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Sample records for hypersensitive response hr

  1. System-Wide Hypersensitive Response-Associated Transcriptome and Metabolome Reprogramming in Tomato

    NARCIS (Netherlands)

    Etalo, D.W.; Stulemeijer, I.J.E.; Esse, van H.P.; Vos, de R.C.H.; Bouwmeester, H.J.; Joosten, M.H.A.J.

    2013-01-01

    The hypersensitive response (HR) is considered to be the hallmark of the resistance response of plants to pathogens. To study HR-associated transcriptome and metabolome reprogramming in tomato (Solanum lycopersicum), we used plants that express both a resistance gene to Cladosporium fulvum and the

  2. Cytoplasmic and nuclear localizations are important for the hypersensitive response conferred by maize autoactive Rp1-D21 protein

    Science.gov (United States)

    Disease resistance (R-) genes have been isolated from many plant species. Most encode nucleotide binding leucine-rich-repeat (NLR) proteins that trigger a rapid localized programmed cell death termed the hypersensitive response (HR) upon pathogen recognition. Despite their structural similarities, d...

  3. Proteomic analysis of S-nitrosylated proteins in Arabidopsis thaliana undergoing hypersensitive response

    DEFF Research Database (Denmark)

    Romero-Puertas, Maria C; Campostrini, Natascia; Mattè, Alessandro

    2008-01-01

    is the identification of the proteins that are subjected to this PTM. By using a proteomic approach involving 2-DE and MS we characterized, for the first time, changes in S-nitrosylated proteins in Arabidopsis thaliana undergoing HR. The 16 S-nitrosylated proteins identified are mostly enzymes serving intermediary......Nitric oxide (NO) has a fundamental role in the plant hypersensitive disease resistance response (HR), and S-nitrosylation is emerging as an important mechanism for the transduction of its bioactivity. A key step toward elucidating the mechanisms by which NO functions during the HR...... metabolism, signaling and antioxidant defense. The study of the effects of S-nitrosylation on the activity of the identified proteins and its role during the execution of the disease resistance response will help to understand S-nitrosylation function and significance in plants....

  4. Hypersensitivity Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

    2015-01-01

    Immune-mediated tissue damage or hypersensitivity can be mediated by autospecific IgG antibodies. Pathology results from activation of complement, and antibody-dependent cellular cytotoxicity, mediated by inflammatory effector leukocytes include macrophages, natural killer cells, and granulocytes...... as a therapy for NMO, NMO-like pathology is significantly reduced in mice lacking the Type I IFN receptor. In MS, there is evidence for intrathecal synthesis of antibodies as well as blood-brain barrier (BBB) breakdown, whereas in NMO, IgG accesses the CNS from blood. Transfer models involve either direct...

  5. A quick and robust method for quantification of the hypersensitive response in plants

    Directory of Open Access Journals (Sweden)

    Oskar N. Johansson

    2015-12-01

    Full Text Available One of the most studied defense reactions of plants against microbial pathogens is the hypersensitive response (HR. The HR is a complex multicellular process that involves programmed cell death at the site of infection. A standard method to quantify plant defense and the HR is to measure the release of cellular electrolytes into water after infiltration with pathogenic bacteria. In this type of experiment, the bacteria are typically delivered into the plant tissue through syringe infiltration. Here we report the development of a vacuum infiltration protocol that allows multiple plant lines to be infiltrated simultaneously and assayed for defense responses. Vacuum infiltration did not induce more wounding response in Arabidopsis leaf tissue than syringe inoculation, whereas throughput and reproducibility were improved. The method was used to study HR-induced electrolyte loss after treatment with the bacterium Pseudomonas syringae pv. tomato DC3000 harboring the effector AvrRpm1, AvrRpt2 or AvrRps4. Specifically, the influence of bacterial titer on AvrRpm1-induced HR was investigated. Not only the amplitude, but also the timing of the maximum rate of the HR reaction was found to be dose-dependent. Finally, using vacuum infiltration, we were able quantify induction of phospholipase D activity after AvrRpm1 recognition in leaves labeled with 33PO4.

  6. Prevalence Of Dentine Hypersensitivity And Its Response To Non ...

    African Journals Online (AJOL)

    Ebonyi Medical Journal ... Objective This study aims to determine the prevalence of tooth hypersensitivity and its response to non-surgical treatment modalities at the Periodontics Clinic of the University of Benin Teaching Hospital (UBTH), Benin City. ... All clinical oral examinations were carried out at the Periodontics clinic.

  7. Ralstonia solanacearum type III secretion system effector Rip36 induces a hypersensitive response in the nonhost wild eggplant Solanum torvum.

    Science.gov (United States)

    Nahar, Kamrun; Matsumoto, Iyo; Taguchi, Fumiko; Inagaki, Yoshishige; Yamamoto, Mikihiro; Toyoda, Kazuhiro; Shiraishi, Tomonori; Ichinose, Yuki; Mukaihara, Takafumi

    2014-04-01

    Ralstonia solanacearum is a Gram-negative soil-borne bacterium that causes bacterial wilt disease in more than 200 plant species, including economically important Solanaceae species. In R. solanacearum, the hypersensitive response and pathogenicity (Hrp) type III secretion system is required for both the ability to induce the hypersensitive response (HR) in nonhost plants and pathogenicity in host plants. Recently, 72 effector genes, called rip (Ralstonia protein injected into plant cells), have been identified in R. solanacearum RS1000. RS1002, a spontaneous nalixidic acid-resistant derivative of RS1000, induced strong HR in the nonhost wild eggplant Solanum torvum in an Hrp-dependent manner. An Agrobacterium-mediated transient expression system revealed that Rip36, a putative Zn-dependent protease effector of R. solanacearum, induced HR in S. torvum. A mutation in the putative Zn-binding motif (E149A) completely abolished the ability to induce HR. In agreement with this result, the RS1002-derived Δrip36 and rip36E149A mutants lost the ability to induce HR in S. torvum. An E149A mutation had no effect on the translocation of Rip36 into plant cells. These results indicate that Rip36 is an avirulent factor that induces HR in S. torvum and that a putative Zn-dependent protease motif is essential for this activity.

  8. Regulation of murine hypersensitive responses by Fc receptors

    Directory of Open Access Journals (Sweden)

    Toshiyuki Takai

    1998-01-01

    Full Text Available Humoral and cellular immune responses communicate with each other via Fc receptors (FcR expressed on various hematopoietic cells. Recent studies on several FcR knockout mice demonstrated pivotal roles of an IgG/FcγR system in the regulation of immune responses and the onset of hypersensitivity. The γ subunit of FcR is an essential component of the complex and is required for both receptor assembly and signal transduction. FcR γ chain-deficient mice have lost the functional expression of FcεRI, FcγRI, and FcγRIII and are unable to mount several types of hypersensitive reactions, including the skin Arthus reaction. In contrast, FcγRII-deficient mice exhibit augmented humoral immune responses and IgG-mediated anaphylaxis reactions. Thus, the regulatory system of murine hypersensitive responses involves both positive and negative signaling through FcR. In B cells, FcγRIIb modulates membrane Ig-induced Ca2+ mobilization by inhibiting Ca2+ influx through phosphorylation of its immunoreceptor tyrosine-based inhibition motif and recruitment of cytoplasmic phosphatases. Elucidation of the detailed mechanisms of negative regulatory signaling in the inflammatory effector cells by FcγRIIb as well as several groups of potent inhibitory molecules expressed on such cells should be valuable in the development of novel therapeutic procedures for allergic disorders.

  9. Differential responses of primary auditory cortex in autistic spectrum disorder with auditory hypersensitivity.

    Science.gov (United States)

    Matsuzaki, Junko; Kagitani-Shimono, Kuriko; Goto, Tetsu; Sanefuji, Wakako; Yamamoto, Tomoka; Sakai, Saeko; Uchida, Hiroyuki; Hirata, Masayuki; Mohri, Ikuko; Yorifuji, Shiro; Taniike, Masako

    2012-01-25

    The aim of this study was to investigate the differential responses of the primary auditory cortex to auditory stimuli in autistic spectrum disorder with or without auditory hypersensitivity. Auditory-evoked field values were obtained from 18 boys (nine with and nine without auditory hypersensitivity) with autistic spectrum disorder and 12 age-matched controls. Autistic disorder with hypersensitivity showed significantly more delayed M50/M100 peak latencies than autistic disorder without hypersensitivity or the control. M50 dipole moments in the hypersensitivity group were larger than those in the other two groups [corrected]. M50/M100 peak latencies were correlated with the severity of auditory hypersensitivity; furthermore, severe hypersensitivity induced more behavioral problems. This study indicates auditory hypersensitivity in autistic spectrum disorder as a characteristic response of the primary auditory cortex, possibly resulting from neurological immaturity or functional abnormalities in it. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  10. Differences in intensity and specificity of hypersensitive response induction in Nicotiana spp. by INF1, INF2A, and INF2B of Phytophthora infestans

    NARCIS (Netherlands)

    Huitema, E.; Vleeshouwers, V.G.A.A.; Cakir, C.; Kamoun, S.; Govers, F.

    2005-01-01

    Elicitins form a family of structurally related proteins that induce the hypersensitive response (HR) in plants, particularly Nicotiana spp. The elicitin family is composed of several classes. Most species of the plant-pathogenic oomycete genus Phytophthora produce the well-characterized 10-kDa

  11. The Xanthomonas effector XopJ triggers a conditional hypersensitive response upon treatment of N. benthamiana leaves with salicylic acid

    Directory of Open Access Journals (Sweden)

    Suayib eÜstün

    2015-08-01

    Full Text Available XopJ is a Xanthomonas type III effector protein that promotes bacterial virulence on susceptible pepper plants through the inhibition of the host cell proteasome and a resultant suppression of salicylic acid (SA – dependent defense responses. We show here that Nicotiana benthamiana leaves transiently expressing XopJ display hypersensitive response (HR –like symptoms when exogenously treated with SA. This apparent avirulence function of XopJ was further dependent on effector myristoylation as well as on an intact catalytic triad, suggesting a requirement of its enzymatic activity for HR-like symptom elicitation. The ability of XopJ to cause a HR-like symptom development upon SA treatment was lost upon silencing of SGT1 and NDR1, respectively, but was independent of EDS1 silencing, suggesting that XopJ is recognized by an R protein of the CC-NBS-LRR class. Furthermore, silencing of NPR1 abolished the elicitation of HR-like symptoms in XopJ expressing leaves after SA application. Measurement of the proteasome activity indicated that proteasome inhibition by XopJ was alleviated in the presence of SA, an effect that was not observed in NPR1 silenced plants. Our results suggest that XopJ - triggered HR-like symptoms are closely related to the virulence function of the effector and that XopJ follows a two-signal model in order to elicit a response in the non-host plant N. benthamiana.

  12. Capsicum annuum WRKY transcription factor d (CaWRKYd) regulates hypersensitive response and defense response upon Tobacco mosaic virus infection.

    Science.gov (United States)

    Huh, Sung Un; Choi, La Mee; Lee, Gil-Je; Kim, Young Jin; Paek, Kyung-Hee

    2012-12-01

    WRKY transcription factors regulate biotic, abiotic, and developmental processes. In terms of plant defense, WRKY factors have important roles as positive and negative regulators via transcriptional regulation or protein-protein interaction. Here, we report the characterization of the gene encoding Capsicum annuum WRKY transcription factor d (CaWRKYd) isolated from microarray analysis in the Tobacco mosaic virus (TMV)-P(0)-inoculated hot pepper plants. CaWRKYd belongs to the WRKY IIa group, a very small clade in the WRKY subfamily, and WRKY IIa group has positive/negative regulatory roles in Arabidopsis and rice. CaWRKYd transcripts were induced by various plant defense-related hormone treatments and TMV-P(0) inoculation. Silencing of CaWRKYd affected TMV-P(0)-mediated hypersensitive response (HR) cell death and accumulation of TMV-P(0) coat protein in local and systemic leaves. Furthermore, expression of some pathogenesis-related (PR) genes and HR-related genes was reduced in the CaWRKYd-silenced plants compared with TRV2 vector control plants upon TMV-P(0) inoculation. CaWRKYd was confirmed to bind to the W-box. Thus CaWRKYd is a newly identified Capsicum annuum WRKY transcription factor that appears to be involved in TMV-P(0)-mediated HR cell death by regulating downstream gene expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Effects of bacterial populations, temperature and exogenous hydrogen peroxide on the induction of the hypersensitive response in Nicotiana tabacum against Xanthomonas perforans

    Directory of Open Access Journals (Sweden)

    Farahani Ali Safaie

    2017-06-01

    Full Text Available The objective of this study was to investigate the effects of inoculum concentration, plant post-inoculation incubation temperature and exogenous hydrogen peroxide (H2O2 on the induction of the hypersensitive response (HR in Nicotiana tabacum against Xanthomonas perforans. Inoculation of leaves with X. perforans at a concentration of 108 CFU · ml−1 and incubation of plants at 30°C resulted in the strongest HR elicitation. Furthermore, an exogenous supply of H2O2 accelerated X. perforans-induced HR, whereas in planta H2O2 removal by application of catalase led to a delay in HR development. Our data suggest that H2O2 has an important role in HR of N. tabacum against X. perforans.

  14. Calcium is involved in the R Mc1 (blb)-mediated hypersensitive response against Meloidogyne chitwoodi in potato.

    Science.gov (United States)

    Davies, Laura J; Brown, Charles R; Elling, Axel A

    2015-01-01

    Functional characterization of the Columbia root-knot nematode resistance gene R Mc1 ( blb ) in potato revealed the R gene-mediated resistance is dependent on a hypersensitive response and involves calcium. The resistance (R) gene R Mc1(blb) confers resistance against the plant-parasitic nematode, Meloidogyne chitwoodi. Avirulent and virulent nematodes were used to functionally characterize the R Mc1(blb)-mediated resistance mechanism in potato (Solanum tuberosum). Histological observations indicated a hypersensitive response (HR) occurred during avirulent nematode infection. This was confirmed by quantifying reactive oxygen species activity in response to avirulent and virulent M. chitwoodi. To gain an insight into the signal transduction pathways mediating the R Mc1(blb)-induced HR, chemical inhibitors were utilized. Inhibiting Ca(2+) channels caused a significant reduction in electrolyte leakage, an indicator of cell death. Labeling with a Ca(2+)-sensitive dye revealed high Ca(2+) levels in the root cells surrounding avirulent nematodes. Furthermore, the calcium-dependent protein kinase (CDPK), StCDPK4 had a higher transcript level in R Mc1(blb) potato roots infected with avirulent nematodes in comparison to roots infected with virulent M. chitwoodi. The results of this study indicate Ca(2+) plays a role in the R Mc1(blb)-mediated resistance against M. chitwoodi in potato.

  15. Heritability of HR and BP Response To Exercise Training in the HERITAGE Family Study.

    Science.gov (United States)

    Rice, Treva; Gagnon, Jacques; Leon, Arthur S.; Skinner, James S.; Wilmore, Jack H.; Bouchard, Claude; Rao, D. C.

    2002-01-01

    Assessed the heritability of response to exercise training in resting blood pressure (BP) and heart rate (HR) among sedentary Caucasians comprising 98 families who completed an exercise training program. Results indicated that the trainability of systolic BP and HR in families with elevated BP was partially determined by genetic factors. Diastolic…

  16. Live Imaging of the Skin Immune Responses: Visualization of the Contact Hypersensitivity Response.

    Science.gov (United States)

    Egawa, Gyohei; Honda, Tetsuya; Kabashima, Kenji

    2018-01-01

    A variety of immune cells are involved in cutaneous immune responses. Over the last decade, intravital imaging has become an important technique used to capture the dynamic behavior of immune cells in the physiological context. In this chapter, we describe essential techniques for visualizing immune cells in the skin, focusing on the contact hypersensitivity response. Using fluorescent dyes and transgenic reporter animals, many kinds of immune cells and skin components can be visualized in three dimensions and in a noninvasive manner.

  17. Ant allergens and hypersensitivity reactions in response to ant stings.

    Science.gov (United States)

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

    Hypersensitivity reactions caused by ant stings are increasingly recognized as an important cause of death by anaphylaxis. Only some species of ants ( e.g. Solenopsis spp., Myrmecia spp., and Pachycondyla spp.) cause allergic reactions. Ant species are identified by evaluating the morphologic structures of worker ants or by molecular techniques. Ant venom contains substances, including acids and alkaloids, that cause toxic reactions, and those from Solenopsis invicta or the imported fire ant have been widely studied. Piperidine alkaloids and low protein contents can cause local reactions (sterile pustules) and systemic reactions (anaphylaxis). Imported fire ant venoms are cross-reactive; for example, the Sol i 1 allergen from S. invicta has cross-reactivity with yellow jacket phospholipase. The Sol i 3 allergen is a member of the antigen 5 family that has amino acid sequence identity with vespid antigen 5. The clinical presentations of ant hypersensitivity are categorized into immediate and delayed reactions: immediate reactions, such as small local reactions, large local reactions, and systemic reactions, occur within 1-4 hours after the ant stings, whereas delayed reactions, such as serum sickness and vasculitis, usually occur more than 4 hours after the stings. Tools for the diagnosis of ant hypersensitivity are skin testing, serum specific IgE, and sting challenge tests. Management of ant hypersensitivity can be divided into immediate (epinephrine, corticosteroids), symptomatic (antihistamines, bronchodilators), supportive (fluid resuscitation, oxygen therapy), and preventive (re-sting avoidance and immunotherapy) treatments.

  18. Humoral immune response and delayed type hypersensitivity to influenza vaccine in patients with diabetes mellitus

    NARCIS (Netherlands)

    R.J.A. Diepersloot (Rob); K.P. Bouter (Karel Paul); W.E.Ph. Beyer (Walter); N. Masurel (Nic); J.B. Hoekstra

    1987-01-01

    textabstractThe antibody response and delayed type hypersensitivity reaction to commercially available trivalent influenza vaccine in 159 patients with diabetes mellitus was compared with response and reaction in 28 healthy volunteers. A correction for prevaccination titres was made. No differences

  19. De novo foliar transcriptome of Chenopodium amaranticolor and analysis of its gene expression during virus-induced hypersensitive response.

    Science.gov (United States)

    Zhang, Yongqiang; Pei, Xinwu; Zhang, Chao; Lu, Zifeng; Wang, Zhixing; Jia, Shirong; Li, Weimin

    2012-01-01

    The hypersensitive response (HR) system of Chenopodium spp. confers broad-spectrum virus resistance. However, little knowledge exists at the genomic level for Chenopodium, thus impeding the advanced molecular research of this attractive feature. Hence, we took advantage of RNA-seq to survey the foliar transcriptome of C. amaranticolor, a Chenopodium species widely used as laboratory indicator for pathogenic viruses, in order to facilitate the characterization of the HR-type of virus resistance. Using Illumina HiSeq™ 2000 platform, we obtained 39,868,984 reads with 3,588,208,560 bp, which were assembled into 112,452 unigenes (3,847 clusters and 108,605 singletons). BlastX search against the NCBI NR database identified 61,698 sequences with a cut-off E-value above 10(-5). Assembled sequences were annotated with gene descriptions, GO, COG and KEGG terms, respectively. A total number of 738 resistance gene analogs (RGAs) and homology sequences of 6 key signaling proteins within the R proteins-directed signaling pathway were identified. Based on this transcriptome data, we investigated the gene expression profiles over the stage of HR induced by Tobacco mosaic virus and Cucumber mosaic virus by using digital gene expression analysis. Numerous candidate genes specifically or commonly regulated by these two distinct viruses at early and late stages of the HR were identified, and the dynamic changes of the differently expressed genes enriched in the pathway of plant-pathogen interaction were particularly emphasized. To our knowledge, this study is the first description of the genetic makeup of C. amaranticolor, providing deep insight into the comprehensive gene expression information at transcriptional level in this species. The 738 RGAs as well as the differentially regulated genes, particularly the common genes regulated by both TMV and CMV, are suitable candidates which merit further functional characterization to dissect the molecular mechanisms and regulatory

  20. Revealing the importance of meristems and roots for the development of hypersensitive responses and full foliar resistance to Phytophthora infestans in the resistant potato cultivar Sarpo Mira

    DEFF Research Database (Denmark)

    Orlowska, Elzbieta Zofia; Basile, Alessio; Kandzia, Izabela

    2012-01-01

    The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots a......-associated compounds that increase systemic resistance. Based on the literature and on the presented results, a model is proposed for mechanisms involved in Sarpo Mira resistance that may apply to other resistant potato cultivars......The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots....... Additionally, the antimicrobial activity of plant extracts was assessed. The presented data show that roots are needed to achieve full pathogen resistance, that the removal of meristems in detached leaves inhibits the formation of HR lesions, that PR genes are differentially regulated in detached leaves...

  1. Host Defenses in Experimental Scrub Typhus: Delayed-Type Hypersensitivity Responses of Inbred Mice

    OpenAIRE

    Jerrells, Thomas R.; Osterman, Joseph V.

    1982-01-01

    Delayed-type hypersensitivity responses of inbred mice during the course of lethal and chronic infections with strains of Rickettsia tsutsugamushi were evaluated by using the influx of radiolabeled cells into antigen-injected ears. Congenic strains of C3H mice, which previously have been shown to be resistant (C3H/RV) or sensitive (C3H/HeDub) to lethal intraperitoneal infection with the Gilliam strain of rickettsiae, both expressed delayed-type hypersensitivity early in the course of infectio...

  2. Methanosphaera stadtmanae induces a type IV hypersensitivity response in a mouse model of airway inflammation.

    Science.gov (United States)

    Bernatchez, Emilie; Gold, Matthew J; Langlois, Anick; Blais-Lecours, Pascale; Boucher, Magali; Duchaine, Caroline; Marsolais, David; McNagny, Kelly M; Blanchet, Marie-Renée

    2017-04-01

    Despite improved awareness of work-related diseases and preventive measures, many workers are still at high risk of developing occupational hypersensitivity airway diseases. This stems from a lack of knowledge of bioaerosol composition and their potential effects on human health. Recently, archaea species were identified in bioaerosols, raising the possibility that they play a major role in exposure-related pathology. Specifically, Methanosphaera stadtmanae (MSS) and Methanobrevibacter smithii (MBS) are found in high concentrations in agricultural environments and respiratory exposure to crude extract demonstrates immunomodulatory activity in mice. Nevertheless, our knowledge of the specific impact of methanogens exposure on airway immunity and their potential to induce airway hypersensitivity responses in workers remains scant. Analysis of the lung mucosal response to methanogen crude extracts in mice demonstrated that MSS and MBS predominantly induced TH17 airway inflammation, typical of a type IV hypersensitivity response. Furthermore, the response to MSS was associated with antigen-specific IgG1 and IgG2a production. However, despite the presence of eosinophils after MSS exposure, only a weak TH2 response and no airway hyperresponsiveness were observed. Finally, using eosinophil and mast cell-deficient mice, we confirmed that these cells are dispensable for the TH17 response to MSS, although eosinophils likely contribute to the exacerbation of inflammatory processes induced by MSS crude extract exposure. We conclude that, as MSS induces a clear type IV hypersensitivity lung response, it has the potential to be harmful to workers frequently exposed to this methanogen, and that preventive measures should be taken to avoid chronic hypersensitivity disease development in workers. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Characterization of the draining lymph node response in the mouse drug allergy model: A model for drug hypersensitivity reactions.

    Science.gov (United States)

    Zhu, Xu; Cole, Susan H; Kawabata, Thomas T; Whritenour, Jessica

    2015-01-01

    The mouse drug allergy model (MDAM) was developed as a tool to predict the potential of systemically administered drugs to produce hypersensitivity reactions (HR). Drugs associated with HR in the clinic produce a marked increase in the cellularity of the draining lymph nodes (DLN) in the MDAM. The objective of this study was to characterize the changes in the DLN following exposure to drugs associated with HR and to investigate whether lymphocyte migration and/or proliferation play a role in the response. These endpoints were also investigated in the local lymph node assay (LLNA) to determine whether responses between the two assays occur via similar mechanisms. Results demonstrated that total numbers of T- and B-cells were proportionally increased in the DLN of mice treated with positive control drugs (i.e. abacavir, amoxicillin, ofloxacin, and sulfamethoxazole) compared to animals administered the vehicle or negative control drugs (metformin and cimetidine). In contrast, a significant increase in the B-cell population of the DLN was observed for 2,4-dinitrofluorobenzene (DNFB) following the LLNA protocol. Down-regulation of CD62L and up-regulation of CCR7 were observed for T-cells from the DLN of the positive control treated mice in the MDAM, but not with DNFB in the LLNA. A mild increase in T-cell proliferation was observed in the MDAM with positive control drugs, while DNFB in the LLNA induced proliferation within the B-cell population only. Anti-CD40L antibody administration inhibited MDAM responses to positive control drugs, but did not affect DNFB-induced increases in total cell number in the LLNA. These results suggest that the increased cellularity of the DLN in the MDAM may be the result of drug-induced alterations in lymphocyte migration and/or effects on lymphocyte proliferation. Moreover, it appears that different mechanisms may be involved in driving the MDAM and LLNA responses.

  4. Elicitation of hypersensitive responses in Nicotiana glutinosa by the suppressor of RNA silencing protein P0 from poleroviruses.

    Science.gov (United States)

    Wang, Ken-Der; Empleo, Roman; Nguyen, Tan Tri V; Moffett, Peter; Sacco, Melanie Ann

    2015-06-01

    Plant disease resistance (R) proteins that confer resistance to viruses recognize viral gene products with diverse functions, including viral suppressors of RNA silencing (VSRs). The P0 protein from poleroviruses is a VSR that targets the ARGONAUTE1 (AGO1) protein for degradation, thereby disrupting RNA silencing and antiviral defences. Here, we report resistance against poleroviruses in Nicotiana glutinosa directed against Turnip yellows virus (TuYV) and Potato leafroll virus (PLRV). The P0 proteins from TuYV (P0(T) (u) ), PLRV (P0(PL) ) and Cucurbit aphid-borne yellows virus (P0(CA) ) were found to elicit a hypersensitive response (HR) in N. glutinosa accession TW59, whereas other accessions recognized P0(PL) only. Genetic analysis showed that recognition of P0(T) (u) by a resistance gene designated RPO1 (Resistance to POleroviruses 1) is inherited as a dominant allele. Expression of P0 from a Potato virus X (PVX) expression vector transferred recognition to the recombinant virus on plants expressing RPO1, supporting P0 as the unique Polerovirus factor eliciting resistance. The induction of HR required a functional P0 protein, as P0(T) (u) mutants with substitutions in the F-box motif that abolished VSR activity were unable to elicit HR. We surmised that the broad P0 recognition seen in TW59 and the requirement for the F-box protein motif could indicate detection of P0-induced AGO1 degradation and disruption of RNA silencing; however, other viral silencing suppressors, including the PVX P25 that also causes AGO1 degradation, failed to elicit HR in N. glutinosa. Investigation of P0 elicitation of RPO1 could provide insight into P0 activities within the cell that trigger resistance. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  5. HR Connect

    Data.gov (United States)

    US Agency for International Development — HR Connect is the USAID HR personnel system which allows HR professionals to process HR actions related to employee's personal and position information. This system...

  6. TaAbc1, a Member of Abc1-Like Family Involved in Hypersensitive Response against the Stripe Rust Fungal Pathogen in Wheat

    Science.gov (United States)

    Wang, Xiaojing; Wang, Xiaojie; Duan, Yinghui; Yin, Shuining; Zhang, Hongchang; Huang, Li; Kang, Zhensheng

    2013-01-01

    To search for genes involved in wheat (Triticum aestivum L.) defense response to the infection of stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst), we identified and cloned a new wheat gene similar to the genes in the Abc1-like gene family. The new gene, designated as TaAbc1, encodes a 717-amino acid, 80.35 kD protein. The TaAbc1 protein contains two conserved domains shared by Abc1-like proteins, two trans-membrane domains at the C-terminal, and a 36-amino acid chloroplast targeting presequence at the N-terminal. Characterization of TaAbc1 expression revealed that gene expression was tissue-specific and could be up-regulated by biotic agents (e.g., stripe rust pathogen) and/or by an abiotic stress like wounding. High-fold induction was associated with the hypersensitive response (HR) triggered only by avirulent stripe rust pathotypes, suggesting that TaAbc1 is a rust-pathotype specific HR-mediator. Down-regulating TaAbc1 reduced HR but not the overall resistance level in Suwon11 to CYR23, suggesting TaAbc1 was involved in HR against stripe rust, but overall host resistance is not HR-dependent. PMID:23527058

  7. High cytokinin levels induce a hypersensitive-like response in tobacco.

    Science.gov (United States)

    Novák, Jan; Pavlů, Jaroslav; Novák, Ondřej; Nožková-Hlaváčková, Vladimíra; Špundová, Martina; Hlavinka, Jan; Koukalová, Šárka; Skalák, Jan; Černý, Martin; Brzobohatý, Břetislav

    2013-07-01

    Cytokinins are positive regulators of shoot development. However, it has previously been demonstrated that efficient activation of the cytokinin biosynthesis gene ipt can cause necrotic lesions and wilting in tobacco leaves. Some plant pathogens reportedly use their ability to produce cytokinins in disease development. In response to pathogen attacks, plants can trigger a hypersensitive response that rapidly kills cells near the infection site, depriving the pathogen of nutrients and preventing its spread. In this study, a diverse set of processes that link ipt activation to necrotic lesion formation were investigated in order to evaluate the potential of cytokinins as signals and/or mediators in plant defence against pathogens. The binary pOp-ipt/LhGR system for dexamethasone-inducible ipt expression was used to increase endogenous cytokinin levels in transgenic tobacco. Changes in the levels of cytokinins and the stress hormones salicylic, jasmonic and abscisic acid following ipt activation were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS). Trends in hydrogen peroxide content and lipid peroxidation were monitored using the potassium iodide and malondialdehyde assays. The subcellular distribution of hydrogen peroxide was investigated using 3,3'-diaminobenzidine staining. The dynamics of transcripts related to photosynthesis and pathogen response were analysed by reverse transcription followed by quantitative PCR. The effects of cytokinins on photosynthesis were deciphered by analysing changes in chlorophyll fluorescence and leaf gas exchange. Plants can produce sufficiently high levels of cytokinins to trigger fast cell death without any intervening chlorosis - a hallmark of the hypersensitive response. The results suggest that chloroplastic hydrogen peroxide orchestrates the molecular responses underpinning the hypersensitive-like response, including the inhibition of photosynthesis, elevated levels of

  8. Artificial Agrobacterium tumefaciens strains exhibit diverse mechanisms to repress Xanthomonas oryzae pv. oryzae-induced hypersensitive response and non-host resistance in Nicotiana benthamiana.

    Science.gov (United States)

    Li, Wen; Cao, Jia-Yi; Xu, You-Ping; Cai, Xin-Zhong

    2017-05-01

    Xanthomonas oryzae pv. oryzae (Xoo) rapidly triggers a hypersensitive response (HR) and non-host resistance in its non-host plant Nicotiana benthamiana. Here, we report that Agrobacterium tumefaciens strain GV3101 blocks Xoo-induced HR in N. benthamiana when pre-infiltrated or co-infiltrated, but not when post-infiltrated at 4 h after Xoo inoculation. This suppression by A. tumefaciens is local and highly efficient to Xoo. The HR-inhibiting efficiency of A. tumefaciens is strain dependent. Strain C58C1 has almost no effect on Xoo-induced HR, whereas strains GV3101, EHA105 and LBA4404 nearly completely block HR formation. Intriguingly, these three HR-inhibiting strains employ different strategies to repress HR. Strain GV3101 displays strong antibiotic activity and thus suppresses Xoo growth. Comparison of the genotype and Xoo antibiosis activity of wild-type A. tumefaciens strain C58 and a set of C58-derived strains reveals that this Xoo antibiosis activity of A. tumefaciens is negatively, but not solely, regulated by the transferred-DNA (T-DNA) of the Ti plasmid pTiC58. Unlike GV3101, strains LBA4404 and EHA105 exhibit no significant antibiotic effect on Xoo, but rather abolish hydrogen peroxide accumulation. In addition, expression assays indicate that strains LBA4404 and EHA105 may inhibit Xoo-induced HR by suppression of the expression of Xoo type III secretion system (T3SS) effector genes hpa1 and hrpD6. Collectively, our results unveil the multiple levels of effects of A. tumefaciens on Xoo in N. benthamiana and provide insights into the molecular mechanisms underlying the bacterial antibiosis of A. tumefaciens and the non-host resistance induced by Xoo. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  9. De novo foliar transcriptome of Chenopodium amaranticolor and analysis of its gene expression during virus-induced hypersensitive response.

