tbuckley/cabot-search huggingface dataset:
Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts
Authors: Victor Turcanu, Soheila J. Maleki, Gideon Lack
Journal: Journal of Clinical Investigation (2003)

Comparing lymphocyte responses to allergenic and nonallergenic foods could reveal the differences between pathogenic and normal immune responses to foods. Defining the cytokine-producing phenotypes of peanut-specific lymphocytes from peanut-allergic children, children who outgrew peanut allergy, and children who have always tolerated peanuts may be useful for understanding the mechanisms of food tolerance. Investigating immune responses against foods is hindered, however, by the fact that circulating food antigen-specific lymphocytes are very rare. In a novel approach we used carboxyfluorescein succinimidyl ester to detect peanut-specific lymphocytes by flow cytometry. We confirmed that these cells are indeed peanut specific by cloning. Peanut-allergic donors show Th2 polarization of cytokine production by peanut-specific cells (IFN-gamma (low), TNF-alpha (low), IL-4 (high), IL-5 (high), IL-13 (high)). Conversely, nonallergic children and children who have outgrown their allergy show Th1 skewing to peanut antigens (IFN-gamma(high), TNF-alpha (high), IL-4 (low), IL-5 (low), IL-13(low)), similarly to nonallergenic food antigens (beta-lactoglobulin, OVA). This finding suggests that peanut antigens do not intrinsically induce Th2 skewing, but that the type of response depends upon the donor's allergic status. In conclusion, food allergic status is characterized by a Th2 response whereas Th1-skewed responses underlie oral tolerance.
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors vs Conventional Chemotherapy in Non–Small Cell Lung Cancer Harboring Wild-Type Epidermal Growth Factor Receptor
Authors: June-Koo Lee, Seokyung Hahn, Dong-Wan Kim, Koung Jin Suh, Bhumsuk Keam, Tae Min Kim, Se-Hoon Lee, Dae Seog Heo
Journal: JAMA (2014)

Current guidelines recommend both epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy drugs as standard treatment options for patients with wild-type (WT) EGFR who were previously treated for non-small cell lung cancer (NSCLC). However, it is not clear that EGFR TKIs are as efficacious as chemotherapy in patients with WT EGFR.To determine the association between first-generation EGFR TKI vs chemotherapy and survival in advanced NSCLC patients with WT EGFR.PubMed, EMBASE, Cochrane database, and meeting abstracts of the American Society of Clinical Oncology and European Society of Medical Oncology through December 2013.Eligible studies were randomized controlled trials comparing EGFR TKI with conventional chemotherapy in patients with advanced NSCLC. Out of 1947 retrieved articles, 11 trials incorporating 1605 patients with WT EGFR were included.Two reviewers extracted trial characteristics and outcomes. The risk of bias was evaluated using the Cochrane tool. All measures were pooled using random-effects models and 95% CIs were calculated.The primary outcome was progression-free survival (PFS), measured as hazard ratios (HRs). The secondary outcomes were objective response rate and overall survival, expressed as relative risks and HRs, respectively.Among patients with WT EGFR tumors, chemotherapy was associated with improvement of PFS, compared with TKI (HR for TKI, 1.41; 95% CI, 1.10-1.81). No statistically significant subgroup difference was identified in terms of line of treatment (first-line vs second- or later-line), experimental drug, dominant ethnicity, or EGFR mutation analysis method. Trials using more sensitive platforms than direct sequencing were associated with a significant PFS benefit with chemotherapy (HR for TKI, 1.84; 95% CI, 1.35-2.52). The association of chemotherapy with improvement in PFS was also significant in second- or later-line trials (HR, 1.34; 95% CI, 1.09-1.65). The objective response rate was higher with chemotherapy (92/549, 16.8%, vs 39/540, 7.2%, for TKI; relative risk for TKI, 1.11; 95% CI, 1.02-1.21); however, no statistically significant difference was observed with respect to overall survival (HR for TKI, 1.08; 95% CI, 0.96-1.22).Among patients with advanced NSCLC harboring WT EGFR, conventional chemotherapy, compared with first-generation EGFR TKI, was associated with improvement in PFS but not overall survival.
The epidemiological importance of `ay' and `ad' subtypes of the HB-Ag
Authors: F. Pons-Romero, J. Heathcote, S. Sherlock
Journal: Gut (1974)

