tbuckley/cabot-search huggingface dataset:
Screening of atopic allergy in 5‐year‐old children – a comparison of the diagnostic properties of Phadiatop Paediatric and Phadiatop
Authors: G. Lilja, E. Kusoffsky, S. G. O. Johansson, H. Öman
Journal: Allergy (1995)

The ability of Phadiatop Paediatric (PP), Phadiatop (P), mixed‐food RAST (MF), and the combination of P and MF to identify children with atopic allergy was evaluated among 193 children who had a family history of atopic disease, and who had an average age of 5 years. If atopy is defined as the presence of at least one positive skin prick test ( 2 +) to common food and/or inhalant allergens, P had a sensitivity of 86%, a specificity of 94%, and an efficacy of 92%. These figures were somewhat better than the results with PP. However, when P was combined with MF, the sensitivity increased to 89%, but at the expense of lowered specificity (83%) and efficacy (84%). If the tests were related only to clinical signs/symptoms of atopic disease, the sensitivity and efficacy were, at maximum, 63% and 81%, respectively. There was a discrepancy between the results of P and PP in 9% of the children. One explanation of this discrepancy may be that PP seems to be incapable of detecting children with respiratory allergies induced by pollens from birch and related trees. The results indicate that in 5–6‐year‐old children P should be preferred to PP and to the combination of P and MF for atopy screening, at least in places where birch pollen is a common allergen.
Exposure–response analysis of allergy and respiratory symptoms in endotoxin-exposed adults
Authors: L. A. M. Smit, D. Heederik, G. Doekes, C. Blom, I. van Zweden, I. M. Wouters
Journal: European Respiratory Journal (2008)

The objective of the present study was to investigate exposure–response relationships between current endotoxin exposure and allergic and respiratory symptoms in adults, taking into account farming exposures during childhood. A cross-sectional study was conducted among 877 Dutch farmers and agricultural industry workers in 2006. Based on 249 full-shift personal airborne endotoxin samples, a job-exposure matrix was constructed to assign endotoxin exposure levels to all participants. Associations between endotoxin exposure and questionnaire data on symptoms were studied by multiple logistic regression. Adjusted odds ratios (OR) for an interquartile range increase in endotoxin level were elevated for respiratory symptoms such as wheezing (OR 1.41 (95% confidence interval 1.16–1.72)), wheezing with shortness of breath (1.50 (1.18–1.90)) and daily cough (1.29 (1.03–1.62)). In contrast, endotoxin was strongly associated with a decreased prevalence of hay fever (0.62 (0.49–0.78)). Workers who had grown up on a farm had a lower prevalence of hay fever, but no evidence was found of effect modification by farm childhood. In conclusion, occupational endotoxin exposure in adulthood is associated with an increased risk of asthma-like symptoms but a reduced prevalence of hay fever.
Structural and functional properties of region II-plus of the malaria circumsporozoite protein.
Authors: P Sinnis, P Clavijo, D Fenyö, B T Chait, C Cerami, V Nussenzweig
Journal: The Journal of Experimental Medicine (1994)

During feeding, infected mosquitos inject malaria sporozoites into the host circulation. Within minutes, the parasites are found in the liver where they initiate the first stage of malaria infection. All species of malaria sporozoites are uniformly covered by the circumsporozoite protein (CS), which contains a conserved COOH-terminal sequence called region II-plus. We have previously shown that region II-plus is the parasite's hepatocyte-binding ligand and that this ligand binds to heparan sulfate proteoglycans (HSPGs) on the hepatocyte membrane. Using a series of substituted region II-plus peptides, we show here that the downstream basic amino acids as well as the interdispersed hydrophobic residues are required for binding of CS to hepatocyte HSPGs. We also show that this positively charged stretch of amino acids must be aggregated in order to bind to the receptor. On the basis of this information, we have synthesized a multiple antigen peptide that mimics the hepatocyte-binding ligand. This construct inhibits both CS binding to HepG2 cells in vitro as well as CS clearance in mice.
Hyperactivity of the IL33-ST2 axis during postnatal alveolarization increases susceptibility to house dust mite sensitization via skewing of CD11b+ dendritic cells
Authors: Ismé De Kleer, Monique Willart, Mirjam Kool, Maud Plantinga, Rudi Hendriks, Hamida Hammad, Bart Lambrecht
Journal: European Respiratory Journal (2014)

