tbuckley/cabot-search huggingface dataset:
Multiple Evolutionary Mechanisms Drive Papillomavirus Diversification
Authors: M. Gottschling, A. Stamatakis, I. Nindl, E. Stockfleth, A. Alonso, I. G. Bravo
Journal: Molecular Biology and Evolution (2007)

The circular, double-stranded 8-kb DNA genome of papillomaviruses (PVes) consists mainly of 4 large genes, E1, E2, L2, and L1. Approximately 150 papillomavirus genomes have been sequenced to date. We analyzed a representative sample of 53 PVes genomes using maximum likelihood, Bayesian inference, maximum parsimony, and distance-based methods both on nucleotide (nt) and on amino acid (aa) alignments. When the 4 genes were analyzed separately, aa-inferred phylogenies contradicted each other less than nt-inferred trees (judged by partition homogeneity tests). In particular, gene combinations including the L2 gene generated significant incongruence (P < 0.001). Combined analyses of the remaining genes E1-E2-L1 produced a well-supported phylogeny including supertaxon beta + gamma + pi + xi-PVes (infecting Artiodactyla, Carnivora, Primates, and Rodentia) and supertaxon kappa + lambda + mu + nu + sigma-PVes (infecting Carnivora, Lagomorpha, Primates, and Rodentia). Based on the tree topology, host-linked evolution appears plausible at shallow, rather than deeper, taxonomic levels. Diversification within PVes may also involve adaptive radiation establishing different niches (within a single-host species) and recombination events (within single-host cells). Heterogeneous groups of closely related PVes infecting, for example, humans and domestic animals such as hamster, dog, and cattle suggest multiple infections across species borders. Additional evolutionary phenomena such as strong codon usage preferences, and computational biases including reconstruction artifacts and insufficient taxon sampling, may contribute to the incomplete resolution of deep phylogenetic nodes. The molecular data globally supports a complex evolutionary scenario for PVes, which is driven by multiple mechanisms but not exclusively by coevolution with corresponding hosts.
Human organ-specific autoimmune disease. Molecular cloning and expression of an autoantibody gene repertoire for a major autoantigen reveals an antigenic immunodominant region and restricted immunoglobulin gene usage in the target organ.
Authors: G D Chazenbalk, S Portolano, D Russo, J S Hutchison, B Rapoport, S McLachlan
Journal: Journal of Clinical Investigation (1993)

The most common organ-specific autoimmune disease in humans involves the thyroid. Autoantibodies against thyroid peroxidase (TPO) are present in the sera of virtually all patients with active disease. We report the molecular cloning of the genes for 30 high-affinity, IgG-class human autoantibodies to TPO from thyroid-infiltrating B cells. Analysis of the putative germline genes used for the TPO human autoantibodies suggests the use of only five different H and L chain combinations involving four H chains and three L chains. In addition, the same combination of H and L chains was found in multiple patients. The F(ab) proteins expressed by these genes define two major, closely associated domains (A and B) in an immunodominant region on TPO. These A and B domains contain the binding sites of approximately 80% of IgG-class TPO autoantibodies in the sera of patients with autoimmune thyroid disease. The present information permits analysis, not previously possible, of the relationship between autoantibody H and L chain genes and the antigenic domains on an autoantigen. Our data, obtained using target organ-derived autoantibodies, indicate that there is restriction in H and L chain usage in relation to the interaction with specific antigenic domains in human, organ-specific autoimmune disease.
A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0-42 months
Authors: N. Wadonda-Kabondo, J.A.C. Sterne, J. Golding, C.T.C. Kennedy, C.B. Archer, M.G.S. Dunnill
Journal: British Journal of Dermatology (2003)

Journal Article A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0–42 months Get access N. Wadonda‐Kabondo, N. Wadonda‐Kabondo Departments of Child Health and Social Medicine, University of Bristol, Bristol, U.K Search for other works by this author on: Oxford Academic Google Scholar J.A.C. Sterne, J.A.C. Sterne Departments of Child Health and Social Medicine, University of Bristol, Bristol, U.K Search for other works by this author on: Oxford Academic Google Scholar J. Golding, J. Golding Departments of Child Health and Social Medicine, University of Bristol, Bristol, U.K Search for other works by this author on: Oxford Academic Google Scholar C.T.C. Kennedy, C.T.C. Kennedy Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K Search for other works by this author on: Oxford Academic Google Scholar C.B. Archer, C.B. Archer Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K Search for other works by this author on: Oxford Academic Google Scholar M.G.S. Dunnill, M.G.S. Dunnill Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K Dr M.G.S.Dunnill. Tel.: 0117 9282785. Fax: 0117 9282845. E‐mail: giles.dunnill@ubht.swest.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar The alspac study team The alspac study team Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 5, 1 November 2003, Pages 1023–1028, https://doi.org/10.1111/j.1365-2133.2003.05605.x Published: 01 November 2003 Article history Accepted: 25 February 2003 Published: 01 November 2003
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients
Authors: Paolo Fardin, Annalisa Barla, Sofia Mosci, Lorenzo Rosasco, Alessandro Verri, Rogier Versteeg, Huib N Caron, Jan J Molenaar, Ingrid Øra, Alessandra Eva, Maura Puppo, Luigi Varesio
Journal: Molecular Cancer (2010)

Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo) taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of neuroblastoma tumor independently from MYCN amplification. Our results demonstrate that the NB-hypo is a novel and independent prognostic factor for neuroblastoma and support the view that hypoxia is negatively correlated with tumors' outcome. We show the power of the biology-driven approach in defining hypoxia as a critical molecular program in neuroblastoma and the potential for improvement in the current criteria for risk stratification.
Resistance of Gram-negative Bacteria to Purified Bactericidal Leukocyte Proteins
Authors: Jerrold Weiss, Susan Beckerdite-Quagliata, Peter Elsbach
Journal: Journal of Clinical Investigation (1980)

The sensitivity or resistance of gram-negative bacteria to antibacterial systems appears to be related to the length of the saccharide chain of the bacterial envelope lipopolysaccharides (LPS). To explore this relationship further, we made use of two bactericidal, membrane-active cationic proteins, recently purified to near homogeneity, one from human and one from rabbit polymorphonuclear leukocytes (PMN). We have studied the effects of these two closely similar proteins on strains of Salmonella typhimurium and Escherichia coli, each separate strain differing in the saccharide chain length of its outer membrane LPS. Binding of these proteins to the bacterial outer membrane is required for killing, and is accompanied by an almost immediate increase in outer membrane permeability to normally impermeant actinomycin D. Sensitivity to the bactericidal and permeability-increasing activities of the human and rabbit proteins increases with decreasing LPS-saccharide chain length (chemotype: [S < Ra < Rb3 < Rc < Rd1]). S. typhimurium G-30 and E. coli J5, mutant strains lacking UDP-galactose-4-epimerase, synthesize incomplete LPS (chemotype Rc) when grown without galactose, and are then as sensitive to both PMN proteins as the S. typhimurium strains 395 R10 (Rd1) and R5 (Rb3). However, when these mutants are grown with galactose, they synthesize complete LPS (chemotype S) and exhibit nearly the same relative insensitivity as the smooth strains S. typhimurium 395 MS and E. coli 0111:B4.
Reconciling schizophrenic deficits in top-down and bottom-up processes: Not yet
Authors: Angus W. MacDonald
Journal: Behavioral and Brain Sciences (2003)

Abstract This commentary challenges the authors to use their computational modeling techniques to support one of their central claims: that schizophrenic deficits in bottom-up (Gestalt-type tasks) and top-down (cognitive control tasks) context processing tasks arise from the same dysfunction. Further clarification about the limits of cognitive coordination would also strengthen the hypothesis.
Associations between Breast Cancer Susceptibility Gene Polymorphisms and Clinicopathological Features
Authors: Wonshik Han, Daehee Kang, In Ae Park, Seok Won Kim, Ji Yeon Bae, Ki-Wook Chung, Dong-Young Noh
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Genetic polymorphisms may affect not only cancer development but also cancer progression, and as a result could influence cancer phenotypes. The aim of this study was to examine the relationship between breast cancer susceptibility gene polymorphisms and clinicopathological features. Experimental Design: We genotyped 664 Korean primary breast cancer patients for 17 single-nucleotide polymorphisms (SNPs) in nine genes, using a high-throughput SNP scoring method. Results: CYP1A1 codon 462 Ile/Val or Val/Val variants and the CYP1B1 codon 432 Leu/Val variant were found more in breast cancer patients ≤35 years of age at onset than the common homozygote [odds ratio (OR), 1.6 and 1.7, respectively]. In combination analysis of these two SNPs, the OR was 1.9 when one of them was heterozygous or a rare homozygous form, and increased to 2.3 when both were variants (P = 0.006). Cases with Ile/Val at CYP1A1 codon 462 were 2.6-fold and those with Val/Val were 5.1-fold more likely to have first-degree relatives with breast cancer than those with Ile/Ile (P = 0.002). In the haplotype study of BRCA1, the 2430C/2731T/3667G/4427C/4956G homozygote showed less estrogen receptor negativity than the most common diplotype (OR, 0.5; 95% confidence interval, 0.26–0.94). TP53 codon 72 Arg/Pro or Pro/Pro variants were associated with negative axillary lymph node status (OR, 0.7; 95% confidence interval, 0.49–0.94). Conclusions: These results indicate that polymorphisms of some selected breast cancer susceptibility genes are associated with the clinicopathological phenotypes of breast cancer.
Cue-Induced Cocaine Craving: Neuroanatomical Specificity for Drug Users and Drug Stimuli
Authors: Hugh Garavan, John Pankiewicz, Alan Bloom, Jung-Ki Cho, Lori Sperry, Thomas J. Ross, Betty Jo Salmeron, Robert Risinger, Dan Kelley, Elliot A. Stein
Journal: American Journal of Psychiatry (2000)

Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood.To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity).Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film.These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.
Home ventilation: need a user support number?
Authors: P. Delguste, D. Rodenstein
Journal: European Respiratory Journal (2010)

ontemporary homes can include a number of electrical devices aimed at making life easier, such as washing machines, dishwashers and vacuum cleaners.One can also find devices aimed at improving lifestyle, such as exercise bicycles or rowing machines.However, one can also find other types of devices that are aimed at supporting or saving people's life.These can include continuous positive airway pressure machines, home dialysis machines, oxygen concentrators and home respirators.All these devices have electrical plugs, knobs, switches, light bulbs, LEDs and screens.However, the manipulation of these devices is not at all similar, and the interactions between the devices and the users have quite different meanings.Despite the obvious differences between these machines, it remains true that a malfunctioning washing machine or a malfunctioning respirator will require a similar reaction: call the user support number.Respiratory physicians do not have a long tradition of home life support treatment and every piece of information concerning this issue is worth learning.In the present issue of the European Respiratory Journal, CHATWIN et al.[1] present data on the call centre they established to support more than 1,000 patients on home respirators.The Respiratory Unit of the Royal Brompton Hospital (London, UK) serves a vast geographical area.In order to allow patients to reach them, they established a communication protocol based on telephone numbers patients can call day and night in case they need to or they feel they need to.These calls can be made for a number of reasons; from simple concerns such as asking for spare part replacement, to more disturbing ones such alarms coming on during the night or to a respirator becoming noisy all of a sudden, to very serious ones such as a respirator breakdown in a respirator dependent patient.CHATWIN et al.[1] have recorded and analysed all calls received during a 6-month period, from a population of 1,211 patients, from paediatrics to geriatrics, who were followed up at their centre.All patients had had a training process within the Royal Brompton Hospital unit, and all patients or families were deemed able to understand the use of home respirators, adequately fit and assembly/disassembly the mask and interfaces, start and stop the machines, and even to unlock the settings in order to change them according to telephonic instructions if this was thought useful by the on-call personnel.A personalised information set was delivered to each patient with written instructions and information on their respirator, settings and interfaces, spare part numbers, etc.
Effect of Omalizumab on Symptoms of Seasonal Allergic Rhinitis&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Thomas B. Casale
Journal: JAMA (2001)

ContextSeasonal allergic rhinitis is a common IgE-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation.ObjectiveTo assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis.DesignRandomized, double-blind, dose-ranging, placebo-controlled trial conducted from July 25 through November 21, 1997.SettingTwenty-five outpatient centers throughout the United States.PatientsFive hundred thirty-six patients aged 12 to 75 years with at least a 2-year history of moderate to severe ragweed-induced seasonal allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL.InterventionsPatients were randomly assigned to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just prior to ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments).Main Outcome MeasuresSelf-assessed daily nasal symptom severity scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of treatment.ResultsNasal symptom severity scores were significantly lower in patients who received 300 mg of omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98, respectively; P = .002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during peak season. The frequency of adverse events was not significantly different among the omalizumab and placebo groups.ConclusionOmalizumab decreased serum free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis.
Low shear stress can initiate von Willebrand factor-dependent platelet aggregation in patients with type IIB and platelet-type von Willebrand disease.
Authors: M Murata, M Fukuyama, K Satoh, Y Fujimura, A Yoshioka, H Takahashi, M Handa, Y Kawai, K Watanabe, Y Ikeda
Journal: Journal of Clinical Investigation (1993)