The distribution of the subtypes ;ay' and ;ad' has been assessed in 159 hepatitis B antigen (HB-Ag) positive subjects with a variety of associated hepatic conditions. A specific subtype could not be correlated with any particular hepatic pathology when the whole group was considered. However, the distribution of these two subtypes did vary according to the geographical origin of the subject or infection, or the presumed route of infection, so that there was an apparent association of one subtype with a certain disease state. Subtyping performed on 10 HB-Ag-positive households showed the subtype to be the same within nine, emphasizing the epidemiological rather than the pathological importance of the ;ay' and ;ad' subtypes of the HB-Ag.
Interleukin-17–producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity
Authors: Hye Young Kim, Hyun Jun Lee, Ya-Jen Chang, Muriel Pichavant, Stephanie A Shore, Katherine A Fitzgerald, Yoichiro Iwakura, Elliot Israel, Kenneth Bolger, John Faul, Rosemarie H DeKruyff, Dale T Umetsu
Journal: Nature Medicine (2013)
Molecular Pathways: Interleukin-15 Signaling in Health and in Cancer
Authors: Anjali Mishra, Laura Sullivan, Michael A. Caligiuri
Journal: Clinical Cancer Research (2014)

Interleukin-15 (IL-15) is a proinflammatory cytokine involved in the development, survival, proliferation, and activation of multiple lymphocyte lineages utilizing a variety of signaling pathways. IL-15 utilizes three distinct receptor chains in at least two different combinations to signal and exert its effects on the immune system. The binding of IL-15 to its receptor complex activates an "immune-enhancing" signaling cascade in natural killer cells and subsets of T cells, as well as the induction of a number of proto-oncogenes. Additional studies have explored the role of IL-15 in the development and progression of cancer, notably leukemia of large granular lymphocytes, cutaneous T-cell lymphoma, and multiple myeloma. This review provides an overview of the molecular events in the IL-15 signaling pathway and the aberrancies in its regulation that are associated with chronic inflammation and cancer. We briefly explore the potential therapeutic opportunities that have arisen as a result of these studies to further the treatment of cancer. These involve both targeting the disruption of IL-15 signaling as well as IL-15-mediated enhancement of innate and antigen-specific immunity.
Synaptic Mechanisms for Plasticity in Neocortex
Authors: Daniel E. Feldman
Journal: Annual Review of Neuroscience (2009)

Sensory experience and learning alter sensory representations in cerebral cortex. The synaptic mechanisms underlying sensory cortical plasticity have long been sought. Recent work indicates that long-term cortical plasticity is a complex, multicomponent process involving multiple synaptic and cellular mechanisms. Sensory use, disuse, and training drive long-term potentiation and depression (LTP and LTD), homeostatic synaptic plasticity and plasticity of intrinsic excitability, and structural changes including formation, removal, and morphological remodeling of cortical synapses and dendritic spines. Both excitatory and inhibitory circuits are strongly regulated by experience. This review summarizes these findings and proposes that these mechanisms map onto specific functional components of plasticity, which occur in common across the primary somatosensory, visual, and auditory cortices.
Analysis of the mechanism of unresponsiveness produced by haptens painted on skin exposed to low dose ultraviolet radiation.
Authors: C A Elmets, P R Bergstresser, R E Tigelaar, P J Wood, J W Streilein
Journal: The Journal of Experimental Medicine (1983)

Acute, low dose ultraviolet B radiation of murine body wall skin followed by local application of DNFB produces a state of antigen-specific unresponsiveness. This state is maintained at least in part by an Lyt-1+ T cell that effects unresponsiveness by impairing the induction phase of contact hypersensitivity. The absence of suppressor cells capable of acting at the effector stage of immunity suggests that tolerogenic signals derived from the skin establish suppressor networks that are incomplete and perhaps different from networks that are induced by systemic administration of tolerogens. It is proposed that ultraviolet radiation produces its effects by impairing the antigen-presenting potential of resident Langerhans cells in whose absence hapten-derivatized keratinocytes (or their products) are able to deliver a tolerogenic signal.
Serologic Analysis of Human Tumor Antigens. I. Antisarcoma Antibodies in the Sera of Patients With Osteogenic Sarcomas
Authors: W P Thorpe, S A Rosenberg
Journal: JNCI Journal of the National Cancer Institute (1979)

