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Sample records for reducing ige levels

  1. Sex steroid hormones and circulating IgE levels.

    PubMed

    Mathur, S; Mathur, R S; Goust, J M; Williamson, H O; Fudenberg, H H

    1977-12-01

    The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti-Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunoglobulins, especially anti-Candida antibodies. PMID:606452

  2. Alcohol-induced alterations in serum immunoglobulin e (IgE) levels in human subjects.

    PubMed

    González-Quintela, Arturo; Vidal, Carmen; Gude, Francisco

    2002-05-01

    The association of alcohol intake with total serum IgE concentrations in humans is discussed in the present review. The possible relationship of regular alcohol intake with both the risk of allergic sensitization and serum allergen-specific IgE values is also reviewed. Several studies consistently show that total serum IgE concentrations are increased in alcoholics when compared with healthy controls. Total serum IgE levels decrease after ethanol abstinence in alcoholics. Total serum IgE is increased in moderate alcohol consumers with respect to abstainers. Alcohol consumption in mothers may be associated with increased cord blood IgE levels in their offspring. IgE elevation in alcohol consumers is independent of potential confounders such as age, sex, liver disease, cigarette smoking or atopic status. Experimental studies in animals further support that ethanol administration is followed by an increase in serum IgE concentrations. In atopic patients, regular alcohol consumption is associated with increased serum specific IgE levels against some aeroallergens. Preliminary reports suggest that alcohol intake is associated to variable risk of sensitization to some aeroallergens. The possible mechanisms of alcohol-induced alterations in IgE levels and IgE-mediated diseases are discussed. PMID:11991851

  3. Comparison of IgE expression at the mRNA and protein levels in vitro.

    PubMed Central

    Turner, K J; Creany, J; Coelen, R J; Cameron, K J; Holt, B J; Beilharz, M W

    1991-01-01

    The regulating effects of IL-4 and pokeweed mitogen on IgE synthesis in vitro by human peripheral blood leucocytes has been compared with the corresponding effect of these regulators on the expression of IgE mRNA. The latter was measured by dot blot hybridization with an oligonucleotide coding for a unique six amino acid region of the CH epsilon 2 domain. Specificity of the oligonucleotide probe was established by its inability to hybridize with RNA extracted from HMY-2 (IgG) and XQ-15 (IgM) secreting cell lines whilst producing intense signals with RNA extracted from the IgE secreting cell line U266. Whilst IgE mRNA was detected in RNA extracted from PBL of both atopic and control subjects, spontaneous IgE synthesis was restricted to atopic PBL. IL-4 increased both IgE mRNA and IgE synthesis in all PBL samples but PWM, while significantly increasing IgE mRNA expression either failed to modify IgE synthesis or actively suppressed it. The assay system employed to quantitate IgE synthesis in vitro was shown to be inhibited by both IgE binding factors and IgG anti-IgE autoantibodies which are produced in PBL cultures. IgE mRNA levels might therefore more accurately monitor the regulatory effects of IL-4 and PWM on IgE synthesis than quantitation of the IgE by radioimmunoassay. Images Figure 1 PMID:1783428

  4. Evidence for a locus regulating total serum IgE levels mapping to chromosome 5

    SciTech Connect

    Meyers, D.A.; Xu, J.; Levitt, R.C.

    1994-09-15

    Genetic studies of total serum IgE levels were preformed since high IgE levels correlate with clinical expression of allergy and asthma. Families ascertained through a parent with asthma were genotyped for markers on 5q where there are multiple candidate genes that may influence the control of IgE and inflammation. Evidence for linkage of the IgE phenotype to 5q was obtained by both sib-pair and lod score analysis with evidence for recessive inheritance of high IgE levels from segregation analysis. These findings represent a major step in mapping genes important in the regulation of allergic responses and the pathogenesis of asthma. 52 refs., 3 tabs.

  5. Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo*

    PubMed Central

    Cuevas-Gonzalez, Juan Carlos; Lievanos-Estrada, Zahide; Vega-Memije, Maria Elisa; Hojyo-Tomoka, Maria Teresa; Dominguez-Soto, Luciano

    2016-01-01

    BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate. PMID:26982774

  6. Treatment with oleic acid reduces IgE binding to peanut and cashew allergens.

    PubMed

    Chung, Si-Yin; Mattison, Christopher P; Reed, Shawndrika; Wasserman, Richard L; Desormeaux, Wendy A

    2015-08-01

    Oleic acid (OA) is known to bind and change the bioactivities of proteins, such as α-lactalbumin and β-lactoglobulin in vitro. The objective of this study was to determine if OA binds to allergens from a peanut extract or cashew allergen and changes their allergenic properties. Peanut extract or cashew allergen (Ana o 2) was treated with or without 5mM sodium oleate at 70°C for 60 min (T1) or under the same conditions with an additional overnight incubation at 37°C (T2). After treatment, the samples were dialyzed and analyzed by SDS-PAGE and for OA content. IgE binding was evaluated by ELISA and western blot, using a pooled serum or plasma from individuals with peanut or cashew allergies. Results showed that OA at a concentration of 5mM reduced IgE binding to the allergens. Peanut sample T2 exhibited a lower IgE binding and a higher OA content (protein-bound) than T1. Cashew allergen T2 also showed a reduction in IgE binding. We conclude that OA reduces the allergenic properties of peanut extract and cashew allergen by binding to the allergens. Our findings indicate that OA in the form of sodium oleate may be potentially useful as a coating to reduce the allergenic properties of peanut and cashew allergens. PMID:25766831

  7. Domestic exposure to fungi and total serum IgE levels in asthmatic children.

    PubMed

    Su, Huey-Jen Jenny; Wu, Pei-Chih; Lei, Huan-Yao; Wang, Jiu-Yao

    2005-08-14

    We measured the number of airborne, viable fungi and house dust mite (HDM) allergen levels in the homes of a group of asthmatic children. Blood samples were drawn and the amounts of total and specific serum IgE were determined. The association between the number of fungal colonies, dust mite allergen exposure, and specific and total IgE was evaluated. The number of viable airborne fungi was high (20,543 CFU/m(3)) in those investigated houses. Der p1 concentrations on child's mattress exceeding 2 microg/g were found in 78.6% of the houses. A quantitative dose-response relationship was demonstrated between the exposure to viable, airborne molds and the amount of total IgE (r = 0.4399 and P = .0249) and the level was further increased in children with coexposure to viable fungi and HDM. PMID:16106103

  8. Decreased Level of IgE is Associated with Breast Cancer and Allergic Diseases

    PubMed Central

    Zhang, Huayi; Guo, Gang; Jianzhong, Cao; Zheng, Yaqin

    2016-01-01

    Background The aim of this study was to explore the prevalence of type I allergic diseases in patients with breast cancer by carrying out a questionnaire survey and IgE detection in a healthy population and in patients with breast cancer. Material/Method There were 309 patients enrolled and they were further divided into the type I allergic disease group, the newly diagnosed breast cancer with type I allergic disease group, the re-visit breast cancer with type I allergic disease group, and the re-visit breast cancer without type I allergic disease group, as well as a healthy control group. Serum total IgE level was detected by immunoassay. Results The IgE value in the healthy population with type I allergic diseases (89.3±51.4 IU/ml) was significantly higher than in those without type I allergic diseases (45.6±65.1 IU/ml). There was no significant difference between IgE values in the re-visit breast cancer patients with type I allergic disease (25.1±65.1 IU/ml) and those without type I allergic disease (23.0±45.9 IU/ml). The area under the ROC curve was 0.618±0.04, sensitivity was 78%, specificity was 47.1%, Youden index was 0.251, and IgE threshold was 32.6 IU/ml. Conclusions The patients with newly diagnosed breast cancer were susceptible to type I allergic disease at about the same levels as in the healthy population. There was no correlation between breast cancer and type I allergic disease. PMID:26901362

  9. Evidence for two unlinked loci regulating total serum IgE levels

    SciTech Connect

    Xu, J.; Levitt, R.C.; Taylor, E.W.

    1995-08-01

    Studies investigating the genetic control of total serum IgE levels are of major importance in understanding basic pathophysiologic mechanisms in atopy and asthma, since IgE levels predict onset and correlate with the clinical expression of these disorders. Previous analysis of data from 92 families, ascertained through a parent with asthma, showed evidence for recessive inheritance of high IgE levels with linkage to chromosome 5q. Since there was significant residual familial correlation in the one-locus segregation analysis, two-locu segregation and linkage analyses were performed. Segregation analyses provided evidence for a second major locus unlinked to the locus on 5q. Utilization of this two-locus model corroborates the previous evidence for linkage between this trait and markers on 5q{sub 31}-q{sub 33}. The LODs for the most informative marker D5S436 increased from 3.00 at 10% recombination to 4.67 at 9% recombination when the two-locus model was used. Additional linkage studies are needed to map this second locus. These results demonstrate the importance of performing multilocus segregation and linkage analyses for quantitative traits that are related to the phenotype of a complex disorder. This approach has given further insight into the genetics of allergy and asthma by providing evidence for a two-locus model. 34 refs., 3 figs.

  10. IL-1, IL-4 production and IgE levels in acute and chronic fasciolosis before and after triclabendazole treatment.

    PubMed

    Allam, A F; Osman, M M; el-Sayed, M H; Demian, S R

    2000-12-01

    IL-1 generation by mononuclear phagocytes, IL-4 production by Th2 lymphocytes and IgE levels in serum were measured in eight patients with acute fasciolosis and seven patients in the chronic stage of the disease before and after triclabendazole treatment. Results were compared with those of a control group of ten individuals. The monocytes and lymphocytes from patients with acute and chronic fasciolosis produced significantly lower levels of IL-1 and IL-4 respectively, particularly in the chronic phase of the disease, as compared to the control. A significant increase in IgE level in both acute and chronic fasciolosis was observed. The level was significantly higher in acute as compared to chronic cases. After treatment with triclabendazole IL-1, IL-4 and IgE levels moved towards the control indicating obvious improvement in the immunological responses of the patients. PMID:11198376

  11. Treatment of cashew extracts with Aspergillopepsin reduces IgE binding to cashew allergens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cashew nuts can cause serious and sometimes life threatening reactions in people that suffer from food allergies. These reactions are mediated by immunoglobulin E binding (IgE) to allergenic cashew proteins. Enzymes from Aspergillus fungal species are used in many industrial and pharmaceutical appli...

  12. Adrenocortical function during prolonged treatment with clobetasone butyrate in children with chronic atopic dermatitis and elevated IgE levels.

    PubMed

    Boner, A L; Richelli, C; De Stefano, G; Antolini, I; Aprili, F; Mengoni, M

    1985-01-01

    Twelve children with chronic atopic dermatitis and elevated IgE levels (age range: 2-13 years; mean age = 8.2 +/- 3.5 years) were selected for the study and treated with clobetasone butyrate (0.05% cream) thrice daily during the first week, then twice daily for three weeks. Adrenocortical function was evaluated at the beginning and the end of treatment period. The results show that there was no statistically significant change in adrenal function during the study period (tetracosactrin test). The results of the immunological studies, namely total IgE using the paper disc radioimmunoassay technique, specific IgE using the radioallergosorbent test and immunoglobulin levels are given. PMID:4018942

  13. Influence of Mansonella perstans microfilaraemia on total IgE levels in Gabonese patients co-infected with Loa loa.

    PubMed

    Bouyou-Akotet, M K; Moussavou Boussougou, M N; Ovono-Abessolo, F; Owono-Medang, M; Kombila, M

    2014-03-01

    Mansonella (M.) perstans filariasis is widely found in Africa, including Gabon where Loa loa is also endemic. This study reports the total IgE titres according to different bioclinical forms of single or co-infection with L. loa and M. perstans in 138 patients and 20 healthy controls. The median parasite density was significantly higher in cases of loiasis. IgE titres were higher in patients with microscopic dual-infection and in the group of patients with occult loiasis plus M. perstans microfilaraemia (8425 [5292-20,679]KUI/L and 6304 [1045-10,326]KUI/L, respectively), compared to individuals with either microfilaraemic Loa loa (3368 [1414-7074]KUI/L) or Mansonella (4370 [1478-7334]KUI/L) single infections (p<0.01). IgE levels were positively correlated with M. perstans microfilaraemia (rho=0.27; p<0.01). Compared to single infections, dual M. perstans-L. loa infection induces very high total IgE titres. Studies correlating IgE titres and clinical symptoms are needed to confirm the involvement of this immunoglobulin in the pathological processes during filariasis. PMID:24280145

  14. IgE Sensitization to Aspergillus fumigatus Is Associated with Reduced Lung Function in Asthma

    PubMed Central

    Fairs, Abbie; Agbetile, Joshua; Hargadon, Beverley; Bourne, Michelle; Monteiro, William R.; Brightling, Christopher E.; Bradding, Peter; Green, Ruth H.; Mutalithas, Kugathasan; Desai, Dhananjay; Pavord, Ian D.; Wardlaw, Andrew J.; Pashley, Catherine H.

    2010-01-01

    Rationale: The importance of Aspergillus fumigatus sensitization and colonization of the airways in patients with asthma is unclear. Objectives: To define the relationship between the clinical and laboratory features of A. fumigatus–associated asthma. Methods: We studied 79 patients with asthma (89% classed as GINA 4 or 5) classified into 3 groups according to A. fumigatus sensitization: (1) IgE-sensitized (immediate cutaneous reactivity > 3 mm and/or IgE > 0.35 kU/L); (2) IgG-only–sensitized (IgG > 40 mg/L); and (3) nonsensitized. These were compared with 14 healthy control subjects. Sputum culture was focused toward detection of A. fumigatus and compared with clinical assessment data. Measurements and Main Results: A. fumigatus was cultured from 63% of IgE-sensitized patients with asthma (n = 40), 39% of IgG-only–sensitized patients with asthma (n = 13), 31% of nonsensitized patients with asthma (n = 26) and 7% of healthy control subjects (n = 14). Patients sensitized to A. fumigatus compared with nonsensitized patients with asthma had lower lung function (postbronchodilator FEV1 % predicted, mean [SEM]: 68 [±5]% versus 88 [±5]%; P < 0.05), more bronchiectasis (68% versus 35%; P < 0.05), and more sputum neutrophils (median [interquartile range]: 80.9 [50.1–94.1]% versus 49.5 [21.2–71.4]%; P < 0.01). In a multilinear regression model, A. fumigatus–IgE sensitization and sputum neutrophil differential cell count were important predictors of lung function (P = 0.016), supported by culture of A. fumigatus (P = 0.046) and eosinophil differential cell count (P = 0.024). Conclusions: A. fumigatus detection in sputum is associated with A. fumigatus–IgE sensitization, neutrophilic airway inflammation, and reduced lung function. This supports the concept that development of fixed airflow obstruction in asthma is consequent upon the damaging effects of airway colonization with A. fumigatus. PMID:20639442

  15. Genome-wide Association Study and Admixture Mapping Reveal New Loci Associated with Total IgE Levels in Latinos

    PubMed Central

    Pino-Yanes, Maria; Gignoux, Christopher R.; Galanter, Joshua M.; Levin, Albert M.; Campbell, Catarina D.; Eng, Celeste; Huntsman, Scott; Nishimura, Katherine K.; Gourraud, Pierre-Antoine; Mohajeri, Kiana; O'Roak, Brian J.; Hu, Donglei; Mathias, Rasika A.; Nguyen, Elizabeth A.; Roth, Lindsey A.; Padhukasahasram, Badri; Moreno-Estrada, Andres; Sandoval, Karla; Winkler, Cheryl A.; Lurmann, Fred; Davis, Adam; Farber, Harold J.; Meade, Kelley; Avila, Pedro C.; Serebrisky, Denise; Chapela, Rocio; Ford, Jean G.; Lenoir, Michael A.; Thyne, Shannon M.; Brigino-Buenaventura, Emerita; Borrell, Luisa N.; Rodriguez-Cintron, William; Sen, Saunak; Kumar, Rajesh; Rodriguez-Santana, Jose R.; Bustamante, Carlos D.; Martinez, Fernando D.; Raby, Benjamin A.; Weiss, Scott T.; Nicolae, Dan L.; Ober, Carole; Meyers, Deborah A.; Bleecker, Eugene R.; Mack, Steven J.; Hernandez, Ryan D.; Eichler, Evan E.; Barnes, Kathleen C.; Williams, L. Keoki; Torgerson, Dara G.; Burchard, Esteban G.

    2014-01-01

    Background Immunoglobulin E (IgE) is a key mediator of allergic inflammation and is frequently elevated in allergic disorders. Objective To identify genetic variants associated with IgE levels in Latinos. Methods We performed a genome-wide association study (GWAS) and admixture mapping of total IgE levels in 3,334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1,564 European Americans, and 3,187 African Americans from independent studies. Results We confirmed associations of six genes identified by previous GWAS and identified a novel genome-wide significant association of a polymorphism in ZNF365 with total IgE (rs200076616, p=2.3x10−8). We next identified four admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) where local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower levels of IgE (p=4.95x10−8). All but 22q13.1 were replicated in an independent sample of Latinos, and two of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified six genome-wide significant single nucleotide polymorphisms in Latinos, two of which replicated in European Americans. Another SNP was peak-wide significant within 14q23.2 in African Americans (rs1741099, p=3.7x10−6), and replicated in non-African American samples (p=0.011). Conclusion We confirmed genetic associations at six genes, and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse, multi-ethnic populations to uncover novel loci associated with total IgE levels. PMID:25488688

  16. Inverse Association between Prediagnostic IgE Levels and the Risk of Brain Tumors: A Systematic Review and Meta-Analysis

    PubMed Central

    Ma, Chong; Cao, Lei; Zhao, Jianping; Ming, Xing; Shang, Ming; Zong, Hailiang; Du, Hai; Li, Kai; He, Xiaoguang; Xu, Hongsheng

    2015-01-01

    An inverse association between allergic conditions and glioma risk has been suggested in many epidemiological studies. However, the evidence is inadequate to draw robust conclusions for the association between prediagnostic IgE levels and brain tumors risk. The aim of this study was to provide more precise estimates for this association by meta-analysis of all published studies. Overall, 8 individual studies with 2,461 cases and 3,934 controls were included in our study. A decreased risk of brain tumors (RR = 0.73, 95% CI 0.61–0.86, P < 0.001) was observed in relation to elevated level of total IgE. The negative association was significant between elevated total IgE level and the risk of glioma (RR = 0.74, 95% CI 0.62–0.88, P = 0.001). However, no significant relationship was demonstrated between testing positive for respiratory allergen-specific IgE and brain tumors risk. In addition, the role of prediagnostic IgE levels in brain tumors risk did not alter in men and women. The present study suggests that increased level of total prediagnostic IgE but not respiratory allergen-specific IgE plays a protective role in brain tumors risk, glioma in particular. More studies are warranted for further elucidation of the meningioma risk related to prediagnostic IgE levels. PMID:26448931

  17. A Nonsynonymous FCER1B SNP is Associated with Risk of Developing Allergic Rhinitis and with IgE Levels

    PubMed Central

    Amo, Gemma; García-Menaya, Jesús; Campo, Paloma; Cordobés, Concepción; Serón, M Carmen Plaza; Ayuso, Pedro; Esguevillas, Gara; Blanca, Miguel; Agúndez, Jose A.G.; García-Martín, Elena

    2016-01-01

    Allergic rhinitis is associated with elevated serum IgE levels. IgE response is mediated by the high-affinity IgE receptor (FcεRI), which is polymorphic. Studies analyzing the association between allergic rhinitis and FcεRI variants have been conducted with controversial results. The objective of this study is to analyze, in 1,041 individuals, the putative clinical association of allergic rhinitis with common polymorphisms in FcεRI subunits genes. These SNPs included FECR1A rs2494262, rs2427837 and rs2251746; FECR1B rs1441586, rs569108 and rs512555; FCER1G rs11587213, rs2070901 and rs11421. Statistically significant differences were observed for the FCER1B rs569108 and rs512555 polymorphisms frequencies when comparing patients with allergic rhinitis without asthma and controls. The OR (95% CI) value for the 237Gly allele (rs569108) is equal to 0.26 (0.08–0.86, P = 0.017) and for the G allele (rs512555) it is equal to 0.27 (0.08–0.88, P = 0.020). These two SNPs are linked (D’ = 1.0, LOD = 56.05). Also observed was a statistically significant trend towards lower IgE values among allergic rhinitis patients with variant alleles for both SNPs. In conclusion, in patients with allergic rhinitis without asthma, the FCER1B rs569108 and rs512555 polymorphisms are associated with increased risk of developing allergic rhinitis and with lower IgE levels. PMID:26792385

  18. Alopecia universalis associated with impaired interleukin-4 production and low serum IgE level.

    PubMed

    Tokura, Yoshiki; Sugita, Kazunari; Kabashima, Kenji; Ito, Taisuke; Yagi, Hiroaki

    2007-08-01

    A 17-year-old female presented with alopecia universalis, which appeared following widespread eczematous dermatitis. An immunohistochemical study demonstrated that CD8(+) T cells infiltrated into hair follicles with satellite cell necrosis of keratinocytes. The precedence of the autosensitization dermatitis suggested that T cells concerned with the eczematous reaction also attacked hair follicles, or alternatively, that those T cells sequentially activated another population of cytotoxic T cells. We found that she had a continuously low level of serum IgE (<1 units/ml), and this abnormality urged us to investigate interleukin (IL)-4 production of T cells. Although the patient had a normal number of CD4(+) T cells, the production of IL-4, but not IL-10, was profoundly impaired as assessed by a reverse transcriptase polymerase chain reaction analysis, suggesting the possible relationship between the baldness and IL-4 reduction. The autoimmune hair loss might occur via activation of cytotoxic T cells and Th(1) cells as a result of a relief from IL-4 control. PMID:17637364

  19. Asthma Symptoms and Specific IgE Levels among Toluene Diisocyanate (TDI) Exposed Workers in Tehran, Iran

    PubMed Central

    SHARIFI, Laleh; KARIMI, Akram; SHOKOUHI SHOORMASTI, Raheleh; MIRI, Sara; HEYDAR NAZHAD, Hassan; BOKAIE, Saied; FAZLOLLAHI, Mohammad Reza; SADEGHNIIAT HAGHIGHI, Khosro; POURPAK, Zahra; MOIN, Mostafa

    2013-01-01

    Background Toluene diisocyanate (TDI) is an imperative chemical substance used in the production of polyurethane foams, elastomers, paints and coatings that cause a variety of health problems in workers who are exposed in work places. This study aimed to determine the asthma symptoms and serum specific IgE levels in TDI exposed workers and comparing the results with healthy control group. Methods: All the plants that use TDI in the manufacturing of paint and glue in the west of Tehran Province entered to the study and all the workers (550) completed modified initial questionnaire of the NIOSH, the questions were consisted of asthma symptoms. For each symptomatic exposed worker one healthy, sex and age matched control selected. Total IgE and Specific TDI IgE tests were done for each case and control groups. Results: Among 550 TDI exposed workers, 26(4.7%) had asthma symptoms. Nine (34.6%) of symptomatic workers who were exposed to TDI were active cigarette consumer versus 3(11.5%) unexposed workers, P=0.049(CI= 0.953–17.29) OR=4.059. Nine (34.6%) workers had positive family history of atopy versus 1(3.8%) unexposed workers, P=0.0138 (CI= 1.45–305.41) OR=13.24. TDI specific IgE was found in 2 TDI exposed workers and 1 unexposed worker (P=0.5). Mean of total IgE was 339.05 in exposed workers (P=0.201). Conclusion: This study provides clinical and paraclinical data of workers exposed to TDI and points to a relation between atopy and smoking habit with asthma symptoms that offer preventing recommendations for TDI exposed workers and their heath administrators. PMID:23785679

  20. Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination.

    PubMed

    Garman, Lori; Smith, Kenneth; Muns, Emily E; Velte, Cathy A; Spooner, Christina E; Munroe, Melissa E; Farris, A Darise; Nelson, Michael R; Engler, Renata J M; James, Judith A

    2016-08-01

    Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection (n = 75), individuals with LLRs (n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals (n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs (P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C-reactive protein (P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile. PMID:27280620

  1. The alpha and beta subchain of Amb a 1, the major ragweed-pollen allergen show divergent reactivity at the IgE and T-cell level.

    PubMed

    Wopfner, Nicole; Jahn-Schmid, Beatrice; Schmidt, Georg; Christ, Tanja; Hubinger, Gudrun; Briza, Peter; Radauer, Christian; Bohle, Barbara; Vogel, Lothar; Ebner, Christof; Asero, Riccardo; Ferreira, Fatima; Schwarzenbacher, Robert

    2009-06-01

    Ragweed is one of the most important pollen allergens in North America and parts of Europe. Although the major allergen Amb a 1 was isolated and cloned in 1991, recombinant Amb a 1 was not explored further to improve diagnosis and specific immunotherapy of ragweed-pollen allergy. In the present study the immunological properties of natural Amb a 1 and its proteolytical cleavage products was investigated in detail and compared with recombinant produced Amb a 1 variants. Characterization of natural Amb a 1 and the identification of its proteolytic fragments, designated Amb a 1 alpha and Amb a 1 beta, was performed by N-terminal sequencing and mass spectroscopy. Amb a 1 and fragments were further produced in Escherichia coli, purified, and immunologically characterized. Amb a 1-specific T-cell cultures were used to compare the T-cell response to the different Amb a 1 variants. Divergent immunological properties of Amb a 1 alpha (aa 181-396) and Amb a 1 beta (aa 26-180) were revealed. Amb a 1 beta contained important IgE epitopes, whereas Amb a 1 alpha showed low IgE binding. When compared to natural Amb a 1, all recombinant variants possessed >100-fold reduced IgE-mediated mediator release activity. At the T-cell level recombinant and natural Amb a 1 stimulated comparable T-cell responses and the T-cell reactivity was largely directed to the C-terminal part. The results demonstrated that recombinant Amb a 1 alpha behaves as hypoallergen with reduced IgE binding but preservation of the major T-cell reactivity. In addition, recombinant Amb a 1 alpha can be easily purified to homogeneity in large quantity and therefore represents an ideal candidate for specific immunotherapy. PMID:19269031

  2. Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis

    USGS Publications Warehouse

    Devalapalli, A.P.; Lesher, A.; Shieh, K.; Solow, J.S.; Everett, M.L.; Edala, A.S.; Whitt, P.; Long, Renee R.; Newton, N.; Parker, W.

    2006-01-01

    To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

  3. Attenuation of IgE Affinity for FcεRI Radically Reduces the Allergic Response in Vitro and in Vivo*

    PubMed Central

    Hunt, James; Bracher, Marguerite G.; Shi, Jianguo; Fleury, Sébastien; Dombrowicz, David; Gould, Hannah J.; Sutton, Brian J.; Beavil, Andrew J.

    2008-01-01

    The high affinity of IgE for its receptor, FcεRI (Ka ∼ 1010 m–1), is responsible for the persistence of mast cell sensitization. Cross-linking of FcεRI-bound IgE by multivalent allergen leads to cellular activation and release of pro-inflammatory mediators responsible for the symptoms of allergic disease. We previously demonstrated that limiting the IgE-FcεRI interaction to just one of the two Cε3 domains in IgE-Fc, which together constitute the high affinity binding site, results in 1000-fold reduced affinity. Such attenuation, effected by a small molecule binding to part of the IgE:FcεRI interface or a distant allosteric site, rather than complete blocking of the interaction, may represent a viable approach to the treatment of allergic disease. However, the degree to which the interaction would need to be disrupted is unclear, because the importance of high affinity for immediate hypersensitivity has never been investigated. We have incorporated into human IgE a mutation, R334S, previously characterized in IgE-Fc, which reduces its affinity for FcεRI ∼50-fold. We have compared the ability of wild type and R334S IgE to stimulate allergen-induced mast cell activation in vitro and in vivo. We confirmed the expected difference in affinity between wild type and mutant IgE for FcεRI (∼50-fold) and found that, in vitro, mast cell degranulation was reduced proportionately. The effect in vivo was also marked, with a 75% reduction in the passive cutaneous anaphylaxis response. We have therefore demonstrated that the high affinity of IgE for FcεRI is critical to the allergic response, and that even moderate attenuation of this affinity has a substantial effect in vivo. PMID:18703499

  4. Listening to mozart reduces allergic skin wheal responses and in vitro allergen-specific IgE production in atopic dermatitis patients with latex allergy.

    PubMed

    Kimata, Hajime

    2003-01-01

    In atopic dermatitis patients with latex allergy, listening to Mozart reduced skin wheal responses induced by latex, but not by histamine, whereas listening to Beethoven failed to produce similar results. Listening to Mozart also decreased in vitro total IgE and latex-specific IgE production with concomitant skewing of the cytokine pattern toward the Th1 type, that is, an increase in Th1 cytokine production and decrease in Th2 cytokine production by peripheral blood mononuclear cells, whereas listening to Beethoven failed to do so. These results suggest that therapy using specific types of music may be an effective treatment of allergic diseases. PMID:14977243

  5. Minimizing fucosylation in insect cell-derived glycoproteins reduces binding to IgE antibodies from the sera of patients with allergy

    PubMed Central

    Palmberger, Dieter; Ashjaei, Kazem; Strell, Stephanie; Hoffmann-Sommergruber, Karin; Grabherr, Reingard

    2016-01-01

    The baculovirus/insect cell system has proven to be a very powerful tool for the expression of several therapeutics. Nevertheless, these products sometimes suffer from reduced biological activity and unwanted side effects. Several studies have demonstrated that glycosylation can greatly influence the structure, function, half-life, antigenicity and immunogenicity of various glycoproteins. Yet, the glycosylation pattern of insect cell-derived products is not favourable for many applications. Especially the presence of core α1,3-linked fucose bears the risk of causing immediate hypersensitivity reactions in patients with allergy. In this study we evaluated the impact of fucose residues on the allergenic potential of an insect cell-expressed vaccine candidate. In order to block the GDP-L-fucose de novo synthesis pathway, we integrated the Pseudomonas aeruginosa GDP-6-deoxy-D-lyxo-4-hexulose reductase (RMD) gene into a baculovirus backbone. This virus was then used for the expression of soluble influenza A virus hemagglutinin. Expression studies showed that the co-expression of RMD did not influence the overall level of recombinant protein secretion. We confirmed the result of our strategy by analysing PNGase A-released N-glycans using MALDI-TOF-MS. In order to evaluate the biological impact of defucosylation of influenza HA we tested the binding activity of IgE derived from the sera of patients with allergy to the purified antigen. The nonfucosylated hemagglutinin showed a 10-fold decrease in IgE binding levels as compared to wildtype variants. PMID:24753388

  6. Extra-intestinal symptoms in patients with irritable bowel syndrome: related to high total IgE levels and atopic sensitization?

    PubMed

    Vara, Ellen Johanne; Valeur, Jørgen; Hausken, Trygve; Lied, Gülen Arslan

    2016-08-01

    Objective We have previously found that high levels of total IgE, but not atopic sensitization, was a significant predictor for functional gastrointestinal (GI) symptoms. In this study, we aimed to assess the prevalence of extra-intestinal symptoms in IBS patients, and explore their relation to total IgE levels and atopic sensitization. Materials and methods Seventy-one patients with functional GI complaints were included. Severity of GI symptoms, fatigue and musculoskeletal pain was evaluated using the following questionnaires: IBS-Severity Scoring System (IBS-SSS), Fatigue Impact Scale (FIS), FibroFatigue Scale (FFS), and Visual Analog Scales (VAS) for musculoskeletal pain. Levels of total IgE and specific IgE-antibodies were analyzed. Results Fatigue and musculoskeletal pain were demonstrated in 78.9 and 43.7% of the patients, respectively. IBS-SSS scores were significantly correlated with fatigue scores and musculoskeletal pain. Patients with fatigue and musculoskeletal pain had significantly higher IBS-SSS scores than patients without fatigue and musculoskeletal pain. Total IgE levels were significantly higher in IBS patients compared to a healthy control group from a previous study. However, neither total IgE nor atopic sensitization was significantly associated with extra-intestinal symptoms. Conclusions IBS, fatigue, and musculoskeletal pain were significantly associated. Total IgE levels were higher in IBS patients than healthy controls, but not related to intestinal or extra-intestinal symptom severity. Atopy was not associated with any of the co-morbidities. Thus, the clinical significance of high IgE levels in IBS remains unclear and further studies are warranted to explore a common underlying mechanism for the co-morbid triad of IBS, fatigue, and musculoskeletal pain. PMID:27161383

  7. [The comparative characteristic of level of histamine, IgE and IgG in blood and the lymph at the experimental anaphylactic shock and Artyus phenomenon].

    PubMed

    Alieva, T R; Allahverdieva, L I

    2015-01-01

    Maintenance changes of histamine and levels of immunoglobulin E and G in blood and lymph are studied at the ex- perimental anaphylactic and Artyus phenomenon. Experiments were conducted in two series on 27 rabbits of "Chinchilla" breed. As control are served the investigated indicators of concentration of histamine and levels of IgE and IgG in blood and lymph of intact animals. Results of research have shown that, at the experimental anaphylactic shock increase the level of IgE and decrease the level of IgG. At the Artyus phenomenon increase of level of IgG and the decrease in level of IgE more expressed in blood, than in lymph is marked. Concentration of histamine raises, both at the anaphylactic shock, and at the of Artyus phenomenon, but is more expressed at anaphylaxis, and also in blood, than in lymph. Key words: anaphylactic shock; Artyus phenomenon; histamine; immunoglobulin PMID:26852600

  8. Association of Macrophage Migration Inhibitory Factor Polymorphisms with Total Plasma IgE Levels in Patients with Atopic Dermatitis in Korea.

    PubMed

    Kim, Jung Soo; Choi, Jinyoung; Hahn, Hyung-Jin; Lee, Young-Bok; Yu, Dong-Soo; Kim, Jin-Wou

    2016-01-01

    The macrophage migration inhibitory factor (MIF) gene is located on human chromosome 22q11.2 and is linked to atopic phenotypes. Plasma MIF and log [total IgE] levels are significantly elevated in atopic dermatitis (AD) patients. The aim of this study was to evaluate the relationship between two MIF polymorphisms, -173 G to C and -794 CATT5-8, and total plasma IgE levels in AD patients in Korea. We performed PCR-RFLP analysis in 178 AD patients and 80 control subjects to determine whether MIF SNPs are associated with susceptibility to AD. Plasma total IgE and MIF levels were determined, and then logistic regression analyses were performed to determine the associations between a SNP or haplotype and plasma total IgE or MIF levels. The -173 G/C polymorphism, located in the MIF promoter, was significantly associated with AD; the odds ratios (ORs) for the CC homozygotes and GC heterozygotes were 9.3 and 2.5, respectively. The MIF C/5-CATT and the MIF C/7-CATT haplotypes were significantly associated with AD; the ORs for the MIF C/5-CATT and MIF C/7-CATT haplotypes were 9.7 and 4.5, respectively. Log [total IgE] levels were highly associated with the MIF -794 7-CATT polymorphism. Notably, the MIF C/7-CATT haplotype was associated with a decrease in plasma log [total IgE] levels in a gene dose-dependent manner. Although log [MIF] levels were not associated with the MIF polymorphisms, the frequencies of the MIF C/5-CATT haplotype-containing genotypes decreased in order of MIF levels. Our results demonstrate that MIF promoter polymorphisms in the -173 C allele and the MIF C/5-CATT and C/7-CATT haplotypes were significantly associated with an increased risk for AD. In particular, the -794 7-CATT locus and the MIF C/7-CATT haplotype were significantly associated with decreased total IgE levels in the plasma, suggesting that these polymorphisms might be a marker for intrinsic AD rather than extrinsic AD that shows high total IgE levels and presence of allergen-specific IgE

  9. Levels of anti-BP180 NC16A IgE do not correlate with severity of disease in the early stages of bullous pemphigoid.

    PubMed

    Bing, Liu; Xiping, Zhou; Li, Li; Jun, Peng; Yi-Xia, Wang; Min, Yang; Qing, Liu; Qiu-Ning, Sun; Hong-Zhong, Jin; Ya-Gang, Zuo

    2015-11-01

    Bullous pemphigoid (BP), a common autoimmune skin disease, is associated with IgG autoantibodies against the hemidesmosomal proteins, BP180 and BP230. In addition to IgG, IgE has been shown to play a role in the disease. However, the association between disease activity and IgE specific to the NC16A domain of BP180 in blister fluid remains unclear. Our objective was to evaluate the correlation between BP disease activity and BP180 NC16A-specific IgE sera and blister fluid titers, and to analyze changes during treatment. We evaluated the levels of anti-BP180 IgE autoantibodies in the sera and blister fluids of 37 BP patients using an Enzyme-linked immunosorbent assay. We also observed changes in the levels of these antibodies in 2 BP patients at 4 or 5 different time points (day 0 when the patient first visited our hospital, day 5, day 14, day 39 and day 62 for patient 1; day 0, day 4, day 8 and day 17 for patient 2). We also collected extra serum samples from the 2 patients when the disease was controlled (blister disappeared) (day 85, day 104 and day 146 for patient 1 and day 123, day 158 and day 189 for the other patient). IgE anti-BP180 antibodies were detected in the serum of 72.97 % of the patients. There was no correlation between disease activity scores and BP180 NC16A IgE titers in serum (r = -0.077, p > 0.05) or in blister fluid (r = 0.262, p > 0.05). The levels of the autoantibody in serum were positively correlated with that in blister fluid (r = 0.6651, p < 0.001); however, the levels continued to rise despite effective control of the disease in the initial two to 6 weeks of diagnosis. The level of this autoantibody reached a peak on day 39 for patient 1 and on day 17 for patient 2 although the systemic and topical medication of steroid had controlled the disease process effectively. We conclude that levels of anti-BP180 NC16A IgE are higher in the sera than blister fluids. These levels could generally reflect disease severity throughout the course of

  10. Reduced β-lactoglobulin IgE binding upon in vitro digestion as a result of the interaction of the protein with casein glycomacropeptide.

    PubMed

    Martinez, María J; Martos, Gustavo; Molina, Elena; Pilosof, Ana M R

    2016-02-01

    The aim of this work was to evaluate the effect of the presence of casein glycomacropeptide (CMP) on the in vitro digestibility and potential allergenicity of β-lactoglobulin (β-lg)-CMP mixtures. The digestion products were analyzed by RP-HPLC and RP-HPLC-ESI-MS/MS. The potential allergenicity of the digestion products was studied by human IgE binding by inhibition ELISA with serum samples from children with clinical allergic symptoms to β-lg. No differences were observed by HPLC in the mixtures hydrolysates due to CMP-β-lg interactions. RP-HPLC-ESI-MS/MS results showed different peptides occurring in the mixtures hydrolysates. Additionally, it was observed a significant reduction of β-lg IgE binding in the presence of CMP. The disappearance of epitopes in the digested mixtures could explain the lower IgE binding observed in these systems compared to β-lg. It can be concluded that the presence of CMP in products containing β-lg may modify the digestion products that may reduce the potential allergenicity of β-lg. PMID:26304433

  11. Total IgE as a Serodiagnostic Marker to Aid Murine Fur Mite Detection

    PubMed Central

    Roble, Gordon S; Boteler, William; Riedel, Elyn; Lipman, Neil S

    2012-01-01

    Mites of 3 genera—Myobia, Myocoptes, and Radfordia—continue to plague laboratory mouse facilities, even with use of stringent biosecurity measures. Mites often spread before diagnosis, predominantly because of detection difficulty. Current detection methods have suboptimal sensitivity, are time-consuming, and are costly. A sensitive serodiagnostic technique would facilitate detection and ease workload. We evaluated whether total IgE increases could serve as a serodiagnostic marker to identify mite infestations. Variables affecting total IgE levels including infestation duration, sex, age, mite species, soiled-bedding exposure, and ivermectin treatment were investigated in Swiss Webster mice. Strain- and pinworm-associated effects were examined by using C57BL/6 mice and Swiss Webster mice dually infested with Syphacia obvelata and Aspiculuris tetraptera, respectively. Mite infestations led to significant increases in IgE levels within 2 to 4 wk. Total IgE threshold levels and corresponding sensitivity and specificity values were determined along the continuum of a receiver-operating characteristic curve. A threshold of 81 ng/mL was chosen for Swiss Webster mice; values above this point should trigger screening by a secondary, more specific method. Sex-associated differences were not significant. Age, strain, and infecting parasite caused variability in IgE responses. Mice exposed to soiled bedding showed a delayed yet significant increase in total IgE. Treatment with ivermectin reduced total IgE levels within 2 wk. Our data suggest that increases in total IgE in Swiss Webster and C57BL/6 mice warrant investigation, especially because mite infestations can rapidly elevate total IgE levels. We propose that using total IgE levels routinely in serologic panels will enhance biosecurity. PMID:22776120

  12. [Investigation of mold fungi in air samples of elementary schools and evaluation of allergen-specific IgE levels in students' sera].

    PubMed

    Ovet, Habibe; Ergin, Cağrı; Kaleli, Ilknur

    2012-04-01

    Atmospheric fungal spores play important role in allergic reactions in atopic individuals. Monitorization of those spores found in the environment of atopic cases is crucial for the choice of the antigens that will be included in allergen screening procedures and precautions to be taken against mold-originated health problems. Since most of the people spend plenty of time indoors in recent years, the effects of exposure to indoor air fungi on human health have gained importance. This study was aimed to investigate the indoor air mold distribution of elementary schools in Denizli province (located in west Anatolia, Turkey) and to compare the allergen-specific IgE levels of children against the most frequently detected mold genus. A questionnaire (MM080) was distributed to the 4967 students (6-8 year-old) attending first and second degrees of 16 different elementary schools with scattered locations in city center. This questionnaire form included the questions related to the general information about the child, school environment, allergic complaints since last year, home environment and nutrition. Response rate to the questionnaire was 51.6% (2565/4967). Air samples were collected from 18 classrooms in March 2009, during which high rates of allergic symptoms were observed according to the questionnaire results. Mold fungi belonging to 10 different genera (Penicillium spp. 46%; Aspergillus spp. 18%; Cladosporium spp. 17%; Alternaria spp. 15%; Drechslera spp. 1%; Chrysosporium, Fusarium, Conidiobolus and Cladothecium species 0.5%; unidentified 1%) were isolated from indoor air of classrooms. Since the most frequently detected mold was Penicillium spp. (46%), the 48 children with atopic symptoms were called to the hospital for the determination of total IgE and Penicillium specific IgE in their sera. Twenty two students accepted the invitation and serum total IgE (Immulite 2000; Diagnostic Product Corporation, USA) and allergen-specific IgE (Penicillium brevicompactum

  13. Influence of experimental alcohol administration on serum immunoglobulin levels: contrasting effects on IgE and other immunoglobulin classes.

    PubMed

    Alonso, M; Gomez-Rial, J; Gude, F; Vidal, C; Gonzalez-Quintela, A

    2012-01-01

    In humans, alcoholic liver disease is associated with hypergammaglobulinemia, particularly with high serum concentrations of IgA. Furthermore, alcohol consumption is associated with high concentrations of IgE and low concentrations of IgG. However, there is little experimental evidence to corroborate these observational findings. The objective of the present study was to investigate the potential short-term effects of alcohol administration on serum immunoglobulin concentrations in mice, and the potential influence of sex and strain on these effects. Eight mouse groups were defined by strain (Swiss vs C57BL/6), sex (male vs female), and experimental procedure (alcohol administration vs control diet). Alcohol was administered in a semi-liquid diet (6.5%v/v); control animals received an isocaloric semi-liquid diet. Immunoglobulin concentrations (IgE, IgA, IgM, IgG1, IgG2a, IgG2b, and IgG3) were measured at baseline and weekly thereafter for 4 weeks. Serum Th1 (interferon-gamma) and Th2 (IL-4 and IL-13) cytokines were measured at week 4. We found significant variations in baseline immunoglobulin concentrations depending upon mouse sex and strain. Alcohol administration was quickly followed by an increase in serum IgE concentrations in all experimental groups. IgE increase was correlated with serum IL-13 increase. In contrast, alcohol administration was not associated with significant changes in serum IgA and IgM concentration, and appeared to decrease IgG subclass concentrations. Alcohol effects on immunoglobulin concentrations were independent of mouse strain and sex. In conclusion, alcohol administration in mice had contrasting effects on IgE and other immunoglobulin classes. This experimental evidence confirms observational results in humans. PMID:23058015

  14. Topical Application of Chrysanthemum indicum L. Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-γ, and IL-4 in Nc/Nga Mice

    PubMed Central

    Park, Sunmin; Lee, Jung Bok; Kang, Suna

    2012-01-01

    Chrysanthemum indicum L. (CIL) is widely used as an anti-inflammatory agent in Asia and our preliminary study revealed that CIL reduced interleukin (IL)-4 and IL-13 in 2,4-dinitrochlorobenzene (DNCB)-treated HaCaT cells, a human keratinocyte cell line. We investigated the atopic dermatitis (AD) effect of topically applied CIL in mice with AD-like symptoms. After topical application of 1,3-butylen glycol (control), CIL-Low (5%), CIL-High (30%), or 0.1% hydrocortisone (HC) on the AD-like skin lesions in DNCB-treated NC/Nga mice for 5 weeks, the ear thickness, mast cell infiltration, and serum immunoglobulin E (IgE), IgG1, IL-4 and interferon (IFN)-γ were measured. The gene expressions of IL-4, IL-13, and IFN-γ in the dorsal skin were assayed. CIL treatment dosedependently reduced severity of clinical symptoms of dorsal skin, ear thickness, and the number of mast cells and eosinophils. CIL-High significantly decreased serum IgE, IgG1, IL-4, and IFN-γ levels and reduced mRNA levels of IFN-γ, IL-4, and IL-13 in dorsal skin lesion. The improvement by CIL-High was similar to HC, but without its adverse effects such as skin atrophy maceration, and secondary infection. In conclusion, CIL may be an effective alternative substance for the management of AD. PMID:22454686

  15. Prenatal exposure to phthalates, bisphenol A and perfluoroalkyl substances and cord blood levels of IgE, TSLP and IL-33.

    PubMed

    Ashley-Martin, Jillian; Dodds, Linda; Levy, Adrian R; Platt, Robert W; Marshall, Jean S; Arbuckle, Tye E

    2015-07-01

    The fetal time period is a critical window of immune system development and resulting heightened susceptibility to the adverse effects of environmental exposures. Epidemiologists and toxicologists have hypothesized that phthalates, bisphenol A (BPA) and perfluoroalkyl substance have immunotoxic properties. Immunotoxic effects of chemicals may manifest in an altered immune system profile at birth. Immunoglobulin E, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) are integral in the etiology of childhood allergy and detectable at birth. The objective of this study was to determine the association between maternal levels of phthalates, bisphenol A (BPA), and perfluoroalkyl substances and elevated umbilical cord blood levels of IgE, TSLP, and IL-33. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Of these women, 1258 had a singleton, term birth and cord blood sample. A Bayesian hierarchical model was employed to determine associations between log-transformed continuous variables and immune system biomarkers while adjusting for potential confounding from correlated environmental contaminants. Inverse, nonlinear associations were observed between maternal urinary MCPP levels and elevated levels of both IL-33/TSLP and IgE and between maternal urinary BPA levels and elevated levels of IL-33/TSLP. In this primarily urban Canadian population of pregnant women and their newborns, maternal urinary and plasma concentrations of phthalate metabolites, BPA, and perfluoroalkyl substances were not associated with immunotoxic effects that manifest as increased odds of elevated levels of IgE, TSLP or IL-33. PMID:25913155

  16. Human IgE binding capacity of tryptic peptides from bovine alpha-lactalbumin.

    PubMed

    Maynard, F; Jost, R; Wal, J M

    1997-08-01

    The specific IgE binding capacity of native bovine alpha-lactalbumin (alpha-La), a globular whey protein, and tryptic peptides was investigated using 19 sera from patients with cow's milk protein allergy. The specific anti-bovine alpha-La IgE titers ranged from 0.6 to 125 IU/ml. Highly purified tryptic peptides from native and disulfide-bond-reduced alpha-La were obtained by reverse phase chromatography. By ELISA technique using immobilized native protein or peptides, 11 of the 19 sera reacted exclusively with intact protein while 8 of them also presented a specific IgE response to different tryptic peptides. Polyclonal IgE population specificity was not related to anti-bovine alpha-La IgE levels. Sequence (17G-K58) and larger peptides sharing this sequence were most strongly and frequently recognized. Competitive ELISA inhibition tests confirmed this IgE-specific response and gave also clear evidence for IgE binding to smaller peptides corresponding to sequences (6C-R10):S-S:(115L-L123) and (109A-L123). IgE binding to native alpha-La and large peptides confirmed the importance of conformational epitope(s). However, in some sera reduced and S-alkylated peptide (59I-K94) exhibited a similar or higher IgE binding capacity than the native corresponding fragment, suggesting the existence of sequential epitope(s) exposed through protein denaturation. Moreover, IgE binding sequences were also located within hydrophobic regions of alpha-La and/or within parts with high sequence homology to human alpha-La. PMID:9250594

  17. 129/SvJ mice have mutated CD23 and hyper IgE

    PubMed Central

    Ford, Jill W.; Sturgill, Jamie L.; Conrad, Daniel H.

    2009-01-01

    CD23, the low affinity IgE receptor, is hypothesized to function as a negative regulator of IgE production. Upon discovering reduced CD23 surface levels in 129/SvJ inbred mice, we sought to further investigate 129/SvJ CD23 and to examine its influence on IgE levels. Five amino acid substitutions were found in 129/SvJ CD23. Identical mutations were also observed in CD23 from New Zealand Black and 129P1/ReJ mice. 129/SvJ B cells proliferated more rapidly than those from BALB/c after stimulation with IL-4 and CD40 ligand trimer. However, in vitro IgE levels in supernatants from stimulated 129/SvJ B cells were significantly reduced. Contrary to the in vitro findings, the 129/SvJ CD23 mutations correlated with a hyper IgE phenotype in vivo and 129/SvJ were able to clear Nippostrongylus brasiliensis infection more rapidly than either BALB/c or C57BL/6. Overall, this study further suggests that CD23 is an important regulatory factor for IgE production. PMID:18828998

  18. Effective anthelmintic therapy of residents living in endemic area of high prevalence for Hookworm and Schistosoma mansoni infections enhances the levels of allergy risk factor anti-Der p1 IgE

    PubMed Central

    Campolina, Sabrina S.; Araujo, Marcio S.S.; Rezende, Tércia M.R.L.; Matoso, Leonardo; Quites, Humberto F.O.; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo A.; Gazzinelli, Andrea; Correa-Oliveira, Rodrigo

    2013-01-01

    In this work were investigated the relationship between Hookworm/Schistosoma mansoni infections and allergy related risk factors in two endemic areas with distinct prevalence of infections and co-infection. The intensity of infections, eosinophilia, allergy risk factors, infections status and anti-Der p1 IgE levels before and 2 years (population 1) and 3 years (population 2) after anthelmintic treatment, were evaluated. It was observed that the population with lower prevalence and intensity of infection (population 2) had lower eosinophils counts (>600/mm3) and higher animal contact than the population with higher parasites intensity (population 1). After anthelmintic treatment the intensity of S. mansoni single infection decreased, but no changes were observed in Hookworm and co-infected individuals. The anthelmintic treatment also enhanced anti-Der p1 IgE optical density in ELISA on the subgroups that became negative for helminth infection regardless of their previous infection condition in population 1. Facing that, we evaluated the anti-Der p1 IgE reactivity index, and the ratio (after/before treatment) was significantly higher in patients co-infected before treatment. On the other hand, no association between anti-Der p1 IgE reactivity index and the intensity of infections were observed. In conclusion, effective anthelmintic therapy of subjects from endemic areas with high prevalence of Hookworm and S. mansoni infections enhances anti-Der p1 IgE levels. PMID:25905031

  19. Effective anthelmintic therapy of residents living in endemic area of high prevalence for Hookworm and Schistosoma mansoni infections enhances the levels of allergy risk factor anti-Der p1 IgE.

    PubMed

    Campolina, Sabrina S; Araujo, Marcio S S; Rezende, Tércia M R L; Matoso, Leonardo; Quites, Humberto F O; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo A; Gazzinelli, Andrea; Correa-Oliveira, Rodrigo

    2015-01-01

    In this work were investigated the relationship between Hookworm/Schistosoma mansoni infections and allergy related risk factors in two endemic areas with distinct prevalence of infections and co-infection. The intensity of infections, eosinophilia, allergy risk factors, infections status and anti-Der p1 IgE levels before and 2 years (population 1) and 3 years (population 2) after anthelmintic treatment, were evaluated. It was observed that the population with lower prevalence and intensity of infection (population 2) had lower eosinophils counts (>600/mm(3)) and higher animal contact than the population with higher parasites intensity (population 1). After anthelmintic treatment the intensity of S. mansoni single infection decreased, but no changes were observed in Hookworm and co-infected individuals. The anthelmintic treatment also enhanced anti-Der p1 IgE optical density in ELISA on the subgroups that became negative for helminth infection regardless of their previous infection condition in population 1. Facing that, we evaluated the anti-Der p1 IgE reactivity index, and the ratio (after/before treatment) was significantly higher in patients co-infected before treatment. On the other hand, no association between anti-Der p1 IgE reactivity index and the intensity of infections were observed. In conclusion, effective anthelmintic therapy of subjects from endemic areas with high prevalence of Hookworm and S. mansoni infections enhances anti-Der p1 IgE levels. PMID:25905031

  20. No effect of interleukin-2 on IgE levels given in addition to antiretroviral therapy in HIV-infected adults with CD4 >300 cells/mm3.

    PubMed

    Ananworanich, Jintanat; Chantaphakul, Hiroshi; Teeratakulpisarn, Somsong; Siangphoe, Umaporn; Ubolyam, Sasiwimol; Chuenyam, Theshinee; Ungsedhaphan, Chaiwat; Lange, Joep; Cooper, David; Phanuphak, Praphan; Ruxrungtham, Kiat

    2005-03-01

    HIV-infected patients may have frequent atopy caused by an imbalance of Th1 and Th2 cytokines. The objective of the present study was to investigate whether IL-2 given in addition to antiretrovirals (ARV) would result in lower IgE levels and less allergic symptoms. Patients naive to IL-2 (n=28) began IL-2 plus ARV and were followed for 12 months. IgE, eosinophil and CD4 counts, HIV RNA, symptom scoring, PFT and skin prick test (SPT) were performed. It was found that the baseline median CD4 and IgE were 386.5 cells/mm3 and 63.5 IU/ml, respectively. Four patients had allergic rhinitis (AR) and 61% had a positive SPT to at least 1 antigen. At month 12, patients had higher CD4 counts (p < 0.001) compared to the baseline; however, there were no differences in IgE levels, allergic symptom scores or HIV RNA. The eosinophil count was higher after IL-2 administration. It was concluded that IL-2 plus ARV resulted in higher CD4 counts but had no effect on atopy. PMID:15997871

  1. IgE immunotherapy

    PubMed Central

    Josephs, Debra H; Spicer, James F; Karagiannis, Panagiotis; Gould, Hannah J; Karagiannis, Sophia N

    2014-01-01

    The importance of antibodies in activating immune responses against tumors is now better appreciated with the emergence of checkpoint blockade antibodies and with engineered antibody Fc domains featuring enhanced capacity to focus potent effector cells against cancer cells. Antibodies designed with Fc regions of the IgE class can confer natural, potent, long-lived immune surveillance in tissues through tenacious engagement of high-affinity cognate Fc receptors on distinct, often tumor-resident immune effector cells, and through ability to activate these cells under tumor-induced Th2-biased conditions. Here, we review the properties that make IgE a contributor to the allergic response and a critical player in the protection against parasites, which also support IgE as a novel anti-cancer modality. We discuss IgE-based active and passive immunotherapeutic approaches in disparate in vitro and in vivo model systems, collectively suggesting the potential of IgE immunotherapies in oncology. Translation toward clinical application is now in progress. PMID:24423620

  2. Immunoglobulin (Ig)E Expression Pattern in Lung: Relation to Systemic IgE and Asthma Phenotypes

    PubMed Central

    Balzar, Silvana; Strand, Matthew; Rhodes, Diane; Wenzel, Sally E.

    2007-01-01

    Background: Immunoglobulin E (IgE)-mediated responses contribute to allergy and asthma. Little is understood regarding the relationship of tissue IgE to systemic IgE, inflammation or clinical outcomes. Objectives: To evaluate local IgE expression and cellular inflammation in proximal and distal lung of normal subjects and subjects with asthma of varying severity and relate those tissue parameters to systemic IgE levels, atopy, lung function and history of severe exacerbations of asthma. Methods: Tissue from over 90 subjects with eosinophilic (SAeo+) and non-eosinophilic (SAeo−) severe asthma, mild asthma and normal subjects were immunostained for IgE, signal-amplifying isoform of IgE receptor (FcεRIβ) and markers of mast cells, eosinophils and lymphocytes. Tissue expression of IgE, FcεRIβ, cellular inflammation, serum IgE and atopy were compared. Regression models were used to determine the relationship of local and systemic IgE to lung function and severe exacerbations of asthma. Results: Mast cell-bound IgE was present along airways, but absent in lung parenchyma. While the groups were similar in systemic/serum IgE and atopy, local/tissue IgE was highest in SAeo+ and correlated with eosinophils and lymphocytes (rs=0.52; p<0.0001 and rs=0.23; p=0.03, respectively). Higher local IgE was associated with better lung function, but also with more severe exacerbations of asthma. Conclusion: Local IgE appears to be primarily a component of responses within the mucosal immune compartment and is related to cellular inflammation, lung function and clinical outcomes in asthma. Clinical Implications: Local/airway IgE-related processes rather than systemic markers of atopy may be relevant in determining clinical outcomes in asthma. Capsule Summary: The study reports mucosal distribution of mast cell-bound IgE in human lung and suggests that local IgE and related responses rather than systemic/serum IgE and atopy are more relevant in determining clinical outcomes in

  3. Primary Immunodeficiencies with Elevated IgE.

    PubMed

    Mogensen, Trine H

    2016-01-01

    In recent years a number of primary immunodeficiencies (PIDs) characterized by elevated Immunoglobulin E (IgE) levels have been uncovered and termed as Hyper-IgE syndrome (HIES). In addition to the elevated levels of IgE, patients with these PIDs display a spectrum of infections by staphylococci and fungi, and in some cases viruses, particularly affecting skin and lungs. Most of these PIDs also have a non-infectious phenotype, comprising musculoskeletal, vascular, and neurological abnormalities. The genetic basis for the majority of conditions with elevated IgE has now been established and includes mutations in STAT3, DOCK8, TYK2, and most recently PGM3 molecules. However, in some patients with the relevant phenotype, mutations in these molecules are not identified, suggesting additional genetic etiologies of HIES not yet discovered. As the immunological and molecular basis of HIES is being unraveled, important insights are emerging that may have implications for our understanding of basic principles of immunology and protective immunity as well as for the pathogenesis and clinical management of patients with these complex and challenging PIDs. In this review, are presented the current knowledge on the clinical presentation, infectious phenotype, and the genetic and immunological pathogenesis of hyper-IgE syndromes as well as some other PIDs with elevated levels of IgE. PMID:25970001

  4. Prevention of Th2-like cell responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels.

    PubMed

    Hofstra, C L; Van Ark, I; Hofman, G; Kool, M; Nijkamp, F P; Van Oosterhout, A J

    1998-11-01

    Allergic asthma is thought to be regulated by Th2 cells, and inhibiting this response is a promising mode of intervention. Many studies have focused on differentiation of Th cells to the Th1 or Th2 subset in vitro. IL-4 is essential for Th2 development, while IL-12 induces Th1 development, which can be enhanced by IL-18. In the present study, we investigated whether IL-12 and IL-18 were able to interfere in Th2 development and the associated airway symptoms in a mouse model of allergic asthma. Mice were sensitized with OVA using a protocol that induces IgE production. Repeated challenges by OVA inhalation induced elevated serum levels of IgE, airway hyperresponsiveness, and a predominantly eosinophilic infiltrate in the bronchoalveolar lavage concomitant with the appearance of Ag-specific Th2-like cells in lung tissue and lung-draining lymph nodes. Whereas treatments with neither IL-12 nor IL-18 during the challenge period were effective, combined treatment of IL-12 and IL-18 inhibited Ag-specific Th2-like cell development. This inhibition was associated with an absence of IgE up-regulation, airway hyperresponsiveness, and cellular infiltration in the lavage. These data show that, in vivo, the synergistic action of IL-12 and IL-18 is necessary to prevent Th2-like cell differentiation, and consequently inhibits the development of airway symptoms in a mouse model of allergic asthma. PMID:9794443

  5. Paradoxical Increase of IgE Binding Components during Allergen-Specific Immunotherapy in Pollinosis Patients

    PubMed Central

    Kim, Mi-Ae; Yoon, Moon-Gyung; Jin, Hyun-Jung; Shin, Yoo-Seob

    2014-01-01

    Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens. Graphical Abstract PMID:25045240

  6. Paradoxical increase of IgE binding components during allergen-specific immunotherapy in pollinosis patients.

    PubMed

    Kim, Mi-Ae; Yoon, Moon-Gyung; Jin, Hyun-Jung; Shin, Yoo-Seob; Park, Hae-Sim

    2014-07-01

    Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens. PMID:25045240

  7. Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity.

    PubMed

    Ta, Von; Weldon, Brittany; Yu, Grace; Humblet, Olivier; Neale-May, Susan; Nadeau, Kari

    2011-01-01

    AIMS: To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. STUDY DESIGN: Prospective study. PLACE AND DURATION OF STUDY: Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. METHODOLOGY: We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock's criteria. RESULTS: Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. CONCLUSION: These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2). PMID:22993721

  8. Changes over Time in IgE Sensitization to Allergens of the Fish Parasite Anisakis spp.

    PubMed Central

    Carballeda-Sangiao, Noelia; Rodríguez-Mahillo, Ana I.; Careche, Mercedes; Navas, Alfonso; Moneo, Ignacio; González-Muñoz, Miguel

    2016-01-01

    Background Sensitization to Anisakis spp. can produce allergic reactions after eating raw or undercooked parasitized fish. Specific IgE is detected long after the onset of symptoms, but the changes in specific IgE levels over a long follow-up period are unknown; furthermore, the influence of Anisakis spp. allergen exposure through consumption of fishery products is also unknown. Objective To analyse the changes in IgE sensitization to Anisakis spp. allergens over several years of follow-up and the influence of the consumption of fishery products in IgE sensitization. Methods Total IgE, Anisakis spp.-specific IgE, anti-Ani s 1 and anti-Ani s 4 IgE were repeatedly measured over a median follow-up duration of 49 months in 17 sensitized patients. Results Anisakis spp.-specific IgE was detected in 16/17 patients throughout the follow-up period. The comparison between baseline and last visit measurements showed significant decreases in both total IgE and specific IgE. The specific IgE values had an exponential or polynomial decay trend in 13/17 patients. In 4/17 patients, an increase in specific IgE level with the introduction of fish to the diet was observed. Three patients reported symptoms after eating aquaculture or previously frozen fish, and in two of those patients, symptom presentation was coincident with an increase in specific IgE level. Conclusions IgE sensitization to Anisakis spp. allergens lasts for many years since specific IgE was detectable in some patients after more than 8 years from the allergic episode. Specific IgE monitoring showed that specific IgE titres increase in some allergic patients and that allergen contamination of fishery products can account for the observed increase in Anisakis spp.-specific IgE level. Clinical Relevance Following sensitization to Anisakis spp. allergens, the absence of additional exposure to those allergens does not result in the loss of IgE sensitization. Exposure to Anisakis spp. allergens in fishery products can

  9. Increased proportions of CCR4+ cells among peripheral blood CD4+ cells and serum levels of allergen-specific IgE antibody in canine chronic rhinitis and bronchitis

    PubMed Central

    YAMAYA, Yoshiki; WATARI, Toshihiro

    2014-01-01

    Canine chronic rhinitis (CR) and bronchitis (CB) are suspected to be allergic diseases. The present study tested whether dogs diagnosed with CR or CB present an atopic predisposition based on the ratio of CC chemokine receptor 4 (CCR4)-positive cells among peripheral blood CD4-positive cells (CCR4/CD4) and the serum levels of allergen-specific IgE antibodies. We found that most dogs with CR and CB have a possibility of atopic predisposition, and macrolide therapy constitutes an alternative to corticosteroid therapy in controlling the clinical signs. PMID:25650058

  10. Mathematics Instruction in IGE and Non-IGE Schools. Working Paper 317. Report from the IGE Evaluation Project.

    ERIC Educational Resources Information Center

    Romberg, Thomas A.; And Others

    This report summarizes the data from a comparative study of grades 2 and 5 mathematics instruction and the use of Developing Mathematical Processes (DMP) in IGE and non-IGE settings. These results are part of a five-phase evaluation of the IGE system of elementary schooling. Use of DMP and reported adoption of IGE were not found to be good…

  11. Prenatal exposure to household pets influences fetal IgE production

    PubMed Central

    Aichbhaumik, Niladri; Zoratti, Edward M.; Strickler, Ronald; Wegienka, Ganesa; Ownby, Dennis R.; Havstad, Suzanne; Johnson, Christine Cole

    2013-01-01

    Background Early life pet exposure may protect against allergic sensitization during childhood. Few studies have evaluated the effect of prenatal pet exposure on potential neonatal markers of allergic risk. Objective To investigate whether maternal exposure to pets affects cord blood IgE levels in a population-based, general risk, ethnically mixed birth cohort. Methods Pet keeping during pregnancy was ascertained from women residing in a defined area of Wayne County Michigan and recruited from five staff model obstetric clinics. Maternal venous blood was analyzed for total and allergen-specific IgE along with cord blood total IgE from 1049 infants. Results Compared to infants from households with no cats or dogs kept indoors during pregnancy, infants whose homes had either cats or dogs had significantly reduced mean cord IgE levels [0.34 IU/ml (95%CI 0.30–0.38) vs. 0.24 IU/ml (0.20–0.27) p = 0.025]. Similar effects were apparent in cat-only households [0.21 IU/ml (0.16–0.27), p = 0.020] and dog-only households [0.24 IU/ml (0.19–0.29), p = 0.045]. There was no effect on results when excluding mothers who reported avoiding pets due to allergy-related concerns. Conclusion Mothers with either cats or dogs in their home during pregnancy deliver children with lower cord blood IgE levels compared to mothers who do not live with these pets, supporting the hypothesis that pet exposure influences immune development in a manner that is protective for atopy and is operant even before birth. PMID:18702655

  12. Presence of IgE class antibodies with cardiolipinic and treponemal specificity in syphilis. Quantitative evaluation by IgE prist radio-immuno-assay.

