tbuckley/cabot-search huggingface dataset:
Gene Expression Differences in Normal Esophageal Mucosa Associated with Regression and Progression of Mild and Moderate Squamous Dysplasia in a High-Risk Chinese Population
Authors: Nina Joshi, Laura Lee Johnson, Wen-Qiang Wei, Christian C. Abnet, Zhi-Wei Dong, Philip R. Taylor, Paul J. Limburg, Sanford M. Dawsey, Ernest T. Hawk, You-Lin Qiao, Ilan R. Kirsch
Journal: Cancer Research (2006)

Abstract A randomized, double-blinded, placebo-controlled 2 × 2 factorial chemoprevention trial was conducted in Linxian, China to assess the effects of selenomethionine and celecoxib on the natural history of esophageal squamous dysplasia. Results from this study indicated that asymptomatic adults with mild dysplasia were more likely to show an improvement when treated with selenomethionine compared with placebo (P = 0.02). Prompted by this finding, we examined the molecular profiles associated with regression and progression of dysplastic lesions in normal mucosa from 29 individuals, a subset of the Linxian cohort, using the Affymetrix U133A chip. Twenty differentially expressed genes were associated with regression and 129 were associated with progression when we compared the change in gene expression over time. Genes associated with immune response (n = 15), cell cycle (n = 15), metabolism (n = 15), calcium transport or calcium ion activity (n = 10), regulation of transcription (n = 9), signal transduction (n = 7), cytoskeleton and microtubules (n = 5), nucleotide processing and biosynthesis (n = 4), G-coupled signaling (n = 4), and apoptosis (n = 3) were present in the list of 149 genes. Using the Expression Analysis Systematic Explorer pathway analysis program, only the immune response pathway was significantly overrepresented among these 149 genes. Individuals whose lesions regressed seemed to have higher expression of genes associated with immune stimulation, such as antigen presentation, survival of T cells, and T-cell activation (HLA-DRA, HLA-DPA1, HLA-DBQ1, CD58, and FCER1A). In contrast, individuals whose lesions progressed had higher expression of genes involved in immune suppression and inflammation (CNR2, NFATC4, NFRKB, MBP, INHBB, CMKLR1, CRP, ORMS, SERPINA7, and SERPINA1). These data suggest that local and systemic immune responses may influence the natural history of esophageal squamous dysplasia. (Cancer Res 2006; 66(13): 6851-60)
Press: MMR: the onslaught continues
Authors: H. Bedford
Journal: BMJ (2003)

The controversy surrounding the measles, mumps, and rubella (MMR) vaccine continues to smoulder and every now and then someone stokes the fire. This time it is “top Mail writer” Melanie Phillips in a much hyped series of three articles in the Daily Mail under the banner “MMR: the truth” (11, 12, and 13 March).

Despite a three month globe-trotting investigation, Phillips, a seasoned polemicist, presents nothing new; she simply follows the usual pattern of conspiracy theory. For example, she claims that Professor John O'Leary, a pathologist at Trinity College Dublin, was gagged after announcing that the measles virus he had found in the guts of children with autism was the same strain as that used in the MMR vaccine. And she refers to more “potentially explosive” about-to-be-published research from gastroenterologist Andrew Wakefield—“the doctor at the heart of the MMR furore”—which it is claimed will show that he is right and that the rest of the world …
Interactions Between Electronic Article Surveillance Systems and Implantable Cardioverter-Defibrillators
Authors: William J. Groh, Scott A. Boschee, Erica D. Engelstein, William M. Miles, M. Erick Burton, Peter R. Foster, Barry J. Crevey, Douglas P. Zipes
Journal: Circulation (1999)