Early postnatal programming of Th2 polarized memory to house dust mite (HDM) represents a major risk factor for the subsequent development of asthma. We previously reported that CD11b+ conventional dendritic cells (cDCs) is the main HDM presenting DC subset in the lungs. We now show that in neonatal mice this DC subset is very low in absolute numbers and hardly detectable in the lungs. Despite these low numbers sensitization to aero-allergens can take place directly after birth due to excellent HDM-antigen uptake and migratory capacity of the very few neonatal CD11b+ cDCs around. Even more, neonatal CD11b+ cDCs showed a much stronger Th2 skewing activity compared to their adult counterpart. This difference in Th2 skewing capacity was present at birth due to DC intrinsic IL-12p70 deficiency of neonatal CD11b+ cDCs but increased significantly between postnatal day (PND)7 to 21. This age window is characterized by rapid postnatal alveolarization and lung growth and coincided with highly increased baseline and HDM-induced IL-33 levels as well as high numbers of innate lymphoid cells type 2 (ILC2). Due to a direct Th2 skewing effect of these high IL-33 levels on neonatal lung CD11b+ cDCs but also on monocyte derived (Mo)DCs PND14 mice were increased susceptible to HDM sensitization. As a consequence, in vivo blockade of IL-33 via administration of recombinant soluble ST2-receptor during HDM sensitization had a much stronger effect on reducing lung inflammation in PND14 than in PND3 or adult mice.
Circulating Tumor Cell Isolation and Diagnostics: Toward Routine Clinical Use
Authors: Anja van de Stolpe, Klaus Pantel, Stefan Sleijfer, Leon W. Terstappen, Jaap M.J. den Toonder
Journal: Cancer Research (2011)

From February 7-11, 2011, the multidisciplinary Lorentz Workshop Circulating Tumor Cell (CTC) Isolation and Diagnostics: Toward Routine Clinical Use was held in Leiden (The Netherlands) to discuss progress and define challenges and potential solutions for development of clinically useful circulating tumor cell (CTC) diagnostics. CTCs, captured as "liquid biopsy" from blood, for counting and characterization using pathology and molecular assays, are expected to replace metastatic tissue biopsies to be used to predict drug response and resistance and to monitor therapy response and cancer recurrence. CTCs are highly heterogeneous; therefore, cancer type-specific isolation technologies, as well as complex clinical interpretation software, are required.
Asymmetric directional mutation pressures in bacteria
Authors: Jean R Lobry, Noboru Sueoka
Journal: Genome biology (2002)

When there are no strand-specific biases in mutation and selection rates (that is, in the substitution rates) between the two strands of DNA, the average nucleotide composition is theoretically expected to be A = T and G = C within each strand. Deviations from these equalities are therefore evidence for an asymmetry in selection and/or mutation between the two strands. By focusing on weakly selected regions that could be oriented with respect to replication in 43 out of 51 completely sequenced bacterial chromosomes, we have been able to detect asymmetric directional mutation pressures.Most of the 43 chromosomes were found to be relatively enriched in G over C and T over A, and slightly depleted in G+C, in their weakly selected positions (intergenic regions and third codon positions) in the leading strand compared with the lagging strand. Deviations from A = T and G = C were highly correlated between third codon positions and intergenic regions, with a lower degree of deviation in intergenic regions, and were not correlated with overall genomic G+C content.During the course of bacterial chromosome evolution, the effects of asymmetric directional mutation pressures are commonly observed in weakly selected positions. The degree of deviation from equality is highly variable among species, and within species is higher in third codon positions than in intergenic regions. The orientation of these effects is almost universal and is compatible in most cases with the hypothesis of an excess of cytosine deamination in the single-stranded state during DNA replication. However, the variation in G+C content between species is influenced by factors other than asymmetric mutation pressure.
Increased Toll-Like Receptor (TLR) Activation and TLR Ligands in Recently Diagnosed Type 2 Diabetic Subjects
Authors: Mohan R. Dasu, Sridevi Devaraj, Samuel Park, Ishwarlal Jialal
Journal: Diabetes Care (2010)