    PubMed

    Ionescu, A D; Ivănescu, M

    1992-01-01

    60 serum samples (reactive in VDRL, ELISA-Reiter, FTA-Abs tests) from 25-45 years old male patients with untreated latent syphilis (EL) (30 cases) and persistent positive treated syphilis (ET+) (30 cases) were tested for IgE by IgE-PRIST. On 30 sera from 25-45 years old male healthy persons, normal mean value for serum IgE was established: 159.63 +/- 124.09 U/ml. Cardiolipin and group treponemal IgE fractions were indirectly calculated by the difference between the specific activity induced by sera as such and that induced by sera absorbed with cardiolipin and group treponemal sorbents. In EL, total IgE level was 197 +/- 107 U/ml; cardiolipin IgE -24.9 +/- 8.3 U/ml and group treponemal IgE 35.8 +/- 6.6 U/ml. In ET, total IgE value was 152.6 +/- 122.5 U/ml, cardiolipin IgE -11 +/- 10.5 and group treponemal IgE -26.6 +/- 14.2 U/ml. Summing up the two specificities, the total specific IgE represent about 1/3 from total IgE in EL and 1/5 in ET+. Taking into account the short half-life (2-3 days) of IgE presence of a significant proportion of specific IgE in those two stages proves, by their continuous synthesis paralleling antigenic stimulation, the presence in various tissular zones of viable treponemas as sources of antigens. PMID:1457821

  13. Reduced plasma pyrophosphate levels in hemodialysis patients.

    PubMed

    Lomashvili, Koba A; Khawandi, Wassim; O'Neill, W Charles

    2005-08-01

    Pyrophosphate (PPi) is a known inhibitor of hydroxyapatite formation and has been shown to inhibit medial vascular calcification in vitamin D-toxic rats. It was demonstrated recently that endogenous production of PPi prevents calcification of rat aorta that are cultured in high concentrations of calcium and phosphate. For determining whether PPi metabolism is altered in hemodialysis patients, plasma levels and dialytic clearance of PPi were measured in stable hemodialysis patients. Predialysis plasma [PPi] was 2.26 +/- 0.19 microM in 38 clinically stable hemodialysis patients compared with 3.26 +/- 0.17 in 36 normal subjects (P < 0.01). Approximately 30% of plasma PPi was protein bound, and this was not altered in dialysis patients. There was a weak inverse correlation with age in normal individuals but not in dialysis patients. Plasma [PPi] in dialysis patients was correlated with plasma [PO4(3-)] (r = 0.56) but not with [Ca2+], parathyroid hormone, or the dose of dialysis, and levels did not vary between interdialytic periods of 2 and 3 d. Plasma [PPi] decreased 32 +/- 5% after standard hemodialysis in 17 patients. In vitro clearance of PPi by a 2.1-m2 cellulose acetate dialyzer was 36%, and the mean PPi removal in five patients was 43 +/- 5 micromol, consistent with a similar in vivo clearance. Cleared PPi was greater than the plasma pool but less than the estimated extracellular fluid pool. Erythrocyte PPi content decreased 24 +/- 4%, indicating that intracellular PPi is removed as well. It is concluded that plasma [PPi] is reduced in hemodialysis patients and that PPi is cleared by dialysis. Plasma levels in some patients were below those that have previously been shown to prevent calcification of vessels in culture, suggesting that altered PPi metabolism could contribute to vascular calcification in hemodialysis patients. PMID:15958726

  14. Two Allergen Model Reveals Complex Relationship Between IgE Cross-Linking and Degranulation

    PubMed Central

    Handlogten, Michael W.; Deak, Peter E.; Bilgicer, Basar

    2014-01-01

    Summary Allergy is an immune response to complex mixtures of multiple allergens yet current models use a single synthetic allergen. Multiple allergens were modeled using two well-defined tetravalent allergens each specific for a distinct IgE thus enabling a systematic approach to evaluate the effect of each allergen and percent of allergen specific IgE on mast cell degranulation. We found the overall degranulation response caused by two allergens is additive for low allergen concentrations or low percent specific IgE, does not change for moderate allergen concentrations with moderate to high percent specific IgE, and is reduced for high allergen concentrations with moderate to high percent specific IgE. These results provide further evidence that supra-optimal IgE cross-linking decreases the degranulation response and establishes the two allergen model as a relevant experimental system to elucidate mast cell degranulation mechanisms. PMID:25308278

  15. Specific IgE in the identification of allergens in allergic rhinitis Malaysian patients.

    PubMed

    Choon-Kook, S; Teck-Soong, S L

    1995-06-01

    The specific serum IgE levels to 20 allergens were determined by enzyme immunoassay in 90 Malaysian patients with allergic rhinitis. Ninety-two percent of patients had elevated IgE to at least 1 of the allergens. The housedust mites D. pteronyssinus and D. farinae were the major allergens, elevated IgE to either allergen being present in 86% of the patients. Prick skin tests were carried out in some of the patients, housedust mites, cat fur, dog hair and shrimp were the allergens used. Close correspondence was found between IgE and prick skin tests to the mites. PMID:7488340

  16. CTLA4Fcε, a novel soluble fusion protein that binds B7 molecules and the IgE receptors, and reduces human in vitro soluble CD23 production and lymphocyte proliferation.

    PubMed

    Perez-Witzke, Daniel; Miranda-García, María Auxiliadora; Suárez, Nuris; Becerra, Raquel; Duque, Kharelys; Porras, Verónica; Fuenmayor, Jaheli; Montano, Ramon Fernando

    2016-05-01

    Immunoglobulin E-mediated allergy and certain autoimmune diseases are characterized by the presence of a T helper type 2 (Th2) immune response and allergen-specific or self-reactive IgE. Soluble CD23 (sCD23) is a B-cell factor that fosters IgE class-switching and synthesis, suggesting that sCD23 may be a therapeutic target for these pathologies. We produced a recombinant protein, CTLA4Fcε, by fusing the ectodomain of the immunoregulatory molecule cytotoxic T-lymphocyte antigen 4 (CTLA-4) with a fragment of the IgE H-chain constant region. In SDS-PAGE/inmunoblot analyses, CTLA4Fcε appeared as a 70 000 MW polypeptide that forms homodimers. Flow cytometry showed that CTLA4Fcε binds to IgE receptors FcεRI and FcεRII/CD23, as well as to CTLA-4 counter-receptors CD80 and CD86. Binding of CTLA4Fcε to FcεRII/CD23 appeared stronger than that of IgE. Since the cells used to study CD23 binding express CD80 and CD86, simultaneous binding of CTLA4Fcε to CD23 and CD80/CD86 seems to occur and would explain this difference. As measured by a human CD23-specific ELISA, CTLA4Fcε - but not IgE - induced a concentration-dependent reduction of sCD23 in culture supernatants of RPMI-8866 cells. Our results suggest that the simultaneous binding of CTLA4Fcɛ to CD23-CD80/CD86 may cause the formation of multi-molecular complexes that are either internalized or pose a steric hindrance to enzymatic proteolysis, so blocking sCD23 generation. CTLA4Fcε caused a concentration-dependent reduction of lymphocyte proliferation in human peripheral blood mononuclear cell samples stimulated in vitro with concanavalin A. The ability to bind IgE receptors on effector cells, to regulate the production of sCD23 and to inhibit lymphocyte proliferation suggests that CTLA4Fcɛ has immunomodulatory properties on human Th2 responses. PMID:26801967

  17. Association between egg and staphylococcal superantigen IgE sensitizations in atopic dermatitis.

    PubMed

    Ong, Peck Y

    2014-01-01

    Patients with moderately severe atopic dermatitis (AD) suffer from significant morbidity including secondary infections and psychosocial disturbances. However, there is currently no laboratory test for identifying these patients to implement early treatments. Because IgE sensitization to foods is frequently an early manifestation in infants with AD, this study aims to examine if food IgE levels may identify AD patients with more severe disease, and whether IgE sensitization to food may predict IgE sensitization to staphylococcal superantigens. Fifty-one young children with AD were included in the study. Eczema severity was measured by objective scoring AD. The levels of food and staphylococcal superantigen-specific IgE were measured by Phadia ImmunoCAP system. Of the five common food allergens (cow's milk, egg white, soybean, wheat, and peanut), only IgE levels to egg white correlated significantly with eczema severity in young children with AD. IgE sensitization to egg white was significantly associated with IgE sensitization to staphylococcal superantigens in older children. PMID:24992554

  18. NASA-IGES Translator and Viewer

    NASA Technical Reports Server (NTRS)

    Chou, Jin J.; Logan, Michael A.

    1995-01-01

    NASA-IGES Translator (NIGEStranslator) is a batch program that translates a general IGES (Initial Graphics Exchange Specification) file to a NASA-IGES-Nurbs-Only (NINO) file. IGES is the most popular geometry exchange standard among Computer Aided Geometric Design (CAD) systems. NINO format is a subset of IGES, implementing the simple and yet the most popular NURBS (Non-Uniform Rational B-Splines) representation. NIGEStranslator converts a complex IGES file to the simpler NINO file to simplify the tasks of CFD grid generation for models in CAD format. The NASA-IGES Viewer (NIGESview) is an Open-Inventor-based, highly interactive viewer/ editor for NINO files. Geometry in the IGES files can be viewed, copied, transformed, deleted, and inquired. Users can use NIGEStranslator to translate IGES files from CAD systems to NINO files. The geometry then can be examined with NIGESview. Extraneous geometries can be interactively removed, and the cleaned model can be written to an IGES file, ready to be used in grid generation.

  19. Total IgE Distribution in Food Allergy Suspected Patients in Republic of Macedonia (2001-2011)

    PubMed Central

    Mitkovska, Slavica Hristomanova; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Spiroski, Mirko

    2015-01-01

    BACKGROUND: IgE may be considered the hallmark of allergic disorders. It is easily detected in serum and can be measured as total IgE and as allergen-specific IgE. In fact, the serum IgE assay is used to diagnose an allergy. AIM: The aim of this study is to evaluate, investigate and present the distribution of total serum IgE levels, determined with UniCap system, in food-allergy suspected patients in a Republic of Macedonia. MATERIAL AND METHODS: In this study we analyzed retrospectively 8898 consecutive patients that were admitted for allergy testing at the Institute of Immunobiology and Human Genetics during the ten year period between 01.01.2001 and 01.01.2011. Total IgE levels in patient sera were detected with the in vitro system UniCAP100 (Pharmacia, Uppsala, Sweden). RESULTS: When we analyzed the number of patients according to the total IgE groups, we noted that most of the patients have normal levels of total IgE in serum. However, we also discovered a group of patients with elevated levels of total IgE that are greater than 200 kU/L. The average concentration of total serum IgE is higher in women in the age group 6 (6-7 years), followed by a steep decrease in the age group 9 (9-10 years), and after that the average concentrations of total IgE were mostly constant with the exception of a partial increase in the age group 21 (65-69 years). For men, the average serum concentrations of total IgE were highest in the age group of 6 (6-7 years), which was significantly higher than the average concentrations of total IgE in all other age groups. CONCLUSION: The large number of enrolled patients, a particular strength of this study, revealed that average concentrations of total IgE in men are higher than in women and that total IgE did not decrease with age. On the contrary, increased total IgE levels were found in patients aged 65 and 69 of both genders. We continue our work with analyses of the specific IgE antibodies values toward food and the correlation with

  20. Helminth-induced IgE and protection against allergic disorders.

    PubMed

    Hamid, Firdaus; Amoah, Abena S; van Ree, Ronald; Yazdanbakhsh, Maria

    2015-01-01

    The immune response against helminths and allergens is generally characterized by high levels of IgE and increased numbers of Th2 cells, eosinophils, and mast cells, yet the clinical outcome with respect to immediate hypersensitivity and inflammation is clearly not the same. High levels of IgE are seen to allergens during helminth infections; however, these IgE responses do not translate into allergy symptoms. This chapter summarizes the evidence of the association between helminth infections and allergic disorders. It discusses how helminth infection can lead to IgE cross-reactivity with allergens and how this IgE has poor biological activity. This information is important for developing new diagnostic methods and treatments for allergic disorders in low-to-middle-income countries. PMID:25553796

  1. Cold urticaria, raised IgE and HIV infection.

    PubMed Central

    Yu, R C; Evans, B; Cream, J J

    1995-01-01

    We present a patient with cold urticaria as an unusual and late cutaneous manifestation of acquired immunodeficiency syndrome. The severe CD4 cell depletion and markedly elevated serum IgE levels in our patient provide some insights into certain aspects of immune regulatory mechanisms. PMID:7636829

  2. Serum IgE Concentration in Trisomy 21

    ERIC Educational Resources Information Center

    Lopez, Vicente

    1974-01-01

    Levels of serum IgE (an immunoglobulin carrying reaginic antibody activity) were investigated in 16 Down's syndrome adolescents (12-to 18-years old) and in an equal number of retardates matched for age and sex residing in the same institution. (CL)

  3. IgE deposition in normal skin of patients with rheumatoid arthritis in relation to clinical and laboratory findings.

    PubMed Central

    De Clerck, L S; Westedt, M L; Cats, A; Vermeer, B J; Weltevreden, E F; Bridts, C H; Stevens, W J

    1985-01-01

    Biopsy specimens from apparently normal skin of 28 patients with classical or definite rheumatoid arthritis (RA) were examined for the presence of IgE deposition by a direct immunofluorescence technique. IgE deposition was found in 12 patients (43%) and in none of the 10 controls. This deposition was mainly localised on mast cells, and in three patients perivascular IgE staining was also noted. The skin from nine of the 12 patients also showed deposition of IgM and complement C3 or C4 factor, or both. All 12 patients with skin IgE deposition had raised levels of IgM rheumatoid factor (RF) in the serum. Nine of these also had IgE RF. IgE-containing circulating immune complexes (IgE CIC), raised serum IgE levels, and extra-articular (EA) manifestations were present in respectively 10, nine, and eight skin IgE positive patients. It is suggested that IgE and IgE CIC may be involved in the pathogenesis of RA and its EA manifestations. Images PMID:3904645

  4. Helminths and malaria co-infections are associated with elevated serum IgE

    PubMed Central

    2014-01-01

    Background Both helminth and malaria infections result in a highly polarized immune response characterized by IgE production. This study aimed to investigate the total serum IgE profile in vivo as a measure of Th2 immune response in malaria patients with and without helminth co-infection. Methods A cross sectional observational study composed of microscopically confirmed malaria positive (N = 197) and malaria negative (N = 216) apparently healthy controls with and without helminth infection was conducted at Wondo Genet Health Center, Southern Ethiopia. A pre-designed structured format was utilized to collect socio-demographic and clinical data of the subjects. Detection and quantification of helminths, malaria parasites and determination of serum IgE levels were carried out following standard procedures. Results Irrespective of helminth infection, individuals infected by malaria showed significantly high levels of serum IgE compared with malaria free apparently healthy controls (with and without helminth infections). Moreover, malaria patients co-infected with intestinal helminths showed high level of serum IgE compared with those malaria patients without intestinal helminths (2198 IU/ml versus 1668 IU/ml). A strong statistically significant association was observed between malaria parasite density and elevated serum IgE levels (2047 IU/ml versus 1778 IU/ml; P = 0.001) with high and low parasitaemia (parasite density >50,000 parasite/μl of blood), respectively. Likewise, helminth egg loads were significantly associated with elevated serum IgE levels (P = 0.003). Conclusions The elevated serum IgE response in malaria patients irrespective of helminth infection and its correlation with malaria parasite density and helminth egg intensity support that malaria infection is also a strong driver of IgE production as compared to helminths. PMID:24886689

  5. Incidence, serum IgE and TARC/CCL17 levels in atopic dermatitis associated with other allergic diseases: an update from the Ishigaki cohort.

    PubMed

    Takeuchi, Satoshi; Esaki, Hitokazu; Furusyo, Norihiro; Hayashida, Sayaka; Yamamura, Kazuhiko; Tsuji, Gaku; Takemura, Masaki; Hayashi, Jun; Furue, Masutaka

    2015-04-01

    Population cohort studies are important for understanding the current status of the target disease and its relation to comorbidity, gender, age, or environmental factors. To better understand atopic dermatitis (AD) and its related diseases, we initiated in 2001 a population cohort study of nursery school children from Ishigaki Island, Okinawa, Japan. The cohort study comprised a dermatologist-based physical examination, questionnaire administration, and blood sample analysis. The mean prevalence of AD was 6.3%. Questionnaire-based bronchial asthma and egg allergy in the children and paternal and sibling AD were statistically significant risk factors for AD. Boys with AD had a high incidence of asthma that was coexistent with a high serum total immunoglobulin E level. Also a high incidence of egg allergy was associated with greater AD severity as assessed by TARC/CCL17. PMID:25350554

  6. Glove-derived foreign proteins induce allergen-specific IgE in a mouse model.

    PubMed

    Busch, Marion; Schröder, Claudia; Baron, Jens-Malte; Ott, Hagen; Bruckner, Thomas; Diepgen, Thomas L; Mahler, Vera

    2008-04-01

    Currently, most medical gloves are produced with a low content of natural rubber latex (NRL) protein. However, they may be substituted by proteins of foreign origin to maintain specific properties of the material. The aim of this study was to investigate the allergenicity and immunogenicity of unexpected proteins (i.e., soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All respective allergen sources (extracts from three brands of NRL gloves, soy, and casein) were able to induce significant allergen-specific IgE and IgG(1) responses. On average, the highest IgE induction occurred after immunization with NRL, followed by soy and casein. Certain individuals from each treatment group exhibited levels of specific IgE as high as due to NRL. To analyze further specific IgE responses on a single allergen level, we established a microarray based on recombinant allergens for allergen-specific murine IgE detection. Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against kappa-casein could be detected in mice immunized with NRL glove extract, indicating a sensitization potential of the contained foreign protein. The substitution of genuine latex proteins by proteins of foreign origin may lead to a shift and de novo increase in sensitization to the finished products. PMID:18049454

  7. p110γ/δ Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation

    PubMed Central

    Ammon-Treiber, Susanne; Schwab, Matthias; Piekorz, Roland P.; Hirsch, Emilio; Nürnberg, Bernd; Beer-Hammer, Sandra

    2016-01-01

    The catalytical isoforms p110γ and p110δ of phosphatidylinositide 3-kinase γ (PI3Kγ) and PI3Kδ play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110γ and p110δ reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110γKOδD910A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110γ and p110δ might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110γ/δ-/-) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110γ/δ-/- mice compared to single knock-out and wildtype mice. However, p110γ/δ-/- mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoalveolar space. Moreover, p110γ/δ-/- mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110γ/δ-/- mice do not abolish the protective effect of p110γ/δ-deficiency against OVA-induced allergic airway inflammation. PMID:27442134

  8. Systemic and mucosal IgE antibody responses of horses to infection with Anoplocephala perfoliata.

    PubMed

    Pittaway, Charles E; Lawson, April L; Coles, Gerald C; Wilson, A Douglas

    2014-01-17

    numerous IgE-positive cells within lymphoid follicles in the caecal mucosa close to the site of A. perfoliata attachment and quantitative RT-PCR detected high levels of IgE transcription in the caecal mucosa of all horses. Mucosal synthesis of antibodies was confirmed by the demonstration of A. perfoliata-specific IgG(T) and IgE in the supernatant of lamina propria explant cultures that discriminated clearly between infected and uninfected horses. We conclude that there is an active immune response to A. perfoliata within the caecal mucosa involving local production of both IgG(T) and IgE antibody isotypes; but it remains unclear whether this immune response can reduce or eliminate parasite burden. PMID:24183646

  9. IgE reactivity to carbohydrate moieties of glycoproteins in wheat allergy.

    PubMed

    Song, Tae Won; Hong, Jung Yeon; Lee, Kyung Eun; Kim, Mi Na; Kim, Yoon Hee; Lee, Soo-Young; Kim, Kyung Won; Sohn, Myung Hyun; Kim, Kyu-Earn

    2015-01-01

    Carbohydrate moieties of different glycoproteins, such as cross-reactive carbohydrate determinants (CCDs) and galactose α-1,3-galactose, can induce IgE reactivity with varied clinical significance. In this study, the possible participation of glycan from wheat gliadin, with respect to its IgE-binding capacity, was investigated in children with food allergies to wheat. Total IgE and wheat-specific IgE quantification, documentation of history, and/or oral food challenge (OFC) were performed for 52 children. Subjects with positive wheat-specific IgE were characterized as the symptomatic group, never-exposed group, or asymptomatic group. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and glycan detection in gliadin were performed. IgE binding to gliadin and deglycosylated gliadin was measured by immunoblotting and ELISA. Gliadin-specific IgE was detected and correlated with wheat-specific IgE in the symptomatic, never-exposed, and asymptomatic groups. The glycan range overlapped significantly with the gliadin range. Deglycosylation of gliadin reduced the allergenicity of gliadin. In gliadin, the allergenicity of the glycan portion was greater in the symptomatic group than in the never-exposed and asymptomatic groups. We conclude that N-glycan in gliadin might exhibit allergenicity as a possible carbohydrate epitope in wheat allergy in children. PMID:25976436

  10. IgE reactivity to carbohydrate moieties of glycoproteins in wheat allergy

    PubMed Central

    Song, Tae Won; Hong, Jung Yeon; Lee, Kyung Eun; Kim, Mi Na; Kim, Yoon Hee; Lee, Soo-Young; Kim, Kyung Won

    2015-01-01

    Carbohydrate moieties of different glycoproteins, such as cross-reactive carbohydrate determinants (CCDs) and galactose α-1,3-galactose, can induce IgE reactivity with varied clinical significance. In this study, the possible participation of glycan from wheat gliadin, with respect to its IgE-binding capacity, was investigated in children with food allergies to wheat. Total IgE and wheat-specific IgE quantification, documentation of history, and/or oral food challenge (OFC) were performed for 52 children. Subjects with positive wheat-specific IgE were characterized as the symptomatic group, never-exposed group, or asymptomatic group. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and glycan detection in gliadin were performed. IgE binding to gliadin and deglycosylated gliadin was measured by immunoblotting and ELISA. Gliadin-specific IgE was detected and correlated with wheat-specific IgE in the symptomatic, never-exposed, and asymptomatic groups. The glycan range overlapped significantly with the gliadin range. Deglycosylation of gliadin reduced the allergenicity of gliadin. In gliadin, the allergenicity of the glycan portion was greater in the symptomatic group than in the never-exposed and asymptomatic groups. We conclude that N-glycan in gliadin might exhibit allergenicity as a possible carbohydrate epitope in wheat allergy in children. PMID:25976436

  11. Genetic basis of IgE responsiveness: relevance to the atopic diseases.

    PubMed

    Marsh, D G; Neely, J D; Breazeale, D R; Ghosh, B; Freidhoff, L R; Schou, C; Beaty, T H

    1995-01-01

    Genetic analysis of 170 subjects in 11 extended Amish families revealed evidence for linkage of five markers in chromosome 5q31.1 with a gene controlling total serum IgE levels. No linkage was found between these markers and specific IgE antibody levels. Analysis of total IgE within a subset of 128 IgE-antibody-negative sib pairs confirmed evidence for linkage to 5q31.1, especially IL4 (p = 4 x 10(-6)). These and other data suggest that IL4 or a nearby gene regulates IgE production in a non-antigen-specific (noncognate) fashion and provide evidence for a possible link between asthma and the IL4 gene. PMID:7613143

  12. Increased IgE antibody responses in rats exposed to tobacco smoke

    SciTech Connect

    Zetterstroem, O.N.; Nordvall, S.L.; Bjoerksten, B.A.; Ahlstedt, S.; Stelander, M.

    1985-05-01

    Raised serum IgE levels were found in a high proportion of rats that had been exposed to tobacco smoke twice daily 5 days a week for 8 wk in a Dontenville-type smoking machine. Levels above 1 ng/ml of IgE were found in nine of 20 animals exposed to cigarette smoke and in five of 20 rats exposed to smoke from cigarettes with 1.45% phenylmethyloxidiazole added for possible protection against the effects of the smoke. None of the 20 control rats exhibited similarly increased serum IgE. Exposure to tobacco smoke did not significantly affect the serum concentrations of IgM and IgG. The development of specific IgE and IgG antibodies was also influenced by tobacco smoke exposure. Rats exposed to ovalbumin aerosol developed increased levels of IgG and IgE antibodies, whereas no effect on the development of antibody titers was found in rats immunized by the subcutaneous route. This study demonstrates that exposure to tobacco smoke increases serum IgE levels and enhances sensitization via the airways by a local effect, thus supporting the mucosal theory of atopy.

  13. Pulsed Ultraviolet Light Reduces Immunoglobulin E Binding to Atlantic White Shrimp (Litopenaeus setiferus) Extract

    PubMed Central

    Shriver, Sandra; Yang, Wade; Chung, Si-Yin; Percival, Susan

    2011-01-01

    Pulsed ultraviolet light (PUV), a novel food processing and preservation technology, has been shown to reduce allergen levels in peanut and soybean samples. In this study, the efficacy of using PUV to reduce the reactivity of the major shrimp allergen, tropomyosin (36-kDa), and to attenuate immunoglobulin E (IgE) binding to shrimp extract was examined. Atlantic white shrimp (Litopenaeus setiferus) extract was treated with PUV (3 pulses/s, 10 cm from light source) for 4 min. Tropomyosin was compared in the untreated, boiled, PUV-treated and [boiled+PUV]-treated samples, and changes in the tropomyosin levels were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). IgE binding of the treated extract was analyzed via immunoblot and enzyme-linked immunosorbent assay (ELISA) using pooled human plasma containing IgE antibodies against shrimp allergens. Results showed that levels of tropomyosin and IgE binding were reduced following PUV treatment. However, boiling increased IgE binding, while PUV treatment could offset the increased allergen reactivity caused by boiling. In conclusion, PUV treatment reduced the reactivity of the major shrimp allergen, tropomyosin, and decreased the IgE binding capacity of the shrimp extract. PMID:21845146

  14. Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: an in vitro study.

    PubMed

    Siman, Isabella Lima; de Aquino, Lais Martins; Ynoue, Leandro Hideki; Miranda, Juliana Silva; Pajuaba, Ana Claudia Arantes Marquez; Cunha-Júnior, Jair Pereira; Silva, Deise Aparecida Oliveira; Taketomi, Ernesto Akio

    2013-01-01

    One of the purposes of specific immunotherapy (SIT) is to modulate humoral immune response against allergens with significant increases in allergen-specific IgG levels, commonly associated with blocking activity. The present study investigated in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to Dermatophagoides pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were purified by ammonium sulfate precipitation followed by protein-G affinity chromatography. Purity was checked by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretic profile of the ammonium sulfate precipitated fraction showed strongly stained bands in ligand fraction after chromatography, compatible with molecular weight of human whole IgG molecule. The purity degree was confirmed by detecting strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable of significantly reducing levels of IgE anti-Dpt, resulting in 35%-51% inhibition of IgE reactivity to Dpt in atopic patients sera. This study showed that allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens. This approach reinforces that intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT. PMID:24069042

  15. Synergistic topical application of salt-processed Phellodendron amurense and Sanguisorba officinalis Linne alleviates atopic dermatitis symptoms by reducing levels of immunoglobulin E and pro-inflammatory cytokines in NC/Nga mice.

    PubMed

    Park, Sunmin; Kim, Da Sol; Kang, Suna; Shin, Bae Keun

    2015-11-01

    Atopic dermatitis is a chronic inflammatory skin disease, and salt-processed Phellodendron amurense (CPE) and Sanguisorba officinalis Linne (SOE) are widely used as anti-inflammatory agents in Asia. Therefore, the present study investigated the efficacy of CPE, SOE, and CPE+SOE in the treatment of atopic dermatitis-like symptoms in mice. Following topical application of 1,3‑butylen glycol (control), 30% CPE, 30% SOE, 15% CPE+15% SOE or 0.1% hydrocortisone (HC) on the atopic dermatitis‑like skin lesions of 2,4-dinitrochlorobenzene‑treated NC/Nga mice for 5 weeks, the severity of clinical atopic dermatitis, mast cell infiltration, serum expression levels of immunoglobulin (Ig)E, IgG1, interleukin (IL)-4 and interferon (IFN)-γ, and cytokine expression in the dorsal skin were measured. Compared with the control group, treatment with CPE alleviated the clinical severity of the AD symptoms, with decreased numbers of mast cells, decreased expression levels of serum tumor necrosis factor (TNF)‑α, IL‑4 and IFN‑γ, and decreased expression levels of inflammatory cytokines in the dorsal lesions. Treatment with SOE did not reduce these expression levels, however, the serum expression levels of IgE and IgG1 were suppressed to similar levels as those in the CPE group. Furthermore, synergistic treatment with CPE and SOE relieved the clinical severity of atopic dermatitis, reduced the serum expression levels of IgE, IgG1, TNF‑α, IL‑4 and IFN‑γ, and suppressed the mRNA expression levels of TNF‑α, IL‑4, IL‑13, and IFN‑γ in the dorsal skin lesions. Treatment with CPE+SOE was superior to treatment with HC alone for reducing dermal thickness and suppressing the production of several cytokines. Therefore, combined treatment with CPE and SOE may be an effective alternative intervention for the management of atopic dermatitis. PMID:26397864

  16. Potentiation of IgE responses to third-party antigens mediated by Ascaris suum soluble products.

    PubMed

    Lee, T D; McGibbon, A

    1993-01-01

    A reductive approach was used to examine the potentiation of IgE responses by nematode infection. Ascaris homogenized extract, Ascaris pseudocoelomic (body) fluid (ABF) and purified Ascaris allergen (ABA) were tested for their ability to act as protein carriers and as mediators of potentiated IgE responses to third-party (ovalbumin; OVA) responses. All three nematode products were excellent protein carriers for the hapten dinitrophenol and showed significantly better activity in this respect than OVA. Neither ABF nor ABA enhanced the level of the IgE response to the third-party antigen but both prolonged the response markedly. ABF, but not ABA, induced high levels of total circulating IgE when given at the same time as OVA with alum. The data suggest that the enhancement and prolongation of IgE responses by nematodes may be two separate but related activities. PMID:8400897

  17. Should milk-specific IgE antibodies be measured in adults in primary care?

    PubMed Central

    Anthoni, Sari; Elg, Peter; Haahtela, Tari; Kolho, Kaija-Leena

    2008-01-01

    Objective To study the association of milk-IgE antibodies in serum to milk-related gastrointestinal symptoms in adults in primary care. Design Open clinical study. Setting Five outpatient clinics in primary care in Southern Finland. Subjects A total of 756 subjects who reported milk-related gastrointestinal symptoms in primary care and as controls 101 subjects with no such symptoms. Methods IgE values for specific food antigens were measured (Pharmacia CAP System) in a total of 857 subjects. All food screen-positive samples (>0.35 IU/l) were analysed further for IgE for untreated skimmed milk (milk-IgE) and for boiled milk. Those found positive for milk-IgE were invited for an open milk challenge test. Results Some 5.4% (46/857) of all subjects had a positive IgE antibody screen for food antigens. Of those with a positive food screen, 28% (13/46) had milk-IgE antibodies comprising 1.5% of the total group screened. The prevalence of milk-IgE was not statistically different between those with milk-related symptoms and those with no such symptoms. IgE antibodies for boiled milk were rare. All specific IgE antibody levels were low. Bloating was the only observed symptom in milk challenge tests. Conclusion IgE antibodies to cow's milk were relatively rare in the adult population and were not indicative of milk protein allergy. The observed IgE levels were low and did not correlate with subjective milk-related symptoms. The measurement of milk-specific IgE in adults should be discouraged in outpatient clinics. PMID:18609255

  18. Soluble IgE receptors – elements of the IgE network

    PubMed Central

    Platzer, Barbara; Ruiter, Floortje; van der Mee, John; Fiebiger, Edda

    2011-01-01

    Soluble isoforms of three human IgE Fc receptors, namely FcεRI, FcεRII and galectin-3, can be found in serum. These soluble IgE receptors are a diverse family of proteins unified by the characteristic of interacting with IgE in the extracellular matrix. A truncated form of the alpha-chain of FcεRI, the high affinity IgE receptor, has recently been described as a soluble isoform (sFcεRI). Multiple soluble isoforms of CD23 (sCD23), the low affinity IgE receptor also known as FcεRII, are generated via different mechanisms of extracellular and intracellular proteolysis. The second low affinity IgE receptor, galectin-3, only exists as a secretory protein. We here discuss the physiological roles of these three soluble IgE receptors as elements of the human IgE network. Additionally, we review the potential and current use of sFcεRI, sCD23 and galectin-3 as biomarkers in human disease. PMID:21920387

  19. Role of IgE in autoimmunity.

    PubMed

    Sanjuan, Miguel A; Sagar, Divya; Kolbeck, Roland

    2016-06-01

    There is accumulating evidence to suggest that IgE plays a significant role in autoimmunity. The presence of circulating self-reactive IgE in patients with autoimmune disorders has been long known but, at the same time, largely understudied. However, studies have shown that the increased IgE concentration is not associated with higher prevalence for atopy and allergy in patients with autoimmune diseases, such as systemic lupus erythematosus. IgE-mediated mechanisms are conventionally known to facilitate degranulation of mast cells and basophils and promote TH2 immunity, mechanisms that are not only central to mounting an appropriate defense against parasitic worms, noxious substances, toxins, venoms, and environmental irritants but that also trigger exuberant allergic reactions in patients with allergies. More recently, IgE autoantibodies have been recognized to participate in the self-inflicted damaging immune responses that characterize autoimmunity. Such autoimmune responses include direct damage on tissue-containing autoantigens, activation and migration of basophils to lymph nodes, and, as observed most recently, induction of type 1 interferon responses from plasmacytoid dendritic cells. The importance of IgE as a central pathogenic mechanism in autoimmunity has now been clinically validated by the approval of omalizumab, an anti-IgE mAb, for patients with chronic spontaneous urticaria and for the clinical benefit of patients with bullous pemphigoid. In this review we summarize recent reports describing the prevalence of self-reactive IgE and discuss novel findings that incriminate IgE as central in the pathogenesis of inflammatory autoimmune disorders. PMID:27264000

  20. IgE responses in mouse and man and the persistence of IgE memory.

    PubMed

    Gould, Hannah J; Ramadani, Faruk

    2015-01-01

    Rapid and robust recall or 'memory' responses are an essential feature of adaptive immunity. They constitute a defense against reinfection by pathogens, yet arguably do more harm than good in allergic disease. Immunoglobulin (Ig)E antibodies mediate the allergic reaction characterized by immediate hypersensitivity, a manifestation of IgE memory. The origin of IgE memory remains obscure, mainly due to the low proportion of IgE-expressing B cells in the total B cell population. The recent development of ultrasensitive methods for tracking these cells in vivo has overcome this obstacle, and their use has revealed unexpected pathways to IgE memory in the mouse. Here, we review these findings and consider their bearing on our understanding of IgE memory and allergic disease in man. PMID:25499855

  1. Human IgE is efficiently produced in glycosylated and biologically active form in lepidopteran cells.

    PubMed

    Bantleon, Frank; Wolf, Sara; Seismann, Henning; Dam, Svend; Lorentzen, Andrea; Miehe, Michaela; Jabs, Frederic; Jakob, Thilo; Plum, Melanie; Spillner, Edzard

    2016-04-01

    TH2-biased immunity to parasites and allergens is often associated with increased levels of antigen-specific and high affinity IgE. The role in reacting against minute amounts of target structures and to provoke severe anaphylactic reactions renders IgE a mechanistically outstanding isotype. IgE represents the least abundant serum antibody isotype and exhibits a variety of peculiarities including structure, extensive glycosylation and effector functions. Despite large progress in antibody technologies, however, the recombinant access to isotypes beyond IgG such as IgE still is scarce. The capacity of expression systems has to meet the complex structural conformations and the extensive posttranslational modifications that are indispensable for biological activity. In order to provide alternatives to mammalian expression systems with often low yield and a more complex glycosylation pattern we established the recombinant production of the highly complex IgE isotype in insect cells. Recombinant IgE (rIgE) was efficiently assembled and secreted into the supernatant in yields of >30 mg/L. Purification from serum free medium using different downstream processing methods provided large amounts of rIgE. This exhibited a highly specific interaction with its antigen, therapeutic anti-IgE and its high affinity receptor, the FcεRI. Lectins and glyco-proteomic analyses proved the presence of prototypic insect type N-glycans on the epsilon heavy chain. Mediator release assays demonstrated a biological activity of the rIgE comparable to IgE derived from mammalian cells. In summary the expression in insect cells provides rIgE with variant glycosylation pattern, but retained characteristics and biological activity. Therefore our data contribute to the understanding of functional and structural aspects and potential use of the IgE isotype. PMID:26943931

  2. Diagnostic Utility of Total IgE in Foods, Inhalant, and Multiple Allergies in Saudi Arabia

    PubMed Central

    Al-Mughales, Jamil A.

    2016-01-01

    Objective. To assess the diagnostic significance of total IgE in foods, inhalant, and multiple allergies. Methods. Retrospective review of the laboratory records of patients who presented with clinical suspicion of food or inhalant allergy between January 2013 and December 2014. Total IgE level was defined as positive for a value >195 kU/L; and diagnosis was confirmed by the detection of specific IgE (golden standard) for at least one food or inhalant allergen and at least two allergens in multiple allergies. Results. A total of 1893 (male ratio = 0.68, mean age = 39.0 ± 19.2 years) patients were included. Total IgE had comparable sensitivity (55.8% versus 59.6%) and specificity (83.9% versus 84.4%) in food versus inhalant allergy, respectively, but a superior PPV in inhalant allergy (79.1% versus 54.4%). ROC curve analysis showed a better diagnostic value in inhalant allergies (AUC = 0.817 (95% CI = 0.796–0.837) versus 0.770 (95% CI = 0.707–0.833)). In multiple allergies, total IgE had a relatively good sensitivity (78.6%), while negative IgE testing (<195 kU/L) predicted the absence of multiple allergies with 91.5% certitude. Conclusion. Total IgE assay is not efficient as a diagnostic test for foods, inhalant, or multiple allergies. The best strategy should refer to specific IgE testing guided by a comprehensive atopic history. PMID:27314052

  3. IGES transformer and NURBS in grid generation

    NASA Technical Reports Server (NTRS)

    Yu, Tzu-Yi; Soni, Bharat K.

    1993-01-01

    In the field of Grid Generation and the CAD/CAM, there are numerous geometry output formats which require the designer to spend a great deal of time manipulating geometrical entities in order to achieve a useful sculptured geometrical description for grid generation. Also in this process, there is a danger of losing fidelity of the geometry under consideration. This stresses the importance of a standard geometry definition for the communication link between varying CAD/CAM and grid system. The IGES (Initial Graphics Exchange Specification) file is a widely used communication between CAD/CAM and the analysis tools. The scientists at NASA Research Centers - including NASA Ames, NASA Langley, NASA Lewis, NASA Marshall - have recognized this importance and, therefore, in 1992 they formed the committee of the 'NASA-IGES' which is the subset of the standard IGES. This committee stresses the importance and encourages the CFD community to use the standard IGES file for the interface between the CAD/CAM and CFD analysis. Also, two of the IGES entities -- the NURBS Curve (Entity 126) and NURBS Surface (Entity 128) -- which have many useful geometric properties -- like the convex hull property, local control property and affine invariance, also widely utilized analytical geometries can be accurately represented using NURBS. This is important in today grid generation tools because of the emphasis of the interactive design. To satisfy the geometry transformation between the CAD/CAM system and Grid Generation field, the CAGI (Computer Aided Geometry Design) developed, which include the Geometry Transformation, Geometry Manipulation and Geometry Generation as well as the user interface. This paper will present the successful development IGES file transformer and application of NURBS definition in the grid generation.

  4. Co-stimulation of T cells via CD28 inhibits human IgE production; reversal by pertussis toxin.

    PubMed Central

    Van der Pouw-Kraan, C T; Rensink, H J; Rappuoli, R; Aarden, L A

    1995-01-01

    In lymphocyte cultures, IgE production was achieved by stimulating T cells with anti-CD2 and IL-2. Here we show that anti-CD28, in the presence or absence of IL-2, reduces this IgE production approximately 10-fold. This inhibition of IgE production was almost completely reversed by Pertussis toxin (PT). PT had no effect on IgE production when the cells were stimulated in the absence of anti-CD28. No major effects of PT were found on IgM production. PT had no effect on purified B cells, stimulated with IL-4 and anti-CD40. In the presence of saturating amounts of rIL-4 similar results were obtained, albeit the absolute amounts of IgE produced were higher in all situations. Furthermore, PT-induced IgE production was still dependent on IL-4, as was evident from experiments in which anti-IL-4 was added to the culture. The IgE enhancing effect was dependent on the adenosine diphosphate (ADP)-ribosyltransferase activity of PT, because a mutant molecule lacking this activity was not able to restore anti-CD28-induced inhibition of IgE synthesis. Thus, we show that co-stimulation with anti-CD28 causes an inhibition of T cell-dependent IgE production by B cells, which inhibition can be specifically overcome by PT. An analysis of the molecular pathways underlying this phenomenon may contribute to our understanding of the regulation of IgE synthesis in (patho)physiological conditions. PMID:7882571

  5. Progressive Cross-Reactivity in IgE Responses: an Explanation for the Slow Development of Human Immunity to Schistosomiasis?

    PubMed Central

    Jones, Frances M.; Pinot de Moira, Angela; Protasio, Anna V.; Khalife, Jamal; Dickinson, Harriet A.; Tukahebwa, Edridah M.; Dunne, David W.

    2012-01-01

    People in regions of Schistosoma mansoni endemicity slowly acquire immunity, but why this takes years to develop is still not clear. It has been associated with increases in parasite-specific IgE, induced, some investigators propose, to antigens exposed during the death of adult worms. These antigens include members of the tegumental-allergen-like protein family (TAL1 to TAL13). Previously, in a group of S. mansoni-infected Ugandan males, we showed that IgE responses to three TALs expressed in worms (TAL1, -3, and -5) became more prevalent with age. Now, in a subcohort we examined associations of these responses with resistance to reinfection and use the data to propose a mechanism for the slow development of immunity. IgE was measured 9 weeks posttreatment and at reinfection at 2 years (n = 144). An anti-TAL5 IgE (herein referred to as TAL5 IgE) response was associated with reduced reinfection even after adjusting for age using regression analysis (geometric mean odds ratio, 0.24; P = 0.016). TAL5 IgE responders were a subset of TAL3 IgE responders, themselves a subset of TAL1 responders. TAL3 IgE and TAL5 IgE were highly cross-reactive, with TAL3 the immunizing antigen and TAL5 the cross-reactive antigen. Transcriptional and translational studies show that TAL3 is most abundant in adult worms and that TAL5 is most abundant in infectious larvae. We propose that in chronic schistosomiasis, older individuals have repeatedly experienced IgE antigens exposed when adult worms die (e.g., TAL3) and that this leads to increasing cross-reactivity with antigens of invading larvae (e.g., TAL5). Progressive accumulation of worm/larvae cross-reactivity could explain the age-dependent immunity observed in areas of endemicity. PMID:23006852

  6. Helminth infection alters IgE responses to allergens structurally related to parasite proteins

    PubMed Central

    Santiago, Helton da Costa; Ribeiro-Gomes, Flávia L.; Bennuru, Sasisekhar; Nutman, Thomas B.

    2014-01-01

    Immunological cross-reactivity between environmental allergens and helminth proteins has been demonstrated, though the clinically-related implications of this cross-reactivity have not been addressed. To investigate the impact of molecular similarity among allergens and cross-reactive homologous helminth proteins in IgE-based serologic assessment of allergic disorders in helminth-infected population, we performed Immunocap™ tests in filarial-infected and non-infected individuals for IgE measurements to allergen extracts that contained proteins with high levels of homology with helminth proteins and IgE against representative recombinant allergens with and without helminth homologues were performed. The impact of helminth infection on the levels and function of the IgE to these specific homologous and non-homologous allergens was corroborated in an animal model. We found that having a tissue-invasive filarial infection increased the serological prevalence of Immunocap™ identified IgE directed against house dust mite and cockroach, but not against timothy grass, the latter with few allergens with homologues in helminth infection. IgE ELISA confirmed that filaria-infected individuals had higher IgE prevalences to those recombinant allergens that had homologues in helminths. Mice infected with helminth Heligmosomoides polygyrus displayed increased levels of IgE and positive skin tests to allergens with homologues in the parasite. These results show that cross-reactivity among allergens and helminth proteins can have practical implications altering serologic approaches to allergen testing and brings a new perspective to the Hygiene Hypothesis. PMID:25404363

  7. Helminth infection alters IgE responses to allergens structurally related to parasite proteins.

    PubMed

    Santiago, Helton da Costa; Ribeiro-Gomes, Flávia L; Bennuru, Sasisekhar; Nutman, Thomas B

    2015-01-01

    Immunological cross-reactivity between environmental allergens and helminth proteins has been demonstrated, although the clinically related implications of this cross-reactivity have not been addressed. To investigate the impact of molecular similarity among allergens and cross-reactive homologous helminth proteins in IgE-based serologic assessment of allergic disorders in a helminth-infected population, we performed ImmunoCAP tests in filarial-infected and noninfected individuals for IgE measurements to allergen extracts that contained proteins with high levels of homology with helminth proteins as well as IgE against representative recombinant allergens with and without helminth homologs. The impact of helminth infection on the levels and function of the IgE to these specific homologous and nonhomologous allergens was corroborated in an animal model. We found that having a tissue-invasive filarial infection increased the serological prevalence of ImmunoCAP-identified IgE directed against house dust mite and cockroach, but not against timothy grass, the latter with few allergens with homologs in helminth infection. IgE ELISA confirmed that filaria-infected individuals had higher IgE prevalences to those recombinant allergens that had homologs in helminths. Mice infected with the helminth Heligmosomoides polygyrus displayed increased levels of IgE and positive skin tests to allergens with homologs in the parasite. These results show that cross-reactivity among allergens and helminth proteins can have practical implications, altering serologic approaches to allergen testing and bringing a new perspective to the "hygiene hypothesis." PMID:25404363

  8. Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma

    PubMed Central

    Commins, Scott P.; Kelly, Libby A.; Rönmark, Eva; James, Hayley R.; Pochan, Shawna L.; Peters, Edward J.; Lundbäck, Bo; Nganga, Lucy W.; Cooper, Philip J.; Hoskins, Janelle M.; Eapen, Saju S.; Matos, Luis A.; McBride, Dane C.; Heymann, Peter W.; Woodfolk, Judith A.; Perzanowski, Matthew S.

    2012-01-01

    Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract. Objectives: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens. Methods: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131). Measurements and Main Results: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001). Conclusions: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled. PMID:22281828

  9. Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid.

    PubMed

    Messingham, Kelly N; Holahan, Heather M; Frydman, Alexandra S; Fullenkamp, Colleen; Srikantha, Rupasree; Fairley, Janet A

    2014-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE ≥ 400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils. PMID:25255430

  10. Low level laser therapy reduces inflammation in activated Achilles tendinitis

    NASA Astrophysics Data System (ADS)

    Bjordal, Jan M.; Iversen, Vegard; Lopes-Martins, Rodrigo Alvaro B.

    2006-02-01

    Objective: Low level laser therapy (LLLT) has been forwarded as therapy for osteoarthritis and tendinopathy. Results in animal and cell studies suggest that LLLT may act through a biological mechanism of inflammatory modulation. The current study was designed to investigate if LLLT has an anti-inflammatory effect on activated tendinitis of the Achilles tendon. Methods: Seven patients with bilateral Achilles tendonitis (14 tendons) who had aggravated symptoms by pain-inducing activity immediately prior to the study. LLLT (1.8 Joules for each of three points along the Achilles tendon with 904nm infrared laser) and placebo LLLT were administered to either Achilles tendons in a random order to which patients and therapist were blinded. Inflammation was examined by 1) mini-invasive microdialysis for measuring the concentration of inflammatory marker PGE II in the peritendinous tissue, 2) ultrasound with Doppler measurement of peri- and intratendinous blood flow, 3) pressure pain algometry and 4) single hop test. Results: PGE 2- levels were significantly reduced at 75, 90 and 105 minutes after active LLLT compared both to pre-treatment levels (p=0.026) and to placebo LLLT (p=0.009). Changes in pressure pain threshold (PPT) were significantly different (P=0.012) between groups. PPT increased by a mean value of 0.19 kg/cm2 [95%CI:0.04 to 0.34] after treatment in the active LLLT group, while pressure pain threshold was reduced by -0.20 kg/cm2 [95%CI:-0.45 to 0.05] after placebo LLLT. Conclusion: LLLT can be used to reduce inflammatory musculskeletal pain as it reduces inflammation and increases pressure pain threshold levels in activity-induced pain episodes of Achilles tendinopathy.

  11. Flagellin modulates IgE expression in B cells to initiate food allergy in mice

    PubMed Central

    Li, Lin-Jing; Ma, Na; Zeng, Lu; Mo, Li-Hua; Li, Xiao-Xi; Xu, Ling-Zhi; Yang, Bo; Liu, Zhi-Gang; Feng, Bai-Sui; Zheng, Peng-Yuan; Zhang, Huan-Ping; Yang, Ping-Chang

    2016-01-01

    The initiation mechanism of IgE expression has not been fully understood. Flagellin (FGN) is an important microbial factor in the regulation of immune responses in the intestine. This study tests a hypothesis that FGN plays a crucial role in the isotype switching of IgE in B cells and the initiation of food allergy. In this study, the expression of IgE in B cells was analyzed by real time RT-PCR, Western blotting and chromatin immunoprecipitation. A mouse model was developed to assess the role of Toll like receptor-5 in the development of IgE-mediated allergic reaction in the intestinal mucosa. The results showed that exposure to FGN suppressed the expression of Bcl6 in B cells via increasing the levels of histone deacetylase (HDAC) 7; the latter up regulated the levels of methylated H3K9 and H3K27, down regulated RNA polymerase II and STAT3 (signal transducer and activator of transcription 3) at the Bcl6 promoter locus. Exposure to FGN and IL-4 markedly increased the expression of IgE in B cells via activating p300, H3K4, Pol II and STAT6 at the IgE promoter locus. As compared with the sensitized wild mice, the sensitized TLR5-deficient mice showed no detectable OVA-specific IgE in the serum; mast cells in the intestinal mucosa were not activated, no apparent allergic symptoms were evoked after the specific antigen challenge. In conclusion, FGN facilitates the initiation of food allergy in mice by triggering IgE transcription in B cells in a Th2 polarization environment via activating HDAC7 and suppressing Bcl6 expression. PMID:27398157

  12. IgE Immunoadsorption Knocks Down the Risk of Food-Related Anaphylaxis.

    PubMed

    Dahdah, Lamia; Ceccarelli, Stefano; Amendola, Silvia; Campagnano, Pietro; Cancrini, Caterina; Mazzina, Oscar; Fiocchi, Alessandro

    2015-12-01

    The effects of an immunoadsorption procedure, specifically designed to remove immunoglobulin E (IgE), on food-induced anaphylaxis have never been evaluated. We evaluate the effects of IgE removal on the allergic thresholds to foods. A 6-year-old boy with anaphylaxis to multiple foods and steroid-resistant unstable allergic asthma displayed serum IgE levels of 2800 to 3500 kU/L. To lower IgE serum concentrations, which could be overridden by a high dose of omalizumab, 1.5 plasma volumes were exchanged in 8 apheresis sessions. During the procedure, serum IgE levels fell to 309 kU/L. After the procedure, the threshold of reactivity to baked milk increased from 0.125 to 5 g of milk protein (full tolerance) after the first session, and the threshold of reactivity to hazelnut increased from 0.037 to 0.142 g of protein after the first session, 0.377 g after the eighth, and 1.067 g (full tolerance) after the first administration of omalizumab. Immediately after the sixth IgE immunoadsorption, we started omalizumab therapy. In the next 40 days, the threshold of reactivity to hazelnut increased to 7.730 (full tolerance). Asthma control was obtained, treatment with montelukast was stopped, and fluticasone was tapered from 500 to 175 μg/day. The boy became partially or fully tolerant to all the tested foods, and quality of life was improved. IgE immunoadsorption, used to establish the starting basis for omalizumab administration, is able to increase the tolerance threshold to foods. PMID:26620068

  13. The Prevalence of Serum Specific IgE to Superantigens in Asthma and Allergic Rhinitis Patients.

    PubMed

    Liu, Jing Nan; Shin, Yoo Seob; Yoo, Hye-Soo; Nam, Young Hee; Jin, Hyun Jung; Ye, Young-Min; Nahm, Dong-Ho; Park, Hae-Sim

    2014-05-01

    Staphylococcus aureus is the most common bacterium present in upper respiratory tract, and the toxins it produced are involved in allergic inflammation pathogenesis. In this study, we investigated the clinical significance of IgE in association with staphylococcal superantigens in allergic asthma with rhinitis (BAwAR) and allergic rhinitis alone (AR). We recruited 100 patients with BAwAR (group I), 100 patients with AR (group II), and 88 healthy controls (group III). Patients were clinically diagnosed by physicians, and were sensitized to house dust mites. Specific IgE antibodies to staphylococcal superantigen A (SEA), B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured using the ImmunoCAP system. Other clinical parameters were retrospectively analyzed. All specific IgE antibodies to SEA, SEB, and TSST-1 were detected most frequently in group I (22%, 21%, and 27%), followed by group II (11%, 14%, and 21%) and group III (4.5%, 3.4%, and 2.3%). Absolute values of serum specific IgE to SEA, SEB, and TSST-1 were also significantly higher in group I (0.300±1.533 kU/L, 0.663±2.933 kU/L, and 0.581±1.931 kU/L) and group II (0.502±2.011 kU/L, 0.695±3.337 kU/L, and 1.067±4.688 kU/L) compared to those in group III (0.03±0.133 kU/L, 0.03±0.14 kU/L, and 0.028±0.112 kU/L). The prevalence of serum specific IgE to SEA was significantly higher in group I compared to group II (P=0.025). Blood eosinophil counts were significantly higher in patients with specific IgE to SEA or SEB, and higher serum levels of specific IgE to house dust mites were noted in patients with specific IgE to TSST-1. In conclusion, the present study suggested that IgE responses to staphylococcal superantigens are prevalent in the sera of both BAwAR and AR patients. This may contribute to an augmented IgE response to indoor allergens and eosinophilic inflammation. PMID:24843803

  14. Autoimmune Hepatitis in Brazilian Children: IgE and Genetic Polymorphisms in Associated Genes

    PubMed Central

    de Oliveira, Léa Campos; Goldberg, Anna Carla; Marin, Maria Lucia Carnevale; Schneidwind, Karina Rosa; Frade, Amanda Farage; Kalil, Jorge; Miura, Irene Kasue; Pugliese, Renata Pereira Sustovich; Danesi, Vera Lucia Baggio; Porta, Gilda

    2015-01-01

    Pediatric autoimmune hepatitis (AIH) patients present hypergammaglobulinemia, periportal CD8+ cytotoxic T cell infiltration, and cirrhosis. Autoantibody profile defines AIH types 1 and 2 in addition to strong association with HLA-DRB1. We previously detected increased IgE serum levels and sought to compare clinical and histological features according to IgE levels in AIH (n = 74, ages 1–14 years) patients. Additionally, we typed 117 patients and 227 controls for functional polymorphisms of IL4, IL13, IL5, and IL4RA genes involved in IgE switching and eosinophil maturation that might contribute to overall genetic susceptibility to AIH. Serum IgE levels were high in 55% of AIH-1, but only in 12% of AIH-2 (P = 0.003) patients. Liver IgE was present in 91.3% of AIH-1 patients. The A alleles at both IL13 rs20541 and IL4RA rs1805011 were associated with AIH-1 (P = 0.024, OR = 1.55 and P < 0.0001, OR = 2.15, resp.). Furthermore, individuals presenting homozygosis for the A allele at IL4RA rs1805011 and HLA-DRB1∗03 and/or ∗13 allele had sixfold greater risk to develop the disease (OR = 14.00, P < 0.001). The novel association suggests an additional role for IgE-linked immune response genes in the pathogenesis of AIH. PMID:26693492

  15. Low stimulus environments: reducing noise levels in continuing care.

    PubMed

    Brown, Juliette; Fawzi, Waleed; Shah, Amar; Joyce, Margaret; Holt, Genevieve; McCarthy, Cathy; Stevenson, Carmel; Marange, Rosca; Shakes, Joy; Solomon-Ayeh, Kwesi

    2016-01-01

    In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi-disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to

  16. Low stimulus environments: reducing noise levels in continuing care

    PubMed Central

    Brown, Juliette; Fawzi, Waleed; Shah, Amar; Joyce, Margaret; Holt, Genevieve; McCarthy, Cathy; Stevenson, Carmel; Marange, Rosca; Shakes, Joy; Solomon-Ayeh, Kwesi

    2016-01-01

    In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi-disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to

  17. Serum IgE and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

    PubMed Central

    Olson, Sara H.; Hsu, Meier; Wiemels, Joseph L.; Bracci, Paige M.; Zhou, Mi; Patoka, Joseph; Reisacher, William I.; Wang, Julie; Kurtz, Robert C.; Silverman, Debra T.; Stolzenberg-Solomon, Rachael Z.

    2014-01-01

    Epidemiologic studies have consistently found that self-reported allergies are associated with reduced risk of pancreatic cancer. Our aim was to prospectively assess the relationship between serum IgE, a marker of allergy, and risk. This nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) included subjects enrolled in 1994-2001 and followed through 2010. There were 283 cases of pancreatic cancer and 544 controls matched on age, gender, race, and calendar date of blood draw. Using the ImmunoCAP system, we measured total IgE (normal, borderline, elevated), IgE to respiratory allergens, and IgE to food allergens (negative or positive) in serum collected at baseline. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. We assessed interactions with age, gender, smoking, body mass index, and time between randomization and case diagnosis. Overall, there was no association between the IgE measures and risk. We found a statistically significant interaction by baseline age: in those aged >65, elevated risks were observed for borderline total IgE (OR=1.43; 95% CI, 0.88-2.32) and elevated total IgE (OR=1.98; 95% CI, 1.16-3.37) and positive IgE to food allergens (OR=2.83; 95% CI, 1.29-6.20); among participants <65, ORs were <1. Other interactions were not statistically significant. The reduced risk of pancreatic cancer associated with self-reported allergies is not reflected in serum IgE. PMID:24718282

  18. IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids.

    PubMed

    Chung, Si-Yin; Reed, Shawndrika

    2015-01-01

    The objective of this study was to determine if D-amino acids (D-aas) bind and inhibit immunoglobulin E (IgE) binding to peanut allergens. D-aas such as D-Asp (aspartic acid), D-Glu (glutamic acid), combined D-[Asp/Glu] and others were each prepared in a cocktail of 9 other D-aas, along with L-amino acids (L-aas) and controls. Each sample was mixed with a pooled plasma from peanut-allergic donors, and tested by ELISA (enzyme-linked immunosorbent assay) and Western blots for IgE binding to peanut allergens. Results showed that D-[Asp/Glu] (4 mg/ml) inhibited IgE binding (75%) while D-Glu, D-Asp and other D-aas had no inhibitory effect. A higher inhibition was seen with D-[Asp/Glu] than with L-[Asp/Glu]. We concluded that IgE was specific for D-[Asp/Glu], not D-Asp or D-Glu, and that D-[Asp/Glu] was more reactive than was L-[Asp/Glu] in IgE inhibition. The finding indicates that D-[Asp/Glu] may have the potential for removing IgE or reducing IgE binding to peanut allergens in vitro. PMID:25053052

  19. Unsaturated fatty acids supplementation reduces blood lead level in rats.

    PubMed

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: "super lecithin" (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  20. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

    PubMed Central

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: “super lecithin” (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  1. Seasonal split influenza vaccine induced IgE sensitization against influenza vaccine.

    PubMed

    Nakayama, Tetsuo; Kumagai, Takuji; Nishimura, Naoko; Ozaki, Takao; Okafuji, Teruo; Suzuki, Eitaro; Miyata, Akiko; Okada, Kenji; Ihara, Toshiaki

    2015-11-01

    Although anaphylaxis is an extremely rare vaccine-associated adverse event, it occurred in young children following administration of the 2011/12 seasonal split influenza vaccine, which contained 2-phenoxyethanol as the preservative. These children had high levels of IgE antibodies against influenza vaccine components. We herein investigated why these children were sensitized. One hundred and seventeen series of serum samples were obtained immediately before, and one month after the first and second immunizations with the HA split vaccine of 2011/12. Forty-two sequential serum samples were collected in the acute and convalescent phases (2 and 4 weeks) after natural infection with H1N1 Pdm in 2009. IgE antibodies developed following the vaccination of young children with seasonal split vaccines, whereas no significant IgE response was observed following natural infection with H1N1 Pdm 2009. The prevalence of IgE antibodies was not influenced by outbreaks of H1N1 Pdm. Repeated immunization with the HA split vaccine induced IgE sensitization against the influenza vaccine irrespective of the H1N1, H3N2, or B influenza subtypes. The reasons why anaphylaxis only occurred in recipients of the influenza vaccine containing 2-phenoxyethanol are still being investigated, and the size distribution of antigen particles may have shifted to a slightly larger size. Since the fundamental reason was IgE sensitization, current split formulation for the seasonal influenza vaccine needs to be reconsidered to prevent the induction of IgE sensitization. PMID:26188254

  2. Ricin enhances IgE responses by inhibiting a subpopulation of early-activated IgE regulatory CD8+ T cells.

    PubMed Central

    Diaz-Sanchez, D; Lee, T H; Kemeny, D M

    1993-01-01

    Ricin, a toxic lectin from castor beans greatly enhances IgE responses to bee venom phospholipase A2 (PLA2) in high and low IgE responder strains of rat. The increase in IgE is accompanied by a 60% reduction in the number of CD8+ but not CD4+ T cells in the spleen. Optimal enhancement of IgE by ricin occurs when it is given at the same time as the antigen or 24 hr later, suggesting that it acts on cells which were activated as a consequence of immunization. Radio ligand-binding studies with 125I ricin were used to compare the number of ricin binding sites on CD4+ and CD8+ T cells. No difference was seen in either the affinity or the number of receptors for ricin on the CD4+ and CD8+ T cells of unimmunized rats. In contrast, CD8+ T cells taken from rats which had been immunized with 10 micrograms of PLA2 24 hr earlier demonstrated considerably more ricin receptors (3.9 x 10(7) +/- 2.2 x 10(6) binding sites/cell) than CD4+ T cells (3.19 x 10(6) +/- 1.08 x 10(6) binding sites/cell). However the affinity of the receptors for ricin was unchanged. Cytofluorographic analysis with fluorescein isothiocyanate (FITC)-labelled ricin confirmed these observations and indicated that increased ricin binding occurred on a subpopulation of CD8+ T cells. The effect of CD8+ T cells on IgE regulation was investigated by adoptive transfer. 1 x 10(8) highly purified (> 98%) splenic CD8+ T cells collected from Brown Norway rats 3 days after immunization with 10 micrograms of PLA2 were adoptively transferred to naive, syngeneic recipients. The IgE antibody response to PLA2 + A1(OH)3 seen in these animals was reduced by 91%. Adoptive transfer of CD4+ T cells from the same donor animals did not induce suppression and nor did adoptive transfer of CD8+ T cells from animals given both ricin and PLA2. However, when recipients of CD8+ T cells taken from rats immunized with PLA2 were immunized with a different antigen [ovalbumin (OVA)] and A1(OH)3 the IgE antibody response was also suppressed

  3. Cellular lesion responsible for exaggerated IgE synthesis accompanying allergic breakthrough

    SciTech Connect

    Marcelletti, J.F.; Katz, D.H.