Using absorptions with human fetal tissue, we attempted to detect reactivity in the sera of patients with osteogenic sarcomas against antigens on autologous osteogenic sarcoma cells that are not on autologous normal cells. Quantitative absorptions revealed that 108 viable human fetal cells were capable of absorbing all reactivity from sarcoma-bearing patients’ sera against autologous skin cells in tissue culture. In 2 patients with osteogenic sarcomas, exhaustive quantitative absorption with human fetal tissue removed all reactivity against autologous normal skin cells but left activity against autologous osteogenic sarcoma cells in tissue culture. The sarcoma-reactive serum from 1 patient (J. B.) was tested against the normal and sarcoma cells from 4 additional patients. This serum reacted with osteogenic sarcoma cells from only 1 other patient (L. S.) and with none of the normal cells. After fetal absorption, sera from all 5 patients, however, reacted with sarcoma cells from patients J. B. and L. S. but not with normal cells from J. B. and L. S. Sera from patients with osteogenic sarcomas appeared to contain antibodies against both fetal- and tumor-related antigens expressed on osteogenic sarcoma cells in tissue culture. Reactivity against the tumor cells but not against the normal cells was apparent only following extensive absorption of these sera with human fetal tissue.
RNA-Binding Proteins hnRNP A2/B1 and CUGBP1 Suppress Fragile X CGG Premutation Repeat-Induced Neurodegeneration in a Drosophila Model of FXTAS
Authors: Oyinkan A. Sofola, Peng Jin, Yunlong Qin, Ranhui Duan, Huijie Liu, Maria de Haro, David L. Nelson, Juan Botas
Journal: Neuron (2007)
The sinus venosus progenitors separate and diversify from the first and second heart fields early in development
Authors: Mathilda T.M. Mommersteeg, Jorge N. Domínguez, Cornelia Wiese, Julia Norden, Corrie de Gier-de Vries, John B.E. Burch, Andreas Kispert, Nigel A. Brown, Antoon F.M. Moorman, Vincent M. Christoffels
Journal: Cardiovascular Research (2010)

During development, the heart tube grows by differentiation of Isl1+/Nkx2-5+ progenitors to the arterial and venous pole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18+ progenitors were proposed to form the Tbx18+/Nkx2-5− sinus venosus and proepicardium. To elucidate the relationship between these contributions, we investigated the origin of the Tbx18+ sinus venosus progenitor population in the cardiogenic mesoderm and its spatial and temporal relation to the second heart field during murine heart development. Explant culture revealed that the Tbx18+ cell population has the potential to form Nkx2-5− sinus venosus myocardium. Three-dimensional reconstruction of expression patterns showed that during heart tube elongation, the Tbx18+ progenitors remained spatially and temporally separate from the Isl1+ second heart field, only overlapping with the Isl1+ domain at the right lateral side of the inflow tract, where the sinus node developed. Consistently, genetic lineage analysis revealed that the Tbx18+ descendants formed the sinus venosus myocardium, but did not contribute to the pulmonary vein myocardium that developed in the Isl1+ second heart field. By means of DiI labelling and expression analysis, the origin of the sinus venosus progenitor population was traced to the lateral rim of splanchnic mesoderm that down-regulated Nkx2-5 expression ∼2 days before its differentiation into sinus venosus myocardium. Our data indicate that the cardiogenic mesoderm contains an additional progenitor subpopulation that contributes to the sinus venosus myocardium. After patterning of the cardiogenic mesoderm, this progenitor population remains spatially separated and genetically distinctive from the second heart field subpopulation.
Selection of housekeeping genes for real-time PCR in atopic human bronchial epithelial cells
Authors: J-Q. He, A. J. Sandford, I-M. Wang, S. Stepaniants, D. A. Knight, A. Kicic, S. M. Stick, P. D. Paré
Journal: European Respiratory Journal (2008)

