tbuckley/cabot-search huggingface dataset:
Modification of surface antigens in blood CD8+ T-lymphocytes in COPD: effects of smoking
Authors: A Koch, M Gaczkowski, G Sturton, P Staib, T Schinköthe, E Klein, A Rubbert, K Bacon, K Wassermann, E Erdmann
Journal: European Respiratory Journal (2006)

In contrast to the effects of cigarette smoke on T-lymphocyte subsets in the airways, it has not yet been determined whether smoking has immunomodulatory effects on surface antigens of peripheral blood T-lymphocytes and, if that is the case, whether these effects differ in smokers with and without chronic obstructive pulmonary disease (COPD). The present authors have, therefore, examined the expression of the surface activation marker CD28, the levels of cytotoxic effector lymphocytes (CD27-/CD45RA+) and the expression of the lung type (Tc)1-specific chemokine receptor CXCR<sub>3</sub>+ on peripheral blood CD8+ T-lymphocytes. The present authors have also studied the chemotactic activity of CD8+ T-lymphocytes on monocyte chemotactic protein (MCP)-1 and compared 13 nonsmoking controls, 12 smokers with COPD and 14 smokers without airflow limitation. There was a decrease in the total count of CD8+ T-cells and an increase in the CD4+/CD8+ ratio in smokers with COPD compared with smokers without COPD and controls. Expression of the Tc1-specific chemokine receptor CXCR<sub>3</sub>+ by CD8+ T-cells was increased in smokers with COPD compared with smokers without COPD and controls. The expression of activated and of cytotoxic effector CD8+ T-cells in smokers with and without COPD showed an increase compared with controls. CD8+ T-cells from smokers with and without COPD showed a decrease in chemotactic activity to MCP-1 compared with controls. In conclusion, chronic obstructive pulmonary disease may be a systemic immunomodulatory disease associated with the modification of surface antigens in blood CD8+ T-lymphocytes.
The relationship between acid and bile reflux and symptoms in gastro-oesophageal reflux disease.
Authors: R E Marshall, A Anggiansah, W A Owen, W J Owen
Journal: Gut (1997)

BACKGROUND: The role of bile in the genesis of oesophageal symptoms and disease is incompletely understood. A new method of ambulatory bile monitoring may help to define this role. AIMS: To establish the relationship between symptom events and acid and bile reflux episodes. PATIENTS: 59 consecutive patients presenting for further investigation of gastro-oesophageal reflux disease. METHODS: All patients underwent combined ambulatory pH and bile monitoring. For each patient, a symptom index (SI) was calculated in relation to both acid reflux and bile reflux episodes. RESULTS: Patients were divided into those without (group 1, n = 21) and those with (group 2, n = 38) acid reflux. A total of 394 symptoms were identified in 59 patients. In group 1, there were fewer symptom events per patient (mean 4.1) than group 2 (mean 8.1). Twenty three per cent of symptom events were associated with acid reflux in group 1 and 41% in group 2. Only 6% of symptom events in both groups were related to bile reflux. In group 1 both the acid and bile related SI score were low. In group 2 the bile related SI score was low, but the acid related SI score was high. CONCLUSIONS: Symptoms are much more often related to acid reflux than bile reflux. Bile reflux does not seem to be a major factor in producing oesophageal symptoms.
Negative Trials for Foreseeable Safety Reasons in Advanced Hepatocellular Carcinoma: How Long Are We Going to Take Lightly Pharmacokinetics of Tyrosine Kinase Inhibitors?
Authors: Mohamed Bouattour, Benoît Rousseau, Johanna Wassermann, Audrey Payancé, Olivier Huillard
Journal: Journal of Clinical Oncology (2015)
Medical journals and the mass media: moving from love and hate to love
Authors: R. Smith
Journal: Journal of the Royal Society of Medicine (2006)