    1989-05-01

    Appropriate levels of IgE are maintained by a cellular and molecular network composed of (1) a suppressive, Ly-1+, CD4+ T cell-dependent arm that is activated by inappropriate high levels of IgE and (2) an enhancing, CD8+ T cell-dependent arm that controls this suppression in a feedback regulatory manner. Ly-1+ T cells also function to counterbalance (inhibit) the activity of these latter CD8+ T cells. It has been previously shown that Ly-1+ T cells can reverse low-dose irradiation-induced enhancement of IgE antibody responses (i.e., allergic breakthrough). We have analyzed lymphocytes isolated from mice subjected to low-dose irradiation to determine which component of this network is defective in such animals. Stimulation of normal lymphocytes with IgE in vitro resulted in the release of lymphokines that suppress IgE antibody responses. In contrast, similar stimulation of lymphocytes from irradiated mice did not elicit secretion of such suppressive lymphokines, unless the cells were depleted of CD8+ T cells or reconstituted with normal Ly-1+ T cells. Because Ly-1+ T cells of irradiated mice could not reconstitute the response, we conclude that this functional subset of CD4+ T cells, which normally controls CD8+ T cell activity in this network, is defective in animals that exhibit irradiation-induced allergic breakthrough.

  4. [Radioimmunologic determination of total IgE and allergen-specific IgE-antibodies in diffuse neurodermitis].

    PubMed

    Pürschel, W; Zeidler, U; Kuse, M

    1975-10-01

    Total IgE levels in sera of 165 patients with atopic dermatitis and 79 patients with dermatoses as well as normal control patients were determined by radioimmunoassay (Phadebas, Pharmacia). Although the mean value for patients with atopic dermatitis was found far above the mean value for normal controls, 38% of patients showed total IgE serum levels within the normal range. Highest IgE serum levels were observed in patients with the generalized form of the disease and in patients with asthma and allergic rhinitis. No direct correlation however, to severity of disease could be found. In a series of 50 patients prick tests were compared to total IgE serum levels and to levels of allergen specific antibodies determined by radioallergosorbent-test (RAST). Extracts of grass pollens and of animal dandruff were used. There was complete agreement between results of skin testing and RAST in at least 80%. While cross reactions were common with grass pollen extracts in RAST, there was no cross-over with animal dandruff. No correlation was found between titer of allergen specific antibody and severity of skin lesions. IgE specific antibody could be detected in 48% of patients with normal total IgE serum levels and in 82% of patients with elevated values. PMID:1201945

  5. Biomonitoring of prenatal analgesic intake and correlation with infantile anti-aeroallergens IgE.

    PubMed

    Hoeke, H; Roeder, S; Mueller, A; Bertsche, T; Borte, M; Rolle-Kampczyk, U; von Bergen, M; Wissenbach, D K

    2016-06-01

    An association between prenatal acetaminophen or ibuprofen intake and an increased risk of asthma and increased IgE level in children is discussed in various epidemiological studies. Although the molecular mechanistic link is still unknown, the question whether or not acetaminophen and/or ibuprofen are safe pain medications during pregnancy arose. In this study, we associate maternal acetaminophen and ibuprofen intake during pregnancy and breastfeeding to infantile asthma phenotypes and elevated IgE level. Therefore, we analysed questionnaires from a local mother-child cohort and monitored drug intake by LC-MS biomonitoring in urine. No association was found between drug intake and any analysed health outcome using questionnaire data. For the information obtained from biomonitoring, no association was found for ibuprofen and acetaminophen intakes during breastfeeding. However, an association between prenatal acetaminophen intake and increased infantile IgEs related to aeroallergens was statistically detected, but not for asthma phenotypes. PMID:27012463

  6. Elimination of IgE regulatory rat CD8+ T cells in vivo differentially modulates interleukin-4 and interferon-gamma but not interleukin-2 production by splenic T cells.

    PubMed Central

    Diaz-Sanchez, D; Noble, A; Staynov, D Z; Lee, T H; Kemeny, D M

    1993-01-01

    Intraperitoneal immunization of Hooded Lister rats with a soluble antigen such as bee venom phospholipase A2 (PLA2), or ovalbumin (OVA) together with the toxic lectin, ricin, eliminates a population of early-activated CD8+ T cells which regulate IgE production. These early-activated CD8+ T cells are eliminated because they bear increased ricin-binding glycoproteins on their surface. This immunization regimen produces a vigorous and long-lived IgE response. The effect of this treatment on the capacity of splenic T cells to secrete interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and to generate IL-4 RNA message was assessed. IFN-gamma production by phytohaemagglutinin (PHA)- or ionomycin and phorbol myristate acetate (PMA)-stimulated splenocytes or purified splenic T cells from animals immunized with antigen and ricin was substantially reduced as compared with animals which were given saline or antigen alone (P < 0.001 Student's t-test). At the height of the primary IgE response IFN-gamma production by PHA-stimulated splenocytes was positively correlated with the number of CD8+ T cells (r = 0.90, P < 0.001) and inversely related to the level of serum IgE (r = -0.77, P < 0.020); serum IgE was inversely related to the number of CD8+ T cells (r = -0.92, P < 0.001). The reduced capacity of spleen cells from ricin and antigen immunized rats to produce IFN-gamma was first seen 7 days after immunization. The fall in the ability of splenocytes to secrete IFN-gamma closely paralleled the rise in serum IgE. IL-2 was assayed using an IL-2-dependent cell line which responded to rat IL-2 but not IL-4. Production of IL-2 by splenocytes taken from rats immunized with ricin+antigen was not significantly different to that produced by comparable cells obtained from animals immunized with antigen alone or saline. However, the levels of IL-4 mRNA, detected in ionomycin and PMA-stimulated splenocytes using a quantitative polymerase chain reaction (PCR) procedure, were three- to

  7. Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid

    PubMed Central

    Messingham, Kelly N.; Holahan, Heather M.; Frydman, Alexandra S.; Fullenkamp, Colleen; Srikantha, Rupasree; Fairley, Janet A.

    2014-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE≥400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils. PMID:25255430

  8. Enzymatic treatment of peanut kernels to reduce allergen levels.

    PubMed

    Yu, Jianmei; Ahmedna, Mohamed; Goktepe, Ipek; Cheng, Hsiaopo; Maleki, Soheila

    2011-08-01

    This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernels as affected by processing conditions. Two major peanut allergens, Ara h 1 and Ara h 2, were used as indicators of process effectiveness. Enzymatic treatment effectively reduced Ara h 1 and Ara h 2 in roasted peanut kernels by up to 100% under optimal conditions. For instance, treatment of roasted peanut kernels with α-chymotrypsin and trypsin for 1-3h significantly increased the solubility of peanut protein while reducing Ara h 1 and Ara h 2 in peanut kernel extracts by 100% and 98%, respectively, based on ELISA readings. Ara h 1 and Ara h 2 levels in peanut protein extracts were inversely correlated with protein solubility in roasted peanut. Blanching of kernels enhanced the effectiveness of enzyme treatment in roasted peanuts but not in raw peanuts. The optimal concentration of enzyme was determined by response surface to be in the range of 0.1-0.2%. No consistent results were obtained for raw peanut kernels since Ara h 1 and Ara h 2 increased in peanut protein extracts under some treatment conditions and decreased in others. PMID:25214091

  9. Expression of the High Affinity IgE Receptor by Neutrophils of Individuals with Allergic Asthma is Both Minimal and Insensitive to Regulation by Serum IgE

    PubMed Central

    Mora, Juanita; Riggs, Emily K.; Fu, Jun; MacGlashan, Donald W.; Fox, Susan A.; Yu, Byung; Tobin, Mary C.; Thomas, Larry L.

    2009-01-01

    We evaluated the hypothesis that serum IgE regulates neutrophil FcεRI expression in the same manner as described for other FcεRI+ cells. FcεRI expression by neutrophils of 40 asthma subjects and 20 control subjects did not correlate with serum IgE levels, whereas FcεRI expression by basophils of the same subjects showed a highly significant correlation. The level of FcεRI expression by neutrophils of both asthma and control subjects was approximately 1% of that for basophil FcεRI expression. IgE+ neutrophils were minimally detectable, and FcεRI α subunit was not detected in Western blots of neutrophil membranes and cytosol. The neutrophil FcεRI did not support anti-IgE stimulated superoxide release or IgE-induced increase in neutrophil survival. We conclude that FcεRI expression by neutrophils of both asthma patients and control individuals is minimal at best and that, if present, neutrophil FcεRI expression, unlike that of other human FcεRI+ cells, is not regulated by serum IgE. PMID:19359220

  10. Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and systemic lupus erythematosus

    SciTech Connect

    Terr, A.I.; Moss, R.B.; Strober, S.

    1987-12-01

    Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer T cells does not appear to influence preexisting levels of IgE antibodies.

  11. Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.

    PubMed

    Kimata, Hajime

    2003-11-01

    The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients. PMID:14637240

  12. Calcium Deficiency Reduces Circulating Levels of FGF23

    PubMed Central

    Rodriguez-Ortiz, María E.; Lopez, Ignacio; Muñoz-Castañeda, Juan R.; Martinez-Moreno, Julio M.; Ramírez, Alan Peralta; Pineda, Carmen; Canalejo, Antonio; Jaeger, Philippe; Aguilera-Tejero, Escolastico; Felsenfeld, Arnold; Almaden, Yolanda

    2012-01-01

    Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia. PMID:22581996

  13. Population Characteristics May Reduce the Levels of Individual Call Identity

    PubMed Central

    Delgado, María del Mar; Caferri, Eleonora; Méndez, Maria; Godoy, José A.; Campioni, Letizia; Penteriani, Vincenzo

    2013-01-01

    Individual variability influences the demographic and evolutionary dynamics of spatially structured populations, and conversely ecological and evolutionary dynamics provide the context under which variations at the individual level occur. Therefore, it is essential to identify and characterize the importance of the different factors that may promote or hinder individual variability. Animal signaling is a prime example of a type of behavior that is largely dependent on both the features of individuals and the characteristics of the population to which they belong. After 10 years studying the dynamics of a population of a long-lived species, the eagle owl (Bubo bubo), we investigated the emergence and maintenance of traits that reveal individual identity by focusing on vocal features. We found that individuals inhabiting a high density population characterized by a relative lack of heterogeneity (in terms of prey availability and breeding success) among breeding sites might be selected for reducing the levels of identity. Two non-mutually exclusive hypotheses may explain the structural call patterns we detected: (1) similarity in calls may be principally a consequence of the particular characteristics of the population; and (2) high density may encourage individuals to mimic each other’s vocalizations in a cascade effect, leading to a widespread and unique communication network. PMID:24204869

  14. Reducing ethylene levels along the food supply chain: a key to reducing food waste?

    PubMed

    Blanke, Michael M

    2014-09-01

    Excessive waste along the food supply chain of 71 (UK, Netherlands) to 82 (Germany) kg per head per year sparked widespread criticism of the agricultural food business and provides a great challenge and task for all its players and stakeholders. Origins of this food waste include private households, restaurants and canteens, as well as supermarkets, and indicate that 59-65% of this food waste can be avoided. Since ∼50% of the food waste is fruit and vegetables, monitoring and control of their natural ripening gas - ethylene - is suggested here as one possible key to reducing food waste. Ethylene accelerates ripening of climacteric fruits, and accumulation of ethylene in the supply chain can lead to fruit decay and waste. While ethylene was determined using a stationary gas chromatograph with gas cylinders, the new generation of portable sensor-based instruments now enables continuous in situ determination of ethylene along the food chain, a prerequisite to managing and maintaining the quality and ripeness of fruits and identifying hot spots of ethylene accumulation along the supply chain. Ethylene levels were measured in a first trial, along the supply chain of apple fruit from harvest to the consumer, and ranged from 10 ppb in the CA fruit store with an ethylene scrubber, 70 ppb in the fruit bin, to 500 ppb on the sorting belt in the grading facility, to ppm levels in perforated plastic bags of apples. This paper also takes into account exogenous ethylene originating from sources other than the fruit itself. Countermeasures are discussed, such as the potential of breeding for low-ethylene fruit, applications of ethylene inhibitors (e.g. 1-MCP) and absorber strips (e.g. 'It's Fresh', Ryan'), packages (e.g. 'Peakfresh'), both at the wholesale and retail level, vents and cooling for the supply chain, sale of class II produce ('Wunderlinge'), collection (rather than waste) of produce on the 'sell by' date ('Die Tafel') and whole crop purchase (WCP) to aid reducing

  15. Effect of maternal lifestyle on cord blood IgE factor.

    PubMed

    Shirakawa, T; Morimoto, K; Sasaki, S; Taniguchi, K; Motonaga, M; Akahori, W; Akahori, S; Akahori, T; Ohmori, H; Kuroda, E; Okabe, K; Yugari, K; Yamana, M

    1997-06-01

    During recent decades much interest has been focused on the possibility of predicting and preventing atopic diseases during pregnancy. The idea of being able to detect a predisposition early and take suitable environmental measures in order to avoid overt allergy is an attractive position. Elevated cord IgE of around 1.0 IU/ml has been proposed as a predictor in western children. However, there remains no information about the effect of maternal lifestyle during pregnancy on these levels. Total IgE levels were therefore determined using Pharmacia CAP system and PRIST, with sensitivities of 0.01 kU/l and 0.25 kU/l, respectively, from serum samples taken from 1138 Japanese pairs of cord blood and pregnant women responding to a questionnaire regarding 17 health practices, intake of 32 food allergens and 5 environmental factors. Of these, 28 (2.5%) pairs of samples were excluded from further analysis because of high contamination of IgA (> 15.4 mg/ml) in cord blood. Median cord blood IgE was 0.286 kU/l and geometric mean IgE was 66.25 kU/l in maternal sera using CAP system; there was no significant correlation between maternal log (IgE) and cord blood IgE. Similar results were obtained from PRIST, whose correlation with CAP system was significant (r = 0.884, p < 0.001 for maternal and r = 0.765, p < 0.001 for cord blood). Multiple logistic analysis demonstrated that avoidance of simultaneous exposure to hens' eggs and cow's milk (relative risk = 1.3, p < 0.05) as well as soy beans (relative risk = 2.8, p < 0.01) should be advised to mothers with positive allergic histories and/or high total IgE (> 400 IU/ml), especially in women aged more than 35 years who are pregnant with a male child. However, maintenance of healthy lifestyles, especially taking proper exercise and sleeping, and avoidance of inhalant allergens during late pregnancy may be a more important strategy for the reduction of cord blood IgE levels. PMID:9258545

  16. Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites

    PubMed Central

    Platzer, Barbara; Baker, Kristi; Vera, Miguel Pinilla; Singer, Kathleen; Panduro, Marisella; Lexmond, Willem S.; Turner, Devin; Vargas, Sara O.; Kinet, Jean-Pierre; Maurer, Dieter; Baron, Rebecca M.; Blumberg, Richard S.; Fiebiger, Edda

    2014-01-01

    Antigen-mediated crosslinking of Immunoglobulin E (IgE) bound to mast cells/basophils via FcεRI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express FcεRI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/FcεRI signals for DC function remain poorly understood. We show that humanized mice that express FcεRI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcεRI crosslinking fails to induce maturation or production of inflammatory mediators in human DCs and FcεRI-humanized DCs. Furthermore, conferring expression of FcεRI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/FcεRI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/FcεRI crosslinking on papain or LPS-stimulated DCs inhibits the production of pro-inflammatory cytokines and chemokines. Migration assays confirm that the IgE-dependent decrease in cytokine production results in diminished recruitment of mast cell progenitors; providing a mechanistic explanation for the reduced mast cell-dependent allergic phenotype observed in FcεRI-humanized mice. Our study demonstrates a novel immune regulatory function of IgE and proposes that DC-intrinsic IgE signals serve as a feedback mechanism to restrain allergic tissue inflammation. PMID:25227985

  17. Combined effect of smoking habits and occupational exposure to hard metal on total IgE antibodies

    SciTech Connect

    Shirakawa, T.; Kusaka, Y.; Morimoto, K. )

    1992-06-01

    A survey was made within a population of workers (n = 706) exposed to hard metal dust (an alloy including cobalt), an agent known to cause occupational allergy. Twenty-seven (4 percent) of 733 workers were eliminated from consideration in this study because of atopic status identified prior to starting work in the plant. Using a Phadebas PRIST, the subjects' total IgE levels were determined and related to their smoking and exposure status. Nonexposed male smokers (n = 135) had a higher geometric mean IgE level (39.7 IU/ml) than did nonexposed subjects who had never smoked (33.1 IU/ml; n = 99); those with a higher Brinkman index (greater than 300), a smoking index obtained by multiplying the number of cigarettes per day by the duration of smoking in years, had significantly (p less than 0.05) decreased IgE levels. Although ex-smokers (n = 72) had a higher geometric mean IgE level (73.3 IU/ml) than did those who had never smoked, their serum IgE level declined with age since the time they quit smoking, regardless of their hard metal exposure status. Hard metal (cobalt) exposure may play a significant role as an adjuvant in the production of total IgE. A multivariate analysis demonstrated that hard metal exposure and a smoking habit together arithmetically (p less than 0.05) increased total IgE levels. These two factors may be preventable risk factors for occupational allergy in hard metal workers.

  18. A locus regulating total serum IgE maps to chromosome 5q

    SciTech Connect

    Amelung, P.J.; Panhuysen, C.I.M.; Postma, D.S. |

    1994-09-01

    Familial aggregation of allergy has been demonstrated in numerous past studies. However, allergy is a complex disorder which is not inherited as a simple Mendelian trait. Total serum IgE levels correlate with the clinical expression of allergy and asthma and can be utilized as a quantitative measure of the allergic phenotype. We studied 92 families from Northern Holland ascertained through a parent with asthma who were originally studied between 1962-1970. Since there is a large number of candidate genes on chromosome 5q, families were genotyped for markers in this region. These genes either directly or indirectly regulate IgE production and the activation and proliferation of cellular elements that are involved in inflammation associated with allergy and asthma. They include IL-4, IL-3, IL-5, IL-9, IL-12, IL-13 and GM-CSF. Segregation analyses revealed recessive inheritance of `high` levels with a mean for the `low` phenotype of 1.51 (32 IU) and 2.52 (331 IU) for the `high` phenotype. Linkage of log IgE with markers on 5q was tested using the sib-pair and the LOD score methods with the genetic model obtained from the segregation analyses. These results provide evidence for a locus controlling IgE levels near the cytokine gene cluster on 5q. This region appears critical in susceptibility to allergy and asthma.

  19. Reduced cadmium levels in human kidney cortex in sweden.

    PubMed Central

    Friis, L; Petersson, L; Edling, C

    1998-01-01

    Environmental pollution with the nephrotoxic metal cadmium is considered a potential health risk for the general population. In 1976 it was reported that the cadmium concentration in human kidney cortex in Sweden had increased in parallel with increasing levels in soil and grain during the twentieth century. Since the cadmium concentration in farming lands is still increasing, the present study was undertaken to further elucidate whether the cadmium concentration in the kidney is still increasing. Kidney cortex biopsies were collected at 171 autopsies of victims to sudden and accidental death during 1995 and 1996, and the cadmium concentrations were determined and compared with previously published Swedish data obtained from forensic autopsies. The geometric mean cadmium concentration in kidney cortex in subjects 40 years of age and younger was about 40% of the concentration found in the 1970s, while the reduction was less pronounced among older people. The highest individual concentration of cadmium was 41.5 microg/g wet weight (ww). The geometric mean concentration was less than 14 microg/g ww at ages around 50 years of age, when the cadmium concentration in kidney cortex is highest, as compared with approximately 20 microg/g ww in the 1970s. There was also a reduction in cadmium concentrations among nonsmokers; thus, a decrease in tobacco smoking in Sweden during the last decades is not the only explanation for the reduction of cadmium in the kidney cortex. Other reasons for this reduction could be changes in dietary habits and reduced cadmium contamination from Swedish industries. Images Figure 1 PMID:9485480

  20. Nanoparticles rapidly assess specific IgE in plasma

    NASA Astrophysics Data System (ADS)

    Ashraf, Sarmadia; Qadri, Shahnaz; al-Ramadi, Basel; Haik, Yousef

    2012-08-01

    Allergy is the sixth leading cause of chronic disease in the world. This study demonstrates the feasibility of detecting allergy indicators in human plasma, noninvasively, at the point of care and with a comparable efficiency and reduced turnaround time compared with the gold standard. Peanut allergy was utilized as a model due to its widespread occurrence among the US population and fatality if not treated. The detection procedure utilized magnetic nanoparticles that were coated with an allergen layer (peanut protein extract). Peanut immunoglobulin E (IgE) was detected in concentrations close to the minimum detection range of CAP assay. The results were obtained in minutes compared with the CAP assay which requires more than 3 h.

  1. Crossreactivity of IgE antibody against Dermatophagoides farinae with Limulus polyphemus agglutinin.

    PubMed

    Shibasaki, M; Isoyama, S; Sumazaki, R; Takita, H

    1994-04-01

    Crossreactivity of IgE antibody against Dermatophagoides farinae (Der f) with Limulus polyphemus agglutinin (LPA) was examined using RAST and immunoblot analysis. Of 40 Der f-sensitive asthmatic patients, 28 revealed a positive RAST reaction to LPA, while none of 20 Der f-insensitive hay fever patients showed this reaction. LPA-specific RAST levels of the 40 asthmatic patients correlated with their Der f-specific levels. The RAST reactivity to LPA was competitively inhibited by the addition of either soluble Der f or LPA, but not by the specific inhibitory sugar of sialic acid. LPA could also induce histamine release from leucocytes of Der f-sensitive asthmatic patients. IgE immunoblot analyses showed that the positive RAST sera for LPA had a strong IgE binding activity to the 30 kDa and 80 kDa components of Der f body extract, whereas gel filtration studies showed that the high molecular weight fractions above 150 kDa retained antigenic constituents associated with IgE reactivity to LPA. These results suggest that the antigenic materials of Dermatophagoides mites share some determinants with the haemagglutinin of horseshoe crabs. PMID:7518731

  2. Decreased immunoglobulin E (IgE) binding to cashew allergens following sodium sulfite treatment and heating.

    PubMed

    Mattison, Christopher P; Desormeaux, Wendy A; Wasserman, Richard L; Yoshioka-Tarver, Megumi; Condon, Brian; Grimm, Casey C

    2014-07-16

    Cashew nut and other nut allergies can result in serious and sometimes life-threatening reactions. Linear and conformational epitopes within food allergens are important for immunoglobulin E (IgE) binding. Methods that disrupt allergen structure can lower IgE binding and lessen the likelihood of food allergy reactions. Previous structural and biochemical data have indicated that 2S albumins from tree nuts and peanuts are potent allergens, and that their structures are sensitive to strong reducing agents such as dithiothreitol. This study demonstrates that the generally regarded as safe (GRAS) compound sodium sulfite effectively disrupted the structure of the cashew 2S albumin, Ana o 3, in a temperature-dependent manner. This study also showed that sulfite is effective at disrupting the disulfide bond within the cashew legumin, Ana o 2. Immunoblotting and ELISA demonstrated that the binding of cashew proteins by rabbit IgG or IgE from cashew-allergic patients was markedly lowered following treatment with sodium sulfite and heating. The results indicate that incorporation of sodium sulfite, or other food grade reagents with similar redox potential, may be useful processing methods to lower or eliminate IgE binding to food allergens. PMID:24926808

  3. IgE, allergy, and risk of glioma: update from the San Francisco Bay Area Adult Glioma Study in the temozolomide era.

    PubMed

    Wiemels, Joseph L; Wilson, David; Patil, Chirag; Patoka, Joseph; McCoy, Lucie; Rice, Terri; Schwartzbaum, Judith; Heimberger, Amy; Sampson, John H; Chang, Susan; Prados, Michael; Wiencke, John K; Wrensch, Margaret

    2009-08-01

    The consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that immunoglobulin E (IgE) levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechanism that inhibits or prevents glioma. We sought to extend these results with a new and larger series of patients (n = 535 with questionnaire data; 393 with IgE measures) and controls (n = 532 with questionnaire data; 470 with IgE measures). As expected, glioma cases were less likely than controls to report history of allergies [among self-reported cases, Odds ratios (OR) = 0.59, 95% confidence interval (CI): 0.41-0.85]. IgE levels also were lower in glioma cases versus controls (OR per unit log IgE = 0.89, 95% CI (0.82-0.98). However, this inverse relationship was only apparent among cases receiving temozolomide, a treatment which became part of the "standard of care" for glioblastoma patients during the study period. Among patients receiving temozolomide, IgE levels in cases whose blood samples were obtained within 30 days of diagnosis were slightly higher than controls, whereas IgE levels in cases whose blood sample was obtained >60 days after diagnosis were significantly lower than controls (OR = 0.80; 95% CI: 0.71-0.89). Thus, although our results robustly confirm the inverse association between allergy and glioma, the results for IgE are affected by temozolomide treatments which may have influenced IgE levels. These results have implications for the study of immunologic factors in glioma as well as for immunotherapy protocols for treating glioma. PMID:19408307

  4. IgE, Allergy, and Risk of Glioma: Update from the San Francisco Bay Area Adult Glioma Study in the Temozolomide Era

    PubMed Central

    Wiemels, Joseph L.; Wilson, David; Patel, Chirag; Patoka, Joseph; McCoy, Lucie; Rice, Terri; Schwartzbaum, Judith; Heimberger, Amy; Sampson, John H.; Chang, Susan; Prados, Michael; Wiencke, John K.; Wrensch, Margaret

    2009-01-01

    The consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that IgE levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechanism that inhibits or prevents glioma. We sought to extend these results with a new and larger series of patients (n=535 with questionnaire data; 393 with IgE measures) and controls (n=532 with questionnaire data; 470 with IgE measures). As expected, glioma cases were less likely than controls to report history of allergies (among self-reported cases, OR = 0.59, 95% CI: 0.41–0.85). IgE levels also were lower in glioma cases versus controls (OR per unit log IgE=0.89, 95% CI (0.82–0.98). However, this inverse relationship was only apparent among cases receiving temozolomide, a treatment which became part of the “standard of care” for glioblastoma patients during the study period. Among patients receiving temozolomide, IgE levels in cases whose blood samples were obtained within 30 days of diagnosis were slightly higher than controls, while IgE levels in cases whose blood sample was obtained >60 days after diagnosis were significantly lower than controls (OR = 0.80; 95% CI: 0.71–0.89). Thus, while our results robustly confirm the inverse association between allergy and glioma, the results for IgE are affected by temozolomide treatments which may have influenced IgE levels. These results have implications for the study of immunologic factors in glioma as well as for immunotherapy protocols for treating glioma. PMID:19408307

  5. Screening for IgE mediated allergy among people working in the Marseilles harbour.

    PubMed

    Panzani, R C; Falagiani, P; Riva, G; Mercier, P; Delord

    1993-01-01

    Screening for IgE mediated allergy by RASTs to professional (castor bean, green coffee, peanut, soy protein, wheat, rice), and non professional (pollens, mites, cat, Alternaria tenuis) air borne antigens among 36 people working in the Marseilles harbour has showed rather unexpected findings: only one case of IgE positivity to Dermatophagoides pteronyssinus (class I) and one case of IgE positivity to castor bean seed (Ricinus communis) (class IV). IgG4 specific antibodies against castor bean and green coffee were also measured by an ELISA technique, with eleven cases of positivity to castor bean and only one case to green coffee being recorded. Several explanations can be put forward for the low incidence of IgE responses to the commonest airborne antigens and to the professional antigens (castor bean being the only offender), and for the rather high incidence of specific IgG4 antibodies to castor bean. Most likely, the low incidence of latent atopy is the result of a natural selection among the workers who gave up their job if experiencing of discomfort. As far as the elevated IgG4 antibody levels to castor bean are concerned, these are probably natural blocking antibodies. PMID:8328353

  6. Enzymatic treatment of peanut kernels to reduce allergen levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernel by processing conditions, such as, pretreatment with heat and proteolysis at different enzyme concentrations and treatment times. Two major peanut allergens, Ara h 1 and Ara h 2, were used as indicator...

  7. Effects of Nasal Corticosteroids on Boosts of Systemic Allergen-Specific IgE Production Induced by Nasal Allergen Exposure

    PubMed Central

    Egger, Cornelia; Lupinek, Christian; Ristl, Robin; Lemell, Patrick; Horak, Friedrich; Zieglmayer, Petra; Spitzauer, Susanne; Valenta, Rudolf; Niederberger, Verena

    2015-01-01

    Background Allergen exposure via the respiratory tract and in particular via the nasal mucosa boosts systemic allergen-specific IgE production. Intranasal corticosteroids (INCS) represent a first line treatment of allergic rhinitis but their effects on this boost of allergen-specific IgE production are unclear. Aim Here we aimed to determine in a double-blind, placebo-controlled study whether therapeutic doses of an INCS preparation, i.e., nasal fluticasone propionate, have effects on boosts of allergen-specific IgE following nasal allergen exposure. Methods Subjects (n = 48) suffering from grass and birch pollen allergy were treated with daily fluticasone propionate or placebo nasal spray for four weeks. After two weeks of treatment, subjects underwent nasal provocation with either birch pollen allergen Bet v 1 or grass pollen allergen Phl p 5. Bet v 1 and Phl p 5-specific IgE, IgG1–4, IgM and IgA levels were measured in serum samples obtained at the time of provocation and one, two, four, six and eight weeks thereafter. Results Nasal allergen provocation induced a median increase to 141.1% of serum IgE levels to allergens used for provocation but not to control allergens 4 weeks after provocation. There were no significant differences regarding the boosts of allergen-specific IgE between INCS- and placebo-treated subjects. Conclusion In conclusion, the application of fluticasone propionate had no significant effects on the boosts of systemic allergen-specific IgE production following nasal allergen exposure. Trial Registration http://clinicaltrials.gov/ NCT00755066 PMID:25705889

  8. Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity

    PubMed Central

    Fitzsimmons, Colin Matthew; Falcone, Franco Harald; Dunne, David William

    2014-01-01

    The Th2 immune response, culminating in eosinophilia and IgE production, is not only characteristic of allergy but also of infection by parasitic worms (helminths). Anti-parasite IgE has been associated with immunity against a range of helminth infections and many believe that IgE and its receptors evolved to help counter metazoan parasites. Allergens (IgE-antigens) are present in only a small minority of protein families and known IgE targets in helminths belong to these same families (e.g., EF-hand proteins, tropomyosin, and PR-1 proteins). During some helminth infection, especially with the well adapted hookworm, the Th2 response is moderated by parasite-expressed molecules. This has been associated with reduced allergy in helminth endemic areas and worm infection or products have been proposed as treatments for allergic conditions. However, some infections (especially Ascaris) are associated with increased allergy and this has been linked to cross-reactivity between worm proteins (e.g., tropomyosins) and highly similar molecules in dust-mites and insects. The overlap between allergy and helminth infection is best illustrated in Anisakis simplex, a nematode that when consumed in under-cooked fish can be both an infective helminth and a food allergen. Nearly 20 molecular allergens have been isolated from this species, including tropomyosin (Ani s 3) and the EF-hand protein, Ani s troponin. In this review, we highlight aspects of the biology and biochemistry of helminths that may have influenced the evolution of the IgE response. We compare dominant IgE-antigens in worms with clinically important environmental allergens and suggest that arrays of such molecules will provide important information on anti-worm immunity as well as allergy. PMID:24592267

  9. Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity.

    PubMed

    Fitzsimmons, Colin Matthew; Falcone, Franco Harald; Dunne, David William

    2014-01-01

    The Th2 immune response, culminating in eosinophilia and IgE production, is not only characteristic of allergy but also of infection by parasitic worms (helminths). Anti-parasite IgE has been associated with immunity against a range of helminth infections and many believe that IgE and its receptors evolved to help counter metazoan parasites. Allergens (IgE-antigens) are present in only a small minority of protein families and known IgE targets in helminths belong to these same families (e.g., EF-hand proteins, tropomyosin, and PR-1 proteins). During some helminth infection, especially with the well adapted hookworm, the Th2 response is moderated by parasite-expressed molecules. This has been associated with reduced allergy in helminth endemic areas and worm infection or products have been proposed as treatments for allergic conditions. However, some infections (especially Ascaris) are associated with increased allergy and this has been linked to cross-reactivity between worm proteins (e.g., tropomyosins) and highly similar molecules in dust-mites and insects. The overlap between allergy and helminth infection is best illustrated in Anisakis simplex, a nematode that when consumed in under-cooked fish can be both an infective helminth and a food allergen. Nearly 20 molecular allergens have been isolated from this species, including tropomyosin (Ani s 3) and the EF-hand protein, Ani s troponin. In this review, we highlight aspects of the biology and biochemistry of helminths that may have influenced the evolution of the IgE response. We compare dominant IgE-antigens in worms with clinically important environmental allergens and suggest that arrays of such molecules will provide important information on anti-worm immunity as well as allergy. PMID:24592267

  10. Purification and characterization of IgE produced by human myeloma cell line, U266.

    PubMed

    Ikeyama, S; Nakagawa, S; Arakawa, M; Sugino, H; Kakinuma, A

    1986-02-01

    Human IgE was isolated for the first time from the supernatant of the culture fluid of a human myeloma cell line, U266. The purification procedure consisted of salting out from the supernatant with ammonium sulfate, affinity chromatography on a lysine-Sepharose 4B column, ion exchange chromatography on a DEAE-Sephacel column, gel filtration and recycling chromatography on a Sephacryl S-300 column and removal of bovine proteins on an anti-bovine serum rabbit IgG-Sepharose 4B column. One hundred and twenty eight milligrams of IgE was recovered from 461 of culture fluid. The purification was extremely simplified by the introduction of immunoaffinity chromatography using the monoclonal antibody prepared by immunizing a mouse with an IgE preparation obtained by the above method: about 3.3 mg was recovered from 960 ml of culture fluid. The purified preparation was homogeneous as judged by the double-immunodiffusion test and end group analysis. The amino acid and carbohydrate compositions of the preparation coincided with those reported on other preparations obtained from the sera of myeloma patients. Our preparation, however, showed two bands with apparent mol. wts of 240,000 and 230,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. When it was reduced with dithiothreitol and analyzed by electrophoresis, it gave two heavy chains and one light chain with apparent mol. wts of 80,000 and 76,000, and 28,000, respectively. On the other hand, the IgE molecule that was synthesized and secreted into the medium in the presence of tunicamycin (0.5 microgram/ml) gave only one heavy chain and one light chain with apparent mol. wts of 62,000 and 28,000, respectively. These results demonstrated that the two IgE molecular species contained in our preparation differed from each other in the carbohydrate moiety in their heavy chains. PMID:3702874

  11. IgE Immunotherapy Against Cancer

    PubMed Central

    Leoh, Lai Sum

    2015-01-01

    The success of antibody therapy in cancer is consistent with the ability of these molecules to activate immune responses against tumors. Experience in clinical applications, antibody design, and advancement in technology have enabled antibodies to be engineered with enhanced efficacy against cancer cells. This allows re-evaluation of current antibody approaches dominated by antibodies of the IgG class with a new light. Antibodies of the IgE class play a central role in allergic reactions and have many properties that may be advantageous for cancer therapy. IgE-based active and passive immunotherapeutic approaches have been shown to be effective in both in vitro and in vivo models of cancer, suggesting the potential use of these approaches in humans. Further studies on the anticancer efficacy and safety profile of these IgE-based approaches are warranted in preparation for translation toward clinical application. PMID:25553797

  12. Health Promotion to Reduce Blood Pressure Level among Older Blacks.

    ERIC Educational Resources Information Center

    Haber, David

    1986-01-01

    Low-income Black elders completed a 10-week health promotion program for the purpose of lowering or stabilizing blood pressure levels. Comparisons were made between classes that met weekly versus three times a week, and between yoga and aerobics formats. A peer-led program was developed that continued for 10 months after the professionally-led…

  13. Reducing nursing students' anxiety level and increasing retention of materials.

    PubMed

    Phillips, A P

    1988-01-01

    The purpose of this descriptive study is to examine the effects active learning, collaboration and modified group testing have on reducing students' anxiety and increasing learning and retention of material. Subjects consist of 34 associate degree nursing students enrolled in the Advanced Adult Health nursing class at North Georgia College. Most of the students are married, have children and work part time. A self-reporting questionnaire suggests a reduction of the students' anxiety during the quarter. The attitudinal questionnaire reveals an atmosphere of collaboration among peers. Data evaluating learning and retention of material were analyzed using the parametric (T-test) and nonparametric (Wiley Rank Sum test) methods. Examination of the Null Hypotheses I and II suggests there were increased learning and retention of material as evidenced by higher grades on the comprehensive final examination than on the quizzes given after presentation of content. Principles of andragogy as defined by Knowles (1980) and cooperation with peers as described by Johnson, Johnson, Holabec, and Roy (1984), Johnson, Johnson, and Maruyama (1983), and Johnson and Johnson (1975) form the theoretical foundation. PMID:2828575

  14. Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels

    PubMed Central

    Bartolome, Fernando; Wu, Hsiu-Chuan; Burchell, Victoria S.; Preza, Elisavet; Wray, Selina; Mahoney, Colin J.; Fox, Nick C.; Calvo, Andrea; Canosa, Antonio; Moglia, Cristina; Mandrioli, Jessica; Chiò, Adriano; Orrell, Richard W.; Houlden, Henry; Hardy, John; Abramov, Andrey Y.; Plun-Favreau, Helene

    2013-01-01

    Summary Valosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget’s disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%–2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death. PMID:23498975

  15. The correlation between anti phospholipase A2 specific IgE and clinical symptoms after a bee sting in beekeepers

    PubMed Central

    Matysiak, Joanna; Bręborowicz, Anna; Dereziński, Paweł; Kokot, Zenon J.

    2016-01-01

    Introduction Beekeepers are a group of people with high exposure to honeybee stings and with a very high risk of allergy to bee venom. Therefore, they are a proper population to study the correlations between clinical symptoms and results of diagnostic tests. Aim The primary aim of our study was to assess the correlations between total IgE, venom- and phospholipase A2-specific IgE and clinical symptoms after a bee sting in beekeepers. The secondary aim was to compare the results of diagnostic tests in beekeepers and in individuals with standard exposure to bees. Material and methods Fifty-four individuals were divided into two groups: beekeepers and control group. The levels of total IgE (tIgE), venom-specific IgE (venom sIgE), and phospholipase A2-specific IgE (phospholipase A2 sIgE) were analyzed. Results Our study showed no statistically significant correlation between the clinical symptoms after a sting and tIgE in the entire analyzed group. There was also no correlation between venom sIgE level and clinical symptoms either in beekeepers or in the group with standard exposure to bees. We observed a statistically significant correlation between phospholipase A2 sIgE level and clinical signs after a sting in the group of beekeepers, whereas no such correlation was detected in the control group. Significantly higher venom-specific IgE levels in the beekeepers, as compared to control individuals were shown. Conclusions In beekeepers, the severity of clinical symptoms after a bee sting correlated better with phospholipase A2 sIgE than with venom sIgE levels. PMID:27512356

  16. IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching.

    PubMed

    Kashiwada, Masaki; Levy, Deborah M; McKeag, Lisa; Murray, Keri; Schröder, Andreas J; Canfield, Stephen M; Traver, Geri; Rothman, Paul B

    2010-01-12

    IL-4 signaling promotes IgE class switching through STAT6 activation and the induction of Ig germ-line epsilon (GLepsilon) transcription. Previously, we and others identified a transcription factor, Nfil3, as a gene induced by IL-4 stimulation in B cells. However, the precise roles of nuclear factor, IL-3-regulated (NFIL3) in IL-4 signaling are unknown. Here, we report that NFIL3 is important for IgE class switching. NFIL3-deficient mice show impaired IgE class switching, and this defect is B-cell intrinsic. The induction of GLepsilon transcripts after LPS and IL-4 stimulation is significantly reduced in NFIL3-deficient B cells. Expression of NFIL3 in NFIL3-deficient B cells restores the impairment of IgE production, and overexpression of NFIL3 in the presence of cycloheximide induces GLepsilon transcripts. Moreover, NFIL3 binds to Iepsilon promoter in vivo. Together, these results identify NFIL3 as a key regulator of IL-4-induced GLepsilon transcription in response to IL-4 and subsequent IgE class switching. PMID:20080759

  17. Clinical and radiological signs of ABPA associated with airways infection with Aspergillus in the absence of specific IgE.

    PubMed

    Sunzini, F; Barbato, C; Canofari, C; Lugari, L; Perricone, R; Bergamini, A

    2016-09-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus that mainly affects patients with asthma. For diagnosis, elevated serum IgE level are needed according to Greenberger and Patterson criteria. We report a case of 43 years-old woman who developed ABPA with productive cough, fever and radiological findings of multiple confluent areas of consolidation in both upper lobes. Laboratory tests showed elevated peripheral eosinophil counts (9.3 x 10(3)/ml). In bronchial washing A. galactomannans and A. Fumigatus were isolated, although we found normal levels of serum IgE, and the absence of serum IgG and IgE antibodies to Aspergillus and A. galactomannans. In conclusion, clinical and radiological signs of ABPA can be associated with Aspergillus infection also in the absence of a specific serum antibody reaction. PMID:27608478

  18. Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation.

    PubMed

    Kerzel, Sebastian; Rogosch, Tobias; Struecker, Benjamin; Maier, Rolf F; Kabesch, Michael; Zemlin, Michael

    2016-06-15

    The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis. PMID:27183570

  19. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes.

    PubMed

    Nanthirudjanar, Tharnath; Furumoto, Hidehiro; Zheng, Jiawen; Kim, Young-Il; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2015-11-01

    Hydroxy and oxo fatty acids were recently found to be produced as intermediates during gut microbial fatty acid metabolism. Lactobacillus plantarum produces these fatty acids from unsaturated fatty acids such as linoleic acid. In this study, we investigated the effects of these gut microbial fatty acid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fatty acids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fatty acid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia. PMID:26399511

  20. Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with Chronic Idiopathic Urticaria for detection of antibody against IgE or IgE receptor (FcεRIα).

    PubMed

    Sajedi, Vahid; Movahedi, Masoud; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Gharagozlou, Mohammad; Ghareguzlou, Mohammad; Shafiei, Alireza; Soheili, Habib; Sanajian, Nahal

    2011-06-01

    Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologus serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment. PMID:21625019

  1. Elimination of IgE regulatory rat CD8+ T cells in vivo increases the co-ordinate expression of Th2 cytokines IL-4, IL-5 and IL-10.

    PubMed Central

    Noble, A; Staynov, D Z; Diaz-Sanchez, D; Lee, T H; Kemeny, D M

    1993-01-01

    Immunization of rats with soluble antigen (ovalbumin) and the castor bean toxin, ricin, eliminates a subpopulation of CD8+ T cells which suppress IgE responses in vivo. This treatment also reduces the ability of splenic T cells to produce interferon-gamma (IFN-gamma) and enhances their capacity to make interleukin-4 (IL-4). In this report we describe the effect of immunization with ricin and antigen on the expression of mRNA for other T-helper type 2 (Th2) cytokines--IL-5 and IL-10--and their relationship to serum IgE and IL-4 mRNA expression. Splenocytes were taken from rats at different times after immunization with antigen or ricin and antigen and activated in vitro with phorbol myristate acetate (PMA) and ionomycin for 6 hr and total RNA extracted and reverse transcribed. Cytokine gene expression was detected using a quantitative polymerase chain reaction (PCR). Expression of IL-4, IL-5, and IL-10 was increased 7-20-fold 11 days after immunization with ricin and antigen (from 0.107% to 0.769% beta-actin for IL-4, from 0.0167% to 0.381% beta-actin for IL-5, and from 0.0581% to 0.954% beta-actin for IL-10), and preceded maximum serum IgE levels by 4-5 days. There was no increase in IgE or mRNA for these cytokines in rats immunized with antigen alone. The level of IL-4, IL-5, and IL-10 expression declined rapidly after 12 days. Our results suggest that immunization with antigen and ricin preferentially induces a Th2 response, and that CD8+ T cells may play a part in down-regulating the development of Th2 T cells. PMID:8262562

  2. Interpreting IgE sensitization tests in food allergy.

    PubMed

    Chokshi, Niti Y; Sicherer, Scott H

    2016-01-01

    Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy. PMID:26666347

  3. DOE DEF RIM-to-IGES. File Writer documentation manual

    SciTech Connect

    Fritsche, K.L.; Leake, P.S.

    1986-03-01

    This document will define the design specifications for the RIM-to-IGES File Writer Program. It describes the purpose of the File Writer, lists references, defines the structure of the program, and discusses the Fortran/RIM interface.

  4. Mechanisms of Anaphylaxis Beyond IgE.

    PubMed

    Muñoz-Cano, R; Picado, C; Valero, A; Bartra, J

    2016-01-01

    Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators derived from mast cells and basophils. Food allergens are the main triggers of anaphylaxis, accounting for 33%-56% of all cases and up to 81% of cases of anaphylaxis in children. Human anaphylaxis is generally thought to be mediated by IgE, with mast cells and basophils as key players, although alternative mechanisms have been proposed. Neutrophils and macrophages have also been implicated in anaphylactic reactions, as have IgG-dependent, complement, and contact system activation. Not all allergic reactions are anaphylactic, and the presence of the so-called accompanying factors (cofactors or augmenting factors) may explain why some conditions lead to anaphylaxis, while in other cases the allergen elicits a milder reaction or is even tolerated. In the presence of these factors, allergic reactions may be induced at lower doses of allergen or become more severe. Cofactors are reported to be relevant in up to 30% of anaphylactic episodes. Nonsteroidal anti-inflammatory drugs and exercise are the best-documented cofactors, although estrogens, angiotensin-converting enzyme inhibitors, β-blockers, lipid-lowering drugs, and alcohol have also been involved. The mechanisms underlying anaphylaxis are complex and involve several interrelated pathways. Some of these pathways may be key to the development of anaphylaxis, while others may only modulate the severity of the reaction. An understanding of predisposing and augmenting factors could lead to the development of new prophylactic and therapeutic approaches. PMID:27164622

  5. The capacity of interleukin-4 to induce in vitro IgE synthesis by B cells of patients with common variable immunodeficiency.

    PubMed Central

    Pastorelli, G; Roncarolo, M G; Peronne, C; Tovo, P A; de Vries, J E

    1990-01-01

    Interleukin-4 (IL-4) has been shown to induce IgE synthesis by peripheral blood mononuclear cells (PBMC) of normal donors in vitro. However, induction of PBMC of patients with common variable immunodeficiency (CVI) with IL-4 resulted in IgE production in only two out of eight cases tested. PBMC of the first patient that produced IgE in response to IL-4 also secreted normal levels of IL-4 upon activation. PBMC of the second patient secreted very low levels of IL-4 in vitro which may account for the very low serum IgE levels in this patient. Of the other six patients who had very low serum IgE levels and whose PBMC failed to produce IgE in response to IL-4 in vitro, five did not secrete IL-4 upon in vitro activation. The capacity of the T cells to produce IL-4 was intact in the sixth patient. Collectively our data indicate that PBMC of the majority of patients with CVI are defective since they failed to respond appropriately to IL-4 and they failed to produce IL-4, contributing to the view that CVI is a heterogeneous disorder in which a variety of T and B cell defects occur. PMID:2119918

  6. A murine model of allergic bronchopulmonary aspergillosis with elevated eosinophils and IgE.

    PubMed

    Kurup, V P; Mauze, S; Choi, H; Seymour, B W; Coffman, R L

    1992-06-15

    A model of allergic bronchopulmonary aspergillosis was developed by exposing BALB/c mice to Aspergillus fumigatus (AF) Ag. Animals immunized intranasally (i.n.) with soluble AF Ag produced low levels of serum IgE compared to animals given alum precipitated AF Ag i.p. The latter treatment also produced higher levels of serum IgG1 and AF-specific IgG1 than soluble AF given i.p. or i.n.. Blood and lung eosinophilia was detected in mice repeatedly exposed to AF by i.n. but not in the groups injected i.p. Particulate AF Ag-induced striking blood and lung eosinophilia and elevated levels of serum IgE in mice preexposed to AF Ag. The results indicate that route of inoculation and physical nature of Ag determine the immune response and can be manipulated to obtain enhanced IgE, eosinophils, or both in the animal model. PMID:1602128

  7. Specific IgE response in patients with brucellosis.

    PubMed Central

    Araj, G. F.; Lulu, A. R.; Khateeb, M. I.; Haj, M.

    1990-01-01

    In the search to find discriminative serological markers to differentiate between patients with acute brucellosis and those with chronic brucellosis, an enzyme-linked immunosorbent assay (ELISA) was used to determine and compare the brucella-specific IgE response in 80 sera from patients with acute brucellosis, 37 sera from patients with chronic brucellosis, 26 sera from patients with positive blood cultures for bacteria other than brucella and 51 sera from healthy controls. The IgE findings were compared to brucella-specific IgG, IgM, IgA and IgG1-4 demonstrated by ELISA, and to microagglutination test (MAT) results. Elevated (positive) antibrucella IgE titres were detected in 89 and 81% of sera from patients with acute and chronic brucellosis respectively. The predominant antibodies found in patients with acute brucellosis were of the IgG, IgM, IgA, IgE, IgG1 and IgG3 types while in chronic brucellosis IgG, IgA, IgE and IgG4 were found. Although IgE can be detected in patients with brucellosis, it does not discriminate between the acute and chronic stages of the disease. PMID:2249721

  8. Selective transport of IgE into ovine mammary secretions.

    PubMed

    Hine, B C; Hunt, P W; Beasley, A M; Windon, R G; Glover, S A; Colditz, I G

    2010-10-01

    Immunoglobulin (Ig) E is actively transported into ovine colostrum. Here we examine the degree of selectivity and the mechanism by which this transfer occurs in sheep. Results indicate that during colostrogenesis in sheep, transfer of immunoglobulins was most selective for IgG1 and IgA followed by IgE, IgM and IgG2. In milk, selectivity was greatest for IgA, followed by IgM, IgE, IgG1 and IgG2. The neonatal Fc receptor (FcRn) and poly immunoglobulin receptor (pIgR) mediate the transport of IgG1 and IgA across the ovine mammary epithelium respectively. In primates and rodents, the low-affinity IgE receptor, Fc epsilonRII, functions to transport IgE across the intestinal epithelium. We therefore investigated the expression of the low-affinity IgE receptor (CD23), pIgR and FcRn transcripts in the ovine mammary gland. The expression profiles of FcRn, pIgR and CD23 mRNA reflected concentrations of their Ig ligands in mammary secretions. These findings suggest a role for CD23 in transport of IgE across the mammary epithelium of sheep. PMID:20226487

  9. Investigation of IGES for CAD/CAE data transfer

    NASA Technical Reports Server (NTRS)

    Zobrist, George W.

    1989-01-01

    In a CAD/CAE facility there is always the possibility that one may want to transfer the design graphics database from the native system to a non-native system. This may occur because of dissimilar systems within an organization or a new CAD/CAE system is to be purchased. The Initial Graphics Exchange Specification (IGES) was developed in an attempt to solve this scenario. IGES is a neutral database format into which the CAD/CAE native database format can be translated to and from. Translating the native design database format to IGES requires a pre-processor and transling from IGES to the native database format requires a post-processor. IGES is an artifice to represent CAD/CAE product data in a neutral environment to allow interfacing applications, archive the database, interchange of product data between dissimilar CAD/CAE systems, and other applications. The intent here is to present test data on translating design product data from a CAD/CAE system to itself and to translate data initially prepared in IGES format to various native design formats. This information can be utilized in planning potential procurement and developing a design discipline within the CAD/CAE community.

  10. Recreation of the 28-entity IGES test file using the ComputerVision CADDS 4X

    NASA Technical Reports Server (NTRS)

    Kuan, Anchyi; Shah, Saurin; Smith, Kevin

    1987-01-01

    An Initial Graphics Exchange Specification (IGES) test file is called the 28 Entity IGES Test File. This file contains 28 geometric and annotation entities which are considered the basic entities that an IGES translator for any CAD system should support. The main purpose was to determine how the IGES preprocessor supports the 28 entities through recreation of the 28 Entity IGES Test File on the ComputerVision CADDS 4X. Test procedure is described and test results are presented.

  11. Adrenergic Regulation of IgE Involves Modulation of CD23 and ADAM10 Expression on Exosomes1

    PubMed Central

    Padro, Caroline J.; Shawler, Todd M.; Gormley, Matthew G.; Sanders, Virginia M.

    2013-01-01

    Soluble CD23 (sCD23) plays a role in the positive regulation of an IgE response. Engagement of the beta-2 adrenergic receptor (β2AR) on a B cell is known to enhance the level of both sCD23 and IgE, although the mechanism by which this occurs is not completely understood. We report herein that, in comparison to a CD40L/IL-4-primed murine B cell alone, β2AR engagement on a primed B cell increased gene expression of ADAM10, which is the primary sheddase of CD23, and protein expression of both CD23 and ADAM10, in a PKA- and p38 MAPK-dependent manner, and promoted the localization of these proteins to exosomes as early as two days after priming, as determined by both Western blot and flow cytometry, and confirmed by electron microscopy. In comparison to isolated exosomes released from primed B cells alone, the transfer of exosomes released from β2AR agonist-exposed primed B cells to cultures of recipient primed B cells resulted in an increase in the level of IgE produced per cell, without affecting the number of cells producing IgE, as determined by ELISPOT. These effects still occurred when a β2AR antagonist was added along with the transfer to block residual agonist, and failed to occur when exosomes were isolated from β2AR-deficient B cells. These findings suggest that the mechanism responsible for mediating the β2AR-induced increase in IgE involves a shuttling of the β2AR-induced increase in CD23 and ADAM10 proteins to exosomes that subsequently mediate an increase in IgE. PMID:24140643

  12. Serum IgE concentration and other immune manifestations of treatment with gold salts are linked to the MHC and IL4 regions in the rat

    SciTech Connect

    Kermarrec, N.; Blanpied, C.; Druet, P.

    1996-01-01

    A subset of patients with rheumatoid arthritis occasionally develops skin reactions and glomerulonephritis and exhibits an increase in serum IgE concentration when treated with gold salts. Brown-Norway (BN) rats injected with aurothiopropanolsulfonate (ATPS) also manifest an autoimmune glomerulonephritis and increased serum IgE concentration, whereas Lewis (LEW) rats are resistant to complications. Here, we show linkage between responses to ATPS in a (BN x LEW) F2 cohort and the major histocompatibility complex (RT1) on rat chromosome 20 and between markers in the region of IL4 and other candidate genes on rat chromosome 10. Recently, human serum IgE concentration has been reported to be linked to the IL-4 region. Taken together, these findings raise the possibility that homologous genes could be implicated in ATPS manifestations in the rat and in the regulation of IgE levels in the human. 10 refs., 1 fig., 2 tabs.

  13. Inhibitory effect of chaga mushroom extract on compound 48/80-induced anaphylactic shock and IgE production in mice.

    PubMed

    Yoon, Taek Joon; Lee, Sue Jung; Kim, Eun Young; Cho, Eun Hee; Kang, Tae Bong; Yu, Kwang-Won; Suh, Hyung Joo

    2013-04-01

    Chaga mushrooms (Inonotus obliquus) are hypothesised to exhibit general immune-potentiating, anti-inflammatory, and antitumor properties, but their anti-allergic activities are not fully understood. Therefore, this study investigated whether a chaga mushroom extract (C-HE) might have anti-allergic activity. This activity was assessed through the levels of the IgE Ab produced in response to an allergen (OVA). The administration of C-HE prophylactically inhibited the systemic anaphylactic shock induced by compound 48/80 in mice. The oral administration of C-HE significantly reduced the total IgE levels in mice and slightly affected the production of IgG1. Furthermore, spleen cell cultures harvested from OVA-sensitised mice that had received C-HE orally showed a significant increase in Th1-derived responses (IFN-γ production). Therefore, our results suggest that the chaga mushroom extract may be used as an anti-allergic functional food. PMID:23535020

  14. Constructing a hybrid molecule with low capacity of IgE binding from Chenopodium album pollen allergens.

    PubMed

    Nouri, Hamid Reza; Varasteh, Abdolreza; Vahedi, Fatemeh; Chamani, Jamshidkhan; Afsharzadeh, Danial; Sankian, Mojtaba

    2012-05-30

    Allergen specific immunotherapy is the only remedy to prevent the progression of allergic diseases. Nowadays, using of recombinant allergens with reduced IgE-binding capacity is an ideal tool for allergen immunotherapy. Therefore, in this study we focused on a hybrid molecule (HM) production with reduced IgE reactivity from Chenopodium album pollen allergens. By means of genetic engineering, a head to tail structure of the three allergens of the C. album pollen was designed. The resulting DNA construct coding for a 46kDa HM was inserted into an expression vector and expressed as hexahistidine tagged fusion protein in Escherichia coli. IgE reactivity of the HM was evaluated by western blotting, inhibition ELISA and in vivo skin prick test and its immunogenic property was tested by proliferation assay. The recombinant HM was expressed and purified by nickel-affinity chromatography. Comparison of the recombinant HM with a mixture of three recombinant allergens, as well as natural allergens in the whole C. album pollen extract via immunological experiments revealed that it has a much lower potential of IgE reactivity. Furthermore, in vivo skin prick tests showed that it has a significantly lower potency to induce cutaneous reactions than the mixture of recombinant wild type allergens and whole extract while, it had been preserved immunogenic properties. Our results have demonstrated that assembling three allergens of C. album in a hybrid molecule can reduce its IgE reactivity. PMID:22504204

  15. An extended study of seroprevalence of anti-Anisakis simplex IgE antibodies in Norwegian blood donors.

    PubMed

    Lin, A H; Nepstad, I; Florvaag, E; Egaas, E; Van Do, T

    2014-01-01

    During the last decade, cases of the fish parasite Anisakis simplex infection and allergy in human have increased in countries with high fish consumption. Our aim was to perform an extended seroprevalence study of anti-IgE antibodies against this parasite in Norway, one of the high fish-consuming countries. At the Department of Immunology and Transfusion Medicine and the Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway, two main groups of anonymized serum samples were collected; the first (n = 993) from recently recruited blood donors (designated 'BDO') and the second (n = 414) from patient with total IgE levels ≥1000 kU/l (designated 'IGE+'). The sera were analysed by the ImmunoCAP(®) method for total IgE and IgE antibodies against A. simplex, house dust mite (HDM), shrimp, cod, crab, brine shrimp and shrimp tropomyosin. The A. simplex positive sera were further tested by an enzyme-linked immunosorbent assay (ELISA) method, which uses 2 recombinant (r) major allergens, rAni s 1 and rAni s 7 as target antigens. SDS-PAGE and Western immunoblotting analyses were also performed. Whereas the prevalences by ImmunoCAP(®) were 0.4% and 16.2% in the BDO and IGE+ groups, respectively, analyses with recombinant allergens showed only 0.0% and 0.2%. Cross-reactivity and immunoblotting analyses suggested that most of the ImmunoCAP(®) positive sera were probably false-positive due to cross-sensitization to shrimp and HDM. However, positivity due to other A. simplex antigens should also be considered. Compared with other high fish-consuming countries, we observed a very low seroprevalence of anti-Anisakis IgE antibodies in a Norwegian population. PMID:24219706

  16. Functional and phenotypic analysis of human T-cell clones which stimulate IgE production in vitro.

    PubMed Central

    Quint, D J; Bolton, E J; McNamee, L A; Solari, R; Hissey, P H; Champion, B R; MacKenzie, A R; Zanders, E D

    1989-01-01

    Peripheral blood mononuclear cells (PBMC) from a patient suffering from the hyper IgE syndrome were used to generate phytohaemagglutinin (PHA)-expanded T-cell clones (all CD4+, CD8-, CD23-). A selection of the clones was tested for their ability to help IgE secretion by culturing with normal B cells in the presence of solid-phase antibody to CD3. Supernatants were harvested on Day 7 and assayed by ELISA for IgE, IgG and IgM. Lymphokine secretion by the clones was assessed by culturing clones for 24 hr with solid-phase antibody to CD3 followed by assay of the supernatants for IL-2, IL-4 and interferon-gamma (IFN-gamma) production. In addition, clones were analysed by flow cytometry for CDw29 and CD45R expression. Initial experiments with seven clones indicated that those clones that could help IgE secretion also stimulated optimal IgG and IgM responses. All clones appeared to secrete IL-2, IL-4 and IFN-gamma, although the amounts of each varied. These results confirm recent findings that human T-cell clones do not fall into Tinf (Th1) and Th (Th2) type subsets as described in the mouse. There was no clear correlation between the lymphokines secreted by the clones and their capacity to help IgE production. However, the helper function of the clones for all isotypes, including IgE, appeared to be related to the level of expression of the surface antigen CDw29. PMID:2525520

  17. Influence of protein expression system on elicitation of IgE antibody responses: experience with lactoferrin.

    PubMed

    Almond, Rachael J; Flanagan, Brian F; Kimber, Ian; Dearman, Rebecca J

    2012-11-15

    With increased interest in genetically modified (GM) crop plants there is an important need to understand the properties that contribute to the ability of such novel proteins to provoke immune and/or allergic responses. One characteristic that may be relevant is glycosylation, particularly as novel expression systems (e.g. bacterial to plant) will impact on the protein glycoprofile. The allergenicity (IgE inducing) and immunogenicity (IgG inducing) properties of wild type native human lactoferrin (NLF) from human milk (hm) and neutrophil granules (n) and a recombinant molecule produced in rice (RLF) have been assessed. These forms of lactoferrin have identical amino acid sequences, but different glycosylation patterns: hmNLF and nNLF have complex glycoprofiles including Lewis (Le)(x) structures, with particularly high levels of Le(x) expressed by nNLF, whereas RLF is simpler and rich in mannose residues. Antibody responses induced in BALB/c strain mice by intraperitoneal exposure to the different forms of lactoferrin were characterised. Immunisation with both forms of NLF stimulated substantial IgG and IgE antibody responses. In contrast, the recombinant molecule was considerably less immunogenic and failed to stimulate detectable IgE, irrespective of endotoxin and iron content. The glycans did not contribute to epitope formation, with equivalent IgE and IgG binding recorded for high titre anti-NLF antisera regardless of whether the immunising NLF or the recombinant molecule were used substrates in the analyses. These data demonstrate that differential glycosylation profiles can have a profound impact on protein allergenicity and immunogenicity, with mannose and Le(x) exhibiting opposing effects. These results have clear relevance for characterising the allergenic hazards of novel proteins in GM crops. PMID:22813905

  18. Molecular mechanisms of IgE mediated food allergy.

    PubMed

    Kumar, Sandeep; Verma, Alok Kumar; Das, Mukul; Dwivedi, Premendra D

    2012-08-01

    The purpose of this review is to collate current knowledge and recent advances in molecular mechanism behind the immediate type hypersensitivity of foods. Food allergy is a growing concern of human health in developed as well as developing countries now days. Food allergic reactions are mostly IgE mediated and also known as immediate type hypersensitivity or type I reaction. This review encompasses a wide range of molecular events during IgE mediated reactions like primary exposure of allergens, processing of allergens by antigen presenting cells, role of transcription factors like GATA-3, STAT-6, NF-AT, c-maf, c-kit and NF-κB, Treg cells, toll like receptors, cytokines and chemokines, class switch to IgE, FcεR1 receptor, priming of IgE on mast cells or basophils, signaling events followed by secondary exposure of allergens, degranulation and release of mediators like leukotrienes, histamines, prostaglandins, β-hexosaminidase and ultimately anaphylaxis. This review may be helpful to beginners as well as experts working in the field of allergy and immunology because of the stepwise explanations of molecular mechanisms involved in IgE mediated reactions. PMID:22668720

  19. Serum IgE levels in coronary artery disease.

    PubMed

    Kounis, Nicholas G; Hahalis, George

    2016-08-01

    The development and progression of atherosclerosis and its predisposition for unstable angina, myocardial infarction and stroke is associated with traditional risk factors such as family history, cigarette smoking, hypertension, dyslipidemia, diabetes mellitus, obesity, imbalance of the hemostatic/fibrinolytic system and sedentary lifestyle. However, much of the variability in atherosclerosis and its manifestations still remains unexplained. Nowadays, there is increasing evidence that immunologic mechanisms play a major role in etiology, prediction of coronary plaque instability and foreseeing severe reaction leading to an actual coronary event. Cells of the immune system such as macrophages, mast cells and T-lymphocytes are major components of human atheromatous plaque. These cells participate in a vicious immune cycle and activate each others via bidirectional stimuli. For example, mast cells can activate macrophages and may enhance T-cell activation. Inducible macrophage protein 1a may activate mast cells, while CD169+ macrophages activate CD8 T cells. T cells may mediate mast-cell activation and proliferation and regulate macrophage activity. Mediators secreted by these cells, including histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines and chemokines, can induce coronary artery spasm and atheromatous plaque erosion and rupture, culminating in the development of acute coronary syndromes. PMID:27288268

  20. IgE receptor signaling in food allergy pathogenesis.

    PubMed

    Oettgen, Hans C; Burton, Oliver T

    2015-10-01

    The pathogenesis of food allergy remains poorly understood. Recent advances in the use of murine models have led to discoveries that mast cells and IgE receptor signaling not only drive immediate hypersensitivity reactions but also exert an immunoregulatory function, promoting the development of allergic sensitivity to foods. We review the evidence that IgE, IgE receptors, key signaling kinases and mast cells impair oral tolerance to ingested foods, preventing the induction of regulatory T cells (Treg) and promoting the acquisition of pro-allergic T helper (Th) 2 responses. We discuss innovative strategies that that could be implemented to counteract these immunoregulatory effects of IgE-mediated mast cell activation, and potentially reverse established sensitization, curing food allergy. PMID:26296054

  1. The sequential appearance of IgG subclasses and IgE during the course of Trichinella spiralis infection.

    PubMed Central

    Ljungström, I; Hammarström, L; Kociecka, W; Smith, C I

    1988-01-01

    Earlier studies have shown that IgG1 and IgG4 are the dominant IgG subclasses in the specific response during a chronic helminthic infection. It has also been suggested that IgG4 production results from chronic or repetitive antigenic stimulation and a correlation between IgG4 and IgE levels exists. An outbreak of Trichinella spiralis infection in Poland provided the opportunity to follow the sequential appearance of the IgG subclass and IgE responses in 15 patients during the early stage of Trichinella infection and to compare these observations in sera obtained one year later from the same patients. The results show that the sequential appearance of the IgG subclasses were IgG1 before IgG3 and IgG3 before IgG4. IgG1 antibodies dominated the immune response in all patients. A statistically significant increase in the number of IgG4 positive sera was observed in patients during the chronic stage compared to the findings during the early stage of infection (13% vs 73%; p less than 0.001), supporting the view that IgG4 results from a chronic antigenic stimulation. A correlation between the appearance of IgG4 and IgE was not found. The highest levels of IgE were seen in the first serum samples obtained, with a decrease during the course of infection. PMID:3224442

  2. Enhanced expression of neuropeptide S (NPS) receptor in eosinophils from severe asthmatics and subjects with total IgE above 100IU/ml.