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    Yongqiang Zhang

    Full Text Available BACKGROUND: The hypersensitive response (HR system of Chenopodium spp. confers broad-spectrum virus resistance. However, little knowledge exists at the genomic level for Chenopodium, thus impeding the advanced molecular research of this attractive feature. Hence, we took advantage of RNA-seq to survey the foliar transcriptome of C. amaranticolor, a Chenopodium species widely used as laboratory indicator for pathogenic viruses, in order to facilitate the characterization of the HR-type of virus resistance. METHODOLOGY AND PRINCIPAL FINDINGS: Using Illumina HiSeq™ 2000 platform, we obtained 39,868,984 reads with 3,588,208,560 bp, which were assembled into 112,452 unigenes (3,847 clusters and 108,605 singletons. BlastX search against the NCBI NR database identified 61,698 sequences with a cut-off E-value above 10(-5. Assembled sequences were annotated with gene descriptions, GO, COG and KEGG terms, respectively. A total number of 738 resistance gene analogs (RGAs and homology sequences of 6 key signaling proteins within the R proteins-directed signaling pathway were identified. Based on this transcriptome data, we investigated the gene expression profiles over the stage of HR induced by Tobacco mosaic virus and Cucumber mosaic virus by using digital gene expression analysis. Numerous candidate genes specifically or commonly regulated by these two distinct viruses at early and late stages of the HR were identified, and the dynamic changes of the differently expressed genes enriched in the pathway of plant-pathogen interaction were particularly emphasized. CONCLUSIONS: To our knowledge, this study is the first description of the genetic makeup of C. amaranticolor, providing deep insight into the comprehensive gene expression information at transcriptional level in this species. The 738 RGAs as well as the differentially regulated genes, particularly the common genes regulated by both TMV and CMV, are suitable candidates which merit further

  10. Dufulin activates HrBP1 to produce antiviral responses in tobacco.

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    Zhuo Chen

    Full Text Available BACKGROUND: Dufulin is a new antiviral agent that is highly effective against plant viruses and acts by activating systemic acquired resistance (SAR in plants. In recent years, it has been used widely to prevent and control tobacco and rice viral diseases in China. However, its targets and mechanism of action are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, differential in-gel electrophoresis (DIGE and classical two-dimensional electrophoresis (2-DE techniques were combined with mass spectrometry (MS to identify the target of Dufulin. More than 40 proteins were found to be differentially expressed (≥1.5 fold or ≤1.5 fold upon Dufulin treatment in Nicotiana tabacum K(326. Based on annotations in the Gene Ontology (GO and the Kyoto Encyclopedia of Genes and Genomes (KEGG databases, these proteins were found to be related to disease resistance. Directed acyclic graph (DAG analysis of the various pathways demonstrated harpin binding protein-1 (HrBP1 as the target of action of Dufulin. Additionally, western blotting, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR, and real time PCR analyses were also conducted to identify the specific mechanism of action of Dufulin. Our results show that activation of HrBP1 triggers the salicylic acid (SA signaling pathway and thereby produces antiviral responses in the plant host. A protective assay based on lesion counting further confirmed the antiviral activity of Dufulin. CONCLUSION: This study identified HrBP1 as a target protein of Dufulin and that Dufulin can activate the SA signaling pathway to induce host plants to generate antiviral responses.

  11. Dufulin activates HrBP1 to produce antiviral responses in tobacco.

    Science.gov (United States)

    Chen, Zhuo; Zeng, Mengjiao; Song, Baoan; Hou, Chengrui; Hu, Deyu; Li, Xiangyang; Wang, Zhenchao; Fan, Huitao; Bi, Liang; Liu, Jiaju; Yu, Dandan; Jin, Linhong; Yang, Song

    2012-01-01

    Dufulin is a new antiviral agent that is highly effective against plant viruses and acts by activating systemic acquired resistance (SAR) in plants. In recent years, it has been used widely to prevent and control tobacco and rice viral diseases in China. However, its targets and mechanism of action are still poorly understood. Here, differential in-gel electrophoresis (DIGE) and classical two-dimensional electrophoresis (2-DE) techniques were combined with mass spectrometry (MS) to identify the target of Dufulin. More than 40 proteins were found to be differentially expressed (≥1.5 fold or ≤1.5 fold) upon Dufulin treatment in Nicotiana tabacum K(326). Based on annotations in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, these proteins were found to be related to disease resistance. Directed acyclic graph (DAG) analysis of the various pathways demonstrated harpin binding protein-1 (HrBP1) as the target of action of Dufulin. Additionally, western blotting, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and real time PCR analyses were also conducted to identify the specific mechanism of action of Dufulin. Our results show that activation of HrBP1 triggers the salicylic acid (SA) signaling pathway and thereby produces antiviral responses in the plant host. A protective assay based on lesion counting further confirmed the antiviral activity of Dufulin. This study identified HrBP1 as a target protein of Dufulin and that Dufulin can activate the SA signaling pathway to induce host plants to generate antiviral responses.

  12. Functional regions of HpaXm as elicitors with specific heat tolerance induce the hypersensitive response or plant growth promotion in nonhost plants.

    Science.gov (United States)

    Liu, Yue; Zhou, Xiaoyun; Liu, Wenbo; Xiong, Xiaohui; Lv, Chuyang; Zhou, Xiang; Miao, Weiguo

    2018-01-01

    HpaXm produced by the cotton leaf blight bacterium Xanthomonas citri subsp. malvacearum is a novel harpin elicitor of the induced hypersensitive response (HR) in tobacco. We investigated whether fragments of HpaXm, compared with fragments of Hpa1Xoo, are sufficient for HR or plant growth promotion (PGP) elicitation using four synthetic peptides (HpaXm35-51, HpaXm10-39, Hpa1Xoo36-52 and Hpa1Xoo10-40). We also heated the fragments to determine the heat tolerance of the functional fragments. HpaXm35-51 and Hpa1Xoo36-52 induced hypersensitive response (HR). Bursts of reactive oxygen intermediates (ROI) induced by HpaXm35-51 and Hpa1Xoo36-52 were earlier and stronger than those induced by HpaXm and Hpa1Xoo. In plants treated with HpaXm35-51 or Hpa1Xoo36-52, the expression of the HR marker genes Hin1 and Hsr203J and the active oxygen metabolism related gene AOX were significantly upregulated. These findings suggest that the predicted α-helical structures of the HpaXm35-51 and Hpa1Xoo36-52 fragments are crucial for HR. PGP result by soaking seeds in unheated/heated HpaXm10-39 or Hpa1Xoo10-40 solution prior to transfer, which obviously enhances root growth and the aerial parts of plants. The PGP related gene NtEXP6 was greatly enhanced when plants were sprayed with a solution of HpaXm10-39 or Hpa1Xoo10-40; heated fragment treatments induced higher levels of NtEXP6 expression than unheated HpaXm fragments. In addition, HR marker genes induced by the heated fragments had lower expression levels than when induced with unheated HpaXm fragments. Moreover, the expression levels of HR marker genes and PGP related genes induced by treatment with Hpa1Xoo fragments before or after heating were the opposite of those induced by HpaXm fragments. Different functional fragments of harpin and different harpins with the same functional region have different degrees of heat tolerance. Therefore, the heat resistance of harpin is conservative, but the degree of heat tolerance of the

  13. Sulfate supply influences compartment specific glutathione metabolism and confers enhanced resistance to Tobacco mosaic virus during a hypersensitive response

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    Király, Lóránt; Künstler, András; Höller, Kerstin; Fattinger, Maria; Juhász, Csilla; Müller, Maria; Gullner, Gábor; Zechmann, Bernd

    2012-01-01

    Sufficient sulfate supply has been linked to the development of sulfur induced resistance or sulfur enhanced defense (SIR/SED) in plants. In this study we investigated the effects of sulfate (S) supply on the response of genetically resistant tobacco (Nicotiana tabacum cv. Samsun NN) to Tobacco mosaic virus (TMV). Plants grown with sufficient sulfate (+S plants) developed significantly less necrotic lesions during a hypersensitive response (HR) when compared to plants grown without sulfate (−S plants). In +S plants reduced TMV accumulation was evident on the level of viral RNA. Enhanced virus resistance correlated with elevated levels of cysteine and glutathione and early induction of a Tau class glutathione S-transferase and a salicylic acid-binding catalase gene. These data indicate that the elevated antioxidant capacity of +S plants was able to reduce the effects of HR, leading to enhanced virus resistance. Expression of pathogenesis-related genes was also markedly up-regulated in +S plants after TMV-inoculation. On the subcellular level, comparison of TMV-inoculated +S and −S plants revealed that +S plants contained 55–132 % higher glutathione levels in mitochondria, chloroplasts, nuclei, peroxisomes and the cytosol than −S plants. Interestingly, mitochondria were the only organelles where TMV-inoculation resulted in a decrease of glutathione levels when compared to mock-inoculated plants. This was particularly obvious in −S plants, where the development of necrotic lesions was more pronounced. In summary, the overall higher antioxidative capacity and elevated activation of defense genes in +S plants indicate that sufficient sulfate supply enhances a preexisting plant defense reaction resulting in reduced symptom development and virus accumulation. PMID:22122784

  14. Random mutagenesis of the nucleotide-binding domain of NRC1 (NB-LRR Required for Hypersensitive Response-Associated Cell Death-1), a downstream signalling nucleotide-binding, leucine-rich repeat (NB-LRR) protein, identifies gain-of-function mutations in the nucleotide-binding pocket

    NARCIS (Netherlands)

    Sueldo, D.J.; Shimels, M.Z.; Spiridon, L.N.; Caldararu, O.; Petrescu, A.J.; Joosten, M.H.A.J.; Tameling, W.I.L.

    2015-01-01

    •Plant nucleotide-binding, leucine-rich repeat (NB-LRR) proteins confer immunity to pathogens possessing the corresponding avirulence proteins. Activation of NB-LRR proteins is often associated with induction of the hypersensitive response (HR), a form of programmed cell death. •NRC1 (NB-LRR

  15. Transcriptomic analysis of Prunus domestica undergoing hypersensitive response to plum pox virus infection.

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    Bernardo Rodamilans

    Full Text Available Plum pox virus (PPV infects Prunus trees around the globe, posing serious fruit production problems and causing severe economic losses. One variety of Prunus domestica, named 'Jojo', develops a hypersensitive response to viral infection. Here we compared infected and non-infected samples using next-generation RNA sequencing to characterize the genetic complexity of the viral population in infected samples and to identify genes involved in development of the resistance response. Analysis of viral reads from the infected samples allowed reconstruction of a PPV-D consensus sequence. De novo reconstruction showed a second viral isolate of the PPV-Rec strain. RNA-seq analysis of PPV-infected 'Jojo' trees identified 2,234 and 786 unigenes that were significantly up- or downregulated, respectively (false discovery rate; FDR≤0.01. Expression of genes associated with defense was generally enhanced, while expression of those related to photosynthesis was repressed. Of the total of 3,020 differentially expressed unigenes, 154 were characterized as potential resistance genes, 10 of which were included in the NBS-LRR type. Given their possible role in plant defense, we selected 75 additional unigenes as candidates for further study. The combination of next-generation sequencing and a Prunus variety that develops a hypersensitive response to PPV infection provided an opportunity to study the factors involved in this plant defense mechanism. Transcriptomic analysis presented an overview of the changes that occur during PPV infection as a whole, and identified candidates suitable for further functional characterization.

  16. Transcriptomic analysis of Prunus domestica undergoing hypersensitive response to plum pox virus infection.

    Science.gov (United States)

    Rodamilans, Bernardo; San León, David; Mühlberger, Louisa; Candresse, Thierry; Neumüller, Michael; Oliveros, Juan Carlos; García, Juan Antonio

    2014-01-01

    Plum pox virus (PPV) infects Prunus trees around the globe, posing serious fruit production problems and causing severe economic losses. One variety of Prunus domestica, named 'Jojo', develops a hypersensitive response to viral infection. Here we compared infected and non-infected samples using next-generation RNA sequencing to characterize the genetic complexity of the viral population in infected samples and to identify genes involved in development of the resistance response. Analysis of viral reads from the infected samples allowed reconstruction of a PPV-D consensus sequence. De novo reconstruction showed a second viral isolate of the PPV-Rec strain. RNA-seq analysis of PPV-infected 'Jojo' trees identified 2,234 and 786 unigenes that were significantly up- or downregulated, respectively (false discovery rate; FDR≤0.01). Expression of genes associated with defense was generally enhanced, while expression of those related to photosynthesis was repressed. Of the total of 3,020 differentially expressed unigenes, 154 were characterized as potential resistance genes, 10 of which were included in the NBS-LRR type. Given their possible role in plant defense, we selected 75 additional unigenes as candidates for further study. The combination of next-generation sequencing and a Prunus variety that develops a hypersensitive response to PPV infection provided an opportunity to study the factors involved in this plant defense mechanism. Transcriptomic analysis presented an overview of the changes that occur during PPV infection as a whole, and identified candidates suitable for further functional characterization.

  17. Relationship between systemic inflammation and delayed-type hypersensitivity response to Candida antigen in older adults.

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    Brandt D Pence

    Full Text Available Research has shown that aging is associated with increased systemic inflammation as well as a reduction in the strength of immune responses. However, little evidence exists linking the decrease in cell-mediated immunity in older adults with other health parameters. We sought to examine the relationship between cell-mediated immunity as measured in vivo by the delayed-type hypersensitivity (DTH response to candida antigen and demographic and physiological variables in older (65-80 y.o. adults. Candida antigen response was not related to gender or obesity, or to a number of other physiological variables including fitness and body composition. However, positive responders had significantly lower serum C-reactive protein levels (CRP, p4.75 mg•L(-1. Therefore, positive responses to candida antigen in older adults appears to be related to lower levels of systemic inflammation.

  18. Using classification and regression tree modelling to investigate response shift patterns in dentine hypersensitivity

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    Carolina Machuca

    2017-08-01

    Full Text Available Abstract Background Dentine hypersensitivity (DH affects people’s quality of life (QoL. However changes in the internal meaning of QoL, known as Response shift (RS may undermine longitudinal assessment of QoL. This study aimed to describe patterns of RS in people with DH using Classification and Regression Trees (CRT and to explore the convergent validity of CRT with the then-test and ideals approaches. Methods Data from an 8-week clinical trial of mouthwashes for dentine hypersensitivity (n = 75 using the Dentine Hypersensitivity Experience Questionnaire (DHEQ as the outcome measure, were analysed. CRT was used to examine 8-week changes in DHEQ total score as a dependent variable with clinical status for DH and each DHEQ subscale score (restrictions, coping, social, emotional and identity as independent variables. Recalibration was inferred when the clinical change was not consistent with the DHEQ change score using a minimally important difference for DHEQ of 22 points. Reprioritization was inferred by changes in the relative importance of each subscale to the model over time. Results Overall, 50.7% of participants experienced a clinical improvement in their DH after treatment and 22.7% experienced an important improvement in their quality of life. Thirty-six per cent shifted their internal standards downward and 14.7% upwards, suggesting recalibration. Reprioritization occurred over time among the social and emotional impacts of DH. Conclusions CRT was a useful method to reveal both, the types and nature of RS in people with a mild health condition and demonstrated convergent validity with design based approaches to detect RS.

  19. Nadroparin carries a potentially high risk of inducing cutaneous delayed-type hypersensitivity responses.

    Science.gov (United States)

    Schindewolf, Marc; Recke, Andreas; Zillikens, Detlef; Lindhoff-Last, Edelgard; Ludwig, Ralf J

    2017-07-01

    Heparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin-induced skin lesions occur frequently (in 7.5-39% of patients). Skin lesions may be the only clinical manifestation of life-threatening immune-mediated heparin-induced thrombocytopenia, but are commonly caused by a delayed-type hypersensitivity response [heparin-induced delayed-type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified. To identify possible risk factors for heparin-induced skin lesions from three independent clinical trials in a combined analysis. A pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis. Obesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7-77.9). The high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Plant innate immunity induced by flagellin suppresses the hypersensitive response in non-host plants elicited by Pseudomonas syringae pv. averrhoi.

    Science.gov (United States)

    Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

    2012-01-01

    A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction.

  1. Plant innate immunity induced by flagellin suppresses the hypersensitive response in non-host plants elicited by Pseudomonas syringae pv. averrhoi.

    Directory of Open Access Journals (Sweden)

    Chia-Fong Wei

    Full Text Available A new pathogen, Pseudomonas syringae pv. averrhoi (Pav, which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta, glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns contributed to induce the PAMP-triggered immunity (PTI. Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction.

  2. Catechol-O-Methyltransferase Deficiency Leads to Hypersensitivity of the Pressor Response Against Angiotensin II.

    Science.gov (United States)

    Ueki, Norikazu; Kanasaki, Keizo; Kanasaki, Megumi; Takeda, Satoru; Koya, Daisuke

    2017-06-01

    Catechol-O-methyltransferase (COMT) metabolizes 2-hydroxyestradiol into 2-methoxyestradiol (2-ME); COMT deficiency has shown to be associated with hypertension in men and preeclampsia, the disease associated with hypersensitivity of pressor response against angiotensin II (Ang II). Here, we found that COMT deficiency could explain the hypersensitivity of pressor response against Ang II in mice because of the lack of 2-ME-dependent suppression of angiotensin II receptor type 1 (AT1R). Male C57BL/6 mice were subjected to COMT inhibitor (COMTi: 25 mg/kg per day) or oil (control) for 4 weeks, with or without low-dose Ang II infusion (ANGII: 70 ng/kg per minute) for the last 3 weeks. The Ang II-infused mice were treated with 2-ME (10 ng/d) or vehicle for the last 1 week. We obtained the following experimental groups: control, ANGII, COMTi, COMTi+ANGII, and COMTi+ANGII+2-ME. We performed similar experiments using the in vivo administration of small interfering RNA of COMT instead of COMTi. Neither ANGII nor COMTi exhibited significant alterations in systolic blood pressure. Compared with ANGII or COMTi, COMTi+ANGII displayed significantly higher systolic blood pressure, albuminuria, and glomerular endotheliosis; 2-ME normalized such alterations. Similar phenotypes were observed in COMT small interfering RNA-treated mice. In the aorta of COMT-deficient mice, AT1R expression was increased; 2-ME suppressed AT1R expression. The 2-ME exhibited peroxisome proliferator-activated receptor γ agonistic activity in vitro and ex vivo plasma from pregnant female mice as well. In vitro, 2-ME suppressed both basal and Ang II-induced AT1R levels in a peroxisome proliferator-activated receptor γ-dependent manner. The 2-ME is relevant to combat COMT deficiency-associated hypertensive disorders via suppression of AT1R by its peroxisome proliferator-activated receptor γ activity. © 2017 American Heart Association, Inc.

  3. Copper hypersensitivity

    DEFF Research Database (Denmark)

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-01-01

    hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common...

  4. Immunosuppressive Effect of Litsea cubeba L. Essential Oil on Dendritic Cell and Contact Hypersensitivity Responses

    Directory of Open Access Journals (Sweden)

    Hsin-Chun Chen

    2016-08-01

    Full Text Available Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC and gas chromatography/mass spectrometry (GC/MS with direct injection (DI/GC or headspace-solid phase microextraction (HS-SPME/GC. In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial. An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases.

  5. Immunologic responses against hydrolyzed soy protein in dogs with experimentally induced soy hypersensitivity.

    Science.gov (United States)

    Puigdemont, Anna; Brazís, Pilar; Serra, Montserrat; Fondati, Alessandra

    2006-03-01

    To assess whether dogs with experimentally induced type I hypersensitivity against soy protein would respond to soy hydrolysate and develop cutaneous or gastrointestinal tract reactions after intradermal and oral challenge exposure. 12 naïve Beagle pups (9 sensitized and 3 control dogs). 9 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization period, serum concentrations of soy-specific IgE were determined and an intradermal test was performed to confirm the dogs were sensitized against soy protein. An intradermal challenge test and an oral challenge test with native and hydrolyzed soy protein were conducted on 6 sensitized and 2 control dogs. High serum concentrations of soy-specific IgE and positive results for the intradermal test were observed for the 9 sensitized dogs after completion of the sesitization process. Sensitized dogs challenge exposed with hydrolyzed soy protein had a reduced inflammatory response after intradermal injection and no clinical response after an oral challenge exposure, compared with responses after intradermal and oral challenge exposure with native soy protein. Soy-sensitized dogs did not respond to oral administration of hydrolyzed soy protein. Thus, hydrolyzed soy protein may be useful in diets formulated for the management of dogs with adverse reactions to food.

  6. Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.

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    Rajwahrdhan Yadav

    2010-08-01

    Full Text Available Pertussis toxin (PTX, an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU and experimental autoimmune encephalomyelitis (EAE in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180, encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55 or ovalbumin (OVA. PTX injection of mice immunized to IRBP peptide161-180 led to (i the development of EAU as shown by histopathology of the retina, (ii pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards

  7. Delayed-type hypersensitivity and hepatitis B vaccine responses, in vivo markers of cellular and humoral immune function, and the risk of AIDS or death.

    Science.gov (United States)

    Patterson, Shane B; Landrum, Michael L; Okulicz, Jason F

    2014-06-05

    Delayed-type hypersensitivity (DTH) test responsiveness is associated with HIV disease progression; however it is unknown whether other immune markers, such as hepatitis B virus (HBV) vaccine seroresponse, also predict HIV outcomes. Eligible participants received HBV vaccine after HIV diagnosis, had non-anergic DTH testing at the time of last HBV vaccination, and available post-vaccine HBV antibody responses. The risk of progression to AIDS or death from the time of last HBV vaccination was evaluated. Of 369 eligible participants with non-anergic DTH responses, 148 (40%) were HBV vaccine responders. In a multivariate model adjusted for age, CD4 count, viral load, and number of vaccinations, HBV vaccine non-responders had an increased risk of progression to AIDS or death (HR 1.81; 95% CI, 1.03-3.19). HBV vaccine seroresponses were independent of DTH responses which suggest that non-response to HBV vaccine is not solely due to cell-mediated immune dysfunction in HIV-infected persons. Published by Elsevier Ltd.

  8. Hypersensitivity pneumonitis.

    Science.gov (United States)

    Yi, Eunhee S

    2002-11-01

    Hypersensitivity pneumonitis (HP) is a group of immunologically mediated lung diseases caused by the inhalation of environmental agents in susceptible individuals. Most HP patients are non-smokers and have been exposed to organic dusts from vegetable or animal products. Some HP cases are associated with exposures to relatively simple chemical compounds. HP may present as an acute, subacute, or chronic disease and may follow various clinical courses. The type of exposure is thought to be more important in the clinical outcome than the nature of the antigen. A diagnosis of HP is often considered on the basis of clinical history of exposure with resulting respiratory symptoms, but the definitive diagnosis requires a constellation of clinical, radiologic, laboratory, and pathologic findings. The characteristic histologic triad in HP includes bronchiolitis, interstitial lymphocytic infiltration, and granulomas; however, biopsy in HP cases may lack the diagnostic triad and manifest as nonspecific interstitial pneumonia (NSIP). Avoiding exposure to the offending antigen(s) is usually sufficient to resolve symptoms and physiological abnormalities. Pulmonary fibrosis and physiological abnormalities occurring in chronic HP may be irreversible. Steroid therapy is helpful for symptomatic relief, but probably does not affect the long-term prognosis. Type III and type IV hypersensitivity reactions are involved in the pathogenesis; alveolar macrophages and T cells (Th-1 type) play a central role in the immune responses after antigen exposure via their increased interaction and secretion of regulatory mediators.

  9. Tissue-specific expression of a soybean hypersensitive-induced response (HIR) protein gene promoter.

    Science.gov (United States)

    Koellhoffer, Jessica P; Xing, Aiqiu; Moon, Bryan P; Li, Zhongsen

    2015-02-01

    A Glycine max gene encoding a putative protein similar to hypersensitive-induced response proteins (HIR) was identified as a gene with preferred expressions in flowers and developing seeds by whole transcriptome gene expression profiling. Its promoter gm-hir1 was cloned and revealed to strongly express a fluorescence reporter gene primarily in integuments, anther tapetum, and seed coat with unique tissue-specificity. Expression in the inner integument was apparent prior to pollination, while expression in the outer integument started to develop from the micropylar end outward as the embryo matured. A 5'-deletion study showed that the promoter can be truncated to 600 bp long relative to the translation start site without affecting expression. A positive regulatory element was identified between 600 and 481 bp that controls expression in the inner integument, with no noticeable effect on expression in the outer integument or tapetum. Additionally, removal of the 5'UTR intron had no effect on levels or location of gm-hir1 expression while truncation to 370 bp resulted in a complete loss of expression suggesting that elements controlling both the outer integument and tapetum expression are located within the 481-370 bp region.

  10. An NB-LRR protein required for HR signalling mediated by both extra- and intracellular resistance proteins.

    NARCIS (Netherlands)

    Gabriels, S.H.E.J.; Vossen, J.H.; Ekengren, S.K.; van Ooijen, G.; Abd-El-Haliem, A.M.; van den Berg, G.C.M.; Rainey, D.Y.; Martin, G.B.; Takken, F.L.W.; de Wit, P.J.G.M.; Joosten, M.H.A.J.

    2007-01-01

    Tomato (Solanum lycopersicum) Cf resistance genes confer hypersensitive response (HR)-associated resistance to strains of the pathogenic fungus Cladosporium fulvum that express the matching avirulence (Avr) gene. Previously, we identified an Avr4-responsive tomato (ART) gene that is required for

  11. An NB-LRR protein required for HR signalling mediated by both extra- and intracellular resistance proteins

    NARCIS (Netherlands)

    Gabriëls, S.H.E.J.; Vossen, J.H.; Ekengren, S.K.; Ooijen, van G.; Abd-El-Haliem, A.M.; Berg, van den G.C.M.; Rainey, D.Y.; Martin, G.B.; Takken, F.L.W.; Wit, de P.J.G.M.; Joosten, M.H.A.J.

    2007-01-01

    Tomato (Solanum lycopersicum) Cf resistance genes confer hypersensitive response (HR)-associated resistance to strains of the pathogenic fungus Cladosporium fulvum that express the matching avirulence (Avr) gene. Previously, we identified an Avr4-responsive tomato (ART) gene that is required for

  12. Potential role of blood dendritic cells in elicitation phase of contact hypersensitivity response – preliminary study

    Directory of Open Access Journals (Sweden)

    Aleksandra Lesiak

    2016-06-01

    Full Text Available Introduction . In contrast to our broad knowledge about the role of dendritic cells in the sensitization phase of the contact hypersensitivity response (CHS, very little is known about their function in the effector phase. The pathophysiological mechanism of blood dendritic cells’ participation in the inflammatory response in CHS is an emerging subject of study and needs to be scrutinized. Objective . To assess the presence and type of human blood dendritic cells (BDC – plasmacytoid DC (pDC and myeloid DC (mDC – at the elicitation site of CHS. Material and methods. The study group consisted of 25 healthy volunteers with a mean age of 22.3 ±6.1. Each patient before the trial was sensitized with DPCP, and after 3 weeks skin biopsies were taken from the elicitation site and were immunohistochemically stained with monoclonal mouse IgG1 antibodies against blood dendritic cell antigens (BDCA. Results . Skin biopsies were divided into two groups: group 1 where the CHS score was assessed as 0 (no reaction; n = 7 and group 2 where the CHS score was assessed as 1 (any response noted; n = 18. Compared to group 1, group 2 had a significantly lower percentage of pDC (60% vs. 15% respectively in the inflammatory infiltrate site. We also observed that the percentage of mDC was higher in group 2 compared to group 1, although this result was not statistically significant. Conclusions . Our findings provide some data on composition of inflammatory infiltrate in the elicitation phase of CHS. We suggest that the imbalance between pDC and mDC may be a key to understanding the effector phase of CHS.

  13. A novel hairpin library-based approach to identify NBS-LRR genes required for effector-triggered hypersensitive response in Nicotiana benthamiana.

    Science.gov (United States)

    Brendolise, Cyril; Montefiori, Mirco; Dinis, Romain; Peeters, Nemo; Storey, Roy D; Rikkerink, Erik H

    2017-01-01

    PTI and ETI are the two major defence mechanisms in plants. ETI is triggered by the detection of pathogen effectors, or their activity, in the plant cell and most of the time involves internal receptors known as resistance (R) genes. An increasing number of R genes responsible for recognition of specific effectors have been characterised over the years; however, methods to identify R genes are often challenging and cannot always be translated to crop plants. We present a novel method to identify R genes responsible for the recognition of specific effectors that trigger a hypersensitive response (HR) in Nicotiana benthamiana. This method is based on the genome-wide identification of most of the potential R genes of N. benthamiana and a systematic silencing of these potential R genes in a simple transient expression assay. A hairpin-RNAi library was constructed covering 345 R gene candidates of N. benthamiana. This library was then validated using several previously described R genes. Our approach indeed confirmed that Prf, NRC2a/b and NRC3 are required for the HR that is mediated in N. benthamiana by Pto/avrPto (prf, NRC2a/b and NRC3) and by Cf4/avr4 (NRC2a/b and NRC3). We also confirmed that NRG1, in association with N, is required for the Tobacco Mosaic Virus (TMV)-mediated HR in N. benthamiana. We present a novel approach combining bioinformatics, multiple-gene silencing and transient expression assay screening to rapidly identify one-to-one relationships between pathogen effectors and host R genes in N. benthamiana. This approach allowed the identification of previously described R genes responsible for detection of avirulence determinants from Pseudomonas, Cladosporium and TMV, demonstrating that the method could be applied to any effectors/proteins originating from a broad range of plant pathogens that trigger an HR in N. benthamiana. Moreover, with the increasing availability of genome sequences from model and crop plants and pathogens, this approach could be

  14. Diclofenac hypersensitivity: antibody responses to the parent drug and relevant metabolites.

    Directory of Open Access Journals (Sweden)

    Andrea Harrer

    2010-10-01

    Full Text Available Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs like diclofenac (DF can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug- and/or metabolite-specific antibodies in selective DF hypersensitivity.DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14% displayed drug/metabolite-specific IgG.We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded.

  15. Coronatine inhibits stomatal closure and delays hypersensitive response cell death induced by nonhost bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Seonghee Lee

    2013-02-01

    Full Text Available Pseudomonas syringae is the most widespread bacterial pathogen in plants. Several strains of P. syringae produce a phytotoxin, coronatine (COR, which acts as a jasmonic acid mimic and inhibits plant defense responses and contributes to disease symptom development. In this study, we found that COR inhibits early defense responses during nonhost disease resistance. Stomatal closure induced by a nonhost pathogen, P. syringae pv. tabaci, was disrupted by COR in tomato epidermal peels. In addition, nonhost HR cell death triggered by P. syringae pv. tabaci on tomato was remarkably delayed when COR was supplemented along with P. syringae pv. tabaci inoculation. Using isochorismate synthase (ICS-silenced tomato plants and transcript profiles of genes in SA- and JA-related defense pathways, we show that COR suppresses SA-mediated defense during nonhost resistance.