Background —In patients with implantable cardioverter-defibrillators (ICDs). inappropriate shocks have been reported with exposure to electronic article surveillance systems. The risk to patients with ICDs of walking through or lingering near surveillance systems requires further investigation. Methods and Results —We evaluated the response in ICD function in 170 subjects during a 10- to 15-second midgate walk-through of and during extreme (2 minutes within 6 in of the gate) exposure to 3 common article surveillance systems. Complete testing was done in 169 subjects. During a 10- to 15-second (very slow) walk-through of the 3 surveillance systems, no interactions were observed that would negatively affect ICD function. During extreme exposure (169 subjects) and during extreme exposure and pacing via the ICD (126 subjects), interactions between the ICD and the article surveillance systems were observed in 19 subjects. In 7 subjects, this interaction was clinically relevant and would have likely (3 subjects) and possibly (4 subjects) resulted in ICD shocks. In 12 subjects, the interaction was minor. Conclusions —It is safe for a patient with an ICD to walk through electronic article surveillance systems. Lingering in a surveillance system may result in an inappropriate ICD shock.
Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver
Authors: Hiromi Gunshin, Yuko Fujiwara, Angel O. Custodio, Cristina DiRenzo, Sylvie Robine, Nancy C. Andrews
Journal: Journal of Clinical Investigation (2005)

Solute carrier family 11, member 2 (SLC11A2) is the only transmembrane iron transporter known to be involved in cellular iron uptake. It is widely expressed and has been postulated to play important roles in intestinal iron absorption, erythroid iron utilization, hepatic iron accumulation, placental iron transfer, and other processes. Previous studies have suggested that other transporters might exist, but their physiological significance remained uncertain. To define the activities of Slc11a2 in vivo, we inactivated the murine gene that encodes it globally and selectively. We found that fetal Slc11a2 is not needed for materno-fetal iron transfer but that Slc11a2 activity is essential for intestinal non-heme iron absorption after birth. Slc11a2 is also required for normal hemoglobin production during the development of erythroid precursors. However, hepatocytes and most other cells must have an alternative, as-yet-unknown, iron uptake mechanism. We previously showed that Slc11a2 serves as the primary portal for intestinal iron entry in hemochromatosis. However, inactivation of murine Hfe ameliorates the phenotype of animals lacking Slc11a2.
Additive role of exhaled NO and blood eosinophil count to predict wheezing in a random population sample
Authors: Andrei Malinovschi, Joao Fonseca, Tiago Jacinto, Kjell Alving, Christer Janson
Journal: European Respiratory Journal (2012)

The fraction of nitric oxide in exhaled air (FeNO) and blood eosinophil count (B-Eos), markers of local and systemic eosinophil activation, respectively, are increased in asthma. Little is known about the relation to reported wheezing in a random population sample or the additive value of these two methods.  FeNO (NIOX Mino) and B-Eos were measured in 12,408 subjects aged 6-79 years from the National Health and Nutrition Examination Survey 2007-08 and 2009-10. Current wheezing, hay fever and smoking habits were questionnaire-assessed.  Subjects with wheezing had higher FeNO and B-Eos than subjects without wheezing (p 50 ppb) related to a higher wheezing prevalence than normal FeNO (14% and 25% vs 12% for normal FeNO, p=0.001). Slightly increased B-Eos (300-500 Eos/mm3) and high B-Eos (>500 Eos/mm3) related to a higher wheezing prevalence than normal B-Eos (17% and 22% vs 11% for normal B-Eos, p  In conclusion, the prevalence of wheezing increased in this random population sample with increased FeNO and blood eosinophil count and the predictive values of these biomarkers for wheezing is additive. The clinical importance of these findings in asthma with regard to phenotyping and individualized treatment has to be determined.
Positive selection and the molecular evolution of a gene of male reproduction, Acp26Aa of Drosophila
Authors: S. C. Tsaur, C. I. Wu
Journal: Molecular Biology and Evolution (1997)

