jalovec, Thomas G Frazier, R Dirk Noyes, André Robidoux, Hugh MC Scarth, Norman Wolmark
Journal: The Lancet Oncology (2010)
Meta-Analysis: Respiratory Tolerance to Regular β<sub>2</sub>-Agonist Use in Patients with Asthma
Authors: Shelley R. Salpeter, Thomas M. Ormiston, Edwin E. Salpeter
Journal: Annals of Internal Medicine (2004)

The regular administration of beta2-agonists may be associated with the development of tolerance to their effects.To assess the effect of regular beta2-agonist use on respiratory function and beta2-receptor function in asthmatic patients.Comprehensive searches of the EMBASE, MEDLINE, and CINAHL databases from 1966 to June 2003 and references of identified articles and reviews.Randomized, placebo-controlled trials that studied at least 1 week of regular beta2-agonist administration in patients with asthma and did not allow "as-needed" beta2-agonist use in the placebo group.Outcomes measured in the active treatment and placebo groups were the change in FEV1 in response to treatment and subsequent beta2-agonist administration, the provocative concentration of bronchoconstrictive agents causing a 20% reduction in FEV1 (PC20), and in vitro variables of leukocyte beta2-receptor function.Pooled results of 22 trials showed that regular beta2-agonist use, compared with placebo, did not change the mean FEV1 after treatment or the net FEV1 treatment effect but substantially reduced the following: the peak FEV1 response to subsequent beta2-agonist administration (change, -17.8% [95% CI, -27.2% to -8.5%]); the FEV1 dose response to subsequent beta2-agonists (-34.8% [CI, -45.7% to -24%]); the PC20 to combined bronchoconstrictive stimuli (-26% [CI, -37% to -11%]); and leukocyte beta2-receptor density (-18.3% [CI, -31.6% to -5.1%]), binding affinity (-23.1% [CI, -39.4% to -6.8%]), and in vitro response to isoproterenol (-32.7% [CI, -56.5% to -9.0%]).Regular beta2-agonist use for at least 1 week in patients with asthma results in tolerance to the drug's bronchodilator and nonbronchodilator effects and may be associated with poorer disease control compared with placebo.
Increased content of hydrogen peroxide in the expired breath of cigarette smokers
Authors: D Nowak, A Antczak, M Krol, T Pietras, B Shariati, P Bialasiewicz, K Jeczkowski, P Kula
Journal: European Respiratory Journal (1996)

Cigarette smoking causes an influx of mononuclear phagocytes and polymorphonuclear leucocytes into the lower airways. These cells have altered oxygen metabolism and release more H2O2 than phagocytes from nonsmokers. In this study, we intended to determine whether asymptomatic cigarette smokers exhale more H2O2 than healthy nonsmokers. The content of H2O2 in the expired condensate of 27 nonsmokers and 33 cigarette smokers was measured spectrofluorimetrically (homovanillic acid method). The mean H2O2 level in the expired breath condensate of all cigarette smokers was about fivefold higher than that found in the whole nonsmoker group (0.24 +/- 0.32 versus 0.05 +/- 0.11 nM). However, only 16 smokers (49%) and 6 nonsmokers (22%) had detectable levels of H2O2 in expired breath that reached values 0.49 +/- 0.28 and 0.23 +/- 0.10 nM, respectively. Although the cigarette smoking status was similar for both male and female smokers, females expired 2.5 fold less H2O2 than males (0.15 +/- 0.24 (n = 21) versus 0.38 +/- 0.39 (n = 12) nM. No correlation was found between expired H2O2 levels and cigarette smoking status expressed as the daily cigarette consumption, cumulative cigarette consumption and urinary cotinine concentration. It is suggested that in some smokers, expressed H2O2 can be a noninvasive marker of oxidant overload in the lower airways related to cigarette smoking.
Electrophysiology for CliniciansBarrero GarciaMiguel A.KhairyPaulMacleLaurentNattelStanley, eds.254 pages. Minneapolis, MN, USA: Cardiotext Publishing LLC,2011. $69.00. ISBN: 978-1935395140
Authors: Daniel D. Correa de Sa, Daniel L. Lustgarten
Journal: Circulation (2012)