Medical journals are the main conduit by which medical research reaches the public; and the public seem to be ever more interested in medical stories.Consequently, the mass media pay ever more attention to medical journals.In Britain Friday morning is 'Lancet and BMJ' morning.Virtually every week the morning's media will include stories from one or the other, and often both; although editors may sometimes be critical of the media, they love the attention.But is this passion for publicity corrupting the journals?Should the journals, far from courting the mass media, be keeping them at a distance?
Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation
Authors: Shuang Wu, Wenjun Yu, Xiaoyan Qu, Rong Wang, Ji Xu, Qiguo Zhang, Jiaren Xu, Jianyong Li, Lijuan Chen
Journal: Journal of Hematology & Oncology (2014)

Dysregulated microRNA (miRNA) expression contributes to cancer cell proliferation, apoptosis and angiogenesis. Angiogenesis is a hallmark of multiple myeloma (MM) development and progression. Argonaute 2 (AGO2) protein, a core component of the RNA-induced silencing complex (RISC), can directly bind to miRNAs and mediate target messenger RNA (mRNA) degradation. A previous study showed that AGO2 knockdown suppressed human umbilical vein endothelial cell (HUVEC) growth and tube formation. However, the roles and molecular mechanisms of AGO2-induced myeloma angiogenesis are not yet fully understood. The aim of this study was to characterize these roles and effects and their associated mechanisms.Supernatants from AGO2-overexpressing MM lines induced HUVEC migration and accelerated tube formation. Conversely, supernatants from AGO2-knockdown MM lines suppressed HUVEC cell migration and tube formation. Moreover, a chick chorioallantoic membrane (CAM) assay was used to demonstrate that AGO2 could drive neovessel formation in MM lines in vivo. Using an miRNA microarray, we observed that 25 miRNAs were upregulated and 7 were downregulated in response to AGO2. Most let-7 family members and 2 miR-17/92 cluster members (miR-17a and miR-92-1), all known pro-angiogenic miRNAs, were positively regulated by AGO2 whereas anti-angiogenic miRNAs such as miR-145 and miR-361 were negatively regulated by AGO2.We conclude that AGO2 can drive neovessel formation in vitro and in vivo by dysregulating the expression of some angiogenic miRNAs. The pro-angiogenic miRNAs of the let-7 family and the miR-17/92 cluster, along with the anti-angiogenic miRNA miR-145, play crucial roles in AGO2-mediated angiogenesis by targeting angiogenesis-related genes.
Free Cholesterol Accumulation in Macrophage Membranes Activates Toll-Like Receptors and p38 Mitogen-Activated Protein Kinase and Induces Cathepsin K
Authors: Yu Sun, Minako Ishibashi, Tracie Seimon, Mingsum Lee, Sudarshana M. Sharma, Katherine A. Fitzgerald, Andriy O. Samokhin, Yibin Wang, Scott Sayers, Masanori Aikawa, W. Gray Jerome, Michael C. Ostrowski, Dieter Bromme, Peter Libby, Ira A. Tabas, Carrie L. Welch, Alan R. Tall
Journal: Circulation Research (2009)

The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c- Apoe −/− mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K ( Ctsk ) expression. We now show increased cathepsin K immunostaining and increased cysteinyl proteinase activity using near infrared fluorescence imaging over proximal aortas of Apoe −/− , Npc1 −/− mice. In mechanistic studies, cholesterol loading of macrophage plasma membranes (cyclodextrin–cholesterol) or endosomal system (AcLDL+U18666A or Npc1 null mutation) activated Toll-like receptor (TLR) signaling, leading to sustained phosphorylation of p38 mitogen-activated protein kinase and induction of p38 targets, including Ctsk , S100a8 , Mmp8 , and Mmp14 . Studies in macrophages from knockout mice showed major roles for TLR4, following plasma membrane cholesterol loading, and for TLR3, after late endosomal loading. TLR signaling via p38 led to phosphorylation and activation of the transcription factor Microphthalmia transcription factor, acting at E-box elements in the Ctsk promoter. These studies suggest that free cholesterol enrichment of either plasma or endosomal membranes in macrophages leads to activation of signaling via various TLRs, prolonged p38 mitogen-activated protein kinase activation, and induction of Mmps , Ctsk , and S100a8 , potentially contributing to plaque complications.
Statistical properties of the variation at linked microsatellite loci: implications for the history of human Y chromosomes [published erratum appears in Mol Biol Evol 1997 Mar;14(3):354]
Authors: D. B. Goldstein, L. A. Zhivotovsky, K. Nayar, A. R. Linares, L. L. Cavalli-Sforza, M. W. Feldman
Journal: Molecular Biology and Evolution (1996)