Platelets exposed to shear stress aggregate in the absence of exogenously added agonists, utilizing distinct platelet membrane receptors and ligands depending upon the level of shear stress applied. Using a modified cone and plate type viscometer, we previously demonstrated that, under low shear stress (18 dyn/cm2), aggregation is mediated by platelet membrane glycoprotein (GP) IIb-IIIa and fibrinogen, whereas aggregation induced by high shear stress (108 dyn/cm2) requires the binding of von Willebrand factor (vWF) to both GPIb-IX and GPIIb-IIIa (Ikeda, Y., M. Handa, K. Kawano, T. Kamata, M. Murata, Y. Araki, H. Anbo, Y. Kawai, K. Watanabe, I. Itagaki, et al. 1991. J. Clin. Invest. 87:1234-1240). Here we report that vWF-dependent aggregation occurs under low shear stress in citrated platelet-rich plasma (PRP) from two types of congenital bleeding disorders, platelet-type von Willebrand disease (vWD) and type IIB vWD, in both of which ristocetin-induced aggregation is known to be heightened. Aggregation induced by low shear stress was enhanced in both types of disorders compared to normal controls, and the enhancement was completely abolished by anti-vWF monoclonal antibody NMC-4, which blocks the GPIb-binding site on vWF. Under high shear stress, the extent of maximal aggregation was not different between controls and the patient groups although maximal aggregation was reached much more quickly in the latter. When citrated PRP was exposed to a gradient of shear stress (6 to 108 dyn/cm2 over a 5-min period), vWF-dependent aggregation, as judged from the inhibitory effect of NMC-4, first occurred at 14 dyn/cm2 in platelet-type vWD and at 10-12 dyn/cm2 in type IIB vWD, as compared with more than 81 +/- 20.1 dyn/cm2 in control platelets. These results suggest that an abnormality in either vWF or GPIb-IX triggers the aggregation-inducing interaction of the two molecules under low shear stress, which might explain the intravascular platelet clumping, that presumably underlies the thrombocytopenia observed in these bleeding disorders.
Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial
Authors: Andrea Vaclavkova, Sergio Chimenti, Petr Arenberger, Peter Holló, Paul-Gunther Sator, Michel Burcklen, Mylène Stefani, Daniele D'Ambrosio
Journal: The Lancet (2014)
Glutathione <i>S</i> -Transferase Polymorphisms, Passive Smoking, Obesity, and Heart Rate Variability in Nonsmokers
Authors: Nicole M. Probst-Hensch, Medea Imboden, Denise Felber Dietrich, Jean-Claude Barthélemy, Ursula Ackermann-Liebrich, Wolfgang Berger, Jean-Michel Gaspoz, Joel Schwartz
Journal: Environmental Health Perspectives (2008)

BackgroundDisturbances of heart rate variability (HRV) may represent one pathway by which second-hand smoke (SHS) and air pollutants affect cardiovascular morbidity and mortality. The mechanisms are poorly understood.ObjectivesWe investigated the hypothesis that oxidative stress alters cardiac autonomic control. We studied the association of polymorphisms in oxidant-scavenging glutathione S-transferase (GST) genes and their interactions with SHS and obesity with HRV.MethodsA total of 1,133 nonsmokers > 50 years of age from a population-based Swiss cohort underwent ambulatory 24-hr electrocardiogram monitoring and reported on lifestyle and medical history. We genotyped GSTM1 and GSTT1 gene deletions and a GSTP1 (Ile105Val) single nucleotide polymorphism and analyzed genotype–HRV associations by multiple linear regressions.ResultsHomozygous GSTT1 null genotypes exhibited an average 10% decrease in total power (TP) and low-frequency-domain HRV parameters. All three polymorphisms modified the cross-sectional associations of HRV with SHS and obesity. Homozygous GSTM1 null genotypes with > 2 hr/day of SHS exposure exhibited a 26% lower TP [95% confidence interval (CI), 11 to 39%], versus a reduction of −5% (95% CI, −22 to 17%) in subjects with the gene and the same SHS exposure compared with GSTM1 carriers without SHS exposure. Similarly, obese GSTM1 null genotypes had, on average, a 22% (95% CI, 12 to 31%) lower TP, whereas with the gene present obesity was associated with only a 3% decline (95% CI, −15% to 10%) compared with nonobese GSTM1 carriers.ConclusionsGST deficiency is associated with significant HRV alterations in the general population. Its interaction with SHS and obesity in reducing HRV is consistent with an impact of oxidative stress on the autonomous nervous system.