  16. Detection of drug-responsive B lymphocytes and antidrug IgG in patients with β-lactam hypersensitivity.

    Science.gov (United States)

    Amali, M O; Sullivan, A; Jenkins, R E; Farrell, J; Meng, X; Faulkner, L; Whitaker, P; Peckham, D; Park, B K; Naisbitt, D J

    2017-06-01

    Delayed-type β-lactam hypersensitivity develops in subset of patients. The cellular immunological processes that underlie the drug-specific response have been described; however, little is known about involvement of the humoral immune system. Thus, the aim of this study was to utilize piperacillin hypersensitivity as an exemplar to (i) develop cell culture methods for the detection of drug-specific B-cell responses, (ii) characterize drug-specific IgG subtypes and (iii) assess reactivity of IgG antibodies against proteins modified to different levels with piperacillin haptens. IgG secretion and CD19(+) CD27(+) expression on B cells were measured using ELISPOT and flow cytometry, respectively. A piperacillin-BSA adduct was used as an antigen in ELISA antibody binding studies. Adducts generated using different ratios of drug to protein were used to determine the degree of conjugation required to detect IgG binding. B cells from hypersensitive patients, but not controls, were stimulated to secrete IgG and increase CD27 expression when cultured with soluble piperacillin. A piperacillin-BSA adduct with cyclized and hydrolysed forms of the hapten bound to eight lysine residues was used to detect hapten-specific IgG 1-4 subclasses in patient plasma. Hapten inhibition and the use of structurally unrelated hapten-BSA adducts confirmed antigen specificity. Antibody binding was detected with antigens generated at piperacillin/BSA ratios of 10:1 and above, which corresponded to a minimum epitope density of 1 for antibody binding. These data show that antigen-specific B lymphocytes and T lymphocytes are activated in piperacillin-hypersensitive patients. Further work is needed to define the role different IgG subtypes play in regulating the iatrogenic disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

    Science.gov (United States)

    While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were or...

  18. Transcriptome Analysis of Capsicum Chlorosis Virus-Induced Hypersensitive Resistance Response in Bell Capsicum.

    Directory of Open Access Journals (Sweden)

    Shirani M K Widana Gamage

    Full Text Available Capsicum chlorosis virus (CaCV is an emerging pathogen of capsicum, tomato and peanut crops in Australia and South-East Asia. Commercial capsicum cultivars with CaCV resistance are not yet available, but CaCV resistance identified in Capsicum chinense is being introgressed into commercial Bell capsicum. However, our knowledge of the molecular mechanisms leading to the resistance response to CaCV infection is limited. Therefore, transcriptome and expression profiling data provide an important resource to better understand CaCV resistance mechanisms.We assembled capsicum transcriptomes and analysed gene expression using Illumina HiSeq platform combined with a tag-based digital gene expression system. Total RNA extracted from CaCV/mock inoculated CaCV resistant (R and susceptible (S capsicum at the time point when R line showed a strong hypersensitive response to CaCV infection was used in transcriptome assembly. Gene expression profiles of R and S capsicum in CaCV- and buffer-inoculated conditions were compared. None of the genes were differentially expressed (DE between R and S cultivars when mock-inoculated, while 2484 genes were DE when inoculated with CaCV. Functional classification revealed that the most highly up-regulated DE genes in R capsicum included pathogenesis-related genes, cell death-associated genes, genes associated with hormone-mediated signalling pathways and genes encoding enzymes involved in synthesis of defense-related secondary metabolites. We selected 15 genes to confirm DE expression levels by real-time quantitative PCR.DE transcript profiling data provided comprehensive gene expression information to gain an understanding of the underlying CaCV resistance mechanisms. Further, we identified candidate CaCV resistance genes in the CaCV-resistant C. annuum x C. chinense breeding line. This knowledge will be useful in future for fine mapping of the CaCV resistance locus and potential genetic engineering of resistance into Ca

  19. New ABA-Hypersensitive Arabidopsis Mutants Are Affected in Loci Mediating Responses to Water Deficit and Dickeya dadantii Infection

    Science.gov (United States)

    Plessis, Anne; Cournol, Raphaël; Effroy, Delphine; Silva Pérez, Viridiana; Botran, Lucy; Kraepiel, Yvan; Frey, Anne; Sotta, Bruno; Cornic, Gabriel; Leung, Jeffrey; Giraudat, Jérôme; Marion-Poll, Annie; North, Helen M.

    2011-01-01

    On water deficit, abscisic acid (ABA) induces stomata closure to reduce water loss by transpiration. To identify Arabidopsis thaliana mutants which transpire less on drought, infrared thermal imaging of leaf temperature has been used to screen for suppressors of an ABA-deficient mutant (aba3-1) cold-leaf phenotype. Three novel mutants, called hot ABA-deficiency suppressor (has), have been identified with hot-leaf phenotypes in the absence of the aba3 mutation. The defective genes imparted no apparent modification to ABA production on water deficit, were inherited recessively and enhanced ABA responses indicating that the proteins encoded are negative regulators of ABA signalling. All three mutants showed ABA-hypersensitive stomata closure and inhibition of root elongation with little modification of growth and development in non-stressed conditions. The has2 mutant also exhibited increased germination inhibition by ABA, while ABA-inducible gene expression was not modified on dehydration, indicating the mutated gene affects early ABA-signalling responses that do not modify transcript levels. In contrast, weak ABA-hypersensitivity relative to mutant developmental phenotypes suggests that HAS3 regulates drought responses by both ABA-dependent and independent pathways. has1 mutant phenotypes were only apparent on stress or ABA treatments, and included reduced water loss on rapid dehydration. The HAS1 locus thus has the required characteristics for a targeted approach to improving resistance to water deficit. In contrast to has2, has1 exhibited only minor changes in susceptibility to Dickeya dadantii despite similar ABA-hypersensitivity, indicating that crosstalk between ABA responses to this pathogen and drought stress can occur through more than one point in the signalling pathway. PMID:21633512

  20. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan

    2009-01-01

    expression. Here, we examined receptor-mediated HR PCD responses in autophagy-deficient Arabidopsis knockout mutants (atg), and show that infection-induced lesions are contained in atg mutants. We also provide evidence that HR cell death initiated via Toll/Interleukin-1 (TIR)-type immune receptors through...... the defense regulator EDS1 is suppressed in atg mutants. Furthermore, we demonstrate that PCD triggered by coiled-coil (CC)-type immune receptors via NDR1 is either autophagy-independent or engages autophagic components with cathepsins and other unidentified cell death mediators. Thus, autophagic cell death......Autophagy has been implicated as a prosurvival mechanism to restrict programmed cell death (PCD) associated with the pathogen-triggered hypersensitive response (HR) during plant innate immunity. This model is based on the observation that HR lesions spread in plants with reduced autophagy gene...

  1. Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice

    Directory of Open Access Journals (Sweden)

    Zhao Meng

    2012-07-01

    Full Text Available Abstract Background Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1 in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results A single intraperitoneal administration of oxaliplatin (1–10 mg/kg induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg, also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg, or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg in a dose-dependent manner, while capsaicin (TRPV1 agonist-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG neurons with oxaliplatin (30–300 μM for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons

  2. Examining the Latent Class Structure of CO2 Hypersensitivity using Time Course Trajectories of Panic Response Systems

    Science.gov (United States)

    Roberson-Nay, Roxann; Beadel, Jessica R.; Gorlin, Eugenia I.; Latendresse, Shawn J.; Teachman, Bethany A.

    2014-01-01

    Background and Objectives Carbon dioxide (CO2) hypersensitivity is hypothesized to be a robust endophenotypic marker of panic spectrum vulnerability. The goal of the current study was to explore the latent class trajectories of three primary response systems theoretically associated with CO2 hypersensitivity: subjective anxiety, panic symptoms, and respiratory rate (fR). Methods Participants (n=376; 56% female) underwent a maintained 7.5% CO2 breathing task that included three phases: baseline, CO2 air breathing, and recovery. Growth mixture modeling was used to compare response classes (1..n) to identify the best-fit model for each marker. Panic correlates also were examined to determine class differences in panic vulnerability. Results For subjective anxiety ratings, a three-class model was selected, with individuals in one class reporting an acute increase in anxiety during 7.5% CO2 breathing and a return to pre-CO2 levels during recovery. A second, smaller latent class was distinguished by elevated anxiety across all three phases. The third class reported low anxiety reported during room air, a mild increase in anxiety during 7.5% CO2 breathing, and a return to baseline during recovery. Latent class trajectories for fR yielded one class whereas panic symptom response yielded two classes. Limitations This study examined CO2 hypersensitivity in one of the largest samples to date, but did not ascertain a general population sample thereby limiting generalizability. Moreover, a true resting baseline measure of fR was not measured. Conclusions Two classes potentially representing different risk pathways were observed. Implications of results will be discussed in the context of panic risk research. PMID:25496936

  3. Purification and characterization of a novel hypersensitive response-inducing elicitor from Magnaporthe oryzae that triggers defense response in rice.

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    Mingjia Chen

    Full Text Available BACKGROUND: Magnaporthe oryzae, the rice blast fungus, might secrete certain proteins related to plant-fungal pathogen interactions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we report the purification, characterization, and gene cloning of a novel hypersensitive response-inducing protein elicitor (MoHrip1 secreted by M. oryzae. The protein fraction was purified and identified by de novo sequencing, and the sequence matched the genomic sequence of a putative protein from M. oryzae strain 70-15 (GenBank accession No. XP_366602.1. The elicitor-encoding gene mohrip1 was isolated; it consisted of a 429 bp cDNA, which encodes a polypeptide of 142 amino acids with a molecular weight of 14.322 kDa and a pI of 4.53. The deduced protein, MoHrip1, was expressed in E. coli. And the expression protein collected from bacterium also forms necrotic lesions in tobacco. MoHrip1 could induce the early events of the defense response, including hydrogen peroxide production, callose deposition, and alkalization of the extracellular medium, in tobacco. Moreover, MoHrip1-treated rice seedlings possessed significantly enhanced systemic resistance to M. oryzae compared to the control seedlings. The real-time PCR results indicated that the expression of some pathogenesis-related genes and genes involved in signal transduction could also be induced by MoHrip1. CONCLUSION/SIGNIFICANCE: The results demonstrate that MoHrip1 triggers defense responses in rice and could be used for controlling rice blast disease.

  4. Sphingolipids as new biomarkers for assessment of delayed-type hypersensitivity and response to triptolide.

    Science.gov (United States)

    Qu, Feng; Wu, Cai-Sheng; Hou, Jin-Feng; Jin, Ying; Zhang, Jin-Lan

    2012-01-01

    Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism. High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation. As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation. These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples.

  5. Hypersensitive Response of Plasmid-Encoded AHL Synthase Gene to Lifestyle and Nutrient by Ensifer adhaerens X097

    Directory of Open Access Journals (Sweden)

    Yanhua Zeng

    2017-06-01

    Full Text Available It is known that some bacteria, especially members of the family Rhizobiaceae, have multiple N-acyl homoserine lactones (AHL synthase genes and produce multiple AHL signals. However, how bacteria selectively utilize these multiple genes and signals to cope with changing environments is poorly understood. Ensifer adhaerens is an important microorganism in terms of biotechnology, ecology and evolutionary. In this study, we investigated the AHL-based QS system of E. adhaerens X097 and its response to different lifestyles or nutrients. Draft genome sequence data indicated that X097 harbored three distinct AHL synthase genes (ensI1, 2, 3 and seven luxR homologs, which was different from other E. adhaerens strains. In vitro expression indicated that plasmid-encoded ensI1 and ensI2 directed production of multiple AHLs, while chromosome-encoded ensI3 only directed production of C14-HSL. Predicted three dimensional structure of EnsI3 was quite different from that of EnsI1 and EnsI2. X097 produced different AHL profiles in Luria-Bertani (LB and NFB medium, under biofilm and planktonic lifestyle, respectively. Notably, expression of ensI1 and ensI2 but not ensI3 is hypersensitive to different lifestyles and nutrients. The hypersensitive response of plasmid-encoded AHL synthase genes to different culture conditions may shed a light on the phylogenetic development of AHL synthase genes in Rhizobiaceae family.

  6. Ranitidine for improvement of delayed hypersensitivity response in patients with sepsis

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Witt, K; Moesgaard, F

    1989-01-01

    Twenty-five patients admitted to intensive or high-dependency surgical care units were randomized to receive ranitidine intravenously 50 mg every 6 hours for 8 days or no ranitidine. All had septicemia or intra-abdominal sepsis, with body temperature greater than or equal to 38.5 degrees C for more...... hypersensitivity improved in patients treated with ranitidine (p less than 0.001), but was unchanged in the untreated group (p greater than 0.7). These observations may suggest potential beneficial effects of ranitidine therapy in patients with trauma-induced immunosuppression....

  7. Equine Culicoides hypersensitivity: evaluation of a skin test and of humoral response.

    Science.gov (United States)

    Ferroglio, E; Pregel, P; Accossato, A; Taricco, I; Bollo, E; Rossi, L; Trisciuoglio, A

    2006-02-01

    Intradermal tests were carried out on 18 horses with clinical signs of Culicoides hypersensitivity (CHS) and 23 horses without clinical signs of CHS, and sera from these horses were analysed by SDS-PAGE and Western blotting (W-B). Intradermal injections of 0.1 ml of 25 microg/microl sterile Culicoides extract, 0.1 ml of 1:10,000 histamine (positive control) and 0.1 ml of physiological saline (negative control) were made in the dermis of the middle region of the neck. Analysis of reactions indicated that a 1 cm wheal and a skinfold thickness >10% at 24 h represented a valid cut-off between horses with and without CHS. In these conditions the test, even in winter when clinical signs were absent, had 100% sensitivity and specificity. The W-B was performed after running Culicoides extract on a 12% polyacrylamide gel. The test revealed the presence of several bands with molecular weight ranging from 6 to 200 kDa. In particular, a band of 65 kDa was predominantly found in hypersensitive horses by using an anti-IgE antibody while in normal horses the same band was mainly detected by using an anti-IgG antibody. Our results demonstrated that the skin test is a valid diagnostic test, with high sensitivity and specificity and that the band of about 65 kDa probably corresponds to the allergen involved in the pathogenesis of CHS.

  8. Effects of repeated administration of intradermal skin test by Mantoux method on delayed-type hypersensitivity responses in healthy young and elderly subjects

    Science.gov (United States)

    Multi-test CMI to test immune response is no longer commercially available. DTH response is a highly suitable marker of immune function. Because delayed-type hypersensitivity (DTH) skin test can predict morbidity and mortality, it may be clinically meaningful test to evaluate the effect of nutrition...

  9. Hypersensitive tourists

    DEFF Research Database (Denmark)

    Jensen, Martin Trandberg

    2016-01-01

    This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests that aller......This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests...

  10. Delayed-type hypersensitivity in response to L-asparaginase in a case of acute lymphoblastic leukemia.

    Science.gov (United States)

    Narazaki, Hidehiko; Kaizu, Kiyohiko; Miyatake, Chiharu; Koizumi, Shinya; Asano, Takeshi; Fujino, Osamu

    2012-01-01

    L-asparaginase (L-Asp) is an important reagent for acute lymphoblastic leukemia because asparagine is required for the malignant growth of tumor cells, especially lymphoblastic leukemia cells. An allergic response to L-Asp is not unusual because L-Asp is derived from Escherichia coli and is often recognized as a foreign protein. The hypersensitivity induced by L-Asp is of the immediate type in most cases. We report on a 5-year-old girl who was hospitalized for precursor T-cell lymphoblastic leukemia. She was treated according to a Tokyo Children's Cancer Study Group protocol (TCCSG ALL L09-1603 HEX/BFM). During the intensification phase, blisters with erythema developed on the arm proximal to the catheter insertion site owing to a delayed-type hypersensitivity reaction caused by intravenous L-Asp administration. She was treated with additional methylprednisolone, tapered dexamethasone, and an antihistamine for the allergic reaction. No asparaginases other than E. coli L-Asp have been approved for use in Japan. Other asparaginases, such as polyethylene glycol L-Asp and Erwinia L-Asp should be quickly approved for use as alternative chemotherapy reagents in Japan.

  11. CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

    DEFF Research Database (Denmark)

    Fjelbye, Jonas; Antvorskov, Julie C; Buschard, Karsten

    2015-01-01

    Conflicting observations have been reported concerning the role of CD1d-dependent natural killer T (NKT) cells in contact hypersensitivity (CHS), supporting either a disease-promoting or downregulatory function. We studied the role of NKT cells in CHS by comparing the immune response in CD1d...

  12. Proton extrusion is an essential signalling component in the HR of epidermal single cells in the barley-powdery mildew interaction

    DEFF Research Database (Denmark)

    Zhou, F.S.; Andersen, C.H.; Burhenne, K.

    2000-01-01

    We propose a model for activation of the epidermal cell hypersensitive response (HR) in the barley/powdery mildew interaction. The model suggests that the plasma membrane proton pump (H+-ATPase) of epidermal cells is activated following penetration by an avirulent powdery mildew fungus. This will...

  13. Identification of tomato phosphatidylinositol-specific phospholipase-C (PI-PLC) family members and the role of PLC4 and PLC6 in HR and disease resistance

    NARCIS (Netherlands)

    Vossen, J.H.; Abd-El-Haliem, A.; Fradin, E.F.; Berg, van den G.C.M.; Ekengren, S.K.; Meijer, H.J.G.; Seifi Abdolabad, A.R.; Bai, Y.; Have, ten A.; Munnik, T.; Thomma, B.P.H.J.; Joosten, M.H.A.J.

    2010-01-01

    The perception of pathogen-derived elicitors by plants has been suggested to involve phosphatidylinositol-specific phospholipase-C (PI-PLC) signalling. Here we show that PLC isoforms are required for the hypersensitive response (HR) and disease resistance. We characterised the tomato [Solanum

  14. Dentin hypersensitive: Ethiology and treatment

    Directory of Open Access Journals (Sweden)

    Nuryanni Dihin Utami

    2017-08-01

    Full Text Available Dentin hypersensitivity is a response in exposed dentine with a symptom of clinically sharp and short pain. This condition may occur to exposed dentine due to gingival recession or enamel loss. Dentin hypersensitivity treatment aimed to either occlude the open dentinal tubules or block the neural response of the pulp. Invasive treatment are pulpectomy, restoration or surgery, while non invasive treatment are usually done by using tooth paste or mouthwash which is added by desensitizing agent

  15. Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis.

    Science.gov (United States)

    Wang, Zhigang; Chen, Zhe; Chen, Tao; Yi, Tao; Zheng, Zhou; Fan, Hong; Chen, Zebin

    2017-02-01

    Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer(+)CD8(+) cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

  16. Gender differences in delayed-type hypersensitivity response: effects of stress and coping in first-year law students.

    Science.gov (United States)

    Flynn, Sarah McQueary; Schipper, Lindsey J; Roach, Abbey R; Segerstrom, Suzanne C

    2009-07-01

    Law students show significant deficits in emotional and physical well-being compared with groups of students in other areas of higher education. Furthermore, evidence suggests that these effects may be worse for women than for men. The use of active coping can positively affect immunity under stress, but this may be most true for men in the context of law school. The current study examined the delayed-type hypersensitivity (DTH) skin responses of first-year law students (n=121) and a comparison group (n=30). Students' health behaviors, self-evaluative emotions, and coping strategies were also reported. Male law students had larger DTH responses than females, but this gender effect was not present in the comparison group. Endorsement of perseverance under stress (n=19), an active coping strategy, moderated the gender effect on immunity. Perseverance associated with larger DTH responses and more positive self-evaluative emotion, but only among men. These results indicate that active coping may be less efficacious for women than for men in law school, which in turn may limit women's opportunities to attenuate negative effects of law school.

  17. H.R. 3221: Student Aid and Fiscal Responsibility Act of 2009. Congressional Budget Office Cost Estimate

    Science.gov (United States)

    Congressional Budget Office, 2009

    2009-01-01

    H.R. 3221 would amend the Higher Education Act of 1965, which authorizes most federal postsecondary education programs. It would prohibit new federally guaranteed loans from being made under the Federal Family Education Loan (FFEL) Program and would increase direct spending for the Federal Pell Grant Program and other programs. The elimination of…

  18. hpaR, a putative marR family transcriptional regulator, is positively controlled by HrpG and HrpX and involved in the pathogenesis, hypersensitive response, and extracellular protease production of Xanthomonas campestris pathovar campestris.

    Science.gov (United States)

    Wei, Ke; Tang, Dong-Jie; He, Yong-Qiang; Feng, Jia-Xun; Jiang, Bo-Le; Lu, Guang-Tao; Chen, Baoshan; Tang, Ji-Liang

    2007-03-01

    The MarR family of transcriptional regulators of bacteria are involved in the regulation of many cellular processes, including pathogenesis. In this work, we have demonstrated genetically that hpaR (hpa, hrp associated), which encodes a putative MarR family regulator, is involved in the hypersensitive response (HR), pathogenicity, and extracellular protease production of the phytopathogenic bacterium Xanthomonas campestris pathovar campestris. A mutation in hpaR resulted in complete loss of virulence in the host plant cabbage, a delayed and weakened HR in the nonhost plant pepper ECW-10R, and an increase in extracellular protease production. Detection of the beta-glucuronidase activity of a plasmid-driven hpaR promoter-gusA reporter revealed that the expression of hpaR is positively controlled by HrpG and HrpX and is suppressed in rich medium while being strongly induced in minimal and hrp-inducing media and inside the host. These findings indicate that hpaR belongs to the hrpG and hrpX regulon and that HrpX regulates the extracellular protease production via hpaR in X. campestris pv. campestris.

  19. Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome.

    Science.gov (United States)

    Kounis, Nicholas G; Giannopoulos, Sotiris; Tsigkas, Grigorios G; Goudevenos, John

    2012-04-19

    The use of drug eluting stents constitutes a major breakthrough in current interventional cardiology because it is more than halves the need of repeat interventions. It is incontrovertible that coronary stents, in general, have been beneficial for the vast majority of patients. A small increase in thrombosis, following DES implantation, is offset by a diminished risk of complications associated with repeat vascularization. However, late and, especially, very late stent thrombosis is a much feared complication because it is associated with myocardial infarction with increased mortality. Despite that stent thrombosis is thought to be multifactorial, so far clinical reports and reported pathology findings in patients died from coronary stent thrombosis as well as animal studies and experiments, point toward a hypersensitivity inflammation. The stented and thrombotic areas are infiltrated by interacting, via bidirectional stimuli inflammatory cells including eosinophils, macrophages, T-cells and mast cells. Stented regions constitute an ideal surrounding for endothelial damage and dysfunction, together with hemorheologic changes and turbulence as well as platelet dysfunction, coagulation and fibrinolytic disturbances. Drug eluting stent components include the metal strut which contains nickel, chromium, manganese, titanium, molybdenum, the polymer coating and the impregnated drugs which for the first generation stents are: the antimicrotubule antineoplastic agent paclitaxel and the anti-inflammatory, immunosuppressive and antiproliferative agent sirolimus. The newer stents which are called cobalt-chromiun stents and elute the sirolimus analogs everolimus and zotarolimus both contain nickel and other metals. All these components constitute an antigenic complex inside the coronary arteries which apply chronic, continuous, repetitive and persistent inflammatory action capable to induced Kounis syndrome and stent thrombosis. Allergic inflammation goes through three phases

  20. Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay.

    Science.gov (United States)

    Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao

    2016-09-15

    Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response

    Science.gov (United States)

    Pallandre, Jean-René; Borg, Christophe; Loeffert, Sophie; Gbaguidi-Haore, Houssein; Millon, Laurence

    2013-01-01

    Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4+ T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested. PMID:23720369

  2. Hypersensitive response-like reaction is associated with hybrid necrosis in interspecific crosses between tetraploid wheat and Aegilops tauschii coss.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Mizuno

    Full Text Available BACKGROUND: Hybrid speciation is classified into homoploid and polyploid based on ploidy level. Common wheat is an allohexaploid species that originated from a naturally occurring interploidy cross between tetraploid wheat and diploid wild wheat Aegilops tauschii Coss. Aegilops tauschii provides wide naturally occurring genetic variation. Sometimes its triploid hybrids with tetraploid wheat show the following four types of hybrid growth abnormalities: types II and III hybrid necrosis, hybrid chlorosis, and severe growth abortion. The growth abnormalities in the triploid hybrids could act as postzygotic hybridization barriers to prevent formation of hexaploid wheat. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report on the geographical and phylogenetic distribution of Ae. tauschii accessions inducing the hybrid growth abnormalities and showed that they are widely distributed across growth habitats in Ae. tauschii. Molecular and cytological characterization of the type III necrosis phenotype was performed. The hybrid abnormality causing accessions were widely distributed across growth habitats in Ae. tauschii. Transcriptome analysis showed that a number of defense-related genes such as pathogenesis-related genes were highly up-regulated in the type III necrosis lines. Transmission electron microscope observation revealed that cell death occurred accompanied by generation of reactive oxygen species in leaves undergoing type III necrosis. The reduction of photosynthetic activity occurred prior to the appearance of necrotic symptoms on the leaves exhibiting hybrid necrosis. CONCLUSIONS/SIGNIFICANCE: Taking these results together strongly suggests that an autoimmune response might be triggered by intergenomic incompatibility between the tetraploid wheat and Ae. tauschii genomes in type III necrosis, and that genetically programmed cell death could be regarded as a hypersensitive response-like cell death similar to that observed in Arabidopsis

  3. Hypersensitive Response-Like Reaction Is Associated with Hybrid Necrosis in Interspecific Crosses between Tetraploid Wheat and Aegilops tauschii Coss

    Science.gov (United States)

    Mizuno, Nobuyuki; Hosogi, Naoki; Park, Pyoyun; Takumi, Shigeo

    2010-01-01

    Background Hybrid speciation is classified into homoploid and polyploid based on ploidy level. Common wheat is an allohexaploid species that originated from a naturally occurring interploidy cross between tetraploid wheat and diploid wild wheat Aegilops tauschii Coss. Aegilops tauschii provides wide naturally occurring genetic variation. Sometimes its triploid hybrids with tetraploid wheat show the following four types of hybrid growth abnormalities: types II and III hybrid necrosis, hybrid chlorosis, and severe growth abortion. The growth abnormalities in the triploid hybrids could act as postzygotic hybridization barriers to prevent formation of hexaploid wheat. Methodology/Principal Findings Here, we report on the geographical and phylogenetic distribution of Ae. tauschii accessions inducing the hybrid growth abnormalities and showed that they are widely distributed across growth habitats in Ae. tauschii. Molecular and cytological characterization of the type III necrosis phenotype was performed. The hybrid abnormality causing accessions were widely distributed across growth habitats in Ae. tauschii. Transcriptome analysis showed that a number of defense-related genes such as pathogenesis-related genes were highly up-regulated in the type III necrosis lines. Transmission electron microscope observation revealed that cell death occurred accompanied by generation of reactive oxygen species in leaves undergoing type III necrosis. The reduction of photosynthetic activity occurred prior to the appearance of necrotic symptoms on the leaves exhibiting hybrid necrosis. Conclusions/Significance Taking these results together strongly suggests that an autoimmune response might be triggered by intergenomic incompatibility between the tetraploid wheat and Ae. tauschii genomes in type III necrosis, and that genetically programmed cell death could be regarded as a hypersensitive response-like cell death similar to that observed in Arabidopsis intraspecific and Nicotiana

  4. Fra TR til HR?

    DEFF Research Database (Denmark)

    Hagedorn-Rasmussen, Peter; Gleerup, Janne; Bojesen, Anders

    2013-01-01

    Introduktion til temanummer 'Fra TR til HR? Arbejdsmiljøets rolle i moderne arbejdspladsudvikling'......Introduktion til temanummer 'Fra TR til HR? Arbejdsmiljøets rolle i moderne arbejdspladsudvikling'...

  5. Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin.

    Science.gov (United States)

    Correa da Rosa, Joel; Malajian, Dana; Shemer, Avner; Rozenblit, Mariya; Dhingra, Nikhil; Czarnowicki, Tali; Khattri, Saakshi; Ungar, Benjamin; Finney, Robert; Xu, Hui; Zheng, Xiuzhong; Estrada, Yeriel D; Peng, Xiangyu; Suárez-Fariñas, Mayte; Krueger, James G; Guttman-Yassky, Emma

    2015-03-01

    Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated. We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge. Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber). Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, TH1-subset, and TH2-subset genes in nickel-related AD responses, with increased TH17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD. Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of TH1 products, some increases in levels of TH17 products, and inconsistent upregulation in levels of TH2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased TH2, TH17, and

  6. Role of autophagy in disease resistance and hypersensitive response-associated cell death

    DEFF Research Database (Denmark)

    Hofius, Daniel; Munch, David; Bressendorff, Simon

    2011-01-01

    Ancient autophagy pathways are emerging as key defense modules in host eukaryotic cells against microbial pathogens. Apart from actively eliminating intracellular intruders, autophagy is also responsible for cell survival, for example by reducing the deleterious effects of endoplasmic reticulum...... stress. At the same time, autophagy can contribute to cellular suicide. The concurrent engagement of autophagy in these processes during infection may sometimes mask its contribution to differing pro-survival and pro-death decisions. The importance of autophagy in innate immunity in mammals is well...

  7. Transcriptome Analysis of the Sm-Mediated Hypersensitive Response to Stemphylium lycopersici in Tomato

    Directory of Open Access Journals (Sweden)

    Huanhuan Yang

    2017-07-01

    Full Text Available Gray leaf spot disease caused by Stemphylium lycopersici is a major disease in cultivated tomato plants and threatens tomato-growing areas worldwide. Sm is a single dominant gene that confers resistance to tomato gray leaf spot disease agent. However, the underlying molecular mechanism remains unclear. Here, resistant (cv. Motelle, containing the Sm gene and susceptible (cv. Moneymaker plants were inoculated with virulent Stemphylium lycopersici isolate at a time point at which both cultivars showed a strong response to S. lycopersici infection. Transcriptome analyses were performed in both cultivars using RNA-seq. The number of differentially expressed genes (DEGs was higher in Motelle than Moneymaker. Functional classification revealed that most DEGs were involved in plant–pathogen interactions, plant hormone signal transduction, regulation of autophagy, glycerophospholipid metabolism, and α-linolenic acid metabolism. Moreover, the genes that were significantly up-regulated in Sm tomatoes were involved in plant–pathogen interaction pathways. A total of 26 genes were selected for confirmation of differentially expressed levels by quantitative real-time PCR. This knowledge will yield new insights into the molecular mechanism of Sm responses to S. lycopersici infection.

  8. Uitdagingen in HR implementatie

    NARCIS (Netherlands)

    Bos-Nehles, Anna Christina; Boon, C.

    2006-01-01

    Veel wetenschappers gaan ervan uit dat de door organisaties ontwikkelde hr-strategie naadloos overgaat in de geïmplementeerde hr-strategie. Maar in werkelijkheid ontstaat er vaak een grote kloof tussen die twee: hr-strategieën worden geïmplementeerd zonder een duidelijke richtlijn, en sommige

  9. Hypersensitive response of Sesamum prostratum Retz. elicitated by Fusarium oxysporum f. sesame (Schelt) Jacz Butler.

    Science.gov (United States)

    Rajab, Reeja; Rajan, S Sajitha; Satheesh, L Shilpa; Harish, S R; Sunukumar, S S; Sandeep, B S; Mohan, T C Kishor; Murugan, K

    2009-10-01

    Aim of this study was to investigate the intensity and timing of the ROS formation, lipid peroxidation and expression of antioxidant enzymes as initial responses of calli of Sesamum prostratum (SP) against Fusarium oxysporum f. sesame crude toxin metabolite of varying concentrations. 2,4 dichlorophenoxy acetic acid (2,4-D) / coconut milk combinations were found to be more efficient among different hormonal regimes (2,4 -D, 2,4-D/casein hydrosylate and 2,4-D/ coconut milk). The concentration of hydrogen peroxide and lipid peroxidation were higher (13.2 and 5.7-folds, respectively) after 6 h in the treated callus confirmed the oxidative stress. An increase in total phenolics was also detected in inoculated callus. Increased activity of antioxidative enzymes viz., NADPH oxidase and superoxide dismutase (SOD) corroborate with the high level of ROSs, such as O2*- and H2O2. The poor activity of catalase confirmed the oxidative burst in the callus leading to necrosis. Activity of peroxidase was at par with total phenolics. Similarly, phenylalanine ammonia lyase (PAL) also showed high activity revealing the active phase in the synthesis of secondary metabolites in the plant. The oxidative burst generated in the interaction between Sesamum and F. oxysporum f. sesame toxin might be the first line of defense by the host mounted against the invading necrotrophic pathogen. The results suggested that the rapid production of reactive oxygen species in the callus in response to fungal toxin had been proposed to orchestrate the establishment of different defensive barriers against the pathogens.