The stability of housekeeping genes (HKGs) is critical when performing real-time quantitative PCR. To date, the stability of common HKGs has not been systematically compared in human airway epithelial cells (AEC) in normal and atopic subjects. Expression levels of 12 HKGs were measured in AECs from a cohort of 30 healthy atopic nonasthmatic or atopic asthmatic children. Gene expression stability was determined using three different Visual Basic for Applications applets (geNorm, NormFinder and BestKeeper). All 12 HKGs were expressed in AECs. However, the hypoxanthine ribosyltransferase and TATA-binding protein genes were excluded from further analysis due to low expression levels. The cyclophilin A gene was ranked the most stable by all three methods. The expression levels of the β-actin and glyceraldehyde-3-phosphate dehydrogenase genes were significantly different between the three groups of patients, with atopic asthmatics showing the highest expression levels for both genes. The results suggest that the cyclophilin A gene is the most suitable housekeeping gene analysed for expression studies utilising uncultured bronchial airway epithelial cells from healthy and asthmatic children, and highlight the importance of validating housekeeping genes for each experimental model.
Telomere Length in White Blood Cell DNA and Lung Cancer: A Pooled Analysis of Three Prospective Cohorts
Authors: Wei Jie Seow, Richard M. Cawthon, Mark P. Purdue, Wei Hu, Yu-Tang Gao, Wen-Yi Huang, Stephanie J. Weinstein, Bu-Tian Ji, Jarmo Virtamo, H. Dean Hosgood, Bryan A. Bassig, Xiao-Ou Shu, Qiuyin Cai, Yong-Bing Xiang, Shen Min, Wong-Ho Chow, Sonja I. Berndt, Christopher Kim, Unhee Lim, Demetrius Albanes, Neil E. Caporaso, Stephen Chanock, Wei Zheng, Nathaniel Rothman, Qing Lan
Journal: Cancer Research (2014)

We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations.
Patterns of Protein Evolution in Tetrahymena thermophila: Implications for Estimates of Effective Population Size
Authors: Laura A. Katz, Oona Snoeyenbos-West, F. Paul Doerder
Journal: Molecular Biology and Evolution (2005)

High levels of synonymous substitutions among alleles of the surface antigen SerH led to the hypothesis that Tetrahymena thermophila has a tremendously large effective population size, one that is greater than estimated for many prokaryotes (Lynch, M., and J. S. Conery. 2003. Science 302:1401–1404.). Here we show that SerH is unusual as there are substantially lower levels of synonymous variation at five additional loci (four nuclear and one mitochondrial) characterized from T. thermophila populations. Hence, the effective population size of T. thermophila, a model single-celled eukaryote, is lower and more consistent with estimates from other microbial eukaryotes. Moreover, reanalysis of SerH polymorphism data indicates that this protein evolves through a combination of vertical transmission of alleles and concerted evolution of repeat units within alleles. SerH may be under balancing selection due to a mechanism analogous to the maintenance of antigenic variation in vertebrate immune systems. Finally, the dual nature of ciliate genomes and particularly the amitotic divisions of processed macronuclear genomes may make it difficult to estimate accurately effective population size from synonymous polymorphisms. This is because selection and drift operate on processed chromosomes in macronuclei, where assortment of alleles, disruption of linkage groups, and recombination can alter the genetic landscape relative to more canonical eukaryotic genomes.
EFFECT OF ISOLATED CENTRAL NERVOUS SYSTEM LEUKAEMIA ON BONE MARROW REMISSION AND SURVIVAL IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKAEMIA
Authors: MarkE Nesbit, HarlandN Sather, Jorge Ortega, GiulioJ D'Angio, LeslieL Robison, Milton Donaldson, G.Denman Hammond
Journal: The Lancet (1981)
DYSTROPHIN-ASSOCIATED PROTEINS AND THE MUSCULAR DYSTROPHIES
Authors: Robert H. Brown
Journal: Annual Review of Medicine (1997)