Individuals with type 2 diabetes have a myriad of metabolic aberrations including increased inflammation, increasing their cardiovascular risk. Toll-like receptors (TLRs) and their ligands play a key role in insulin resistance and atherosclerosis. However, there is a paucity of data examining the expression and activity of TLRs in type 2 diabetes. Thus, in the present study, we examined TLR2 and TLR4 mRNA and protein expression, their ligands, and signaling in monocytes of recently diagnosed type 2 diabetic patients.TLR mRNA, protein expression, TLR ligands, and TLR signaling were measured in freshly isolated monocytes from healthy human control subjects (n = 23) and type 2 diabetic subjects (n = 23) using real-time RT-PCR, Western blot, and flow cytometric assays.Type 2 diabetic subjects had significantly increased TLR2, TLR4 mRNA, and protein in monocytes compared with control subjects (P < 0.05). Increased TLR2 and TLR4 expression correlated with BMI, homeostasis model assessment-insulin resistance (HOMA-IR), glucose, A1C, N(epsilon)-(carboxymethyl) lysine (CML), and free fatty acid (FFA). Ligands of TLR2 and TLR4, namely, HSP60, HSP70, HMGB1, endotoxin, and hyaluronan levels, were elevated in type 2 diabetic subjects and positively correlated with TLR2 and TLR4. Type 2 diabetic subjects showed increased MyD88, phosphorylated IRAK-1, Trif, TICAM-1, IRF-3, and NF-kappaB p65 expression in monocytes compared with control subjects. Furthermore, TLR-MyD88-NF-kappaB signaling resulted in elevated levels of cytokines (P < 0.05), but increased interleukin (IL)-1beta, interferon (IFN)-gamma, and endotoxin were not significant when adjusted for BMI.In this comprehensive study, we make the novel observation that TLR2 and TLR4 expression and their ligands, signaling, and functional activation are increased in recently diagnosed type 2 diabetes and contribute to the proinflammatory state.
Ekphrasis in colour categorisation: Time for research, or time for revolution?
Authors: Darren Van Laar
Journal: Behavioral and Brain Sciences (1997)

Saunders and van Brakel propose that we rethink or reject much of current colour theory. Many of the problems they cite appear to call for further research rather than a radical rethinking of colour theory. The controversy described in this target article appears to be itself a case of “ekphrasis,” or something that does not exist.
Reliability of self assessed joint counts in ankylosing spondylitis
Authors: A Spoorenberg
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> To determine the reliability of self reported joint counts to assess pain or swelling in ankylosing spondylitis (AS). <b>Methods:</b> 217 outpatients fulfilling the modified New York criteria for AS were asked to mark painful joints and swollen joints on two mannequins presenting 44 and 40 joints respectively. A doctor or research nurse assessed the same joints for pain and swelling on the same day, after completion by the patient, without information on the results of the patient9s assessment. <b>Results:</b> Forty six (21%) patients reported one or more swollen joints (mean number of swollen joints 0.5, range 0–8); the doctor found one or more swollen joints in 54 (25%) of the patients (mean number of swollen joints 0.8, range 0–31). The overall agreement on the number of swollen joints between patients and doctor was moderate (intraclass correlation coefficient (ICC) 0.53). Agreement on individual swollen joints was poor to moderate (κ 0.1–0.64). 128 (60%) patients reported tender joints (mean number of joints 2.4, range 0–26). The doctors reported one of more tender joints in 50% of the patients (mean number of tender joints 2.2, range 0–34). The overall agreement was also moderate (ICC 0.71). The agreement on individual tender joints was again poor to moderate (κ 0.19–0.43). There was only high concordance between doctors and patients on the absence of swollen joints (82%). The concordance on the presence of monoarthritis, oligoarthritis, or polyarthritis was low (17–22%). <b>Conclusion:</b> Owing to these discrepancies in assessment of individual joints and total number of affected joints, joint counts in AS assessed by doctors cannot be replaced by joint counts reported by the patients. Patients are only able to judge if their joints are not swollen.
miRNA Dysregulation in Breast Cancer
Authors: Laoighse Mulrane, Sharon F. McGee, William M. Gallagher, Darran P. O'Connor
Journal: Cancer Research (2013)

Abstract miRNAs have emerged, in the last decade, as key players in the carcinogenic process, with many candidates identified as playing important roles in many aspects of tumor development, growth, metastasis, and drug resistance. More recently, polymorphisms in miRNAs themselves or in their binding sites in target genes have been identified to incur increased risk of breast cancer in certain populations. In addition, epigenetic regulation and differential expression of processing enzymes has been shown to contribute to the aberrant expression of miRNAs in breast cancer. This review focuses on the area of miRNA dysregulation in breast cancer through both genetic and epigenetic mechanisms, and the impact of this dysregulation on breast cancer risk and resistance to therapies. Cancer Res; 73(22); 6554–62. ©2013 AACR.
Expression of Nicotinic Acetylcholine Receptor Subunit Genes in Non–Small-Cell Lung Cancer Reveals Differences between Smokers and Nonsmokers
Authors: David Chi-leung Lam, Luc Girard, Ruben Ramirez, Wing-shun Chau, Wai-sing Suen, Shelley Sheridan, Vicky P.C. Tin, Lap-ping Chung, Maria P. Wong, Jerry W. Shay, Adi F. Gazdar, Wah-kit Lam, John D. Minna
Journal: Cancer Research (2007)