It has recently been suggested that observed levels of variation at microsatellite loci can be used to infer patterns of selection in genomes and to assess demographic history. In order to evaluate the feasibility of these suggestions it is necessary to know something about how levels of variation at microsatellite loci are expected to fluctuate due simply to stochasticity in the processes of mutation and inheritance (genetic sampling). Here we use recently derived properties of the stepwise mutation model to place confidence intervals around the variance in repeat score that is expected at mutation-drift equilibrium and outline a statistical test for whether an observed value differs significantly from expectation. We also develop confidence intervals for the time course of the buildup of variation following a complete elimination of variation, such as might be caused by a selective sweep or an extreme population bottleneck. We apply these methods to the variation observed at human Y-specific microsatellites. Although a number of authors have suggested the possibility of a very recent sweep, our analyses suggest that a sweep or extreme bottleneck is unlikely to have occurred anytime during the last approximately 74,000 years. To generate this result we use a recently estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with the variation observed at autosomal microsatellite loci to estimate the human effective population size. This estimate is 18,000, implying an effective number of 4,500 Y chromosomes. One important general conclusion to emerge from this study is that in order to reject mutation-drift equilibrium at a set of linked microsatellite loci it is necessary to have an unreasonably large number of loci unless the observed variance is far below that expected at mutation-drift equilibrium.
Insulin-Based Versus Triple Oral Therapy for Newly Diagnosed Type 2 Diabetes
Authors: Ildiko Lingvay, Jaime L. Legendre, Polina F. Kaloyanova, Song Zhang, Beverley Adams-Huet, Philip Raskin
Journal: Diabetes Care (2009)

Early use of insulin after diagnosis of type 2 diabetes is met with resistance because of associated weight gain, hypoglycemia, and fear of decreased compliance and quality of life (QoL).In treatment-naive patients with newly diagnosed type 2 diabetes, insulin and metformin were initiated for a 3-month lead-in period, then patients were randomly assigned to insulin and metformin (insulin group) or metformin, pioglitazone, and glyburide (oral group) for 36 months. Hypoglycemic events, compliance, A1C, weight, QoL, and treatment satisfaction were assessed.Of 29 patients randomly assigned into each group, 83% (insulin group) and 72% (oral group) completed this 3-year study. At study completion, A1C was 6.1 +/- 0.6% (insulin group) versus 6.0 +/- 0.8% (oral group). Weight increased similarly in both groups (P = 0.09) by 4.47 kg (95% CI 0.89-8.04 kg) (insulin group) and 7.15 kg (95% CI 4.18-10.13 kg) (orals group). Hypoglycemic events did not differ between groups (mild 0.51 event/person-month in the insulin group vs. 0.68 event/person-month in the orals group, P = 0.18 and severe 0.04 event/person-year in the insulin group vs. 0.09 event/person-year in the orals group, P = 0.53). Compliance, QoL, and treatment satisfaction were similar between groups, with 100% of patients randomly assigned to insulin willing to continue such treatment.When compared with a clinically equivalent treatment regimen, insulin-based therapy is effective and did not cause greater weight gain or hypoglycemia nor decrease compliance, treatment satisfaction, or QoL. Insulin is safe, well-accepted, and effective for ongoing treatment of patients with newly diagnosed type 2 diabetes.
UEMS charter on the training of rheumatologists in Europe
Authors: J A P Da Silva, K-L Faarvang, K Bandilla, A D Woolf
Journal: Annals of the Rheumatic Diseases (2007)

The Treaty of Rome provides for the free exchange of persons, services, goods and capital within the European Community. Free exchange of persons and services within the medical sector has been achieved by mutual recognition of basic and specialist medical qualifications brought into effect by the Commission of the European Communities (EC) in 1975. The Directives have been consolidated in the Directive 93/16/EEC of 5 April 1993.

This Directive 93/16 specifies that Member States shall ensure that the training leading to a diploma, certificate or other evidence of formal qualifications in specialised medicine, meets a number of minimum quality criteria, including duration, content, setting and quality control. It also establishes that Member States shall designate the authorities and bodies competent to issue or receive the diplomas, certificates and other evidence of formal qualifications.