  10. Odor provocation test for laryngeal hypersensitivity.

    Science.gov (United States)

    Gartner-Schmidt, Jackie L; Rosen, Clark A; Radhakrishnan, Nandhakumar; Ferguson, Berrylin J

    2008-05-01

    This study was to present an odor provocation/challenge test for laryngeal hypersensitivity in a suspected odor induced dysphonic patient. The second aim was to rule out secondary gain from organic laryngeal hypersensitivity. Two steps were taken for this purpose. First, because the evaluation of hypersensitivity may be affected by the perception of odor, the study investigated laryngeal hypersensitivity during nasal and oral breathing separately to disentangle possible cognitive reactions to odors. Second, a healthy control (HC) participant was used with the identical testing protocol for nasal breathing to minimize unbiased results. The HC's response to nasal breathing of the odors showed no response to all the stimuli. The participant with possible secondary gain issues responded differently to the odors when presented nasally versus orally. Oral breathing showed less severe and less frequent laryngeal hypersensitive reactions. This suggests that laryngeal hypersensitivity was either due to the odor, cognitive information, sensory changes in olfaction leading to psychological conditioning, or for any possible secondary gain. Hence, it is difficult to indicate the precise reason (cause and effect) for the participant's laryngeal hypersensitivity; however, this study describes the first structured, controlled, repeatable, and randomized design to investigate odor induced laryngeal hypersensitivity and decipher possible secondary gain from true laryngeal hypersensitivity.

  11. Caretakers or HR Managers

    Directory of Open Access Journals (Sweden)

    James Baba Abugre

    2014-08-01

    Full Text Available Do human resources (HR managers in developing countries have the clout to make strategic decisions during mergers and acquisitions (M&As? This study aims at establishing the major roles played by HR managers in M&As of public sector companies in Ghana. The research examined the M&As of 10 Ghanaian companies where 10 HR managers gave detailed narratives of their roles and the part they played in the M&A processes. The qualitative method used to solicit the narratives of the HR managers resulted in the following findings: that HR managers in Ghana have a limited role in the planning process of the M&A; that indigenous HR managers perform several tasks in the course of the M&A to get employees stable before and after the M&A processes; nevertheless, they are not part of the policy formulators. The article makes a modest input of the significance of indigenous HR role in international M&As as a panacea to solving the global crises by advocating the empowerment of HR managers in developing context to be partners in the initial commencement of M&As.

  12. The Multi-Resistant Reaction of Drought-Tolerant Coffee 'Conilon Clone 14' to Meloidogyne spp. and Late Hypersensitive-Like Response in Coffea canephora.

    Science.gov (United States)

    Lima, Edriana A; Furlanetto, Cleber; Nicole, Michel; Gomes, Ana C M M; Almeida, Maria R A; Jorge-Júnior, Aldemiro; Correa, Valdir R; Salgado, Sônia Maria; Ferrão, Maria A G; Carneiro, Regina M D G

    2015-06-01

    Root-knot nematodes (RKN), Meloidogyne spp., have major economic impact on coffee production in Central and South America. Genetic control of RKN constitutes an essential part for integrated pest management strategy. The objective of this study was to evaluate the resistance of Coffea canephora genotypes (clones) to Meloidogyne spp. Sensitive and drought-tolerant coffee genotypes were used to infer their resistance using nematode reproduction factor and histopathology. Eight clonal genotypes were highly resistant to M. paranaensis. 'Clone 14' (drought-tolerant) and 'ESN2010-04' were the only genotypes highly resistant and moderately resistant, respectively, to both M. incognita races 3 and 1. Several clones were highly resistant to both avirulent and virulent M. exigua. Clone 14 and ESN2010-04 showed multiple resistance to major RKNs tested. Roots of 'clone 14' (resistant) and 'clone 22' (susceptible) were histologically studied against infection by M. incognita race 3 and M. paranaensis. Reduction of juvenile (J2) penetration in clone 14 was first seen at 2 to 6 days after inoculation (DAI). Apparent early hypersensitive reaction (HR) was seen in root cortex between 4 and 6 DAI, which led to cell death and prevention of some nematode development. At 12 to 20 DAI, giant cells formed in the vascular cylinder, besides normal development into J3/J4. From 32 to 45 DAI, giant cells were completely degenerated. Late, intense HR and cell death were frequently observed around young females and giant cells reported for the first time in coffee pathosystem. These results provide rational bases for future studies, including prospection, characterization, and expression profiling of genomic loci involved in both drought tolerance and resistance to multiple RKN species.

  13. Putting HR outsourcing into practice.

    Science.gov (United States)

    Berger, Michael

    2007-01-01

    Faced with the time-consuming responsibility of human resources (HR) management, a growing number of medical practices are outsourcing their HR to professional employer organizations (PEOs) so they can concentrate on their core business. A PEO functions as an HR department-minus the high overhead-managing daily administrative tasks such as payroll processing and related tax filings, employee benefits, and workers' compensation coverage and claims resolution. PEOs help physicians' offices keep up with the piles of paperwork that never seem to shrink, freeing doctors to focus on patient care and building their practice. Because of their volume buying power, PEOs are able to offer employees of small medical practices big-company benefits-everything from health, dental, and vision coverage to long-term disability insurance and tuition assistance. A fledgling industry only a decade ago, HR outsourcing has morphed into a blossoming industry. Enlisting the services of a PEO is now considered de rigueur in many small business circles.

  14. Climate hypersensitivity to solar forcing?

    Directory of Open Access Journals (Sweden)

    W. Soon

    2000-05-01

    Full Text Available We compare the equilibrium climate responses of a quasi-dynamical energy balance model to radiative forcing by equivalent changes in CO2, solar total irradiance (Stot and solar UV (SUV. The response is largest in the SUV case, in which the imposed UV radiative forcing is preferentially absorbed in the layer above 250 mb, in contrast to the weak response from global-columnar radiative loading by increases in CO2 or Stot. The hypersensitive response of the climate system to solar UV forcing is caused by strongly coupled feedback involving vertical static stability, tropical thick cirrus ice clouds and stratospheric ozone. This mechanism offers a plausible explanation of the apparent hypersensitivity of climate to solar forcing, as suggested by analyses of recent climatic records. The model hypersensitivity strongly depends on climate parameters, especially cloud radiative properties, but is effective for arguably realistic values of these parameters. The proposed solar forcing mechanism should be further confirmed using other models (e.g., general circulation models that may better capture radiative and dynamical couplings of the troposphere and stratosphere.Key words: Meteorology and atmospheric dynamics (climatology · general or miscellaneous · Solar physics · astrophysics · and astronomy (ultraviolet emissions

  15. HR som business partner

    DEFF Research Database (Denmark)

    Søndergård, Birger; Jensen, André Barsøe

    2014-01-01

    De fleste af os vælger at antage, at forandringer kan styres, i hvert fald til en vis grad. Ellers ville man også kunne falde i en slags handlingslammelse, og det er ikke, hvad der efterspørges fra HR’s ansvarlige. Der kræves resultater. HR er gennem en årrække blevet langt mere strategisk, hvor ...

  16. Delayed-type hypersensitivity response to crude and fractionated antigens from Fonsecaea pedrosoi CMMI 1 grown in different culture media.

    Science.gov (United States)

    Corbellini, Valeriano Antonio; Scroferneker, Maria Lúcia; Carissimi, Mariana; Santolin, Luciane Domingues

    2006-07-01

    Chromoblastomycosis is a subcutaneous fungal disease caused by dematiaceous fungi, especially by Fonsecaea pedrosoi, regarded as its major causative agent in Brazil. In recent years there has been a decline in the use of skin testing for delayed-type hypersensitivity (DTH) in epidemiological surveys of fungal infections, mainly because of the unpredictability of positive reactions and lack of specificity of the antigens used. The aim of the present study was to assess delayed-type skin tests in guinea pigs experimentally infected with F. pedrosoi using exoantigens prepared from two culture filtrates. Sixteen adult male guinea pigs were inoculated intratesticularly with fungal cells and submitted to sensitivity assays 4 weeks after inoculation. They received an intradermal injection with crude and fractionated antigens from Alviano's and Smith's cultures, and were assessed 24 and 48 h thereafter. Except for one animal, all of them had positive indurations after 48 h. There were no statistical differences between the measurements at 24 and 48 h for each exoantigen used, neither among the induration measurements at 48 h when different preparations were compared. Our results suggest that a delayed-type skin test using antigens produced in synthetic media may be useful for the assessment of primary exposure to chromoblastomycosis.

  17. Lazarus1, a DUF300 Protein, Contributes to Programmed Cell Death Associated with Arabidopsis acd11 and the Hypersensitive Response

    DEFF Research Database (Denmark)

    Malinovsky, F.G.; Brodersen, P.; Fiil, B.K.

    2010-01-01

    , the subcellular localization pattern of LAZ1 suggests that it may have transport functions for yet unknown, death-related signaling molecules at the plasma membrane and/or endosomal compartments. In summary, our results validate the utility of the large-scale suppressor screen to identify novel components...... associated with the HR, in addition to its role in acd11-related death. Furthermore, the similar topology of a plant and human DUF300 proteins suggests similar functions in PCD across the eukaryotic kingdoms, although a direct role for TMEM34 in cell death control remains to be established. Finally...

  18. Hypersensitivity reactions to heparins.

    Science.gov (United States)

    Gonzalez-Delgado, Purificación; Fernandez, Javier

    2016-08-01

    This article provides an update on hypersensitivity reactions to heparins and novel oral anticoagulants, with special emphasis on diagnostic methods and management of patients. Although heparins are drugs widely used, hypersensitivity reactions are uncommon. Cutaneous delayed hypersensitivity reactions after subcutaneous administration affects up to 7.5% of patients. Heparin-induced thrombocytopenia is another unusual but severe condition in which early recognition is crucial. Immediate hypersensitivity reactions to heparins have been also reported, but with the novel oral anticoagulants are much more uncommon, although reports of exanthemas have been notified.Skin tests and subcutaneous provocation test are useful tools in the diagnosis of hypersensitivity reactions, except in heparin-induced thrombocytopenia in which biopsy of lesional skin and in-vitro tests are the modalities of choice to confirm the diagnosis.Management of hypersensitivity reactions includes finding an alternative depending on the type of reaction. Fondaparinux and novel oral anticoagulants may be safe alternatives. Delayed skin lesions after subcutaneous heparin are the most common type of hypersensitivity reactions, followed by life-threatening heparin-induced thrombocytopenia. Immediate reactions are uncommon. Allergologic studies may be useful to find an alternative option in patients with skin lesions in which heparin-induced thrombocytopenia has been previously excluded, as well as in heparin immediate reactions.

  19. Accumulation of gentisic acid as associated with systemic infections but not with the hypersensitive response in plant-pathogen interactions.

    Science.gov (United States)

    Bellés, José M; Garro, Rafael; Pallás, Vicente; Fayos, Joaquín; Rodrigo, Ismael; Conejero, Vicente

    2006-02-01

    In the present work we have studied the accumulation of gentisic acid (2,5-dihydroxybenzoic acid, a metabolic derivative of salicylic acid, SA) in the plant-pathogen systems, Cucumis sativus and Gynura aurantiaca, infected with either prunus necrotic ringspot virus (PNRSV) or the exocortis viroid (CEVd), respectively. Both pathogens produced systemic infections and accumulated large amounts of the intermediary signal molecule gentisic acid as ascertained by electrospray ionization mass spectrometry (ESI-MS) coupled on line with high performance liquid chromatography (HPLC). The compound was found mostly in a conjugated (beta-glucoside) form. Gentisic acid has also been found to accumulate (although at lower levels) in cucumber inoculated with low doses of Pseudomonas syringae pv. tomato, producing a nonnecrotic reaction. In contrast, when cucumber was inoculated with high doses of this pathogen, a hypersensitive reaction occurred, but no gentisic-acid signal was induced. This is consistent with our results supporting the idea that gentisic-acid signaling may be restricted to nonnecrotizing reactions of the host plant (Bellés et al. in Mol Plant-Microbe Interact 12:227-235, 1999). In cucumber and Gynura plants, the activity of gentisic acid as inducing signal was different to that of SA, thus confirming the data found for tomato. Exogenously supplied gentisic acid was able to induce peroxidase activity in both Gynura and cucumber plants in a similar way as SA or pathogens. However, gentisic-acid treatments strongly induced polyphenol oxidase activity in cucumber, whereas pathogen infection or SA treatment resulted in a lower induction of this enzyme. Nevertheless, gentisic acid did not induce other defensive proteins which are induced by SA in these plants. This indicates that gentisic acid could act as an additional signal to SA for the activation of plant defenses in cucumber and Gynura plants.

  20. Gastrointestinal Immune Response to the Shrimp Allergen Tropomyosin: Histological and Immunological Analysis in an Animal Model of Shrimp Tropomyosin Hypersensitivity.

    Science.gov (United States)

    Lam, Yin Fan; Tong, Ka Kui; Kwan, Kin Ming; Tsuneyama, Koichi; Shu, Shang-An; Leung, Patrick S C; Chu, Ka Hou

    2015-01-01

    Shellfish hypersensitivity is among the most common food allergies. A murine model of IgE-mediated shrimp allergy has been established in our laboratory. The aim of this study is to determine the intestinal histological changes and cytokine expression profile of this model sensitized with the major shellfish allergen tropomyosin. Female Balb/c mice orally sensitized and challenged with recombinant tropomyosin were sacrificed. Continuous sections of duodenum, jejunum and ileum were prepared using the Swiss roll technique for histological and immunological analysis. Duodenal epithelial cell apoptosis and migration were examined. mRNA expression of IL-4, IL-6, IL-10, IL-13, IL-18 and IFN-γ in intestinal tissue was measured via RT-PCR. In tropomyosin-sensitized and challenged mice, an increased number of eosinophils, mast cells and goblet cells was found 24 h after challenge. There were also increased mast cell and goblet cell numbers at 72 h after challenge, but the level of eosinophils decreased. Differences compared with control mice are most prominent at the duodenum compared to the distal regions. In addition, TUNEL assay indicates a significantly higher apoptosis rate in sensitized mice sacrificed 72 h after challenge, and mRNA expression showed a biased Th2/Th1 cytokine profile and a higher level of murine mast cell protease 1. This study documented a multitude of histological and immunological changes in the gut in a murine model of shrimp allergy. Even without repetitive intragastric challenge, shrimp tropomyosin induces an increase in the number of inflammatory cells to varying degrees within the small intestine. This model provides an important tool for testing new therapeutic interventions. © 2015 S. Karger AG, Basel.

  1. Rice Hypersensitive Induced Reaction Protein 1 (OsHIR1 associates with plasma membrane and triggers hypersensitive cell death

    Directory of Open Access Journals (Sweden)

    Sun Sai-Ming

    2010-12-01

    Full Text Available Abstract Background In plants, HIR (Hypersensitive Induced Reaction proteins, members of the PID (Proliferation, Ion and Death superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley. However, not much was known about the HIR proteins in rice. Since rice is an important cereal crop consumed by more than 50% of the populations in Asia and Africa, it is crucial to understand the mechanisms of disease responses in this plant. We previously identified the rice HIR1 (OsHIR1 as an interacting partner of the OsLRR1 (rice Leucine-Rich Repeat protein 1. Here we show that OsHIR1 triggers hypersensitive cell death and its localization to the plasma membrane is enhanced by OsLRR1. Result Through electron microscopy studies using wild type rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a minor portion localized to the tonoplast. Moreover, the plasma membrane localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the plasma membrane was confirmed by double-labeling electron microscopy. Pathogen inoculation studies using transgenic Arabidopsis thaliana expressing either OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However, OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive response lesions and contained lower titers of the invading pathogen, when compared to OsLRR1 transgenic plants. Conclusion The OsHIR1 protein is mainly localized to the plasma membrane, and its subcellular localization in that compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the plant

  2. Er HR ude i tovene?

    DEFF Research Database (Denmark)

    Poulfelt, Flemming

    2015-01-01

    HR: Er der behov for nytænkning i HR-land? Artikler i Harvard Business Review - bakket op af en dansk undersøgelse - konkluderer, at HR stadig mangler gennemslagskraft i virksomhederne. Er HR ude i tovene? ... For i undersøgelsen "Ny Dansk Ledelse" (maj 2015), som er baseret på danske lederes...

  3. INNOVATION IN HR RECRUITMENT

    Directory of Open Access Journals (Sweden)

    Alexander L. Ivanov

    2013-01-01

    Full Text Available The article is devoted to research of innovations in HR recruitment. The following issues, related to impact of innovations on recruitment development, are discussed: do innovative technologies mean prospects or threats for traditional recruitment? The research is based on the transformations review, which had an impact on all staff selection areas. The article describes up-to-date approaches and leading practices, which allow to draw a conclusion, that recruitment is highly sensitive against scientific and technical progress and has high innovation potential.

  4. Regulatory B cells induced by ultraviolet B through toll-like receptor 4 signalling contribute to the suppression of contact hypersensitivity responses in mice.

    Science.gov (United States)

    Liu, Xiaoming; Huang, Haiyan; Gao, Hongbin; Wu, Xia; Zhang, Wei; Yu, Bo; Dou, Xia

    2017-12-05

    Ultraviolet (UV) B irradiation is known to suppress contact hypersensitivity (CHS) responses in mouse models by suppressing immune responses. However, the cellular mechanisms responsible for UVB-induced systemic suppression remain unclear. Regulatory B cells have been reported to play an inhibitory role during CHS. It is presently unknown whether regulatory B cells contribute to the effect of UVB phototherapy. To investigate the inductive effect of UVB on regulatory B cells and the underlying mechanisms by using a CHS mouse model. CHS was induced with oxazolone, and evaluated by histopathology, flow cytometry, and quantitative real-time polymerase chain reaction. We found that UVB irradiation induced regulatory B cell expansion and ameliorated CHS. UVB-induced regulatory B cells contribute to systemic immunosuppression by inhibiting the proliferation of T cells. Moreover, we determined that toll-like receptor (TLR) 4, the expression of which was upregulated in B cells after UVB exposure, played an essential role in the induction of regulatory B cells. Our data identified regulatory B cells as regulators of UVB-induced immunosuppression in CHS, and suggest the importance of the UVB-TLR4 axis in the generation of regulatory B cells. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. An NB-LRR protein required for HR signalling mediated by both extra- and intracellular resistance proteins.

    Science.gov (United States)

    Gabriëls, Suzan H E J; Vossen, Jack H; Ekengren, Sophia K; van Ooijen, Gerben; Abd-El-Haliem, Ahmed M; van den Berg, Grardy C M; Rainey, Daphne Y; Martin, Gregory B; Takken, Frank L W; de Wit, Pierre J G M; Joosten, Matthieu H A J

    2007-04-01

    Tomato (Solanum lycopersicum) Cf resistance genes confer hypersensitive response (HR)-associated resistance to strains of the pathogenic fungus Cladosporium fulvum that express the matching avirulence (Avr) gene. Previously, we identified an Avr4-responsive tomato (ART) gene that is required for Cf-4/Avr4-induced HR in Nicotiana benthamiana as demonstrated by virus-induced gene silencing (VIGS). The gene encodes a CC-NB-LRR type resistance (R) protein analogue that we have designated NRC1 (NB-LRR protein required for HR-associated cell death 1). Here we describe that knock-down of NRC1 in tomato not only affects the Cf-4/Avr4-induced HR but also compromises Cf-4-mediated resistance to C. fulvum. In addition, VIGS using NRC1 in N. benthamiana revealed that this protein is also required for the HR induced by the R proteins Cf-9, LeEix, Pto, Rx and Mi. Transient expression of NRC1(D481V), which encodes a constitutively active NRC1 mutant protein, triggers an elicitor-independent HR. Subsequently, we transiently expressed this auto-activating protein in N. benthamiana silenced for genes known to be involved in HR signalling, thereby allowing NRC1 to be positioned in an HR signalling pathway. We found that NRC1 requires RAR1 and SGT1 to be functional, whereas it does not require NDR1 and EDS1. As the Cf-4 protein requires EDS1 for its function, we hypothesize that NRC1 functions downstream of EDS1. We also found that NRC1 acts upstream of a MAP kinase pathway. We conclude that Cf-mediated resistance signalling requires a downstream NB-LRR protein that also functions in cell death signalling pathways triggered by other R proteins.

  6. Hypersensitivity to Suture Anchors

    OpenAIRE

    Masafumi Goto; Masafumi Gotoh; Yasuhiro Mitsui; Ryo Tanesue; Takahiro Okawa; Fujio Higuchi; Naoto Shiba

    2013-01-01

    Hypersensitivity to suture anchor is extremely rare. Herein, we present a case in which hypersensitivity to suture anchor was strongly suspected. The right rotator cuff of a 50-year-old woman was repaired with a metal suture anchor. Three weeks after the surgery, she developed erythema around her face, trunk, and hands, accompanied by itching. Infection was unlikely because no abnormalities were detected by blood testing or by medical examination. Suspicious of a metallic allergy, a dermatolo...

  7. Epidemiology of dentin hypersensitivity

    OpenAIRE

    Splieth, Christian H.; Tachou, Aikaterini

    2012-01-01

    Objective In contrast to the well-established caries epidemiology, data on dentin hypersensitivity seem to be scarce and contradictory. This review evaluates the available literature on dentin hypersensitivity and assesses its prevalence, distribution, and potential changes. Materials and methods The systematic search was performed to identify and select relevant publications with several key words in electronic databases. In addition, the articles? bibliographies were consulted. Results Prev...

  8. Histopathological Characterization of Cutaneous Delayed-type Hypersensitivity and Correlations with Intestinal Pathology and Systemic Immune Responses in Sheep with Paratuberculosis.

    Science.gov (United States)

    Gulliver, E L; Plain, K M; Begg, D J; Whittington, R J

    2015-01-01

    Cell-mediated immunity has been exploited historically in the diagnosis of mycobacterial diseases through elicitation of a delayed-type hypersensitivity (DTH) reaction following intradermal injection of an antigen. Here we describe the histopathological features of the cutaneous DTH reaction and its association with intestinal pathology and systemic immune responses in sheep with Mycobacterium avium subspecies paratuberculosis (MAP) infection. A mixed mononuclear cellular infiltrate dominated the DTH reaction and was present in perivascular and periadnexal patterns. Multiple multinucleate giant cells were present in the cellular infiltrate in one sheep while plasma cells were an obvious feature in six others. Sheep with paucibacillary intestinal lesions had the greatest degrees of cutaneous induration, more severe cellular infiltration in DTH lesions and high systemic interferon (IFN)-γ production. In contrast, sheep with multibacillary intestinal lesions, and particularly those with dissemination of MAP to extra-intestinal tissues, had minimal cutaneous induration, nil to mild cellular infiltration in DTH lesions and high serum anti-MAP antibody levels. Systemic IFN-γ production generally was augmented following skin sensitization. In general, the gross and histopathological features of the cutaneous DTH response matched the stage of paratuberculosis reflected by intestinal pathology and systemic measures of humoral and cellular immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Combined dermal exposure to permethrin and cis-urocanic acid suppresses the contact hypersensitivity response in C57BL/6N mice in an additive manner.

    Science.gov (United States)

    Prater, M R; Blaylock, B L; Holladay, S D

    2005-01-14

    Cutaneous exposure to the pyrethroid insecticide permethrin significantly suppresses contact hypersensitivity (CH) response to oxazolone in C57BL/6N mice. Additionally, cis-urocanic acid (cUCA), an endogenous cutaneous chromophore isomerized to its active form following exposure to ultraviolet radiation, modulates cell-mediated cutaneous immune responses. This study describes cutaneous immune alterations following combined topical permethrin and intradermal cUCA exposure. Female C57BL/6N mice were administered 5, 50 or 100 microg cUCA daily for 5 consecutive days. CH was then evaluated by the mouse ear swelling test (MEST) response to oxazolone. Decreased responses of 52.3%, 76.3% and 76.3%, respectively, as compared to controls were observed. Then, mice were co-exposed to 5 microg cUCA daily for 5 days and 1.5, 5, 15, or 25 microL permethrin, on either day 1, 3 or 5 of the cUCA treatment to evaluate combined immunomodulatory effects of the two chemicals, or cUCA daily for 5 days followed by permethrin on day 3, 5, or 7 after the last cUCA injection to demonstrate prolonged immunosuppressive effects. Two days after final treatment, mice were sensitized with oxazolone and MEST was performed. Mice receiving five cUCA injections and permethrin topically on cUCA injection day 1 showed up to 93.3% suppression of MEST compared to vehicle control. CH was suppressed by 87.5%, 86.6% and 74.2% in mice treated with 25 muL permethrin on days 3, 5 and 7 after cUCA, respectively, compared to vehicle control. Taken together, these data indicate co-exposure to cUCA and permethrin profoundly suppresses cell-mediated cutaneous immunity.

  10. Anandamide attenuates Th-17 cell-mediated delayed-type hypersensitivity response by triggering IL-10 production and consequent microRNA induction.

    Directory of Open Access Journals (Sweden)

    Austin R Jackson

    Full Text Available Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions. However, their role in the regulation of Th17 cells has not been studied previously. In the current study, we used methylated Bovine Serum Albumin [mBSA]-induced delayed type hypersensitivity [DTH] response in C57BL/6 mice, mediated by Th17 cells, as a model to test the anti-inflammatory effects of endocannabinoids. Administration of anandamide [AEA], a member of the endocannabinoid family, into mice resulted in significant mitigation of mBSA-induced inflammation, including foot pad swelling, cell infiltration, and cell proliferation in the draining lymph nodes [LN]. AEA treatment significantly reduced IL-17 and IFN-γ production, as well as decreased RORγt expression while causing significant induction of IL-10 in the draining LNs. IL-10 was critical for the AEA-induced mitigation of DTH response inasmuch as neutralization of IL-10 reversed the effects of AEA. We next analyzed miRNA from the LN cells and found that 100 out of 609 miRNA species were differentially regulated in AEA-treated mice when compared to controls. Several of these miRNAs targeted proinflammatory mediators. Interestingly, many of these miRNA were also upregulated upon in vitro treatment of LN cells with IL-10. Together, the current study demonstrates that AEA may suppress Th-17 cell-mediated DTH response by inducing IL-10 which in turn triggers miRNA that target proinflammatory pathways.

  11. Stat5 gene dosage in T cells modulates CD8+ T-cell homeostasis and attenuates contact hypersensitivity response in mice.

    Science.gov (United States)

    Nivarthi, H; Prchal-Murphy, M; Swoboda, A; Hager, M; Schlederer, M; Kenner, L; Tuckermann, J; Sexl, V; Moriggl, R; Ermakova, O

    2015-01-01

    Contact hypersensitivity assay (CHS) faithfully models human allergies. The Stat5 transcription factors are essential for both lymphocyte development and acute immune responses. Although consequences of Stat5 ablation and transgenic overexpression for the lymphocyte development and functions have been extensively studied, the role of Stat5 gene dosage in contact allergies has not been addressed. We investigated the effect of Stat5 gene dosage modulation in contact allergies using CHS in mice. Transgenic animals heterozygous for the germline Stat5 null allele were subjected to CHS. To dissect cell type sensitive to Stat5 gene dosage, animals with Stat5 haplo-insufficiency in T cells, where one Stat5 allele was removed by Lck-Cre-mediated deletion (Stat5(ΔT/+)), were tested by CHS. Frequency of T cells, B cells, and monocytes were analyzed in Stat5(ΔT/+) and wild-type animals by flow cytometry. Proliferation of Stat5(ΔT/+) CD8(+) T cells was studied in vitro by stimulation with IL-4 and IL-2 cytokines, and changes in the expression of Stat5 target genes were assayed by quantitative real-time PCR assay. Haplo-insufficiency of Stat5 in T cells leads to the reduction in CD8(+) T cells in all lymphoid organs and attenuates CHS response. Stat5(ΔT/+) CD8(+) T cells failed to fully activate Stat5-dependent expression of cell cycle/survival target genes, such as Bcl2 and Pim1, and to proliferate efficiently in response to IL-2 and IL-4 cytokine. Our data identify Stat5 as a dose-dependent regulator of CD8(+) T-cell functions in contact allergies and suggest that modulation of Stat5 dosage could be used to target contact allergies in humans. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Delayed-type hypersensitivity (DTH) test anergy does not impact CD4 reconstitution or normalization of DTH responses during antiretroviral therapy.

    Science.gov (United States)

    Minidis, Natascha M; Mesner, Octavio; Agan, Brian K; Okulicz, Jason F

    2014-01-01

    Delayed-type hypersensitivity (DTH) testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)-suppressive HAART in the U.S. Military HIV Natural History Study. Treatment-naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302). DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0-1) or non-anergic (≥2). Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation. Non-anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/μL, interquartile range (IQR) 315-517 vs. 373 cells/μL, IQR 228-487; p=0.104) and VL (4.3 log10 copies/mL, IQR 3.4-4.9 vs. 4.4 log10 copies/mL, IQR 3.6-5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/μL, IQR 115-358) and anergic groups (246 cells/μL, IQR 136-358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0

  13. The magnitude and kinetics of delayed-type hypersensitivity responses in mice vaccinated with irradiated cercariae of Schistoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Ratcliffe, E.C.; Wilson, R.A. (York Univ. (United Kingdom). Dept. of Biology)

    1991-08-01

    A footpad assay was used to measure the DTH of mice to soluble worm antigens (SWAP), and to living day 7 lung schistosomula, following vaccination and challenge infections with Schistosoma mansoni. DTH to SWAP was first observed on day 10, and reached its maximum on day 17 post-vaccination. Treatment of mice with anti-CD4 antibody on the 3 days prior to footpad challenge completely abrogated this response. Reactivity to living parasites was of a slower order than that to SWAP; it also peaked earlier, on day 10 post-vaccination. By day 35, responsiveness to both sets of antigens had declined almost to control levels. There was no correlation between the level of DTH to living schistosomula, at any time, and the degree of resistance subsequently developed. Percutaneous challenge of vaccinated mice was followed by a resurgence of reactivity to SWAP. This secondary response occurred more rapidly than the primary response, peaking on day 7 post-challenge, and was of a similar magnitude. We were unable to detect a similar recall of DTH to living schistosomula, possibly because the assay was insufficiently sensitive. We conclude that the intensity and kinetics of DTH responsiveness are crucial features of the irradiated vaccine model, and suggest that further investigation of cell-mediated immune reaction, particularly those occuring in the lungs, is vital to a better understanding of events underlying the development and expression of immunity. (author).

  14. Chronic loss of noradrenergic tone produces β-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens.

    Science.gov (United States)

    Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J; Bowles, Dawn E; Meyer, Rebecca C; Hall, Randy A; Ko, Daijin; Paladini, Carlos A; Weinshenker, David

    2016-01-01

    Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs. © 2014 Society for the Study of Addiction.

  15. Dentin hypersensitivity: prevalence, etiology, pathogenesis, and management

    NARCIS (Netherlands)

    van Loveren, C.; Schmidlin, P.R.; Martens, L.C.; Amaechi, B.T.; Amaechi, B.T.

    2015-01-01

    Dentin hypersensitivity is simply defined as a short sharply painful reaction of the exposed and innervated pulp-dentin complex in response to stimuli being typically thermal, evaporative, tactile, osmotic, or chemical and which reaction cannot be attributed to any dental defect or pathology. To be

  16. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

    Science.gov (United States)

    Boiko, Nina; Medrano, Geraldo; Montano, Elizabeth; Jiang, Nan; Williams, Claire R; Madungwe, Ngonidzashe B; Bopassa, Jean C; Kim, Charles C; Parrish, Jay Z; Hargreaves, Kenneth M; Stockand, James D; Eaton, Benjamin A

    2017-01-01

    Chemotherapy induced peripheral neuropathy (CIPN), a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1) channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  17. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

    Directory of Open Access Journals (Sweden)

    Nina Boiko

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN, a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1 channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  18. Efficacy of broad-spectrum sunscreens against the suppression of elicitation of delayed-type hypersensitivity responses in humans depends on the level of ultraviolet A protection.