The gene for a male ejaculatory protein, Acp26Aa, in four sibling species of the Drosophila melanogaster subgroup has previously been shown to have a nonsynonymous rate (Ka) of nucleotide substitution that is indistinguishable from the synonymous rate (Ks). By examining this gene in two other species of this subgroup, we found that Ka is generally large and can sometimes be more than twice as large as Ks. This suggests that positive selection may be operating at this locus of male reproduction.
Do patients wish to be involved in decision making in the consultation? A cross sectional survey with video vignettes
Authors: B. McKinstry
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To determine patients9 preferences for a shared or directed style of consultation in the decision making part of the general practice consultation. <b>Design:</b> Structured interview, with video vignettes of acted consultations. <b>Setting:</b> 5 practices in Lothian, Scotland. <b>Participants:</b> 410 patients (adults and adults accompanying children) attending surgery appointments. <b>Main outcome measures:</b> Preference for shared or directed form of video vignette for five different presenting conditions. <b>Results:</b> Patients varied in their preference for involvement in decision making in the consultation. Under multiple regression analysis, patients9 preference was found to be independently predicted by the problem viewed (patients presented with physical problems preferred a directed approach), patients9 age (patients aged 61 or older were more likely to prefer the directed approach), social class (social classes I and II were more likely to prefer the shared approach), and smoking status (smokers more likely to prefer the shared approach). Those patients who were able to answer (or who thought their doctor9s style similar to those in the vignettes) were more likely to describe their own doctor9s style as similar to their preferred style. No major association in preference was found with sex, frequency of attendance, or perceived chronic ill health. <b>Conclusion:</b> Patients may vary in their desire for involvement in decision making in consultations. Although this variation seems to depend on the presenting problem, age, social class, and smoking status, these associations are not absolute, with large minorities in each group. Doctors need the skills, knowledge of their patients, and the time to determine on which occasions, with which illnesses, and at which level their patients wish to be involved in decision making.
C-Rel Regulates Interleukin 12 P70 Expression in Cd8+ Dendritic Cells by Specifically Inducing <i>p35</i> Gene Transcription
Authors: Raelene Grumont, Hubertus Hochrein, Meredith O'Keeffe, Raffi Gugasyan, Christine White, Irina Caminschi, Wendy Cook, Steve Gerondakis
Journal: The Journal of Experimental Medicine (2001)

Interleukin 12 (IL-12) is a 70-kD proinflammatory cytokine produced by antigen presenting cells that is essential for the induction of T helper type 1 development. It comprises 35-kD (p35) and 40-kD (p40) polypeptides encoded by separate genes that are induced by a range of stimuli that include lipopolysaccharide (LPS), DNA, and CD40 ligand. To date, the regulation of IL-12 expression at the transcriptional level has mainly been examined in macrophages and restricted almost exclusively to the p40 gene. Here we show that in CD8+ dendritic cells, major producers of IL-12 p70, the Rel/nuclear factor (NF)-κB signaling pathway is necessary for the induction of IL-12 in response to microbial stimuli. In contrast to macrophages which require c-Rel for p40 transcription, in CD8+ dendritic cells, the induced expression of p35 rather than p40 by inactivated Staphylococcus aureus, DNA, or LPS is c-Rel dependent and regulated directly by c-Rel complexes binding to the p35 promoter. This data establishes the IL-12 p35 gene as a new target of c-Rel and shows that the regulation of IL-12 p70 expression at the transcriptional level by Rel/NF-κB is controlled through both the p35 and p40 genes in a cell type–specific fashion.
Congruence in Control-Region Sequence and Restriction-Site Variation in Mitochondrial DNA of Brook Charr (Salvelinus Fontinalis Mitchill)
Authors: Louis Bernatchez, Roy G. Danzmann
Journal: Molecular Biology and Evolution (1993)