    PubMed

    Ilmarinen, Pinja; James, Anna; Moilanen, Eeva; Pulkkinen, Ville; Daham, Kameran; Saarelainen, Seppo; Laitinen, Tarja; Dahlén, Sven-Erik; Kere, Juha; Dahlén, Barbro; Kankaanranta, Hannu

    2014-01-01

    Eosinophils are inflammatory cells of particular relevance to asthma exacerbations. Neuropeptide S (NPS) receptor was identified in a search for asthma susceptibility genes, where the risk haplotypes of the NPS receptor gene associated with total serum IgE above 100IU/ml and asthma. The aim of the present study was to investigate and compare expression of NPS receptor in human peripheral blood eosinophils derived from subjects with total serum IgE above and below 100IU/ml and patients with different phenotypes of asthma. Additionally, we aimed to study the function of NPS receptor in human eosinophils. We found higher NPS receptor protein expression in eosinophils derived from subjects with high IgE when compared to those from subjects with low IgE and the level of NPS receptor positively correlated with serum IgE. NPS receptor expression was also higher in eosinophils from patients with severe asthma than in cells from mild asthmatics or healthy controls. The receptor agonist NPS was a chemotactic agent for eosinophils. NPS also increased N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated CD11b integrin levels in eosinophils from subjects with high IgE. Furthermore, eosinophils from those subjects exhibited Ca(2+) mobilization but not cAMP rise in response to NPS. Altogether, NPS receptor may have a pathological role in individuals with severe asthma and/or elevated serum IgE levels as eosinophils from these patients express higher levels of NPS receptor protein and respond to NPS by enhanced migration and adhesion molecule expression. PMID:24239856

  3. Increased local IgE production induced by common aeroallergens and phenotypic alteration of mast cells in Chinese eosinophilic, but not non-eosinophilic, chronic rhinosinusitis with nasal polyps

    PubMed Central

    Cao, Ping-Ping; Zhang, Ya-Na; Liao, Bo; Ma, Jin; Wang, Bao-Feng; Wang, Heng; Zeng, Ming; Liu, Wei-Hong; Schleimer, Robert P.; Liu, Zheng

    2014-01-01

    Background Eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) display distinct patterns of inflammation. However, the pathogenic mechanisms underlying the heterogeneity of CRSwNP need further investigation. Objective To investigate local immunoglobulin E (IgE) production and phenotype of mast cells in eosinophilic and non-eosinophilic CRSwNP in Chinese. Methods Total and specific IgE levels were analyzed by means of the ImmunoCAP system. The molecular steps involved in class switch recombination to IgE were investigated using RT-PCR assays. Mast cell phenotypes, IgE- and high affinity IgE receptor (FcεRI)-positive cells, and allergen binding to specific IgE in sinonasal mucosa were determined by means of immunohistochemistry. Results Compared with controls and non-eosinophilic CRSwNP, local total IgE levels were increased, and local specific IgE to common aeroallergens was more frequently found, in Chinese eosinophilic CRSwNP independent of atopy and without significant association with Staphylococcus aureus enterotoxins. The ε germline gene transcript was also more frequently detected in eosinophilic CRSwNP. The number of IgE- and FcεRI-positive cells was increased in eosinophilic CRSwNP. Most IgE- and FcεRI-positive cells were mast cells. Dust mite antigens could bind to IgE on mast cells in situ. The number of mast cells positive for both tryptase and chymase and activated mast cells was increased in eosinophilic CRSwNP and the number of activated mast cells positively correlated with local IgE level, eotaxin-1 level, and eosinophil count in CRSwNP. Conclusions and Clinical Relevance The local IgE induced by common aeroallergens may mediate mast cell activation and contribute to subsequent eosinophilic inflammation in Chinese CRSwNP. This study offers a rationale for considering intervention strategies designed to target “local allergy” in eosinophilic CRSwNP. PMID:24597471

  4. The Extracellular Domains of IgG1 and T Cell-Derived IL-4/IL-13 Are Critical for the Polyclonal Memory IgE Response In Vivo

    PubMed Central

    Turqueti-Neves, Adriana; Otte, Manuel; Schwartz, Christian; Schmitt, Michaela Erika Renate; Lindner, Cornelia; Pabst, Oliver; Yu, Philipp; Voehringer, David

    2015-01-01

    IgE-mediated activation of mast cells and basophils contributes to protective immunity against helminths but also causes allergic responses. The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells. Here, we used next generation sequencing to uncover a striking overlap between the IgE and IgG1 repertoires in helminth-infected or OVA/alum-immunized wild-type BALB/c mice. The memory IgE response after secondary infection induced a strong increase of IgE+ plasma cells in spleen and lymph nodes. In contrast, germinal center B cells did not increase during secondary infection. Unexpectedly, the memory IgE response was lost in mice where the extracellular part of IgG1 had been replaced with IgE sequences. Adoptive transfer studies revealed that IgG1+ B cells were required and sufficient to constitute the memory IgE response in recipient mice. T cell-derived IL-4/IL-13 was required for the memory IgE response but not for expansion of B cells from memory mice. Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells. Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders. PMID:26523376

  5. Assessment of IgE and IgG4 Binding Capacities of Cow's Milk Proteins Selectively Altered by Proteases.

    PubMed

    Charcosset, Alexandre; Adel-Patient, Karine; Dupont, Christophe; Bernard, Hervé

    2016-05-01

    Specific IgE and IgG4 have been reported to play key roles in the context of IgE-mediated cow's milk allergy (CMA), but the persistence of their epitopes in milk hydrolysates has not been evaluated. Using sera from 32 CMA patients, 6 CMA patients treated by epicutaneous therapy (CM-treated), and 4 CM-tolerant peanut allergic patients, we analyzed the IgE and IgG4 binding capacities related to major milk allergens in processed milk. Different proteases (plasmin, chymosin, α-chymotrypsin, or pepsin) were used progressively and selectively to hydrolyze β-lactoglobulin (β-LG) and casein (CN) in milk. We then showed that proteases differentially affect IgE or IgG4 immunoreactivities of CN and β-LG and also that we could not relate IgE and/or IgG4 levels or specificities to milk hydrolysates to the clinical status of the patients. PMID:27015440

  6. A School-Level Proxy Measure for Individual-level Poverty Using School-Level Eligibility for Free and Reduced-Price Meals

    ERIC Educational Resources Information Center

    Day, Sophia E.; Hinterland, Kinjia; Myers, Christa; Gupta, Leena; Harris, Tiffany G.; Konty, Kevin J.

    2016-01-01

    Background: Socioeconomic status (SES) impacts health outcomes. The Youth Risk Behavior Survey (YRBS), like many school-based data sources, lacks individual-level poverty information. We propose using school-level percentages of student eligibility for free/reduced-price meals (%FRPM) as a proxy for individual-level poverty. Methods: Using the New…

  7. Reduced progesterone levels explain the reduced risk of breast cancer in obese premenopausal women: a new hypothesis.

    PubMed

    Dowsett, Mitch; Folkerd, Elizabeth

    2015-01-01

    Understanding the complex relationship between obesity and breast cancer is fundamental to our knowledge of the etiology of this malignancy; changes in the composition of the hormonal milieu are implicit in this process. Estrogens are synthesized from androgens by aromatase in the gonads and in peripheral tissues, principally, adipose tissue. Obesity in women, regardless of their age, leads to more aromatase and more extra-glandular estrogen production. In postmenopausal women, in whom ovarian estrogen production is absent, the increased incidence of breast cancer in women with high body mass index has been attributed to the relatively high plasma levels of estradiol from subcutaneous fat. In contrast, obesity in premenopausal women is associated with a previously unexplained reduced incidence of breast cancer. In obese premenopausal women, the cumulative effect of higher levels of estrogens synthesized in the peripheral tissues, together with ovarian estrogen production, results in a negative feedback on the hypothalamic pituitary controlled release of gonadotrophins and a resultant diminution in ovarian steroid production. As a consequence, the normal balance of estrogen and progesterone levels is disrupted: while estrogen levels are normalized, progesterone production is markedly decreased. Progesterone is a promoter of proliferation in the breast. The low levels of progesterone in obese premenopausal women are consistent with, and we propose, are responsible for, the reduction in breast cancer incidence in these women. PMID:25414027

  8. IgG and IgE Collaboratively Accelerate Expulsion of Strongyloides venezuelensis in a Primary Infection

    PubMed Central

    Matsumoto, Makoto; Sasaki, Yuki; Yasuda, Koubun; Takai, Toshiyuki; Muramatsu, Masamichi; Yoshimoto, Tomohiro

    2013-01-01

    The host deploys a subset of immune responses to expel helminths, which differs depending on the nature of the helminth. Strongyloides venezuelensis, a counterpart of the human pathogen S. stercoralis, naturally infects rodents and has been used as an experimental model. Here we show that induction of immunoglobulin G (IgG) and IgE is a prerequisite for rapid expulsion of S. venezuelensis during a primary infection. Activation-induced cytidine deaminase-deficient (AID−/−) mice, which lack the ability to switch IgM to other isotypes, normally developed T-helper 2 (Th2) cells and intestinal mastocytosis after infection with S. venezuelensis. Although AID−/− mice expelled Nippostrongylus brasiliensis normally, they required a much longer period to expel S. venezuelensis than wild-type (WT) mice. Adoptive transfers of immune sera from S. venezuelensis-infected but not N. brasiliensis-infected mice restored the ability of AID−/− mice to promptly expel S. venezuelensis. Immune serum-derived IgG and IgE induced worm expulsion via Fc γ receptor III (FcγRIII) and Fc ε receptor I (FcεRI), respectively, and a mixture of IgG and IgE showed collaborative effects. Whereas FcγRIII−/− mice or FcεRIα−/− mice normally could expel S. venezuelensis, FcγRIII−/− mice, when their IgE was neutralized by anti-IgE, or FcεRIα−/− mice, when their IgG binding to FcγRIII was blocked by anti-FcγRIII, showed a markedly reduced ability to expel S. venezuelensis. These data reveal that IgG and IgE play redundant roles but act in concert to accelerate S. venezuelensis expulsion. Mast cell-deficient mice, even those equipped with immune serum-derived IgG or IgE, failed to expel S. venezuelensis promptly, suggesting that mast cells are cellular targets of IgG and IgE. PMID:23630966

  9. CLINICALLY RELEVANT IGE-CROSS-REACTIVITY OF NUT ALLERGENS

    EPA Science Inventory

    All data resulting from this study will be catalogued in SDAP .This work will generate important information relating the structure/ physicochemical properties of cross-reactive IgE epitopes to clinical response, and model factors that underlie allergen recognition by the immu...

  10. IGE IN ASTHMATIC HUMAN SERA IS REACTIVE AGAINST MOLD EXTRACTS

    EPA Science Inventory

    Molds have been associated with various health effects including asthma, but their role in induction of asthma is unclear. However, the presence of mold-specific IgE indicates their capacity to induce allergic responses and possibly exacerbate asthma symptoms. This study was und...

  11. Fucoidan prevents C{epsilon} germline transcription and NF{kappa}B p52 translocation for IgE production in B cells

    SciTech Connect

    Oomizu, Souichi; Yanase, Yuhki; Suzuki, Hidenori; Kameyoshi, Yoshikazu; Hide, Michihiro . E-mail: mhide@hiroshima-u.ac.jp

    2006-11-24

    Fucoidan, a dietary fiber contained in seaweed, reduces the increase of antigen-specific IgE in mice exposed to ovalbumin. In this study, we investigated the effect of fucoidan on IgE production and intracellular events in B cells in vitro. Fucoidan inhibited the production of IgE and C{epsilon} germline transcription in murine B cells induced by IL-4 (100 ng/ml) and anti-CD40 antibodies (10 {mu}g/ml), whereas it stimulated cell proliferation. A significant effect of fucoidan on IgE production was observed when B cells were stimulated with a higher dose (5 {mu}g/ml) of anti-CD40 antibodies, but not when stimulated with lower doses (1.25, 2.5 {mu}g/ml), regardless of the IL-4 concentrations. Moreover, nuclear translocation of NF{kappa}B p52, but neither that of NF{kappa}B p65, nor the phosphorylation of JAK1 and STAT6 was reduced by fucoidan. These results suggest that fucoidan inhibited IgE production by preventing the NF{kappa}B p52-mediated pathways activated by CD40.

  12. Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of allergic airway inflammation

    PubMed Central

    Palaniyandi, Senthilkumar; Liu, Xiaoyang; Periasamy, Sivakumar; Ma, Aiying; Tang, Jin; Jenkins, Mark; Tuo, Wenbin; Song, Wenxia; Keegan, Achsah D.; Conrad, Daniel H.; Zhu, Xiaoping

    2015-01-01

    The epithelial lining of the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human low affinity IgE receptor, CD23 (FcεRII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monolayer in vitro. However, it remains unknown whether the CD23-dependent IgE transfer pathway in AECs initiates and facilitates allergic inflammation in vivo, and whether inhibition of this pathway attenuates allergic inflammation. To this end, we show that in wild-type (WT) mice, epithelial CD23 transcytosed both IgE and ovalbumin (OVA)-IgE complexes across the airway epithelial barrier, while neither type of transcytosis was observed in CD23 knockout (KO) mice. In chimeric mice, OVA sensitization and aerosol challenge of WT/WT (bone-marrow transfer from the WT to WT) or CD23KO/WT (CD23KO to WT) chimeric mice, which express CD23 on radioresistant airway structural cells (mainly epithelial cells) resulted in airway eosinophilia, including collagen deposition and a significant increase in goblet cells, and increased airway hyperreactivity. In contrast, the absence of CD23 expression on airway structural or epithelial cells, but not on hematopoietic cells, in WT/CD23KO (the WT to CD23KO) chimeric mice significantly reduced OVA-driven allergic airway inflammation. In addition, inhalation of the CD23-blocking B3B4 antibody in sensitized WT mice before or during airway challenge suppressed the salient features of asthma, including bronchial hyperreactivity. Taken together, these results identify a previously unproven mechanism in which epithelial CD23 plays a central role in the development of allergic inflammation. Further, our study suggests that functional inhibition of CD23 in the airway is a potential therapeutic approach with which to inhibit the development of asthma. PMID:25783969

  13. A single glycan on IgE is indispensable for initiation of anaphylaxis.

    PubMed

    Shade, Kai-Ting C; Platzer, Barbara; Washburn, Nathaniel; Mani, Vinidhra; Bartsch, Yannic C; Conroy, Michelle; Pagan, Jose D; Bosques, Carlos; Mempel, Thorsten R; Fiebiger, Edda; Anthony, Robert M

    2015-04-01

    Immunoglobulin ε (IgE) antibodies are the primary mediators of allergic diseases, which affect more than 1 in 10 individuals worldwide. IgE specific for innocuous environmental antigens, or allergens, binds and sensitizes tissue-resident mast cells expressing the high-affinity IgE receptor, FcεRI. Subsequent allergen exposure cross-links mast cell-bound IgE, resulting in the release of inflammatory mediators and initiation of the allergic cascade. It is well established that precise glycosylation patterns exert profound effects on the biological activity of IgG. However, the contribution of glycosylation to IgE biology is less clear. Here, we demonstrate an absolute requirement for IgE glycosylation in allergic reactions. The obligatory glycan was mapped to a single N-linked oligomannose structure in the constant domain 3 (Cε3) of IgE, at asparagine-394 (N394) in human IgE and N384 in mouse. Genetic disruption of the site or enzymatic removal of the oligomannose glycan altered IgE secondary structure and abrogated IgE binding to FcεRI, rendering IgE incapable of eliciting mast cell degranulation, thereby preventing anaphylaxis. These results underscore an unappreciated and essential requirement of glycosylation in IgE biology. PMID:25824821

  14. Immunoglobulin levels in Iraq.

    PubMed Central

    Al-Agidi, S K; Papiha, S S; Roberts, D F

    1977-01-01

    In a study of immunoglobulin levels in 192 apparently healthy individuals in Iraq, regional differences occur in IgE and IgG. The main levels of IgG, IgM and IgA tend to be low, and of IgE clearly elevated. It is suggested that this pattern may be explained by the presence of intestinal parasites which stimulate IgE production. The genetic differences that exist between the regional populations, and the occurrence of associations of immunoglobulin level with several polymorphic systems, suggests the possibility of a genetic element in the regional immunoglobulin differences. PMID:908174

  15. Low levels of transforming growth factor-beta (TGF-beta) and reduced suppression of Th2-mediated inflammation in hyperreactive human onchocerciasis

    PubMed Central

    KORTEN, S.; HOERAUF, A.; KAIFI, J. T.; BÜTTNER, D. W.

    2011-01-01

    SUMMARY Th2-biased inflammation with eosinophilia and IgE production is a hallmark of helminth infections. It is pronounced in hyperreactive onchocerciasis patients (‘sowda’ or ‘local form’), who efficiently kill microfilariae resulting in severe dermatitis and lymphadenitis. In contrast, hyporeactive patients (‘generalised form’) tolerate high microfilarial loads. This is thought to be mediated by regulatory CD4+ T cells and macrophages producing suppressive cytokines such as IL-10 and transforming growth factor-beta (TGF-β). We investigated whether hyperreactivity was reflected by lower local TGF-β production, analysing stable latent TGF-β1 expression in onchocercomas, lymph nodes and skin from hyperreactive and hyporeactive patients by immunohistochemistry. TGF-β expression was compared with that of IgE, IgG1, IgG4, and the antigen-presenting, CD4+ T cell-inducing MHC class II molecule HLA-DR. TGF-β was weakly and less frequently expressed by various cell types in onchocercomas, skin and lymph nodes from hyperreactive compared to hyporeactive patients. This applied to reactions around living and dead adult worms as well as dead microfilariae. Antigen-presenting cells strongly expressed HLA-DR in both forms, but their numbers were reduced in hyperreactive nodules. Plasma cells produced more IgE and IgG1, but less of the anti-inflammatory antibody IgG4 in hyperreactive onchocercomas. In conclusion, hyperreactivity is linked with reduced local expression of TGF-β, HLA-DR and IgG4, which might contribute to the insufficient down-regulation of inflammation via TGF-β- and HLA-DR-induced regulatory lymphocytes. PMID:20619070

  16. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  17. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    PubMed

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P < 0.05 vs. vehicle). A significant 20% reduction in hepatic LDL receptor protein expression was also observed with empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. PMID:27207551

  18. Tension between reducing sea-level rise and global warming through solar-radiation management

    NASA Astrophysics Data System (ADS)

    Irvine, P. J.; Sriver, R. L.; Keller, K.

    2012-02-01

    Geoengineering using solar-radiation management (SRM) is gaining interest as a potential strategy to reduce future climate change impacts. Basic physics and past observations suggest that reducing insolation will, on average, cool the Earth. It is uncertain, however, whether SRM can reduce climate change stressors such as sea-level rise or rates of surface air temperature change. Here we use an Earth system model of intermediate complexity to quantify the possible response of sea levels and surface air temperatures to projected climate forcings and SRM strategies. We find that SRM strategies introduce a potentially strong tension between the objectives to reduce (1) the rate of temperature change and (2) sea-level rise. This tension arises primarily because surface air temperatures respond faster to radiative forcings than sea levels. Our results show that the forcing required to stop sea-level rise could cause a rapid cooling with a rate similar to the peak business-as-usual warming rate. Furthermore, termination of SRM was found to produce warming rates up to five times greater than the maximum rates under the business-as-usual CO2 scenario, whereas sea-level rise rates were only 30% higher. Reducing these risks requires a slow phase-out of many decades and thus commits future generations.

  19. Down-modulation of antigen-induced activation of murine cultured mast cells sensitized with a highly cytokinergic IgE clone.

    PubMed

    Sakanaka, Mariko; Kurimune, Yuki; Yamada, Keiko; Hyodo, Nao; Natsuhara, Mayuko; Ichikawa, Atsushi; Furuta, Kazuyuki; Tanaka, Satoshi

    2016-06-01

    Accumulating evidence suggests that several IgE clones can activate mast cells during the sensitization phase even in the absence of antigen. They were found to induce pro-inflammatory cytokine release, histamine synthesis, chemotaxis, adhesion, and accelerated maturation of mast cells, although it remains unknown whether antigen-induced responses can be affected by differences of IgE clones. We compared two IgE clones, which were different in the capacity to activate mast cells during sensitization, in terms of potentials to affect antigen-induced degranulation and cytokine releases using IL-3-dependent murine bone marrow-derived cultured mast cells (BMMCs). Antigen-induced degranulation and pro-inflammatory cytokine release were augmented, when BMMCs were sensitized with elevated concentrations of a clone IgE-3, which did not induce phosphorylation of JNK and cytokine release in the absence of antigen, whereas those were significantly rather decreased, when BMMCs were sensitized with elevated concentrations of a clone SPE-7, one of the most potent cytokinergic IgE clones, which intensively induced phosphorylation of JNK. This attenuated response with SPE-7 was accompanied by decreased tyrosine phosphorylation of the cellular proteins including Syk upon antigen stimulation. SP600125, which is known to inhibit JNK, restored the levels of antigen-induced degranulation and phosphorylation of Syk in BMMCs sensitized with higher concentrations of a clone SPE-7 when it was added before sensitization. Treatment with anisomycin, a potent activator of JNK, before IgE sensitization significantly suppressed antigen-induced degranulation. These findings suggest that differences of sensitizing IgE clones can affect antigen-induced responses and activation of JNK during sensitization might suppress antigen-induced activation of mast cells. PMID:27060497

  20. Effect of walnut (Juglans regia) polyphenolic compounds on ovalbumin-specific IgE induction in female BALB/c mice.

    PubMed

    Comstock, Sarah S; Gershwin, Laurel J; Teuber, Suzanne S

    2010-03-01

    English walnuts are implicated in severe, IgE-mediated food allergy in humans. We sought to determine if polyphenolic compounds extracted from the edible nut could promote IgE production to a coadministered allergen. BALB/c mice were sensitized to ovalbumin (OVA) with or without alum (AL) or polyphenolic-enriched extract via intraperitoneal injection. Serum was analyzed for total IgE and OVA-specific IgE, IgG(1,) and IgG(2a/2b). Coadministration of walnut polyphenolic-enriched extract with antigen and AL increased serum concentrations of antigen-specific IgE and IgG(1). When AL was excluded from the injections, polyphenolic extract tended to enhance OVA-specific IgE and IgG(1) over levels induced by OVA alone, but the increase did not reach significance. Serum IgG(2a/2b) levels were similar between mice receiving OVA/AL and OVA/AL with polyphenolics. Thus, walnut polyphenolic extract enhanced the Th2-skewing effect of an aluminum hydroxide adjuvant. This indicates that walnut polyphenolic compounds may play a role in allergic sensitization of genetically predisposed individuals. PMID:20388137

  1. Galectin and aldolase-like molecules are responsible for the specific IgE response in humans exposed to Dirofilaria immitis.

    PubMed

    Pou-Barreto, C; Quispe-Ricalde, M A; Morchón, R; Vázquez, C; Genchi, M; Postigo, I; Valladares, B; Simón, F

    2008-01-01

    Dirofilaria immitis is the agent of the heartworm disease in canids and felids, and of pulmonary dirofilariosis in man. Like other filariae, D. immitis harbours endosymbion Wolbachia bacteriae. In this work we analyse the response of specific IgE antibodies against both D. immitis antigens and the Wolbachia surface protein (WSP) in two groups of persons living in an area of canine endemia, one presenting high levels of total IgE (group 1) and other with normal levels (group 2). Infections with D. immitis were demonstrated by the presence of specific IgG in 228 individuals(48.8%) of the group 1 and only in one of the group 2. Specific IgE antibody response against D. immitis antigens was detected only in individuals of the group 1. IgE response against WSP was not detected in any group. The IgE response was directed mainly against two molecules of 33 and 42 kDa of the antigenic extract of D. immitis. These molecules were identified by mass spectrometry as a galectin and an aldolase, respectively. Their possible role in the survival mechanisms of the parasite and their contribution to development of allergic reactions in individuals resident in areas with heartworm disease are discussed. PMID:19067840

  2. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  3. Structural Basis of IgE Binding to α- and γ-Gliadins: Contribution of Disulfide Bonds and Repetitive and Nonrepetitive Domains.

    PubMed

    Mameri, Hamza; Brossard, Chantal; Gaudin, Jean-Charles; Gohon, Yann; Paty, Evelyne; Beaudouin, Etienne; Moneret-Vautrin, Denise-Anne; Drouet, Martine; Solé, Véronique; Wien, Frank; Lupi, Roberta; Larré, Colette; Snégaroff, Jacques; Denery-Papini, Sandra

    2015-07-29

    Wheat products cause IgE-mediated allergies. The present study aimed to decipher the molecular basis of α- and γ-gliadin allergenicity. Gliadins and their domains, the repetitive N-terminal and the nonrepetitive C-terminal domains, were cloned and expressed in Escherichia coli. Their secondary structures and their IgE binding capacity were compared with those of natural proteins before and after reduction/alkylation. Allergenicity was evaluated with sera from patients who had a wheat food allergy or baker's asthma. The secondary structures of natural and recombinant proteins were slightly different. Compared with natural gliadins, recombinant proteins retained IgE binding but with reduced reactivity. Reduction/alkylation decreased IgE binding for both natural and recombinant gliadins. Although more continuous epitopes were identified in the N-terminal domains of α- and γ-gliadins, both the N-terminal and C-terminal domains contributed to IgE binding. As for other members of the prolamin superfamily, disulfide bonds appear to be of high importance for IgE binding. PMID:26186140

  4. Assessment of the Allergenic Potential of Transgenic Wheat (Triticum aestivum) with Reduced Levels of ω5-Gliadins, the Major Sensitizing Allergen in Wheat-Dependent Exercise-Induced Anaphylaxis.

    PubMed

    Altenbach, Susan B; Tanaka, Charlene K; Pineau, Florence; Lupi, Roberta; Drouet, Martine; Beaudouin, Etienne; Morisset, Martine; Denery-Papini, Sandra

    2015-10-28

    The ω5-gliadins are the major sensitizing allergens in wheat-dependent exercise-induced anaphylaxis (WDEIA). In this study, two-dimensional immunoblot analysis was used to assess the allergenic potential of two transgenic wheat lines in which ω5-gliadin genes were silenced by RNA interference. Sera from 7 of 11 WDEIA patients showed greatly reduced levels of immunoglobulin E (IgE) reactivity to ω5-gliadins in both transgenic lines. However, these sera also showed low levels of reactivity to other gluten proteins. Sera from three patients showed the greatest reactivity to proteins other than ω5-gliadins, either high-molecular-weight glutenin subunits (HMW-GSs), α-gliadins, or non-gluten proteins. The complexity of immunological responses among these patients suggests that flour from the transgenic lines would not be suitable for individuals already diagnosed with WDEIA. However, the introduction of wheat lacking ω5-gliadins could reduce the number of people sensitized to these proteins and thereby decrease the overall incidence of this serious food allergy. PMID:26447559

  5. IgE reactivity to hen egg white allergens in dogs with cutaneous adverse food reactions.

    PubMed

    Shimakura, Hidekatsu; Uchiyama, Jumpei; Saito, Taku; Miyaji, Kazuki; Fujimura, Masato; Masuda, Kenichi; Okamoto, Noriaki; DeBoer, Douglas J; Sakaguchi, Masahiro

    2016-09-01

    Dogs with cutaneous adverse food reactions (CAFR) often have specific IgE to food allergens. Egg white, which is majorly composed of ovomucoid, ovalbumin, ovotransferrin, and lysozyme, is a food allergen in dogs. Information of the IgE reactivity to purified egg white allergens supports accurate diagnosis and efficiency treatment in humans. However, to the best of our knowledge, there have been no studies on the IgE reactivity to purified egg white allergens in dogs. Here, we investigated the IgE reactivity to crude and purified allergens of hen egg white in dogs with CAFR. First, when we examined serum samples from 82 dogs with CAFR for specific IgE to crude egg white by ELISA, 9.8% (8/82) of the dogs with CAFR showed the IgE reactivity to crude egg white. We then used sera from the eight dogs with positive IgE reactivity to crude egg white to examine the IgE reactivity to four purified allergens, ovomucoid, ovalbumin, ovotransferrin, and lysozyme, by ELISA. We found that 75% (6/8) of the dogs showed IgE reactivity to both ovomucoid and ovalbumin, and that 37.5% (3/8) of the dogs showed IgE reactivity to ovotransferrin. None (0/8) showed IgE reactivity to lysozyme. Moreover, validating these results, the immunoblot analyses were performed using the sera of the three dogs showing the highest IgE reactivity to crude egg white. Both anti-ovomucoid and anti-ovalbumin IgE were detected in the sera of these dogs, while anti-ovotransferrin IgE was not detected. Considering these, ovomucoid and ovalbumin appears to be the major egg white allergens in dogs with CAFR. PMID:27436445

  6. IgE in the diagnosis and treatment of allergic disease.

    PubMed

    Platts-Mills, Thomas A E; Schuyler, Alexander J; Erwin, Elizabeth A; Commins, Scott P; Woodfolk, Judith A

    2016-06-01

    Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the "allergic" disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow's milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response. PMID:27264001

  7. High IgE sensitization to maize and rice pollen in the highlands of Madagascar

    PubMed Central

    Ramavovololona; Sénéchal, Hélène; Andrianarisoa, Ange; Rakotoarimanana, Vololona; Godfrin, Dominique; Peltre, Gabriel; Poncet, Pascal; Sutra, Jean-Pierre

    2014-01-01

    Introduction Maize and rice are two crops constituting the main food supply in many under-developed and developing countries. Despite the large area devoted to the culture, the sensitization to the pollen from these plants is reported to be low and often considered as an occupational allergy. Methods Sixty five Malagasy pollen allergic patients were clinically and immunochemically investigated with regard to maize and rice pollen allergens. Pollen extracts were electrophoretically separated in 1 and 2 dimensions and IgE and IgG reactivities detected upon immunoblotting. Results When exploring the sensitization profile of Malagasy allergic patients to maize and rice pollen, it appears that a high proportion of these patients consulting during grass pollinating season were sensitized to both pollen as revealed by skin prick testing (62 vs. 59%) and IgE immunoblotting (85 vs. 40%). Several clinically relevant allergens were recognized by patients’ serum IgE in maize and rice pollen extracts. Conclusion The high levels of maize and rice pollen sensitization should be related, in this tropical region, to a specific environmental exposure including i) a proximity of the population to the allergenic sources and ii) a putative exacerbating effect of a highly polluted urban atmosphere on pollen allergenicity. Cross-reactivities between wild and cultivated grasses and also between rice and maize pollen are involved as well as some specific maize sensitizations. The presence of dense urban and peri-urban agriculture, in various African regions and worldwide, could be a high environmental risk factor for people sensitive to maize pollen. PMID:25870739

  8. IgE and Mast Cells: The Endogenous Adjuvant.

    PubMed

    Oettgen, Hans C; Burton, Oliver T

    2015-01-01

    Mast cells and immunoglobulin E (IgE) are most familiar as the effectors of type I hypersensitivity reactions including anaphylaxis. It is becoming clear however that this pair has important immunomodulatory effects on innate and adaptive cells of the immune system. In this purview, they act as endogenous adjuvants to ignite evolving immune responses, promote the transition of allergic disease into chronic illness, and disrupt the development of active mechanisms of tolerance to ingested foods. Suppression of IgE-mediated mast cell activation can be exerted by molecules targeting IgE, FcɛRI, or signaling kinases including Syk, or by IgG antibodies acting via inhibitory Fcγ receptors. Recent reports indicate that such interventions have promise in the development of strategies to treat allergic disease. PMID:26073985

  9. Effect of passive smoking on frequency of respiratory illnesses and serum immunoglobulin-E (IgE) and interleukin-4 (IL-4) concentrations in exposed children.

    PubMed

    el-Nawawy, A; Soliman, A T; el-Azzouni, O; Amer el-S; Demian, S; el-Sayed, M

    1996-06-01

    We studied the relationship of serum immunoglobulin-E (Ig-E) and interleukin-4 (IL-4) concentrations, eosinophil counts, and frequency of respiratory illness with passive smoking in 70 randomly selected children of smoking parents. Fifty randomly selected age-matched children of non-smoking parents served as controls. Children of smoking parents had higher frequency of respiratory illnesses per year (P < 0.01), significantly higher total leucocytic and eosinophil counts, higher percentage of eosinophils (P < 0.01), and higher serum IgE and IL-4 concentrations (P < 0.05) compared to the control group. Serum IgE level was correlated positively with the average number of smoked cigarettes/day, number of siblings, and total leucocytic count. Interleukin-4 concentrations were significantly correlated with the number of smoked cigarettes and IgE levels. Although IgE levels were higher in children of smoking parents (587 +/- 359 IU/ml) compared to controls (189 +/- 21 IU/ml), they did not differ significantly between children with and those without frequent respiratory illness (605 +/- 365 and 557 +/- 354 IU/ml, respectively). Interleukin-4 concentrations were significantly higher in children of smoking parents with frequent respiratory illness (1.8 +/- 0.5 pg/ml) v. those without frequent respiratory illness (1.3 +/- 0.45 pg/ml). Multiple logistic regression analysis revealed that the overall positivity of the risk factors predisposing to respiratory diseases in the study children was 79 percent, and the highest odds ratio was that for IL-4 (OR = 5.15). In conclusion, there is a significant increase in IL-4 and Ig-E concentrations, high eosinophil count and frequent respiratory symptoms in children of smoking parents. It remains that the current state of knowledge on health risks associated with passive smoking warrants that strong preventive action be promoted. PMID:8699585

  10. Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles"

    PubMed Central

    Khoo, Siew-Kim; Mäkelä, Mika J; Candelaria, Pierre; Hayden, Catherine M; von Hertzen, Leena; Laatikainen, Tiina; Vartiainen, Erkki; Goldblatt, Jack; Haahtela, Tari; LeSouëf, Peter N

    2014-01-01

    Purpose We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. Methods This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. Results The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. Conclusion Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments. PMID:24991459

  11. Application Protocol, Initial Graphics Exchange Specification (IGES), Layered Electrical Product

    SciTech Connect

    O`Connell, L.J.

    1994-12-01

    An application protocol is an information systems engineering view of a specific product The view represents an agreement on the generic activities needed to design and fabricate the product the agreement on the information needed to support those activities, and the specific constructs of a product data standard for use in transferring some or all of the information required. This application protocol describes the data for electrical and electronic products in terms of a product description standard called the Initial Graphics Exchange Specification (IGES). More specifically, the Layered Electrical Product IGES Application Protocol (AP) specifies the mechanisms for defining and exchanging computer-models and their associated data for those products which have been designed in two dimensional geometry so as to be produced as a series of layers in IGES format The AP defines the appropriateness of the data items for describing the geometry of the various parts of a product (shape and location), the connectivity, and the processing and material characteristics. Excluded is the behavioral requirements which the product was intended to satisfy, except as those requirements have been recorded as design rules or product testing requirements.

  12. The Design of the IGE Evaluation Project Phase IV Comparative Studies. Comparative Study of Phase IV IGE Evaluation Project. Phase IV, Project Paper 80-2.

    ERIC Educational Resources Information Center

    Romberg, Thomas A.; And Others

    This paper outlines the design of two Comparative Studies of Phase IV of the Individually Guided Education (IGE) Evaluation Project. More than 2,000 elementary schools in 25 states use the IGE system. The Evaluation Project was designed to gain a comprehensive view of the system's operation and effectiveness. Phase IV investigated pupil outcomes,…

  13. An Action Science Research Approach to Reducing Student Tardiness at the High School Level

    ERIC Educational Resources Information Center

    Gile, Curtis S.

    2013-01-01

    The purpose of this action research study was to design, implement, analyze, and evaluate a series of interventions to reduce student tardiness at the high school level. Another purpose of the study was to determine the underlying values, beliefs, and behaviors associated with student tardiness from a faculty and staff perspective. The study…

  14. PROLONGED FASTING AND CORTISOL REDUCE MYOSTATIN MRNA LEVELS IN TILAPIA LARVAE, SHORT-TERM FASTING ELEVATES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indices in adults, skeletal muscle myostatin mRNA...

  15. Schoolwide Intervention to Reduce Chronic Tardiness at the Middle and High School Levels

    ERIC Educational Resources Information Center

    Tyre, Ashli; Feuerborn, Laura; Pierce, Jennifer

    2011-01-01

    When many students are tardy at the secondary level, teachers must continually restart instruction or delay beginning instructional periods throughout the school day. To address the considerable amount of instructional time lost caused by high rates of tardiness, the authors investigated the results of schoolwide intervention to reduce student…

  16. Evidence for a Peak Shift in a Humoral Response to Helminths: Age Profiles of IgE in the Shuar of Ecuador, the Tsimane of Bolivia, and the U.S. NHANES

    PubMed Central

    Blackwell, Aaron D.; Gurven, Michael D.; Sugiyama, Lawrence S.; Madimenos, Felicia C.; Liebert, Melissa A.; Martin, Melanie A.; Kaplan, Hillard S.; Snodgrass, J. Josh

    2011-01-01

    Background The peak shift model predicts that the age-profile of a pathogen's prevalence depends upon its transmission rate, peaking earlier in populations with higher transmission and declining as partial immunity is acquired. Helminth infections are associated with increased immunoglobulin E (IgE), which may convey partial immunity and influence the peak shift. Although studies have noted peak shifts in helminths, corresponding peak shifts in total IgE have not been investigated, nor has the age-patterning been carefully examined across populations. We test for differences in the age-patterning of IgE between two South American forager-horticulturalist populations and the United States: the Tsimane of Bolivia (n = 832), the Shuar of Ecuador (n = 289), and the U.S. NHANES (n = 8,336). We then examine the relationship between total IgE and helminth prevalences in the Tsimane. Methodology/Principal Findings Total IgE levels were assessed in serum and dried blood spots and age-patterns examined with non-linear regression models. Tsimane had the highest IgE (geometric mean  = 8,182 IU/ml), followed by Shuar (1,252 IU/ml), and NHANES (52 IU/ml). Consistent with predictions, higher population IgE was associated with steeper increases at early ages and earlier peaks: Tsimane IgE peaked at 7 years, Shuar at 10 years, and NHANES at 17 years. For Tsimane, the age-pattern was compared with fecal helminth prevalences. Overall, 57% had detectable eggs or larva, with hookworm (45.4%) and Ascaris lumbricoides (19.9%) the most prevalent. The peak in total IgE occurred around the peak in A. lumbricoides, which was associated with higher IgE in children <10, but with lower IgE in adolescents. Conclusions The age-patterning suggests a peak shift in total IgE similar to that seen in helminth infections, particularly A. lumbricoides. This age-patterning may have implications for understanding the effects of helminths on other health outcomes, such as allergy, growth

  17. Reduction in IgE reactivity of Pacific mackerel parvalbumin by heat treatment.

    PubMed

    Kubota, Hiroyuki; Kobayashi, Ayako; Kobayashi, Yukihiro; Shiomi, Kazuo; Hamada-Sato, Naoko

    2016-09-01

    Parvalbumin, a major fish allergen, has been reported to be highly thermostable. However, little is known as to whether parvalbumin is stable at more than 100°C. Thermostability of the Pacific mackerel parvalbumin was examined by subjecting heated (20-140°C) muscle extracts to SDS-PAGE, western blotting and ELISA. As judged by SDS-PAGE and western blotting with the anti-parvalbumin antiserum recognizing the primary structure, the parvalbumin was not degraded even under severe heating conditions. However, western blotting analysis with the monoclonal antibody recognizing the stereoscopic structure revealed that the parvalbumin undergoes conformational changes in a heating load-dependent manner. Importantly, the IgE reactivity of the parvalbumin determined by ELISA using patient sera was also reduced in a heating load-dependent manner; complete loss of IgE reactivity was induced by heating at 140°C. This study showed that the allergenicity of the Pacific mackerel parvalbumin is considerably less thermostable than assumed for other fish parvalbumins. PMID:27041301

  18. Reduced serum levels of 1 alpha,25-dihydroxyvitamin D during long-term total parenteral nutrition.

    PubMed

    Klein, G L; Horst, R L; Norman, A W; Ament, M E; Slatopolsky, E; Coburn, J W

    1981-05-01

    Painful bone disease, characterized by patchy osteomalacia and inactive bone, can develop in patients treated with total parenteral nutrition for more than 3 months. Serum levels of 1 alpha,25-dihydroxyvitamin D (1 alpha, 25(OH)2D), 24,25-dihydroxyvitamin D and 25-hydroxyvitamin D were measured in seven adults and five children treated with parenteral nutrition for 9 to 60 months. Serum levels of 1 alpha, 25(OH)2D were markedly reduced, while levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were normal. Serum calcium and phosphorus levels were normal or slightly increased, and immunoreactive parathyroid hormone levels were normal or low. Renal function was normal or minimally reduced. Skeletal symptoms disappeared and serum 1 alpha, 25(OH)2D levels rose to normal in one patient when nutrient infusions were discontinued for 6 weeks. Removal of calcium from the nutrient solution for 2 to 4 days was associated with no change in serum 1 alpha, 25(OH)2D in two patients. The cause of the reduction in serum levels of 1 alpha, 25(OH)2D and its role in the pathogenesis of bone disease in these patients remain uncertain. PMID:6786151

  19. A Nonallergenic Birch Pollen Allergy Vaccine Consisting of Hepatitis PreS–Fused Bet v 1 Peptides Focuses Blocking IgG toward IgE Epitopes and Shifts Immune Responses to a Tolerogenic and Th1 Phenotype

    PubMed Central

    Marth, Katharina; Breyer, Isabella; Focke-Tejkl, Margarete; Blatt, Katharina; Shamji, Mohamed H.; Layhadi, Janice; Gieras, Anna; Swoboda, Ines; Zafred, Domen; Keller, Walter; Valent, Peter; Durham, Stephen R.; Valenta, Rudolf

    2014-01-01

    Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients’ IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS–induced IgG inhibited Bet v 1–induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier–based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation. PMID:23440415

  20. Increasing the maximally random jammed density with electric field to reduce the fat level in chocolate

    NASA Astrophysics Data System (ADS)

    Tao, R.; Tang, H.

    Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. For example, a typical molding chocolate has various fat up to 40% in total and chocolate for covering ice cream has fat 50 -60%. Especially, as children are the leading chocolate consumers, reducing the fat level in chocolate products to make them healthier is important and urgent. While this issue was called into attention and elaborated in articles and books decades ago and led to some patent applications, no actual solution was found unfortunately. Why is reducing fat in chocolate so difficult? What is the underlying physical mechanism? We have found that this issue is deeply related to the basic science of soft matters, especially to their viscosity and maximally random jammed (MRJ) density φx. All chocolate productions are handling liquid chocolate, a suspension with cocoa solid particles in melted fat, mainly cocoa butter. The fat level cannot be lower than 1-φxin order to have liquid chocolate to flow. Here we show that that with application of an electric field to liquid chocolate, we can aggregate the suspended particles into prolate spheroids. This microstructure change reduces liquid chocolate's viscosity along the flow direction and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are looking forward to a new class of healthier and tasteful chocolate coming to the market soon. Dept. of Physics, Temple Univ, Philadelphia, PA 19122.

  1. IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis.

    PubMed Central

    Gioud-Paquet, M; Auvinet, M; Raffin, T; Girard, P; Bouvier, M; Lejeune, E; Monier, J C

    1987-01-01

    One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren's syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma. PMID:3813676

  2. Comparative proteomic analysis and IgE binding properties of peanut seed and testa (skin).

    PubMed

    White, Brittany L; Gökce, Emine; Nepomuceno, Angelito I; Muddiman, David C; Sanders, Timothy H; Davis, Jack P

    2013-04-24

    To investigate the protein composition and potential allergenicity of peanut testae or skins, proteome analysis was conducted using nanoLC-MS/MS sequencing. Initial amino acid analysis suggested differences in protein compositions between the blanched seed (skins removed) and skin. Phenolic compounds hindered analysis of proteins in skins when the conventional extraction method was used; therefore, phenol extraction of proteins was necessary. A total of 123 proteins were identified in blanched seed and skins, and 83 of the proteins were common between the two structures. The skins contained all of the known peanut allergens in addition to 38 proteins not identified in the seed. Multiple defense proteins with antifungal activity were identified in the skins. Western blotting using sera from peanut-allergic patients revealed that proteins extracted from both the blanched seed and skin bound significant levels of IgE. However, when phenolic compounds were present in the skin protein extract, no IgE binding was observed. These findings indicate that peanut skins contain potentially allergenic proteins; however, the presence of phenolic compounds may attenuate this effect. PMID:23534881

  3. Food allergen-specific serum IgG and IgE before and after elimination diets in allergic dogs.

    PubMed

    Zimmer, Anja; Bexley, Jennifer; Halliwell, Richard E W; Mueller, Ralf S

    2011-12-15

    Serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for diets to diagnose adverse food reaction (AFR) in dogs with allergic skin disease. Antibody concentrations in blood samples obtained during an unsuccessful diet to help in the choice of diet changes may be influenced by the previous diet. The objective of this paper was to measure food antigen-specific IgE and IgG for the most commonly used 16 food antigens before and after an elimination diet. Levels of food-specific serum IgE and IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Dogs had detectable IgE antibodies to beef, pork, lamb and cows' milk; and detectable IgG antibodies to beef, pork, lamb, cows' milk, chicken and turkey. Of 19 dogs with complete data sets, 14 dogs showed clear improvement during diet and in 7 dogs AFR could be diagnosed by deterioration on rechallenge and subsequent improvement on refeeding the diet. Serum was obtained before and 6-8 weeks after beginning such a diet. There was no significant difference in pre- and post-diet levels for any of the individual allergens nor for the total IgE and IgG concentrations of all antigens (P=0.55 and P=0.53 respectively). In these 19 dogs in which an elimination diet was used for the diagnosis of food allergy and in which 14 were probably food allergic and 7 were proven food allergic there were no significant differences in food-specific antibodies before and after an elimination diet of 6-8 weeks. PMID:21955446

  4. Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

    PubMed

    Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

    2014-12-01

    Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk. PMID:25445987

  5. Obstructive Sleep Apnea and Obesity are Associated With Reduced GPR 120 Plasma Levels in Children

    PubMed Central

    Gozal, David; Kheirandish-Gozal, Leila; Carreras, Alba; Khalyfa, Abdelnaby; Peris, Eduard

    2014-01-01

    Background: Obstructive sleep apnea (OSA) is a common health problem, particularly in obese children, in whom a vicious cycle of obesity and OSA interdependencies promotes increased food intake. G protein-coupled receptor 120 (GPR 120) is a long-chain free fatty acid (FFA) receptor that plays an important role in energy homeostasis, and protects against insulin resistance and systemic inflammation. We hypothesized that GPR 120 levels would be reduced in children with OSA, particularly among obese children. Study Design: Cross-sectional prospectively recruited cohort. Setting: Academic pediatric sleep program. Methods: Two hundred twenty-six children (mean age: 7.0 ± 2.1 y) underwent overnight polysomnographic evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hsCRP) assays, monocyte GPR 120 expression, and plasma GPR 120 levels were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay kits. Results: Obese children and those with OSA had significantly lower GPR 120 monocyte expression and plasma GPR 120 levels. Furthermore, when both obesity and OSA were present, GPR 120 levels were lowest. Linear associations emerged between GPR 120 plasma levels and body mass index (BMI) z score, as well as with apnea-hypopnea index (AHI), saturation of peripheral oxygen (SpO2) nadir, and respiratory arousal index (RAI), with RAI remaining statistically significant when controlling for age, ethnicity, sex, and BMI z score (P < 0.001). Similarly, HOMA-IR was significantly associated with GPR 120 levels, but neither low density lipoprotein nor high density lipoprotein cholesterol or hsCRP levels exhibited significant correlations. Conclusions: G protein-coupled receptor 120 (GPR 120) levels are reduced in pediatric OSA and obesity (particularly when both are present) and may play a role in

  6. Diosgenin attenuates allergen-induced intestinal inflammation and IgE production in a murine model of food allergy.

    PubMed

    Huang, Chung-Hsiung; Ku, Chun-Yao; Jan, Tong-Rong

    2009-10-01

    Diosgenin, the major sapogenin contained in the Chinese yam, has recently been shown to promote systemic T helper 1-type immunity in a murine model of airway hypersensitivity. In this study, we hypothesized that diosgenin might be effective in modulating food allergy. BALB/c mice were either left untreated (naïve; NA) or administered daily with vehicle (VH; olive oil) and/or diosgenin (100 or 200 mg/kg) by gavage throughout the experiment. Except for the NA group, the mice were sensitized with ovalbumin (OVA) and repeatedly challenged with intragastric OVA to induce intestinal allergic responses. Diosgenin demonstrated a suppressive effect on the intestinal inflammation, including the occurrence of diarrhea, the infiltration and degranulation of mast cells, and the presence of mucin-containing goblet cells in the duodenum. A protective effect by diosgenin on reducing the crypt depth of the intestine was also observed in OVA-sensitized and challenged mice. Furthermore, the serum production of OVA-specific IgE, and the total IgE was suppressed. In contrast, OVA-specific IgG (2a) was enhanced by diosgenin treatment in OVA-sensitized mice. These results demonstrated the IN VIVO anti-allergic activity of diosgenin, which is associated with the suppression of IgE production and mast cell infiltration and degranulation. PMID:19343624

  7. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men

    PubMed Central

    2013-01-01

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m2, age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001

  8. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men.

    PubMed

    Berge, Kjetil; Piscitelli, Fabiana; Hoem, Nils; Silvestri, Cristoforo; Meyer, Ingo; Banni, Sebastiano; Di Marzo, Vincenzo

    2013-01-01

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m², age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001

  9. Reducing bullying and victimization: student- and classroom-level mechanisms of change.

    PubMed

    Saarento, Silja; Boulton, Aaron J; Salmivalli, Christina

    2015-01-01

    This longitudinal study examines the mediating mechanisms by which the KiVa antibullying program, based on the Participant Role approach, reduces bullying and victimization among elementary school students. Both student-level mechanisms leading to reduced perpetration of bullying and classroom-level mechanisms leading to reductions in bullying and victimization are considered. Analyses are based on a sample of 7,491 students (49.5% boys) nested within 421 classrooms within 77 schools. At the beginning of program implementation, the children were in Grades 4, 5, and 6 (mean age 11.3 years). Multilevel structural equation modeling was used to analyze whether changes in the hypothesized mediators accounted for later reductions in the outcomes. At the student level, antibullying attitudes and perceptions regarding peers' defending behaviors and teacher attitudes toward bullying mediated the effects of KiVa on self-reported bullying perpetration. The effects on peer-reported bullying were only mediated by antibullying attitudes. At the classroom level, the program effects on both self- and peer-reported bullying were mediated by students' collective perceptions of teacher attitudes toward bullying. Also, perceived reinforcing behaviors predicted bullying but did not emerge as a significant mediator. Finally, bullying mediated the effects of the classroom-level factors on victimization. These findings enhance knowledge of the psychosocial developmental processes contributing to bullying and victimization and shed light on the key mechanisms by which school bullying can successfully be counteracted. PMID:24390403

  10. Disruption of adenosine-5'-phosphosulfate kinase in Arabidopsis reduces levels of sulfated secondary metabolites.

    PubMed

    Mugford, Sarah G; Yoshimoto, Naoko; Reichelt, Michael; Wirtz, Markus; Hill, Lionel; Mugford, Sam T; Nakazato, Yoshimi; Noji, Masaaki; Takahashi, Hideki; Kramell, Robert; Gigolashvili, Tamara; Flügge, Ulf-Ingo; Wasternack, Claus; Gershenzon, Jonathan; Hell, Rüdiger; Saito, Kazuki; Kopriva, Stanislav

    2009-03-01

    Plants can metabolize sulfate by two pathways, which branch at the level of adenosine 5'-phosphosulfate (APS). APS can be reduced to sulfide and incorporated into Cys in the primary sulfate assimilation pathway or phosphorylated by APS kinase to 3'-phosphoadenosine 5'-phosphosulfate, which is the activated sulfate form for sulfation reactions. To assess to what extent APS kinase regulates accumulation of sulfated compounds, we analyzed the corresponding gene family in Arabidopsis thaliana. Analysis of T-DNA insertion knockout lines for each of the four isoforms did not reveal any phenotypical alterations. However, when all six combinations of double mutants were compared, the apk1 apk2 plants were significantly smaller than wild-type plants. The levels of glucosinolates, a major class of sulfated secondary metabolites, and the sulfated 12-hydroxyjasmonate were reduced approximately fivefold in apk1 apk2 plants. Although auxin levels were increased in the apk1 apk2 mutants, as is the case for most plants with compromised glucosinolate synthesis, typical high auxin phenotypes were not observed. The reduction in glucosinolates resulted in increased transcript levels for genes involved in glucosinolate biosynthesis and accumulation of desulfated precursors. It also led to great alterations in sulfur metabolism: the levels of sulfate and thiols increased in the apk1 apk2 plants. The data indicate that the APK1 and APK2 isoforms of APS kinase play a major role in the synthesis of secondary sulfated metabolites and are required for normal growth rates. PMID:19304933

  11. High intensity and reduced volume training attenuates stress and recovery levels in elite swimmers.

    PubMed

    Elbe, Anne-Marie; Rasmussen, Camilla P; Nielsen, Glen; Nordsborg, Nikolai B

    2016-04-01

    This study investigated the effect of increased high-intensity interval training (HIT) at the expense of total training volume on the stress and recovery levels of elite swimmers. Forty-one elite swimmers participated in the study and were randomly assigned to either a HIT or a control group (CON). Eleven swimmers did not complete the questionnaires. For 12 weeks both groups trained ~12 h per week. The amount of HIT was ~5 h vs. 1 h, and total distance was ~17 km vs. ~35 km per week for HIT and CON, respectively. HIT was performed as 6-10 × 10-30 s maximal effort interspersed by 2-4 min of rest. The Recovery Stress Questionnaire - Sport was used to measure the swimmers' stress and recovery levels. After the 12 week intervention, the general stress level was 16.6% (2.6-30.7%; mean and 95% CI) lower and the general recovery level was 6.5% (0.7-12.4%) higher in HIT compared to the CON, after adjusting for baseline values. No significant effects could be observed in sports-specific stress or sports-specific recovery. The results indicate that increasing training intensity and reducing training volume for 12 weeks can reduce general stress and increase general recovery levels in competitive swimmers. PMID:25867005

  12. Ascorbic acid serum levels are reduced in patients with hematological malignancies

    PubMed Central

    Huijskens, Mirelle J.A.J.; Wodzig, Will K.W.H.; Walczak, Mateusz; Germeraad, Wilfred T.V.; Bos, Gerard M.J.

    2016-01-01

    In this paper we demonstrate that patients treated with chemotherapy and/or hematopoietic stem cell transplantation (HSCT) have highly significant reduced serum ascorbic acid (AA) levels compared to healthy controls. We recently observed in in vitro experiments that growth of both T and NK cells from hematopoietic stem cells is positively influenced by AA. It might be of clinical relevance to study the function and recovery of immune cells after intensive treatment, its correlation to AA serum levels and the possible effect of AA supplementation. PMID:27014565

  13. Development of an in vitro model system for studying the interaction of Equus caballus IgE with its high-affinity receptor FcɛRI.

    PubMed

    Sabban, Sari; Ye, Hongtu; Helm, Birgit

    2013-05-15

    The binding of immunoglobulin E (IgE) to its high-affinity receptor (FcɛRI) is the central protein interaction in IgE-mediated allergic reactions. The cross-linking of the IgE/FcɛRI complex, through cognate allergens, on the surface of mast cells and basophil cells results in mediator release, and thus leads to the symptoms of type I hypersensitivity responses in mammals. To develop a baseline value for subsequent equine anti-allergy drug and vaccine research, the interaction of equine IgE with its high-affinity FcɛRI receptor was investigated following the cloning and expression of equine IgE with specificity for NIP-HSA (4-hydroxy-5-iodo-3-nitrophenylacetic acid conjugated to human serum albumin). Receptor recognition and effector functions were assessed in Rat Basophil Leukemia (RBL-2H3.1) cells transfected with the α chain of equine and canine FcɛRI. Results obtained showed that the equine FcɛRI receptor recognizes both equine and canine IgE and supports similar β-hexosaminidase release levels from RBL cells transfected with equine FcɛRI, peaking at 36.68% at 100ngml(-1) antigen and 32.00% at 100ngml(-1) antigen respectively. Furthermore, the binding kinetics of the equine IgE to the equine FcɛRI receptor and the canine IgE to the same receptor was measured to be KA=6.33×10(9)M(-1) and KA=1.84×10(9)M(-1) respectively. This research established basic reagents and vitro assay systems to underpin the development of rational therapeutic intervention strategies to combat equine allergic manifestations. PMID:23485176

  14. Persistence of IgE-associated allergy and allergen-specific IgE despite CD4+ T cell loss in AIDS.

    PubMed

    Marth, Katharina; Wollmann, Eva; Gallerano, Daniela; Ndlovu, Portia; Makupe, Ian; Valenta, Rudolf; Sibanda, Elopy

    2014-01-01

    The infection of CD4+ cells by HIV leads to the progressive destruction of CD4+ T lymphocytes and, after a severe reduction of CD4+ cells, to AIDS. The aim of the study was to investigate whether HIV-infected patients with CD4 cell counts <200 cells/µl can suffer from symptoms of IgE-mediated allergy, produce allergen-specific IgE antibody responses and show boosts of allergen-specific IgE production. HIV-infected patients with CD4 counts ≤ 200 cells/µl suffering from AIDS and from IgE-mediated allergy were studied. Allergy was diagnosed according to case history, physical examination, skin prick testing (SPT), and serological analyses including allergen microarrays. HIV infection was confirmed serologically and the disease was staged clinically. The predominant allergic symptoms in the studied patients were acute allergic rhinitis (73%) followed by asthma (27%) due to IgE-mediated mast cell activation whereas no late phase allergic symptoms such as atopic dermatitis, a mainly T cell-mediated skin manifestation, were found in patients suffering from AIDS. According to IgE serology allergies to house dust mites and grass pollen were most common besides IgE sensitizations to various food allergens. Interestingly, pollen allergen-specific IgE antibody levels in the patients with AIDS and in additional ten IgE-sensitized patients with HIV infections and low CD4 counts appeared to be boosted by seasonal allergen exposure and were not associated with CD4 counts. Our results indicate that secondary allergen-specific IgE production and IgE-mediated allergic inflammation do not require a fully functional CD4+ T lymphocyte repertoire. PMID:24896832

  15. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels

    PubMed Central

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H.; Kim, Yong Hyup

    2016-01-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K+ and Na+ by three orders of magnitude compared to the GO membrane. PMID:27306853

  16. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels.

    PubMed

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H; Kim, Yong Hyup

    2016-01-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K(+) and Na(+) by three orders of magnitude compared to the GO membrane. PMID:27306853

  17. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels

    NASA Astrophysics Data System (ADS)

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H.; Kim, Yong Hyup

    2016-06-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K+ and Na+ by three orders of magnitude compared to the GO membrane.

  18. A retrospective examination of in-home educational visits to reduce childhood lead levels

    SciTech Connect

    Schultz, B. |; Pawel, D.; Murphy, A.

    1999-05-01

    A number of human health effects from lead are well known. However, the means for reducing lead exposure in children has been a subject of uncertainty. This paper presents results of a retrospective study of educational lead reduction interventions in Milwaukee, Wisconsin for children who had elevated blood lead levels between 20 and 24 {micro}g/dl. The study examined Milwaukee Health Department (MHD) records of baseline and follow-up blood lead measurements. A study group of children received an in-home educational visit by an MHD paraprofessional. The educational visits last about an hour and the importance of reducing lead exposure, nutritional suggestions, and dust clean-up practices and behavioral changes that can reduce lead exposure are discussed. After the intervention, the average observed blood lead level declined by 4.2 {micro}g/dl or by about 21%. A decline of 1.2 {micro}g/dl (6%) was also observed in a reference group of 226 children who did not receive an MHD in-home visit. The decline in the reference group may be partially due to education at the clinics taking the blood samples. The study group had a decline in blood lead levels 3.1 {micro}g/dl (15%) greater than the reference group, with the difference between groups being statistically significant with a P value of less than 0.001. Although significant exposures remained in most of the children studied, important lead reductions were observed with this relatively inexpensive and simple intervention. Education in the homes of families at risk for lead poisoning may be an effective component of programs to reduce blood lead levels.