    Science.gov (United States)

    Moyal, D D; Fourtanier, A M

    2003-04-01

    Sunscreens have been designed to protect against sunburn and their efficacy has, therefore, been labeled by the so-called sun protection factor (SPF). Although this value is well determined using a standardized protocol and it affords a good evaluation of the protection against erythema it may be inadequate to provide a relevant measurement of efficacy against other biologic damages. This is particularly true when action spectra and threshold dose are different from those of erythema. In the case of ultraviolet (UV)-induced immune suppression, the action spectrum is not known, so it cannot be asserted that SPF may accurately predict the level of protection against this endpoint. We addressed this issue by measuring in human volunteers the ability of two broad-spectrum SPF 15 sunscreens with different ultraviolet A (UVA) protection levels, to prevent the alteration of the efferent phase of the local delayed-type hypersensitivity (DTH) response to recall antigens (Multitest Pasteur/Mérieux, Lyon, France) after acute solar-simulated UV exposure. We first determined the ultraviolet radiation (UVR) dose needed to induce a significant DTH inhibition in several groups of 15 volunteers. Two minimal erythemal doses (2 MED) were found to be the minimal immunosuppressive dose (MISD). As a result, the immune DTH response is reduced in average by 36%. The lower doses tested (0.5 and 1 MED) were ineffective. Sunscreen-treated groups were exposed to either 1 or 2 MED x SPF doses. As expected, no alteration in DTH response was observed in the groups exposed to 1 MED x SPF whatever the sunscreen applied. In contrast, after exposure to 2 MED x SPF, the DTH response remained unaltered in the group pretreated with the sunscreen product with the higher protection in the UVA range but was significantly suppressed by 55.7% in the group pretreated with sunscreen with a much lower protection in the UVA range. These data suggest that SPF may not be sufficient to predict the ability of

  19. HR Shared Services and the Realignment of HR.

    Science.gov (United States)

    Reilly, P.

    This report examines how adopting the shared services model of human resources (HR) services delivery can help businesses achieve better alignment between their HR service and specific business needs. Chapter 1 provides background information on the research project underlying this report, which included the following data collection activities:…

  20. Managing hypersensitivity to asparaginase in pediatrics, adolescents, and young adults.

    Science.gov (United States)

    Shinnick, Sara E; Browning, Mary L; Koontz, Susannah E

    2013-01-01

    Hypersensitivity reactions to chemotherapeutic drugs have been documented for numerous cancer therapies. Clinical hypersensitivity to Escherichia coli asparaginase has been reported to range from 0% to 75%. Throughout the United States, nurses assume frontline responsibility for the assessment of asparaginase-related hypersensitivity reactions. It is essential that nurses educate themselves on the signs and symptoms of asparaginase-related hypersensitivity reactions as well as current supportive care approaches. The purpose of this review is to summarize acute lymphoblastic leukemia and the role of asparaginase and the pathology of allergic reactions. We will also update nurses on the differences in asparaginase preparations including dosing, half-life, rates of hypersensitivity, and routes of administration. A summary of current management and supportive care strategies will be provided as will a discussion of the relationship between allergy, antibodies, and asparaginase activity.

  1. Delayed-type hypersensitivity (DTH test anergy does not impact CD4 reconstitution or normalization of DTH responses during antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Natascha M Minidis

    2014-02-01

    Full Text Available Introduction: Delayed-type hypersensitivity (DTH testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL-suppressive HAART in the U.S. Military HIV Natural History Study. Methods: Treatment-naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302. DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0–1 or non-anergic (≥2. Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation. Results: Non-anergic responses were observed in 216 (72% participants, while 86 (28% individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/μL, interquartile range (IQR 315–517 vs. 373 cells/μL, IQR 228–487; p=0.104 and VL (4.3 log10 copies/mL, IQR 3.4–4.9 vs. 4.4 log10 copies/mL, IQR 3.6–5.0; p=0.292. Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/μL, IQR 115–358 and anergic groups (246 cells/μL, IQR 136–358; p=0.498. For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%. Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129 nor with AIDS diagnoses

  2. Hypersensitivity to Suture Anchors

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    Masafumi Goto

    2013-01-01

    Full Text Available Hypersensitivity to suture anchor is extremely rare. Herein, we present a case in which hypersensitivity to suture anchor was strongly suspected. The right rotator cuff of a 50-year-old woman was repaired with a metal suture anchor. Three weeks after the surgery, she developed erythema around her face, trunk, and hands, accompanied by itching. Infection was unlikely because no abnormalities were detected by blood testing or by medical examination. Suspicious of a metallic allergy, a dermatologist performed a patch testing 6 months after the first surgery. The patient had negative reactions to tests for titanium, aluminum, and vanadium, which were the principal components of the suture anchor. The anchor was removed 7 months after the first surgery, and the erythema disappeared immediately. When allergic symptoms occur and persist after the use of a metal anchor, removal should be considered as a treatment option even if the patch test result is negative.

  3. Experimental studies of immunologically mediated enteropathy: IV. Correlation between immune effector mechanisms and type of enteropathy during a GvHR in neonatal mice of different ages.

    Science.gov (United States)

    Felstein, M V; Mowat, A M

    1988-01-01

    We have used the intestinal phase of the graft-versus-host-reaction (GvHR) in unirradiated F1 mice as a model for enteropathy due to cell-mediated immunity (CMI). Injection of neonatal (CBA x BALB/c)F1 mice less than 48 h old with CBA spleen cells produced an acute GvHR, which was associated with runting and severe intestinal damage, characterized by villus atrophy. These animals developed specific cytotoxic T lymphocyte (CTL) activity and invariably died. In contrast, 7-day-old F1 mice with GvHR developed a proliferative GvHR, characterized by intense splenomegaly, NK cell activation and intestinal crypt hyperplasia. These mice did not lose weight, had no villus atrophy or CTL activity and all recovered. A similar proliferative phase was also found to precede the established GvHR in 1-2-day-old hosts. Induction of a GvHR in 5-day-old hosts produced a disease with some characteristics of both proliferative and destructive GvHR, with some mice developing weight loss and villus atrophy, while others showed only crypt hyperplasia and NK cell activation. However, there was very little specific CTL activity in any of these animals. These results indicate that markedly different forms of GvHR can be induced in mice during the first week of life and that these are associated with different pathological effects. Although the immunological mechanisms which are activated may also differ between the types of GvHR, our findings support the hypothesis that intestinal damage which includes villus atrophy is merely a progressive form of the delayed type hypersensitivity responsible for a proliferative enteropathy. PMID:3396213

  4. Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.

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    Renata Curciarello

    Full Text Available BACKGROUND: Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. METHODS: Cow's milk protein (CMP-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test to evaluate the in vitro recognition of soybean proteins (SP. Recombinant Gly m 5 (α, a truncated fragment containing the C-terminal domain (α-T and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR. Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. RESULTS: Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. CONCLUSIONS: Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide.

  5. Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.

    Science.gov (United States)

    Curciarello, Renata; Smaldini, Paola L; Candreva, Angela M; González, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A; Petruccelli, Silvana; Docena, Guillermo H

    2014-01-01

    Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide.

  6. Therapeutic effects of a fermented soy product on peanut hypersensitivity is associated with modulation of T-helper type 1 and T-helper type 2 responses.

    Science.gov (United States)

    Zhang, T; Pan, W; Takebe, M; Schofield, B; Sampson, H; Li, X-M

    2008-11-01

    ImmuBalance is a koji fungus (Aspergillus oryzae) and lactic acid fermented soybean product. This unique production process is believed to create a food supplement that helps to induce or maintain normal immune response. To assess possible therapeutic effects of ImmuBalance on peanut (PN) hypersensitivity using a murine model of peanut allergy (PNA). PN allergic C3H/HeJ mice were fed standard mouse chow containing 0.5% or 1.0% ImmuBalance (ImmuBalance 2X), radiation-inactivated 1.0% ImmuBalance (I-ImmuBalance 2X), or regular diet chow (sham) for 4 weeks, beginning 10 weeks after the initial PN sensitization, and then challenged with PN. Anaphylactic symptom scores, plasma histamine, serum PN specific-IgE levels and splenocyte cytokine profiles were determined. While 100% of sham-treated PNA mice developed anaphylactic reactions with a median score of 3.3 following PN challenge, only 50% of ImmuBalance, 30% of ImmuBalance 2X and 40% of I-ImmuBalance 2X-treated mice developed allergic reactions with median scores of 1.0, 0.4 and 0.5 respectively, which were significantly less than that in the sham-treated mice (P<0.05). Plasma histamine and PN specific-IgE levels were also significantly less in all treated mice than in sham-treated mice (P<0.05). Furthermore, IL-4, IL-5 and IL-13 production by PN-stimulated splenocytes in vitro from ImmuBalance fed mice were markedly reduced compared with sham-treated mice, whereas IFN-gamma production was moderately increased. TGF-beta and TNF-alpha production were similar. ImmuBalance protects against PN-induced anaphylaxis when administered as a food supplement in this model. Protection was associated with down-regulation of Th2 responses. This supplement may provide a potential novel therapy for PNA.

  7. Paraben Contact Hypersensitivity

    Directory of Open Access Journals (Sweden)

    A K Bajaj

    1985-01-01

    Full Text Available One hundred patients suspected to be having contact hypersensitivity to topical medicaments were patch tested with methly and propyl parabens along with commercially available topical medicaments. Six patients showed positive reactions to parabens. Two patients each were positive to methyl paraben and propyl paraben and two showed positive reactions to both of these. Three patients each showed positive reactions to soframycin, econazole and nitrofurazone also.

  8. Vaccine-associated hypersensitivity.

    Science.gov (United States)

    McNeil, Michael M; DeStefano, Frank

    2018-02-01

    Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell-mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines' antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being. Published by Elsevier Inc.

  9. [Food hypersensitivity in children].

    Science.gov (United States)

    Kolacek, Sanja

    2011-01-01

    Food hypersensitivity affects children and adults with an increasing prevalence, and is therefore an important public health problem in the majority of developed countries. Moreover, self-reported reactions to food are of several times higher prevalence, compared to hypersensitivity diagnosed following well established evidence-based diagnostic guidelines. In children, allergic food reactions are more common compared to non-allergic food hypersensitivity reactions, and 90% of them are caused with only 8 food allergens: cow's milk, soya, egg, fish, shellfish, peanut, tree-nuts and gluten. Diagnosis should be based on challenge tests with the potentially offending food allergens. Concerning other, more conservative diagnostic procedures, negative serology and negative skin-prick tests can exclude IgE-mediated food allergy, but positive tests, due to high rate of false positive reactions are not sufficient for diagnosis. Strict dietary avoidance of incriminated allergens is the only well established management strategy. However, this should be applied only if food allergy is well documented - following the exposition tests. Introducing elimination diet in a paediatric population, particularly with the elimination of multiple foods, could cause inappropriate growth and disturb organ maturation. Concerning allergy prevention, avoidance of allergens is not efficacious either during pregnancy and lactation or weaning period, and is therefore, not recommended neither as a population preventive measure, nor in children at risk.

  10. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

    Science.gov (United States)

    Chang, Xiaoli; Heene, Ernst; Qiao, Fei; Nick, Peter

    2011-01-01

    Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR), while susceptible European Vitis vinifera cv. 'Pinot Noir' does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy) transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. 'Pinot Noir' accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative δ-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5) transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death.

  11. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

    Directory of Open Access Journals (Sweden)

    Xiaoli Chang

    Full Text Available Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR, while susceptible European Vitis vinifera cv. 'Pinot Noir' does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. 'Pinot Noir' accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative δ-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5 transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death.

  12. Lung delayed-type hypersensitivity in stressed mice.

    OpenAIRE

    Blecha, F; Topliff, D

    1984-01-01

    The influence of an immobilization stressor on lung cellular immune responses was studied. Delayed-type hypersensitivity to sheep erythrocytes was used to evaluate in vivo lung cellular immunity. Mice were sensitized intravenously and challenged intratracheally with sheep erythrocytes. Three hours prior to challenge all mice were injected intravenously with chromium-51 labeled mononuclear cells from syngeneic mice. The delayed-type hypersensitivity response was measured by counting the radioa...

  13. Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty.

    Science.gov (United States)

    Mitchelson, Andrew J; Wilson, Craig J; Mihalko, William M; Grupp, Thomas M; Manning, Blaine T; Dennis, Douglas A; Goodman, Stuart B; Tzeng, Tony H; Vasdev, Sonia; Saleh, Khaled J

    2015-01-01

    The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected.

  14. Immediate-type hypersensitivity drug reactions.

    Science.gov (United States)

    Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A

    2014-07-01

    Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. © 2013 The British Pharmacological Society.

  15. Sulphasalazine Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Hatice Şanlı

    2013-05-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is one of the most dangerous drug reactions. Mortality and morbidity is increased by consequent systemic organ involvement. Maculopapular eruptions are the most common lesions accompanying DIHS, however, the morphology of skin lesions may vary. The most common cause of DIHS is the use of aromatic anticonvulsant drugs. However, one must not forget that other drugs may also cause DIHS. Early recognition of the condition is the most important step in the treatment. Herein, we present a case of DIHS triggered by sulphasalazine and associated with pustular eruption and maculopapular eruption.

  16. Strategic HR Policy and Planning Officer | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The incumbent is responsible for developing new policy or revising existing policies for the full range of human resources areas in the Centre, as well as the management of related projects in line with Centre's priorities and Strategic HR Plan. The incumbent is responsible for liaising and supporting members of the HR team ...

  17. [Multi-factoriality of dentine hypersensitivity].

    Science.gov (United States)

    Stojsin, Ivana; Petrović, Ljubomir; Stojanac, Igor; Drobac, Milan

    2008-01-01

    Dentine hypersensitivity has been defined as a sharp, short pain arising from exposed dentin in response to stimuli typically thermal, evaporative tactile, osmoticor, chemical and which cannot be ascribed to any other form of dental defect or pathology. The most affected patients range in age from 20 to 40. The following teeth tend to be most sensitive: cuspids, premnolars and incisors, location-concentrated on the facial surface. MORPHOLOGICAL BASES OF DENTINE HYPERSENSITIVITY: Sensitive teeth have much greater numbers of open tubules per unit area and the average diameter of tubules is almost 2 times greater than tubules in nonsensitive teeth. MECHANISMS OF DENTINE HYPERSENSITIVITY: The most widely accepted theory of how the pain occurs is Brannstroms theory. Dentine hypersensitivity represents a condition of presumable multifactorial pathology. Two processes are essential for its development: (1) dentin must be exposed through either genetic disturbance, enamel defect (lamellae, tufs and spindles), loss of enamel (erosion, abrasion, attrition, abfraction), gingival recession with rapid loss of cementum and (2) the dentin tubules must be open to both the oral cavity and the pulp. Diagnostic protocol for this condition consisted of Medical, Dental Dietary, Oral Hygiene History and Inra-oral examinations with air indexing method. Differential Dianosis: We must take into consideration a numnber of variables such as: dental caries, cracked tooth, restorative sensitivity, medication sensitivity, bleaching sensitivity and abscessed or non-vital tooth. Dentin hypersensitivity is a problem that bothers many patients. Many conditions share the symptoms of tooth sensitivity so differential diagnosis is essential for suitable treatment or preventive measures.

  18. Equine insect bite hypersensitivity: immunoblot analysis of IgE and IgG subclass responses to Culicoides nubeculosus salivary gland extract.

    Science.gov (United States)

    Hellberg, W; Wilson, A D; Mellor, P; Doherr, M G; Torsteinsdottir, S; Zurbriggen, A; Jungi, T; Marti, E

    2006-09-15

    Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides and sometimes Simulium spp. The allergens causing IBH are probably salivary gland proteins from these insects, but they have not yet been identified. The aim of our study was to identify the number and molecular weight of salivary gland extract (SGE) proteins derived from Culicoides nubeculosus which are able to bind IgE antibodies (ab) from the sera of IBH-affected horses. Additionally, we sought to investigate the IgG subclass (IgGa, IgGb and IgGT) reactivity to these proteins. Individual IgE and IgG subclass responses to proteins of C. nubeculosus SGE were evaluated by immunoblot in 42 IBH-affected and 26 healthy horses belonging to different groups (Icelandic horses born in Iceland, Icelandic horses and horses from different breeds born in mainland Europe). Additionally, the specific antibody response was studied before exposure to bites of Culicoides spp. and over a period of 3 years in a cohort of 10 Icelandic horses born in Iceland and imported to Switzerland. Ten IgE-binding protein bands with approximate molecular weights of 75, 66, 52, 48, 47, 32, 22/21, 19, 15, 13/12 kDa were found in the SGE. Five of these bands bound IgE from 50% or more of the horse sera. Thirty-nine of the 42 IBH-affected horses but only 2 of the 26 healthy horses showed IgE-binding to the SGE (p<0.000001). Similarly, more IBH-affected than healthy horses had IgGa ab binding to the Culicoides SGE (19/22 and 9/22, respectively, p<0.01). Sera of IBH-affected horses contained IgE, IgGa and IgGT but not IgGb ab against significantly more protein bands than the sera of the healthy horses. The cohort of 10 Icelandic horses confirmed these results and showed that Culicoides SGE specific IgE correlates with onset of IBH. IBH-affected horses that were born in Iceland had IgGa and IgGT ab (p< or =0.01) as well as IgE ab (p=0.06) against a significantly higher number of

  19. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  20. Hypersensitivity to antihistamines.

    Science.gov (United States)

    Shakouri, Alireza A; Bahna, Sami L

    2013-01-01

    Antihistamines are the cornerstone of allergy therapy and are not expected to cause hypersensitivity reactions. We describe two cases, one had urticaria to multiple anti-H1-preparations and the other had anaphylaxis to hydroxyzine. We also provide a review of the English literature on reported reactions regarding causative preparations and manifestations. The latter showed a wide range; most commonly urticaria/angioedema, contact dermatitis, anaphylaxis, and fixed drug eruption (FDE). Most reported cases were young to middle age adults, with apparent predilection to female subjects. The onset of reactions varied from a few minutes for anaphylaxis and urticaria/angioedema, several hours for maculopapular rashes, or longer for contact dermatitis and FDE. Almost all antihistamines have been reported as causing reactions; cetirizine was the most common oral preparation followed by its parent drug, hydroxyzine. Doxepin cream was the most commonly implicated topical preparation in causing contact dermatitis. A causal relationship is often difficult to recognize because the reaction may be similar to the disease being treated with that antihistamine preparation. Reactions to one preparation are likely to occur, but not always, to other members of the same class. Diagnosis is based on clinical suspicion and may be verified by challenge testing. Except for patch testing in contact dermatitis or fixed eruption, other tests have not shown optimal reliability. In most cases, challenge testing with multiple preparations would identify one or more preparations that can be tolerated. Although hypersensitivity to antihistamines seems to be very rare, awareness of the problem would reduce its misdiagnosis.

  1. Clinical heterogeneity of drug hypersensitivity.

    Science.gov (United States)

    Roujeau, Jean-Claude

    2005-04-15

    Skin is the most frequent target of drug reactions that are reported, may be because they are easily detected. Most (probably more than 90%) are related to drug hypersensitivity, i.e. an individually tailored, unexpected effect mediated by a drug specific activation of the immune response. The clinical presentation of "drug eruptions" is highly variable, from the most common transient and benign erythema that occurs 6-9 days after the introduction of a new drug in 1 to 3 % of users to the most severe forms, that fortunately affect less than 1/10,000 users. Even though there are some overlapping or unclassifiable cases, it is important for clinicians to recognize and categorize severe cutaneous adverse reactions/SCAR (bullous fixed drug eruptions/bFDE, acute generalized exanthematous pustulosis/AGEP, drug reaction with eosinophilia and systemic symptoms/DRESS, Stevens-Johnson syndrome/SJS, toxic epidermal necrolysis/TEN). First they must suspect rapidly that an unusual eruption with high fever and severe constitutional symptoms is caused by a medication and not by an infection. Second they have to look for involvement of organs that differ according to the type of reaction. Third they can determine a prognosis, the mortality rate being virtually 0 for bFDE, 5% for AGEP, 10% for "hypersensitivity syndrome"/DRESS and 25% for SJS or TEN. In addition if some medications are "usual suspects" for all types (e.g. anticonvulsants), some other are more specific of a given pattern (pristinamycine, hydroxychloroquine, diltiazem for AGEP, minocycline for DRESS, anti-infectious sulfonamides, allopurinol for epidermal necrolysis). The "phenotypic" diversity of the final expression drug reactions can be explained by the engagement of a variety of cytokines and inflammatory cells and by regulatory mechanisms. For example, memory cytotoxic T-Cells are key effectors in both localized blisters of bFDE and in extensive blisters of epidermal necrolysis.

  2. Multi-factoriality of dentine hypersensitivity

    OpenAIRE

    Stojšin Ivana; Petrović Ljubomir; Stojanac Igor; Drobac Milan

    2008-01-01

    Introduction. Dentine hypersensitivity has been defined as a sharp, short pain arising from exposed dentin in response to stimuli typically thermal, evaporative tactile, osmoticor, chemical and which cannot be ascribed to any other form of dental defect or pathology. Prevalence. The most affected patients range in age from 20 to 40. The following teeth tend to be most sensitive: cuspids, premolars and incisors, location-concentrated on the facial surface. Morphological bases of dentine hypers...

  3. Hr Pitt mängib hr Smithi / Timo Diener

    Index Scriptorium Estoniae

    Diener, Timo

    2005-01-01

    Brad Pitt actionkomöödias "Hr ja pr Smith" ("Mr and Mrs Smith") : režissöör Doug Liman : Ameerika Ühendriigid 2005. Filmi ümber puhkenud skandaalist ning näitleja plaanitavatest filmirollidest aastal 2006

  4. Drug hypersensitivity in students from São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Luis Felipe Chiaverini Ensina

    2010-01-01

    Full Text Available BACKGROUND: Drug hypersensitivity is responsible for substantial mortality and morbidity, and increased health costs. However, epidemiological data on drug hypersensitivity in general or specific populations are scarce. METHODS: We performed a cross-sectional survey of 1015 university students, using a self-reported questionnaire. RESULTS: The prevalence of self-reported drug hypersensitivity was 12,11% (123/1015. The most frequently implicated drugs were non-steroidal anti-inflammatory drugs (45,9% and beta-lactam and sulfonamide antibiotics (25,40%. The majority of the patients reported dermatological manifestations (99, followed by respiratory (40, digestive (23 and other (19. Forty-five patients had an immediate type reaction, and 76,72% (89 had the drug by oral route. CONCLUSION: The results showed that drug hypersensitivity is highly prevalent in university students, and that nonsteroidal anti-inflammatory drug and antibiotics (beta-lactams and sulfonamide are the most frequently concerned drugs.

  5. Chapter 28: Classification of hypersensitivity reactions.

    Science.gov (United States)

    Uzzaman, Ashraf; Cho, Seong H

    2012-01-01

    The original Gell and Coomb's classification categorizes hypersensitivity reactions into four subtypes according to the type of immune response and the effector mechanism responsible for cell and tissue injury: type I, immediate or IgE mediated; type II, cytotoxic or IgG/IgM mediated; type III, IgG/IgM immune complex mediated; and type IV, delayed-type hypersensitivity or T-cell mediated. The classification has been improved so that type IIa is the former type II and type IIb is antibody-mediated cell stimulating (Graves Disease and the "autoimmune" type of chronic idiopathic urticaria). Type IV has four major categories: type IVa is CD4(+)Th1 lymphocyte mediated with activation of macrophages (granuloma formation and type I diabetes mellitus); type IVb is CD4(+)Th2 lymphocyte mediated with eosinophilic involvement (persistent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of immunologic hypersensitivity.

  6. Dapsone hypersensitivity syndrome with myocarditis.

    Science.gov (United States)

    Pereira, Carmen M; Vaz, Marina; Kotha, Sindhoora; Santosh, N H

    2014-08-01

    Drug hypersensitivity with myocarditis is known to occur with many drugs especially with antiepileptics, sulpha-compounds and daposne. Dapsone (4, 4 diaminodiphenyl sulphone) induced hypersensitivity is known to occur in about 2% of leprosy patients on treatment and an incidence of 1.66% in non-leprosy patients. We report this rare case of dapsone hypersensitivity syndrome in a girl on dapsone who presented with fever, anaemia, jaundice, skin rash, lymphadenopathy, and hepatomegaly and later developed myocarditis. The drug was withdrawn and the patient was treated with steroids. She improved and was discharged. She relapsed after the corticosteroids were discontinued at home.

  7. Cloning of a putative hypersensitive induced reaction gene from wheat infected by stripe rust fungus.

    Science.gov (United States)

    Yu, Xiu-Mei; Yu, Xiu-Dao; Qu, Zhi-Peng; Huang, Xin-Jie; Guo, Jun; Han, Qing-Mei; Zhao, Jie; Huang, Li-Li; Kang, Zhen-Sheng

    2008-01-15

    The hypersensitive response (HR) is one of the most efficient forms of plant defense against biotrophic pathogens and results in localized cell death and the formation of necrotic lesions. In this study, a novel putative hypersensitive induced reaction (HIR) gene from wheat leaves infected by incompatible stripe rust pathogen CY23, designated as Ta-hir1, was identified by using rapid amplification of cDNA ends (RACE). Ta-hir1 encodes 284 amino acids, with a predicted molecular mass of 31.31 KDa. A phylogenetic analysis showed that Ta-hir1 was highly homologous to Hv-hir1 from barley at both cDNA and deduced amino-acid levels. Amino-acid sequence analysis of the wheat HIR protein indicated the presence of the SPFH (Stomatins, Prohibitins, Flotillins and HflK/C) protein domain typical for stomatins which served as a negative regulator of univalent cation permeability, especially for potassium. The expression profile of the Ta-hir1 transcript detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time polymerase chain reaction (real time-PCR), respectively, showed that the highest expression occurred 48 h post inoculation (hpi), which is consistent with our previous histopathology observations during the stripe rust fungus-wheat incompatible reaction.

  8. Defense responses regulated by jasmonate and delayed senescence caused by ethylene receptor mutation contribute to tolerance of petunia to Botrytis cinerea

    Science.gov (United States)

    The death of cells can be a programmed event that occurs when plants are attacked by pathogens. Botrytis cinerea (B. cinerea), a model necrotrophic pathogen, triggers the host cell death response because it produces toxins. A hypersensitive reaction (HR) occurs at the site of contact. In Arabidopsis...

  9. MIGRATION OF ORACLE HR DATABASE

    CERN Multimedia

    ais.support@cern.ch

    2001-01-01

    Restricted services from 3 to 7 November 2001 Due to the migration of the Oracle HR application to the Web, some services which rely on the application's availability may be disturbed from Friday 2 November at 17:30 until Thursday 8 November at 08:30. Amongst those services: HR Division: records office, recruitment, claims and benefits. FI Division: personnel accounting, advances and claims. ST Division: registration office (access cards). SPL Division: external firm staff records. EP Division: users' office. Experiments' secretariats: PIE, Greybook. Divisional secretariats: externals, internal addresses. All information concerning this migration is available at: http://ais.cern.ch We apologize for any inconvenience and thank you in advance for your understanding.

  10. Metal Hypersensitivity in Orthodontic Patients

    Directory of Open Access Journals (Sweden)

    Sandhya Maheshwari Sanjeev K

    2015-06-01

    Full Text Available Orthodontic treatment of individuals with metal hypersensitivity is a matter of concern for the orthodontist. Orthodontic appliances contain metals like Nickel, Cobalt and Chromium etc. Metals may cause allergic reactions and are known as allergens. Reaction to these metals is due to biodegradation of metals in the oral cavity. This may lead to the formation of corrosion products and their exposure to the patient. Nickel is the most common metal to cause hypersensitivity reaction. Chromium ranks second among the metals, known to trigger allergic reactions. The adverse biological reactions to these metals may include hypersensitivity, dermatitis and asthma. In addition, a significant carcinogenic and mutagenic potential has been demonstrated. The orthodontist must be familiar with the best possible alternative treatment modalities to provide the safest, most effective care possible in these cases. The present article focuses on the issue of metal hypersensitivity and its management in orthodontic

  11. Absolute eosinophilia as dapsone hypersensitivity

    Directory of Open Access Journals (Sweden)

    Somani V

    1994-01-01

    Full Text Available A case of lepromatous leprosy (LL on multibacillary multidrug therapy (MBMDT presented with oedema of the acral parts and marked eosinophilia. The case is being reported because of this extremely rare manifestation of dapsone hypersensitivity.

  12. Enhancing HR shared service centers through resource orchestration : uncovering the dynamic capabilities of the administrative expert

    NARCIS (Netherlands)

    Maatman, Marco

    2017-01-01

    Many organizations have introduced transactional HR Shared Service Centers (HR SSCs) that are responsible for supporting the business by providing administrative HR services. Many of these HR SSCs are faced with headcount and cost reduction objectives and therefore unable to respond to the

  13. New Insight of Common Regulatory Pathways in Human Trabecular Meshwork Cells in Response to Dexamethasone and Prednisolone Using an Integrated Quantitative Proteomics: SWATH and MRM-HR Mass Spectrometry.

    Science.gov (United States)

    Shan, Sze Wan; Do, Chi Wai; Lam, Thomas Chuen; Kong, Ricky Pak Wing; Li, King Kit; Chun, Ka Man; Stamer, William Daniel; To, Chi Ho

    2017-10-06

    The molecular pathophysiology of corticosteroid-induced ocular hypertension (CIH) is not well understood. To determine the biological mechanisms of CIH, this study investigated protein expression profiles of human trabecular meshwork (hTM) cells in response to dexamethasone and prednisolone treatment. Both discovery-based sequential windowed data independent acquisition of the total high-resolution mass spectra (SWATH-MS) and targeted based high resolution multiple reaction monitoring (MRM-HR) confirmation were applied using a hybrid quadrupole-time-of-flight mass spectrometer. A comprehensive list of 1759 proteins (1% FDR) was generated from the hTM. Quantitative proteomics revealed 20 differentially expressed proteins (p-value ≤ 0.05 and fold-change ≥ 1.5 or ≤ 0.67) commonly induced by prednisolone and dexamethasone, both at 300 nM. These included connective tissue growth factor (CTGF) and thrombospondin-1 (THBS1), two proteins previously implicated in ocular hypertension, glaucoma, and the transforming growth factor-β pathway. Their gene expressions in response to corticosteroids were further confirmed using reverse-transcription polymerase chain reaction. Together with other novel proteins identified in the data sets, additional pathways implicated by these regulated proteins were the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, integrin cell surface interaction, extracellular matrix (ECM) proteoglycans, and ECM-receptor interaction. Our results indicated that an integrated platform of SWATH-MS and MRM-HR allows high throughput identification and confirmation of novel and known corticosteroid-regulated proteins in trabecular meshwork cells, demonstrating the power of this technique in extending the current understanding of the pathogenesis of CIH.

  14. HR competencies at a merged Higher Education Institution

    Directory of Open Access Journals (Sweden)

    Cecile M. Schultz

    2010-03-01

    Full Text Available Orientation: Certain human resource (HR competencies are essential to assist with the dynamics of change in the higher education landscape.Research purposes: The aim of this study was to determine the HR competencies at a merged higher education institution. Other objectives were to establish the satisfaction of academics, administrative staff and management regarding the HR competencies and the importance thereof.Motivation for the study: Human resource professionals require assistance by providing HR competencies necessary to add value at a merged higher education institution.Research designs, approaches and methods: A quantitative research design was employed as the research strategy. The questionnaire was based on the literature, the business plan and the HR balanced scorecard report. The target population was 1363 permanent staff on one campus and the response rate was 28%. A principal factor analysis, spider charts and box plots were utilised for data analysis. The results indicated business knowledge, HR practices, personal skills and management skills as the vital HR competencies.Practical implications: Staff were not satisfied with the current HR competencies and consequently this necessitated attention to improve the deficient areas.Contribution: This study shows that limited research was done with regard to HR competencies in the South African higher education backdrop.