We compared the congruence in genetic variation and phylogenetic relationships among mitochondrial DNA (mtDNA) haplotypes detected with restriction-fragment-length polymorphisms (RFLPs) and sequence analysis in the brook charr, Sulvelinus fontinalis Mitchill. This was accomplished by analyzing variation both at 172 restriction sites subsampling 903 bp over the entire mitochondrial genome and in the sequence of a 300-bp segment of the control region among the same 33 individuals. The sequence and RFLP analyses were highly congruent both in terms of mtDNA variants detected per number of nucleotides sampled and in assessing phylogenetic relationships among haplotypes. Therefore, variation observed in a small segment of the control region was representative of that existing over the entire genome. The major difference between both approaches was in the number of mutational changes observed per nucleotide in the sequence analysis. This number was approximately twice as high as that in the RFLP analysis. Nevertheless, the level of variation observed in the control region of charr was less than expected a priori on the basis of previous observations in other vertebrates. Lower mutation rates may be related to an unusually low transition : transversion ratio ( 8 : 3 ) for mtDNA intraspecific variation in vertebrates. The combined restriction-site and sequence data resolved at least three distinct phylogenetic groupings in S. fontinalis. However, and despite the high-resolution level of the study (> 1,200 bp screened, or 7% of the mitochondrial genome), some major branching patterns in gene tree topology remained unresolved, which stresses the importance of recognizing large standard errors associated with sequence variability when phylogeny is reconstructed.
Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study
Authors: Timothy Iveson, Ross C Donehower, Irina Davidenko, Sergey Tjulandin, Andrzej Deptala, Mark Harrison, Somanath Nirni, Kuntegowdanahalli Lakshmaiah, Anne Thomas, Yizhou Jiang, Min Zhu, Rui Tang, Abraham Anderson, Sarita Dubey, Kelly S Oliner, Elwyn Loh
Journal: The Lancet Oncology (2014)
Recovery of the ciliated epithelium following acute bronchiolitis in infancy
Authors: J Y W Wong
Journal: Thorax (2005)

Little is known about the longitudinal changes in the ciliated respiratory epithelium of infants following viral bronchiolitis. A study was undertaken to investigate the time required for the ciliated epithelium to return to normal following bronchiolitis in infants treated with inhaled steroids or placebo.Thirty one previously healthy term infants were studied as part of a clinical trial to determine the effect of 12 weeks of treatment with inhaled fluticasone (FP) or placebo via a spacer device (17 FP, 14 placebo). Nineteen healthy children aged 0-6 years previously studied in our department were used as controls. Nasal biopsy specimens were taken from infants with bronchiolitis and ciliary beat frequency (CBF) was measured before treatment and repeated 3, 6, 12, and 24 weeks later. The epithelial ultrastructure was examined by transmission electron microscopy and a normal errors mixed model based on normal controls was used to examine the time for cilia to return to normal in bronchiolitic infants.The mean CBF of infants with bronchiolitis (in Hz) at weeks 0, 3, 6, 12, and 24 were 0.5 (n = 4), 10.9 (n = 4), 12.0 (n = 9), 11.9 (n = 8), and 12.1 (n = 7) in the placebo group and 10.6 (n = 6), 11.4 (n = 9), 8.8 (n = 8), 10.9 (n = 4), and 13.2 (n = 7) in the FP group. The time for the epithelial ultrastructure to normalise was as follows: epithelial integrity score (13.1 weeks), % ciliated cells with loss of cilia (14.0 weeks), and % epithelial cells with abnormalities in projection (16.7 weeks) or mitochondria (15.9 weeks). Inhaled steroids had no significant effects on CBF or epithelial ultrastructure.Ciliary loss and epithelial abnormalities persist on average for 13-17 weeks following acute bronchiolitis in infancy.
Tracheobronchial deposition and clearance in small airways in asthmatic subjects
Authors: K Svartengren, K Philipson, M Svartengren, M Anderson, P Camner
Journal: European Respiratory Journal (1996)