  19. Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure

    PubMed Central

    Miranda da Silva, Cristiane; Peres Leal, Mayara; Brochetti, Robson Alexandre; Braga, Tárcio; Vitoretti, Luana Beatriz; Saraiva Câmara, Niels Olsen; Damazo, Amílcar Sabino; Ligeiro-de-Oliveira, Ana Paula; Chavantes, Maria Cristina; Lino-dos-Santos-Franco, Adriana

    2015-01-01

    Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA), an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1%) or vehicle (distillated water) during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure). Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant. PMID:26569396

  20. Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure.

    PubMed Central

    Neudecker, Philipp; Lehmann, Katrin; Nerkamp, Jörg; Haase, Tanja; Wangorsch, Andrea; Fötisch, Kay; Hoffmann, Silke; Rösch, Paul; Vieths, Stefan; Scheurer, Stephan

    2003-01-01

    Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy. PMID:12943529

  1. Silencing β1,2-xylosyltransferase in Transgenic Tomato Fruits Reveals xylose as Constitutive Component of Ige-Binding Epitopes

    PubMed Central

    Paulus, Kathrin Elisabeth; Mahler, Vera; Pabst, Martin; Kogel, Karl-Heinz; Altmann, Friedrich; Sonnewald, Uwe

    2011-01-01

    Complex plant N-glycans containing β1,2-xylose and core α1,3-fucose are regarded as the major class of the so-called “carbohydrate cross-reactive determinants” reactive with IgE antibodies in sera of many allergic patients, but their clinical relevance is still under debate. Plant glycosyltransferases, β1,2-xylosyltransferase (XylT), and core α1,3-fucosyltransferase (FucT) are responsible for the transfer of β1,2-linked xylose and core α1,3-linked fucose residues to N-glycans of glycoproteins, respectively. To test the clinical relevance of β1,2-xylose-containing epitopes, expression of the tomato β1,2-xylosyltransferase was down-regulated by RNA interference (RNAi) in transgenic plants. Fruits harvested from these transgenic plants were analyzed for accumulation of XylT mRNA, abundance of β1,2-xylose epitopes and their allergenic potential. Based on quantitative real-time PCR analysis XylT mRNA levels were reduced up to 10-fold in independent transgenic lines as compared to untransformed control, whereas no xylosylated N-glycans could be revealed by MS analysis. Immunoblotting using anti-xylose-specific IgG antibodies revealed a strong reduction of β1,2-xylose-containing epitopes. Incubating protein extracts from untransformed controls and XylT_RNAi plants with sera from tomato allergic patients showed a patient-specific reduction in IgE-binding, indicating a reduced allergenic potential of XylT_RNAi tomato fruits, in vitro. To elucidate the clinical relevance of β1,2-xylose-containing complex N-glycans skin prick tests were performed demonstrating a reduced responsiveness of tomato allergic patients, in vivo. This study provides strong evidence for the clinical relevance of β1,2-xylose-containing epitopes in vivo. PMID:22639593

  2. Reducing Benzene and Cresol Levels in National Renewable Energy Laboratory's Pilot-Scale Biorefinergy Scrubber Water

    SciTech Connect

    Buzek, M.L.; Phillips, S.

    2004-01-01

    The Thermochemical Process Development Unit at the National Renewable Energy Laboratory converts biomass into energy by gasification or pyrolysis. The aqueous effluent generated in these processes must be disposed of as hazardous waste according to the Resource Conservation and Recovery Act because certain components exceed the regulatory concentration limit. Gas stripping of the scrubber water was investigated as a method of reducing benzene and cresol levels. A custom-designed packed-bed column was built and a half-factorial experimental design was implemented to determine the effects of gas flow rate, liquid flow rate, and column packing height on the final benzene concentration in the liquid. The experimental results show that packing height had a significant effect on final benzene concentration; gas flow rate and liquid flow rate had little effect. The effects of each design variable on final cresol concentration were not determined. Although the current column design did significantly reduce the benzene and cresol levels in the scrubber water, it did not reduce the concentrations below the regulatory limits. A full-factorial experimental design will be implemented with an increased packing height. Other variables, including column diameter and packing type, will be investigated to determine their effects on final benzene and cresol concentrations. Once the packed-bed column is determined to be effective in reducing contaminant concentrations below the regulatory limit, photocatalytic oxidation will be explored for remediating the benzene and cresol from the gas stream.

  3. Hepcidin bound to α2-macroglobulin reduces ferroportin-1 expression and enhances its activity at reducing serum iron levels.

    PubMed

    Huang, Michael Li-Hsuan; Austin, Christopher J D; Sari, Marie-Agnès; Rahmanto, Yohan Suryo; Ponka, Prem; Vyoral, Daniel; Richardson, Des R

    2013-08-30

    Hepcidin regulates iron metabolism by down-regulating ferroportin-1 (Fpn1). We demonstrated that hepcidin is complexed to the blood transport protein, α2-macroglobulin (α2M) (Peslova, G., Petrak, J., Kuzelova, K., Hrdy, I., Halada, P., Kuchel, P. W., Soe-Lin, S., Ponka, P., Sutak, R., Becker, E., Huang, M. L., Suryo Rahmanto, Y., Richardson, D. R., and Vyoral, D. (2009) Blood 113, 6225-6236). However, nothing is known about the mechanism of hepcidin binding to α2M or the effects of the α2M·hepcidin complex in vivo. We show that decreased Fpn1 expression can be mediated by hepcidin bound to native α2M and also, for the first time, hepcidin bound to methylamine-activated α2M (α2M-MA). Passage of high molecular weight α2M·hepcidin or α2M-MA·hepcidin complexes (≈725 kDa) through a Sephadex G-25 size exclusion column retained their ability to decrease Fpn1 expression. Further studies using ultrafiltration indicated that hepcidin binding to α2M and α2M-MA was labile, resulting in some release from the protein, and this may explain its urinary excretion. To determine whether α2M-MA·hepcidin is delivered to cells via the α2M receptor (Lrp1), we assessed α2M uptake and Fpn1 expression in Lrp1(-/-) and Lrp1(+/+) cells. Interestingly, α2M·hepcidin or α2M-MA·hepcidin demonstrated similar activities at decreasing Fpn1 expression in Lrp1(-/-) and Lrp1(+/+) cells, indicating that Lrp1 is not essential for Fpn1 regulation. In vivo, hepcidin bound to α2M or α2M-MA did not affect plasma clearance of α2M/α2M-MA. However, serum iron levels were reduced to a significantly greater extent in mice treated with α2M·hepcidin or α2M-MA·hepcidin relative to unbound hepcidin. This effect could be mediated by the ability of α2M or α2M-MA to retard kidney filtration of bound hepcidin, increasing its half-life. A model is proposed that suggests that unlike proteases, which are irreversibly bound to activated α2M, hepcidin remains labile and available to down

  4. Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions

    PubMed Central

    Sanchez, Tanit Ganz; Moraes, Fernanda; Casseb, Juliana; Cota, Jaci; Freire, Katya; Roberts, Larry E.

    2016-01-01

    Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID:27265722

  5. Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions.

    PubMed

    Sanchez, Tanit Ganz; Moraes, Fernanda; Casseb, Juliana; Cota, Jaci; Freire, Katya; Roberts, Larry E

    2016-01-01

    Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID:27265722

  6. Reduced activity-dependent protein levels in a mouse model of the fragile X premutation.

    PubMed

    von Leden, Ramona E; Curley, Lindsey C; Greenberg, Gian D; Hunsaker, Michael R; Willemsen, Rob; Berman, Robert F

    2014-03-01

    Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG KI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation. PMID:24462720

  7. QMix® irrigant reduces lipopolysacharide (LPS) levels in an in vitro model

    PubMed Central

    GRÜNDLING, Grasiela Longhi; de MELO, Tiago André Fontoura; MONTAGNER, Francisco; SCARPARO, Roberta Kochenborger; VIER-PELISSER, Fabiana Vieira

    2015-01-01

    The presence of endotoxin inside the root canal has been associated with periapical inflammation, bone resorption and symptomatic conditions. Objectives To determine, in vitro, the effect of QMix® and other three root canal irrigants in reducing the endotoxin content in root canals. Material and Methods Root canals of single-rooted teeth were prepared. Samples were detoxified with Co-60 irradiation and inoculated with E. coli LPS (24 h, at 37°C). After that period, samples were divided into 4 groups, according to the irrigation solution tested: QMix®, 17% EDTA, 2% chlorhexidine solution (CHX), and 3% sodium hypochlorite (NaOCl). LPS quantification was determined by Limulus Amebocyte Lysate (LAL) assay. The initial counting of endotoxins for all samples, and the determination of LPS levels in non-contaminated teeth and in contaminated teeth exposed only to non-pyrogenic water, were used as controls. Results QMix® reduced LPS levels, with a median value of 1.11 endotoxins units (EU)/mL (p<0.001). NaOCl (25.50 EU/mL), chlorhexidine (44.10 EU/mL) and positive control group (26.80 EU/mL) samples had similar results. Higher levels were found with EDTA (176.00 EU/mL) when compared to positive control (p<0.001). There was no significant difference among EDTA, NaOCl and CHX groups. Negative control group (0.005 EU/mL) had statistically significant lower levels of endotoxins when compared to all test groups (p<0.001). Conclusion QMix® decreased LPS levels when compared to the other groups (p<0.001). 3% NaOCl, 2% CHX and 17% EDTA were not able to significantly reduce the root canal endotoxins load. PMID:26398517

  8. QMix® irrigant reduces lipopolysacharide (LPS) levels in an in vitro model.

    PubMed

    Gründling, Grasiela Longhi; Melo, Tiago André Fontoura de; Montagner, Francisco; Scarparo, Roberta Kochenborger; Vier-Pelisser, Fabiana Vieira

    2015-01-01

    The presence of endotoxin inside the root canal has been associated with periapical inflammation, bone resorption and symptomatic conditions.Objectives To determine, in vitro, the effect of QMix® and other three root canal irrigants in reducing the endotoxin content in root canals.Material and Methods Root canals of single-rooted teeth were prepared. Samples were detoxified with Co-60 irradiation and inoculated with E. coli LPS (24 h, at 37°C). After that period, samples were divided into 4 groups, according to the irrigation solution tested: QMix®, 17% EDTA, 2% chlorhexidine solution (CHX), and 3% sodium hypochlorite (NaOCl). LPS quantification was determined by Limulus Amebocyte Lysate (LAL) assay. The initial counting of endotoxins for all samples, and the determination of LPS levels in non-contaminated teeth and in contaminated teeth exposed only to non-pyrogenic water, were used as controls.Results QMix® reduced LPS levels, with a median value of 1.11 endotoxins units (EU)/mL (p<0.001). NaOCl (25.50 EU/mL), chlorhexidine (44.10 EU/mL) and positive control group (26.80 EU/mL) samples had similar results. Higher levels were found with EDTA (176.00 EU/mL) when compared to positive control (p<0.001). There was no significant difference among EDTA, NaOCl and CHX groups. Negative control group (0.005 EU/mL) had statistically significant lower levels of endotoxins when compared to all test groups (p<0.001).Conclusion QMix® decreased LPS levels when compared to the other groups (p<0.001). 3% NaOCl, 2% CHX and 17% EDTA were not able to significantly reduce the root canal endotoxins load. PMID:26398517

  9. Reduced striatal adenosine A2A receptor levels define a molecular subgroup in schizophrenia.

    PubMed

    Villar-Menéndez, Izaskun; Díaz-Sánchez, Sara; Blanch, Marta; Albasanz, José Luis; Pereira-Veiga, Thais; Monje, Alfonso; Planchat, Luis Maria; Ferrer, Isidre; Martín, Mairena; Barrachina, Marta

    2014-04-01

    Schizophrenia (SZ) is a mental disorder of unknown origin. Some scientific evidence seems to indicate that SZ is not a single disease entity, since there are patient groups with clear symptomatic, course and biomarker differences. SZ is characterized by a hyperdopaminergic state related to high dopamine D2 receptor activity. It has also been proposed that there is a hypoadenosynergic state. Adenosine is a nucleoside widely distributed in the organism with neuromodulative and neuroprotective activity in the central nervous system. In the brain, the most abundant adenosine receptors are A1R and A2AR. In the present report, we characterize the presence of both receptors in human postmortem putamens of patients suffering SZ with real time TaqMan PCR, western blotting and radioligand binding assay. We show that A1R levels remain unchanged with respect to age-matched controls, whereas nearly fifty percent of patients have reduced A2AR, at the transcriptional and translational levels. Moreover, we describe how DNA methylation plays a role in the pathological A2AR levels with the bisulfite-sequencing technique. In fact, an increase in 5-methylcytosine percentage in the 5' UTR region of ADORA2A was found in those SZ patients with reduced A2AR levels. Interestingly, there was a relationship between the A2A/β-actin ratio and motor disturbances as assessed with some items of the PANSS, AIMS and SAS scales. Therefore, there may be a subgroup of SZ patients with reduced striatal A2AR levels accompanied by an altered motor phenotype. PMID:24433848

  10. High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age.

    PubMed

    Mangialasche, Francesca; Kivipelto, Miia; Mecocci, Patrizia; Rizzuto, Debora; Palmer, Katie; Winblad, Bengt; Fratiglioni, Laura

    2010-01-01

    In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated. PMID:20413888

  11. Characterization and crystallization of a recombinant IgE Fab fragment in complex with the bovine β-lactoglobulin allergen

    SciTech Connect

    Niemi, Merja Jänis, Janne; Jylhä, Sirpa; Kallio, Johanna M.; Hakulinen, Nina; Laukkanen, Marja-Leena; Takkinen, Kristiina; Rouvinen, Juha

    2008-01-01

    The high-resolution mass-spectrometric characterization, crystallization and X-ray diffraction studies of a recombinant IgE Fab fragment in complex with bovine β-lactoglobulin are reported. A D1 Fab fragment containing the allergen-binding variable domains of the IgE antibody was characterized by ESI FT–ICR mass spectrometry and crystallized with bovine β-lactoglobulin (BLG) using the hanging-drop vapour-diffusion method at 293 K. X-ray data suitable for structure determination were collected to 2.8 Å resolution using synchrotron radiation. The crystal belonged to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 67.0, b = 100.6, c = 168.1 Å. The three-dimensional structure of the D1 Fab fragment–BLG complex will provide the first insight into IgE antibody–allergen interactions at the molecular level.

  12. Carbon Nanofibers Have IgE Adjuvant Capacity but Are Less Potent Than Nanotubes in Promoting Allergic Airway Responses

    PubMed Central

    Samuelsen, Mari; Marioara, Calin Daniel; Løvik, Martinus

    2013-01-01

    There is a growing concern for the possible health impact of nanoparticles. The main objective of this study was to investigate the allergy-promoting capacity of four different carbon nanofiber (CNF) samples in an injection and an airway mouse model of allergy. Secondly, the potency of the CNF was compared to the previously reported allergy-promoting capacity of carbon nanotubes (CNT) in the airway model. Ultrafine carbon black particles (ufCBP) were used as a positive control. Particles were given together with the allergen ovalbumin (OVA) either by subcutaneous injection into the footpad or intranasally to BALB/cA mice. After allergen booster, OVA-specific IgE, IgG1, and IgG2a in serum were measured. In the airway model, inflammation was determined as influx of inflammatory cells (eosinophils, neutrophils, lymphocytes, and macrophages) and by mediators (MCP-1 and TNF-α present in bronchoalveolar fluid (BALF)). CNF and CNT both increased OVA-specific IgE levels in the two models, but in the airway model, the CNT gave a significantly stronger IgE response than the CNF. Furthermore, the CNT and not the CNF promoted eosinophil lung inflammation. Our data therefore suggest that nanotube-associated properties are particularly potent in promoting allergic responses. PMID:24024193

  13. APATHY AND APOE4 ARE ASSOCIATED WITH REDUCED BDNF LEVELS IN ALZHEIMER’S DISEASE

    PubMed Central

    Álvarez, Antón; Aleixandre, Manuel; Linares, Carlos; Masliah, Eliezer; Moessler, Herbert

    2016-01-01

    Reduced brain-derived neurotrophic factor (BDNF) signaling is considered as a pathogenic event in early Alzheimer’s disease (AD), but the influence of apathy and apolipoprotein E epsilon-4 allele (APOE4) on serum BDNF values was not previously investigated in AD. We evaluated serum BDNF levels in AD, amnestic mild cognitive impairment (MCI) and control subjects. Baseline BDNF levels were similar in AD, MCI and controls. AD patients having apathy showed lower BDNF values than patients without apathy (p<0.05). After correction for the influence of apathy, APOE4 carriers showed lower BDNF levels (p<0.01) and MMSE scores (p<0.01) than non-APOE4 carriers in the subgroup of AD females, but not in males. Significant (p<0.05) positive correlations between BDNF values and MMSE scores were only observed in subgroups of AD males and of AD patients without apathy. These results are showing the association of apathy and APOE4 with reduced serum BDNF levels in AD, and are suggesting that BDNF reductions might contribute to the worse cognitive performance exhibited by AD apathetic patients and female APOE4 carriers. PMID:25024337

  14. Preventing and reducing violence against women: innovation in community-level studies.

    PubMed

    Taft, Angela; Small, Rhonda

    2014-01-01

    Intimate partner violence is a serious global problem that damages the health and prosperity of individuals, their families, community, and society. WHO endorses an 'ecological model,' which states that there are multi-level intersecting factors enabling perpetration and victimization of violence. Intervention science to prevent or reduce the problem is in its infancy, and the few existing intervention studies have been targeted at the individual level. In a recent study published in BMC Medicine, Abramsky et al. bring innovation to the field, targeting their intervention trial "SASA!" in Kampala Uganda at all ecological levels, but particularly at the community level. Recruiting and training both male and female community leaders and activists who enabled group and media discussions, the authors focused on the beneficial and abusive detrimental uses of power rather than commencing with the central issue of gender inequality. SASA! successfully reduced community attitudes to tolerance of violence and inequality, men's sexual risk behaviors, and women's experience of physical violence. The study also improved the communities' response to victimized women. SASA! has promise for adaptation and replication in low, middle and high income countries. Please see related article: http://www.biomedcentral.com/1741-7015/12/122. PMID:25286152

  15. Helicopter far-field acoustic levels as a function of reduced rotor speeds

    NASA Technical Reports Server (NTRS)

    Mueller, Arnold W.; Lemasurier, Philip; Smith, Charles D.

    1990-01-01

    This paper will present far-field measured noise levels relative to tests conducted with a model S-76A helicopter. The project was designed to provide supplemental experimental flight data which may be used to further study reduced helicopter rotor speeds (and thus, advancing blade-tip Mach number) effects on far-field acoustic levels. The aircraft was flown in straight and level flight while operating with both the rotor speed and flight speed as test variables. The rotor speed was varied over the range of 107 percent of the main-rotor speed (NR) to 90 percent NR and with the forward flight speed varied over the range of 155 to 35 knots indicated air speed. These conditions produced a wide range of advancing blade-tip Mach numbers to which the noise data are related.

  16. Sulforaphane Restores Cellular Glutathione Levels and Reduces Chronic Periodontitis Neutrophil Hyperactivity In Vitro

    PubMed Central

    Dias, Irundika H. K.; Chapple, Ian L. C.; Milward, Mike; Grant, Melissa M.; Hill, Eric; Brown, James; Griffiths, Helen R.

    2013-01-01

    The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2. - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients’ neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2. - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. PMID:23826097

  17. Oral midazolam reduces cortisol levels during local anaesthesia in children: a randomised controlled trial.

    PubMed

    Gomes, Heloisa Sousa; Corrêa-Faria, Patrícia; Silva, Tarcília Aparecida; Paiva, Saul Martins; Costa, Paulo Sérgio Sucasas; Batista, Aline Carvalho; Costa, Luciane Rezende

    2015-01-01

    Little is known about whether midazolam sedation can reduce salivary cortisol levels and consequently influence children's behaviour during dental treatment. The aim of this study was to evaluate the effect of midazolam sedation on salivary cortisol and its correlation with children's behaviour during restorative dental treatment. Eighteen healthy children, aged two to five years, were randomly assigned to two dental treatment appointments, both with physical restraint: oral midazolam 1 mg/kg (MS) and placebo (PS). An observer assessed the children's behaviour (videos) using the Ohio State University Behavioral Rating Scale (OSUBRS). The children's saliva was collected just after waking up, on arrival at the dental school, 25 minutes after local anaesthesia, and 25 minutes after the end of the procedure. Salivary cortisol levels were determined using the enzyme-linked immunoabsorbent assay. The data were analysed by bivariate tests and multivariate analysis of variance (5% level). Salivary cortisol levels were lower in the MS group than in the PS group at the time of anaesthesia (p = 0.004), but did not vary during the appointment within sedation (p = 0.319) or placebo (p = 0.080) groups. Children's behaviour was negative most of the time and did not differ between MS and PS; however, the behaviour (OSUBRS) did not correlate with salivary cortisol levels. Oral midazolam is able to control salivary cortisol levels during dental treatment of pre-schoolers, which might not lead to better clinical behaviour. PMID:26892359

  18. Maintain levels of nicotine but reduce other smoke constituents: a formula for ''less-hazardous'' cigarettes

    SciTech Connect

    Robinson, J.C.; Young, J.C.; Rickert, W.S.

    1984-09-01

    Twenty-two volunteers who smoked more than 20 cigarettes with ''high'' nicotine yields (0.8 to 1.2 mg) per day participated in an 8-week study designed to test the hypothesis that smoking cigarettes with a constant level of nicotine but reduced deliveries of tar, carbon monoxide, and hydrogen cyanide leads to a decrease in smoke absorption. All subjects smoked their usual high-nicotine brand for the first 3 weeks (P1), and the absorption of smoke constituents was determined from levels of thiocyanate and cotinine in saliva and serum, levels of carbon monoxide in expired air, and levels of carboxyhemoglobin in the blood. During the final 5 weeks (P2), the treatment group (16 subjects) switched to the ''light'' version of their usual brands (similar yields of nicotine but with reduced yields of tar, carbon monoxide, and hydrogen cyanide); the control group (6 subjects) smoked their usual brands for the duration of the study. Average levels of cotinine for the subjects who switched during P2 were not significantly different from those of the control group as was expected. Slight reductions were noted in average expired-air carbon monoxide levels, blood carboxyhemoglobin, and saliva thiocyanate, but these reductions were smaller than anticipated based on brand characteristics. The results suggest that the ratio of smoke constituents is different when individuals, rather than machines, smoke cigarettes. Yields determined under subject-defined conditions are necessary in order to properly evaluate the role of nicotine in the design of ''less-hazardous'' cigarettes.

  19. Evidence that FcRn mediates the transplacental passage of maternal IgE in the form of IgG anti-IgE/IgE immune complexes

    PubMed Central

    Bundhoo, Arvin; Paveglio, Sara; Rafti, Ektor; Dhongade, Ashish; Blumberg, Richard S.; Matson, Adam P.

    2015-01-01

    Background The mechanism(s) responsible for acquisition of maternal antibody isotypes other than IgG are not fully understood. This uncertainty is a major reason underlying the continued controversy regarding whether cord blood (CB) IgE originates in the mother or fetus. Objective To investigate the capacity of maternal IgE to be transported across the placenta in the form of IgG anti-IgE/IgE immune complexes (ICs) and to determine the role of the neonatal Fc receptor (FcRn) in mediating this process. Methods Maternal and CB serum concentrations of IgE, IgG anti-IgE, and IgG anti-IgE/IgE ICs were determined in a cohort of allergic and non-allergic mother/infant dyads. Madin-Darby Canine Kidney (MDCK) cells stably transfected with human FcRn were used to study the binding and transcytosis of IgE in the form of IgG anti-IgE/IgE ICs. Results Maternal and CB serum concentrations of IgG anti-IgE/IgE ICs were highly correlated, regardless of maternal allergic status. IgG anti-IgE/IgE ICs generated in vitro bound strongly to FcRn-expressing MDCK cells and were transcytosed in an FcRn-dependent manner. Conversely, monomeric IgE did not bind to FcRn and was not transcytosed. IgE was detected in solutions of transcytosed IgG anti-IgE/IgE ICs, even though essentially all the IgE remained in complex form. Similarly, the majority of IgE in CB sera was found to be complexed to IgG. Conclusions and Clinical Relevance These data indicate that human FcRn facilitates the transepithelial transport of IgE in the form of IgG anti-IgE/IgE ICs. They also strongly suggest that the majority of IgE in CB sera is the result of FcRn-mediated transcytosis of maternal-derived IgG anti-IgE/IgE ICs. These findings challenge the widespread perception that maternal IgE does not cross the placenta. Measuring maternal or CB levels of IgG anti-IgE/IgE ICs may be a more accurate predictor of allergic risk. PMID:25652137

  20. Analysis of intracellular reducing levels in human hepatocytes on three-dimensional focusing microchip.

    PubMed

    Xu, Chunxiu; Cai, Longfei

    2014-02-01

    A novel three-dimensional hydrodynamic focusing microfluidic device integrated with high-throughput cell sampling and detection of intracellular contents is presented. It has a pivotal role in maintaining the reducing environment in cells. Intracellular reducing species such as vitamin C and glutathione in normal and tumor cells were labeled by a newly synthesized 2,2,6,6-tetramethyl-piperidine-1-oxyl-based fluorescent probe. Hepatocytes are adherent cells, which are prone to attaching to the channel surface. To avoid the attachment of cells on the channel surface, a single channel microchip with three sheath-flow channels located on both sides of and below the sampling channel was developed. Hydrostatic pressure generated by emptying the sample waste reservoir was used as driving force of fluid on the microchip. Owing to the difference between the liquid levels of the reservoirs, the labeled cells were three-dimensional hydrodynamically focused and transported from the sample reservoir to the sample waste reservoir. Hydrostatic pressure takes advantage of its ease of generation on a microfluidic chip without any external pressure pump, which drives three sheath-flow streams to constrain a sample flow stream into a narrow stream to avoid blockage of the sampling channel by adhered cells. The intracellular reducing levels of HepG2 cells and L02 cells were detected by home-built laser-induced fluorescence detector. The analysis throughput achieved in this microfluidic system was about 59-68 cells/min. PMID:23297173

  1. Antagonism of P2Y₁₂ reduces physiological thromboxane levels.

    PubMed

    Bhavaraju, Kamala; Georgakis, Alexander; Jin, Jianguo; Gartner, Theodore Kent; Tomiyama, Yoshiaki; Nurden, Alan; Nurden, Paquita; Kunapuli, Satya P

    2010-01-01

    Antiplatelet therapy for the management of patients with cardiovascular risks often includes a combination therapy of aspirin and clopidogrel, acting through inhibition of thromboxane generation and blockade of G(i)-coupled P2Y₁₂ receptor, respectively. We hypothesized that ADP acting through P2Y₁₂ regulates physiological thromboxane levels. The serum thromboxane levels in mice (n = 3) dosed with clopidogrel and prasugrel were decreased by 83.1 ± 5.3% and 94.26 ± 1.75% respectively compared to untreated mice. Pre-treatment of human blood (n = 3) ex vivo with active metabolites of clopidogrel or prasugrel led to a reduction in thromboxane levels to 16.3 ± 3.2% and 4.9 ± 0.8% respectively, compared to untreated human serum. We also evaluated serum thromboxane levels in P2Y receptor null mice (n = 4). Whereas serum thromboxane levels in P2Y₁ null mice were similar to those in wild type littermates, those in the P2Y₁₂ null mice were inhibited by 83.15 ± 3.8%. Finally, in a pilot study, serum thromboxane levels were reduced by 76.05 ± 8.41% in healthy human volunteers (n = 6) upon dosing with clopidogrel, compared to the levels before dosing. In conclusion, P2Y₁₂ antagonism alone can decrease physiological thromboxane levels. Thus, this study could pave way the for newer/modified treatment regimens for the management of patients with thrombotic complications who are allergic or non-responsive to aspirin. PMID:21067313

  2. Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies

    PubMed Central

    Munari, Enrico; Chaux, Alcides; Vaghasia, Ajay M.; Taheri, Diana; Karram, Sarah; Bezerra, Stephania M.; Gonzalez Roibon, Nilda; Nelson, William G.; Yegnasubramanian, Srinivasan; Netto, George J.; Haffner, Michael C.

    2016-01-01

    Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment. PMID:26785262

  3. CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice.

    PubMed

    Wolf, Risa M; Lei, Xia; Yang, Zhi-Chun; Nyandjo, Maeva; Tan, Stefanie Y; Wong, G William

    2016-03-01

    C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity. PMID:26670485

  4. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

    PubMed

    Zhang, Xilin; Hu, Jin; Zhong, Li; Wang, Na; Yang, Longyu; Liu, Chia-Chen; Li, Huifang; Wang, Xin; Zhou, Ying; Zhang, Yunwu; Xu, Huaxi; Bu, Guojun; Zhuang, Jiangxing

    2016-09-01

    Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy. PMID:27114256

  5. IgE and IgG1 antibody production by a soluble product of Ascaris suum in the guinea-pig.

    PubMed Central

    Stromberg, B E

    1979-01-01

    Third-stage larvae of Ascaris suum cultured to the fourth stage in a chemically defined culture medium produced a substance, the 'ACF antigen', which was allergenic in the guinea-pig. When three different concentrations (3.1, 31 and 62 micrograms) of the ACF antigen were given intraperitoneally, only the highest concentration induced a primary IgE specific antibody response (1:100 titre) as determined with the passive cutaneous anaphylaxis reaction. Upon secondary exposure all concentrations demonstrated a strong IgE response (1:50,000 peak titre) with very little IgG1 activity (1:100). The secondary IgE responses began to rise on the fourth day, peaked on the sixth day and returned to relatively low levels by the fourteenth day (1:100). The intramuscular administration of the ACF antigen did not induce the extremely high titres of IgE as found with the intraperitoneal injection, but rather a low level response (1:500 peak) which did not differ greatly from the IgG1 response. PMID:521052

  6. Experimentally elevated levels of testosterone at independence reduce fitness in a territorial bird.

    PubMed

    Martínez-Padilla, J; Pérez-Rodríguez, L; Mougeot, F; Ludwig, S C; Redpath, S M

    2014-04-01

    Environmental conditions and individual strategies in early life may have a profound effect on fitness. A critical moment in the life of an organism occurs when an individual reaches independence and stops receiving benefits from its relatives. Understanding the consequences of individual strategies at the time of independence requires quantification of their fitness effects. We explored this period in the Red Grouse (Lagopus lagopus scoticus). In this system, testosterone and parasite (Trichostrongylus tenuis) levels are known to influence survival and reproduction, the two key components of individual fitness. We experimentally and simultaneously manipulated testosterone and parasites at three levels (high, intermediate, and control levels for both factors) in 195 young males in five populations using a factorial experimental design. We explored the effects of our treatments on fitness by monitoring reproduction and survival throughout the life of all males and estimating lambda(ind), a rate-sensitive index of fitness. Parasite challenges increased the number of worms with a time lag, as previously found. However, we did not find significant effects of parasite manipulations on fitness, possibly because parasite abundance did not increase to harmful levels. Our hormone manipulation was successful at increasing testosterone at three different levels. Such increases in hormone levels decreased overall fitness. This was caused by reduced offspring production in the first breeding attempt rather than by any effect of the treatment on bird survival. Our results highlight that investing in high testosterone levels at independence, a strategy that might enhance short-term recruitment probability in territorial species such as Red Grouse, has a fitness cost, and can influence the resolution of the trade-off between reproduction and survival later in life. PMID:24933821

  7. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    SciTech Connect

    Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Hernandez-Ochoa, Isabel Paulose, Tessie Leslie, Traci C. Flaws, Jodi A.

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes

  8. Improving patients' sleep: reducing light and noise levels on wards at night.

    PubMed

    Hewart, Carol; Fethney, Loveday

    2016-02-01

    There is much research concerning the psychological and physical effects of sleep deprivation on patients in healthcare systems, yet interrupted sleep on hospital wards at night remains a problem. Staff at Plymouth Hospitals NHS Trust, Devon, wanted to identify the factors that prevent patients from sleeping well at night. Two audits were carried out, between April and August 2015, to assess noise and light levels on wards at night, and to engage nurses in ways of reducing these. A number of recommendations were made based on the audit findings, many of which have been put into practice. PMID:26938911

  9. Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens

    PubMed Central

    Vickery, Brian P.; Lin, Jing; Kulis, Michael; Fu, Zhiyan; Steele, Pamela H.; Jones, Stacie M.; Scurlock, Amy M.; Gimenez, Gustavo; Bardina, Ludmilla; Sampson, Hugh A.; Burks, A. Wesley

    2012-01-01

    Background Peanut-allergic subjects have highly stable pathologic antibody repertoires to the immunodominant B cell epitopes of the major peanut allergens Ara h 1-3. Objective We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. Methods Measurements of total peanut-specific IgE (psIgE) and psIgG4 were made with CAP-FEIA. We analyzed sera from 22 OIT subjects and 6 controls and measured serum specific IgE and IgG4 binding to epitopes of Ara h 1-3 using a high-throughput peptide microarray technique. Antibody affinity was measured using a competitive peptide microarray as previously described. Results At baseline, psIgE and psIgG4 diversity were similar between subjects and controls, and there was broad variation in epitope recognition. After a median 41 months of OIT, polyclonal psIgG4 increased from a median 0.3 mcg/mL (IQR 0.1-0.43) at baseline to 10.5 mcg/mL (3.95-45.48) (p<0.0001) and included de novo specificities. PsIgE was reduced from a median baseline of 85.45 kUA/L (23.05-101.0) to 7.75 kUA/L (2.58-30.55) (p<0.0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated subjects, several subjects generated new IgE specificities even as the total psIgE decreased. Global epitope-specific shifts from IgE to IgG4 binding occurred, including at an informative epitope of Ara h 2. Conclusion OIT differentially alters Ara h 1-3 binding patterns. These changes are variable between subjects, not observed in controls, and include a progressive polyclonal increase in IgG4, with concurrent reduction in IgE amount and diversity. PMID:23199605

  10. Phosphorus speciation by coupled HPLC-ICPMS: low level determination of reduced phosphorus in natural materials

    NASA Astrophysics Data System (ADS)

    Atlas, Zachary; Pasek, Matthew; Sampson, Jacqueline

    2015-04-01

    Phosphorus is a geologically important minor element in the Earth's crust commonly found as relatively insoluble apatite. This constraint causes phosphorus to be a key limiting nutrient in biologic processes. Despite this, phosphorus plays a direct role in the formation of DNA, RNA and other cellular materials. Recent works suggest that since reduced phosphorus is considerably more soluble than oxidized phosphorus that it was integrally involved in the development of life on the early Earth and may continue to play a role in biologic productivity to this day. This work examines a new method for quantification and identification of reduced phosphorus as well as applications to the speciation of organo-phosphates separated by coupled HPLC - ICP-MS. We show that reduced phosphorus species (P1+, P3+ and P5+) are cleanly separated in the HPLC and coupled with the ICPMS reaction cell, using oxygen as a reaction gas to effectively convert elemental P to P-O. Analysis at M/Z= 47 producing lower background and flatter baseline chromatography than analyses performed at M/Z = 31. Results suggest very low detection limits (0.05 μM) for P species analyzed as P-O. Additionally we show that this technique has potential to speciate at least 5 other forms of phosphorus compounds. We verified the efficacy of method on numerous materials including leached Archean rocks, suburban retention pond waters, blood and urine samples and most samples show small but detectible levels of reduced phosphorus and or organo-phaospates. This finding in nearly all substances analyzed supports the assumption that the redox processing of phosphorus has played a significant role throughout the history of the Earth and it's presence in the present environment is nearly ubiquitous with the reduced oxidation state phosphorus compounds, phosphite and hypophosphite, potentially acting as significant constituents in the anaerobic environment.

  11. Reducing greenhouse gas emissions, water use, and grain arsenic levels in rice systems.

    PubMed

    Linquist, Bruce A; Anders, Merle M; Adviento-Borbe, Maria Arlene A; Chaney, Rufus L; Nalley, L Lanier; da Rosa, Eliete F F; van Kessel, Chris

    2015-01-01

    Agriculture is faced with the challenge of providing healthy food for a growing population at minimal environmental cost. Rice (Oryza sativa), the staple crop for the largest number of people on earth, is grown under flooded soil conditions and uses more water and has higher greenhouse gas (GHG) emissions than most crops. The objective of this study was to test the hypothesis that alternate wetting and drying (AWD--flooding the soil and then allowing to dry down before being reflooded) water management practices will maintain grain yields and concurrently reduce water use, greenhouse gas emissions and arsenic (As) levels in rice. Various treatments ranging in frequency and duration of AWD practices were evaluated at three locations over 2 years. Relative to the flooded control treatment and depending on the AWD treatment, yields were reduced by <1-13%; water-use efficiency was improved by 18-63%, global warming potential (GWP of CH4 and N2 O emissions) reduced by 45-90%, and grain As concentrations reduced by up to 64%. In general, as the severity of AWD increased by allowing the soil to dry out more between flood events, yields declined while the other benefits increased. The reduction in GWP was mostly attributed to a reduction in CH4 emissions as changes in N2 O emissions were minimal among treatments. When AWD was practiced early in the growing season followed by flooding for remainder of season, similar yields as the flooded control were obtained but reduced water use (18%), GWP (45%) and yield-scaled GWP (45%); although grain As concentrations were similar or higher. This highlights that multiple environmental benefits can be realized without sacrificing yield but there may be trade-offs to consider. Importantly, adoption of these practices will require that they are economically attractive and can be adapted to field scales. PMID:25099317

  12. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats

    PubMed Central

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-01-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming. PMID:27540589

  13. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats.

    PubMed

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-08-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming. PMID:27540589

  14. Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.

    PubMed

    Pontes, Thaís Brilhante; Chen, Elizabeth Suchi; Gigek, Carolina Oliveira; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Leal, Mariana Ferreira; Demachki, Samia; Assumpção, Paulo Pimentel; Artigiani, Ricardo; Lourenço, Laércio Gomes; Burbano, Rommel Rodriguez; Arruda Cardoso Smith, Marília

    2014-04-01

    Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia. PMID:24338710

  15. Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows

    PubMed Central

    Noyes, Pamela D.; Lema, Sean C.; Macaulay, Laura J.; Douglas, Nora K.; Stapleton, Heather M.

    2013-01-01

    Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (~3 ng/g bw-day) and high dose (~300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3'-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ~65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in the brain and liver in patterns that varied with time and dose, likely in compensation to hypothyroidism. Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting non-linear relationships between BDE-209 exposures and thyroid dysfunction. PMID:23899252

  16. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Astrophysics Data System (ADS)

    Jaworske, D. A.; Degroh, Kim K.; Podojil, G.; McCollum, T.; Anzic, J.

    1992-11-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept of enhancing the lifetime of materials in low Earth orbit is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  17. Probiotic treatment reduces appetite and glucose level in the zebrafish model

    PubMed Central

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-01

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. PMID:26727958

  18. Probiotic treatment reduces appetite and glucose level in the zebrafish model.

    PubMed

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-01

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. PMID:26727958

  19. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, K. K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept for enhancing the lifetime of materials in low Earth orbits is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  20. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, Kim K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept of enhancing the lifetime of materials in low Earth orbit is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  1. Sodium salicylate reduces the level of GABAB receptors in the rat's inferior colliculus.

    PubMed

    Butt, S; Ashraf, F; Porter, L A; Zhang, H

    2016-03-01

    Previous studies have indicated that sodium salicylate (SS) can cause hearing abnormalities through affecting the central auditory system. In order to understand central effects of the drug, we examined how a single intraperitoneal injection of the drug changed the level of subunits of the type-B γ-aminobutyric acid receptor (GABAB receptor) in the rat's inferior colliculus (IC). Immunohistochemical and western blotting experiments were conducted three hours following a drug injection, as previous studies indicated that a tinnitus-like behavior could be reliably induced in rats within this time period. Results revealed that both subunits of the receptor, GABABR1 and GABABR2, reduced their level over the entire area of the IC. Such a reduction was observed in both cell body and neuropil regions. In contrast, no changes were observed in other brain structures such as the cerebellum. Thus, a coincidence existed between a structure-specific reduction in the level of GABAB receptor subunits in the IC and the presence of a tinnitus-like behavior. This coincidence likely suggests that a reduction in the level of GABAB receptor subunits was involved in the generation of a tinnitus-like behavior and/or used by the nervous system to restore normal hearing following application of SS. PMID:26705739

  2. Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.

    PubMed

    Santana-Martínez, R A; Galván-Arzáte, S; Hernández-Pando, R; Chánez-Cárdenas, M E; Avila-Chávez, E; López-Acosta, G; Pedraza-Chaverrí, J; Santamaría, A; Maldonado, P D

    2014-07-11

    Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities. PMID:24814729

  3. IGE and Basic Skills in the 80's: A Case for Effective Schooling.

    ERIC Educational Resources Information Center

    Beck, John J.; Bechtol, William M.

    The educational system known as Individually Guided Education (IGE) will become increasingly important as schools enter a period of retrenchment in the 1980's. Four factors necessary for basic skills achievement can be achieved through the use of IGE: (1) strong leadership by the school principal; (2) time spent in direct instruction by the…

  4. Ferulic acid enhances IgE binding to peanut allergens in western blots.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Because phenolic compounds can precipitate or complex with proteins, we postulated that interactions of phenolics with IgE antibodies help enhance IgE binding to peanut allergens in Western blots. Three different phenolics, such as, ferulic, caffeic and chlorogenic acids were examined. Each was mixe...

  5. Unique maturation program of the IgE response in vivo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A key event in the pathogenesis of asthma and allergies is the production of IgE antibodies. We show here that IgE+ cells are exceptional because they are largely found outside germinal centers and express, from very early on, a genetic program of plasma cells. In spite of their extra-germinal cente...

  6. Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange

    DOE PAGESBeta

    Pennington, Luke F.; Tarchevskaya, Svetlana; Brigger, Daniel; Sathiyamoorthy, Karthik; Graham, Michelle T.; Nadeau, Kari Christine; Eggel, Alexander; Jardetzky, Theodore S.

    2016-05-19

    Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab–Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, inmore » combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. Furthermore, this combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions.« less

  7. Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange

    PubMed Central

    Pennington, Luke F.; Tarchevskaya, Svetlana; Brigger, Daniel; Sathiyamoorthy, Karthik; Graham, Michelle T.; Nadeau, Kari Christine; Eggel, Alexander; Jardetzky, Theodore S.

    2016-01-01

    Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab–Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, in combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. This combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions. PMID:27194387

  8. Computationally predicted IgE epitopes of walnut allergens contribute to cross-reactivity with peanuts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cross reactivity between peanuts and tree nuts implies that similar IgE epitopes are present in their proteins. To determine whether walnut sequences similar to known peanut IgE binding sequences, according to the property distance (PD) scale implemented in the Structural Database of Allergenic Prot...

  9. Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange.

    PubMed

    Pennington, Luke F; Tarchevskaya, Svetlana; Brigger, Daniel; Sathiyamoorthy, Karthik; Graham, Michelle T; Nadeau, Kari Christine; Eggel, Alexander; Jardetzky, Theodore S

    2016-01-01

    Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab-Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, in combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. This combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions. PMID:27194387

  10. The awareness level and needs for education on reducing sugar consumption among mothers with preschool children

    PubMed Central

    Lee, Younhee

    2016-01-01

    BACKGROUND/OBJECTIVES The purpose of this study was to find out the level of knowledge on sugar-related nutrition among mothers with preschool children. SUBJECTS/METHODS The study conducted a survey on 350 mothers whose children attended daycare. The dietary lives of the children and the nutritional knowledge of the mothers on sugar were checked. In order to analyze results, SPSS 18.0 was used. ANOVA and t-test were also performed to analyze recognition and educational needs. RESULTS When the degree of nutritional knowledge was measured and analyzed, the results showed about 11 average points out of 15. The higher a group's nutritional knowledge, the better the dietary habits and activities were and the activities were more ccommon. The group with a low level of nutritional knowledge consumed more foods with high sugar content, but this difference was not statistically significant. Also the children from the group of mothers that provided nutritional education to their children were more likely to engage in better dietary habits and activities. CONCLUSIONS 66.5% respondents did not know about policies to reduce sugar consumption, but most indicated that education on reducing sugar consumption is needed. Therefore, a government-driven search for efficient methods to campaign and publicize sugar reduction is needed in order to continuously provide appropriate education. PMID:27087908

  11. Ultraviolet-ozone treatment reduces levels of disease-associated prion protein and prion infectivity

    USGS Publications Warehouse

    Johnson, C.J.; Gilbert, P.; McKenzie, D.; Pedersen, J.A.; Aiken, Judd M.

    2009-01-01

    Background. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases caused by novel infectious agents referred to as prions. Prions appear to be composed primarily, if not exclusively, of a misfolded isoform of the cellular prion protein. TSE infectivity is remarkably stable and can resist many aggressive decontamination procedures, increasing human, livestock and wildlife exposure to TSEs. Findings. We tested the hypothesis that UV-ozone treatment reduces levels of the pathogenic prion protein and inactivates the infectious agent. We found that UV-ozone treatment decreased the carbon and prion protein content in infected brain homogenate to levels undetectable by dry-ashing carbon analysis or immunoblotting, respectively. After 8 weeks of ashing, UV-ozone treatment reduced the infectious titer of treated material by a factor of at least 105. A small amount of infectivity, however, persisted despite UV-ozone treatment. When bound to either montmorillonite clay or quartz surfaces, PrPTSE was still susceptible to degradation by UV-ozone. Conclusion. Our findings strongly suggest that UV-ozone treatment can degrade pathogenic prion protein and inactivate prions, even when the agent is associated with surfaces. Using larger UV-ozone doses or combining UV-ozone treatment with other decontaminant methods may allow the sterilization of TSE-contaminated materials. ?? 2009 Aiken et al; licensee BioMed Central Ltd.

  12. Itching, pain, and anxiety levels are reduced with massage therapy in burned adolescents.

    PubMed

    Parlak Gürol, Ayşe; Polat, Sevinç; Akçay, Müfide Nuran

    2010-01-01

    Burn can be among the most severe physical and psychologic traumas a person may face. Patients with burns commonly have severe itching and pain. Severe itching has also been associated with anxiety, sleep disturbance, and disruption of daily living activities. The addition of complementary treatments to standard care may lead to improved pain management and may offer a safer approach for reducing pain and procedural anxiety for patients with burns. The authors conducted an experimental study to examine whether the effects of massage therapy reduced burned adolescents' pain, itching, and anxiety levels. Sixty-three adolescents were enrolled in this study shortly after admission (mean days = 3 +/- 0.48) at a burn unit in a large university hospital from February 2008 to June 2009. The measures including the pain, itching, and state anxiety were collected on the first and last days of the 5-week study period. The participants had an average age of 14.07 +/- 1.78 years and came usually from the lower socioeconomic strata. The authors observed that massage therapy reduced all these measures from the first to the last day of this study (P < .001). In most cultures, massage treatments are used to alleviate a wide range of symptoms. Although health professionals agree on the use of nonpharmacologic method for patients with burns, these applications are not yet common. PMID:20453734

  13. Apolipoprotein AI levels are increased in part as a consequence of reduced catabolism in nephrotic rats.

    PubMed

    Kaysen, G A; Hoye, E; Jones, H

    1995-03-01

    Apolipoprotein AI (apo AI) synthesis, measured as the turnover of 125I-labeled apo AI-labeled high-density lipoprotein (HDL), was increased significantly in rats with Heymann nephritis (HN) vs. control Sprague-Dawley (SD) rats. However, fractional apo AI catabolic rate was also significantly less in HN vs. SD. We used 125I-apo AI tyramine cellobiose HDL, a marker retained at the catabolic site, to establish where apo AI catabolism decreased in six HN rats, seven rats with adriamycin (Adria)-induced nephrosis, and six control SD. Total renal apo AI catabolism, plus urinary losses, were the same in all three groups, despite significant urinary apo AI in HN and Adria rats. Apo AI catabolism was reduced in skin in both nephrotic groups, accounting for approximately 44% of reduced in apo AI catabolism. Thus a significant fraction of apo AI is catabolized in skin of normal male rats. Reduced apo AI catabolism in skin contributes to increased plasma levels in nephrotic rats. PMID:7900854

  14. A heuristic re-mapping algorithm reducing inter-level communication in SAMR applications.

    SciTech Connect

    Steensland, Johan; Ray, Jaideep

    2003-07-01

    This paper aims at decreasing execution time for large-scale structured adaptive mesh refinement (SAMR) applications by proposing a new heuristic re-mapping algorithm and experimentally showing its effectiveness in reducing inter-level communication. Tests were done for five different SAMR applications. The overall goal is to engineer a dynamically adaptive meta-partitioner capable of selecting and configuring the most appropriate partitioning strategy at run-time based on current system and application state. Such a metapartitioner can significantly reduce execution times for general SAMR applications. Computer simulations of physical phenomena are becoming increasingly popular as they constitute an important complement to real-life testing. In many cases, such simulations are based on solving partial differential equations by numerical methods. Adaptive methods are crucial to efficiently utilize computer resources such as memory and CPU. But even with adaption, the simulations are computationally demanding and yield huge data sets. Thus parallelization and the efficient partitioning of data become issues of utmost importance. Adaption causes the workload to change dynamically, calling for dynamic (re-) partitioning to maintain efficient resource utilization. The proposed heuristic algorithm reduced inter-level communication substantially. Since the complexity of the proposed algorithm is low, this decrease comes at a relatively low cost. As a consequence, we draw the conclusion that the proposed re-mapping algorithm would be useful to lower overall execution times for many large SAMR applications. Due to its usefulness and its parameterization, the proposed algorithm would constitute a natural and important component of the meta-partitioner.

  15. The 28-entity IGES test file results using ComputerVision CADDS 4X

    NASA Technical Reports Server (NTRS)

    Kuan, Anchyi; Shah, Saurin; Smith, Kevin

    1987-01-01

    The investigation was based on the following steps: (1) Read the 28 Entity IGES (Initial Graphics Exchange Specification) Test File into the CAD data base with the IGES post-processor; (2) Make the modifications to the displayed geometries, which should produce the normalized front view and the drawing entity defined display; (3) Produce the drawing entity defined display of the file as it appears in the CAD system after modification to the geometry; (4) Translate the file back to IGES format using IGES pre-processor; (5) Read the IGES file produced by the pre-processor back into the CAD data base; (6) Produce another drawing entity defined display of the CAD display; and (7) Compare the plots resulting from steps 3 and 6 - they should be identical to each other.

  16. Attenuation of virulence in an apicomplexan hemoparasite results in reduced genome diversity at the population level

    PubMed Central

    2011-01-01

    Background Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. We expected virulence loss to be accompanied by consistent changes at the gene level, and that such changes would be shared among attenuated parasites of diverse geographic and genetic background. Results Surprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains. Conclusions This simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus. PMID:21838895

  17. Sesamol treatment reduces plasma cholesterol and triacylglycerol levels in mouse models of acute and chronic hyperlipidemia.

    PubMed

    Kumar, Nitesh; Mudgal, Jayesh; Parihar, Vipan K; Nayak, Pawan G; Kutty, N Gopalan; Rao, C Mallikarjuna

    2013-06-01

    The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200 mg/kg) significantly (P < 0.05) decreased triacylglycerol absorption in the fat tolerance test by showing a dose-dependent decrease in triacylglycerol levels. The hypolipidemic effect of sesamol at 200 mg/kg was equivalent to 10 mg/kg of orlistat. In the tyloxapol-induced hyperlipidemia model, Sesamol at 200 mg/kg reversed the elevated levels of cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24 h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2 % w/w), cholic acid (1 % w/w) and coconut oil 30 % (v/w) with standard powdered standard animal chow (up to 100 g). Niacin (100 mg/kg) and sesamol (100 mg/kg) significantly (P < 0.05) reduced the elevated body weight compared with the high fat diet control group. Elevated levels of cholesterol and triacylglycerol were significantly (P < 0.05) reversed by the sesamol (50 and 100 mg/kg), implying that it might reduce the absorption and increase the excretion of cholesterol as well. PMID:23504268

  18. Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women

    PubMed Central

    Rong, Ke; Liu, Xiao-yu; Wu, Xu-hua; Li, Xiao-liu; Xia, Qing-quan; Chen, Jiong; Yin, Xiao-fan

    2016-01-01

    Abstract We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose–response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91–0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93–0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98–1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00–1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women. PMID:26986111

  19. Diagnostic accuracy at several reduced radiation dose levels for CT imaging in the diagnosis of appendicitis

    NASA Astrophysics Data System (ADS)

    Zhang, Di; Khatonabadi, Maryam; Kim, Hyun; Jude, Matilda; Zaragoza, Edward; Lee, Margaret; Patel, Maitraya; Poon, Cheryce; Douek, Michael; Andrews-Tang, Denise; Doepke, Laura; McNitt-Gray, Shawn; Cagnon, Chris; DeMarco, John; McNitt-Gray, Michael

    2012-03-01

    Purpose: While several studies have investigated the tradeoffs between radiation dose and image quality (noise) in CT imaging, the purpose of this study was to take this analysis a step further by investigating the tradeoffs between patient radiation dose (including organ dose) and diagnostic accuracy in diagnosis of appendicitis using CT. Methods: This study was IRB approved and utilized data from 20 patients who underwent clinical CT exams for indications of appendicitis. Medical record review established true diagnosis of appendicitis, with 10 positives and 10 negatives. A validated software tool used raw projection data from each scan to create simulated images at lower dose levels (70%, 50%, 30%, 20% of original). An observer study was performed with 6 radiologists reviewing each case at each dose level in random order over several sessions. Readers assessed image quality and provided confidence in their diagnosis of appendicitis, each on a 5 point scale. Liver doses at each case and each dose level were estimated using Monte Carlo simulation based methods. Results: Overall diagnostic accuracy varies across dose levels: 92%, 93%, 91%, 90% and 90% across the 100%, 70%, 50%, 30% and 20% dose levels respectively. And it is 93%, 95%, 88%, 90% and 90% across the 13.5-22mGy, 9.6-13.5mGy, 6.4-9.6mGy, 4-6.4mGy, and 2-4mGy liver dose ranges respectively. Only 4 out of 600 observations were rated "unacceptable" for image quality. Conclusion: The results from this pilot study indicate that the diagnostic accuracy does not change dramatically even at significantly reduced radiation dose.

  20. Sequential serological responses to Aspergillus fumigatus in patients with cystic fibrosis. Use of antigen 'stretching' to delineate IgG and IgE activity.

    PubMed Central

    Edwards, J H; Alfaham, M; Fifield, R; Philpot, C; Clement, M J; Goodchild, M C

    1990-01-01

    Immunogens from Aspergillus fumigatus were fractionated on the basis of molecular weight. Nine fractions ranging from 900 to 10 kDa were used in ELISA and in a radioallergosorbent test (RAST) with sera from cases of allergic bronchopulmonary aspergillosis (ABPA) and from cystic fibrosis (CF) patients with ABPA or other Aspergillus involvement and compared with control subjects. The profile of IgG reactivity to the nine fractions did not vary substantially for all Aspergillus-involved groups producing peaks at greater than 900 kD and 170 kD whereas the profile for control subjects had a peak at greater than 900 kD only. The IgE profile for CF patients with ABPA did not differ from the profile of the RAST-positive CF patients without ABPA and provided only one peak of activity at 24 kD. Recovery from an episode of ABPA in CF patients was accompanied by a fall in both IgG and IgE antibody levels to all nine fractions, whereas increases in IgG and IgE to all fractions were seen during an episode of ABPA. Although there was an exaggerated IgG increase to antigens in the 43-170 kD range during ABPA, a meaningful increase was also observed to unfractionated A. fumigatus antigen preparations. With IgE in one detailed study the 24-kD fraction provided a better indication of Aspergillus involvement than the unfractionated A. fumigatus antigens. Sequential studies of IgG and IgE levels were not able to predict an episode of ABPA but were useful in conjunction with clinical assessment in following the course of the illness. PMID:2165878

  1. Predicting preferred coring level to reduce toner scatter in electrophotographic printing

    NASA Astrophysics Data System (ADS)

    Park, Hyung Jun; Allebach, Jan P.

    2011-01-01

    The electrophotographic process depends on a complex interplay between electrostatically charged toner particles, the developer roller, and the organic photoconductor during development; and between the toner particles, the organic photoconductor, and the paper during transfer. The task of controlling the imaging process is made even more challenging by the fact that colorant planes are developed independently and in succession. At high colorant levels, toner particles for a given colorant plane may be strongly repelled by toner that has already been deposited for previously developed colorant planes. The result is scattering of toner away from the edges of thin lines and character strokes. In previous work, we have proposed a coring method to reduce the occurrence of the toner scatter, and conducted psychophysical experiments to determine the preferred level of coring as a function of line width and colorant level. In this paper, we apply the edge transition width (ETW) metric to physically measure the impact of toner scatter on the sharpness of edges of lines and character strokes. We consider ETW both with and without coring, and compare it to the results from our earlier psychophysical experiments.

  2. Low-level laser therapy (LLLT) reduces inflammatory infiltrate and enhances skeletal muscle repair: Histomorphometric parameters

    NASA Astrophysics Data System (ADS)

    Paiva-Oliveira, E. L.; Lima, N. C.; Silva, P. H.; Sousa, N. T. A.; Barbosa, F. S.; Orsini, M.; Silva, J. G.

    2012-09-01

    Low level laser therapy (LLLT) has been suggested as an effective therapeutics in inflammatory processes modulation and tissue repairing. However, there is a lack of studies that analyze the anti-inflammatory effects of the infrared lasers in muscular skeletal injury. The aim of this study was to investigate the effects of low-level laser therapy 904 nm in the repair process of skeletal muscle tissue. Swiss mice were submitted to cryoinjury and divided in test (LLLT-treated) and control groups. Histological sections were stained with hematoxylin-eosin to assess general morphology and inflammatory influx, and Picrossirus to quantify collagen fibers deposition. Our results showed significant reduction in inflammatory infiltrated in irradiated mice after 4 days of treatment compared to control ( p = 0.01). After 8 days, the irradiated group showed high levels at regenerating myofibers with significant statistically differences in relation at control group ( p < 0.01). Collagen deposition was significantly increased in the final stages of regeneration at test group, when compared with control group ( p = 0.05). Our data suggests that LLLT reduces the inflammatory response in the initial stages of injury and accelerates the process of muscular tissue repair.

  3. Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants

    PubMed Central

    Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

    2016-01-01

    Introduction Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Materials and Methods Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. Results At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Conclusion Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the

  4. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

    PubMed

    Isidori, A M; Caprio, M; Strollo, F; Moretti, C; Frajese, G; Isidori, A; Fabbri, A

    1999-10-01

    Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced

  5. Postmenopausal vegetarians' low serum ferritin level may reduce the risk for metabolic syndrome.

    PubMed

    Kim, Mi-Hyun; Bae, Yun Jung

    2012-10-01

    The present study was conducted to compare the serum ferritin status between the postmenopausal vegetarians and non-vegetarians and to identify the relation of serum ferritin with metabolic syndrome (MetS) risk factors in postmenopausal women. The two study groups consisted of postmenopausal vegetarians (n=59) who maintained a vegetarian diet for over 20 years and age-matched non-vegetarian controls (n=48). Anthropometric measurements, dietary intakes, serum metabolic syndrome-related parameters, and serum ferritin level between the two groups were compared. The vegetarians exhibited significantly lower weight (p<0.01), body mass index (BMI) (p<0.001), percentage of body fat (p<0.001), waist circumference (p<0.01), SBP (p<0.001), DBP (p<0.001), and fasting glucose (p<0.05). According to the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III criteria for MetS applying Korean guidelines for waist circumference, the prevalence of MetS was lower in vegetarians (33.9 %) than in non-vegetarians (47.9 %). Vegetarians had significantly lower serum level of ferritin (p<0.01) than non-vegetarians. In the correlation analysis, serum ferritin was positively related to fasting glucose (r=0.264, p<0.01), triglycerides (r=0.232, p<0.05), and the NCEP score (r=0.214, p<0.05) and negatively related to high-density lipoprotein-cholesterol (r=-0.225, p<0.05) after adjusting for BMI, lifestyle, and dietary factors (animal protein, animal fat, and dietary fiber intake). In conclusion, postmenopausal vegetarians had lower MetS presence and a lower serum ferritin level compared to non-vegetarians. Furthermore, vegetarians' low serum ferritin level may reduce the risk of MetS in postmenopausal women. PMID:22528775

  6. The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE+ cells in memory responses is particularly unclear. IgE B cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate,...

  7. Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The epithelium lining the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human IgE receptor, CD23 (Fc'RII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monola...

  8. Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration.

    PubMed

    Chiang, Huei-Hsin; Forsell, Charlotte; Lilius, Lena; Öijerstedt, Linn; Thordardottir, Steinunn; Shanmugarajan, Krishnan; Westerlund, Marie; Nennesmo, Inger; Thonberg, Håkan; Graff, Caroline

    2013-11-01

    Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease with an age at onset generally below 65 years. Mutations in progranulin (GRN) have been reported to be able to cause FTLD through haploinsufficiency. We have sequenced GRN in 121 patients with FTLD and detected six different mutations in eight patients: p.Gly35Glufs*19, p.Asn118Phefs*4, p.Val200Glyfs*18, p.Tyr294*, p.Cys404* and p.Cys416Leufs*30. Serum was available for five of the mutations, where the serum-GRN levels were found to be >50% reduced compared with FTLD patients without GRN mutations. Moreover, the p.Cys416Leufs*30 mutation segregated in an affected family with different dementia diagnoses. The mutation frequency of GRN mutation was 6.6% in our FTLD cohort. PMID:23463024

  9. [For an efficient and reasonable accreditation of allergen specific IgE].

    PubMed

    Sarrat, Anne; Brabant, Séverine; Charbonnier, Eric; Alyanakian, Marie-Alexandra; Apoil, Pol-André; Bienvenu, Françoise; Jaby, Délia; Lainé, Catherine; Nicaise-Roland, Pascale; Renier, Gilles; Sainte-Laudy, Jean; Tabary, Thierry; Uring-Lambert, Béatrice; Vigneron, Céline; Lambert, Claude

    2013-01-01

    French medical laboratories must be accredited before November 2016 according to NF/EN/ISO 15189 standard. However, technical accreditation guidelines cannot be applied literally for the determination of specific IgE for several reasons: more than 600 allergen tests, lack of international gold standard, limited external quality controls. Furthermore, the technique for determination of specific IgE is CE DM-IVD marked, common to all specificities, automatised, standardized according to a single calibration curve. Thus, we propose an efficient but reasonable solution conform to the idea of the accreditation by validating the process. We recommend: a flexible extend type A; choice of only one representative allergen (Dermatophagoides pteronyssinus) for repeatability and precision (20 tests, 2 levels 0.5-1 and 8-12 kUA/L) performed on patients sera, reproducibility (30 consecutive determinations using an Internal Quality Control/IQC), accuracy (IQC and rare External Quality Controls) compared with peers. Sensitivity, specificity, dynamic range, detection threshold are determinated by the provider. Linearity may be checked if the laboratory practices sample dilution for values higher than the upper limit guaranteed by the provider. In the absence of international gold standard, the uncertainty is not measurable. In case of change of instrument, the results obtained by the systems must be compared through 35 tests of different specificities distributed across the range of calibration and including 5 values close to the detection limit. This methodology allows a scientifically effective verification, technically and financially reasonable, to ensure the excellence of the performance of the laboratory with regard to peers and users (allergologists and patients). PMID:23747670

  10. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge

    PubMed Central

    Liu, Mei; Gill, Jason J.; Young, Ry; Summer, Elizabeth J.

    2015-01-01

    Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages - GordTnk2, Gmala1, and GordDuk1 - had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5–15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment. PMID:26349678

  11. Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52

    NASA Astrophysics Data System (ADS)

    Jo, Chulman; Gundemir, Soner; Pritchard, Susanne; Jin, Youngnam N.; Rahman, Irfan; Johnson, Gail V. W.

    2014-03-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor in the defence against oxidative stress. Here we provide evidence that activation of the Nrf2 pathway reduces the levels of phosphorylated tau by induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in neurons. The expression of NDP52, which we show has three antioxidant response elements (AREs) in its promoter region, is strongly induced by Nrf2, and its overexpression facilitates clearance of phosphorylated tau in the presence of an autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl-insoluble tau accumulates in the brains concurrent with decreased levels of NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical samples of Alzheimer disease cases, and the amount of phosphorylated tau in sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These results suggest that NDP52 plays a key role in autophagy-mediated degradation of phosphorylated tau in vivo.