  15. The prevalence of dentin hypersensitivity in general dental practices in the northwest United States.

    Science.gov (United States)

    Cunha-Cruz, Joana; Wataha, John C; Heaton, Lisa J; Rothen, Marilynn; Sobieraj, Martin; Scott, JoAnna; Berg, Joel

    2013-03-01

    The prevalence of dentin hypersensitivity is uncertain, yet appropriate diagnosis and treatment of dentin hypersensitivity require accurate knowledge regarding its prevalence. The authors conducted a study to estimate the prevalence of dentin hypersensitivity in general dental practices and to investigate associated risk factors. The authors conducted a cross-sectional survey of 787 adult patients from 37 general dental practices within Northwest Practice-based Research Collaborative in Evidence-based DENTistry (PRECEDENT). Dentin hypersensitivity was diagnosed by means of participants' responses to a question regarding pain in their teeth and gingivae, and practitioner-investigators conducted a clinical examination to rule out alternative causes of pain. Participants recorded their pain level on a visual analog scale and the Seattle Scales in response to a one-second air blast. The authors used generalized estimating equation log-linear models to estimate the prevalence and the prevalence ratios. The prevalence of dentin hypersensitivity was 12.3 percent; patients with hypersensitivity had, on average, 3.5 hypersensitive teeth. The prevalence of dentin hypersensitivity was higher among 18- to 44-year olds than among participants 65 years or older; it also was higher in women than in men, in participants with gingival recession than in those without gingival recession and in participants who underwent at-home tooth whitening than in those who did not. Hypersensitivity was not associated with obvious occlusal trauma, noncarious cervical lesions or aggressive toothbrushing habits. One in eight participants from general practices had dentin hypersensitivity, which was a chronic condition causing intermittent, low-level pain. Patients with hypersensitivity were more likely to be younger, to be female and to have a high prevalence of gingival recession and at-home tooth whitening. Given dentin hypersensitivity's prevalence, clinicians should diagnose it only after

  16. Designing HR Organizational Structures in terms of the HR Business Partner Model Principles from the Perspective of Czech Organizations

    Directory of Open Access Journals (Sweden)

    Marek Stříteský

    2014-03-01

    Full Text Available This paper describes new trends related to the concepts contained in HR organizational structures within Czech organizations. In addition, it describes the specifics of the roles played by HR in those organizations which have transformed their HR departments in terms of the principles of the HR Business Partner Model, both in theory based on available resources, and at the practical level based on the results of primary examination. The goal of this paper is to present the key perceptions of the changes made in the HR structure within the organizations, as well as the impact of these changes on the effectiveness of the HR departments concerned. Another goal of the paper is to summarize the responsibilities of the newly created position known as the HR Business Partner in these organizations as well as the demands placed upon the personnel employed in the HR Business Partner role. The paper offers conclusions based on the results of both quantitative and qualitative surveys. It also contains a case study of one organization which has one of the best transformed HR departments, and whose services are classified, by internal clients, as being of high quality.

  17. Hypersensitivity to fluoroquinolones

    Science.gov (United States)

    Fernández, Tahia D.; Ariza, Adriana; Palomares, Francisca; Montañez, María I.; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J.

    2016-01-01

    Abstract Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity–specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = −0.446; P < 0.001 for CD63 and Spearman r = −0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID:27281069

  18. RXLR and CRN Effectors from the Sunflower Downy Mildew Pathogen Plasmopara halstedii Induce Hypersensitive-Like Responses in Resistant Sunflower Lines

    Science.gov (United States)

    Gascuel, Quentin; Buendia, Luis; Pecrix, Yann; Blanchet, Nicolas; Muños, Stéphane; Vear, Felicity; Godiard, Laurence

    2016-01-01

    Plasmopara halstedii is an obligate biotrophic oomycete causing downy mildew disease on sunflower, Helianthus annuus, an economically important oil crop. Severe symptoms of the disease (e.g., plant dwarfism, leaf bleaching, sporulation and production of infertile flower) strongly impair seed yield. Pl resistance genes conferring resistance to specific P. halstedii pathotypes were located on sunflower genetic map but yet not cloned. They are present in cultivated lines to protect them against downy mildew disease. Among the 16 different P. halstedii pathotypes recorded in France, pathotype 710 is frequently found, and therefore continuously controlled in sunflower by different Pl genes. High-throughput sequencing of cDNA from P. halstedii led us to identify potential effectors with the characteristic RXLR or CRN motifs described in other oomycetes. Expression of six P. halstedii putative effectors, five RXLR and one CRN, was analyzed by qRT-PCR in pathogen spores and in the pathogen infecting sunflower leaves and selected for functional analyses. We developed a new method for transient expression in sunflower plant leaves and showed for the first time subcellular localization of P. halstedii effectors fused to a fluorescent protein in sunflower leaf cells. Overexpression of the CRN and of 3 RXLR effectors induced hypersensitive-like cell death reactions in some sunflower near-isogenic lines resistant to pathotype 710 and not in susceptible corresponding lines, suggesting they could be involved in Pl loci-mediated resistances. PMID:28066456

  19. Pharmacogenetics of hypersensitivity drug reactions.

    Science.gov (United States)

    Negrini, Simone; Becquemont, Laurent

    2017-04-01

    Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B*57:01 allele and abacavir hypersensitivity syndrome or HLA-B*15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  20. Next HR Department Public meeting

    CERN Multimedia

    2012-01-01

      Dear Colleagues, I am pleased to invite you to the next public meeting organized by HR Department, which will take place on Monday 25 June at 14:30, for the first time in the Globe (in front of the Reception). The agenda will comprise of: ·         the recent staff member survey results ·         the Diversity at CERN ·         the Learning and Development Policy The first topic concerns, more specifically, staff members. All presentations will be made in English, however, we are pleased to inform you that a simultaneous interpretation in French is foreseen. Should you not be able to attend the meeting, it can also be followed via Webcast and the recording will be made available on Indico. Finally, subject to a favourable weather, refreshments...

  1. Experimental periodontal disease. Immediate hypersensitivity.

    Science.gov (United States)

    Asaro, J P; Nisengard, R; Beutner, E H; Neiders, M

    1983-01-01

    Immediate hypersensitivity reactions were induced in the periodontium and skin of monkeys sensitized with novo alcalase. Animals were challenged in the gingival papillae with 0.1, 1.0, and 10 micrograms of antigen for 1, 3, 5, or 7 consecutive days prior to sacrifice. At the same time, skin sites were challenged with 1 microgram of antigen. With repetitive immediate hypersensitivity reactions, the inflammatory infiltrate changed from one characterized by polymorphonuclear leukocytes to one characterized by plasma cells and lymphocytes. The repetitive gingival exposure to bacterial antigens which occur in periodontal disease could lead to repetitive immediate hypersensitivity reactions. Such reactions could play a role in the histopathology of human periodontal disease.

  2. The 9-lipoxygenase GhLOX1 gene is associated with the hypersensitive reaction of cotton Gossypium hirsutum to Xanthomonas campestris pv malvacearum.

    Science.gov (United States)

    Marmey, Philippe; Jalloul, Aïda; Alhamdia, Majd; Assigbetse, Komi; Cacas, Jean-Luc; Voloudakis, Andreas E; Champion, Antony; Clerivet, Alain; Montillet, Jean-Luc; Nicole, Michel

    2007-08-01

    Hypersensitive reaction (HR) cell death of cotton to the incompatible race 18 from Xanthomonas campestris pathovar malvacearum (Xcm) is associated with 9S-lipoxygenase activity (LOX) responsible for lipid peroxidation. Here, we report the cloning of cotton (Gossypium hirsutum L.) LOX gene (GhLOX1) and the sequencing of its promoter. GhLOX1 was found to be highly expressed during Xcm induced HR. Sequence analysis showed that GhLOX1 is a putative 9-LOX, and GhLOX1 promoter contains SA and JA responsive elements. Investigation on LOX signalisation on cotyledons infiltrated with salicylic acid (SA), or incubated with methyl-jasmonate (MeJA) revealed that both treatments induced LOX activity and GhLOX1 gene expression. HR-like symptoms were observed when LOX substrates were then injected in treated (MeJA and SA) cotyledons or when Xcm compatible race 20 was inoculated on MeJA treated cotyledons. Together these results support the fact that GhLOX1 encodes a 9 LOX whose activity would be involved in cell death during cotton HR.

  3. Réunion publique HR

    CERN Multimedia

    CERN. Geneva

    2010-01-01

    Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanée de cette réunion sera assur...

  4. Next HR Department public meeting

    CERN Multimedia

    2016-01-01

    Dear Colleagues, I am pleased to invite you to the next public meeting organized by the HR Department, which will take place on Tuesday 28 June at 3 p.m. in the Council Chamber. A drink will be served after the meeting as of 16:30 This meeting will be the opportunity to revisit the specificities of the Career Structure measures and Benchmark Jobs, what they entail and how they will be implemented, and to answer your questions. This meeting is also important for me on a personal note, as I will bid you farewell, at least for a few years, taking special leave as of 1 August 2016 to take up the position of Director-General for Human Resources at the European Central Bank in Frankfurt.  Should you not be able to attend the meeting, it can also be followed via Webcast and the recording will be made available on Indico. I look forward to meeting you. Best regards, Anne-Sylvie Catherin Head of the Human Resources Department

  5. Lipid peroxidation in cotton: Xanthomonas interactions and the role of lipoxygenases during the hypersensitive reaction.

    Science.gov (United States)

    Jalloul, A; Montillet, J L; Assigbetsé, K; Agnel, J P; Delannoy, E; Triantaphylidès, C; Daniel, J F; Marmey, P; Geiger, J P; Nicole, M

    2002-10-01

    Lipid peroxidation, often associated with hypersensitive cell death, may be initiated either by active oxygen species (AOS) or lipoxygenases (LOX). Here we report a detailed analysis of this oxidative process in both incompatible and compatible interactions between the cotton cultivar Reba B50 and Xanthomonas campestris pv. malvacearum (Xcm). The hypersensitive reaction (HR) was characterized by a massive production of polyunsaturated fatty acid (PUFA) hydroperoxides together with typical tissue dehydration. Among these, isomers peroxidized on carbon 9, largely predominant, were chiral, showing an excess in the S enantiomer. The HR process was accompanied by an increase in 9S-LOX activity and preceded by transcription of a LOX gene (GhKLox1). These results showed that: (i) AOS produced during the oxidative burst were not involved in PUFA peroxidation during HR; and (ii) as previously described in elicited leaves of tobacco, the massive enzymatic lipid peroxidation was closely associated with hypersensitive cell death. During disease development in this cotton cultivar, the 9-lipoxygenation of PUFAs was late, weak, preceded by a faint accumulation of GhKLox1 transcripts, and associated with chlorosis but not with necrosis. Consequently, the main difference between incompatible and compatible interactions was in the precocity and intensity of the oxidative process, rather than in its nature. These data provide the evidence for a correlation between lipid peroxidation and hypersensitive cell death induced by pathogens.

  6. Murine models of drug hypersensitivity.

    NARCIS (Netherlands)

    Nierkens, S.; Pieters, R.

    2005-01-01

    PURPOSE OF REVIEW: Drug hypersensitivity reactions are relatively rare but may result in severe morbidity and fatalities. Due to the idiosyncratic nature and multifactorial etiology of these reactions, development of a single animal model to study the immunosensitizing mechanisms of all drugs is

  7. Treating hypersensitivity with fluoride varnish.

    Science.gov (United States)

    Gaffar, A

    1999-01-01

    Dentinal hypersensitivity results when stimulation causes the fluid in open dentinal tubules to undergo pressure changes, which activates mechanoreceptor nerves and results in pain. Treatment with fluoride varnish forms a protective layer of calcium fluoride that prevents this fluid flow, thereby reducing dentinal sensitivity.

  8. Treating hypersensitivity with fluoride varnishes.

    Science.gov (United States)

    Gaffar, A

    1998-11-01

    Dentinal hypersensitivity results when stimulation causes the fluid in open dentinal tubules to undergo pressure changes, which activates mechanoreceptor nerves and results in pain. Treatment with fluoride varnish forms a protective layer of calcium fluoride that prevents this fluid flow, thereby reducing dentinal sensitivity.

  9. Anticonvulsant hypersensitivity syndrome | Shamad | Sudanese ...

    African Journals Online (AJOL)

    Anticonvulsant drug hypersensitivity syndrome (AHS) is a severe, life-threatening adverse drug reaction. AHS is a cutaneous eruption associated with the aromatic anticonvulsant drugs: carbamazepine, phenytoin, phenobarbital and lamotrigine. The clinical picture of AHS is characterized by a triad of fever, skin rash and ...

  10. The N protein of Tomato spotted wilt virus (TSWV) is associated with the induction of programmed cell death (PCD) in Capsicum chinense plants, a hypersensitive host to TSWV infection.

    Science.gov (United States)

    Lovato, Fernanda Antinolfi; Inoue-Nagata, Alice Kazuko; Nagata, Tatsuya; de Avila, Antônio Carlos; Pereira, Luiz Alfredo Rodrigues; Resende, Renato Oliveira

    2008-11-01

    In sweet pepper, the Tsw gene, originally described in Capsicum chinense, has been widely used as an efficient gene for inducing a hypersensitivity response (HR) derived Tomato spotted wilt virus (TSWV) resistance. Since previously reported studies suggested that the TSWV-S RNA mutation(s) are associated with the breakdown of Tsw mediated TSWV resistance in peppers, the TSWV genes N (structural nucleocapsid protein) and NS(S) (non-structural silencing suppressor protein) were cloned into a Potato virus X (PVX)-based expression vector, and inoculated into the TSWV-resistant C. chinense genotype, PI 159236, to identify the Tsw-HR viral elicitor. Typical HR-like chlorotic and necrotic lesions followed by leaf abscission were observed only in C. chinense plants inoculated with the PVX-N construct. Cytopathological analyses of these plants identified fragmented genomic DNA, indicative of programmed cell death (PCD), in mesophyll cell nuclei surrounding PVX-N-induced necrotic lesions. The other constructs induced only PVX-like symptoms without HR-like lesions and there were no microscopic signs of PCD. The mechanism of TSWV N-gene HR induction is apparently species specific as the N gene of a related tospovirus, Tomato chlorotic spot virus, was not a HR elicitor and did not cause PCD in infected cells.

  11. Immediate and delayed contact hypersensitivity to verbena plants

    DEFF Research Database (Denmark)

    Potter, P C; Mather, S; Lockey, P

    1995-01-01

    of the patient's specific IgE response to Verbena hybrida, using Western blots and autoradiography, identified the specific 62000 Dalton allergen present in the verbena leaves to which the patient reacted. This is the first report of an IgE-mediated immediate contact hypersensitivity reaction to Verbena hybrida...

  12. Production of monoclonal antibodies specific for native equine IgE and their application to monitor total serum IgE responses in Icelandic and non-Icelandic horses with insect bite dermal hypersensitivity.

    Science.gov (United States)

    Wilson, A Douglas; Harwood, Lisa; Torsteinsdottir, Sigurbjörg; Marti, Eliane

    2006-08-15

    Immunoglobulin E forms a minor component of serum antibody in mammals. In tissues IgE is bound by FcvarepsilonRI receptors on the surface of mast cells and mediates their release of inflammatory substances in response to antigen. IgE and mast cells have a central role in immunity to parasites and the pathogenesis of allergic diseases in horses and other mammals. This paper describes the production of several novel monoclonal antibodies that detect native equine IgE in immunohistology, ELISA and Western blotting. An antigen capture ELISA to quantify equine IgE in serum has been developed using two of these antibodies. The mean serum IgE concentration of a group of 122 adult horses was 23,523ng/ml with a range of 425-82,610ng/ml. Total serum IgE of healthy horses was compared with that of horses with insect bite dermal hypersensitivity (IBDH) an allergic reaction to the bites of blood feeding insects of Culicoides or Simulium spp. IBDH does not occur in Iceland where Culicoides spp. are absent, but following importation into mainland Europe native Icelandic horses have an exceptionally high incidence of this condition. In the present study Icelandic horses with IBDH had significantly higher total IgE than healthy Icelandic horse controls (Phypersensitivity response to insect allergens but indicate that IBDH in Icelandic horses may have a different pathogenesis from the same condition in other breeds.

  13. Clinical efficacy of the Er:YAG laser treatment on hypersensitive dentin

    Directory of Open Access Journals (Sweden)

    Chuan-Hang Yu

    2014-06-01

    Full Text Available Dentin hypersensitivity is a common symptomatic condition that causes discomfort and sometimes severe pain. The purpose of this study was to evaluate the clinical efficacy of the erbium-doped:yttrium, aluminum, and garnet (Er:YAG laser treatment on cervically exposed hypersensitive dentin. Twenty patients with dentin hypersensitivity of caries-free teeth were selected. A visual analog scale (VAS was used to measure dentin sensitivity in response to air stimulus. A 2-minute Er:YAG laser (energy level: 60 mJ/pulse; repetition rate: 2 Hz was applied to cervically exposed hypersensitive dentin. After 4 weeks, the hypersensitive teeth were examined again, and the VAS score was measured again and recorded. No complications such as detrimental pulpal effects were observed. Eighteen participants reported significantly reduced dentin hypersensitivity 4 weeks after the laser desensitization treatment. The VAS scores measured 4 weeks after the Er:YAG laser desensitization treatment were significantly decreased as compared with those measured at the baseline (p < 0.05. In conclusion, the Er:YAG laser desensitization treatment can effectively reduce hypersensitivity of cervically exposed hypersensitive dentin.

  14. Hypersensitivity to Parietaria officinalis pollen in newcomers to the area with the plant.

    Science.gov (United States)

    Cvitanović, S; Marusić, M; Juricić, M; Vrdoljak, E; Petrovecki, M; Rozga, A; Stavljenić-Rukavina, A

    1993-11-01

    Hypersensitivity to Parietaria officinalis (wall pellitory) pollen and other environmental allergens was studied in pollinosis patients allergic to P. officinalis pollen who were born in areas without P. officinalis and later moved to the city of Split, where P. officinalis is responsible for some 65% of pollinosis cases. Highly significant positive correlations were found for both the intensity of skin test reaction and concentration of specific serum IgE with the length of residence in the area. In contrast, the respective data on subjects hypersensitive to P. officinalis pollen allergen, but born and living in the area of Split, revealed a tendency to negative correlation between age and intensity of hypersensitivity to P. officinalis. A number of patients from both groups were tested for presence of serum IgE antibodies specific for 14 common environmental allergens. Hypersensitivity to P. officinalis pollen was associated with hypersensitivity to olive, mugwort, and birch pollen in newcomers; hypersensitivity to birch and, to some extent, olive pollen was significantly more frequent in newcomers than in autochthonous patients who were allergic to P. officinalis pollen. Regardless of whether the patients were autochthons or newcomers to the area with P. officinalis, hypersensitivity to P. officinalis mostly excluded hypersensitivity to Dermatophagoides farinae and D. pteronyssinus, and vice versa.

  15. Drug hypersensitivity syndrome caused by minocycline.

    Science.gov (United States)

    Tsuruta, Daisuke; Someda, Yukiko; Sowa, Junko; Kobayashi, Hiromi; Ishii, Masamitsu

    2006-01-01

    Minocycline is a commonly prescribed drug for the treatment of acne. Its use is generally not associated with systemic side effects. To describe a case of minocycline-induced drug hypersensitivity syndrome in a 20-year-old Japanese woman. Following 2 months of minocycline treatment, the patient developed skin lesions composed of exudative maculopapules, purpuratous macules, and target-like, erythema multiforme-like plaques over most of her body. In addition, she had fever, abnormal liver function tests, eosinophilia, and atypical lymphocytosis. Laboratory tests indicated no elevation of antibody titers against cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6. Her ongoing exposure to minocycline was stopped, and treatment with oral prednisolone was begun. Her signs, symptoms, and laboratory abnormalities then began to resolve. Subsequently, the syndrome was observed to return briefly in response to an oral challenge with minocycline. Minocycline is able to elicit a drug hypersensitivity syndrome that can resemble infectious mononucleosis. This drug reaction can be treated effectively by cessation of exposure to this drug and steroid therapy.

  16. Antibiotic hypersensitivity in patients with CF.

    Science.gov (United States)

    Ramesh, Sujatha

    2002-08-01

    Antibiotic hypersensitivity reactions are relatively common in patients with cystic fibrosis (CF). The nature of the reactions and the mechanisms are no different in CF than the general population. Beta-lactam agents are the most common cause of these reactions. The risk depends on the specific beta-lactam agent used with Penicillins having a higher frequency of allergic reactions. There are several risk factors for developing these allergic responses, especially the increased usage. Since the available choices for antibiotic therapy is limited by the sensitivity of the organisms, management becomes a challenge. It is essential to classify the nature of the hypersensitivity reactions and determine the risks of repeat administration of the drug. Unfortunately, reliable skin tests are not available for all the antibiotics. RAST is of limited value. Recent data on cross-reactions between beta-lactam antibiotics and the option of newer agents offer useful alternative choices. Knowledge of the chemical structures of the antibiotics is useful for selecting suitable substitutes. Desensitization is a viable option in many of the reactions unless otherwise contradicted.

  17. LACK OF REPRODUCIBILITY OF A SINGLE NEGATIVE STING CHALLENGE RESPONSE IN THE ASSESSMENT OF ANAPHYLACTIC RISK IN PATIENTS WITH SUSPECTED YELLOW JACKET HYPERSENSITIVITY

    NARCIS (Netherlands)

    FRANKEN, HH; DUBOIS, AEJ; MINKEMA, HJ; VANDERHEIDE, S; DEMONCHY, JGR

    To investigate the reproducibility of a single negative response to sting challenge with a living insect, we rechallenged a group of 61 patients who showed no clinical response to a first sting challenge. All patients had previously had symptoms suggestive of anaphylaxis after a yellow jacket field

  18. Comparative transcriptomic analysis reveals that Ethylene/H2O2-mediated hypersensitive response and program cell death determine the compatible interaction of Sand pear and alternaria alternata

    Science.gov (United States)

    A major production restriction on sand pear (Pyrus pyrifolia) is black spot disease caused by the necrotrophic fungus Alternaria alternata. However, pear response mechanism to A. alternata is unknown at molecular level. Here, host responses of a resistant cultivar Cuiguan (CG) and a susceptible cult...

  19. Delayed-type hypersensitivity response to KLH in F2 and backcrosses of two immune selected chicken lines: effect of immunisation and selection

    NARCIS (Netherlands)

    Minozzi, G.; Parmentier, H.K.; Bed'hom, B.; Minvielle, F.; Gourichon, D.; Pinard-van der Laan, M.H.

    2008-01-01

    Cell-mediated immune response to keyhole limpet hemocyanin (KLH) was studied in 13 different progeny groups belonging to a second generation cross between two lines of White Leghorn previously selected for 10 generations for high antibody response to Newcastle disease vaccine (ND3) and high

  20. Delayed Hypersensitivity in Psoriasis

    Directory of Open Access Journals (Sweden)

    Bhushan Kumar

    1981-01-01

    Full Text Available Twenty two adult male patients of psoriasis and 100 normal Volunteers Were skin-tested ′ with DNC-B, mumps skin antigen, candidin coccidiodin, PPD, croton Oil and histamine hate Except for ′decreased mine phosphate sensitization seen: with DNCB, the response of psoriabics to, skin testing was comparable with the normals.

  1. Selective immediate hypersensitivity reactions to NSAIDs.

    Science.gov (United States)

    Canto, Maria Gabriela; Andreu, Isabel; Fernandez, Javier; Blanca, Miguel

    2009-08-01

    Selective immediate reactions to NSAIDs imply that patients develop a urticarial/anaphylactic response to a single drug with good tolerance to other compounds. No systematic review of these reactions has yet been made. With the increase in consumption of NSAIDs, these have become one of the most common drugs inducing hypersensitivity reactions. Although cross-intolerance reactions are the most common, a significant proportion is selective responses. As specific IgE antibodies are not always found, there is only indirect evidence supporting an IgE-mediated mechanism in selective NSAID reactors. Selective immediate reactions to NSAIDs must be considered when a patient develops urticaria or anaphylaxis after intake of one drug with good tolerance to drugs from other groups or even a drug from the same group with a slightly different chemical structure. Further research is required to identify the antigenic determinant structures recognized.

  2. COMPETENCIES OF HR PROFESSIONALS: A STUDY ON THE HR COMPETENCIES OF UNIVERSITY STUDENTS1

    OpenAIRE

    Özdemir, Serkan; AKATAY, Ayten; EROĞLU, Umut

    2015-01-01

    The changes in HR operations changed the expectations from an HR professionals in the lastdecades. Today businesses need HR managers and professionals who can contribute strategically tothe organization. As a result of these developments competencies are becoming more important in theselection process of new employees. The purpose of this research is to examine existing literatureconcerning HR competencies and to shed light on what competencies university students on the way tobecoming HR pro...

  3. Low rate of cetuximab hypersensitivity reactions in Northeast Tennessee: An Appalachian effect?

    Science.gov (United States)

    Adams, C Brooke; Street, D Sierra; Crass, Melanie; Bossaer, John B

    2016-12-01

    Cetuximab is a monoclonal antibody with a known risk of hypersensitivity reactions. Early studies showed hypersensitivity reaction rates of 3%, but there appears to be a higher incidence in the southeastern United States. To confirm the findings from nearby institutions that cetuximab-associated hypersensitivity reactions occur in approximately 20% of patients in the southeastern United States. A retrospective chart review was conducted at Johnson City Medical Center in Johnson City, Tennessee. Each patient's first infusion was analyzed for hypersensitivity reaction, as well as for demographic information such as allergy and smoking history, pre-medications, and malignancy type. Data from the first infusion of cetuximab were collected for a total of 71 patients with various malignancies. The overall rate of grade 3 or higher hypersensitivity reaction was 1.4%, and total rate of hypersensitivity reaction was 8.5%. These findings more closely correlate to the early clinical trials and package insert. Both severe (p = 0.001) and any-grade (p = 0.002) hypersensitivity reaction occurred less frequently in one Southeastern Appalachian medical center compared to academic medical centers directly to the east and west. Patients in southern Appalachia may be less likely to develop cetuximab hypersensitivity reactions compared to surrounding areas in the Southeastern U.S. These results lend support to the theory that exposure to lonestar ticks (Amblyomma americanum) may be responsible for the development of IgE antibodies to cetuximab that cause hypersensitivity reactions. The development of quick and reliable bedside predictors of cetuximab hypersensitivity reactions may aid clinicians considering the use of cetuximab. © The Author(s) 2015.

  4. Immunologic evaluation of patients with polychlorinated biphenyl poisoning: evaluation of delayed-type skin hypersensitive response and its relation to clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Chang, K. (National Taiwan Univ., Taipei); Hsieh, K.; Tang, S.; Tung, T.; Lee, T.

    1982-02-01

    Polychlorinated biphenyl (PCB) poisoning causes many physiological abnormalities including immune suppression. Cellular immunity was studied in 30 PCB-poisoned patients and 50 normal human subjects. PCB poisoning caused suppression of cellular immunity such as the delayed-type skin response to streptokinase and streptodornase. The suppression of cellular immunity was correlated with the severity of the disease. Thus evaluation of the immune function may be helpful for the diagnosis of PCB poisoning.

  5. Hypersensitivity to pain in congenital blindness

    DEFF Research Database (Denmark)

    Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano

    2013-01-01

    and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants' attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects......, congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated...... that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing....

  6. Evidence of isolate-specificity in non-hypersensitive resistance in spring wheat (Triticum aestivum) to wheat leaf rust

    NARCIS (Netherlands)

    Qamar, Maqsood; Niks, R.E.

    2007-01-01

    Isolate-specific aspect of non-hypersensitive resistance in wheat to wheat leaf rust was studied at seedling stage in the green house. Isolate-specific response of non-hypersensitive resistance was assessed from latency period (LP) and infection frequency (IF) of two single-pustule isolates of

  7. Electromagnetic hypersensitivity: Fact or fiction?

    Energy Technology Data Exchange (ETDEWEB)

    Genuis, Stephen J., E-mail: sgenuis@ualberta.ca [University of Alberta (Canada); Lipp, Christopher T. [Faculty of Medicine at the University of Calgary (Canada)

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: Black-Right-Pointing-Pointer Many people report symptoms when near devices emanating electromagnetic fields(EMF). Black-Right-Pointing-Pointer Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. Black-Right-Pointing-Pointer Recent evidence suggests pathophysiological change in some individuals with EHS. Black-Right-Pointing-Pointer EHS patients consistently report profound social and personal challenges. Black-Right-Pointing-Pointer Clinicians need to be apprised of the EHS condition and potential interventions.

  8. A cross-sectional study on canine Leishmania (L.) infantum chagasi infection in Amazonian Brazil ratifies a higher prevalence of specific IgG-antibody response than delayed-type hypersensitivity in symptomatic and asymptomatic dogs.

    Science.gov (United States)

    Silveira, Fernando T; Carneiro, Liliane A; Ramos, Patrícia K S; Chagas, Eugênia J; Lima, Luciana V R; Campos, Marliane B; Laurenti, Márcia D; Gomes, Claudia M C; Corbett, Carlos E P

    2012-10-01

    This was a cross-sectional study which analyzed the prevalence and the clinical and immunological spectrum of canine Leishmania (L.) infantum chagasi infection in a cohort of 320 mongrel dogs living in an endemic area of American visceral leishmaniasis in the Amazonian Brazil by using, mainly, the indirect fluorescence antibody test (IFAT-IgG) and the delayed-type hypersensitivity (DTH), and the parasite research by the popliteal lymph node aspiration. The IFAT and DTH reactivity recognized three different immune response profiles: (1) IFAT((+))/DTH((-)) (107 dogs), (2) IFAT((-))/DTH((+)) (18 dogs), and (3) IFAT((+))/DTH((+)) (13 dogs), providing an overall prevalence of infection of 43% (138/320). Thus, the specific prevalence of IFAT( (+) )/DTH( (-) ) 33.4% (107/320) was higher than those of IFAT( (-) )/DTH( (+) ) 5.6% (18/320) and IFAT( (+) )/DTH( (+) ) 4.0% (13/320). Moreover, the frequency of these profiles among 138 infected dogs showed that the IFAT( (+) )/DTH( (-) ) rate of 77.5% (107/138) was also higher than those of 13.0% (18/138) of IFAT( (-) )/DTH( (+) ) and 9.5% (13/138) of IFAT( (+) )/DTH( (+) ) rates. The frequency of asymptomatic dogs (76%-105) was higher than those of symptomatic (16.6%-23) and oligosymptomatic ones (7.4%-10). A total of 16 (11.6%) L. (L.) i. chagasi isolates were obtained from infected dogs, all from the IFAT( (+) ) /DTH( (-) ) profile: 41% (9/22) from symptomatic, 33.3% (3/9) from oligosymptomatic, and 5.2% (4/76) from asymptomatic dogs. These findings strongly suggested that despite the higher frequency of asymptomatic dogs (76%-105), the majority (72.4%-76) was characterized by the IFAT( (+) ) /DTH( (-) ) profile with a doubtful immunogenetic resistance against infection.

  9. Citrus leprosis virus C infection results in hypersensitive-like response, suppression of the JA/ET plant defense pathway and promotion of the colonization of its mite vector.

    Directory of Open Access Journals (Sweden)

    Gabriella Dias Arena

    2016-11-01

    Full Text Available Leprosis is a serious disease of citrus caused by Citrus leprosis virus C (CiLV-C, genus Cilevirus whose transmission is mediated by false-spider mites of the genus Brevipalpus. CiLV-C infection does not systemically spread in any of its known host plants, thus remaining restricted to local lesions around the feeding sites of viruliferous mites. To get insight into this unusual pathosystem, we evaluated the expression profiles of genes involved in defense mechanisms of Arabidopsis thaliana and Citrus sinensis upon infestation with non-viruliferous and viruliferous mites by using reverse transcriptase-qPCR. These results were analyzed together with the production of reactive oxygen species (ROS and the appearance of dead cells as assessed by histochemical assays. After interaction with non-viruliferous mites, plants locally accumulated ROS and triggered the salicylic acid (SA and jasmonate/ethylene (JA/ET pathways. ERF branch of the JA/ET pathways was highly activated. In contrast, JA pathway genes were markedly suppressed upon the CiLV-C infection mediated by viruliferous mites. Viral infection also intensified the ROS burst and cell death, and enhanced the expression of genes involved in the RNA silencing mechanism and SA pathway. After 13 days of infestation of two sets of Arabidopsis plants with non-viruliferous and viruliferous mites, the number of mites in the CiLV-C infected Arabidopsis plants was significantly higher than in those infested with the non-viruliferous ones. Oviposition of the viruliferous mites occurred preferentially in the CiLV-C infected leaves. Based on these results, we postulated the first model of plant/Brevipalpus mite/cilevirus interaction in which cells surrounding the feeding sites of viruliferous mites typify the outcome of a hypersensitive-like response, whereas viral infection induces changes in the behavior of its vector.