Asthma tends to impair mucociliary clearance, as assessed from measurements in large airways. However, very little is known about clearance in the smallest airways of the tracheobronchial region. Deposition and clearance was estimated in 11 subjects with stable asymptomatic asthma and 10 healthy subjects after inhalation of 6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at an extremely slow flow, 0.05 L.s-1. Theoretical calculations and experimental data in healthy subjects using this slow flow support an enhanced deposition in the tracheobronchial region, in particular in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h. Clearance was significant every 24 h both for asthmatic and healthy subjects, with similar fractions of retained particles at all time-points. The fractions of tracheobronchially-deposited particles were on average 41 and 47% for asthmatic and healthy subjects, respectively, as compared to a maximal deposition of 30% using a normal inhalation flow (0.5 L.s-1). No significant correlation was found between lung retention and lung function, either in asthmatics or in healthy subjects. Our results indicate that particles clear equally well from small ciliated airways in asthmatic and healthy subjects, maybe as a consequence of an optimal asthma therapy. Furthermore, our results show that it is possible to enhance tracheobronchial deposition both in healthy and asthmatic subjects, i.e. practically independent of airway dimensions, by inhaling rather large aerosol particles extremely slowly. This may be a useful therapeutic approach.
Toward the Treatment and Prevention of Alzheimer's Disease: Rational Strategies and Recent Progress
Authors: Sam Gandy, Steven T. DeKosky
Journal: Annual Review of Medicine (2013)

Alzheimer's disease (AD) is the major cause of late-life brain failure. In the past 25 years, autosomal dominant forms of AD were found to be primariy attributable to mutations in one of two presenilins, polytopic proteins that contain the catalytic site of the γ-secretase protease that releases the amyloid beta (Aβ) peptide. Some familial AD is also due to mutations in the amyloid precursor protein (APP), but recently a mutation in APP was discovered that reduces Aβ generation and is protective against AD, further implicating amyloid metabolism. Prion-like seeding of amyloid fibrils and neurofibrillary tangles has been invoked to explain the stereotypical spread of AD within the brain. Treatment trials with anti-Aβ antibodies have shown target engagement, if not significant treatment effects. Attention is increasingly focused on presymptomatic intervention, because Aβ mismetabolism begins up to 25 years before symptoms begin. AD trials deriving from new biological information involve extraordinary international collaboration and may hold the best hope for success in the fight against AD.
Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia
Authors: Matej Orešič, Tuulikki Seppänen-Laakso, Daqiang Sun, Jing Tang, Sebastian Therman, Rachael Viehman, Ulla Mustonen, Theo G van Erp, Tuulia Hyötyläinen, Paul Thompson, Arthur W Toga, Matti O Huttunen, Jaana Suvisaari, Jaakko Kaprio, Jouko Lönnqvist, Tyrone D Cannon
Journal: Genome Medicine (2012)

Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission. Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples. In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed. Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.
A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5–FU2 + irinotecan or LV5–FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer
Authors: Y. Bécouarn, P. Senesse, S. Thézenas, E. Boucher, A. Adenis, L. Cany, J.H. Jacob, F. Cvitkovic, C. Montoto-Grillot, M. Ychou
Journal: Annals of Oncology (2007)
Weekly docetaxel in minimally pretreated cancer patients: A dose-escalation study focused on feasibility and cumulative toxicity of long-term administration
Authors: E. Briasoulis, V. Karavasilis, D. Anastasopoulos, E. Tzamakou, G. Fountzilas, D. Rammou, V. Kostadima, N. Pavlidis
Journal: Annals of Oncology (1999)
ERJ at your fingertips
Authors: J.L. Arnold
Journal: European Respiratory Journal (2004)

Have you ever had a headache that lasted 3 yrs? If you have ever tried to log onto ERJ online and failed then you may be partway to understanding the cause of my chronic headache.

In January, 2004, Peter Sterk and Klaus Rabe, the Chief Editors of the ERJ , reported that many readers around the world had complained about the accessibility of the ERJ online 1; and, as the recipient of many of these complaints, I can confirm that this was the case. The reputation of the ERJ , and the impact it has upon the respiratory field, is directly affected by how efficient the dissemination of it is. It has,therefore, been imperative to resolve the problems experienced by our readers.

It is with relief that I report that my “ibuprofen equivalent” comes in the form of a company called HighWire. Whilst this company may be unknown to most of you, their system will be very familiar, as they are responsible for hosting the American Thoracic Society (ATS) journals and 70% of all the other journals cited in the …