  12. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    PubMed

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  13. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    SciTech Connect

    Not Available

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  14. Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells

    PubMed Central

    Han, Ihn; Jung, Ji Hoon; Lee, Eun-Ok; Zhu, Shudong; Chen, Chang-Yan; Kim, Sung-Hoon

    2010-01-01

    Background We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line. Methodology/Principal Findings We showed that PO (IC50  = 17.3 µg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC50 over 200 µg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 µg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 µg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. Conclusions/Significance Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells. PMID:20808805

  15. IgE ELISA using antisera derived from epsilon chain antigenic peptides detects allergen-specific IgE in allergic horses.

    PubMed

    Kalina, Warren V; Pettigrew, Howard D; Gershwin, Laurel J

    2003-05-12

    Equine disease with an allergic etiology is common. Environmental antigens most often implicated as allergens in horses include molds, dusty hay, grass pollen, hay dust mites, and insect saliva. Although intradermal testing with allergen is a useful diagnostic tool for some species, skin testing frequently produces false positive results in horses. Allergen deprivation as a diagnostic tool is often impossible and at best it is ineffective at diagnosing the specific allergic reactivity. Synthesis of IgE after exposure to allergen is the instigator of the allergic process. While IgE exerts its effect after binding strongly to mast cell Fc receptors, the presence of free IgE in the serum can be used to quantify and determine the allergen specificity of the allergic disease. A lack of widely available reagents for detection of equine IgE has limited this approach in horses. We have used the nucleotide sequence of equine IgE to prepare a peptide-based immunogen to elicit equine epsilon chain-specific antisera. Selection of peptides was based on antigenic attributes of the deduced amino acid sequence of the equine epsilon chain. Six peptides were selected for conjugation to carrier molecules and rabbit immunization. Of these, one peptide elicited antisera that was successfully used in enzyme linked immunosorbant assay (ELISA) to screen horse serum from 64 allergic horses for allergen-specific IgE. Twenty-four of the 64 horses showed positive reactivity to one or more of the following allergens: grass, grain mill dust, mosquito, and horsefly. This study demonstrates the usefulness of peptide-based immunogens for development of antisera to rare or difficult to purify antigens such as IgE. Resultant antisera has great usefulness in diagnostic assays for equine allergy and as a research tool. PMID:12730014

  16. Highly charged swelling mica reduces free and extractable Cu levels in Cu-contaminated soils.

    PubMed

    Stuckey, Jason W; Neaman, Alexander; Ravella, Ramesh; Komarneni, Sridhar; Martínez, Carmen Enid

    2008-12-15

    Smelting of copper (Cu) results in the atmospheric deposition of Cu onto surrounding soils. Excess concentrations of Cu in soils can be absorbed by soil biota to toxic levels or leached into the groundwater, threatening the entire ecosystem. A means to restrict Cu mobility and uptake by plants is to remove it from the aqueous phase by applying an adsorptive material. A synthetic clay (highly charged swelling mica) was tested for its ability to decrease the levels of free and 0.1 M KNO3-extractable Cu in 15 surface soils from three different Cu mining areas in central Chile. The soils contained excessive total Cu levels (112-2790 mg Cu (kg soil)(-1)), while extractable Cu ranged from 0.3 to 22.9 mg Cu L(-1). The mica was applied to each soil at rates of 0.1%, 1%, and 2% (w/w). A 2% sodium-montmorillonite treatment and the nonamended soil served as controls. The order of treatment efficacy in reducing extractable Cu and free Cu2+ for low pH soils ( 1% mica > 2% montmorillonite > 0.1% mica. At 120 days, the 2% mica treatment maintained reductions of up to 93% in the free Cu2+ activity and up to 75% in the extractable Cu concentration upon acidification to the original soil pH value. In addition, Cu retention in mica-treated soils was more resistant to acidification than in lime-treated soils. This mica has promise for the remediation of acidic soils with metal contamination at the surface. PMID:19174892

  17. Automated concept-level information extraction to reduce the need for custom software and rules development

    PubMed Central

    Nguyen, Thien M; Goryachev, Sergey; Fiore, Louis D

    2011-01-01

    Objective Despite at least 40 years of promising empirical performance, very few clinical natural language processing (NLP) or information extraction systems currently contribute to medical science or care. The authors address this gap by reducing the need for custom software and rules development with a graphical user interface-driven, highly generalizable approach to concept-level retrieval. Materials and methods A ‘learn by example’ approach combines features derived from open-source NLP pipelines with open-source machine learning classifiers to automatically and iteratively evaluate top-performing configurations. The Fourth i2b2/VA Shared Task Challenge's concept extraction task provided the data sets and metrics used to evaluate performance. Results Top F-measure scores for each of the tasks were medical problems (0.83), treatments (0.82), and tests (0.83). Recall lagged precision in all experiments. Precision was near or above 0.90 in all tasks. Discussion With no customization for the tasks and less than 5 min of end-user time to configure and launch each experiment, the average F-measure was 0.83, one point behind the mean F-measure of the 22 entrants in the competition. Strong precision scores indicate the potential of applying the approach for more specific clinical information extraction tasks. There was not one best configuration, supporting an iterative approach to model creation. Conclusion Acceptable levels of performance can be achieved using fully automated and generalizable approaches to concept-level information extraction. The described implementation and related documentation is available for download. PMID:21697292

  18. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

  19. IgE epitope proximity determines immune complex shape and effector cell activation capacity

    PubMed Central

    Gieras, Anna; Linhart, Birgit; Roux, Kenneth H.; Dutta, Moumita; Khodoun, Marat; Zafred, Domen; Cabauatan, Clarissa R.; Lupinek, Christian; Weber, Milena; Focke-Tejkl, Margarete; Keller, Walter; Finkelman, Fred D.; Valenta, Rudolf

    2016-01-01

    Background IgE-allergen complexes induce mast cell and basophil activation and thus immediate allergic inflammation. They are also important for IgE-facilitated allergen presentation to T cells by antigen-presenting cells. Objective To investigate whether the proximity of IgE binding sites on an allergen affects immune complex shape and subsequent effector cell activation in vitro and in vivo. Methods We constructed artificial allergens by grafting IgE epitopes in different numbers and proximity onto a scaffold protein. The shape of immune complexes formed between artificial allergens and the corresponding IgE was studied by negative-stain electron microscopy. Allergenic activity was determined using basophil activation assays. Mice were primed with IgE, followed by injection of artificial allergens to evaluate their in vivo allergenic activity. Severity of systemic anaphylaxis was measured by changes in body temperature. Results We could demonstrate simultaneous binding of 4 IgE antibodies in close vicinity to each other. The proximity of IgE binding sites on allergens influenced the shape of the resulting immune complexes and the magnitude of effector cell activation and in vivo inflammation. Conclusions Our results demonstrate that the proximity of IgE epitopes on an allergen affects its allergenic activity. We thus identified a novel mechanism by which IgE-allergen complexes regulate allergic inflammation. This mechanism should be important for allergy and other immune complex–mediated diseases. PMID:26684291

  20. Naphthoquinone-tyrptophan reduces neurotoxic Aβ*56 levels and improves cognition in Alzheimer's disease animal model.

    PubMed

    Scherzer-Attali, R; Farfara, D; Cooper, I; Levin, A; Ben-Romano, T; Trudler, D; Vientrov, M; Shaltiel-Karyo, R; Shalev, D E; Segev-Amzaleg, N; Gazit, E; Segal, D; Frenkel, D

    2012-06-01

    An increasing body of evidence indicates a role for oligomers of the amyloid-β peptide (Aβ) in the neurotoxicity of this peptide and the pathology of Alzheimer's disease (AD). Several neurotoxic oligomeric forms of Aβ have been noted ranging from the larger Amyloid β-Derived Diffusible Ligands (ADDLs) to smaller trimers and dimers of Aβ. More recently a dodecameric form of Aβ with a 56 kDa molecular weight, denoted Aβ*56, was shown to cause memory impairment in AD model mice. Here, we present for the first time a potential therapeutic strategy for AD that targets the early stages in the formation of neurotoxic Aβ*56 oligomers using a modified quinone-Tryptophan small molecule N-(3-chloro-1,4-dihydro-1,4-dioxo-2-naphthalenyl)-L-Tryptophan (Cl-NQTrp). Using NMR spectroscopy we show that this compound binds the aromatic recognition core of Aβ and prevents the formation of oligomers. We assessed the effect of Cl-NQTrp in vivo in transgenic flies expressing Aβ(1-42) in their nervous system. When these flies were fed with Cl-NQTrp a marked alleviation of their Aβ-engendered reduced life span and defective locomotion was observed. Finally, intraperitoneal injection of Cl-NQTrp into an aggressive AD mouse model reduced the level of the Aβ*56 species in their brain and reversed their cognitive defects. Further experiments should assess whether this is a direct effect of the drug in the brain or an indirect peripheral effect. This is the first demonstration that targeted reduction of Aβ*56 results in amelioration of AD symptoms. This second generation of tryptophan-modified naphthoquinones could therefore serve as potent disease modifying therapeutic for AD. PMID:22449754

  1. Induction of reaginic (IgE) gonococcal antibodies in the rat by a common antigen of Neisseria gonorrhoeae.

    PubMed

    Ashton, F E; Vijay, H M; Lavergne, G; Brodeur, B R; Diena, B B

    1979-02-01

    An antigen (ZAB) common to Neisseria gonorrhoeae was prepared by stepwise elution of a crude gonococcal antigen (ZA) from columns of diethylaminoethyl cellulose employing 0.02 M phosphate buffers, pH 7.6, containing increasing concentrations of sodium chloride. Rats immunized with ZAB produced reaginic (IgE) antibody which cross-reacted with ZA prepared from eight gonococcal strains by the passive cutaneous anaphylaxis (PCA) test. Heating of the sera at 56 degrees C for 4 h destroyed the PCA activity. The PCA activity of the anti-ZAB rat serum was removed after absorption with ZAB antigen or with rabbit anti-rat IgE but not after absorption with gonococcal lipopolysaccharide or with heat-killed or formalinized gonococci. Treatment of ZAB with trypsin or heating at 100 degrees C for 30 min destroyed or reduced the antigenic activity respectively. Further purification of ZAB by filtration through Sephadex G-100 gave a preparation (ZAB2) which contained the common antigen as shown by the cross-reactivity of anti-ZAB2 rat serum with seven stains of N. gonorrhoeae. Fraction ZAB2 contained material which had a molecular weight less than 13,700 and was associated with the presence of material absorbing at 260 nm. The results of this study indicate that a low molecular weight antigen, which appears to be protein in nature and associated with nuclei acid, is common to the gonococcus and is the main antigenic component inducing reaginic (IgE) antibody in the rat. PMID:108009

  2. Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

    PubMed Central

    Wöhr, Markus; Roullet, Florence I.; Hung, Albert Y.; Sheng, Morgan; Crawley, Jacqueline N.

    2011-01-01

    Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism. PMID:21695253

  3. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    PubMed Central

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  4. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors

    PubMed Central

    Austin, Adelaide; Jiga-Boy, Gabriela M.; Rea, Sara; Newstead, Simon A.; Roderick, Sian; Davis, Nick J.; Clement, R. Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  5. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors.

    PubMed

    Austin, Adelaide; Jiga-Boy, Gabriela M; Rea, Sara; Newstead, Simon A; Roderick, Sian; Davis, Nick J; Clement, R Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  6. Methylene blue reduceslevels and rescues early cognitive deficit by increasing proteasome activity

    PubMed Central

    Medina, David X.; Caccamo, Antonella; Oddo, Salvatore

    2010-01-01

    Promising results have emerged from a phase II clinical trial testing Methylene blue (MB) as a potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months of MB administration have been reported. Despite these reports, no preclinical testing of MB in mammals has been published, and thus its mechanism of action in relation to AD pathology remains unknown. In order to elucidate the effects of MB on AD pathology and to determine its mechanism of action, we used a mouse model (3xTg-AD) that develops age-dependent accumulation of Aβ and tau and cognitive decline. Here, we report that chronic dietary MB treatment reduceslevels and improves learning and memory deficits in the 3xTg-AD mice. The mechanisms underlying the effects of MB on Aβ pathology appears to be mediated by an increase in Aβ clearance as we show that MB increases the chymotrypsin-and trypsin-like activities of the proteasome in the brain. To our knowledge, this is the first report showing that MB increases proteasome function and ameliorates AD-like pathology in vivo. Overall, the data presented here support the use of MB for the treatment of AD and offer a possible mechanism of action. PMID:20731659

  7. Reduced cholesterol levels impair Smoothened activation in Smith–Lemli–Opitz syndrome

    PubMed Central

    Blassberg, Robert; Macrae, James I.; Briscoe, James; Jacob, John

    2016-01-01

    Smith–Lemli–Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium. PMID:26685159

  8. Chemical genoprotection: reducing biological damage to as low as reasonably achievable levels

    PubMed Central

    Alcaraz, M; Armero, D; Martínez-Beneyto, Y; Castillo, J; Benavente-García, O; Fernandez, H; Alcaraz-Saura, M; Canteras, M

    2011-01-01

    Objectives The aim of this study was to evaluate the antioxidant substances present in the human diet with an antimutagenic protective capacity against genotoxic damage induced by exposure to X-rays in an attempt to reduce biological damage to as low a level as reasonably possible. Methods Ten compounds were assessed using the lymphocyte cytokinesis-block micronucleus (MN) cytome test. The compounds studied were added to human blood at 25 μM 5 min before exposure to irradiation by 2 Gy of X-rays. Results The protective capacity of the antioxidant substances assessed was from highest to lowest according to the frequency of the MN generated by X-ray exposure: rosmarinic acid = carnosic acid = δ-tocopherol = l-acid ascorbic = apigenin = amifostine (P < 0.001) > green tea extract = diosmine = rutin = dimetylsulfoxide (P < 0.05) > irradiated control. The reduction in genotoxic damage with the radiation doses administered reached 58%, which represents a significant reduction in X-ray-induced chromosomal damage (P < 0.001). This degree of protection is greater than that obtained with amifostine, a radioprotective compound used in radiotherapy and which is characterised by its high toxicity. Conclusion Several antioxidant substances, common components of the human diet and lacking toxicity, offer protection from the biological harm induced by ionizing radiation. Administering these protective substances to patients before radiological exploration should be considered, even in the case of small radiation doses and regardless of the biological damage expected. PMID:21697157

  9. Developing Community-Level Policy and Practice to Reduce Traffic-Related Air Pollution Exposure

    PubMed Central

    Brugge, Doug; Patton, Allison P.; Bob, Alex; Reisner, Ellin; Lowe, Lydia; Bright, Oliver-John M.; Durant, John L.; Newman, Jim; Zamore, Wig

    2016-01-01

    The literature consistently shows associations of adverse cardiovascular and pulmonary outcomes with residential proximity to highways and major roadways. Air monitoring shows that traffic-related pollutants (TRAP) are elevated within 200–400 m of these roads. Community-level tactics for reducing exposure include the following: 1) HEPA filtration; 2) Appropriate air-intake locations; 3) Sound proofing, insulation and other features; 4) Land-use buffers; 5) Vegetation or wall barriers; 6) Street-side trees, hedges and vegetation; 7) Decking over highways; 8) Urban design including placement of buildings; 9) Garden and park locations; and 10) Active travel locations, including bicycling and walking paths. A multidisciplinary design charrette was held to test the feasibility of incorporating these tactics into near-highway housing and school developments that were in the planning stages. The resulting designs successfully utilized many of the protective tactics and also led to engagement with the designers and developers of the sites. There is a need to increase awareness of TRAP in terms of building design and urban planning. PMID:27413416

  10. Serum IgE, tumor epidermal growth factor receptor expression, and inherited polymorphisms associated with glioma survival.

    PubMed

    Wrensch, Margaret; Wiencke, John K; Wiemels, Joe; Miike, Rei; Patoka, Joe; Moghadassi, Michelle; McMillan, Alex; Kelsey, Karl T; Aldape, Kenneth; Lamborn, Kathleen R; Parsa, Andrew T; Sison, Jennette D; Prados, Michael D

    2006-04-15

    In population-based glioma patients, we examined survival in relation to potentially pertinent constitutive polymorphisms, serologic factors, and tumor genetic and protein alterations in epidermal growth factor receptor (EGFR), MDM2, and TP53. Subjects were newly diagnosed adults residing in the San Francisco Bay Surveillance Epidemiology and End Results Area during 1991 to 1994 and 1997 to 1999 with central neuropathology review (n = 873). Subjects provided blood for serologic studies of IgE and IgG to four herpes viruses and constitutive specimens for genotyping 22 polymorphisms in 13 genes (n = 471). We obtained 595 of 697 astrocytic tumors for marker studies. We determined treatments, vital status, and other factors using registry, interview, medical record, and active follow-up data. Cox regressions for survival were adjusted for age, gender, ethnicity, study series, resection versus biopsy only, radiation, and chemotherapy. Using a stringent P < 0.001, glioma survival was associated with ERCC1 C8092A [hazard ratio (HR), 0.72; 95% confidence limits (95% CL), 0.60-0.86; P = 0.0004] and GSTT1 deletion (HR, 1.64; 95% CL, 1.25-2.16; P = 0.0004); glioblastoma patients with elevated IgE had 9 months longer survival than those with normal or borderline IgE levels (HR, 0.62; 95% CL, 0.47-0.82; P = 0.0007), and EGFR expression in anaplastic astrocytoma was associated with nearly 3-fold poorer survival (HR, 2.97; 95% CL, 1.70-5.19; P = 0.0001). Based on our and others' findings, we recommend further studies to (a) understand relationships of elevated IgE levels and other immunologic factors with improved glioblastoma survival potentially relevant to immunologic therapies and (b) determine which inherited ERCC1 variants or other variants in the 19q13.3 region influence survival. We also suggest that tumor EGFR expression be incorporated into clinical evaluation of anaplastic astrocytoma patients. PMID:16618782

  11. What are the main environmental exposures associated with elevated IgE in Cuban infants? A population-based study

    PubMed Central

    Fundora-Hernández, Hermes; Venero-Fernández, Silvia J; Suárez-Medina, Ramón; Mora-Faife, Esperanza de la C; García-García, Gladys; del Valle-Infante, Ileana; Gómez-Marrero, Liem; Venn, Andrea; Britton, John; Fogarty, Andrew W

    2014-01-01

    Objective Immunoglobulin E (IgE) plays a key role in allergy disease pathogenesis, but little is known about the environmental factors associated with higher IgE levels in infants. The aim of this study was to determine the risk factors for elevated serum total IgE infants living in Havana. Methods Eight hundred and seventy-seven infants provided blood samples. Data on allergic disease symptoms and a wide range of exposures were collected. Results The median IgE was 35IU/ml (interquartile range 13–96). The risk of having an IgE level above the median was higher for children who had been breastfed for 4 months or more (adjusted odds ratio (OR) 1.28; 95% confidence interval (CI): 1.02–1.61) and for children who reported cockroaches in their home (OR 1.30; 95% CI: 1.03–1.63). The risk was lower for children whose mother was in paid employment (OR 0.73; 95% CI: 0.54–0.97 compared with those who did not), for children living in homes where gas and electricity were used for cooking (OR 0.45; 95% CI: 0.32–0.62 compared with electricity only) and for children with domestic pets at birth (OR 0.83; 95% CI: 0.70-1.00). There was no association between paracetamol use and serum IgE levels. Conclusions Associations between gas fuel use and maternal employment indicate that IgE levels in early life are lower in children who may be living in relative affluence. The discrepancy in the effect of early exposure to pets or cockroaches may reflect differences in these allergens, or be confounded by relative affluence. Further investigation of this cohort will determine how these effects translate into the expression of allergic disease in later life. Objectif Les immunoglobulines E (IgE) jouent un rôle clé dans la pathogenèse de la maladie allergique, mais on sait peu sur les facteurs environnementaux associés à des taux plus élevés d'IgE chez les nourrissons. Le but de cette étude était de déterminer les facteurs de risque pour un taux élevé d'IgE s

  12. IgE-tailpiece associates with α-1-antitrypsin (A1AT) to protect IgE from proteolysis without compromising its ability to interact with FcεRI

    PubMed Central

    Quinn, Phyllis M.; Dunne, David W.; Moore, Shona C.; Pleass, Richard J.

    2016-01-01

    Several splice variants of IgE exist in human plasma, including a variant called IgE-tailpiece (IgE-tp) that differs from classical IgE by the replacement of two carboxy-terminal amino acids with eight novel residues that include an ultimate cysteine. To date, the role of the secreted IgE-tp isoform in human immunity is unknown. We show that levels of IgE-tp are raised in helminth-infected donors, and that both the classical form of IgE (IgE-c) and IgE-tp interact with polymers of the serine protease inhibitor alpha-1-antitrypsin (A1AT). The association of IgE-tp with A1AT polymers in plasma protects the antibody from serine protease-mediated degradation, without affecting the functional interaction of IgE-tp with important receptors, including FcεR1. That polymers of A1AT protect IgE from degradation by helminth proteases may explain why these common and normally non-disease causing polymorphic variants of A1AT have been retained by natural selection. The observation that IgE can be complexed with polymeric forms of A1AT may therefore have important consequences for our understanding of the pathophysiology of pulmonary diseases that arise either as a consequence of A1AT-deficiency or through IgE-mediated type 1 hypersensitivity responses. PMID:26842628

  13. Effect of apple pomace fiber and pork fat levels on quality characteristics of uncured, reduced-fat chicken sausages.

    PubMed

    Choi, Yun-Sang; Kim, Young-Boong; Hwang, Ko-Eun; Song, Dong-Heon; Ham, Youn-Kyung; Kim, Hyun-Wook; Sung, Jung-Min; Kim, Cheon-Jei

    2016-06-01

    The effects of reducing pork fat level from 30 to 25 and 20% by partially substituting pork fat with 1 and 2% apple pomace fiber were investigated based on the evaluation of physicochemical properties and textural properties of uncured, reduced-fat chicken sausages. Increased fat level resulted in decreased moisture content, cooking loss, total expressible fluid separation, fat separation, and yellowness of uncured, reduced-fat chicken sausages, whereas, an increase in fat content, caloric energy, pH, lightness, redness, hardness, cohesiveness, gumminess, and chewiness was observed. The results showed that uncured, reduced-fat chicken sausage samples with increased apple pomace fiber level had lower cooking loss, total expressible fluid separation, fat separation, pH, and redness. The results from this study show that inclusion of apple pomace fiber in the formulation will successfully reduce fat content in emulsion sausages, while improving quality characteristics relative to regular-fat (30%) control. PMID:27030694

  14. NASA geometry data exchange specification for computational fluid dynamics (NASA IGES)

    NASA Technical Reports Server (NTRS)

    Blake, Matthew W.; Kerr, Patricia A.; Thorp, Scott A.; Jou, Jin J.

    1994-01-01

    This document specifies a subset of an existing product data exchange specification that is widely used in industry and government. The existing document is called the Initial Graphics Exchange Specification. This document, a subset of IGES, is intended for engineers analyzing product performance using tools such as computational fluid dynamics (CFD) software. This document specifies how to define mathematically and exchange the geometric model of an object. The geometry is represented utilizing nonuniform rational B-splines (NURBS) curves and surfaces. Only surface models are represented; no solid model representation is included. This specification does not include most of the other types of product information available in IGES (e.g., no material properties or surface finish properties) and does not provide all the specific file format details of IGES. The data exchange protocol specified in this document is fully conforming to the American National Standard (ANSI) IGES 5.2.

  15. IGES, a key interface specification for CAD/CAM systems integration

    NASA Technical Reports Server (NTRS)

    Smith, B. M.; Wellington, J.

    1984-01-01

    The Initial Graphics Exchange Specification (IGES) program has focused the efforts of 52 companies on the development and documentation of a means of graphics data base exchange among present day CAD/CAM systems. The project's brief history has seen the evolution of the Specification into preliminary industrial usage marked by public demonstrations of vendor capability, mandatory requests in procurement actions, and a formalization into an American National Standard in September 1981. Recent events have demonstrated intersystem data exchange among seven vendor systems with a total of 30 vendors committing to offer IGES capability. A full range of documentation supports the IGES project and the recently approved IGES Version 2.0 of the Specification.

  16. Self-reactive IgE exacerbates interferon responses associated with autoimmunity

    PubMed Central

    Henault, Jill; Riggs, Jeffrey M.; Karnell, Jodi L.; Liarski, Vladimir M.; Li, Jianqing; Shirinian, Lena; Xu, Linda; Casey, Kerry A.; Smith, Michael A.; Khatry, Deepak B.; Izhak, Liat; Clarke, Lorraine; Herbst, Ronald; Ettinger, Rachel; Petri, Michelle; Clark, Marcus R.; Mustelin, Tomas; Kolbeck, Roland; Sanjuan, Miguel A.

    2015-01-01

    Summary Canonically, IgE mediates allergic immune responses by triggering mast cells and basophils to release histamine and Type 2 helper cytokines. Here, we report that in human systemic lupus erythematosus, IgE antibodies specific for double-stranded DNA activate plasmacytoid dendritic cells (pDCs), an immune cell type linked to viral defense, leading to the secretion of substantial amounts of interferon-α. The concentrations of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC functions by triggering phagocytosis via FcεRI followed by Toll-like receptor 9-mediated DNA sensing in phagosomes. These findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses. PMID:26692173

  17. Reduced gene expression levels after chronic exposure to high concentrations of air pollutants.

    PubMed

    Rossner, Pavel; Tulupova, Elena; Rossnerova, Andrea; Libalova, Helena; Honkova, Katerina; Gmuender, Hans; Pastorkova, Anna; Svecova, Vlasta; Topinka, Jan; Sram, Radim J

    2015-10-01

    We analyzed the ability of particulate matter (PM) and chemicals adsorbed onto it to induce diverse gene expression profiles in subjects living in two regions of the Czech Republic differing in levels and sources of the air pollution. A total of 312 samples from polluted Ostrava region and 154 control samples from Prague were collected in winter 2009, summer 2009 and winter 2010. The highest concentrations of air pollutants were detected in winter 2010 when the subjects were exposed to: PM of aerodynamic diameter <2.5μm (PM2.5) (70 vs. 44.9μg/m(3)); benzo[a]pyrene (9.02 vs. 2.56ng/m(3)) and benzene (10.2 vs. 5.5μg/m(3)) in Ostrava and Prague, respectively. Global gene expression analysis of total RNA extracted from leukocytes was performed using Illumina Expression BeadChips microarrays. The expression of selected genes was verified by quantitative real-time PCR (qRT-PCR). Gene expression profiles differed by locations and seasons. Despite lower concentrations of air pollutants a higher number of differentially expressed genes and affected KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was found in subjects from Prague. In both locations immune response pathways were affected, in Prague also neurodegenerative diseases-related pathways. Over-representation of the latter pathways was associated with the exposure to PM2.5. The qRT-PCR analysis showed a significant decrease in expression of APEX, ATM, FAS, GSTM1, IL1B and RAD21 in subjects from Ostrava, in a comparison of winter 2010 and summer 2009. In Prague, an increase in gene expression was observed for GADD45A and PTGS2. In conclusion, high concentrations of pollutants in Ostrava were not associated with higher number of differentially expressed genes, affected KEGG pathways and expression levels of selected genes. This observation suggests that chronic exposure to air pollution may result in reduced gene expression response with possible negative health consequences. PMID:26298100

  18. An element in the bovine papillomavirus late 3' untranslated region reduces polyadenylated cytoplasmic RNA levels.

    PubMed

    Furth, P A; Baker, C C

    1991-11-01

    Expression of the two bovine papillomavirus type 1 (BPV-1) late genes, L1 and L2, coding for the two capsid proteins, is limited to terminally differentiated keratinocytes in bovine fibropapillomas. This pattern of expression is determined both by the activity of the late promoter and by the inhibition of late region expression in less well differentiated cells. Inhibition of L1 and L2 mRNA production in nonpermissive cells must occur since the late region potentially could be transcribed from early region promoters. Nuclear runoff analysis of the late region has demonstrated that up to 95% of transcripts which are initiated in the early region in nonpermissive cells terminate within the late region upstream of the late polyadenylation site (C. C. Baker and J. Noe, J. Virol. 63:3529-3534, 1989). However, very few of the primary transcripts which include the late polyadenylation site are processed into mRNA. In this study, we have used expression vectors to characterize an inhibitory element active in nonpermissive cells which is located in the late 3' untranslated region (3'UTR). While the late polyadenylation site is functional in these cells, a 53-bp element in the late 3'UTR reduces levels of polyadenylated cytoplasmic RNA. This element inhibited chloramphenicol acetyltransferase (CAT) expression 6- to 10-fold when cloned in the sense orientation into the 3'UTR of a CAT expression vector. No block to expression was seen when the fragment was cloned immediately downstream of the poly(A) site, in an intron upstream of the CAT coding sequence, or in an antisense orientation in the 3'UTR. When the same fragment was deleted from a BPV-1 L1 expression vector, a sixfold increase in mRNA levels was seen. Actinomycin D chase experiments using BPV-1 L1 expression vectors indicated that the element does not destabilize cytoplasmic polyadenylated RNA. Therefore, the element must act before the mature mRNA reaches the cytoplasm. The data presented are consistent with effects

  19. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    USGS Publications Warehouse

    Ransom, Jason I.; Powers, Jenny G.; Hobbs, N. Thompson; Baker, Dan L.

    2014-01-01

    1. Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. 2. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. 3. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. 4. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. 5. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife

  20. Phytochemicals from Tradescantia albiflora Kunth Extracts Reduce Serum Uric Acid Levels in Oxonate-induced Rats

    PubMed Central

    Wang, Wen-Ling; Sheu, Shi-Yuan; Huang, Wen-Dar; Chuang, Ya-Ling; Tseng, Han-Chun; Hwang, Tzann-Shun; Fu, Yuan-Tsung; Kuo, Yueh-Hsiung; Yao, Chun-Hsu; Kuo, Tzong-Fu

    2016-01-01

    Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP

  1. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    PubMed Central

    Ransom, Jason I; Powers, Jenny G; Thompson Hobbs, N; Baker, Dan L

    2014-01-01

    Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife contraception, managers

  2. IgE response to two new allergen proteins of Solanum melongena L. (eggplant).

    PubMed

    Hoseini-Alfatemi, Seyedeh Mahsan; Bayry, Jagadeesh; Sharifi-Rad, Javad

    2015-12-01

    A number of allergens from eggplant (Solanum melongena L.) have been previously identified. In this study, we could detect IgE reactivity of two allergic subjects' sera towards two protein bands of molecular mass of about 35 and 15 kDa. As IgE were reactive to both raw and cooked eggplant extracts, a heat-stable nature of these novel allergens is apparent. PMID:26455782

  3. Computationally predicted IgE epitopes of walnut allergens contribute to cross-reactivity with peanuts

    PubMed Central

    Maleki, Soheila J.; Teuber, Suzanne S.; Cheng, Hsiaopo; Chen, Deliang; Comstock, Sarah S.; Ruan, Sanbao; Schein, Catherine H.

    2011-01-01

    Background Cross reactivity between peanuts and tree nuts implies that similar IgE epitopes are present in their proteins. Objective To determine whether walnut sequences similar to known peanut IgE binding sequences, according to the property distance (PD) scale implemented in the Structural Database of Allergenic Proteins (SDAP), react with IgE from sera of patients with allergy to walnut and/or peanut. Methods Patient sera were characterized by Western blotting for IgE-binding to nut protein extracts, and to peptides from walnut and peanut allergens, similar to known peanut epitopes as defined by low PD values, synthesized on membranes. Competitive ELISA was used to show that peanut and predicted walnut epitope sequences compete with purified Ara h 2 for binding to IgE in serum from a cross-reactive patient. Results Sequences from the vicilin walnut allergen Jug r 2 which had low PD values to epitopes of the peanut allergen Ara h 2, a 2s-albumin, bound IgE in sera from five patients who reacted to either walnut, peanut or both. A walnut epitope recognized by 6 patients mapped to a surface-exposed region on a model of the N-terminal pro-region of Jug r 2. A predicted walnut epitope competed for IgE binding to Ara h 2 in serum as well as the known IgE epitope from Ara h 2. Conclusions Sequences with low PD value (<8.5) to known IgE epitopes could contribute to cross-reactivity between allergens. This further validates the PD scoring method for predicting cross-reactive epitopes in allergens. PMID:21883278

  4. Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years

    PubMed Central

    Simpson, Angela; Lazic, Nevena; Belgrave, Danielle C.M.; Johnson, Phil; Bishop, Christopher; Mills, Clare; Custovic, Adnan

    2015-01-01

    Background The relationship between sensitization to allergens and disease is complex. Objective We sought to identify patterns of response to a broad range of allergen components and investigate associations with asthma, eczema, and hay fever. Methods Serum specific IgE levels to 112 allergen components were measured by using a multiplex array (Immuno Solid-phase Allergen Chip) in a population-based birth cohort. Latent variable modeling was used to identify underlying patterns of component-specific IgE responses; these patterns were then related to asthma, eczema, and hay fever. Results Two hundred twenty-one of 461 children had IgE to 1 or more components. Seventy-one of the 112 components were recognized by 3 or more children. By using latent variable modeling, 61 allergen components clustered into 3 component groups (CG1, CG2, and CG3); protein families within each CG were exclusive to that group. CG1 comprised 27 components from 8 plant protein families. CG2 comprised 7 components of mite allergens from 3 protein families. CG3 included 27 components of plant, animal, and fungal origin from 12 protein families. Each CG included components from different biological sources with structural homology and also nonhomologous proteins arising from the same biological source. Sensitization to CG3 was most strongly associated with asthma (odds ratio [OR], 8.20; 95% CI, 3.49-19.24; P < .001) and lower FEV1 (P < .001). Sensitization to CG1 was associated with hay fever (OR, 12.79; 95% CI, 6.84-23.90; P < .001). Sensitization to CG2 was associated with both asthma (OR, 3.60; 95% CI, 2.05-6.29) and hay fever (OR, 2.52; 95% CI, 1.38-4.61). Conclusions Latent variable modeling with a large number of allergen components identified 3 patterns of IgE responses, each including different protein families. In 11-year-old children the pattern of response to components of multiple allergens appeared to be associated with current asthma and hay fever but not eczema. PMID

  5. New Commercially Available IgG Kits and Time-Resolved Fluorometric IgE Assay for Diagnosis of Allergic Bronchopulmonary Aspergillosis in Patients with Cystic Fibrosis.

    PubMed

    Barrera, Coralie; Richaud-Thiriez, Bénédicte; Rocchi, Steffi; Rognon, Bénédicte; Roussel, Sandrine; Grenouillet, Frédéric; Laboissière, Audrey; Dalphin, Jean-Charles; Reboux, Gabriel; Millon, Laurence

    2015-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is difficult to diagnose; diagnosis relies on clinical, radiological, pathological, and serological criteria. Our aim was to assess the performance of two new commercially available kits and a new in-house assay: an Aspergillus fumigatus enzyme-linked immunosorbent assay (ELISA) IgG kit (Bordier Affinity Products), an Aspergillus Western blotting IgG kit (LDBio Diagnostics), and a new in-house time-resolved fluorometric IgE assay (dissociation-enhanced lanthanide fluorescent immunoassay, or DELFIA) using recombinant proteins from an Aspergillus sp. recently developed by our laboratory for ABPA diagnosis in a retrospective study that included 26 cystic fibrosis patients. Aspergillus fumigatus-specific IgG levels measured by a commercial ELISA kit were in accordance with the level of precipitins currently used in our lab. The ELISA kit could accelerate and help standardize ABPA diagnosis. Aspergillus fumigatus-specific IgE levels measured by ImmunoCAP (Phadia) with A. fumigatus M3 antigen and by DELFIA with a purified protein extract of A. fumigatus were significantly correlated (P < 10(-6)). The results with recombinant antigens glucose-6-phosphate isomerase and mannitol-1-phosphate dehydrogenase were encouraging but must be confirmed with sera from more patients. The DELFIA is an effective tool that can detect specific IgE against more fungal allergens than can be detected with other commercially available tests. PMID:26698651

  6. Label-free colorimetric aptasensor for IgE using DNA pseudoknot probe.

    PubMed

    Chang, Chia-Chen; Chen, Chen-Yu; Zhao, Xihong; Wu, Tzu-Heng; Wei, Shih-Chung; Lin, Chii-Wann

    2014-07-01

    The development of simple and low-cost approaches to the detection of immunoglobulin E (IgE) would provide a method for the early diagnosis and prevention of atopic diseases. The current methods of detection are generally tedious, multi-step processes and are limited by the high cost of the labeled proteins. We describe here a label-free structure-switching colorimetric method for the simple measurement of IgE using DNA pseudoknot probes and gold nanoparticles. In the absence of a target the IgE aptamer probe adopts a pseudoknot conformation that dissociates a capture probe from the unmodified gold nanoparticles. However, when IgE binds to the aptamer probe, the pseudoknot is resolved, leading to a favorable hybridization between the 3' terminal loop of the aptamer probe and the capture probe; this induces the aggregation of the gold nanoparticles. As a result, the colorimetric IgE sensor using this structure-switching mechanism is sensitive, specific and convenient, and the assay works even when challenged with complicated biological matrixes such as vaginal fluids. The proposed method is expected to be of great clinical value for IgE detection and could be used, after appropriate design, for sensing applications of other structured aptamers. PMID:24821053

  7. Serum IgE clearance is facilitated by human FcεRI internalization

    PubMed Central

    Greer, Alexandra M.; Wu, Nan; Putnam, Amy L.; Woodruff, Prescott G.; Wolters, Paul; Kinet, Jean-Pierre; Shin, Jeoung-Sook

    2014-01-01

    The high-affinity IgE receptor FcεRI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcεRI is also constitutively expressed in dendritic cells (DCs) and monocytes in humans; however, the specific functions of the FcεRI expressed by these cells are not completely understood. Here, we found that FcεRI expressed by human blood DC antigen 1–positive (BDCA1+) DCs and monocytes, but not basophils, traffics to endolysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcεRI on BDCA1+ DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FcεRIα (FCER1A-Tg mice) was endocytosed by conventional DCs and monocytes, and endocytosis was associated with rapid clearance of circulating IgE from these mice. Importantly, this rapid IgE clearance was dependent on monocytes or DCs but not basophils. These findings strongly suggest that constitutive internalization of human FcεRI by DCs and monocytes distinctively contributes to serum IgE clearance. PMID:24569373

  8. Ultrasensitive carbohydrate-peptide SPR imaging microarray for diagnosing IgE mediated peanut allergy

    PubMed Central

    Joshi, Amit A.; Peczuh, Mark W.; Kumar, Challa V.; Rusling, James F

    2014-01-01

    Severity of peanut allergies is linked to allergen-specific immunoglobulin E (IgE) antibodies in blood, but diagnostics from assays using glycoprotein allergen mixtures may be inaccurate. Measuring IgEs specific to individual peptide and carbohydrate epitopes of allergenic proteins is promising. We report here the first immunoarray for IgEs utilizing both peptide and carbohydrate epitopes. A surface plasmon resonance imaging (SPRi) microarray was equipped with peptide and β-xylosyl glycoside (BXG) epitopes from major peanut allergen glycoprotein Arachis hypogaea h2 (Ara-h2). A monoclonal anti-IgE antibody was included as positive control. IgEs were precaptured onto magnetic beads loaded with polyclonal anti-IgE antibodies to enhance sensitivity and minimize non-specific binding. As little as 0.1 attomole (0.5 pg/mL) IgE was detected from dilute serum in 45 min. IgEs binding to Ara-h2 peptide and BXG were quantified in 10 μL of patient serum and correlated with standard ImmunoCAP values. PMID:25259443

  9. Combined Inhaled Diesel Exhaust Particles and Allergen Exposure Alter Methylation of T Helper Genes and IgE Production In Vivo

    PubMed Central

    Liu, Jinming; Ballaney, Manisha; Al-alem, Umaima; Quan, Chunli; Jin, Ximei; Perera, Frederica; Chen, Lung-Chi; Miller, Rachel L.

    2008-01-01

    Changes in methylation of CpG sites at the interleukin (IL)-4 and interferon (IFN)-γ promoters are associated with T helper (Th) 2 polarization in vitro. No previous studies have examined whether air pollution or allergen exposure alters methylation of these two genes in vivo. We hypothesized that diesel exhaust particles (DEP) would induce hypermethylation of the IFN-γ promoter and hypomethylation of IL-4 in CD4+ T cells among mice sensitized to the fungus allergen Aspergillus fumigatus.We also hypothesized that DEP-induced methylation changes would affect immunoglobulin (Ig) E regulation. BALB/c mice were exposed to a 3-week course of inhaled DEP exposure while undergoing intranasal sensitization to A. fumigatus. Purified DNA from splenic CD4+ cells underwent bisulfite treatment, PCR amplification, and pyrosequencing. Sera IgE levels were compared with methylation levels at several CpG sites in the IL-4 and IFN-γ promoter. Total IgE production was increased following intranasal sensitization A. fumigatus. IgE production was augmented further following combined exposure to A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus induced hypermethylation at CpG−45, CpG−53, CpG−205 sites of the IFN-γ promoter and hypomethylation at CpG−408 of the IL-4 promoter. Altered methylation of promoters of both genes was correlated significantly with changes in IgE levels. This study is the first to demonstrate that inhaled environmental exposures influence methylation of Th genes in vivo, supporting a new paradigm in asthma pathogenesis. PMID:18042818

  10. Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

    PubMed Central

    Vojdani, Aristo

    2009-01-01

    Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity. PMID:19435515

  11. Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis.

    PubMed

    Agarwal, Ritesh; Aggarwal, Ashutosh N; Sehgal, Inderpaul S; Dhooria, Sahajal; Behera, Digambar; Chakrabarti, Arunaloke

    2016-01-01

    The role of total and specific IgE in monitoring treatment responses in allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. Here in, we evaluate the utility of total and Aspergillus fumigatus specific IgE in the follow-up of ABPA. Eighty-one consecutive treatment-naïve patients of ABPA (acute stage) with pulmonary infiltrates and bronchiectasis underwent measurement of total and A. fumigatus specific IgE at baseline, after 8 weeks of glucocorticoid therapy, and during exacerbations. There was clinical and radiological improvement after treatment with median decline of total IgE by 51.9%. The total IgE declined by at least 35%, 25% and 20% in 69 (85.2%), 76 (93.6%) and 78 (96.3%) patients, respectively. On the other hand, the A. fumigatus specific IgE increased in 42 (51.9%) subjects, and the mean increase was 1.4%, after 8 weeks. Among 13 patients with exacerbation, 12 (92.3%) had a rise of total IgE by >50%. The A. fumigatus specific IgE increased in only five (38.5%) subjects during exacerbation. Thus, the total IgE is a useful test in monitoring treatment responses in ABPA while A. fumigatus specific IgE has limited utility. PMID:26575791

  12. PID in Disguise: Molecular Diagnosis of IRAK-4 Deficiency in an Adult Previously Misdiagnosed With Autosomal Dominant Hyper IgE Syndrome.

    PubMed

    Frans, Glynis; Moens, Leen; Schrijvers, Rik; Wuyts, Greet; Bouckaert, Bernard; Schaballie, Heidi; Dupont, Lieven; Bossuyt, Xavier; Corveleyn, Anniek; Meyts, Isabelle

    2015-11-01

    Autosomal recessive IL-1R-associated kinase 4 (IRAK-4) deficiency is a rare cause of recurrent pyogenic infections with limited inflammatory responses. We describe an adult female patient with severe lung disease who was phenotypically diagnosed as suffering from autosomal dominant Hyper IgE syndrome (AD HIES) because of recurrent skin infections with Staphylococcus aureus, recurrent pneumonia and elevated serum IgE levels. In contrast to findings in AD HIES patients, no abnormalities were found in the Th17 and circulating follicular helper T cell subsets. A panel-based sequencing approach led to the identification of a homozygous IRAK4 stop mutation (c.877C > T, p.Gln293*). PMID:26472314

  13. Performing IgE serum testing due to bioinformatics matches in the allergenicity assessment of GM crops.

    PubMed

    Goodman, Richard E

    2008-10-01

    Proteins introduced into genetically modified (GM) organisms through genetic engineering must be evaluated for their potential to cause allergic disease under various national laws and regulations. The Codex Alimentarius Commission guidance document (2003) calls for testing of serum IgE binding to the introduced protein if the gene was from an allergenic source, or the sequence of the transferred protein has >35% identity in any segment of 80 or more amino acids to a known allergen or shares significant short amino acid identities. The Codex guidance recognized that the assessment will evolve based on new scientific knowledge. Arguably, the current criteria are too conservative as discussed in this paper and they do not provide practical guidance on serum testing. The goals of this paper are: (1) to summarize evidence supporting the level of identity that indicates potential risk of cross-reactivity for those with existing allergies; (2) to provide example bioinformatics results and discuss their interpretation using published examples of proteins expressed in transgenic crops; and (3) to discuss key factors of experimental design and methodology for serum IgE tests to minimize the rate of false negative and false positive identification of potential allergens and cross-reactive proteins. PMID:18715545

  14. Translation of CODEV Lens Model To IGES Input File

    NASA Astrophysics Data System (ADS)

    Wise, T. D.; Carlin, B. B.

    1986-10-01

    The design of modern optical systems is not a trivial task; even more difficult is the requirement for an opticker to accurately describe the physical constraints implicit in his design so that a mechanical designer can correctly mount the optical elements. Typical concerns include setback of baffles, obstruction of clear apertures by mounting hardware, location of the image plane with respect to fiducial marks, and the correct interpretation of systems having odd geometry. The presence of multiple coordinate systems (optical, mechan-ical, system test, and spacecraft) only exacerbates an already difficult situation. A number of successful optical design programs, such as CODEV (1), have come into existence over the years while the development of Computer Aided Design (CAD) and Computer Aided Manufacturing (CAM) has allowed a number of firms to install "paperless" design systems. In such a system, a part which is entered by keyboard, or pallet, is made into a real physical piece on a milling machine which has received its instructions from the design system. However, a persistent problem is the lack of a link between the optical design programs and the mechanical CAD programs. This paper will describe a first step which has been taken to bridge this gap. Starting with the neutral plot file generated by the CODEV optical design program, we have been able to produce a file suitable for input to the ANVIL (2) and GEOMOD (3) software packages, using the International Graphics Exchange Standard (IGES) interface. This is accomplished by software of our design, which runs on a VAX (4) system. A description of the steps to be taken in transferring a design will be provided. We shall also provide some examples of designs on which this technique has been used successfully. Finally, we shall discuss limitations of the existing software and suggest some improvements which might be undertaken.

  15. Oxidized and Reduced Nicotinamide Adenine Dinucleotide Phosphate Levels of Plants Hardened and Unhardened Against Chilling Injury

    PubMed Central

    Kuraishi, Susumu; Arai, Noriko; Ushijima, Tadahiro; Tazaki, Tadayoshi

    1968-01-01

    Pea plants (Pisum sativum L. var. Alaska) subjected to low temperature (5°) in the light acquired resistance against chilling injury. Unhardened plants maintained high NADP and low NADPH levels during illumination at 25° but hardened plants had low NADP and high NADPH levels in the light. When the unhardened plants were transferred to the dark room at 25°, their NADPH levels decreased immediately. On the other hand, hardened plants maintained a high NADPH level for a few hours even in the dark. PMID:16656757

  16. Murine B-cell stimulatory factor 1 (interleukin 4) increases expression of the Fc receptor for IgE on mouse B cells.

    PubMed Central

    Hudak, S A; Gollnick, S O; Conrad, D H; Kehry, M R

    1987-01-01

    We have studied the activity of mouse B-cell stimulatory factor 1 (interleukin 4, IL-4) on resting splenic B cells and on a B-cell hybridoma. Purified T-cell-derived as well as recombinant IL-4 was shown to increase the expression of the low-affinity Fc receptor for IgE (Fc epsilon R) on a majority of B lymphocytes in a 24-hr culture period. Levels of Fc epsilon R expression increased 2- to 3-fold on splenic B cells and up to 6-fold on a B-cell hybridoma. The effect was inhibited by an anti-IL-4 monoclonal antibody and by mouse gamma-interferon. Other recombinant lymphokines exhibited no effect on either Fc epsilon R expression or the induction by IL-4. The presence of IgE during the stimulation with IL-4 resulted in an additional increase in Fc epsilon R expression. These data and results showing that IgE prevents Fc epsilon R turnover while IL-4 increases the rate of Fc epsilon R synthesis suggest that the mechanisms by which IgE and IL-4 increase Fc epsilon R expression are likely to be different. The starting population of splenic B cells expressed low levels of Fc epsilon R and was relatively uniform in size (small). After greater than 48 hr of culture with IL-4, viable B cells had not undergone DNA synthesis and consisted mainly of larger highly Fc epsilon R-positive cells (23%) and medium-sized Fc epsilon R-positive cells (60%). A possible role for Fc epsilon R in certain B-cell maturation pathways is discussed. Images PMID:2955412

  17. Nutrient Plasma Levels Achieved During Treatment that Reduces Noise-Induced Hearing Loss

    PubMed Central

    Le Prell, C. G.; Dolan, D. F.; Bennett, D. C.; Boxer, P. A.

    2011-01-01

    Hearing loss encompasses both temporary and permanent deficits. If temporary threshold shift (TTS) and permanent threshold shift (PTS) share common pathological mechanisms, then agents that reduce PTS should also reduce TTS. Several antioxidant agents have reduced PTS in rodent models; however, reductions in TTS have been inconsistent. This study first determined whether dietary antioxidants (beta-carotene, and vitamins C and E) delivered in combination with magnesium (Mg) reliably increase plasma concentrations of the active agents. Then, additional manipulations tested the hypothesis that these nutrients reduce acute TTS insult in the first 24 hours following loud sound, as well as longer lasting changes in hearing measured up to 7 days post-noise. Saline or nutrients were administered to guinea pigs prior to and after noise exposure. Sound-evoked electrophysiological responses were measured before noise, with tests repeated 1-hour post-noise, as well as 1-, 3-, 5-, and 7-days post-noise. All subjects showed significant functional recovery; subjects treated with nutrients recovered more rapidly, and had better hearing outcomes at early post-noise times as well as the final test time. Thus, this combination of nutrients, which produced significant increases in plasma concentrations of vitamins C and E and Mg, effectively reduced hearing loss at multiple post-noise times. These data suggest free radical formation contributes to TTS as well as PTS insults, and suggest a potential opportunity to prevent TTS in human populations. PMID:21708356

  18. Prolonged fasting and cortisol reduce myostatin mRNA levels in tilapia larvae; short-term fasting elevates.

    PubMed

    Rodgers, Buel D; Weber, Gregory M; Kelley, Kevin M; Levine, Michael A

    2003-05-01

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indexes in adults, skeletal muscle myostatin mRNA levels were unaffected. By contrast, larval myostatin mRNA levels were sometimes elevated after a short-term fast and were consistently reduced with prolonged fasting. These effects were specific for myostatin, as mRNA levels of glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphatase were unchanged. Cortisol levels were elevated in fasted larvae with reduced myostatin mRNA, whereas in addition immersion of larvae in 1 ppm (2.8 microM) cortisol reduced myostatin mRNA in a time-dependent fashion. These results suggest that larval myostatin mRNA levels may initially rise but ultimately fall during a prolonged fast. The reduction is likely mediated by fasting-induced hypercortisolemia, indicating divergent evolutionary mechanisms of glucocorticoid regulation of myostatin mRNA, since these steroids upregulate myostatin gene expression in mammals. PMID:12676749

  19. The use of asparaginase to reduce acrylamide levels in cooked food.

    PubMed

    Xu, Fei; Oruna-Concha, Maria-Jose; Elmore, J Stephen

    2016-11-01

    Strategies proposed for reducing the formation of the suspected carcinogen acrylamide in cooked foods often rely on a reduction in the extent of the Maillard reaction, in which acrylamide is formed from the reaction between asparagine and reducing sugars. However, the Maillard reaction also provides desirable sensory attributes of cooked foods. Mitigation procedures that modify the Maillard reaction may negatively affect flavour and colour. The use of asparaginase to convert asparagine to aspartic acid may provide a means to reduce acrylamide formation, while maintaining sensory quality. This review collates research on the use of enzymes, asparaginase in particular, to mitigate acrylamide formation. Asparaginase is a powerful tool for the food industry and it is likely that its use will increase. However, the potential adverse effects of asparaginase treatment on sensory properties of cooked foods and the need to achieve sufficient enzyme-substrate contact remain areas for future research. PMID:27211635

  20. Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients.

    PubMed

    Untersmayr, Eva; Bakos, Noémi; Schöll, Isabella; Kundi, Michael; Roth-Walter, Franziska; Szalai, Krisztina; Riemer, Angelika B; Ankersmit, Hendrik J; Scheiner, Otto; Boltz-Nitulescu, George; Jensen-Jarolim, Erika

    2005-04-01

    Recently, we have demonstrated that anti-ulcer drugs, such as H2-receptor blockers and proton pump inhibitors, promote the development of immediate type food allergy toward digestion-labile proteins in mice. The aim of this study was to examine the allergological relevance of these findings in humans. In an observational cohort study, we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically. Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. Thus, the relative risk to develop food-specific IgE after anti-acid therapy was 10.5 (95% confidence interval: 1.44-76.48). The long-term effect was evaluated 5 months after therapy. Food-specific IgE could still be measured in 6% of the patients, as well as significantly elevated serum concentrations of ST2, a Th2-specific marker. An unspecific boost during the pollen season could be excluded, as 50 untreated control patients revealed no changes in their IgE pattern. In line with our previous animal experiments, our data strongly suggest that anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients. PMID:15671152

  1. Low-cost household paint abatement to reduce children's blood lead levels

    SciTech Connect

    Taha, T.; Kanarek, M.S.; Schultz, B.D.; Murphy, A.

    1999-11-01

    The purpose was to examine the effectiveness of low-cost abatement on children's blood lead levels. Blood lead was analyzed before and after abatement in 37 homes of children under 7 years old with initial blood lead levels of 25--44 {micro}g/dL. Ninety-five percent of homes were built before 1950. Abatement methods used were wet-scraping and repainting deteriorated surfaces and wrapping window wells with aluminum or vinyl. A control group was retrospectively selected. Control children were under 7 years old, had initial blood lead levels of 25--44 {micro}g/dL and a follow-up level at least 28 days afterward, and did not have abatements performed in their homes between blood lead levels. After abatement, statistically significant declines occurred in the intervention children's blood lead levels. The mean decline was 22%, 1 to 6 months after treatment. After adjustment for seasonality and child's age, the mean decline was 6.0 {micro}g/dL, or 18%. The control children's blood levels did not decline significantly. There was a mean decline of 0.25 {micro}g/dL, or 0.39%. After adjustment for seasonality and age, the mean decline for control children was 1.6 {micro}g/dL, or 1.8%. Low-cost abatement and education are effective short-term interim controls.

  2. [Experience in reducing the levels of raticides during open area disinfestations].

    PubMed

    Turyshev, A G; Korneev, A G; Konstantinova, E L

    2009-01-01

    The experience in combining disinfestation and forestry engineering measures is described to achieve a long-term effect: in minimizing the number of murine rodents, which has considerably reduced the amount of poisoned baits placed into the environment when disinfestation is made in open areas. PMID:19802943

  3. Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis

    PubMed Central

    Bhatt, Dhaval P.; Houdek, Heidi M.; Watt, John A.; Rosenberger, Thad A.

    2013-01-01

    Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/Kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 hr following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP) / (ATP + ADP + AMP)] when compared to controls. However, after 4 hr of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. PMID:23321384

  4. Reducing the substrate dependent scanner leveling effect in low-k1 contact printing

    NASA Astrophysics Data System (ADS)

    Chang, C. S.; Tseng, C. F.; Huang, C. H.; Yang, Elvis; Yang, T. H.; Chen, K. C.

    2015-03-01

    As the scaling down of design rule for high-density memory device, the small depth of focus (DoF) budget may be deteriorated by focus leveling errors, which arises in unpredicted reflectivity from multilayer structures on the topographic wafer. The leveling sensors of ASML scanner use near infrared (NIR) range wavelength which can penetrate through most of films using in semiconductor fabrication such as photo-resist, bottom anti reflective coating (BARC) and dielectric materials. Consequently, the reflected light from underlying substructures would disturb leveling sensors from accurate leveling. The different pattern densities and layout characteristics between array and periphery of a memory chip are expected to result in different leveling signals. Furthermore, the process dependent variations between wafer central and edge areas are also considered to yield different leveling performances during wafer exposure. In this study, lower blind contact immunity was observed for peripheral contacts comparing to the array contacts especially around wafer edge region. In order to overcome this problem, a series of investigations have been carried out. The wafer edge leveling optimization through circuit dependent focus edge clearance (CDFEC) option doesn't get improvement. Air gauge improved process leveling (AGILE) function of ASML immersion scanner doesn't show improved result either. The ILD uniformity improvement and step height treatments around wafer edge such as edge exclusion of film deposition and bevel etching are also ineffective to mitigate the blind contact problem of peripheral patterns. Altering the etch hard-mask stack is finally found to be an effective approach to alleviate the issue. For instance, through either containing high temperature deposition advanced patterning film (APF) in the hard-mask or inserting higher opaque film such as amorphous Si in between the hard-mask stack.

  5. Depression-like behavior and reduced plasma testosterone levels in the senescence-accelerated mouse.

    PubMed

    Egashira, Nobuaki; Koushi, Emi; Okuno, Ryoko; Shirakawa, Atsunori; Mishima, Kenichi; Iwasaki, Katsunori; Oishi, Ryozo; Fujiwara, Michihiro

    2010-05-01

    During aging, levels of testosterone gradually decline in men and low levels of testosterone in aged men are accompanied by increased incidence of depressive disorders. The senescence-accelerated-prone mouse 10 (SAMP10) is well known as an animal model of aging. The purpose of this study was to investigate the motor function, anxiety levels, depression-related emotional responses, attentional function and plasma levels of testosterone and dehydroepiandrosterone (DHEA) in SAMP10. SAMP10 exhibited a significant prolongation of immobility time compared to that of the aged-matched control senescence-accelerated-resistant mouse 1 (SAMR1) in the tail suspension test for measuring depression. Moreover, significant low levels of plasma testosterone but not DHEA were found in SAMP10, and the testosterone levels were inversely correlated with the depression-like behavior. By contrast, we did not observe any significant differences between SAMP10 and SAMR1 in the open-field, rota-rod, elevated plus-maze, marble-burying behavior, or prepulse inhibition test. The results of the present study indicate that testosterone may play an important role in the depression-like behavior in SAMP10. PMID:20117148

  6. A national project to evaluate and reduce high sound pressure levels from music.

    PubMed

    Ryberg, Johanna Bengtsson

    2009-01-01

    The highest recommended sound pressure levels for leisure sounds (music) in Sweden are 100 dB LAeq and 115 dB LAFmax for adults, and 97 dB LAeq and 110 dB LAFmax where children under the age of 13 have access. For arrangements intended for children, levels should be consistently less than 90 dB LAeq. In 2005, a national project was carried out with the aim of improving environments with high sound pressure levels from music, such as concert halls, restaurants, and cinemas. The project covered both live and recorded music. Of Sweden's 290 municipalities, 134 took part in the project, and 93 of these carried out sound measurements. Four hundred and seventy one establishments were investigated, 24% of which exceeded the highest recommended sound pressure levels for leisure sounds in Sweden. Of festival and concert events, 42% exceeded the recommended levels. Those who visit music events/establishments thus run a relatively high risk of exposure to harmful sound levels. Continued supervision in this field is therefore crucial. PMID:19414933

  7. PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: alirocumab.

    PubMed

    Dahagam, Chanukya; Goud, Aditya; Abdelqader, Abdelhai; Hendrani, Aditya; Feinstein, Matthew J; Qamar, Arman; Joshi, Parag H; Swiger, Kristopher J; Byrne, Kathleen; Quispe, Renato; Jones, Steven R; Blumenthal, Roger S; Martin, Seth S

    2016-03-01

    In this review, we examine alirocumab (Praluent(®)), a monoclonal antibody to PCSK9 and its role in reducing LDL-C levels. By comparing the results of various studies and trials we discuss the efficacy and safety of alirocumab. We aim to guide clinicians of the role of alirocumab in clinical practice. Overall, PCSK9 inhibitors are promising new agents in further reducing LDL-C levels in addition to diet and maximally tolerated statin therapy. Long-term outcome studies are currently ongoing and will further delineate the role of PCSK9 inhibitors. PMID:26911710

  8. The application of high-pressure treatment in the reduction of salt levels in reduced-phosphate breakfast sausages.

    PubMed

    O'Flynn, Claire C; Cruz-Romero, Malco C; Troy, Declan; Mullen, Anne M; Kerry, Joe P

    2014-03-01

    This study investigated the effects of high pressure (HP) treatment of pork meat before manufacturing sausages with reduced salt levels and compared them to sausages manufactured with untreated meat (control sausages). A 2×5 factorial design was set up incorporating two pressure levels (0 or 150 MPa) and five salt levels (0.5, 1.0, 1.5, 2.0 and 2.5%). Most quality attributes were affected when salt levels were reduced below 1.5%. Fat loss (FL) was (P<0.05) affected by salt level; samples with <1.5% salt had the highest FL. HP treatment increased emulsion stability and reduced cook loss (CL) compared to control sausages. Increased CL was observed when salt was reduced below 2.0%. Salt reduction below 1.5% adversely affected colour, sensory and texture attributes. Independent of salt, HP treatment affected adversely juiciness and cohesiveness while adhesiveness was improved. Overall, there is potential to manufacture sausages maintaining organoleptic and functional properties traditionally associated with sausages using HP treated meat. PMID:24334049

  9. The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

    PubMed Central

    He, Jin-Shu; Meyer-Hermann, Michael; Xiangying, Deng; Zuan, Lim Yok; Jones, Leigh Ann; Ramakrishna, Lakshmi; de Vries, Victor C.; Dolpady, Jayashree; Aina, Hoi; Joseph, Sabrina; Narayanan, Sriram; Subramaniam, Sharrada; Puthia, Manoj; Wong, Glenn; Xiong, Huizhong; Poidinger, Michael; Urban, Joseph F.; Lafaille, Juan J.

    2013-01-01

    The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE+ cells in memory responses is particularly unclear. IgE+ B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE+ GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B cell receptor function and increased apoptosis. IgE+ GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B cell differentiation fates: direct switching generates IgE+ GC cells, whereas sequential switching gives rise to IgE+ PCs. We propose a comprehensive model for the generation and memory of IgE responses. PMID:24218137

  10. Hydrophobic carboxy-terminal residues dramatically reduce protein levels in the haloarchaeon Haloferax volcanii

    PubMed Central

    Reuter, Christopher J.; Uthandi, Sivakumar; Puentes, Jose A.; Maupin-Furlow, Julie A.

    2010-01-01

    Proteolysis is important not only to cell physiology but also to the successful development of biocatalysts. While a wide-variety of signals are known to trigger protein degradation in bacteria and eukaryotes, these mechanisms are poorly understood in archaea, known for their ability to withstand harsh conditions. Here we present a systematic study in which single C-terminal amino acid residues were added to a reporter protein and shown to influence its levels in an archaeal cell. All 20 amino acid residues were examined for their impact on protein levels, using the reporter protein soluble modified red-shifted GFP (smRS-GFP) expressed in the haloarchaeon Haloferax volcanii as a model system. Addition of hydrophobic residues, including Leu, Cys, Met, Phe, Ala, Tyr, Ile and Val, gave the most pronounced reduction in smRS-GFP levels compared with the addition of either neutral or charged hydrophilic residues. In contrast to the altered protein levels, the C-terminal alterations had no influence on smRS-GFP-specific transcript levels, thus revealing that the effect is post-transcriptional. PMID:19850616

  11. Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans.