Abstract Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non–small-cell lung cancers (NSCLC) may provide information for prevention or therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6 human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR and microarray analysis. Five nonmalignant HBECs were exposed to nicotine in vitro to study the variation of nAChR subunit gene expression with nicotine exposure and removal. NSCLCs from nonsmokers showed higher expression of nAChR α6 (P &amp;lt; 0.001) and β3 (P = 0.007) subunit genes than those from smokers, adjusted for gender. In addition, nAChR α4 (P &amp;lt; 0.001) and β4 (P = 0.029) subunit gene expression showed significant difference between NSCLCs and normal lung. Using Affymetrix GeneChip U133 Sets, 65 differentially expressed genes associated with NSCLC nonsmoking nAChR α6β3 phenotype were identified, which gave high sensitivity and specificity of prediction. nAChR α1, α5, and α7 showed significant reversible changes in expression levels in HBECs upon nicotine exposure. We conclude that between NSCLCs from smokers and nonsmokers, different nAChR subunit gene expression patterns were found, and a 65-gene expression signature was associated with nonsmoking nAChR α6β3 expression. Finally, nicotine exposure in HBECs resulted in reversible differences in nAChR subunit gene expression. These results further implicate nicotine in bronchial carcinogenesis and suggest targeting nAChRs for prevention and therapy in lung cancer. [Cancer Res 2007;67(10):4638–47]
High and Rising Health Care Costs. Part 1: Seeking an Explanation
Authors: Thomas Bodenheimer
Journal: Annals of Internal Medicine (2005)

The United States has the most expensive health care system in the world, with per capita health expenditures far above those of any other nation. For many years, U.S. health care expenditures have been growing above the overall rate of inflation in the economy. A few experts have argued that high and rising costs are not such a serious problem. Most observers disagree with this view, pointing to the negative impact of employee health care costs on employers, the government budgetary problems caused by rising health care expenditures, and an association between high health care costs and reduced access for individuals needing health services. Several explanations have been offered for high and rising health care costs. These include the perspectives that high and rising costs are created by forces external to the health system, by the weakness of a competitive free market within the health system, by the rapid diffusion of new technologies, by excessive costs of administering the health system, by the absence of strong cost-containment measures, and by undue market power of health care providers. This article, the first in a 4-part series, discusses 3 perspectives on health care: 1) Are high and rising health care costs a serious problem? 2) Are rising costs explained by factors outside the health care system? 3) Does the absence of a free market in health care explain why costs are high and rising? The remaining 3 articles in this series address other perspectives on health care costs.
Emerging regulators of vascular smooth muscle cell function in the development and progression of atherosclerosis
Authors: J. L. Johnson
Journal: Cardiovascular Research (2014)

After a period of relative senescence in the field of vascular smooth muscle cell (VSMC) research with particular regards to atherosclerosis, the last few years has witnessed a resurgence, with extensive research re-assessing potential molecular mechanisms and pathways that modulate VSMC behaviour within the atherosclerotic-prone vessel wall and the atherosclerotic plaque itself. Attention has focussed on the pathological contribution of VSMC in plaque calcification; systemic and local mediators such as inflammatory molecules and lipoproteins; autocrine and paracrine regulators which affect cell–cell and cell to matrix contacts alongside cytoskeletal changes. In this brief focused review, recent insights that have been gained into how a myriad of recently identified factors can influence the pathological behaviour of VSMC and their subsequent contribution to atherosclerotic plaque development and progression has been discussed. An overriding theme is the mechanisms involved in the alterations of VSMC function during atherosclerosis.
Epidemiologic Association Between<i>FUT2</i>Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States
Authors: Daniel C. Payne, Rebecca L. Currier, Mary A. Staat, Leila C. Sahni, Rangaraj Selvarangan, Natasha B. Halasa, Janet A. Englund, Geoffrey A. Weinberg, Julie A. Boom, Peter G. Szilagyi, Eileen J. Klein, James Chappell, Christopher J. Harrison, Barbara S. Davidson, Slavica Mijatovic-Rustempasic, Mary D. Moffatt, Monica McNeal, Mary Wikswo, Michael D. Bowen, Ardythe L. Morrow, Umesh D. Parashar
Journal: JAMA Pediatrics (2015)

A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus.We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children.Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013.Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis.One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis.Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.
Circulating Invariant Natural Killer T-Cell Numbers Predict Outcome in Head and Neck Squamous Cell Carcinoma: Updated Analysis With 10-Year Follow-Up
Authors: Famke L. Schneiders, Renée C.G. de Bruin, Alfons J.M. van den Eertwegh, Rik J. Scheper, C. René Leemans, Ruud H. Brakenhoff, Johannes A. Langendijk, Henk M.W. Verheul, Tanja D. de Gruijl, Johan W. Molling, Hans J. van der Vliet
Journal: Journal of Clinical Oncology (2012)