  10. Pathophysiology of stress-induced visceral hypersensitivity

    NARCIS (Netherlands)

    Stanisor, O.I.

    2014-01-01

    Visceral hypersensitivity is observed in the majority of patients with IBS and considered a pathophysiological mechanism. The aim of the work described in this thesis was to obtain a better understanding of the stress-related pathophysiology of visceral hypersensitivity. Investigations were carried

  11. Central hypersensitivity in chronic musculoskeletal pain

    DEFF Research Database (Denmark)

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-01-01

    standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central...

  12. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    OpenAIRE

    Feng, Bin; La, Jun-Ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G.F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

  13. Electromagnetic hypersensitivity: fact or fiction?

    Science.gov (United States)

    Genuis, Stephen J; Lipp, Christopher T

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. The latest on the recent HR staff survey

    CERN Multimedia

    2009-01-01

    The data collected in the framework of the staff survey sent out by the Human Resources (HR) Department in March this year are currently being analysed. The first results concern the response rate and the breakdown of participants. 1328 staff members replied to the questionnaire, representing a response rate of close to 60%. Marie-Luce Falipou, who is in charge of the project within the HR Department, is evidently satisfied with the result: "The high response rate shows that the staff appreciated HR’s efforts to sound out their opinions and felt concerned by the subjects covered in the questionnaire". All the data are now being processed by the team led by Philippe Sarnin, Director of the Social Psychology Department at the University of Lyon2. "The number of responses submitted during the 15 days the form was available on line was very satisfactory. This is a vital factor in ensuring that we are able to build up an accurate pictu...

  15. T-cell effector function and unresponsiveness in the murine lymphocytic choriomeningitis virus infection. I. On the mechanism of a selective suppression of the virus-specific delayed-type hypersensitivity response

    DEFF Research Database (Denmark)

    Marker, O; Thomsen, Allan Randrup

    1986-01-01

    When the virus dose is increased from 10(2) (low dose) to 10(4) LD50 (high dose) a fatal lymphocytic choriomeningitis virus (LCMV) infection is changed into a subclinical one, and a selective virus-specific delayed-type hypersensitivity (DTH) unresponsiveness is induced, while the cytotoxic T...

  16. Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors.

    Science.gov (United States)

    Curatolo, Michele; Müller, Monika; Ashraf, Aroosiah; Neziri, Alban Y; Streitberger, Konrad; Andersen, Ole K; Arendt-Nielsen, Lars

    2015-11-01

    Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics.

  17. Type III Hypersensitivity Reaction to Subcutaneous Insulin Preparations in a Type 1 Diabetic.

    Science.gov (United States)

    Murray, Benjamin R; Jewell, Jolene R; Jackson, Kyle J; Agboola, Olabunmi; Alexander, Brianna R; Sharma, Poonam

    2017-07-01

    Management of type 1 diabetes in patients who have insulin hypersensitivity is a clinical challenge and places patients at risk for recurrent diabetic ketoacidosis (DKA). Hypersensitivity reactions can be due to the patient's response to the insulin molecule itself or one of the injection's non-insulin components. It is therefore crucial for clinicians to quickly recognize the type of hypersensitivity reaction that is occurring and identify potentially immunogenic additives for the purpose of directing therapy as various insulin preparations have differing ingredients. We present the case of a 23-year-old diabetic female with common variable immunodeficiency (CVID) and autoimmune enteropathy who developed a type III hypersensitivity reaction to multiple formulations of subcutaneous insulin after years of use and the challenges of devising a long-term management strategy.

  18. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

    DEFF Research Database (Denmark)

    Ostrov, David A; Grant, Barry J; Pompeu, Yuri A

    2012-01-01

    studies have identified strong linkages between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA...... cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional...... compounds with suspected HLA-linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA-linked hypersensitivities, and guide the development of safer drugs....

  19. Hypersensitivity Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

    2015-01-01

    of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals...

  20. Hypersensitivity reactions in patients receiving hemodialysis.

    Science.gov (United States)

    Butani, Lavjay; Calogiuri, Gianfranco

    2017-06-01

    To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.

    Science.gov (United States)

    Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H

    2017-01-01

    Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (acids), secreted proteins, with no predicted functions were selected for the HR suppression assay using Nicotiana benthamiana, in which each of the proteins were transiently expressed and evaluated for their ability to suppress HR caused by four cytotoxic effector-R gene combinations (Cp/Rx, ATR13/RPP13, Rpt2/RPS-2, and GPA/RBP-1) and one mutated R gene-Pto(Y207D). Nine out of twenty proteins, designated Shr1 to Shr9 (suppressors of hypersensitive response), were found to suppress HR in N. benthamiana. These effectors varied in the effector-R gene defenses they suppressed, indicating these pathogens can interfere with a variety of host defense pathways. In addition to HR suppression, effector Shr7 also suppressed PAMP-triggered immune response triggered by flg22. Finally, delivery of Shr7 through Pseudomonas fluorescens EtHAn suppressed nonspecific HR induced by Pseudomonas syringae DC3000 in wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.

  2. Do line managers’ have ‘linking pin’ in HR roles?

    Directory of Open Access Journals (Sweden)

    Mohamed Ayyub Hassan

    2015-01-01

    Full Text Available Purpose: The present article aims to identify the possible line managers’ involvement factors in human resource (HR initiatives and its ‘linking pin’ to the HR roles. In this regard, few factors have been considered pertinent to line managers’ involvement factors in HR initiatives which are desire, self-efficacy, and HR support. Whereas, the considered dimensions of HR roles reviewed are strategic partner, change agent, employee champion, and administrative expert. Design/methodology/approach: The paper intends to provide a conceptual review of the past literature in the areas of HR roles and line managers and further justify the proposed conceptual framework that will move this work further. Findings: The review also showed that HR devolution to line managers will boost line managers’ participation and responsibility to practice HR roles at the workplace. Research limitations/implications: The main limitation of this review is no empirical evidence provided by the authors to support the literature of the article. All the provided literature is written based on the findings gained from the previous studies. Practical implications: Line managers’ involvement in HR Initiatives can increase the competency diversity among line manager. This in turn can help the organization to operate at high efficiency. Originality/value: There is a notable lack of research conducted to identify line managers’ involvement in HR. Therefore, this article contributes to the literature on the relationship between line managers and HR roles.

  3. Cutaneous Manifestation of Drug Allergy and Hypersensitivity.

    Science.gov (United States)

    Zalewska-Janowska, Anna; Spiewak, Radoslaw; Kowalski, Marek L

    2017-02-01

    Drug hypersensitivity reactions may manifest with either organ-specific or systemic symptoms, but cutaneous eruptions are the most common manifestations. Different medications may cause identical skin symptoms, whereas hypersensitivity to a single drug may manifest with various patterns of symptoms depending on the pathomechanism of hypersensitivity. Drug reactions should be also taken into account in the differential diagnosis of numerous skin rashes. Analysis of morphology of drug-induced lesions, about potential immunologic or nonimmunological mechanisms, is important for the final diagnosis. Thus, here the authors present a morphologic approach to the diagnosis of cutaneous drug-induced eruptions. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Cutaneous drug hypersensitivity : Immunological and genetic perspective

    Directory of Open Access Journals (Sweden)

    Kisalay Ghosh

    2011-01-01

    Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.

  5. Hypersensitivity to contrast media and dyes.

    Science.gov (United States)

    Brockow, Knut; Sánchez-Borges, Mario

    2014-08-01

    This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Immediate-type hypersensitivity to polyethylene glycols

    DEFF Research Database (Denmark)

    Wenande, E; Garvey, L H

    2016-01-01

    Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness...

  7. Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.

    Science.gov (United States)

    King, Tamara; Qu, Chaoling; Okun, Alec; Mercado, Ramon; Ren, Jiyang; Brion, Triza; Lai, Josephine; Porreca, Frank

    2011-09-01

    A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain, allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of an experimental neuropathic pain model were explored. Desensitization of TRPV1-positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor-expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. After nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large-diameter fibers, and inactivation of the brainstem target of these fibers in the nucleus gracilis prevents tactile but not thermal hypersensitivity. Blockade of NPY signaling within the nucleus gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into nucleus gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1-positive fibers and spinal NK-1-positive ascending projections. In contrast, the large-diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. Because inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the nucleus gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect allodynia. Copyright © 2011 International Association for the Study of Pain. Published by

  8. Familial summer-type hypersensitivity pneumonitis in Japan: two case reports and review of the literature.

    Science.gov (United States)

    Nakajima, Akira; Saraya, Takeshi; Mori, Takeshi; Ikeda, Reiko; Sugita, Takashi; Watanabe, Takayasu; Fujiwara, Masachika; Takizawa, Hajime; Goto, Hajime

    2013-09-13

    Hypersensitivity pneumonitis is defined as an allergic lung disease that occurs in response to inhalation of fungal antigens, bacterial antigens, chemicals, dusts, or animal proteins. The incidence of summer-type hypersensitivity pneumonitis is higher in the summer season, especially in Japan, due to the influence of the hot and humid environment and the common style of wood house or old concrete condominiums. The present report describes a case of a middle-aged married couple who lived in the same house and who simultaneously suffered from summer-type hypersensitivity pneumonitis. This report analyzes these two cases in terms of environmental research and its microbiological, radiological, and pathological aspects. This case report is followed by a review of family occurrences of summer-type hypersensitivity pneumonitis from 22 studies with a total of 49 patients (including the two present cases) in Japan. Summer-type hypersensitivity pneumonitis may be unrecognized and misdiagnosed as pneumonia or other respiratory diseases. A greater understanding of the clinical, pathologic, and environmental features of summer-type hypersensitivity pneumonitis might help improve diagnosis and delivery of appropriate management for this condition.

  9. Health-related quality of life in food hypersensitive schoolchildren and their families: parents' perceptions

    Directory of Open Access Journals (Sweden)

    Marklund Birgitta

    2006-08-01

    Full Text Available Abstract Background About 20% of schoolchildren and adolescents in Sweden suffer from perceived food hypersensitivity (e.g. allergy or intolerance. Our knowledge of how child food hypersensitivity affects parents HRQL and what aspects of the hypersensitivity condition relate to HRQL deterioration in the family is limited. Thus the aim of this study was to investigate the parent-reported HRQL in families with a schoolchild considered to be food hypersensitive. The allergy-associated parameters we operated with were number of offending food items, adverse food reactions, additional hypersensitivity, allergic diseases and additional family members with food hypersensitivity. These parameters, along with age and gender were assessed in relation to child, parent and family HRQL. Methods In May 2004, a postal questionnaire was distributed to parents of 220 schoolchildren with parent-reported food hypersensitivity (response rate 74%. Two questionnaires were used: CHQ-PF28 and a study-specific questionnaire including questions on allergy-associated parameters. In order to find factors that predict impact on HRQL, stepwise multiple linear regression analyses were carried out. Results An important predictor of low HRQL was allergic disease (i.e. asthma, eczema, rhino conjunctivitis in addition to food hypersensitivity. The higher the number of allergic diseases, the lower the physical HRQL for the child, the lower the parental HRQL and the more disruption in family activities. Male gender predicted lower physical HRQL than female gender. If the child had sibling(s with food hypersensitivity this predicted lower psychosocial HRQL for the child and lower parental HRQL. Food-induced gastro-intestinal symptoms predicted lower parental HRQL while food-induced breathing difficulties predicted higher psychosocial HRQL for the child and enhanced HRQL with regards to the family's ability to get along. Conclusion The variance in the child's physical HRQL was to a

  10. Type I hypersensitivity reaction as a complication of lepa.

    Science.gov (United States)

    Janthli, Deepa Manjunath; Chaturvedi, Ashutosh; Somashekar, Shruthi; Lohith, B A

    2015-12-01

    Adverse drug reaction is defined as response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological functions. Type I hypersensitivity reaction is known as anaphylactic reaction which is due to immediate immunoglobulin E-mediated reaction. It is characterized by symptoms such as fever nausea, back pain, angiodema, rash, flushing, etc. Lepa generally refers to the application of pastes formed by mixing powder of herbs with water, milk, etc., and liquids. Complementary and alternative medicines are frequently used by the general population. Many people consider them to be without side effects. Ayurvedic treatment involves Shodhana (biopurification), Shaman (pacification), Bahya (external therapy), and Abhyantara karma's (internal therapy) for treating different diseases. One such bahya karma or external therapy is lepa. Even though lepa is said as "Aadhya Upakrama," undue hypersensitivity is observed in many patients. A 60-year-old woman had an adverse reaction to lepa after being administered as an external medication. The observations were erythema, eruptions, and itching. Such case of hypersensitivity is discussed in the present study.

  11. Seminal plasma hypersensitivity reactions: an updated review.

    Science.gov (United States)

    Sublett, J Wesley; Bernstein, Jonathan A

    2011-01-01

    Seminal plasma hypersensitivity manifests as a spectrum of systemic and/or localized clinical symptoms after exposure to specific protein components in seminal fluid. The prevalence of this disease is largely unknown, but it is believed to affect up to 40,000 women in the United States. Although no definitive risk factors have been confirmed, women with systemic reactions are frequently atopic. Prostate-specific antigen is believed to be the major allergen involved in the disorder, but other proteins are likely involved. Interestingly, up to 40%-50% of both systemic and localized seminal plasma hypersensitivity cases can occur after first-time intercourse. Diagnosis is based on clinical history. The gold standard for diagnosing seminal plasma hypersensitivity is prevention of symptoms with the use of a condom. Patients with seminal plasma hypersensitivity demonstrate positive prick skin test and/or serum-specific immunoglobulin E to whole seminal fluid or fractionated seminal plasma proteins. Treatment of seminal plasma hypersensitivity involves either avoidance with the use of condoms, intravaginal graded challenge using dilutions of whole seminal fluid, or subcutaneous desensitization to relevant fractionated seminal plasma proteins obtained from the woman's sexual partner. In most cases, treatment using one or more of the above approaches has been very successful. Infertility has not been demonstrated to be directly related to seminal plasma hypersensitivity, although women with the condition frequently have difficulty conceiving due to their inability to have unprotected sexual intercourse. © 2011 Mount Sinai School of Medicine.

  12. Aspergillus-associated hypersensitivity respiratory disorders.

    Science.gov (United States)

    Shah, Ashok

    2008-01-01

    The mould Aspergillus is responsible for a gamut of respiratory diseases ranging from saprobic colonisation to rapidly invasive disseminated disease. The clinical spectrum of Aspergillus-associated hypersensitivity respiratory disorders includes Aspergillus induced asthma, allergic bronchopulmonary aspergillosis (ABPA), allergic Aspergillus sinusitis (AAS) and hypersensitivity pneumonitis. Inhalant allergens, in patients with allergic asthma, play a key role in bringing about the inflammation present in the airways, and fungi are increasingly being recognised as important inhalant allergens. Aspergillus is linked to asthma in more ways than one. In the asthmatic subjects, the fungal spores are trapped in the thick and viscid secretions that are usually present in the airways. This generally develops in atopic subjects and is sustained by continuous inhalation of Aspergillus antigens, triggering asthma that may be more severe in form. Aspergillus induced asthma is yet to receive the recognition that it deserves. Allergic bronchopulmonary aspergillosis is the best known form of allergic aspergillosis and is an emerging disease in India. An immunologically mediated lung disease, ABPA occurs predominantly in patients with asthma. A set of diagnostic criteria is required as there is no single test that establishes the diagnosis apart from demonstration of central bronchiectasis with normal tapering bronchi, a feature considered to be pathognomonic of ABPA. Radiologically, ABPA is characterised by 'transient pulmonary infiltrates' or 'fleeting shadows', often confused with pulmonary tuberculosis. A comparatively more recently recognised clinical entity, AAS is characterised by mucoid impaction in the paranasal sinuses which is akin to that in ABPA. Although it appears that the patient with ABPA provides a favourable milieu for the occurrence of AAS, it is perhaps surprising that in spite of similar histopathological features the co-existence of both these diseases has

  13. Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor

    Energy Technology Data Exchange (ETDEWEB)

    Karimullina, Elina [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Institute of Plant and Animal Ecology, Russian Academy of Sciences, Ural Branch, Yekaterinburg 620144 (Russian Federation); Li Yangchun; Ginjupalli, Gautam K. [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Baldwin, William S., E-mail: baldwin@clemson.edu [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Biological Sciences, Clemson University, Clemson, SC (United States)

    2012-07-15

    Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

  14. Normal HR with tilt, yet autonomic dysfunction in persons with Down syndrome.

    Science.gov (United States)

    Bunsawat, Kanokwan; Goulopoulou, Styliani; Collier, Scott R; Figueroa, Arturo; Pitetti, Kenneth H; Baynard, Tracy

    2015-02-01

    Persons with Down syndrome (DS) exhibit altered autonomic function at rest and in response to adrenergic stimuli. It is unknown whether a subset of persons with DS that have similar HR responses to a task would have similar responses in HR variability (HRV). This study aimed to compare cardiac autonomic function during upright tilt using HRV analysis in persons with and without DS when persons with and without DS were matched for the change in HR. Persons with (25 ± 2 yr; 30.4 ± 1.9 kg·m, n = 15) and without DS (27 ± 2 yr; 24.7 ± 1.1 kg·m, n = 15) were matched on their HR response to a 5-min tilt at 80°, whereas a subset of persons with DS (28 ± 3 yr; 33.5 ± 2.0 kg·m, n = 11) were not matched for the change in HR. HRV was assessed in both the frequency (natural log transformation (Ln) of low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP)) and time domains (root mean square of successive differences [RMSSD]). Changes in HR were similar in DS-matched and control but lower in DS-not matched. Tilt effects were observed for LnHF, LNTP, and RMSSD in all groups (P HR response to passive upright tilt in the DS-matched, we still observed reduced sympathetic dominance in response to upright tilt in persons with DS.

  15. Student Observation of HR 2282 (Furud)

    Science.gov (United States)

    Estrada, Reed; Estrada, Chris; Anker, Payton; Barrientos, Destiny; Colbert, Charlie; Dondelinger, Edward; Gillette, Lindsey; Goodrow, Jeremy; Izadi, Tara; Mayo, Colin; Milton, Jordan; Stuart, Sarah; Varela, Nick

    2017-04-01

    A selected team of 8th graders measured the separation and the position angle of double star HR 2282 also known as Furud. They used a 22- inch Newtonian Alt/Az telescope to determine the scale constant, separation, and the position angle. The separation angle was 169.6 arc seconds and the position angle was 339.7 degrees. The results were compared to the 1999 Washington Double Star Catalog and were found to be extremely close.

  16. Enabling quaternion derivatives: the generalized HR calculus

    Science.gov (United States)

    Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C.; Mandic, Danilo P.

    2015-01-01

    Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis. PMID:26361555

  17. Enabling quaternion derivatives: the generalized HR calculus.

    Science.gov (United States)

    Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C; Mandic, Danilo P

    2015-08-01

    Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis.

  18. Genetic Predictors of Drug Hypersensitivity.

    Science.gov (United States)

    Cornejo-Garcia, Jose A; Oussalah, Abderrahim; Blanca, Miguel; Gueant-Rodriguez, Rosa-Maria; Mayorga, Cristobalina; Waton, Julie; Barbaud, Annick; Gaeta, Francesco; Romano, Antonino; Gueant, Jean-Louis

    2016-01-01

    Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy to penicillins, but not to cephalosporins and they influence also the sensitization against prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation, HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and contrasted situations of environmental exposure. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Hypersensitive teeth. Part II: Treatment.

    Science.gov (United States)

    Krauser, J T

    1986-09-01

    If the hydrodynamic theory for pain transmission were accepted, occlusion of the patent dentinal tubules would appear to be essential for treatment efficacy. There are many compounds with seemingly varied chemical forms that have been shown to be effective. Their exact mode of action however, is not clearly defined because well-designed, nonbiased, and controlled comparison studies between agents are lacking. The various toothpastes may have ingredients that actually occlude patent tubules or they may cause secondary desensitization by irrational or abrasive action. In any pain study, the nature of the placebo effect and other psychogenic factors play a significant role. Fluoride preparation with and without iontophoresis has been shown to alter tubule structure and form microprecipitates. The natural desensitization process, although slow, is nature's protection, allowing dentinal sclerosis of secondary dentin formation. Although the resin-adhesive systems, especially the new light-cured dentin bonding agents, appear immediately to be effective, the effect on the pulp remains unknown. Perhaps a combination of iontophoresis with sodium fluoride and light-cured dentin bonding material may yield protection and desensitization at a high level of predictability. With the population trends toward a more geriatric society, further research, knowledge, and understanding of dentinal hypersensitivity is of paramount importance. The expected increase in longevity of the dentition suggests that dentin exposure and sensitivity will increase as a clinical problem. There is a clear time-age relationship involved in gingival recession, erosion and attrition of the teeth, and the need for periodontal surgical therapy. For total comprehensive care, patient comfort is important and should be provided along with sound periodontal health and ideal restorative function.

  20. Evaluation of periprocedural hypersensitivity reactions.

    Science.gov (United States)

    Iammatteo, Melissa; Keskin, Taha; Jerschow, Elina

    2017-10-01

    Identifying the cause of periprocedural hypersensitivity reactions (HSRs) remains challenging because of the multitude of medications involved. Antibiotics are the most common cause in the United States, whereas neuromuscular blocking agents are most common in Europe. To identify causative agents for periprocedural HSRs. This study was a 7-year retrospective medical record review of patients evaluated between December 2009 and January 2017 at a drug allergy center in Bronx, New York for periprocedural HSRs, defined as occurring soon before, during, or soon after a medical procedure or operation with or without general anesthesia. Demographics, description of historical HSRs, results of testing to potential causative medications, and tolerance of subsequent anesthesia were reviewed. Thirty-four patients completed a comprehensive evaluation. Skin testing identified an IgE-mediated cause in 22 patients (64.7%). The most common causative class of medications was induction agents (n = 9 [36%]), with midazolam being the most frequently implicated (n = 6 [3 positive skin test results, 3 equivocal skin test results]). Cefazolin was the most common agent identified (n = 8 [32%]) followed by ondansetron (n = 3 [12%]). Sixteen of 22 contacted patients were exposed to subsequent anesthesia, including 3 patients with negative evaluations. One patient experienced a mild urticarial HSR. Induction agents were the most common causative agents in our patients, which differs from other studies. Given the variability in evaluations of periprocedural HSRs across the United States with data published on small sample sizes, there is a need to establish national guidelines to standardize evaluations and to create a national registry to allow for data sharing. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Carboplatin-induced severe hypersensitivity reaction: Role of IgE-dependent basophil activation and FcεRI

    OpenAIRE

    Iwamoto, Takuya; Hirai, Hiroyuki; Yamaguchi, Nozomi; Kobayashi, Natsuki; Sugimoto, Hiroko; Tabata, Tsutomu; Okuda, Masahiro

    2014-01-01

    Basophil activation was observed in patients with a history of carboplatin-induced severe hypersensitivity reaction (HR). However, the precise mechanism by which carboplatin induces basophil activation and the associated surrogate markers remains to be elucidated. To investigate whether IgE-dependent mechanisms, including the overexpression of FcεRI, participate in carboplatin-induced basophil activation, 13 ovarian cancer patients were enrolled: 5 with a history of carboplatin-induced severe...

  2. Diagnosing and managing patients with drug hypersensitivity.

    Science.gov (United States)

    Fernandez, Javier; Doña, Inmaculada

    2018-01-01

    Diagnosing and managing drug hypersensitivity is challenging because there are no clear limits between different types of drug reactions. Distinguishing between type A (predictable) and type B (hypersensitivity) reactions when a drug is introduced on the market is not easy. When many people use a drug, adverse reactions can occur, conditioned by diverse genetic profiles, viral infections or concomitant therapy. Occasionally the only tool clinicians have on which to base the diagnosis is the clinical history. Skins tests or in vitro tests sometimes have low sensitivity or are unavailable, and drug provocation tests may be dangerous or strictly forbidden in case of severe cutaneous reactions. Areas covered: This paper reviews the diagnosis and management of the two main types of immunological reactions: IgE-mediated immediate drug hypersensitivity reactions (IDHRs) and non-immediate drug hypersensitivity reactions (NIDHRs). Expert commentary: Although Europe and the United States use different diagnostic methods, patients with history of drug hypersensitivity must avoid the suspicious drug, and clinicians must assess tolerance to safe alternatives under medical surveillance. Sometimes desensitization may be required. There is a consensus about the need to perform genetic testing for specific drugs and give patients proper documentation to prevent future exposure to culprit drugs.

  3. Iron abundance determination for the solar-like stars HR 4345 and HR 6573

    Directory of Open Access Journals (Sweden)

    Vince Oliver I.

    2004-01-01

    Full Text Available Using the BLACKWELL software package written by R.O. Gray, the iron abundance of the solar-like stars HR 4345 and HR 6573 has been determined. The method is based on determination of the minimum dispersion (or the region of least confusion of the iron abundance versus microturbulent velocity functions for some selected spectral lines of neutral iron. The input data used by BLACKWELL are the observed equivalent widths of several spectral lines of neutral iron. They are obtained from spectra observed at the Observatoire de Haute-Provence, France, with the 1.52-m telescope and Aurelie spectrograph. Reduction of the raw spectra and the measurement of the equivalent widths of spectral lines are carried out using IRAF and SPE software packages. The measured values of iron abundances of HR 4345 and HR 6573 are 7.72±0.03 and 7.63±0.05 respectively.

  4. HrcQ is necessary for Xanthomonas oryzae pv. oryzae HR-induction in non-host tobacco and pathogenicity in host rice

    Directory of Open Access Journals (Sweden)

    Xiaoping Zhang

    2013-12-01

    Full Text Available Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo, is one of the most destructive diseases of rice (Oryza sativa L. worldwide. The type III secretion system (T3SS of Xoo, encoded by the hrp (hypersensitive response and pathogenicity genes, plays critical roles in conferring pathogenicity in host rice and triggering a hypersensitive response (HR in non-host plants. To investigate the major genes conferring the pathogenicity and avirulence of Xoo, we previously constructed a random Tn5-insertion mutant library of Xoo strain PXO99A. We report here the isolation and characterization of a Tn5-insertion mutant PXM69. Tn5-insertion mutants were screened on indica rice JG30, which is highly susceptible to PXO99A, by leaf-cutting inoculation. Four mutants with reduced virulence were obtained after two rounds of screening. Among them, the mutant PXM69 had completely lost virulence to the rice host and ability to elicit HR in non-host tobacco. Southern blotting analysis showed a single copy of a Tn5-insertion in the genome of PXM69. PCR walking and sequencing analysis revealed that the Tn5 transposon was inserted at nucleotide position 70,192–70,201 in the genome of PXO99A, disrupting the type III hrc (hrp-conserved gene hrcQ, the first gene in the D operon of the hrp cluster in Xoo. To confirm the relationship between the Tn5-insertion and the avirulence phenotype of PXM69, we used the marker exchange mutagenesis to create a PXO99A mutant, ΔhrcQ::KAN, in which the hrcQ was disrupted by a kanamycin-encoding gene cassette at the same site as that of the Tn5-insertion. ΔhrcQ::KAN showed the same phenotype as mutant PXM69. Reintroduction of the wild-type hrcQ gene partially complemented the pathogenic function of PXM69. RT-PCR and cellulase secretion assays showed that the Tn5-disruption of hrcQ did not affect transcription of downstream genes in the D operon and function of the type II secretion system. Our results provide new insights into

  5. Clinical Correlates of Carbon Dioxide Hypersensitivity in Children.

    Science.gov (United States)

    Rappaport, Lance M; Sheerin, Christina; Carney, Dever M; Towbin, Kenneth E; Leibenluft, Ellen; Pine, Daniel S; Brotman, Melissa A; Roberson-Nay, Roxann; Hettema, John M

    2017-12-01

    Hypersensitivity to carbon dioxide (CO 2 )-enriched air may be a promising risk marker for anxiety disorders. Among adult and adolescent samples, heterogeneity in distress response to the CO 2 challenge task indexes 3 underlying classes of individuals, which distinguish between sustained and acute threat response as markers for internalizing disorders, broadly, and anxiety disorders, specifically. The present study examines latent classes in children's response to the CO 2 challenge task to clarify the association of CO 2 hypersensitivity with anxiety and internalizing symptomatology in childhood. Healthy children from a community twin sample (N = 538; age 9-13 years) rated anxious distress every 2 minutes while breathing air enriched to 7.5% CO 2 for 8 minutes. Latent growth mixture modeling evaluated potential classes of individuals with characteristic trajectories of distress during the task to clarify the association with internalizing disorder symptoms and related traits (e.g., anxiety sensitivity, irritability). Although all participants reported increased distress during the task, interindividual heterogeneity in distress indexed 3 underlying classes: a consistently low class ("low"), a consistently high class ("high"), and participants who demonstrated markedly increased acute distress ("acute"). Compared to the low class, the high class reported greater internalizing psychopathology, whereas membership in the acute class was associated with experiencing a panic-like event during the task. As in older individuals, 3 distinct trajectories emerged to capture interindividual heterogeneity in children's distress during the CO 2 challenge task. These classes were distinguished by clinical validators that reinforce the association of CO 2 hypersensitivity and internalizing disorder phenotypes in children. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.

  6. The Dynamical Structure of HR 8799's Inner Debris Disk.

    Science.gov (United States)

    Contro, B; Wittenmyer, Robert A; Horner, J; Marshall, Jonathan P

    2015-06-01

    The HR 8799 system, with its four giant planets and two debris belts, has an architecture closely mirroring that of our Solar system where the inner, warm asteroid belt and outer, cool Edgeworth-Kuiper belt bracket the giant planets. As such, it is a valuable laboratory for examining exoplanetary dynamics and debris disk-exoplanet interactions. Whilst the outer debris belt of HR 8799 has been well resolved by previous observations, the spatial extent of the inner disk remains unknown. This leaves a significant question mark over both the location of the planetesimals responsible for producing the belt's visible dust and the physical properties of those grains. We have performed the most extensive simulations to date of the inner, unresolved debris belt around HR 8799, using UNSW Australia's Katana supercomputing facility to follow the dynamical evolution of a model inner disk comprising 300,298 particles for a period of 60 Ma. These simulations have enabled the characterisation of the extent and structure of the inner disk in detail, and will in future allow us to provide a first estimate of the small-body impact rate and water delivery prospects for possible (as-yet undetected) terrestrial planet (s) in the inner system.

  7. Acupoint Specificity on Colorectal Hypersensitivity Alleviated by Acupuncture and the Correlation with the Brain-Gut Axis.

    Science.gov (United States)

    Wang, Shao-Jun; Yang, Hao-Yan; Wang, Fang; Li, Si-Ting

    2015-06-01

    This project was focused on the study of the effect of the different acupoints on visceral hypersensitivity and the correlation with the brain-gut axis. By using a mouse model of zymosan-induced colorectal hypersensitivity, and observing the response of hypersensitivity model to colorectal distension stimulation in acupuncture at different acupoints, we selected the specific acupoints. With immunohistochemical staining method, we observed c-fos expression, distribution and changes after acupuncture on sensory pathway, including colorectum, spinal dorsal horn and different regions of brain center in the model with colorectal distension stimulation, and evaluated the acupuncture effect on brain-gut axis. The results revealed that the effectiveness of acupuncture for alleviating visceral hypersensitivity was different at individual acupoint, meaning Tianshu (ST25), Zusanli (ST36) and Shangjuxu (ST37) > Quchi (LI11) and Dachangshu (BL25) > Ciliao (BL32). C-fos expression was concentrated in anterior cingulate cortex, hypothalamus, spinal dorsal horn and colorectum in model of zymosan-induced colorectal hypersensitivity and it was down-regulated after acupuncture. The results demonstrates that the acupoint specificity presents in acupuncture for relieving visceral hypersensitivity and the effects are more predominated at the acupoints on stomach meridian innervated by the same or adjacent spinal ganglion segments. The model of zymosan-induced colorectal hypersensitivity can be the animal model simulating brain-gut interaction.

  8. EXPRESS: Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats.

    Science.gov (United States)

    Cao, Dong-Yuan; Bai, Guang; Ji, Yaping; Karpowicz, Jane M; Traub, Richard J

    2016-01-01

    Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stressinduced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome.