    PubMed

    Gato, Nobuki; Kadowaki, Akio; Hashimoto, Natsumi; Yokoyama, Shin-ichiro; Matsumoto, Kenji

    2013-01-01

    Bile acid-binding agents are known to lower blood cholesterol levels and have been clinically used for the treatment of hypercholesterolemia. We previously showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had bile acid-binding properties. In this study, we performed a randomized, double-blind, placebo-controlled trial to investigate the hypocholesterolemic effects of tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12 weeks. Plasma total cholesterol levels decreased significantly in the low-dose (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001) groups. In addition, plasma low-density lipoprotein cholesterol levels decreased significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001). These improvements were not accompanied by changes in plasma high-density lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that tannin-rich fiber from young persimmon fruits is a useful food material for treating hypercholesterolemia. PMID:23171573

  12. Use of cationic polymers to reduce pathogen levels during dairy manure separation.

    PubMed

    Liu, Zong; Carroll, Zachary S; Long, Sharon C; Gunasekaran, Sundaram; Runge, Troy

    2016-01-15

    Various separation technologies are used to deal with the enormous amounts of animal waste that large livestock operations generate. When the recycled waste stream is land applied, it is essential to lower the pathogen load to safeguard the health of livestock and humans. We investigated whether cationic polymers, used as a flocculent in the solid/liquid separation process, could reduce the pathogen indicator load in the animal waste stream. The effects of low charge density cationic polyacrylamide (CPAM) and high charge density cationic polydicyandiamide (PDCD) were investigated. Results demonstrated that CPAM was more effective than PDCD for manure coagulation and flocculation, while PDCD was more effective than CPAM in reducing the pathogen indicator loads. However, their combined use, CPAM followed by PDCD, resulted in both improved solids separation and pathogen indicator reduction. PMID:26513324

  13. Future development programs. [for defining the emission problem and developing hardware to reduce pollutant levels

    NASA Technical Reports Server (NTRS)

    Jedrziewski, S.

    1976-01-01

    The emission problem or source points were defined and new materials, hardware, or operational procedures were developed to exercise the trends defined by the data collected. The programs to reduce the emission output of aircraft powerplants were listed. Continued establishment of baseline emissions for various engine models, continued characterization of effect of production tolerances on emissions, carbureted engine development and flight tests, and cylinder cooling/fin design programs were several of the programs investigated.

  14. Could low dead-space syringes really reduce HIV transmission to low levels?

    PubMed

    Vickerman, P; Martin, N K; Hickman, M

    2013-01-01

    Studies published by Zule and colleagues have suggested that use of low dead-space syringes (LDSS) instead of high dead-space syringes (HDSS) by injecting drug users (IDUs) could dramatically reduce HIV transmission. However, evidence is limited because experiments have considered a small range of syringe types and have been unable to reliably estimate the efficacy of using LDSS for reducing HIV transmission. We critically appraise available evidence to determine whether using LDSS is likely to dramatically reduce HIV transmission. We systematically review the literature on the dead-space volume of syringes and estimate the factor difference in blood volume transferred from sharing LDSS or HDSS. Existing data on the relationship between host viral load and HIV transmission risk is used to evaluate the likely efficacy of using LDSS instead of HDSS. An HIV transmission model is used to make conservative impact projections for switching to using LDSS, and explore the implications of heterogeneity in IDU transmission risk and syringe preferences. Although highly variable, reviewed studies suggest that HDSS have on average 10 times the dead-space volume of LDSS and could result in 6/54/489 times more blood being transferred after 0/1/2 water rinses. Assuming a conservative 2-fold increase in HIV transmission risk per 10-fold increase in infected blood inoculum, HDSS use could be associated with a mean 1.7/3.6/6.5-fold increase in transmission risk compared to LDSS for 0/1/2 rinses. However, even for a low efficacy estimate, modelling suggests that partially transferring to LDSS use from using HDSS could dramatically reduce HIV prevalence (generally >33% if LDSS use is 50%), but impact will depend on IDU behavioural heterogeneity and syringe preference. Indirect evidence suggests that encouraging HDSS users to use LDSS could be a powerful HIV prevention strategy. There is an urgent need to evaluate the real life effectiveness of this strategy. PMID:23206493

  15. Feeding Jerusalem artichoke reduced skatole level and changed intestinal microbiota in the gut of entire male pigs.

    PubMed

    Vhile, S G; Kjos, N P; Sørum, H; Overland, M

    2012-05-01

    Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH. PMID:22558928

  16. Effects of Bordetella pertussis components on IgE and IgG1 responses.

    PubMed

    Sekiya, K

    1983-01-01

    The effect of dermonecrotic toxin (DNT), fimbrial hemagglutinin (FHA), K-agglutinogen, lipopolysaccharide (LPS), and pertussigen from Bordetella pertussis on the production of IgE and IgG1 antibodies to hen egg albumin (Ea) was investigated in C57BL/6 mice. The IgE antibody contents were determined by passive cutaneous anaphylaxis (PCA) in the skin of Lewis rats, while the IgG1 antibody contents were determined by PCA reactions on the skin of mice using sera that had been heated for 3 hr at 56 C to destroy the IgE antibodies. Among the B. pertussis components tested, pertussigen was the most effective adjuvant for increasing the IgE and IgG1 antibodies to Ea. LPS also moderately increased both types of antibodies, and FHA slightly increased the IgG1 titers. When LPS was given 5 days before Ea, it suppressed both IgE and IgG1 titers while FHA had only slight adjuvant action on both type of antibodies. When each of the components was tested for its ability to modify the adjuvant action of pertussigen, it was found that only DNT interfered significantly with the adjuvanticity of pertussigen when given on the day of immunization with Ea. When the components were given 5 days before Ea, DNT produced significant suppression of only the IgG1 response. LPS, FHA, and K-agglutinogen did not significantly affect the adjuvant action of pertussigen. PMID:6321910

  17. Clonal differences in IgE antibodies affect cutaneous anaphylaxis-associated thermal sensitivity in mice

    PubMed Central

    Mack, Madison; Tonc, Elena; Ashbaugh, Alyssa; Wetzel, Abigail; Sykes, Akilah; Engblom, Camilla; Shabani, Estela; Mora-Solano, Carolina; Trier, Anna; Swanson, Linnea; Ewan, Emily; Martinov, Tijana; Chatterjea, Devavani

    2014-01-01

    Cellular and molecular mediators of immune responses are increasingly implicated in acute and chronic pain pathophysiologies. Here we demonstrate that passive cutaneous IgE/Ag anaphylaxis provokes increased thermal sensitivity in the hind paw tissue of mice. The murine anti-DNP IgE antibodies SPE-7 and ε26 are known to induce differential cytokine production in bone marrow cultured mast cells in vitro without antigen challenge. We found a novel, antigen-dependent heterogeneity in the thermal pain responses elicited in the hind paws between SPE-7 and ε26 sensitized DNP-challenged mice. Mice experienced pronounced hind paw thermal sensitivity lasting 6 hours after DNP challenge when sensitized with SPE-7 but not ε26 IgE. The two IgE clones induced equivalent hind paw edema, neutrophil influx, cytokine production, and reduction in tissue histamine content in vivo, and bound to the same or overlapping epitopes on the DNP antigen in vitro. Therefore IgE antibodies against the same antigen can induce comparable inflammation, yet contribute to markedly different anaphylaxis-associated pain within an allergic response, suggesting that non-canonical IgE binding partners such as sensory neurons may play a role in allergy-related pain responses. PMID:25149207

  18. Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination

    PubMed Central

    Wesemann, Duane R.; Magee, Jennifer M.; Boboila, Cristian; Calado, Dinis Pedro; Gallagher, Michael P.; Portuguese, Andrew J.; Manis, John P.; Zhou, Xiaolong; Recher, Mike; Rajewsky, Klaus; Notarangelo, Luigi D.

    2011-01-01

    Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cμ (IgM) constant regions (CH) exons with downstream CH exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from Cμ to Cγ1 (IgG1) and Cε (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although Cε CSR can occur directly from Cμ, most mature peripheral B cells undergo CSR to Cε indirectly, namely from Cμ to Cγ1, and subsequently to Cε. Physiological mechanisms that influence CSR to Cγ1 versus Cε are incompletely understood. In this study, we report a role for B cell developmental maturity in IgE CSR. Based in part on a novel flow cytometric IgE CSR assay, we show that immature B cells preferentially switch to IgE versus IgG1 through a mechanism involving increased direct CSR from Cμ to Cε. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation. PMID:22143888

  19. Clonal differences in IgE antibodies affect cutaneous anaphylaxis-associated thermal sensitivity in mice.

    PubMed

    Mack, Madison; Tonc, Elena; Ashbaugh, Alyssa; Wetzel, Abigail; Sykes, Akilah; Engblom, Camilla; Shabani, Estela; Mora-Solano, Carolina; Trier, Anna; Swanson, Linnea; Ewan, Emily; Martinov, Tijana; Chatterjea, Devavani

    2014-11-01

    Cellular and molecular mediators of immune responses are increasingly implicated in acute and chronic pain pathophysiologies. Here we demonstrate that passive cutaneous IgE/Ag anaphylaxis provokes increased thermal sensitivity in the hind paw tissue of mice. The murine anti-DNP IgE antibodies SPE-7 and ɛ26 are known to induce differential cytokine production in bone marrow cultured mast cells in vitro without antigen challenge. We found a novel, antigen-dependent heterogeneity in the thermal pain responses elicited in the hind paws between SPE-7 and ɛ26 sensitized DNP-challenged mice. Mice experienced pronounced hind paw thermal sensitivity lasting 6h after DNP challenge when sensitized with SPE-7 but not ɛ26 IgE. The two IgE clones induced equivalent hind paw edema, neutrophil influx, cytokine production, and reduction in tissue histamine content in vivo, and bound to the same or overlapping epitopes on the DNP antigen in vitro. Therefore IgE antibodies against the same antigen can induce comparable inflammation, yet contribute to markedly different anaphylaxis-associated pain within an allergic response, suggesting that non-canonical IgE binding partners such as sensory neurons may play a role in allergy-related pain responses. PMID:25149207

  20. INCREASING SAFETY AND REDUCING ENVIRONMENTAL DAMAGE RISK FROM AGING HIGH-LEVEL RADIOACTIVE WASTE TANKS

    EPA Science Inventory

    There exists a paramount need for improved understanding of the behavior of high-level nuclear waste containers and the impact on structural integrity in terms of leak tightness and mechanical stability. The current program, which at the time of this writing is in its early stage...

  1. The mathematical model reduces the effect of distance to the scatter images gray level

    NASA Astrophysics Data System (ADS)

    Sun, Li-na

    2013-09-01

    In x-ray scanning system, scatter images are obtained to provide information on material density. The forward and backward scatter is related to solid angle. Scatter is therefore dependent on the distance of the scanned object from the x-ray source. In the real world, an object may be placed anywhere on the conveyer belt, so the measured intensity will contain errors relative to the ideal intensity. This makes classification results less reliable. Extraction of characteristic values L associated with the density; need to know the gray levels of scatter images, so how to base on forward scatter and back scatter images to determine the scatter image gray level is first necessary to solve the problem. The author combined with the forward scatter and backscatter images,then established higher order gray-level mathematical model of scattering images, to eliminate the impact of distance on the scatter images, to obtain more accurate gray level of scatter image. Then compare the error use of LMS algorithm and the LS algorithm to solving mathematical model parameters, LS algorithm ultimately prove less error and experimental validation of the superiority of the LS algorithm.

  2. Phosphorothioate Oligonucleotides Reduce PrPSc Levels and Prion Infectivity in Cultured Cells

    PubMed Central

    Karpuj, Marcela V; Giles, Kurt; Gelibter-Niv, Sagit; Scott, Michael R; Lingappa, Vishwanath R; Szoka, Francis C; Peretz, David; Denetclaw, Wilfred; Prusiner, Stanley B

    2007-01-01

    Prions are composed solely of the disease-causing prion protein (PrPSc) that is formed from the cellular isoform PrPC by a posttranslational process. Here we report that short phosphorothioate DNA (PS-DNA) oligonucleotides diminished the levels of both PrPC and PrPSc in prion-infected neuroblastoma (ScN2a) cells. The effect of PS-DNA on PrP levels was independent of the nucleotide sequence. The effective concentration (EC50) of PS-DNA required to achieve half-maximal diminution of PrPSc was ~70 nM, whereas the EC50 of PS-DNA for PrPC was more than 50-fold greater. This finding indicated that diminished levels of PrPSc after exposure to PS-DNA are unlikely to be due to decreased PrPC levels. Bioassays in transgenic mice demonstrated a substantial diminution in the prion infectivity after ScN2a cells were exposed to PS-DNAs. Whether PS-DNA will be useful in the treatment of prion disease in people or livestock remains to be established. PMID:17592554

  3. A method for reducing the level of spurious signals in surface acoustic wave filters

    NASA Astrophysics Data System (ADS)

    Borodii, Iu. N.; Grankin, I. M.; Zapunnyi, A. P.; Kolomeiko, A. V.

    1986-03-01

    A method for reducing spurious signals in surface acoustic wave (SAW) filters is proposed whereby both bulk and reflected wave signals are attenuated by electrodes of special configuration providing synphase addition of the useful signal and nonsynphase addition of spurious signal components. The electrodes of the input and output converters are made with a common focus point and equal angular apertures. The shape of the electrodes of the focusing converters on anisotropic crystal surfaces is determined by the corresponding SAW group velocity curve. An implementation of the method proposed here is examined together with some test results.

  4. Treatment with oleic acid reduces IgE binding to peanut and cashew allergens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oleic acid (OA) is known to bind and change the bioactivities of proteins, such as a-lactalbumin and ß-lactoglobulin in vitro. The objective of this study was to determine if OA binds to allergens from a peanut extract or cashew allergen and changes their allergenic properties. Peanut extract or c...

  5. Reduced Levels of Membrane-Bound Alkaline Phosphatase Are Common to Lepidopteran Strains Resistant to Cry Toxins from Bacillus thuringiensis

    PubMed Central

    Jurat-Fuentes, Juan Luis; Karumbaiah, Lohitash; Jakka, Siva Rama Krishna; Ning, Changming; Liu, Chenxi; Wu, Kongming; Jackson, Jerreme; Gould, Fred; Blanco, Carlos; Portilla, Maribel; Perera, Omaththage; Adang, Michael

    2011-01-01

    Development of insect resistance is one of the main concerns with the use of transgenic crops expressing Cry toxins from the bacterium Bacillus thuringiensis. Identification of biomarkers would assist in the development of sensitive DNA-based methods to monitor evolution of resistance to Bt toxins in natural populations. We report on the proteomic and genomic detection of reduced levels of midgut membrane-bound alkaline phosphatase (mALP) as a common feature in strains of Cry-resistant Heliothis virescens, Helicoverpa armigera and Spodoptera frugiperda when compared to susceptible larvae. Reduced levels of H. virescens mALP protein (HvmALP) were detected by two dimensional differential in-gel electrophoresis (2D-DIGE) analysis in Cry-resistant compared to susceptible larvae, further supported by alkaline phosphatase activity assays and Western blotting. Through quantitative real-time polymerase chain reaction (qRT-PCR) we demonstrate that the reduction in HvmALP protein levels in resistant larvae are the result of reduced transcript amounts. Similar reductions in ALP activity and mALP transcript levels were also detected for a Cry1Ac-resistant strain of H. armigera and field-derived strains of S. frugiperda resistant to Cry1Fa. Considering the unique resistance and cross-resistance phenotypes of the insect strains used in this work, our data suggest that reduced mALP expression should be targeted for development of effective biomarkers for resistance to Cry toxins in lepidopteran pests. PMID:21390253

  6. METHODS FOR CONDUCTING SNAIL (APLEXA HYPNORUM) EMBRYO THROUGH ADULT EXPOSURES: EFFECTS OF CADMIUM AND REDUCED PH LEVELS

    EPA Science Inventory

    Two separate embryo through adult exposures were conducted with cadmium and with reduced pH levels to validate various test methodologies and to determine the feasibility of testing and ease of handling the freshwater snail (Aplexa hypnorum) in a test system designed for fish bio...

  7. Increased plasma neopterin levels are associated with reduced endothelial function and arterial elasticity in hypertension.

    PubMed

    Zhang, Y-Y; Tong, X-Z; Xia, W-H; Xie, W-L; Yu, B-B; Zhang, B; Chen, L; Tao, J

    2016-07-01

    Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77±0.18 versus 0.61±0.16, P=0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659, P<0.001; hypertension: r=0.487, P=0.021), and inversely associated with impaired brachial flow-mediated dilation (FMD; control: r=-0.735, P<0.001; hypertension: r=-0.557, P=0.005). Fifteen hypertensives received 3 months of standard antihypertensive treatment. Three months later, their plasma neopterin levels decreased (log-neopterin: 0.63±0.17 versus 0.50±0.19, P=0.001), whereas arterial elasticity (baPWV: 1764±101 versus 1685±96 cm s(-1), P=0.272) and endothelial function (FMD: 5.92±1.43% versus 7.73±1.31%, P<0.05) were improved. The decline in neopterin levels was linearly correlated with baPWV decrease (r=0.800, P<0.001), FMD improvement (r=0.670, P=0.006) and blood pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension. PMID

  8. Exposure to Organic Solvents Used in Dry Cleaning Reduces Low and High Level Visual Function

    PubMed Central

    Jiménez Barbosa, Ingrid Astrid

    2015-01-01

    Purpose To investigate whether exposure to occupational levels of organic solvents in the dry cleaning industry is associated with neurotoxic symptoms and visual deficits in the perception of basic visual features such as luminance contrast and colour, higher level processing of global motion and form (Experiment 1), and cognitive function as measured in a visual search task (Experiment 2). Methods The Q16 neurotoxic questionnaire, a commonly used measure of neurotoxicity (by the World Health Organization), was administered to assess the neurotoxic status of a group of 33 dry cleaners exposed to occupational levels of organic solvents (OS) and 35 age-matched non dry-cleaners who had never worked in the dry cleaning industry. In Experiment 1, to assess visual function, contrast sensitivity, colour/hue discrimination (Munsell Hue 100 test), global motion and form thresholds were assessed using computerised psychophysical tests. Sensitivity to global motion or form structure was quantified by varying the pattern coherence of global dot motion (GDM) and Glass pattern (oriented dot pairs) respectively (i.e., the percentage of dots/dot pairs that contribute to the perception of global structure). In Experiment 2, a letter visual-search task was used to measure reaction times (as a function of the number of elements: 4, 8, 16, 32, 64 and 100) in both parallel and serial search conditions. Results Dry cleaners exposed to organic solvents had significantly higher scores on the Q16 compared to non dry-cleaners indicating that dry cleaners experienced more neurotoxic symptoms on average. The contrast sensitivity function for dry cleaners was significantly lower at all spatial frequencies relative to non dry-cleaners, which is consistent with previous studies. Poorer colour discrimination performance was also noted in dry cleaners than non dry-cleaners, particularly along the blue/yellow axis. In a new finding, we report that global form and motion thresholds for dry cleaners

  9. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    PubMed

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type. PMID:25198797

  10. A single mouse monoclonal antibody, E58 modulates multiple IgE epitopes on group 1 cedar pollen allergens.

    PubMed

    Goldblum, Randall M; Ning, Bo; Judy, Barbara M; Holthauzen, Luis Marcelo F; van Bavel, Julius; Kamijo, Atsushi; Midoro-Horiuti, Terumi

    2016-06-01

    We recently described a dominant role for conformational epitopes on the group 1 allergen of the mountain cedar (Juniperus ashei, Cupressaceae), Jun a 1, in pollen hypersensitivity in South Central U.S.A. Since these epitopes are surface exposed and are likely to be flexible, they may be susceptible to molecular or physical perturbations. This may make Jun a 1 a potential target for new forms of therapy for cedar pollinosis. Here, we describe a mouse monoclonal antibody, termed E58, which binds to the group 1 allergens of the cedar pollens from three highly populated regions of the world (central U.S.A., France and Japan). Upon binding to these allergens, E58 strongly reduces the binding of patient's IgE antibodies to these dominant allergens. This characteristic of E58, and potentially other similar antibodies, suggests an opportunity to develop preventative or therapeutic agents that may inhibit cedar pollen sensitization or prevent their allergic reactions. PMID:27174188

  11. Regional growth management policies: Toward reducing global warming at state and local levels

    SciTech Connect

    Purdie, J.

    1995-09-01

    State and local governments in the United States are accepting mandates to coordinate legislated land use and growth management planning with vigorous environmental protection and resource conservation. These mandates, implemented or planned in states with populations totaling over 100 million, will directly impact growth patterns and ultimately affect the level of atmospheric gases and particulates generated within their borders. This paper addresses the issues of growth management and land use planning at the local, state and regional levels and identifies areas impacting global warming. A review of existing systems will be presented, and recommendations will be made to improve monitoring of growth management mechanisms and organizational structures with the goal of global atmospheric improvement. The issues discussed include urban sprawl, transportation, and growth patterns as managed by policies also designed to protect environments and provide for sustainable growth. Areas for improved coordination between jurisdictions to ease global warming will also be examined.

  12. Effectiveness of flushing on reducing lead and copper levels in school drinking water.

    PubMed Central

    Murphy, E A

    1993-01-01

    Samples from drinking water fountains in 50 schools in New Jersey were collected at specific times during a typical school day and analyzed for lead, copper, pH, alkalinity, and hardness. First-draw lead and copper levels (medians 0.010 mg/l and 0.26 mg/l, respectively) decreased significantly after 10 min of flushing in the morning (medians 0.005 mg/l lead and 0.068 mg/l copper), but levels increased significantly by lunchtime (medians 0.007 mg/l lead and 0.12 mg/l copper) after normal use of fountains in the morning by students. Corrosive water, as defined by the aggressive index, contained significantly higher levels of lead and copper (medians 0.012 mg/l and 0.605 mg/l, respectively) than noncorrosive water (medians 0.005 mg/l and 0.03 mg/l, respectively). Images p240-a PMID:8404761

  13. by ligand exchange: utilizing energy level alignment for efficiently reducing carrier rec ombination

    NASA Astrophysics Data System (ADS)

    Wang, Xia; Kou, Dong-Xing; Zhou, Wen-Hui; Zhou, Zheng-Ji; Wu, Si-Xin; Cao, Xuan

    2014-05-01

    In this work, we employed a convenient one-step synthesis method for synthesizing Cu2ZnSnSe4 (CZTSe) nanocrystals (NCs) in an excess selenium environment. This excess selenium situation enhanced the reaction of metal acetylacetonates with selenium, resulting in the burst nucleation of NCs at relatively low temperatures. The phase morphology and surface and optoelectronic properties of NCs before and after ligand exchange were discussed in depth. It was found that pure tetragonal-phase structure CZTSe NCs with approximately 1.7-eV bandgap could be synthesized. The removal of large organic molecules on CZTSe NCs after ligand exchange by S2- decreased the resistivity. The bandgap of the films after ligand exchange by 550°C selenization was also decreased due to better crystallinity. For potential application in CZTSe solar cells, we constructed an energy level diagram to explain the mutual effect between the absorption layer and CdS layer. Using cyclic voltammetry (CV) measurement, we found that the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of CZTSe films shifted down after ligand exchange. After energy level alignment at the CdS/CZTSe interface, a type I band alignment structure was more conveniently formed after ligand exchange. This structure acted as the barrier against injection electrons from ZnO to the CZTSe layer, and recombination would subsequently be depressed.

  14. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal. PMID:23831729

  15. Optical Mass Gauging System for Measuring Liquid Levels in a Reduced Gravity Environment

    NASA Technical Reports Server (NTRS)

    Sullenberger, Ryan M.; Munoz, Wesley M.; Lyon, Matt P.; Vogel, Kenny; Yalin, Azer P.; Korman, Valentin; Polzin, Kurt A.

    2010-01-01

    A compact and rugged fiber-coupled liquid volume sensor designed for flight on a sounding rocket platform is presented. The sensor consists of a Mach-Zehnder interferometer capable of measuring the amount of liquid contained in a tank under any gravitational conditions, including a microgravity environment, by detecting small changes in the index of refraction of the gas contained within a sensing region. By monitoring changes in the interference fringe pattern as the system undergoes a small compression provided by a piston, the ullage volume of a tank can be directly measured allowing for a determination of the liquid volume. To demonstrate the technique, data are acquired using two tanks containing different volumes of liquid, which are representative of the levels of liquid in a tank at different time periods during a mission. The two tanks are independently exposed to the measurement apparatus, allowing for a determination of the liquid level in each. In a controlled, laboratory test of the unit, the system demonstrated a capability of measuring a liquid level in an individual tank of 10.53 mL with a 2% error. The overall random uncertainty for the flight system is higher than that one test, at +/- 1.5 mL.

  16. Low level laser therapy reduces oxidative stress in cortical neurons in vitro

    NASA Astrophysics Data System (ADS)

    Huang, Ying-Ying; Tedford, Clark E.; McCarthy, Thomas; Hamblin, Michael R.

    2012-03-01

    It is accepted that the mechanisms of low level laser therapy (LLLT) involves photons that are absorbed in the mitochondria of cells and lead to increase of mitochondrial metabolism resulting in more electron transport, increase of mitochondrial membrane potential, and more ATP production. Intracellular calcium changes are seen that correlate with mitochondrial stimulation. The situation with two other intermediates is more complex however: reactive oxygen species (ROS) and nitric oxide (NO). Evidence exists that low levels of ROS are produced by LLLT in normal cells that can be beneficial by (for instance) activating NF-kB. However high fluences of light can produce large amounts of ROS that can damage the cells. In oxidatively stressed cells the situation may be different. We exposed primary cultured cortical neurons to hydrogen peroxide (H2O2) or cobalt chloride (CoCl2) oxidative insults in the presence or absence of LLLT (810-nm laser at 0.3 or 3 J/cm2). Cell viability of cortical neurons was determined by lactate dehydrogenase assay. ROS in neurons was detected using an ROS probe, MitoRox with confocal microscopy. Results showed that LLLT dose-dependently reversed ROS production and protected cortical neurons against H2O2 or CoCl2 induced oxidative injury in cultured cortical neurons. Conclusion: LLLT can protect cortical neurons against oxidative stress by reversing the levels of ROS.

  17. Effectiveness of mandated oxygenated fuel usage to reduce carbon monoxide exhaust levels in Colorado

    SciTech Connect

    Cagle, G.A.

    1989-01-01

    An examination of Colorado Automobile Inspection and Readjustment (A.I.R.) two-speed exhaust emissions testing results was undertaken to evaluate changes in carbon monoxide exhaust levels due to the use of oxygenated fuels. Vehicles utilized within the study were separated according to their various emission control technologies: precatalyst (1938 to 1974), catalyst (1975 to 1980), and closed-loop (1981 to 1988). It was found that pre-catalyst and catalyst vehicles utilizing oxygenated fuels had significant reductions in carbon monoxide exhaust levels at 2,500 R.P.M. Results for closed-loop vehicles at 2,500 R.P.M. showed no significant reductions in carbon monoxide exhaust levels. Further examination of idle data for closed-loop vehicles indicated that a small percentage of these vehicles were considered gross-emitters based on the 1.5 percent cut-point set in Colorado. Results of the study indicated that the impact of oxygenated fuels, as well as the rationale for using such fuels as a carbon monoxide reduction strategy, may be difficult to justify as newer, more sophisticated light-duty vehicles comprise a larger proportion of the overall vehicle population in Colorado.

  18. Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease

    PubMed Central

    Khermesh, Khen; D'Erchia, Anna Maria; Barak, Michal; Annese, Anita; Wachtel, Chaim; Levanon, Erez Y.; Picardi, Ernesto; Eisenberg, Eli

    2016-01-01

    Adenosine to inosine (A-to-I) RNA editing, catalyzed by the ADAR enzyme family, acts on dsRNA structures within pre-mRNA molecules. Editing of the coding part of the mRNA may lead to recoding, amino acid substitution in the resulting protein, possibly modifying its biochemical and biophysical properties. Altered RNA editing patterns have been observed in various neurological pathologies. Here, we present a comprehensive study of recoding by RNA editing in Alzheimer's disease (AD), the most common cause of irreversible dementia. We have used a targeted resequencing approach supplemented by a microfluidic-based high-throughput PCR coupled with next-generation sequencing to accurately quantify A-to-I RNA editing levels in a preselected set of target sites, mostly located within the coding sequence of synaptic genes. Overall, editing levels decreased in AD patients’ brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. Differential RNA editing levels were observed in 35 target sites within 22 genes. These results may shed light on a possible association between the neurodegenerative processes typical for AD and deficient RNA editing. PMID:26655226

  19. HLA reduces KIR expression level and frequency in a humanized mouse model1

    PubMed Central

    van Bergen, Jeroen; Thompson, Allan; Retière, Christelle; van Pel, Melissa; Salvatori, Daniela; Lemonnier, François; Raulet, David; Trowsdale, John; Koning, Frits

    2014-01-01

    Many human Natural Killer (NK) cells are prevented from killing autologous cells by virtue of inhibitory Killer cell Immunoglobulin-like Receptors (KIR) binding `self' HLA class I molecules. Individual NK cells stably express a selected set of KIR, but it is currently disputed whether the fraction of NK cells expressing a particular inhibitory KIR is influenced by the presence of the corresponding HLA ligand. This issue has been particularly hard to tackle in a statistically meaningful way due to the extreme polymorphism of the KIR and HLA loci, with widely varying affinities for individual KIR and HLA allele combinations. Here, we use a transgenic mouse model to investigate the effect of HLA on KIR repertoire and function. In this model system, a functional interaction between HLA-Cw3 and KIR2DL2 reduced both the surface expression of KIR2DL2 as well as the frequency of KIR2DL2+ cells. PMID:23390293

  20. Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

    PubMed Central

    Espino, Javier; Mediero, Matías; Lozano, Graciela M; Bejarano, Ignacio; Ortiz, Águeda; García, Juan F; Pariente, José A; Rodríguez, Ana B

    2009-01-01

    Background Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia. Methods Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2. Results Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia. Conclusion Our results suggest that spermatozoa from

  1. Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome.

    PubMed

    Han, Guang-Ming; Meza, Jane L; Soliman, Ghada A; Islam, K M Monirul; Watanabe-Galloway, Shinobu

    2016-05-01

    Metabolic syndrome increases the risk of mortality. Increased oxidative stress and inflammation may play an important role in the high mortality of individuals with metabolic syndrome. Previous studies have suggested that lycopene intake might be related to the reduced oxidative stress and decreased inflammation. Using data from the National Health and Nutrition Examination Survey, we examined the hypothesis that lycopene is associated with mortality among individuals with metabolic syndrome. A total of 2499 participants 20 years and older with metabolic syndrome were divided into 3 groups based on their serum concentration of lycopene using the tertile rank method. The National Health and Nutrition Examination Survey from years 2001 to 2006 was linked to the mortality file for mortality follow-up data through December 31, 2011, to determine the mortality rate and hazard ratios (HR) for the 3 serum lycopene concentration groups. The mean survival time was significantly higher in the group with the highest serum lycopene concentration (120.6 months; 95% confidence interval [CI], 118.8-122.3) and the medium group (116.3 months; 95% CI, 115.2-117.4), compared with the group with lowest serum lycopene concentration (107.4 months; 95% CI, 106.5-108.3). After adjusting for possible confounding factors, participants in the highest (HR, 0.61; P = .0113) and in the second highest (HR, 0.67; P = .0497) serum lycopene concentration groups showed significantly lower HRs of mortality when compared with participants in the lower serum lycopene concentration. The data suggest that higher serum lycopene concentration has a significant association with the reduced risk of mortality among individuals with metabolic syndrome. PMID:27101758

  2. Public acceptability of population-level interventions to reduce alcohol consumption: a discrete choice experiment.

    PubMed

    Pechey, Rachel; Burge, Peter; Mentzakis, Emmanouil; Suhrcke, Marc; Marteau, Theresa M

    2014-07-01

    Public acceptability influences policy action, but the most acceptable policies are not always the most effective. This discrete choice experiment provides a novel investigation of the acceptability of different interventions to reduce alcohol consumption and the effect of information on expected effectiveness, using a UK general population sample of 1202 adults. Policy options included high, medium and low intensity versions of: Minimum Unit Pricing (MUP) for alcohol; reducing numbers of alcohol retail outlets; and regulating alcohol advertising. Outcomes of interventions were predicted for: alcohol-related crimes; alcohol-related hospital admissions; and heavy drinkers. First, the models obtained were used to predict preferences if expected outcomes of interventions were not taken into account. In such models around half of participants or more were predicted to prefer the status quo over implementing outlet reductions or higher intensity MUP. Second, preferences were predicted when information on expected outcomes was considered, with most participants now choosing any given intervention over the status quo. Acceptability of MUP interventions increased by the greatest extent: from 43% to 63% preferring MUP of £1 to the status quo. Respondents' own drinking behaviour also influenced preferences, with around 90% of non-drinkers being predicted to choose all interventions over the status quo, and with more moderate than heavy drinkers favouring a given policy over the status quo. Importantly, the study findings suggest public acceptability of alcohol interventions is dependent on both the nature of the policy and its expected effectiveness. Policy-makers struggling to mobilise support for hitherto unpopular but promising policies should consider giving greater prominence to their expected outcomes. PMID:24858928

  3. The 11S globulin Sin a 2 from yellow mustard seeds shows IgE cross-reactivity with homologous counterparts from tree nuts and peanut

    PubMed Central

    2012-01-01

    Background The 11S globulin Sin a 2 is a marker to predict severity of symptoms in mustard allergic patients. The potential implication of Sin a 2 in cross-reactivity with tree nuts and peanut has not been investigated so far. In this work, we studied at the IgG and IgE level the involvement of the 11S globulin Sin a 2 in cross-reactivity among mustard, tree nuts and peanut. Methods Eleven well-characterized mustard-allergic patients sensitized to Sin a 2 were included in the study. A specific anti-Sin a 2 serum was obtained in rabbit. Skin prick tests (SPT), enzyme-linked immunosorbent assay (ELISA), immunoblotting and IgG or IgE-inhibition immunoblotting experiments using purified Sin a 2, Sin a 1, Sin a 3, mustard, almond, hazelnut, pistachio, walnut or peanut extracts were performed. Results The rabbit anti-Sin a 2 serum showed high affinity and specificity to Sin a 2, which allowed us to demonstrate that Sin a 2 shares IgG epitopes with allergenic 11S globulins from tree nuts (almond, hazelnut, pistachio and walnut) but not from peanut. All the patients included in the study had positive skin prick test to tree nuts and/or peanut and we subdivided them into two different groups according to their clinical symptoms after ingestion of such allergenic sources. We showed that 11S globulins contain conserved IgE epitopes involved in cross-reactivity among mustard, tree nuts and peanut as well as species-specific IgE epitopes. Conclusions The allergenic 11S globulin Sin a 2 from mustard is involved in cross-reactivity at the IgE level with tree nuts and peanut. Although the clinical relevance of the cross-reactive IgE epitopes present in 11S globulins needs to be investigated in further detail, our results contribute to improve the diagnosis and management of mustard allergic patients sensitized to Sin a 2. PMID:23231956

  4. (Reduce uncertainty in projection of future sea-level change due to ice wastage)

    SciTech Connect

    Meier, M.F.

    1991-01-01

    Three basic goals were stated in the original proposal. These were: (1) develop an understanding of the heat and mass flow into subfreezing snow and firn, in order to model the evolution of the temperature distribution and the infiltration rates through the firn; (2) relate changes in climate, as given by general circulation model predictions, to changes in the surface mass and energy balances of glaciers; and (3) use the above results to analyze the effects of changed surface mass and energy balances on the flow of meltwater through snow and firn, and on the runoff from these glaciers, in a CO{sub 2}-affected climate. This final report summarizes our progress toward these goals. The primary product of this research program has been the communication of this progress in the form of publications in the scientific literature and presentations at scientific meetings. Our research activities in the past three years have provided a new basis for modeling of multiphase flow in subfreezing snow, new field data on the structural properties of arctic firn pertinent to hydrological modeling, and estimates of sea level change in response to changing patterns of runoff from the Greenland Ice Sheet. We conclude that forecasts of future sea level changes from all glacier runoff sources may be in error by amounts on the order of +8 cm over the next 150 years, due to the lag in generating runoff to the sea. Our specific research products include two distributed-parameter models of water flow through snow with melting and freezing, a theoretical model of wetting-front advance into subfreezing snow for inclusion in a future model, and a simple large-scale model of the response of Greenland runoff in a changing climate which provides estimates of the effect of melt water refreezing phenomena on sea level changes in response to a range of possible future climates.

  5. Reiki brief report: using Reiki to reduce stress levels in a nine-year-old child.

    PubMed

    Bukowski, Elaine L; Berardi, Diana

    2014-01-01

    A nine-year-old female with a history of perinatal stroke, seizures, and type-I diabetes was seen for six weeks of Reiki to determine the effects of Reiki on relaxation, and in turn, the prevention of future seizures. The secondary and tertiary aims were to determine the effects of Reiki on sleep patterns and the stress levels of the mother. There was a decrease in stress in both the child and the mother, as measured by a modified Perceived Stress Scale and a Perceived Stress Scale, respectively. There was no change in the child's overall sense of well-being, as measured by a global questionnaire. There was a positive change in sleep patterns on 33.3% of the nights during which the study occurred, as reported on a sleep log kept by the mother. The child and the Reiki Master (a Reiki practitioner who has completed all three levels of Reiki certification training and trains and certifies individuals in the practice of Reiki as well as provides Reiki to individuals) experienced warmth and tingling sensations on the same area of the child during the Reiki sessions. The child relaxed within the first five to seven minutes of each session as reported by the Reiki Master. There were no reports of seizures during this study. Reiki may be a useful adjunct for children with increased stress levels and sleep disturbances secondary to their medical condition. Further research is warranted to evaluate the use of Reiki in children, particularly with a large sample size, and to evaluate the long-term use of Reiki and its effects on adequate sleep. PMID:25037669

  6. Reduced Levels of Proteasome Products in a Mouse Striatal Cell Model of Huntington’s Disease

    PubMed Central

    Dasgupta, Sayani; Fishman, Michael A.; Mahallati, Hana; Castro, Leandro M.; Tashima, Alexandre K.; Ferro, Emer S.; Fricker, Lloyd D.

    2015-01-01

    Huntington’s disease is the result of a long polyglutamine tract in the gene encoding huntingtin protein, which in turn causes a large number of cellular changes and ultimately results in neurodegeneration of striatal neurons. Although many theories have been proposed, the precise mechanism by which the polyglutamine expansion causes cellular changes is not certain. Some evidence supports the hypothesis that the long polyglutamine tract inhibits the proteasome, a multiprotein complex involved in protein degradation. However, other studies report normal proteasome function in cells expressing long polyglutamine tracts. The controversy may be due to the methods used to examine proteasome activity in each of the previous studies. In the present study, we measured proteasome function by examining levels of endogenous peptides that are products of proteasome cleavage. Peptide levels were compared among mouse striatal cell lines expressing either 7 glutamines (STHdhQ7/Q7) or 111 glutamines in the huntingtin protein, either heterozygous (STHdhQ7/Q111) or homozygous (STHdhQ111/Q111). Both of the cell lines expressing huntingtin with 111 glutamines showed a large reduction in nearly all of the peptides detected in the cells, relative to levels of these peptides in cells homozygous for 7 glutamines. Treatment of STHdhQ7/Q7 cells with proteasome inhibitors epoxomicin or bortezomib also caused a large reduction in most of these peptides, suggesting that they are products of proteasome-mediated cleavage of cellular proteins. Taken together, these results support the hypothesis that proteasome function is impaired by the expression of huntingtin protein containing long polyglutamine tracts. PMID:26691307

  7. Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

    NASA Technical Reports Server (NTRS)

    Haller, R. G.; Clausen, T.; Vissing, J.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

  8. Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks

    SciTech Connect

    Steffler, Eric D.; McClintock, Frank A.; Lloyd, W. Randolph; Rashid, Mark M.; Williamson, Richard L.

    2005-06-01

    Cracks of various shapes and sizes exist in large high-level waste (HLW) tanks at several DOE sites. There is justifiable concern that these cracks could grow to become unstable causing a substantial release of liquid contaminants to the environment. Accurate prediction of crack growth behavior in the tanks, especially during accident scenarios, is not possible with existing analysis methodologies. This research project responds to this problem by developing an improved ability to predict crack growth in material structure combinations that are ductile (Fig. 1). This new model not only addresses the problem for these tanks, but also has applicability to any crack in any ductile structure.

  9. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease

    PubMed Central

    Babu, D. B. Gandhi; Chavva, Sunanda; Waghray, Shefali

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  10. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease.

    PubMed

    Babu, D B Gandhi; Chavva, Sunanda; Waghray, Shefali; Allam, Neeharika Satya Jyothi; Kondaiah, Marella

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  11. Opportunities for State-Level Action to Reduce Firearm Violence: Proceeding From the Evidence

    PubMed Central

    Braga, Anthony A.

    2011-01-01

    Firearm violence remains an important problem, and a large body of evidence shows that guns used in crime follow generally predictable paths from manufacturer to criminal end user. Policy initiatives based on that evidence have been shown to be effective. A recently published study conducted by a leading policy organization presents new evidence and makes specific recommendations for action by state-level policymakers. Unfortunately, the study's analysis is overly simplified, and the recommendations are therefore misleading. We suggest alternatives that are evidence based. PMID:21778510

  12. Arginine vasotocin reduces levels of cooperative behaviour in a cleaner fish.

    PubMed

    Cardoso, Sónia C; Paitio, José R; Oliveira, Rui F; Bshary, Redouan; Soares, Marta C

    2015-02-01

    Cooperation between unrelated individuals usually involves investments that often mean a decrease in immediate payoffs, but ensure future benefits. Here we investigated the potential role of the neuropeptides Arginine-vasotocin (AVT) and Isotocin (IT) as proximate agents affecting individuals' cooperative levels in the Indo-pacific bluestreak cleaner wrasse Labroides dimidiatus. Their 'client' reef fish partners only benefit from interacting if cleaners eat ectoparasites and refrain from gleaning preferred client mucus. Thus, cleaners must control their impulse to eat according to their preference, and eat less preferred items to maintain ongoing interactions and avoid clients' leaving or punishing. We found that solely the experimental transient higher dosage of AVT led to a decrease of cleaners' willingness to feed against their preference, while IT and AVT antagonists had no significant effects. The sole effect of AVT on cleaner's performance may imply a link between AVT's influence and a potential activation of a stress response. Our results confirm the importance of the AVT/AVP system as an agent affecting levels of cooperation, offering a potential mechanistic pathway for the reported flexible service quality that cleaners provide their clients. PMID:25449412

  13. Acrylamide in Caribbean foods - residual levels and their relation to reducing sugar and asparagine content.

    PubMed

    Bent, Grace-Anne; Maragh, Paul; Dasgupta, Tara

    2012-07-15

    The acrylamide levels in commercial and homemade Caribbean foods were determined by pre-derivatisation of acrylamide to 2-bromopropenamide and analysed by gas chromatography with mass spectrometric (GC/MS) detection. Over 100 Caribbean food samples were analysed for the presence of acrylamide. These samples include: biscuits, breakfast cereals, banana chips and home-prepared foods: breadfruit; Artocarpus altilis, banana fritters, and dumplings. The limit of detection (LOD) for the GC/MS method was found to be dependent on the type of column used for the GC/MS analysis. The DB-1701 and the DB-VRX columns gave LODs of 20 and 4 μg/kg, respectively. Acrylamide has not been found in raw foods or foods which have been cooked by boiling. Its content in all other foods had concentrations in the range, 65-3,640 μg/kg. The relationship between acrylamide levels and precursor concentration as well as the health implications of our findings are discussed. PMID:25683419

  14. Ethanol exposure affects gene expression in the embryonic organizer and reduces retinoic acid levels.

    PubMed

    Yelin, Ronit; Schyr, Racheli Ben-Haroush; Kot, Hadas; Zins, Sharon; Frumkin, Ayala; Pillemer, Graciela; Fainsod, Abraham

    2005-03-01

    Fetal Alcohol Spectrum Disorder (FASD) is a set of developmental malformations caused by alcohol consumption during pregnancy. Fetal Alcohol Syndrome (FAS), the strongest manifestation of FASD, results in short stature, microcephally and facial dysmorphogenesis including microphthalmia. Using Xenopus embryos as a model developmental system, we show that ethanol exposure recapitulates many aspects of FAS, including a shortened rostro-caudal axis, microcephally and microphthalmia. Temporal analysis revealed that Xenopus embryos are most sensitive to ethanol exposure between late blastula and early/mid gastrula stages. This window of sensitivity overlaps with the formation and early function of the embryonic organizer, Spemann's organizer. Molecular analysis revealed that ethanol exposure of embryos induces changes in the domains and levels of organizer-specific gene expression, identifying Spemann's organizer as an early target of ethanol. Ethanol also induces a defect in convergent extension movements that delays gastrulation movements and may affect the overall length. We show that mechanistically, ethanol is antagonistic to retinol (Vitamin A) and retinal conversion to retinoic acid, and that the organizer is active in retinoic acid signaling during early gastrulation. The model suggests that FASD is induced in part by an ethanol-dependent reduction in retinoic acid levels that are necessary for the normal function of Spemann's organizer. PMID:15708568

  15. Epidemiological survey of anti-flea IgE in dogs in Japan by using an antigen-specific IgE quantitative measurement method

    PubMed Central

    Ichikawa, Y.; Beugnet, F.

    2012-01-01

    In Japan, an epidemiological survey was performed in dogs from October to December 2008 by using a quantitative measurement method for antigen-specific IgE towards specific Ctenocephalides felis antigens. 214 dogs from 22 veterinary clinics were included. These clinics were located as follows, from North to South: Hokkaido, Aomori, Fukushima, Tochigi, Saitama, Chiba, Tokyo (Tama-City and Ota-ku), Kanagawa, Gifu, Niigata, Kyoto, Nara, Osaka, Hyogo, Kagawa, Ehime, Hiroshima, Yamaguchi, Fukuoka, Kumamoto and Kagoshima. 110 dogs (51.4%) were seropositive for flea-specific IgE. No differences were associated with gender or breed. This survey confirms that flea infestation in dogs is a common problem in Japan. It especially shows that the infestation also occurs in Northern Japan where fleas are considered uncommon by the vet. PMID:22550629

  16. The efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery: a systematic review

    NASA Astrophysics Data System (ADS)

    Moshari, Amirabbas; Vatanpour, Mehdi; Zakershahrak, Mehrsa

    2016-03-01

    Introduction: LLLT in oral cavity believed to reduce pain after endodontic surgery and wisdom tooth removal, to accelerate wound healing and to have an anti-inflammatory and regenerative effect. The aim of this systematic review therefore was to assess the proof available for the efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery. Methods: The PubMed service of the U.S. National Library of Medicine was searched with applicable search strategies. No language restriction was applied. The last electronic search was accomplished on August 31, 2015. All randomized clinical trials on the efficiency of low-level laser treatment in reducing pain and swelling after endodontic surgery was considered for the Meta-analysis. Quality consideration of the included randomized clinical trials was appraised according to CONSORT guidelines. Results: Only two randomized clinical trials were attained. These studies clarified that laser treatment could reduce pain and swelling, but the results were not significant. Conclusions: Low-level laser therapy can be advantageous for the reduction of postoperative pain but there is no strong confirmation for its efficiency. Its clinical utility and applicability relating to endodontic surgery, Along with the optimal energy dosage and the number of laser treatments needed after surgery, still, demand further research and experiment.

  17. Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels

    PubMed Central

    do Nascimento Campos Ribeiro, Joycellane Alline; Serquiz, Alexandre Coellho; dos Santos Silva, Priscila Fabíola; Barbosa, Patrícia Batista Barra Medeiros; Sampaio, Tarcísio Bruno Montenegro; de Araújo, Raimundo Fernandes; de Oliveira, Adeliana Silva; Machado, Richele Janaina Araújo; Maciel, Bruna Leal Lima; Uchôa, Adriana Ferreira; dos Santos, Elizeu Antunes; de Araújo Morais, Ana Heloneida

    2015-01-01

    OBJECTIVES: Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats. METHODS: A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30–60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed. RESULTS: The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water. CONCLUSION: The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated. PMID:25789523

  18. Stigmasterol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat.

    PubMed

    Batta, Ashok K; Xu, Guorong; Honda, Akira; Miyazaki, Teruo; Salen, Gerald

    2006-03-01

    Plant sterols compete with cholesterol (cholest-5-en-3beta-ol) for intestinal absorption to limit absorption and lower plasma concentrations of cholesterol. Stigmasterol (24-ethyl-cholesta-5,22-dien-3beta-ol; Delta(22) derivative of sitosterol [24-ethyl-cholest-5-en-3beta-ol]), but not campesterol (24-methyl-cholest-5-en-3beta-ol) and sitosterol, is reported to inhibit cholesterol biosynthesis via inhibition of sterol Delta(24)-reductase in human Caco-2 and HL-60 cell lines. We studied the effect of feeding 0.5% stigmasterol on plasma and liver sterols and intestinal cholesterol and sitosterol absorption in 12 wild-type Kyoto (WKY) and 12 Wistar rats. After 3 weeks of feeding, cholesterol and sitosterol absorption was determined in 6 rats from each group by plasma dual-isotope ratio method. After 3 more weeks, plasma and hepatic sterols and hepatic enzyme activities were determined in all rats. After feeding stigmasterol, baseline plasma cholesterol was 1.3 times and plant sterols 3 times greater in WKY compared with Wistar rats. Stigmasterol feeding lowered plasma cholesterol by approximately 11%, whereas plasma campesterol and sitosterol levels were virtually unchanged in both rat strains, and stigmasterol constituted 3.2% of plasma sterols in WKY rats and 1% in Wistar rats. After 6 weeks of feeding, cholesterol and sitosterol absorption decreased 23% and 30%, respectively, in WKY, and 22% and 16%, respectively, in the Wistar rats as compared with untreated rats. The intestinal bacteria in both rat strains metabolized stigmasterol to mainly the 5beta-H stanol (>40%), with only small amounts of 5alpha-H derivative (approximately 1.5%), whereas the C-22 double bond was resistant to bacterial metabolism. Hepatic stigmasterol levels increased from 11 microg/g liver tissue to 104 mug/g in WKY rats and from 5 microg/g liver tissue to 21 microg/g in Wistar rats. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was suppressed 4-fold in the WKY and almost 1.8-fold

  19. [Cutaneous allergen test in children: frequency of conversion of prick-test reactions, IgE concentrations in serum and course of the disease in young asthmatics during or without treatment with "Dinatrium cromoglicicum" inhalation (author's transl)].

    PubMed

    Arndt, M

    1975-11-01

    Among 62 children with asthma or/and hay fever 32 were treated symptomatically. 30 were treated with DNCG inhalations. 22 asthmatics with proved inhalation-allergy responded well or very well to DNCG inhalations, 3 others only fairly. Of 5 patients without proved allergy 4 showed a fair response, 1 none. In group I (without DNCG) 4 out of 20 negative prick-tests became definitely positive at a follow-up examination, in group II (with DNCG) 9 out of 14. The follow-up examinations tended to be done during a time when symptoms were reduced or absent. In group II there were 7 of 9 children with good effect of DNCG. IgE assays in serum were clearly lower in "non-allergics" than in sensitized patients. The IgE was raised only in children where the follow-up showed a positive reaction. One might assume that when the clinical symptoms improve, IgE or mediator substances in the tissues, particularly in mast cells, are accumulated so that cutaneous skin-reactions now become clearly positive. IgE concentration in serum did not show correlated changes. Assessment of the clinical course of the illness apart, conversion of prick testing might indicate protective action of DNCG inhalations in bronchial asthma due to inhalation allergy. PMID:814366

  20. Syntaxin-4 is essential for IgE secretion by plasma cells

    SciTech Connect

    Rahman, Arman; DeCourcey, Joseph; Larbi, Nadia Ben; Loughran, Sinéad T.; Walls, Dermot; Loscher, Christine E.

    2013-10-11

    Highlights: •Knock-down of syntaxin-4 in U266 plasma cells resulted in reduction of IgE secretion. •Knock-down of syntaxin-4 also leads to the accumulation of IgE in the cell. •Immuno-fluorescence staining shows co-localisation of IgE and syntaxin-4 in U266 cells. •Findings suggest a critical requirement for syntaxin-4 in IgE secretion from plasma cells. -- Abstract: The humoral immune system provides a crucial first defense against the invasion of microbial pathogens via the secretion of antigen specific immunoglobulins (Ig). The secretion of Ig is carried out by terminally differentiated B-lymphocytes called plasma cells. Despite the key role of plasma cells in the immune response, the mechanisms by which they constitutively traffic large volumes of Ig out of the cell is poorly understood. The involvement of Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in the regulation of protein trafficking from cells has been well documented. Syntaxin-4, a member of the Qa SNARE syntaxin family has been implicated in fusion events at the plasma membrane in a number of cells in the immune system. In this work we show that knock-down of syntaxin-4 in the multiple myeloma U266 human plasma cell line results in a loss of IgE secretion and accumulation of IgE within the cells. Furthermore, we show that IgE co-localises with syntaxin-4 in U266 plasma cells suggesting direct involvement in secretion at the plasma membrane. This study demonstrates that syntaxin-4 plays a critical role in the secretion of IgE from plasma cells and sheds some light on the mechanisms by which these cells constitutively traffic vesicles to the surface for secretion. An understanding of this machinery may be beneficial in identifying potential therapeutic targets in multiple myeloma and autoimmune disease where over-production of Ig leads to severe pathology in patients.

  1. Projected Near-Future Levels of Temperature and pCO2 Reduce Coral Fertilization Success

    PubMed Central

    Albright, Rebecca; Mason, Benjamin

    2013-01-01

    Increases in atmospheric carbon dioxide (pCO2) are projected to contribute to a 1.1–6.4°C rise in global average surface temperatures and a 0.14–0.35 reduction in the average pH of the global surface ocean by 2100. If realized, these changes are expected to have negative consequences for reef-building corals including increased frequency and severity of coral bleaching and reduced rates of calcification and reef accretion. Much less is known regarding the independent and combined effects of temperature and pCO2 on critical early life history processes such as fertilization. Here we show that increases in temperature (+3°C) and pCO2 (+400 µatm) projected for this century negatively impact fertilization success of a common Indo-Pacific coral species, Acropora tenuis. While maximum fertilization did not differ among treatments, the sperm concentration required to obtain 50% of maximum fertilization increased 6- to 8- fold with the addition of a single factor (temperature or CO2) and nearly 50- fold when both factors interact. Our results indicate that near-future changes in temperature and pCO2 narrow the range of sperm concentrations that are capable of yielding high fertilization success in A. tenuis. Increased sperm limitation, in conjunction with adult population decline, may have severe consequences for coral reproductive success. Impaired sexual reproduction will further challenge corals by inhibiting population recovery and adaptation potential. PMID:23457572

  2. Projected near-future levels of temperature and pCO2 reduce coral fertilization success.

    PubMed

    Albright, Rebecca; Mason, Benjamin

    2013-01-01

    Increases in atmospheric carbon dioxide (pCO2) are projected to contribute to a 1.1-6.4°C rise in global average surface temperatures and a 0.14-0.35 reduction in the average pH of the global surface ocean by 2100. If realized, these changes are expected to have negative consequences for reef-building corals including increased frequency and severity of coral bleaching and reduced rates of calcification and reef accretion. Much less is known regarding the independent and combined effects of temperature and pCO2 on critical early life history processes such as fertilization. Here we show that increases in temperature (+3°C) and pCO2 (+400 µatm) projected for this century negatively impact fertilization success of a common Indo-Pacific coral species, Acropora tenuis. While maximum fertilization did not differ among treatments, the sperm concentration required to obtain 50% of maximum fertilization increased 6- to 8- fold with the addition of a single factor (temperature or CO2) and nearly 50- fold when both factors interact. Our results indicate that near-future changes in temperature and pCO2 narrow the range of sperm concentrations that are capable of yielding high fertilization success in A. tenuis. Increased sperm limitation, in conjunction with adult population decline, may have severe consequences for coral reproductive success. Impaired sexual reproduction will further challenge corals by inhibiting population recovery and adaptation potential. PMID:23457572

  3. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress

    PubMed Central

    Saliba, Flávia G.; Adiwardana, Natanael S.; Uehara, Eliane U.; Silvestre, Renata N.; Leite, Victor V.; Faleiros, Francisca T.V.; Padovani, Flávia H.P.; De Gobbi, Juliana I.F.

    2016-01-01

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  4. Vitamins A, C, and E May Reduce Intestinal 210Po Levels after Ingestion.

    PubMed

    Kemp, Francis W; Portugal, Frank; Akudugu, John M; Neti, Prasad V S V; Ferraris, Ronaldo P; Howell, Roger W

    2016-07-01

    Damage to the gut mucosa is a probable contributory cause of death from ingested Po. Therefore, medical products are needed that can prevent, mitigate, and/or repair gastrointestinal (GI) damage caused by high-LET radiation emitted by Po. The present studies investigated the capacity of a diet highly enriched with vitamins A, C, and E (vitamin ACE) to protect against intestinal mucosal damage indicated by functional reductions in nutrient transport caused by orally ingested Po. Mice were gavaged with 0 or 18.5 kBq Po-citrate and fed a control or vitamin ACE-enriched diet (the latter beginning either 96 h before or immediately after gavage). Mouse intestines significantly retained Po on day 8 post-gavage. The concentration of Po in intestinal tissues was significantly (p<0.05) lower in all vitamin ACE groups compared to control. There were borderline significant Po-induced reductions in intestinal absorption of D-fructose. The combination of vitamins A, C, and E may reduce Po incorporation in the intestines when given before, or enhance decorporation when provided after, Po gavage. PMID:27218295

  5. Pro: Reducing salt intake at population level: is it really a public health priority?

    PubMed

    Cappuccio, Francesco P

    2016-09-01

    A reduction in salt intake reduces blood pressure, stroke and other cardiovascular events, including chronic kidney disease, by as much as 23% (i.e. 1.25 million deaths worldwide). It is effective in both genders, any age, ethnic group, and in high-, medium- and low-income countries. Population salt reduction programmes are both feasible and effective (preventive imperative). Salt reduction programmes are cost-saving in all settings (high-, middle- and low-income countries) (economic imperative). Public health policies are powerful, rapid, equitable and cost-saving (political imperative). The important shift in public health has not occurred without obstinate opposition from organizations concerned primarily with the profits deriving from population high salt intake and less with public health benefits. A key component of the denial strategy is misinformation (with 'pseudo' controversies). In general, poor science has been used to create uncertainty and to support inaction. This paper summarizes the evidence in favour of a global salt reduction strategy and analyses the peddling of well-worn myths behind the false controversies. PMID:27488355

  6. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress.

    PubMed

    Saliba, Flávia G; Adiwardana, Natanael S; Uehara, Eliane U; Silvestre, Renata N; Leite, Victor V; Faleiros, Francisca T V; Padovani, Flávia H P; De Gobbi, Juliana I F

    2016-03-31

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  7. Displacement Behaviour Is Associated with Reduced Stress Levels among Men but Not Women

    PubMed Central

    Mohiyeddini, Changiz; Bauer, Stephanie; Semple, Stuart

    2013-01-01

    Sex differences in the ability to cope with stress may contribute to the higher prevalence of stress-related disorders among women compared to men. We recently provided evidence that displacement behaviour - activities such as scratching and face touching - represents an important strategy for coping with stressful situations: in a healthy population of men, displacement behaviour during a social stress test attenuated the relationship between anxiety experienced prior to this test, and the subsequent self-reported experience of stress. Here, we extend this work to look at physiological and cognitive (in addition to self-reported) measures of stress, and study both men and women in order to investigate whether sex moderates the link between displacement behaviour and the response to stress. In a healthy study population, we quantified displacement behaviour, heart rate and cognitive performance during the Trier Social Stress Test, and used self-report questionnaires to assess the experience of stress afterwards. Men engaged in displacement behaviour about twice as often as women, and subsequently reported lower levels of stress. Bivariate correlations revealed that for men, higher rates of displacement behaviour were associated with decreased self-reported stress, fewer mistakes in the cognitive task and a trend towards lower heart rate; no relationships between displacement behaviour and stress measures were found for women. Moreover, moderation analyses revealed that high rates of displacement behaviour were associated with lower stress levels in men but not in women, and that high displacement behaviour rates were associated with poorer cognitive performance in women, but not men. These results point to an important sex difference in coping strategies, and highlight new avenues for research into sex biases in stress-related disorders. PMID:23457555

  8. Effects of carvedilol reduce conjunctivitis through changes in inflammation, NGF and VEGF levels in a rat model

    PubMed Central

    CHEN, YING; HONG, XIANFEI

    2016-01-01

    Carvedilol is a novel third generation β-blocker that acts as an antagonist of β and α adrenergic receptors, and is able to regulate various cell factors. In addition, it possesses antioxidant activity, is capable of reversing cardiac remodeling effects and has anti-arrhythmic effects. The present study aimed to investigate whether the effects of carvedilol were able to reduce conjunctivitis clinical scores. Initially, 24 Sprague Dawley (SD) rats were randomly divided into three equal groups as follows: Control group, model group and carvedilol group. The model and carvedilol group adult SD rats were injected with lipopolysaccharide (LPS) to induce conjunctivitis. In the carvedilol group, the eight SD rats with LPS-induced conjunctivitis also received 50 mg/kg/day of carvedilol for 4 weeks. Next, the effects carvedilol were assessed utilizing a system of clinical sign scores, and an enzyme-linked immunosorbent assay was used to determine the expression levels of interleukin-1β (IL-1β), IL-6, IL-8 and tumor necrosis factor-α (TNF-α). Finally, nuclear factor-κB (NF-κB), nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) were analyzed by western blotting. Carvedilol was observed to significantly reduce clinical sign scores in a dose-dependent manner (P<0.01), and reduce IL-1β, IL-6, IL-8 and TNF-α expression levels (P<0.01) in the LPS-induced rat model of conjunctivitis. Carvedilol was also able to significantly reduce the protein expression levels of NF-κB, and induce the protein expression levels of NGF and VEGF in the LPS-induced rat model of conjunctivitis (P<0.01). In conclusion, the effects of carvedilol may reduce conjunctivitis clinical scores through inflammation, NGF and VEGF in LPS-induced rat models. PMID:27168839

  9. Type 1 Ig-E mediated allergy to human insulin, insulin analogues and beta-lactam antibiotics*

    PubMed Central

    Andrade, Pedro; Barros, Luísa; Gonçalo, Margarida

    2012-01-01

    Insulin, a crucial therapeutic agent for diabetes mellitus, has been rarely associated with hypersensitivity events. We present a 69-year-old type-2 diabetic patient with urticariform lesions on the sites of subcutaneous injection of insulin. The patient denied any known allergies, except for an unspecific cutaneous reaction after intramuscular penicillin administration in childhood. Prick tests revealed positive reactions to all tested human insulins and insulin analogues. Serum IgE levels were above normal range and RAST tests were positive for human, bovine and porcine insulins, as well as beta-lactams. Type 1 IgE-mediated allergy to insulin analogues demands a prompt diagnosis and represents a significant therapeutic challenge in diabetic patients. PMID:23197216

  10. Auxotrophic Mutations Reduce Tolerance of Saccharomyces cerevisiae to Very High Levels of Ethanol Stress

    PubMed Central

    Swinnen, Steve; Goovaerts, Annelies; Schaerlaekens, Kristien; Dumortier, Françoise; Verdyck, Pieter; Souvereyns, Kris; Van Zeebroeck, Griet; Foulquié-Moreno, María R.

    2015-01-01

    Very high ethanol tolerance is a distinctive trait of the yeast Saccharomyces cerevisiae with notable ecological and industrial importance. Although many genes have been shown to be required for moderate ethanol tolerance (i.e., 6 to 12%) in laboratory strains, little is known of the much higher ethanol tolerance (i.e., 16 to 20%) in natural and industrial strains. We have analyzed the genetic basis of very high ethanol tolerance in a Brazilian bioethanol production strain by genetic mapping with laboratory strains containing artificially inserted oligonucleotide markers. The first locus contained the ura3Δ0 mutation of the laboratory strain as the causative mutation. Analysis of other auxotrophies also revealed significant linkage for LYS2, LEU2, HIS3, and MET15. Tolerance to only very high ethanol concentrations was reduced by auxotrophies, while the effect was reversed at lower concentrations. Evaluation of other stress conditions showed that the link with auxotrophy is dependent on the type of stress and the type of auxotrophy. When the concentration of the auxotrophic nutrient is close to that limiting growth, more stress factors can inhibit growth of an auxotrophic strain. We show that very high ethanol concentrations inhibit the uptake of leucine more than that of uracil, but the 500-fold-lower uracil uptake activity may explain the strong linkage between uracil auxotrophy and ethanol sensitivity compared to leucine auxotrophy. Since very high concentrations of ethanol inhibit the uptake of auxotrophic nutrients, the active uptake of scarce nutrients may be a major limiting factor for growth under conditions of ethanol stress. PMID:26116212

  11. Relationship of Organizational Structure and Leadership Behavior to Staff Satisfaction in IGE Schools. Technical Report No. 412.