The UEMS (Union Europeenne des Medecins Specialistes) is the representative organisation of all medical specialists in the EC. The UEMS is constituted by the representative organisations of medical specialists in the member states of the EC and the EFTA countries as well as associate members and observers from other European countries. One of its statutory purposes is the formulation of a common policy in the field of training.

The UEMS Section of Rheumatology is the representative body of rheumatologists within UEMS. Members of the UEMS Section of Rheumatology are appointed by the appropriate professional organisations of the specialties in the EC member states and EFTA countries in accordance with UEMS rules of procedure.

The European Board of Rheumatology was set up by the relevant UEMS Section of Rheumatology with the purpose of guaranteeing the highest standards of care for rheumatological conditions in the EC member states by ensuring that the training of specialists is raised to an adequate level.

Working in cooperation with the European Commission, UEMS …
THE IMPORTANCE OF VASCULAR COMPLICATIONS AFTER TRANS-FEMORAL TRANS-CATHETER AORTIC VALVE REPLACEMENT (TAVR): INSIGHTS FROM THE PARTNER TRIAL
Authors: Philippe Genereux, John Webb, Jeffrey Moses, Susheel Kodali, Mathew Williams, Michael Mack, D. Craig Miller, Lars Svensson, E. Murat Tuzcu, Craig Smith, Martin Leon
Journal: Journal of the American College of Cardiology (2012)
ZINBA integrates local covariates with DNA-seq data to identify broad and narrow regions of enrichment, even within amplified genomic regions
Authors: Naim U Rashid, Paul G Giresi, Joseph G Ibrahim, Wei Sun, Jason D Lieb
Journal: Genome biology (2011)

ZINBA (Zero-Inflated Negative Binomial Algorithm) identifies genomic regions enriched in a variety of ChIP-seq and related next-generation sequencing experiments (DNA-seq), calling both broad and narrow modes of enrichment across a range of signal-to-noise ratios. ZINBA models and accounts for factors that co-vary with background or experimental signal, such as G/C content, and identifies enrichment in genomes with complex local copy number variations. ZINBA provides a single unified framework for analyzing DNA-seq experiments in challenging genomic contexts. Software website: http://code.google.com/p/zinba/
Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy.
Authors: W P Vaughan, J E Karp, P J Burke
Journal: Journal of Clinical Oncology (1983)

Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have "secondary" acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of "primary" acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively.
Comparison of One-Day Versus One-Hour Application of Topical Gatifloxacin in Eliminating Conjunctival Bacterial Flora
Authors: Jason M. Moss, David Nguyen, Yueyi I. Liu, Kuldev Singh, Artis Montague, Peter R. Egbert, Herminia Mino De Kaspar, Christopher N. Ta
Journal: Ophthalmology (2008)
Inhibition of Tumor-Induced Migration of Bovine Capillary Endothelial Cells by Mouse and Rabbit Tumor Necrosis Factor
Authors: Yukiko Mano-Hirano, Noboru Sato, Yoshio Sawasaki, Katsuyuki Haranaka, Nobuko Satomi, Hideo Nariuchi, Tamotsu Goto
Journal: JNCI Journal of the National Cancer Institute (1987)

The effect of tumor necrosis factor (TNF) on the tumor-induced endothelial migration was evaluated with the use of a phagokinetic track assay. TNF from both ddy mice and Japanese albino rabbits (sp act, 3-5 X 10(5) U/mg, respectively) was found to inhibit the migration of bovine capillary endothelial (BCE) cells stimulated by factors from tumor cells, such as the medium conditioned with mouse sarcoma 180 cells or human meningioma extract. These TNF preparations, however, did not affect the spontaneous migration of the BCE cells. When mouse TNF was further fractionated by polyacrylamide gel electrophoresis, only TNF-positive fractions showed an inhibitory activity on the tumor-induced endothelial motility. Moreover, monoclonal antibody against rabbit TNF completely neutralized its migration-inhibitory activity. These findings indicate that the observed inhibitory effect of TNF preparations on the endothelial motility evoked by tumor is exclusively ascribed to the function of TNF. This activity presumably is involved in the suppression of tumor angiogenesis in vivo.
A comparative study of FVC, FEV1, and TLC in non-smoking Saudi students at Eastern Province, Saudi Arabia with Caucasian reference values
Authors: Noor AL-Khathlan, Stephanie Enright, Mohammmed Amr El-Noueam
Journal: European Respiratory Journal (2012)