▪ Abstract Discovery of the gene encoding the protein dystrophin delineated not only the cause of Duchenne dystrophy but also an expanding family of at least eight different dystrophin-associated muscle proteins. These include two that span the membrane (the dystroglycans), at least five within the membrane (the sarcoglycans), and a submembrane protein (utrophin). In recent years, defects in the genes for several of these proteins have been identified in several different muscular dystrophies. The spectrum of clinical deficits associated with these genetic lesions is broad, but typically it encompasses both milder proximal myopathies characteristic of limb-girdle dystrophy and more severe disorders reminiscent of Duchenne dystrophy. These discoveries will provide the basis both for improved understanding of physiology of this complex of proteins at the muscle membrane and for new strategies in the treatment of muscular dystrophy.
Cardiomyopathic and Channelopathic Causes of Sudden Unexplained Death in Infants and Children
Authors: David J. Tester, Michael J. Ackerman
Journal: Annual Review of Medicine (2008)

In the past decade there has been an increasing awareness of distinct, potentially lethal heritable cardiomyopathic and channelopathic syndromes as they pertain to sudden cardiac death in infants and children. This review highlights current clinical and molecular findings of two highly relevant structural cardiac abnormalities evident at autopsy, namely hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, as well as the cardiac channelopathies of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome, which may account for one third of autopsy-negative sudden unexplained deaths (SUDs) during childhood and adolescence. We also explore the role of postmortem genetic analysis (molecular autopsy) in cases of SUD, provide a critical analysis of the current spectrum and prevalence of channelopathies as the pathogenic basis for sudden infant death syndrome (SIDS), and provide a brief synopsis on genetic testing for such potentially lethal cardiac disorders.
Multiple signaling pathways regulate NF-κB–dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells
Authors: Matthias Goebeler, Reinhard Gillitzer, Karin Kilian, Kathrin Utzel, Eva-Bettina Bröcker, Ulf R. Rapp, Stephan Ludwig
Journal: Blood (2001)
Rim calcification in primary liver cell carcinoma mimicking hydatid disease.
Authors: A W Mitchell, J N Higgins, J Tate, R Dick
Journal: Gut (1994)

The case described is of a primary liver cell carcinoma (PLCC), which was initially misdiagnosed as hepatic hydatid disease. The computed tomographic appearances of hepatic hydatid disease are often characteristic although not specific. When supported by the clinical findings, however, they will probably not be confused with other liver masses. In this case the presence of peripheral rim calcification, commonly seen in hydatid disease but which has not been previously noted in PLCC, lead to an erroneous diagnosis.
Potential Overtreatment and Undertreatment of Diabetes in Different Patient Age Groups in Primary Care After the Introduction of Performance Measures
Authors: Sieta T. de Vries, Jaco Voorham, Flora M. Haaijer-Ruskamp, Petra Denig
Journal: Diabetes Care (2014)

To assess whether after the introduction of diabetes performance measures decreases in undertreatment correspond with increases in overtreatment for blood pressure (BP) and glycemic control in different patient age groups.We conducted a cohort study using data from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database. General practices were included when data were available from 1 year before to at least 1 year after the introduction of diabetes performance measures. Included patients had a confirmed diagnosis of type 2 diabetes. Potential overtreatment was defined as prescribing maximum treatment or a treatment intensification to patients with a sustained low-risk factor level. Potential undertreatment was defined as a lack of treatment intensification in patients with a sustained high-risk factor level. Percentages of over- and undertreated patients at baseline were compared with those in subsequent years, and stratified analyses were performed for different patient age groups.For BP, undertreatment significantly decreased from 61 to 57% in the first year after the introduction of performance measures. In patients >75 years of age, undertreatment decreased from 65 to ∼61%. Overtreatment was relatively stable (∼16%). For glycemic control, undertreatment significantly increased from 49 to 53%, and overtreatment remained relatively stable (∼7%).The improvement of BP undertreatment after introduction of the performance measures did not correspond with an increase in overtreatment. The performance measures appeared to have little impact on improving glucose-regulating treatment. The trends did not differ among patient age groups.