    ERIC Educational Resources Information Center

    Mendenhall, Diana Reed

    The purposes of this study were to determine the relationship of structural aspects of the school organization and leadership behavior in schools to job satisfaction within Individually Guided Education (IGE) schools, and to determine whether organizational structure or leadership behavior had more impact on job satisfaction in IGE schools. Data…

  12. Reducing Lissencephaly-1 levels augments mitochondrial transport and has a protective effect in adult Drosophila neurons

    PubMed Central

    Vagnoni, Alessio; Hoffmann, Patrick C.; Bullock, Simon L.

    2016-01-01

    ABSTRACT Defective transport of mitochondria in axons is implicated in the pathogenesis of several age-associated neurodegenerative diseases. However, the regulation and function of axonal mitochondrial motility during normal ageing is poorly understood. Here, we use novel imaging procedures to characterise axonal transport of these organelles in the adult Drosophila wing nerve. During early adult life there is a boost and progressive decline in the proportion of mitochondria that are motile, which is not due to general changes in cargo transport. Experimental inhibition of the mitochondrial transport machinery specifically in adulthood accelerates the appearance of focal protein accumulations in ageing axons, which is suggestive of defects in protein homeostasis. Unexpectedly, lowering levels of Lissencephaly-1 (Lis1), a dynein motor co-factor, augments axonal mitochondrial transport in ageing wing neurons. Lis1 mutations suppress focal protein accumulations in ageing neurons, including those caused by interfering with the mitochondrial transport machinery. Our data provide new insights into the dynamics of mitochondrial motility in adult neurons in vivo, identify Lis1 as a negative regulator of transport of these organelles, and provide evidence of a link between mitochondrial movement and neuronal protein homeostasis. PMID:26598558

  13. Enhanced fluorescence cyanide detection at physiologically lethal levels: reduced ICT-based signal transduction.

    PubMed

    Badugu, Ramachandram; Lakowicz, Joseph R; Geddes, Chris D

    2005-03-16

    Three water-soluble fluorescent probes have been specifically designed to determine free cyanide concentrations up to physiologically lethal levels, >20 microM. The probes have been designed in such a way as to afford many notable sensing features, which render them unique with regard to signal transduction, photophysical characteristics, and their application to physiological cyanide determination and safeguard. The probes are readily able to reversibly bind free aqueous cyanide with dissociation constants around 4 microM3. Subsequent cyanide binding modulates the intramolecular charge transfer within the probes, a change in the electronic properties within the probes, resulting in enhanced fluorescence optical signals as a function of increased solution cyanide concentration. The ground-state chelation with cyanide produces wavelength shifts, which also enable the probes to sense cyanide in both an excitation and emission ratiometric manner, in addition to enhanced fluorescence signaling. This has enabled a generic cyanide sensing platform to be realized that is not dependent on fluorescent probe concentration, probe photodegradation, or fluctuations in the intensity of any employed excitation sources, ideal for remote cyanide sensing applications. Further, the >600 nm fluorescence emission of the probes potentially allows for enhanced fluorescence ratiometric cyanide sensing in the optical window of tissues and blood, facilitating their use for the transdermal monitoring of cyanide for mammalian safeguard or postmortem in fire victims, both areas of active research. PMID:15755185

  14. Numerical method for reducing stress level in GaAs crystals

    NASA Astrophysics Data System (ADS)

    Dupret, F.; Nicodème, P.; Ryckmans, Y.

    1989-09-01

    We have developed a numerical method based on the finite element technique for calculating heat transfer in crystal growth furnaces. Our model is global, as it entirely relies upon external control parameters, such as the pulling rate and the power input, while internal heat exchange is calculated on the basis of geometrical and material properties of all constituents of the puller. Radiative exchanges within the furnace are calculated with the assumptions of an axisymmetric geometry and of diffuse-gray surfaces. The viewed and hidden parts of the bodies are taken into account. The influence of the meniscus at the tri-junction is also investigated. It is generally agreed that the presence of structural defects in the grown crystal is related to thermoelastic stresses generated during growth. A finite element prediction of these thermal stresses is coupled to the global heat transfer calculation. The aim of this paper is to show how the thermal stress level in the crystal can be decreased by modifying the thermal exchanges inside the furnace. We study the evolution of the temperature and stress fields during growth and research the optimal pulling rate to obtain a flat solid-liquid interface. Moreover we point out how the temperature gradients and the stress field in the crystal could be affected using a heat shield inside the crucible. Different configurations are studied. Performing quasi-steady simulations at different growth stages, we show that our global numerical model provides a powerful tool for the computer-aided design of crystal growth furnaces.

  15. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  16. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth

    PubMed Central

    Rogan, Mark P.; Reznikov, Leah R.; Pezzulo, Alejandro A.; Gansemer, Nicholas D.; Samuel, Melissa; Prather, Randall S.; Zabner, Joseph; Fredericks, Douglas C.; McCray, Paul B.; Welsh, Michael J.; Stoltz, David A.

    2010-01-01

    People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF. PMID:21059918

  17. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth.

    PubMed

    Rogan, Mark P; Reznikov, Leah R; Pezzulo, Alejandro A; Gansemer, Nicholas D; Samuel, Melissa; Prather, Randall S; Zabner, Joseph; Fredericks, Douglas C; McCray, Paul B; Welsh, Michael J; Stoltz, David A

    2010-11-23

    People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF. PMID:21059918

  18. Clinical efficiency of low-level diode laser in reducing dentin hypersensitivity

    NASA Astrophysics Data System (ADS)

    Clavijo, E. M. A.; Clavijo, V. R. G.; Bandéca, M. C.; Nadalin, M. R.; Andrade, M. F.; Saad, J. R. C.; Pelegrine, A. A.

    2009-10-01

    Dentin hipersensitivity (DH) is a relatively common clinical condition, especially in periodontal patients after treatment. In this study it was evaluated 28 teeth who presented dentin hypersensitivity. The teeth were subjected to clinical and radiographic exams and were divided into groups following the treatment and the time of examination after application proposed: GI: PO 3% (Potassium Oxalate—group control)/Baseline; GII: PO 3%/3 days after first session; GIII: PO 3%/6 days; GIV: PO 3%/30 days; GV: PO 3%/60 days; GVI: PO 3%/90 days; GVII: Laser (Low_level diode laser with 110 mW/cm2)/Baseline; GVIII: Laser/7 days after first session; GIX: Laser/14 days; GX: Laser/30 days; GXI: Laser/60 days; and GXII: Laser/90 days. The groups I-VI, the teeth were subjected to 3 applications (GI-GIII) of desensitizing agent at regular intervals of seven days. The Groups VII-XI, each tooth was subjected to three applications (GVII-GIX) in three different points (mesial, meddle and distal surfaces) with an interval of 72 h. The time of application in each point was of 33 s and the patients from both groups were followed up to 90 days. The nonparametric test Friedman (α = 0.05) was applied and the test of Mann Whitney (α = 0.05) was used to compare the time of examination between groups. The application of Laser was effective 6 days after first session and to PO was 30 days. It was observed that both treatments were effective for the reduction of dentin hypersensitivity, however the laser presented better effectiveness.

  19. Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training.

    PubMed

    Schrott, Lisa M; Franklin, La 'Tonya M; Serrano, Peter A

    2008-03-10

    Prenatal exposure to opiates, which is invariably followed by postnatal withdrawal, can affect cognitive performance. To further characterize these effects, we examined radial 8-arm maze performance and expression of brain derived neurotrophic factor (BDNF) in male rats prenatally exposed to the opiate l-alpha-acetylmethadol (LAAM). Female rats received 1.0 mg/kg/day LAAM or water via daily oral gavage for 28 days prior to breeding, during breeding, and throughout pregnancy. Pups were fostered to non-treated lactating dams at birth and underwent neonatal opiate withdrawal. At 5-6 months, prenatal water- and LAAM-exposed males (n=6 each; non-littermates) received radial arm maze training consisting of ten trials a day for five days and three retention trials on day six. Rats prenatally exposed to LAAM had poorer maze performance, decreased percent correct responding and more reference and working memory errors than prenatal water-treated controls. However, they were able to acquire the task by the end of training. There were no differences between the groups on retention 24 h after testing. Following retention testing, hippocampi were removed and protein extracted from cytosol and synaptic fractions. Western blots were used to measure levels of mature and precursor BDNF protein, as well as the BDNF receptor TrkB. BDNF precursor protein was significantly decreased in the synaptic fraction of trained prenatal LAAM-treated rats compared to prenatal water-treated trained controls. No effects were found for the full-length or truncated TrkB receptor. In untrained rats, prenatal treatment did not affect any of the measures. These data suggest that prenatal opiate exposure and/or postnatal withdrawal compromise expression of proteins involved in the neural plasticity underlying learning. PMID:18262500

  20. Con: Reducing salt intake at the population level: is it really a public health priority?

    PubMed

    Graudal, Niels

    2016-09-01

    Scientific evidence to support the recommended salt intake of < 5.8 g/day is virtually non-existingent. There are no randomized controlled trials (RCTs) to investigate the effect of salt reduction (SR) below 5.8 g on health outcomes. The effect of SR on blood pressure (BP) reaches maximal efficacy at 1 week. RCTs in healthy individuals lasting at least 1 week show that the effect of SR on BP is <1 mmHg, but that SR has significant side effects, including increases in renin, aldosterone, noradrenalin, adrenalin, cholesterol and triglyceride. Still, disregarding confounders and side effects, health authorities use BP effects obtained in studies of pre-hypertensive and hypertensive patients to recommend SR in the healthy population and use these biased BP effects in statistical models indirectly to project millions of saved lives. These fantasy projections are in contrast to real data from prospective observational population studies directly associating salt intake with mortality, which show that salt intake <5.8 g/day is associated with an increased mortality of ∼15%. The population studies also show that a very high salt intake >12.2 g is associated with increased mortality. However, since <5% of populations consume such high amounts of salt, SR at the population level should not be a public health priority. Consequently, this policy should be abolished, not because any attempt to implement it has failed, and not because it costs taxpayers and food consumers unnecessary billions of dollars, but because-if implemented-it might kill people instead of saving them. PMID:27488354

  1. Altered Refractive Development in Mice With Reduced Levels of Retinal Dopamine

    PubMed Central

    Bergen, Michael A.; Park, Han na; Chakraborty, Ranjay; Landis, Erica G.; Sidhu, Curran; He, Li; Iuvone, P. Michael; Pardue, Machelle T.

    2016-01-01

    Purpose The neuromodulator dopamine (DA) has been implicated in the prevention of excessive ocular elongation and myopia in various animal models. This study used retina-specific DA knockout mice to investigate the role of retinal DA in refractive development and susceptibility to experimental myopia. Methods Measurements of refractive error, corneal curvature, and ocular biometrics were obtained as a function of age for both untreated and form-deprived (FD) groups of retina-specific tyrosine hydroxylase knockout (rTHKO) and control (Ctrl) mice. Retinas from each group were analyzed by HPLC for levels of DA and its primary metabolite (DOPAC). Results Under normal visual conditions, rTHKO mice showed significantly myopic refractions (F(1,188) = 7.602, P < 0.001) and steeper corneas (main effect of genotype F(1,180) = 5.1, P < 0.01) at 4 and 6 weeks of age compared with Ctrl mice. Retina-specific THKO mice also had thinner corneas (main effect of genotype F(1,181) = 37.17, P < 0.001), thinner retinas (F(6,181) = 6.07, P < 0.001), and shorter axial lengths (F(6,181) = 3.78, P < 0.01) than Ctrl mice. Retina-specific THKO retinas contained less than 15% of DA and DOPAC compared with Ctrl retinas, and the remaining DA had a significantly higher turnover, as indicated by DOPAC/DA ratios (Student's t-test, P < 0.05). Retina-specific THKO mice showed similar, yet more variable, responses to 6 weeks of FD compared with Ctrl mice. Conclusions Diminished retinal DA induced spontaneous myopia in mice raised under laboratory conditions without form deprivation. The relative myopic shift in rTHKO mice may be explained by steeper corneas, an unexpected finding. The chronic loss of DA did not significantly alter the FD myopia response in rTHKO mice.

  2. Disruption of Adenosine-5′-Phosphosulfate Kinase in Arabidopsis Reduces Levels of Sulfated Secondary Metabolites[W

    PubMed Central

    Mugford, Sarah G.; Yoshimoto, Naoko; Reichelt, Michael; Wirtz, Markus; Hill, Lionel; Mugford, Sam T.; Nakazato, Yoshimi; Noji, Masaaki; Takahashi, Hideki; Kramell, Robert; Gigolashvili, Tamara; Flügge, Ulf-Ingo; Wasternack, Claus; Gershenzon, Jonathan; Hell, Rüdiger; Saito, Kazuki; Kopriva, Stanislav

    2009-01-01

    Plants can metabolize sulfate by two pathways, which branch at the level of adenosine 5′-phosphosulfate (APS). APS can be reduced to sulfide and incorporated into Cys in the primary sulfate assimilation pathway or phosphorylated by APS kinase to 3′-phosphoadenosine 5′-phosphosulfate, which is the activated sulfate form for sulfation reactions. To assess to what extent APS kinase regulates accumulation of sulfated compounds, we analyzed the corresponding gene family in Arabidopsis thaliana. Analysis of T-DNA insertion knockout lines for each of the four isoforms did not reveal any phenotypical alterations. However, when all six combinations of double mutants were compared, the apk1 apk2 plants were significantly smaller than wild-type plants. The levels of glucosinolates, a major class of sulfated secondary metabolites, and the sulfated 12-hydroxyjasmonate were reduced approximately fivefold in apk1 apk2 plants. Although auxin levels were increased in the apk1 apk2 mutants, as is the case for most plants with compromised glucosinolate synthesis, typical high auxin phenotypes were not observed. The reduction in glucosinolates resulted in increased transcript levels for genes involved in glucosinolate biosynthesis and accumulation of desulfated precursors. It also led to great alterations in sulfur metabolism: the levels of sulfate and thiols increased in the apk1 apk2 plants. The data indicate that the APK1 and APK2 isoforms of APS kinase play a major role in the synthesis of secondary sulfated metabolites and are required for normal growth rates. PMID:19304933

  3. Brain BDNF levels elevation induced by physical training is reduced after unilateral common carotid artery occlusion in rats.

    PubMed

    Banoujaafar, Hayat; Van Hoecke, Jacques; Mossiat, Claude M; Marie, Christine

    2014-10-01

    We investigated the contribution of blood flow elevation in the cerebrovasculature to physical training-induced brain-derived neurotrophic factor (BDNF) levels elevation in the brain. Brain-derived neurotrophic factor protein levels were measured in the motor cortex 24 h after the last session of a forced treadmill walking (30 minutes a day, 18 m/minute for 7 consecutive days). Unilateral common carotid artery occlusion and modulation of exercise intensity (0 versus -10% inclination of the treadmill) were used as strategies to reduce the (normal) elevation of flow in the cerebrovasculature occurring during exercise. Administration of N-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg before each exercise sessions) and genetic hypertension (spontaneously hypertensive rats) were used as approaches to reduce stimulation of nitric oxide production in response to shear stress elevation. Vascular occlusion totally and partially abolished the effect of physical training on BDNF levels in the hemisphere ipsilateral and contralateral to occlusion, respectively. BDNF levels were higher after high than low exercise intensity. In addition, both genetic hypertension and L-NAME treatment blunted the effects of physical training on BDNF. From these results, we propose that elevation of brain BDNF levels elicited by physical training involves changes in cerebral hemodynamics. PMID:25052557

  4. The problems of reducing the noise level on open sites of machine building plants and living areas

    NASA Astrophysics Data System (ADS)

    Bulkin, V. V.; Kalinichenko, M. V.

    2015-09-01

    In this article there is an analysis of using noise-absorbing screens on the basis Helmholtz resonator to reduce the level of acoustic noise on open industrial sites of machinebuilding plants and adjacent living areas. A design realization of this screen was considered, the characteristic of which is a variable depth of the resonator chamber and the change of the clearance of the resonator throat. The evaluation of the efficiency of using the screen was performed using experimental modeling with an acoustic chamber and a screen model. It was shown that in the majority of the cases there is some attenuation of the acoustic signal in the zone in front of the screen. A conclusion was made about the possibility of reducing noise level in industrial and living zone

  5. Forest fragmentation reduces parasitism via species loss at multiple trophic levels.

    PubMed

    Fenoglio, Maria Silvina; Srivastava, Diane; Valladares, Graciela; Cagnolo, Luciano; Salvo, Adriana

    2012-11-01

    Although there is accumulating evidence from artificially assembled communities that reductions of species diversity result in diminished ecosystem functioning, it is not yet clear how real-world changes in diversity affect the flow of energy between trophic levels in multi-trophic contexts. In central Argentina, forest fragmentation has led to species loss of plants, herbivore and parasitoid insects, decline in trophic processes (herbivory and parasitism), and food web contraction. Here we examine if and how loss of parasitoid species following fragmentation causes decreased parasitism rates, by analyzing food webs of leaf miners and parasitoids from 19 forest fragments of decreasing size. We asked three questions: Do reductions in parasitoid richness following fragmentation directly or indirectly affect parasitism rate? Are changes in community parasitism rate driven by changes in the parasitism rate of individual leaf miner species, or changes in leaf miner composition, or both? Which traits of species determine the effects of food web change on parasitism rates? We found that habitat loss initiated a bottom-up cascade of extinctions from plants to leaf miners to parasitoids, with reductions in parasitoid richness ultimately driving decreases in parasitism rates. This relationship between parasitoid richness and parasitism depended on changes in the relative abundance (but not occurrence) of leaf miners such that parasitoid-rich fragments were dominated by leaf miner species that supported high rates of parasitism. Surprisingly, we found that only a small subset of species in the food web could account for much of the increase in parasitism with parasitoid richness: lepidopteran miners that attained exceptionally high densities in some fragments and their largely specialist parasitoids. How specialized a parasitoid is, and the relative abundance of leaf miners, had important effects on the diversity-parasitism rate relationship, but not other leaf miner traits

  6. Evaluating the Wald Test for Item-Level Comparison of Saturated and Reduced Models in Cognitive Diagnosis

    ERIC Educational Resources Information Center

    de la Torre, Jimmy; Lee, Young-Sun

    2013-01-01

    This article used the Wald test to evaluate the item-level fit of a saturated cognitive diagnosis model (CDM) relative to the fits of the reduced models it subsumes. A simulation study was carried out to examine the Type I error and power of the Wald test in the context of the G-DINA model. Results show that when the sample size is small and a…

  7. Body condition loss and increased serum levels of nonesterified fatty acids enhance progesterone levels at estrus and reduce estrous activity and insemination rates in postpartum dairy cows.

    PubMed

    Lüttgenau, J; Purschke, S; Tsousis, G; Bruckmaier, R M; Bollwein, H

    2016-03-01

    Data from 96 Holstein Friesian cows on a commercial dairy farm were used to investigate whether body condition and serum levels of nonesterified fatty acids (NEFAs) postpartum (pp) affect progesterone (P4) levels, estrous activity, and fertility in dairy cows. The examination period started 14 days before the expected calving date and ended either when a cow was inseminated or at a maximum of 90 days pp. Body condition score (BCS; 1-5 scale) and backfat thickness (BFT) were determined every 2 weeks. Blood for analysis of NEFA and P4 concentrations was sampled weekly during the first 35 days pp and then every 48 hours until an ovulation was observed. Transrectal ultrasonography of the ovaries started at 21 days pp and was performed after blood sampling. If cows were not inseminated because of silent ovulation, sampling and ultrasonography continued on Days 7, 14, and 18 after ovulation and again every 48 hours until the next ovulation. Estrous activity was continuously measured with the Heatime estrus detection system. Pregnancy controls were performed ultrasonographically 28 and 42 days after AI. Cows with increased NEFA levels at 28 days pp had an increased risk of maintaining minimum P4 levels above 0.4 ng/mL at first recognized estrus (P = 0.03). Higher NEFA levels at Day 7 were associated with lower probability for a cow to have elevated P4 levels (≥2 ng/mL) by Day 35 pp, indicating delayed commencement of luteal activity (C-LA). Estrous activity was not influenced (P > 0.10) by minimum P4 concentrations at estrus, but more animals with C-LA until Day 35 pp showed estrous activity compared to cows without C-LA throughout this period (P = 0.006). Estrous activity was lower in cows with a low BCS 14 days pp (P = 0.02) and with a low BFT 42 days pp (P = 0.03). Moreover, the probability to exhibit estrus was reduced with higher NEFA levels at 21 days pp (P = 0.01). Eighty-five cows were inseminated and 37 (44%) got pregnant after insemination. Higher NEFA levels

  8. Defects Along the Th17 Differentiation Pathway Underlie Genetically Distinct Forms of the Hyper IgE Syndrome

    PubMed Central

    Khatib, Shadi Al; Keles, Sevgi; Garcia-Lloret, Maria; Karakoc-Aydiner, Elif; Reisli, Ismail; Artac, Hasibe; Camcioglu, Yildiz; Cokugras, Haluk; Somer, Ayper; Kutukculer, Necil; Yilmaz, Mustafa; Ikinciogullari, Aydan; Yegin, Olcay; Yüksek, Mutlu; Genel, Ferah; Kucukosmanoglu, Ercan; Baki, Ali; Bahceciler, Nerin N; Rambhatla, Anupama; Nickerson, Derek W.; McGhee, Sean; Barlan, Isil B; Chatila, Talal

    2010-01-01

    Background The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE and diminished inflammatory responses. It exists as autosomal dominant (AD) and recessive (AR) forms that manifest common and distinguishing clinical features. A majority of those with AD-HIES suffers from heterozygous mutations in Signal Transducer and Activator of Transcription 3 (STAT3) and impaired Th17 differentiation. Objective To elucidate mechanisms underlying different forms of HIES. Methods A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by interferon alpha (IFNα) was assessed by intracellular staining with anti-phospho (p)STAT3 and pSTAT1 antibodies. Th17 and Th1 cell differentiation was assessed by measuring the production of IL-17 and IFNγ, respectively. Results Six subjects had STAT3 mutations affecting the DNA binding, SH2 and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative HIES subjects exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, while pSTAT1 activation was unaffected. Both patient groups exhibited impaired Th17 responses, but whereas STAT3 mutations abrogated early steps in Th17 differentiation, the defect(s) in HIES patients with normal STAT3 affected more distal steps. Conclusion In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired Th17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome. PMID:19577286

  9. Increased Hepatic Fatty Acids Uptake and Oxidation by LRPPRC-Driven Oxidative Phosphorylation Reduces Blood Lipid Levels

    PubMed Central

    Lei, Shi; Sun, Run-zhu; Wang, Di; Gong, Mei-zhen; Su, Xiang-ping; Yi, Fei; Peng, Zheng-wu

    2016-01-01

    Hyperlipidemia is one of the major risk factors of atherosclerosis and other cardiovascular diseases. This study aimed to investigate the impact of leucine rich pentatricopeptide repeat containing protein (LRPPRC)-driven hepatic oxidative phoshorylation on blood lipid levels. The hepatic LRPPRC level was modulated by liver-specific transgenic or adeno-associated virus 8 carried shRNA targeting Lrpprc (aav-shLrpprc). Mice were fed with a high fat diet to induce obesity. Gene expression was analyzed by quantitative real-time PCR and / or western blot. The hepatic ATP level, hepatic and serum lipids contents, and mitochondria oxidative phosphorylation (OxPhos) complex activities were measured using specific assay kits. The uptake and oxidation of fatty acid by hepatocytes were assessed using 14C-palmitate. LRPPRC regulated the expression of genes encoded by mitochondrial genome but not those by nuclear genome involved in mitochondria biogenesis, OxPhos, and lipid metabolism. Increased OxPhos in liver mediated by LRPPRC resulted in the increase of hepatic ATP level. Lrpprc promoted palmitate uptake and oxidation by hypatocytes. The hepatic and serum triglyceride and total cholesterol levels were inversely associated with the hepatic LRPPRC level. These data demonstrated that LRPPRC-driven hepatic OxPhos could promote fatty acids uptake and oxidation by hepatocytes and reduce both hepatic and circulating triglyceride and cholesterol levels. PMID:27462273

  10. Increased Hepatic Fatty Acids Uptake and Oxidation by LRPPRC-Driven Oxidative Phosphorylation Reduces Blood Lipid Levels.

    PubMed

    Lei, Shi; Sun, Run-Zhu; Wang, Di; Gong, Mei-Zhen; Su, Xiang-Ping; Yi, Fei; Peng, Zheng-Wu

    2016-01-01

    Hyperlipidemia is one of the major risk factors of atherosclerosis and other cardiovascular diseases. This study aimed to investigate the impact of leucine rich pentatricopeptide repeat containing protein (LRPPRC)-driven hepatic oxidative phoshorylation on blood lipid levels. The hepatic LRPPRC level was modulated by liver-specific transgenic or adeno-associated virus 8 carried shRNA targeting Lrpprc (aav-shLrpprc). Mice were fed with a high fat diet to induce obesity. Gene expression was analyzed by quantitative real-time PCR and / or western blot. The hepatic ATP level, hepatic and serum lipids contents, and mitochondria oxidative phosphorylation (OxPhos) complex activities were measured using specific assay kits. The uptake and oxidation of fatty acid by hepatocytes were assessed using (14)C-palmitate. LRPPRC regulated the expression of genes encoded by mitochondrial genome but not those by nuclear genome involved in mitochondria biogenesis, OxPhos, and lipid metabolism. Increased OxPhos in liver mediated by LRPPRC resulted in the increase of hepatic ATP level. Lrpprc promoted palmitate uptake and oxidation by hypatocytes. The hepatic and serum triglyceride and total cholesterol levels were inversely associated with the hepatic LRPPRC level. These data demonstrated that LRPPRC-driven hepatic OxPhos could promote fatty acids uptake and oxidation by hepatocytes and reduce both hepatic and circulating triglyceride and cholesterol levels. PMID:27462273

  11. A multi-level system quality improvement intervention to reduce racial disparities in hypertension care and control: study protocol

    PubMed Central

    2013-01-01

    Background Racial disparities in blood pressure control have been well documented in the United States. Research suggests that many factors contribute to this disparity, including barriers to care at patient, clinician, healthcare system, and community levels. To date, few interventions aimed at reducing hypertension disparities have addressed factors at all of these levels. This paper describes the design of Project ReD CHiP (Reducing Disparities and Controlling Hypertension in Primary Care), a multi-level system quality improvement project. By intervening on multiple levels, this project aims to reduce disparities in blood pressure control and improve guideline concordant hypertension care. Methods Using a pragmatic trial design, we are implementing three complementary multi-level interventions designed to improve blood pressure measurement, provide patient care management services and offer expanded provider education resources in six primary care clinics in Baltimore, Maryland. We are staggering the introduction of the interventions and will use Statistical Process Control (SPC) charting to determine if there are changes in outcomes at each clinic after implementation of each intervention. The main hypothesis is that each intervention will have an additive effect on improvements in guideline concordant care and reductions in hypertension disparities, but the combination of all three interventions will result in the greatest impact, followed by blood pressure measurement with care management support, blood pressure measurement with provider education, and blood pressure measurement only. This study also examines how organizational functioning and cultural competence affect the success of the interventions. Discussion As a quality improvement project, Project ReD CHiP employs a novel study design that specifically targets multi-level factors known to contribute to hypertension disparities. To facilitate its implementation and improve its sustainability, we have

  12. Overexpression of hydroxynitrile lyase in cassava roots elevates protein and free amino acids while reducing residual cyanogen levels.

    PubMed

    Narayanan, Narayanan N; Ihemere, Uzoma; Ellery, Claire; Sayre, Richard T

    2011-01-01

    Cassava is the major source of calories for more than 250 million Sub-Saharan Africans, however, it has the lowest protein-to-energy ratio of any major staple food crop in the world. A cassava-based diet provides less than 30% of the minimum daily requirement for protein. Moreover, both leaves and roots contain potentially toxic levels of cyanogenic glucosides. The major cyanogen in cassava is linamarin which is stored in the vacuole. Upon tissue disruption linamarin is deglycosylated by the apolplastic enzyme, linamarase, producing acetone cyanohydrin. Acetone cyanohydrin can spontaneously decompose at pHs >5.0 or temperatures >35°C, or is enzymatically broken down by hydroxynitrile lyase (HNL) to produce acetone and free cyanide which is then volatilized. Unlike leaves, cassava roots have little HNL activity. The lack of HNL activity in roots is associated with the accumulation of potentially toxic levels of acetone cyanohydrin in poorly processed roots. We hypothesized that the over-expression of HNL in cassava roots under the control of a root-specific, patatin promoter would not only accelerate cyanogenesis during food processing, resulting in a safer food product, but lead to increased root protein levels since HNL is sequestered in the cell wall. Transgenic lines expressing a patatin-driven HNL gene construct exhibited a 2-20 fold increase in relative HNL mRNA levels in roots when compared with wild type resulting in a threefold increase in total root protein in 7 month old plants. After food processing, HNL overexpressing lines had substantially reduced acetone cyanohydrin and cyanide levels in roots relative to wild-type roots. Furthermore, steady state linamarin levels in intact tissues were reduced by 80% in transgenic cassava roots. These results suggest that enhanced linamarin metabolism contributed to the elevated root protein levels. PMID:21799761

  13. Structural characterization and IgE epitope analysis of arginine kinase from Scylla paramamosain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arginine kinase (AK) has been reported as the pan-allergen of shellfish, however, there is limited information about its IgE epitopes and structural characteristics. In this study, AK from Scylla paramamosain was purified and characterized. The purified AK was a glycoprotein with the molecular weigh...

  14. Delayed Anaphylaxis to Red Meat Associated With Specific IgE Antibodies to Galactose

    PubMed Central

    Wen, Liping; Zhou, Junxiong; Sun, Jin-lu; Sun, Yi; Wu, Kai; Katial, Rohit

    2015-01-01

    A novel delayed anaphylactic reaction to red meat, associated with tick bites and IgE antibodies against galactose-α-1, 3-galactose (α-gal), was reported in 2009 in the US, Australia and Europe. In this case, serum specific IgE to galactose-α-1, 3-galactose (>100 kU/L) and IgE to multiple non-primate mammalian proteins were positive. However, the pathogenesis of this disease remains unclear. We report the first case in Asia of delayed anaphylactic reaction to red meat, which was induced by bites from the hard tick, Hematophagous ixodidae. We confirmed the increased concentration of IgE reactive epitopes in non-primate mammalian organs, which may be rich in α-gal proteins in lymphatic and endothelial tissues. All confirmed ticks associated with this disorder in the literature and in our case belonged to the hard tick family. We hypothesize that hard tick saliva is enriched with blood-type substances, such as oligosaccharides, from the non-primate mammal victim's blood after days to weeks of blood sucking, which sensitizes humans through the injection route while blood sucking. PMID:25553269

  15. Elevated serum IgE, eosinophilia, and lung function in rubber workers

    SciTech Connect

    Bascom, R.; Baser, M.E.; Thomas, R.J.; Fisher, J.F.; Yang, W.N.; Baker, J.H. )

    1990-01-01

    We previously reported an outbreak of acute respiratory illness associated with eosinophilia in a group of rubber workers who performed a thermoinjection process in which synthetic rubber was heated and then injected onto metal molds. This study was conducted to determine if persistent respiratory health effects were associated with this work area and to explore the possible allergic etiology of this syndrome. A survey was performed 1 mo after a major improvement in area ventilation and consisted of baseline, cross-shift, and cross-week spirometry; diffusing capacity; serum immunoglobulin E (IgE), total eosinophil count; and skin patch testing. Baseline lung function, cross-shift, and cross-week spirometry were not significantly worse in the exposed group as compared to the control group. However, either eosinophilia (greater than 450/mm3) or elevated serum IgE (greater than 470 ng/ml) were present in 44% of exposed workers vs. 11% of the control group (p = .003). Nine months later, neither eosinophilia nor elevated IgE were associated with employment in this work area. We conclude that employment in the thermoinjection process was associated with eosinophilia and elevated IgE, which suggests sensitization to one of the components of the rubber, although no effect on pulmonary function could be demonstrated.

  16. Effect of d-amino acids on IgE binding to peanut allergens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    D-amino acids are formed when L-amino acids are exposed to heat. The objective was to determine the existence of D-amino acids in roasted peanut and their effect on IgE binding. Raw and roasted peanut protein extracts were hydrolyzed in 6 N HCL under vacuum. The hydrolysates were then analyzed for D...

  17. A National Evaluation of the I/D/E/A Change Program for IGE.

    ERIC Educational Resources Information Center

    Paden, Jon S.

    A survey was conducted to determine attitudes of administrators, teachers, students, and parents of students in schools using the Institute for Development of Educational Activities, Inc. (I/D/E/A) Change Program for Individually Guided Education (IGE). The study took over two years, and reached a sample of the 1,200 schools in 36 states.…

  18. Intrathecal synthesis of IgE in children with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis

    PubMed Central

    Padilla-Docal, Barbara; Dorta-Contreras, Alberto J; Bu-Coifiu-Fanego, Raisa; Hernández, Hermes Fundora; Barroso, Jesús Callol; Sanchez-Martinez, Consuelo

    2008-01-01

    Background Eosinophilic meningoencephalitis caused by the helminth Angiostrongylus cantonensis, is an emerging infectious disease in America. The objective of this paper was to determine if the intrathecal synthesis of immunoglobulin E is produced during the acute phase of the disease. Methods Thirteen patients, mean age 4.5 years were studied; a diagnostic lumbar puncture was performed and serum samples taken. Immunoglobulin E (IgE) in serum and in cerebrospinal fluid (CSF) was quantified by nephelometry. Control patients had other infections or other neurological diseases. Results The mean cell count in the CSF was 500 × 10-6 cells/L and of these 23% were eosinophils. In blood the eosinophils were 13%. The chief symptoms of the patients were migraine, vomiting and fever and 50% presented some meningeal signs. IgE intrathecal synthesis analyzed by the corresponding quotient diagram (Reibergram) was observed in all patients. No intrathecal IgE synthesis was seen in control patients. Conclusion Intrathecal synthesis of IgE demonstrates the participation of this immunoglobulin in the destruction of the third stage larvae of the parasite in the CSF. The test should be considered in our environment as a tool to aid diagnosis. PMID:19032790

  19. Heat-induced alterations in cashew allergen solubility and IgE binding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cashew nuts are included in a group of 8 foods that commonly cause food allergies. IgE binding to allergens within the nuts can cause allergic reactions that can be severe. Foods containing cashew nuts must be labeled to prevent accidental exposure to people who suffer from allergy to cashew nuts....

  20. Multiple IgE recognition on the major allergen of the Parietaria pollen Par j 2.

    PubMed

    Longo, Valeria; Costa, Maria Assunta; Cibella, Fabio; Cuttitta, Giuseppina; La Grutta, Stefania; Colombo, Paolo

    2015-02-01

    The interaction between IgE antibodies and allergens is a key event in triggering an allergic reaction. The characterization of this region provides information of paramount importance for diagnosis and therapy. Par j 2 Lipid Transfer Protein is one of the most important allergens in southern Europe and a well-established marker of sensitization in Parietaria pollen allergy. The main aim of this study was to map the IgE binding regions of this allergen and to study the pattern of reactivity of individual Parietaria-allergic patients. By means of gene fragmentation, six overlapping peptides were expressed in Escherichia coli, and their IgE binding activity was evaluated by immunoblotting in a cohort of 79 Parietaria-allergic patients. Our results showed that Pj-allergic patients display a heterogeneous pattern of IgE binding to the different recombinant fragments, and that patients reacted simultaneously against several protein domains spread all the over the molecule, even in fragments which do not contain structural features resembling the native allergen. Our results reveal the presence of a large number of linear and conformational epitopes on the Par j 2 sequence, which probably explains the high allergenic activity of this allergen. PMID:25284812

  1. Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

    SciTech Connect

    Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

    1987-03-01

    Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects.

  2. Adverse childhood experiences associate to reduced glutamate levels in the hippocampus of patients affected by mood disorders.

    PubMed

    Poletti, Sara; Locatelli, Clara; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

    2016-11-01

    Adverse childhood experiences (ACE) can possibly permanently alter the stress response system, affect the glutamatergic system and influence hippocampal volume in mood disorders. The aim of the study is to investigate the association between glutamate levels in the hippocampus, measured through single proton magnetic resonance spectroscopy (1H-MRS), and ACE in patients affected by mood disorders and healthy controls. Higher levels of early stress associate to reduced levels of Glx/Cr in the hippocampus in depressed patients but not in healthy controls. Exposure to stress during early life could lead to a hypofunctionality of the glutamatergic system in the hippocampus of depressed patients. Abnormalities of glutamatergic signaling could then possibly underpin the structural and functional abnormalities observed in patients affected by mood disorders. PMID:27449360

  3. Reduced level of sex-specific antigen (H-Y antigen) on lymphocytes in some patients with bilateral cryptorchidism.

    PubMed

    Fedder, J; Hansen, L G; Hjort, T

    1989-01-01

    Sex-specific (Sxs) antigen on the surface of nucleated cells from normal human males seems to be essential for the formation of testes. The relative quantity of the antigen on lymphocytes was evaluated by absorption experiments in a complement-dependent cytotoxicity test or in an ELISA technique using antisera against Sxs antigen produced by immunization of female rats. Lymphocytes from 13 normal males were Sxs-antigen positive, and cells from 12 normal females were characterized as Sxs-antigen negative. However, in the testing of lymphocytes from nine boys with bilateral cryptorchidism, only six revealed a normal male absorption pattern, whereas the antigen level on cells from three boys, all of them with normal karyotype, was reduced compared with the normal male level. No correlation between Sxs-antigen level and testosterone response after treatment with hCG could be demonstrated. PMID:2565709

  4. Flea fitness is reduced by high fractional concentrations of CO₂ that simulate levels found in their hosts' burrows.

    PubMed

    Downs, Cynthia J; Pinshow, Berry; Khokhlova, Irina S; Krasnov, Boris R

    2015-11-01

    Nidicolous ectoparasites such as fleas and gamasid mites that feed on small and medium-sized mammals spend much of their time in their hosts' burrows, which provide an environment for living, and often feeding, to their pre-imaginal and/or adult stages. Thus, these ectoparasites should be adapted to environmental conditions in burrows, including high fractional concentrations of CO2 (F(CO2)). We examined how a high F(CO2) (0.04) affected survival and reproductive success of a hematophagous ectoparasite of burrowing rodents using fleas Xenopsylla ramesis and Sundevall's jirds Meriones crassus. In the first experiment, fleas fed on hosts housed in high-CO2 (F(CO2) =0.04) or atmospheric-CO2 (F(CO2) ≈0.0004) air, and were allowed to breed. In a second experiment, fleas were maintained in high CO2 or CO2-free air with no hosts to determine how CO2 levels affect survival and activity levels. We found that at high F(CO2) fleas laid fewer eggs, reducing reproductive success. In addition, at high F(CO2), activity levels and survival of fleas were reduced. Our results indicate that fleas do not perform well in the F(CO2) used in this experiment. Previous research indicated that the type and intensity of the effects of CO2 concentration on the fitness of an insect depend on the F(CO2) used, so we advise caution when generalizing inferences drawn to insects exposed to other F(CO2). If, however, F(CO2) found in natural mammal burrows brings about reduced fitness in fleas in general, then burrowing hosts may benefit from reduced parasite infestation if burrow air F(CO2) is high. PMID:26582933

  5. Auricular Acupressure Reduces Anxiety Levels and Improves Outcomes of in Vitro Fertilization: A Prospective, Randomized and Controlled Study

    PubMed Central

    Qu, Fan; Zhang, Dan; Chen, Lu-Ting; Wang, Fang-Fang; Pan, Jie-Xue; Zhu, Yi-Min; Ma, Chun-Mei; Huang, Yi-Ting; Ye, Xiao-Qun; Sun, Sai-Jun; Zheng, Wen-Jun; Zhang, Run-Ju; Xu, Jian; Xing, Lan-Feng; Huang, He-Feng

    2014-01-01

    The study was to explore whether auricular acupressure (AA) can relieve anxiety during the period from trans-vaginal oocyte retrieval to the embryo transfer in IVF treatment and whether AA can improve the outcomes of IVF. 305 infertile patients with tubal blockage who were referred for IVF were included. The women were randomized into a control group with 102 cases, a Sham-AA group with 102 cases and an AA group with 101 cases. The anxiety levels were rated with Spielberger's State Trait Anxiety Inventory and the Amsterdam Preoperative Anxiety and Information Scale. Data of clinical pregnancy rate (CPR), implantation rate (IR) and live birth rate (LBR) were obtained. The levels of neuropeptide Y (NPY) and transforming growth factor alpha (TGF-alpha) in the follicular fluids were detected with ELISA. After treatment, in AA group, the levels of state anxiety, preoperative anxiety and need-for-information were significantly lower, whereas CPR, IR, LBR and NPY levels in the follicular fluids were markedly higher than Sham-AA group and control group. We concluded that AA could help to reduce anxiety levels associated with IVF and improves the outcomes of IVF partly through increasing the levels of NPY in the follicular fluids. PMID:24848522

  6. Circulating Heat Shock Protein 60 Levels Are Elevated in HIV Patients and Are Reduced by Anti-Retroviral Therapy

    PubMed Central

    Anraku, Itaru; Rajasuriar, Reena; Dobbin, Caroline; Brown, Richard; Lewin, Sharon R.; Suhrbier, Andreas

    2012-01-01

    Circulating heat shock protein 60 (Hsp60) and heat shock protein 10 (Hsp10) have been associated with pro- and anti-inflammatory activity, respectively. To determine whether these heat shock proteins might be associated with the immune activation seen in HIV-infected patients, the plasma levels of Hsp60 and Hsp10 were determined in a cohort of 20 HIV-infected patients before and after effective combination anti-retroviral therapy (cART). We show for the first time that circulating Hsp60 levels are elevated in HIV-infected patients, with levels significantly reduced after cART, but still higher than those in HIV-negative individuals. Hsp60 levels correlated significantly with viral load, CD4 counts, and circulating soluble CD14 and lipopolysaccharide levels. No differences or correlations were seen for Hsp10 levels. Elevated circulating Hsp60 may contribute to the immune dysfunction and non-AIDS clinical events seen in HIV-infected patients. PMID:23028910

  7. Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients.

    PubMed

    Khan, Sikandar G; Oh, Kyu-Seon; Shahlavi, Tala; Ueda, Takahiro; Busch, David B; Inui, Hiroki; Emmert, Steffen; Imoto, Kyoko; Muniz-Medina, Vanessa; Baker, Carl C; DiGiovanna, John J; Schmidt, Deborah; Khadavi, Arash; Metin, Ahmet; Gozukara, Engin; Slor, Hanoch; Sarasin, Alain; Kraemer, Kenneth H

    2006-01-01

    Xeroderma pigmentosum group C (XP-C) is a rare autosomal recessive disorder. Patients with two mutant alleles of the XPC DNA repair gene have sun sensitivity and a 1000-fold increase in skin cancers. Clinically normal parents of XP-C patients have one mutant allele and one normal allele. As a step toward evaluating cancer risk in these XPC heterozygotes we characterized cells from 16 XP families. We identified 15 causative mutations (5 frameshift, 6 nonsense and 4 splicing) in the XPC gene in cells from 16 XP probands. All had premature termination codons (PTC) and absence of normal XPC protein on western blotting. The cell lines from 26 parents were heterozygous for the same mutations. We employed a real-time quantitative reverse transcriptase-PCR assay as a rapid and sensitive method to measure XPC mRNA levels. The mean XPC mRNA levels in the cell lines from the XP-C probands were 24% (P<10(-7)) of that in 10 normal controls. This reduced XPC mRNA level in cells from XP-C patients was caused by the PTC that induces nonsense-mediated mRNA decay. The mean XPC mRNA levels in cell lines from the heterozygous XP-C carriers were intermediate (59%, P=10(-4)) between the values for the XP patients and the normal controls. This study demonstrates reduced XPC mRNA levels in XP-C patients and heterozygotes. Thus, XPC mRNA levels may be evaluated as a marker of cancer susceptibility in carriers of mutations in the XPC gene. PMID:16081512

  8. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    SciTech Connect

    Almeida, Luciana O.; Goto, Renata N.; Neto, Marinaldo P.C.; Sousa, Lucas O.; Curti, Carlos; Leopoldino, Andréia M.

    2015-03-06

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3.

  9. Leptin resistance is not the primary cause of weight gain associated with reduced sex hormone levels in female mice.

    PubMed

    da Silva, Regina P; Zampieri, Thais T; Pedroso, João A B; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; Furigo, Isadora C; Câmara, Niels O; Frazão, Renata; Donato, Jose

    2014-11-01

    Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin, and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 d or 24 wk after ovariectomy) but not 7 days after the surgery. In addition, we observed a progressive decrease in the coexpression of LepR and estrogen receptor-α in the hypothalamus after the ovariectomy, resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin-resistance state. PMID:25144922

  10. Epigenetic Alterations in Human Liver From Subjects With Type 2 Diabetes in Parallel With Reduced Folate Levels

    PubMed Central

    Matte, Ashok; Perfilyev, Alexander; de Mello, Vanessa D.; Käkelä, Pirjo; Pihlajamäki, Jussi

    2015-01-01

    Objective: Epigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown whether epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and nondiabetic controls and related epigenetic alterations to gene expression and circulating folate levels. Research Design and Methods: Liver biopsies were obtained from 35 diabetic and 60 nondiabetic subjects, which are part of the Kuopio Obesity Surgery Study. The genome-wide DNA methylation pattern was analyzed in the liver using the HumanMethylation450 BeadChip. RNA expression was analyzed from a subset of subjects using the HumanHT-12 Expression BeadChip. Results: After correction for multiple testing, we identified 251 individual CpG sites that exhibit differential DNA methylation in liver obtained from T2D compared with nondiabetic subjects (Q < .05). These include CpG sites annotated to genes that are biologically relevant to the development of T2D such as GRB10, ABCC3, MOGAT1, and PRDM16. The vast majority of the significant CpG sites (94%) displayed decreased DNA methylation in liver from subjects with T2D. The hypomethylation found in liver from diabetic subjects may be explained by reduced folate levels. Indeed, subjects with T2D had significantly reduced erythrocyte folate levels compared with nondiabetic subjects. We further identified 29 genes that displayed both differential DNA methylation and gene expression in human T2D liver including the imprinted gene H19. Conclusions: Our study highlights the importance of epigenetic and transcriptional changes in the liver from subjects with T2D. Reduced circulating folate levels may provide an explanation for hypomethylation in the human diabetic liver. PMID:26418287

  11. Immunization with Hypoallergens of Shrimp Allergen Tropomyosin Inhibits Shrimp Tropomyosin Specific IgE Reactivity

    PubMed Central

    Wai, Christine Y. Y.; Leung, Nicki Y. H.; Ho, Marco H. K.; Gershwin, Laurel J.; Shu, Shang An; Leung, Patrick S. C.; Chu, Ka Hou

    2014-01-01

    Designer proteins deprived of its IgE-binding reactivity are being sought as a regimen for allergen-specific immunotherapy. Although shrimp tropomyosin (Met e 1) has long been identified as the major shellfish allergen, no immunotherapy is currently available. In this study, we aim at identifying the Met e 1 IgE epitopes for construction of hypoallergens and to determine the IgE inhibitory capacity of the hypoallergens. IgE-binding epitopes were defined by three online computational models, ELISA and dot-blot using sera from shrimp allergy patients. Based on the epitope data, two hypoallergenic derivatives were constructed by site-directed mutagenesis (MEM49) and epitope deletion (MED171). Nine regions on Met e 1 were defined as the major IgE-binding epitopes. Both hypoallergens MEM49 and MED171 showed marked reduction in their in vitro reactivity towards IgE from shrimp allergy patients and Met e 1-sensitized mice, as well as considerable decrease in induction of mast cell degranulation as demonstrated in passive cutaneous anaphylaxis assay. Both hypoallergens were able to induce Met e 1-recognizing IgG antibodies in mice, specifically IgG2a antibodies, that strongly inhibited IgE from shrimp allergy subjects and Met e 1-sensitized mice from binding to Met e 1. These results indicate that the two designer hypoallergenic molecules MEM49 and MED171 exhibit desirable preclinical characteristics, including marked reduction in IgE reactivity and allergenicity, as well as ability to induce blocking IgG antibodies. This approach therefore offers promises for development of immunotherapeutic regimen for shrimp tropomyosin allergy. PMID:25365343

  12. Association Between PTPN22 Polymorphisms and IgE Responses to Staphylococcal Superantigens in Chronic Urticaria.

    PubMed

    Palikhe, Sailesh; Kim, Seung Hyun; Pham, Le Duy; Ye, Young Min; Park, Hae Sim

    2015-05-01

    Protein tyrosine phosphatase-22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. A polymorphism of the PTPN22 gene has been found to be associated with chronic urticaria (CU). We investigated the associations between PTPN22 gene polymorphisms and CU characteristics, including serum specific IgE antibodies response to toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA). CU patients (n=409) and normal healthy controls (n=388) were enrolled in the present study. Serum specific IgE to TSST-1 and SEA were measured by ImmunoCAP®. Five PTPN22 single nucleotide polymorphisms, -1123G>C, 1858C>T, 13145A>G, 14943C>T, and 20628A>G, were genotyped. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the 2 groups. CU patients carrying the GG genotype at 20628A>G (P=0.035) or haplotype 3 [GGG] (P=0.047) had a significantly higher prevalence of serum specific IgE to TSST-1 compared to non-carriers. Similarly, CT/TT genotype at 14943C>T had a significantly higher prevalence of serum specific IgE to SEA (P=0.045). The findings suggest that the PTPN22 gene polymorphisms at 20628A>G and 14943C>T may enhance serum specific IgE responses to TSST-1 and SEA, which may contribute to CU pathogenesis. PMID:25749762

  13. IgE Sensitization Profiles Differ between Adult Patients with Severe and Moderate Atopic Dermatitis

    PubMed Central

    Johansson, Catharina; Lupinek, Christian; Lundeberg, Lena; Crameri, Reto; Valenta, Rudolf; Scheynius, Annika

    2016-01-01

    Background Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors. Aim To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens. Methodology Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins. Results IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD. Conclusion We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD. PMID:27228091

  14. The economic benefits of reducing the levels of nitrogen dioxide (NO2) near primary schools: The case of London.

    PubMed

    Guerriero, Carla; Chatzidiakou, Lia; Cairns, John; Mumovic, Dejan

    2016-10-01

    Providing a healthy school environment is a priority for child health. The aim of this study is to develop a methodology that allows quantification of the potential economic benefit of reducing indoor exposure to nitrogen dioxide (NO2) in children attending primary schools. Using environmental and health data collected in primary schools in London, this study estimates that, on average, 82 asthma exacerbations per school can be averted each year by reducing outdoor NO2 concentrations. The study expands upon previous analyses in two ways: first it assesses the health benefits of reducing children's exposure to indoor NO2 while at school, second it considers the children's perspective in the economic evaluation. Using a willingness to pay approach, the study quantifies that the monetary benefits of reducing children's indoor NO2 exposure while at school would range between £2.5 k per school if a child's perspective based on child's budget is adopted up to £60 k if a parent's perspective is considered. This study highlights that designers, engineers, policymakers and stakeholders need to consider the reduction of outdoor pollution, and particularly NO2 levels, near primary schools as there may be substantial health and monetary benefits. PMID:27451292

  15. Myofibroblast keratinocyte growth factor reduces tight junctional integrity and increases claudin-2 levels in polarized Caco-2 cells

    PubMed Central

    Kim, Tae Il; Poulin, Emily J.; Blask, Elliot; Bukhalid, Raghida; Whitehead, Robert H.; Franklin, Jeffrey L.; Coffey, Robert J.

    2013-01-01

    The colonic epithelium is composed of a polarized monolayer sheathed by a layer of pericryptal myofibroblasts (PCMFs). We mimicked these cellular compartments in vitro to assess the effects of paracrine-acting PCMF-derived factors on tight junction (TJ) integrity, as measured by transepithelial electrical resistance (TER). Co-culture with 18Co PCMFs, or basolateral administration of 18Co conditioned medium (CM), significantly reduced TER of polarized Caco-2 cells. Amongst candidate paracrine factors, only keratinocyte growth factor (KGF) reduced Caco-2 TER; basolateral KGF treatment led to time- and concentration-dependent increases in claudin-2 levels. We also demonstrate amphiregulin (AREG), produced largely by Caco-2 cells, increased claudin-2 levels, leading to epidermal growth factor receptor-mediated TER reduction. We propose that colonic epithelial TJ integrity can be modulated by paracrine KGF and autocrine AREG through increased claudin-2 levels. KGF-regulated claudin-2 induction may have implications for inflammatory bowel disease, where both KGF and claudin-2 are upregulated. PMID:22946653

  16. High serum levels of proinflammatory markers during epileptogenesis. Can omega-3 fatty acid administration reduce this process?

    PubMed

    Gouveia, Telma Luciana Furtado; Vieira de Sousa, Paula Viviane; de Almeida, Sandro Soares; Nejm, Mariana Bocca; Vieira de Brito, Joíse Marques; Cysneiros, Roberta Monterazzo; de Brito, Marlon Vilela; Salu, Bruno Ramos; Oliva, Maria Luiza Vilela; Scorza, Fúlvio Alexandre; Naffah-Mazzacoratti, Maria da Graça

    2015-10-01

    During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cytokines such as IL-1β, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures. PMID:26318793

  17. Talampanel reduces the level of motoneuronal calcium in transgenic mutant SOD1 mice only if applied presymptomatically

    PubMed Central

    Paizs, Melinda; Tortarolo, Massimo; Bendotti, Caterina; Engelhardt, Jozsef I; Siklós, László

    2011-01-01

    We tested the efficacy of treatment with talampanel in a mutant SOD1 mouse model of ALS by measuring intracellular calcium levels and loss of spinal motor neurons. We intended to mimic the clinical study; hence, treatment was started when the clinical symptoms were already present. The data were compared with the results of similar treatment started at a presymptomatic stage. Transgenic and wild-type mice were treated either with talampanel or with vehicle, starting in pre-symptomatic or symptomatic stages. The density of motor neurons was determined by the physical disector, and their intracellular calcium level was assayed electron microscopically. Results showed that motor neurons in the SOD1 mice exhibited an elevated calcium level, which could be reduced, but not restored, with talampanel only when the treatment was started presymptomatically. Treatment in either presymptomatic or symptomatic stages failed to rescue the motor neurons. We conclude that talampanel reduces motoneuronal calcium in a mouse model of ALS, but its efficacy declines as the disease progresses, suggesting that medication initiation in the earlier stages of the disease might be more effective. PMID:21623665

  18. Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice.

    PubMed

    Ejaz, Asma; Martinez-Guino, Laura; Goldfine, Allison B; Ribas-Aulinas, Francesc; De Nigris, Valeria; Ribó, Sílvia; Gonzalez-Franquesa, Alba; Garcia-Roves, Pablo M; Li, Elizabeth; Dreyfuss, Jonathan M; Gall, Walt; Kim, Jason K; Bottiglieri, Teodoro; Villarroya, Francesc; Gerszten, Robert E; Patti, Mary-Elizabeth; Lerin, Carles

    2016-04-01

    Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans. PMID:26858359

  19. Reduced genetic diversity and increased reproductive isolation follow population-level loss of larval dispersal in a marine gastropod.

    PubMed

    Ellingson, Ryan A; Krug, Patrick J

    2016-01-01

    Population-level consequences of dispersal ability remain poorly understood, especially for marine animals in which dispersal is typically considered a species-level trait governed by oceanographic transport of microscopic larvae. Transitions from dispersive (planktotrophic) to nondispersive, aplanktonic larvae are predicted to reduce connectivity, genetic diversity within populations, and the spatial scale at which reproductive isolation evolves. However, larval dimorphism within a species is rare, precluding population-level tests. We show the sea slug Costasiella ocellifera expresses both larval morphs in Florida and the Caribbean, regions with divergent mitochondrial lineages. Planktotrophy predominated at 11 sites, 10 of which formed a highly connected and genetically diverse Caribbean metapopulation. Four populations expressed mainly aplanktonic development and had markedly reduced connectivity, and lower genetic diversity at one mitochondrial and six nuclear loci. Aplanktonic dams showed partial postzygotic isolation in most interpopulation crosses, regardless of genetic or geographic distance to the sire's source, suggesting that outbreeding depression affects fragmented populations. Dams from genetically isolated and neighboring populations also exhibited premating isolation, consistent with reinforcement contingent on historical interaction. By increasing self-recruitment and genetic drift, the loss of dispersal may thus initiate a feedback loop resulting in the evolution of reproductive isolation over small spatial scales in the sea. PMID:26635309

  20. Update of upper level turbulence forecast by reducing unphysical components of topography in the numerical weather prediction model

    NASA Astrophysics Data System (ADS)

    Park, Sang-Hun; Kim, Jung-Hoon; Sharman, Robert D.; Klemp, Joseph B.

    2016-07-01

    On 2 November 2015, unrealistically large areas of light-or-stronger turbulence were predicted by the WRF-RAP (Weather Research and Forecast Rapid Refresh)-based operational turbulence forecast system over the western U.S. mountainous regions, which were not supported by available observations. These areas are reduced by applying additional terrain averaging, which damps out the unphysical components of small-scale (~2Δx) energy aloft induced by unfiltered topography in the initialization of the WRF model. First, a control simulation with the same design of the WRF-RAP model shows that the large-scale atmospheric conditions are well simulated but predict strong turbulence over the western mountainous region. Four experiments with different levels of additional terrain smoothing are applied in the initialization of the model integrations, which significantly reduce spurious mountain-wave-like features, leading to better turbulence forecasts more consistent with the observed data.

  1. Serum Malassezia-specific IgE in dogs with recurrent Malassezia otitis externa without concurrent skin disease.

    PubMed

    Layne, Elizabeth A; DeBoer, Douglas J

    2016-08-01

    Immediate-type hypersensitivity (ITH), mediated by IgE, to Malassezia pachydermatis is recognized in atopic dogs with recurrent yeast dermatitis and otitis externa (OE). Malassezia-associated OE commonly occurs in dogs without other signs of atopic dermatitis (AD). The aim of this study was to detect Malassezia-specific IgE in the sera of dogs with recurrent Malassezia OE without concurrent skin disease. Sera from healthy dogs were used for comparison. An FcεRIα-based ELISA was used to measure Malassezia-specific IgE. There was no significant difference between number of positive affected dogs (6/21, 29%) and number of positive unaffected dogs (15/86, 17%) (P=0.36). There was also no significant difference in the concentrations of Malassezia-specific IgE between the two groups (P=0.97). Malassezia-specific IgE did not distinguish between patient groups so, as with other canine allergens, serum IgE reactivity for Malassezia could not be used to differentiate between diseased and healthy patients. The presence of Malassezia-specific IgE in some of the affected dogs might indicate ITH to Malassezia in those dogs. Evaluation of ITH via intradermal test reactivity and response to allergen-specific immunotherapy might clarify the role of Malassezia-associated ITH in similarly affected dogs. PMID:27288851

  2. Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes

    PubMed Central

    Perry, John R.B.; Weedon, Michael N.; Langenberg, Claudia; Jackson, Anne U.; Lyssenko, Valeriya; Sparsø, Thomas; Thorleifsson, Gudmar; Grallert, Harald; Ferrucci, Luigi; Maggio, Marcello; Paolisso, Giuseppe; Walker, Mark; Palmer, Colin N.A.; Payne, Felicity; Young, Elizabeth; Herder, Christian; Narisu, Narisu; Morken, Mario A.; Bonnycastle, Lori L.; Owen, Katharine R.; Shields, Beverley; Knight, Beatrice; Bennett, Amanda; Groves, Christopher J.; Ruokonen, Aimo; Jarvelin, Marjo Riitta; Pearson, Ewan; Pascoe, Laura; Ferrannini, Ele; Bornstein, Stefan R.; Stringham, Heather M.; Scott, Laura J.; Kuusisto, Johanna; Nilsson, Peter; Neptin, Malin; Gjesing, Anette P.; Pisinger, Charlotta; Lauritzen, Torsten; Sandbaek, Annelli; Sampson, Mike; Zeggini, MAGIC, Ele; Lindgren, Cecilia M.; Steinthorsdottir, Valgerdur; Thorsteinsdottir, Unnur; Hansen, Torben; Schwarz, Peter; Illig, Thomas; Laakso, Markku; Stefansson, Kari; Morris, Andrew D.; Groop, Leif; Pedersen, Oluf; Boehnke, Michael; Barroso, Inês; Wareham, Nicholas J.; Hattersley, Andrew T.; McCarthy, Mark I.; Frayling, Timothy M.

    2010-01-01

    Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 × 10−5], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes. PMID:19933169

  3. PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: evolocumab.

    PubMed

    Dahagam, Chanukya; Goud, Aditya; Abdelqader, Abdelhai; Hendrani, Aditya; Feinstein, Matthew J; Qamar, Arman; Joshi, Parag H; Swiger, Kristopher J; Byrne, Kathleen; Quispe, Renato; Jones, Steven R; Blumenthal, Roger S; Martin, Seth S

    2016-03-01

    Patients with familial hypercholesterolemia or statin intolerance are especially challenging to manage since LDL cholesterol levels often remain considerably elevated despite clinicians' best efforts. With statins regarded as first-line pharmacologic therapy by the current American College of Cardiology/American Heart Association guidelines to reduce LDL cholesterol and cardiovascular risk, there is now a critical need to determine when other agents will play a role beyond maximally tolerated statin therapy and lifestyle changes. In this review, we take a closer look at evolocumab (Repatha(®)), one of the new injectable human monoclonal antibodies to PCSK9 and its efficacy and safety properties from the results of various trials. PMID:26911578

  4. Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus).

    PubMed

    Agnvall, Beatrix; Katajamaa, Rebecca; Altimiras, Jordi; Jensen, Per

    2015-09-01

    Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication. PMID:26382075

  5. Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus)

    PubMed Central

    Agnvall, Beatrix; Katajamaa, Rebecca; Altimiras, Jordi; Jensen, Per

    2015-01-01

    Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44–48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication. PMID:26382075

  6. Quinolizidine alkaloids reduced mortality in EV71-infected mice by compensating for the levels of T cells.

    PubMed

    Yang, Yajun; Guan, Feifei; Bai, Lin; Zhang, Li; Liu, Jiangning; Pan, Xiandao; Zhang, Lianfeng

    2015-09-01

    Recent outbreak of hand, foot and mouse disease caused by enterovirus 71 is a serious threat to infants and children in Asia-Pacific countries. No vaccines or antiviral therapies are available against this infection. In this study, we found that quinolizidine alkaloids could improve the levels of T cells in mice. The structure-activity relationships demonstrated that the oxidation and double bonds are important for the excellent potency. Oxysophocarpine, the most effective compound of six quinolizidine alkaloids, could also relieve symptoms and reduce mortality in lethal enterovirus 71-infected mice through compensating for the decreased levels of T cells. This work suggested that quinolizidine alkaloids have the potential against enterovirus 71 for further development of novel antiviral drugs. PMID:26189894

  7. Does Genetic Regulation of IgE Begin In-Utero? Evidence from TH1/TH2 Gene Polymorphisms and Cord Blood Total IgE

    PubMed Central

    Hong, Xiumei; Tsai, Hui-Ju; Liu, Xin; Arguelles, Lester; Kumar, Rajesh; Wang, Guoying; Kuptsova-Clarkson, Nataliya; Pearson, Colleen; Ortiz, Kathryn; Bonzagni, Anthony; Apollon, Stephanie; Fu, Lingling; Pongracic, Jacqueline A; Schleimer, Robert; Holt, Patrick G.; Bauchner, Howard; Wang, Xiaobin

    2010-01-01

    Background Elucidation of early life factors is critical to understand the development of allergic diseases, especially those manifesting in early life such as food allergies and atopic dermatitis. Cord blood IgE (CBIgE) is a recognized risk factor for the subsequent development of allergic diseases. In contrast to num