Introduction:  It is well-known that pulmonary function testing (PFT) values vary with height, age, gender, and ethnicity. 1  The influence of ethnic variation on PFT in particular has been the topic of numerous studies conducted globally. 1  ,2  In Saudi Arabia (SA), the currently available reference values (RV) for PFT are based on data from the Caucasian population. We aimed to compare Saudi measured values, for forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ) and total lung capacity (TLC), with Caucasian RV.   Methods:  Healthy non-smoker university students were recruited to perform spirometry and plethysmography. Measurements were obtained according to ATS/ERS recommendations, standardized for height and age and compared with Caucasian RV.   Results:  We studied 128 subjects, 16 of which were excluded for technical reasons. Significant difference (p 1  and TLC for Saudis were found to be lower than the means of RV for Caucasians by about 10%, 5% and 8% respectively for males and 16%, 12% and 5% respectively for females.   Discussion:  Matching the reference and patient populations when selecting RV for PFT is significant. 3  The observed differences we found between Saudi9s PF and Caucasian RV can be deemed of great importance and maybe explained in terms of environmental and life-style factors. However, larger study is required to confirm these findings.  1. Hankinson et al. 1999 AJRCCM; 159:179-187  2. Al-Riyami et al. 2004 Respirology; 9:387-391  3. Wanger et al. 2005 ERJ; 26:511-522.
Complex Principal Component and Correlation Structure of 16 Yeast Genomic Variables
Authors: F. J. Theis, N. Latif, P. Wong, D. Frishman
Journal: Molecular Biology and Evolution (2011)

A quickly growing number of characteristics reflecting various aspects of gene function and evolution can be either measured experimentally or computed from DNA and protein sequences. The study of pairwise correlations between such quantitative genomic variables as well as collective analysis of their interrelations by multidimensional methods have delivered crucial insights into the processes of molecular evolution. Here, we present a principal component analysis (PCA) of 16 genomic variables from Saccharomyces cerevisiae, the largest data set analyzed so far. Because many missing values and potential outliers hinder the direct calculation of principal components, we introduce the application of Bayesian PCA. We confirm some of the previously established correlations, such as evolutionary rate versus protein expression, and reveal new correlations such as those between translational efficiency, phosphorylation density, and protein age. Although the first principal component primarily contrasts genomic change and protein expression, the second component separates variables related to gene existence and expressed protein functions. Enrichment analysis on genes affecting variable correlations unveils classes of influential genes. For example, although ribosomal and nuclear transport genes make important contributions to the correlation between protein isoelectric point and molecular weight, protein synthesis and amino acid metabolism genes help cause the lack of significant correlation between propensity for gene loss and protein age. We present the novel Quagmire database (Quantitative Genomics Resource) which allows exploring relationships between more genomic variables in three model organisms—Escherichia coli, S. cerevisiae, and Homo sapiens (http://webclu.bio.wzw.tum.de:18080/quagmire).
Attention Deficit/Hyperactivity Disorder Across the Lifespan
Authors: Timothy E. Wilens, Joseph Biederman, Thomas J. Spencer
Journal: Annual Review of Medicine (2002)

▪ Abstract Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder presenting for treatment in youth. ADHD is often chronic with prominent symptoms and impairment spanning into adulthood. ADHD is often associated with co-occurring anxiety, mood, and disruptive disorders, as well as substance abuse. The diagnosis of ADHD by careful review of symptoms and impairment is both reliable and valid. Recent genetic, imaging, neurochemistry, and neuropsychological data support the biological underpinning of the disorder. All aspects of an individual's life must be considered in the diagnosis and treatment of ADHD. Pharmacotherapy, including stimulants, antidepressants, and antihypertensives, plays a fundamental role in the management of ADHD across the lifespan.