  9. Association of tinnitus and electromagnetic hypersensitivity: hints for a shared pathophysiology?

    Directory of Open Access Journals (Sweden)

    Michael Landgrebe

    Full Text Available BACKGROUND: Tinnitus is a frequent condition with high morbidity and impairment in quality of life. The pathophysiology is still incompletely understood. Electromagnetic fields are discussed to be involved in the multi-factorial pathogenesis of tinnitus, but data proofing this relationship are very limited. Potential health hazards of electromagnetic fields (EMF have been under discussion for long. Especially, individuals claiming themselves to be electromagnetic hypersensitive suffer from a variety of unspecific symptoms, which they attribute to EMF-exposure. The aim of the study was to elucidate the relationship between EMF-exposure, electromagnetic hypersensitivity and tinnitus using a case-control design. METHODOLOGY: Tinnitus occurrence and tinnitus severity were assessed by questionnaires in 89 electromagnetic hypersensitive patients and 107 controls matched for age-, gender, living surroundings and workplace. Using a logistic regression approach, potential risk factors for the development of tinnitus were evaluated. FINDINGS: Tinnitus was significantly more frequent in the electromagnetic hypersensitive group (50.72% vs. 17.5% whereas tinnitus duration and severity did not differ between groups. Electromagnetic hypersensitivity and tinnitus were independent risk factors for sleep disturbances. However, measures of individual EMF-exposure like e.g. cell phone use did not show any association with tinnitus. CONCLUSIONS: Our data indicate that tinnitus is associated with subjective electromagnetic hypersensitivity. An individual vulnerability probably due to an over activated cortical distress network seems to be responsible for, both, electromagnetic hypersensitivity and tinnitus. Hence, therapeutic efforts should focus on treatment strategies (e.g. cognitive behavioral therapy aiming at normalizing this dysfunctional distress network.

  10. Drug hypersensitivity in clonal mast cell disorders

    DEFF Research Database (Denmark)

    Bonadonna, P; Pagani, M; Aberer, W

    2015-01-01

    and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs...... tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC......, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum...

  11. General aspects of hypersensitivity pneumonitis in Turkey.

    Science.gov (United States)

    Cımrın, Arif Hikmet; Göksel, Ozlem; Demirel, Yavuz Selim

    2010-01-01

    Hypersensitivity pneumonitis prevalence rates are between 5 and 15% of the overall population exposed to known inciting antigens but a small number of cases have been reported from Turkey until now. We aimed to present a broad picture of hypersensitivity pneumonitis in Turkey, thus promoting interest in this relatively common disease in developing countries. Search engines were utilized to retrieve the cases reported from Turkey. Other published journals and meeting abstracts which have not been registered into electronic databases were manually reviewed. Twenty-two cases from 13 reports were characterized by demographics, clinical features, occupational and environmental exposures, diagnostic tools and prognostic data. The majority of the group consisted of women (68.2%) and had a positive history for contact with an avian (59%). Mean exposure period was 69 ± 77.6 months. The most common reported clinical form was chronic hypersensitivity pneumonitis (58.8%). Reticulonodular pattern was the basic pathological finding (45%). Restrictive impairments of the forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) of the lungs were the basic pathologies observed in pulmonary function tests. Interstitial fibrosis was the most common pathological finding (61.5%). Few cases reported with preponderance of chronic hypersensitivity pneumonitis with avian exposure from 70 million populations suggest that many hypersensitivity pneumonitis cases, especially acute forms, have been ignored. Also, hypersensitivity pneumonitis somehow appears to be a neglected occupational disease. The present situation should be considered as a common problem currently faced by developing countries and occupational groups under risk must be investigated promptly.

  12. Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations

    DEFF Research Database (Denmark)

    Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo

    2016-01-01

    Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...

  13. Murine eosinophils labeled with indium-111 oxine: localization to delayed hypersensitivity reactions against a schistosomal antigen and to lymphokine in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Rand, T.H.; Clanton, J.A.; Runge, V.; English, D.; Colley, D.G.

    1983-04-01

    We have evaluated a method for quantitation of eosinophil migration to stimuli in vivo. Upon transfusion into normal syngeneic mice, 111In-labeled eosinophils had an intravascular half-life of 9.5 hr and distributed predominantly into spleen, bone marrow, and liver. In either Schistosoma mansoni-infected mice or recipients of lymphoid cells from infected mice, intradermal (ear pinna) injection of the schistosomal egg antigenic preparation (SEA) elicited time-dependent accumulation of 111In-labeled eosinophils detectable by either gamma scintillation counting of tissue samples or by nuclear medicine external imaging. Intradermal administration of a lymphokine fraction (containing eosinophil stimulation promoter activity) similarly caused accumulation of 111In-labeled eosinophils. Both reactions depended on the concentration of stimulus (SEA or lymphokine). 111In-labeled neutrophils or macrophages or 125I-albumin did not preferentially accumulate at the reactions examined to the extent found with 111In-labeled eosinophils, indicating that localization of label depends on an active process and is due to eosinophils rather than a contaminating cell type. The method was used to estimate how long eosinotactic lymphokine remained at dermal sites: 60% of initial activity was present 12 hr after injection. The model is discussed with regard to the role of lymphokines in hypersensitivity reactions with eosinophil involvement, such as the granulomatous response to S. mansoni eggs.

  14. To share or not to share: thats the question! When does sharing of HR services maximize perceived HR service value?

    NARCIS (Netherlands)

    Meijerink, Jeroen Gerard; Hofman, Erwin; Hemels, Hinse

    2011-01-01

    Nowadays, organizations can rely on a variety of delivery channels for offering HR services to employees, such as HR shared service centres, embedded HR professionals or electronic HRM. However, when should organizations opt for one of the many HR delivery channels that are at their disposal to

  15. Acupuncture compared to oral antihistamine for type I hypersensitivity itch and skin response in adults with atopic dermatitis – a patient and examiner blinded, randomized, placebo-controlled, crossover trial

    Science.gov (United States)

    Pfab, Florian; Kirchner, Marie-Therese; Huss-Marp, Johannes; Schuster, Tibor; Schalock, Peter C.; Fuqin, Jiang; Athanasiadis, Georgios I.; Behrendt, Heidrun; Ring, Johannes; Darsow, Ulf; Napadow, Vitaly

    2012-01-01

    Background Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and anti-histamine itch therapy (cetirizine) on type-I-hypersensitivity itch and skin reaction in AD using a patient and examiner blinded, randomized, placebo-controlled, crossover trial. Methods Allergen–induced itch was evaluated in 20 AD patients after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC), and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 minutes, using our validated model. Outcome parameters included itch intensity, wheal and flare size, and the D2 Attention test. Results Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared to all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7, p0.1), though both therapies were significantly superior to their respective placebo interventions (p<0.05). Flare size following VAp was significantly smaller (p=0.034) than PAp. D2 attention test score was significantly lower following VC compared to all other groups (p<0.001). Conclusions Both VA and cetirizine significantly reduced type-I-hypersensitivity itch in AD patients, compared to both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially due to counter-irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention. PMID:22313287

  16. Evaluation of a new premedication protocol for administration of equine rabies immunoglobulin in patients with hypersensitivity.

    Science.gov (United States)

    Sudarshan, M K; Kodandaram, N S; Venkatesh, G M; Mahendra, B J; Ashwath Narayana, D H; Parasuramalu, B G

    2007-01-01

    The present study was undertaken to standardize skin testing and to develop a safe and effective premedication protocol for administration of ERIG in those with skin test positivity/hypersensitivity. A method of grading of skin testing was developed using injection histamine as a positive control. This was evaluated by using it on 517 subjects who had severe (WHO category III) exposure to rabies. A premedication protocol consisting of injections pheniramine, ranitidine, hydrocortisone and adrenaline was evaluated by using it on fifty one subjects who were skin test positive/hypersensitive to ERIG. The premedication protocol was safe and effective as all the S1 subjects could be administered the full dose of ERIG despite being skin test positive/hypersensitive to ERIG. Besides the premedication drugs/protocol did not affect the immune response to vaccine and ERIG therapy.

  17. Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation ...

    African Journals Online (AJOL)

    Annals of Medical and Health Sciences Research | Mar-Apr 2015 | Vol 5 | Issue 2 |. Amalgam Contact. Hypersensitivity. Lesion: An Unusual. Presentation‑Report of a. Rare Case ... 1Department of Medical Physics, School of Medicine,. 2Ionizing and Non‑ionizing Radiation Protection Research. Center, 3Student Research ...

  18. Agrobacterium -induced hypersensitive necrotic reaction in plant ...

    African Journals Online (AJOL)

    High necrosis and poor survival rate of target plant tissues are some of the major factors that affect the efficiency of Agrobacterium-mediated T-DNA transfer into plant cells. These factors may be the result of, or linked to, hypersensitive defense reaction in plants to Agrobacterium infection, which may involve the recognition ...

  19. Flagellate erythema as manifestation of food hypersensitivity

    Directory of Open Access Journals (Sweden)

    Jaheersha Pakran

    2017-07-01

    Full Text Available Food hypersensitivity can present in myriad forms leaving the physician baffled. Here we present a case of flagellate dermatitis in an elderly female with bronchial asthma on omalizumab injections, after ingestion of canned shiitake mushrooms. Knowledge about shiitake mushroom dermatitis is important due to increasing prevalence worldwide because of changing culinary preferences.

  20. Dentine hypersensitivity: real or imagined | Gbadebo | Nigerian ...

    African Journals Online (AJOL)

    Background: Dentine hypersensitivity is a common presentation of cause of pain and or discomfort with mastication which has been shown to affect the quality of life of the affected individual. It is also a common cause of presentation at the dental clinics. However, the cause, diagnosis and possible management to give relief ...

  1. Delayed type IV hypersensitivity reaction to porcine acellular dermal matrix masquerading as infection resulting in multiple debridements.

    Science.gov (United States)

    Vedak, P; St John, J; Watson, A; Garibyan, L; Mihm, M C; Nazarian, R M; Levins, P C; Cetrulo, C L; Schalock, P; Kroshinsky, D

    2017-06-01

    Delayed type IV hypersensitivity reactions are well established in the surgical setting with respect to external exposure via topical antibiotics and internal exposure via synthetic materials. In contrast, biologic matrix is derived from decellularized human or animal tissues and is consequently believed to elicit a minimal host inflammatory response. We report a case of delayed type IV hypersensitivity reaction secondary to a biologic comprised of porcine-derived acellular dermal matrix, [Strattice™]. While biologic matrix is often preferred over synthetic mesh due to its decreased risk for infection, this case emphasizes that potential for hypersensitivity to the material persists. Type IV hypersensitivity reactions should be included in the differential diagnosis for suspected post-operative infections.

  2. Immediate hypersensitivity reactions to ibuprofen and other arylpropionic acid derivatives.

    Science.gov (United States)

    Blanca-López, N; Pérez-Alzate, D; Andreu, I; Doña, I; Agúndez, J A; García-Martín, E; Salas, M; Miranda, M Á; Torres, M J; Cornejo-García, J A; Blanca, M; Canto, G

    2016-07-01

    Although ibuprofen and other arylpropionic acid derivatives (APs) are the most common medicines involved in hypersensitivity drug reactions (HDRs) to NSAIDs, no patient series studies have been performed regarding immediate selective reactions (SRs) to these drugs. To characterize patients with immediate selective HDRs to ibuprofen and other APs through clinical history and challenge. Subjects who developed an HDR to APs less than 1 h after drug intake were included. Tolerance to aspirin was assessed and challenge was performed with ibuprofen in all cases, and additionally with the culprit drug (if different) in those patients that tolerated ibuprofen. Serum tryptase levels and tryptase immunohistochemical staining in skin biopsies were also assessed in some patients with a positive DPT to ibuprofen. From a total of 245 patients with a confirmed history of HDRs to APs, 17% were classified as selective immediate hypersensitivity reactors by both clinical history and challenge. A selective response to naproxen and dexketoprofen with tolerance to ibuprofen was found in 16 of 20 cases. Significant differences in serum tryptase levels were observed between 2 and 24 h in the 11 cases that were studied further. Within the group of patients with HDRs to NSAIDs, APs can induce immediate SRs. Within this group, selective responses to a single drug or responders to several APs may exist, suggesting potential immunological cross-reactivity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Dysmenorrhoea is associated with hypersensitivity in the sigmoid colon and rectum

    DEFF Research Database (Denmark)

    Brinkert, Willem; Dimcevski, Georg; Arendt-Nielsen, Lars

    2007-01-01

    if dysmenorrhoea is associated with hypersensitivity in the referred somatic skin area or in the large bowel, i.e., viscero-visceral hyperalgesia. We measured skin sensitivity in the referred area of the sigmoid colon as well as stimulus-response relationships in the sigmoid colon and rectum. The latter were...

  4. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*.

    Science.gov (United States)

    Kowalski, Marek L; Makowska, J S; Blanca, M; Bavbek, S; Bochenek, G; Bousquet, J; Bousquet, P; Celik, G; Demoly, P; Gomes, E R; Niżankowska-Mogilnicka, E; Romano, A; Sanchez-Borges, M; Sanz, M; Torres, M J; De Weck, A; Szczeklik, A; Brockow, K

    2011-07-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs. © 2011 John Wiley & Sons A/S.

  5. Learning and Development Policy available on HR web

    CERN Multimedia

    2012-01-01

    The full text of CERN’s “Learning and Development Policy” is now available in English and French on the HR training website: cern.ch/hr-training/. This new policy was presented to all personnel in the HR Public meeting held on Monday 25 June, and the slides and the video recording remain available on Indico. Pascale Goy, Head of the Learning and Development Group in HR, is available for more information: pascale.goy@cern.ch , tel. 62232.

  6. Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs.

    Science.gov (United States)

    Dona, Inmaculada; Salas, Maria; Perkins, James R; Barrionuevo, Esther; Gaeta, Francesco; Cornejo-Garcia, Jose A; Campo, Paloma; Torres, Maria Jose

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs, and they are classified in two groups: those induced by nonspecific immunological mechanisms (non-allergic or cross-intolerance (CI) reactions), or by specific immunological mechanisms (allergic or selective reactions (SR)). The pathogenesis of CI is associated with their pharmacological activity (COX-1 inhibition), with symptoms due to an imbalance in the arachidonic acid pathway, independently of their chemical structure. SRs are mediated by specific IgE- or by a T-cell response and can be induced by a single NSAID or a class of chemically related NSAIDs, with patients tolerating chemically unrelated compounds. NSAIDs hypersensitivity reactions have been classified in five main groups: i) NSAIDs-exacerbated respiratory disease (NERD); ii) NSAIDs-exacerbated cutaneous disease (NECD); iii) NSAIDs-induced urticaria/angioedema (NIUA); iv) Single NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA); v) Single NSAID-induced delayed reactions (SNIDRs). Although this classification described above is widely accepted by most authors some phenotypes such as blended reactions do not fit. Therefore more research is needed in this topic. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Case of immediate hypersensitivity to beer.

    Science.gov (United States)

    Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko

    2016-06-01

    We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.

  8. Respiratory hypersensitivity reactions to NSAIDs in Europe

    DEFF Research Database (Denmark)

    Makowska, J S; Burney, P; Jarvis, D

    2016-01-01

    . Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. RESULTS: The mean......BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper...... prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants...

  9. 7th drug hypersensitivity meeting: part one

    OpenAIRE

    Carr, Daniel F.; Chung, Wen-Hung; Jenkiins, Rosalind E.; Chaponda, Mas; Nwikue, Gospel; Cornejo Castro, Elena M; Antoine, Daniel J.; Pirmohamed, Munir; Wuillemin, Natascha; Dina, Dolores; Eriksson, Klara K.; Yerly, Daniel; Mckinnin, Elizabeth; Ostrov, David; Peters, Bjoern

    2016-01-01

    Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics ...

  10. Delayed hypersensitivity to aminopenicillins is related to major histocompatibility complex genes.

    Science.gov (United States)

    Romano, A; De Santis, A; Romito, A; Di Fonso, M; Venuti, A; Gasbarrini, G B; Manna, R

    1998-05-01

    Although in some cases delayed hypersensitivity may be observed, beta-lactam antibiotics frequently induce immediate allergic IgE-mediated reactions with the specificity localized in the acyl-side chain structure. Generally, delayed immunologic reactions are related to sensitized T lymphocytes and major histocompatibility complex restricted. To investigate the prevalence of HLA class I and II antigens in patients with delayed hypersensitivity to aminopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity. We assessed 24 patients with history of delayed hypersensitivity to aminopenicillins using (1) skin test with penicilloyl polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin; (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin, ampicillin, and penicillin V in 18/24 patients. All patients were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by chi2 test 2 x 2 contingency tables, according to Svejgaard, were used for comparison between patients and random Italian population (522 subjects). In the patients group we found higher prevalence of HLA A2 (12/24 = 50%, RR = 6.76 P mechanisms involved in adverse reactions to aminopenicillins in vivo are related to genetic markers of immune response and confirms that the presentation of penicillin-hapten determinants to lymphocyte is major histocompatibility complex restricted.

  11. [Hypersensitivity pneumonitis induced by Hypsizigus marumoreus].

    Science.gov (United States)

    Takaku, Yotaro; Takayanagi, Noboru; Minagawa, Shunsuke; Tsuchiya, Yutaka; Hijikata, Naoya; Hara, Kenichiro; Yamaji, Tomohisa; Tokunaga, Daido; Saito, Hiroo; Ubukata, Mikio; Kurashima, Kazuyoshi; Yanagisawa, Tsutomu; Sugita, Yutaka; Kawabata, Yoshinori

    2009-10-01

    We present the case of a 53-year-old woman who was employed at a mushroom (Pleurotus eryngii and Hypsizigus marumoreus) cultivation factory for 15 years. She was admitted to our hospital because of fever and dry cough. Chest radiography and CT scanning revealed diffuse ground glass opacity and centrilobular nodules in both lung fields. Serum KL-6 was elevated. In the bronchoalveolar lavage fluid, the CD4/CD8 ratio was reduced, and the lymphocyte fraction was very high. Transbronchial lung biopsy specimens showed lymphocyte alveolitis. After admission, the patient's symptoms improved rapidly without medication. Although these findings are compatible with hypersensitivity pneumonitis, it was difficult to identify a causative antigen. Serum antibody against Trichosporon was positive. A lymphocyte stimulation test of the peripheral blood was positive against extracts of P. eryngii and H. marumoreus. Furthermore, precipitins against the extracts of H. marumoreus were detected by a double immunodiffusion test. Therefore, we decided to conduct a challenge test using H. marumoreus. As an inhalation provocation test with H. marumoreus conducted in a sickroom caused the same clinical symptoms and signs as experienced in the workplace, we diagnosed hypersensitivity pneumonitis caused by H. marumoreus. A provocation test, in which antigen exposure is limited using a closed space, such as a sickroom, was simple, safe and effective for determining the antigen causing hypersensitivity pneumonitis.

  12. How valid and applicable are current diagnostic criteria and assessment methods for dentin hypersensitivity? An overview.

    Science.gov (United States)

    Gernhardt, Christian R

    2013-03-01

    Although dentin hypersensitivity is a common clinical condition and is generally reported by the patient after experiencing a sharp, short pain caused by one of several different external stimuli, it is often inadequately understood. The purpose of this paper is to discuss different available diagnostic approaches and assessment methods used in order to suggest a basis to diagnose, monitor, and measure these challenging painful conditions related to dentin hypersensitivity in daily practice and scientific projects properly. A PubMed literature search strategy including the following MeSH terms were used as follows: "dentin sensitivity"[MeSH Terms] OR "dentin"[All Fields] AND "sensitivity"[All Fields] OR "dentin sensitivity"[All Fields] OR "dentin"[All Fields] AND "hypersensitivity"[All Fields] OR "dentin hypersensitivity"[All Fields] AND "diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "diagnosis"[MeSH Terms] AND "assessment"[All Fields] AND ("methods"[Subheading] OR "methods"[All Fields] OR "methods"[MeSH Terms]. Furthermore, alternative terms such as "validity," "reliability," "root," "cervical," "diagnostic criteria," and "hypersensitivities" were additionally evaluated. The literature search, also including the alternative terms and journals, revealed only a small number of specific papers related to valid diagnosis, diagnostic criteria, and assessment methods of dentin hypersensitivity. Outcomes from these publications showed that the response to different stimuli varies substantially from one person to another and is, due to individual factors, often difficult to assess correctly. Furthermore, the cause of the reported pain can vary, and the patient's description of the history, symptoms, and discomfort might be different from one to another, not allowing a reliable and valid diagnosis. The dental practitioner, using a variety of diagnostic and measurement techniques each day, will often have difficulties in differentiating dentin hypersensitivity from

  13. Analysis list: Hr39 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Hr39 Embryo + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Hr39.1.tsv ...http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Hr39.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Hr3...9.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Hr39.Embryo.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Embryo.gml ...

  14. Low Dose Radiation Hypersensitivity is Caused by p53-dependent Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Enns, L; Bogen, K; Wizniak, J; Murtha, A; Weinfeld, M

    2004-04-08

    Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses below 50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times post irradiation, we examined the response of human A549 lung carcinoma, T98G glioma and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (annexin-V binding). We observed that caspase-3 activation and annexin-V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and annexin-V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no HRS and apoptosis was not detectable by annexin-V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.

  15. CD8+ T cell migration to the skin requires CD4+ help in a murine model of contact hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Nanna Fyhrquist

    Full Text Available The relative roles of CD4+ and CD8+ T cells in contact hypersensitivity responses have not been fully solved, and remain an important question. Using an adoptive transfer model, we investigated the role of the respective T cell subset. Magnetic bead separated CD4+ and CD8+ T cells from oxazolone sensitized C57BL/6 mice were transferred into RAG-/- mice, followed by hapten challenge and analysis of inflammatory parameters at 24 hours post exposure. The CD4+ T cell recipient mice developed partial contact hypersensitivity responses to oxazolone. CD8+ T cells caused significant amplification of the response in recipients of both CD4+ and CD8+ T cells including ear swelling, type 1 inflammatory mediators, and cell killing. Unexpectedly, CD8+ T cells were not sufficient to mediate contact hypersensitivity, although abundantly present in the lymph nodes in the CD8+ T cell reconstituted mice. There were no signs of inflammation at the site of hapten exposure, indicating impaired recruitment of CD8+ T cells in the absence of CD4+ T cells. These data show that CD4+ T cells mediate contact hypersensitivity to oxazolone, but CD8+ T cells contribute with the most potent effector mechanisms. Moreover, our results suggest that CD4+ T cell function is required for the mobilization of CD8+ effector T cells to the site of hapten exposure. The results shed new light on the relative importance of CD4+ and CD8+ T cells during the effector phase of contact hypersensitivity.

  16. Overexpression of the transcription factor NF-YC9 confers abscisic acid hypersensitivity in Arabidopsis.

    Science.gov (United States)

    Bi, Chao; Ma, Yu; Wang, Xiao-Fang; Zhang, Da-Peng

    2017-11-01

    Nuclear factor Y (NF-Y) family proteins are involved in many developmental processes and responses to environmental cues in plants, but whether and how they regulate phytohormone abscisic acid (ABA) signaling need further studies. In the present study, we showed that over-expression of the NF-YC9 gene confers ABA hypersensitivity in both the early seedling growth and stomatal response, while down-regulation of NF-YC9 does not affect ABA response in these processes. We also showed that over-expression of the NF-YC9 gene confers salt and osmotic hypersensitivity in early seedling growth, which is likely to be directly associated with the ABA hypersensitivity. Further, we observed that NF-YC9 physically interacts with the ABA-responsive bZIP transcription factor ABA-INSENSITIVE5 (ABI5), and facilitates the function of ABI5 to bind and activate the promoter of a target gene EM6. Additionally, NF-YC9 up-regulates expression of the ABI5 gene in response to ABA. These findings show that NF-YC9 may be involved in ABA signaling as a positive regulator and likely functions redundantly together with other NF-YC members, and support the model that the NF-YC9 mediates ABA signaling via targeting to and aiding the ABA-responsive transcription factors such as ABI5.

  17. A Role For HR In Corporate Ethics? South African Practitioners’ Perspectives

    Directory of Open Access Journals (Sweden)

    L. J. van Vuuren

    2006-11-01

    Full Text Available Since few South African organisations have as yet appointed ethics officers, there is often a lack of clarity on who should take responsibility for coordinating organisations’ ethics management efforts. The purpose of this paper was to assess HR (the Human Resource function and its practitioners as a possible contender to assume responsibility for ethics management in SA organisations. To this end a mail survey was conducted among registered HR practitioners (N=410. Two factors related to 1 the extent of HR’s ethics management competence and 2 HR’s responsibility for ethics management, were identified. The results showed that HR practitioners on average believe that they indeed have an ethics management competence and that they should be involved in ethics management. However, practitioners with a great deal of exposure to organisations that manage ethics believe to a lesser extent that they should be involved in ethics management. The implications of the findings are discussed.

  18. Role of transient receptor potential melastatin 2 (TRPM2) channels in visceral nociception and hypersensitivity.

    Science.gov (United States)

    Matsumoto, Kenjiro; Takagi, Kanako; Kato, Atsumi; Ishibashi, Takuya; Mori, Yasuo; Tashima, Kimihito; Mitsumoto, Atsushi; Kato, Shinichi; Horie, Syunji

    2016-11-01

    Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca(2+)-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity. Therefore, we investigated the expression of TRPM2 channels and their involvement in visceral nociception in normal physiology and under pathological conditions that cause visceral hypersensitivity in rats. TRPM2 immunoreactivities were detected in the mucosa and muscle layer of the rat gastrointestinal tract. TRPM2 immunopositive cell bodies were almost completely co-localized with calretinin- and NeuN-positive cells in the myenteric plexus. We found that the majority of the TRPM2-immunoreactive cells were double-labeled with the retrograde marker fluorogold in lumbar 6/sacral 1 dorsal root ganglia (DRG), indicating that TRPM2 is expressed in spinal primary afferents innervating the distal colon. Subtypes of TRPM2-immunopositive DRG neurons were labeled by the A-fiber marker NF200, the C-fiber marker IB4, substance P, calcitonin gene-related peptide, or P2X3 receptor. We found that oral administration of the TRPM2 inhibitor econazole (30mg/kg) reduced the visceromotor response (VMR) to noxious colorectal distention (CRD) at 80mmHg in control rats. Expression of TRPM2 in the mucosa of the distal colon was increased in a trinitrobenzene sulfonic acid-induced colitis model. The VMR to CRD significantly increased in colitis model rats compared with control rats at 40, 60, and 80mmHg. Econazole restored visceral hypersensitivity to the control level. Furthermore, TRPM2-deficient mice showed significantly attenuated trinitrobenzene sulfonic acid induced visceral hypersensitivity compared with wild-type mice. In conclusion, TRPM2 channels contribute to visceral nociception in response to noxious stimuli under normal conditions and visceral

  19. The potential utility of iodinated contrast media (ICM) skin testing in patients with ICM hypersensitivity.

    Science.gov (United States)

    Ahn, Young-Hwan; Koh, Young-Il; Kim, Joo-Hee; Ban, Ga-Young; Lee, Yeon-Kyung; Hong, Ga-Na; Jin, U-Ram; Choi, Byung-Joo; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min

    2015-03-01

    Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.

  20. Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients.

    Science.gov (United States)

    Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

    2016-06-14

    To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research.

  1. The Effect of Various Concentrations of Nitrous Oxide and Oxygen on the Hypersensitive Gag Reflex.

    Science.gov (United States)

    De Veaux, Candace K E; Montagnese, Thomas A; Heima, Masahiro; Aminoshariae, Anita; Mickel, Andre

    2016-01-01

    The purpose of this study was to compare the effectiveness of various concentrations of N2O/O2 on obtunding a hypersensitive gag reflex. We hypothesized that the administration of nitrous oxide and oxygen would obtund a hypersensitive gag reflex enough to allow a patient to tolerate the placement and holding of a digital x-ray sensor long enough to obtain a dental radiograph. Volunteers claiming to have a hypersensitive gag reflex were first screened to validate their claim and then tested by placing a size 2 digital x-ray sensor in the position for a periapical radiograph of the right mandibular molar area and holding it in place for 10 seconds. Subjects were first tested using room air only, then 30%, 50%, or 70% nitrous oxide until they were able to tolerate the sensor without gagging or discomfort. A visual analog scale was used for subjective responses, and other statistical tests were used to analyze the results. We found that for some subjects, 30% nitrous oxide was sufficient; for others, 50% was needed; and for the remainder of the subjects, 70% was sufficient to tolerate the test. Using a combination of 70% nitrous oxide and 30% oxygen allowed all patients claiming to have a hypersensitive gag reflex to tolerate the placement and holding of a digital x-ray sensor long enough to take a periapical radiograph.

  2. Desensitization of delayed-type hypersensitivity in mice: suppressive environment

    Directory of Open Access Journals (Sweden)

    Takashi Katsura

    1993-01-01

    Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.

  3. The gap between research and practice: a replication study on the HR professionals' beliefs about effective human resource practices

    NARCIS (Netherlands)

    Sanders, Karin; van Riemsdijk, Maarten; Groen, B.A.C.

    2008-01-01

    In 2002 Rynes, Colbert and Brown asked human resource (HR) professionals to what extent they agreed with various HR research findings. Responses from 959 American participants showed that there are large discrepancies between research findings and practitioners' beliefs about effective human

  4. Systemic Immediate Hypersensitive Reactions after Treatment with Sweet Bee Venom: A Case Report

    Directory of Open Access Journals (Sweden)

    NaYoung Jo

    2015-12-01

    Full Text Available Objectives: A previous study showed that bee venom (BV could cause anaphylaxis or other hypersensitivity reactions. Although hypersensitivity reactions due to sweet bee venom (SBV have been reported, SBV has been reported to be associated with significantly reduced sensitization compared to BV. Although no systemic immediate hypersensitive response accompanied by abnormal vital signs has been reported with respect to SBV, we report a systemic immediate hypersensitive response that we experienced while trying to use SBV clinically. Methods: The patient had undergone BV treatment several times at other Oriental medicine clinics and had experienced no adverse reactions. She came to acupuncture & moxibustion department at Semyung university hospital of Oriental medicine (Je-cheon, Korea complaining of facial hypoesthesia and was treated using SBV injections, her first SBV treatment. SBV, 0.05 cc, was injected at each of 8 acupoints, for a total of 0.40 cc: Jichang (ST4, Daeyeong (ST5, Hyeopgeo (ST6, Hagwan (ST7, Yepung (TE17, Imun (TE21, Cheonghoe (GB2, and Gwallyeo (SI18. Results: The patient showed systemic immediate hypersensitive reactions. The main symptoms were abdominal pain, nausea and perspiration, but common symptoms associated with hypersensitivity, such as edema, were mild. Abdominal pain was the most long-lasting symptom and was accompanied by nausea. Her body temperature decreased due to sweating. Her diastolic blood pressure could not be measured on three occasions. She remained alert, though the symptoms persisted. The following treatments were conducted in sequence; intramuscular epinephrine, 1 mg/mL, injection, intramuscular dexamethasone, 5 mg/mL, injection, intramuscular buscopan, 20 mg/mL, injection, oxygen (O2 inhalation therapy, 1 L/minutes, via a nasal prong, and intravascular injection of normal saline, 1 L. After 12 hours of treatment, the symptoms had completely disappeared. Conclusion: This case shows that the use of SBV

  5. The Perceived Importance of HR duties to Danish line managers

    DEFF Research Database (Denmark)

    Brandl, Julia; Madsen, Mona Toft; Madsen, Henning

    2009-01-01

    Today, HR scholars widely acknowledge that realising HRM requires the involvement of all managers and that the personal motivation of line managers plays an important role in their successful involvement. Yet, previous research has neglected to study how line managers rate the importance of parti......Today, HR scholars widely acknowledge that realising HRM requires the involvement of all managers and that the personal motivation of line managers plays an important role in their successful involvement. Yet, previous research has neglected to study how line managers rate the importance...... of particular HR duties and how the importance assigned to HR duties varies across managers. Based on a survey of 1,500 Danish managers, we find that 'motivating others' is considered the most important HR duty whereas 'team building', 'handling conflicts' and 'coaching' are considered the least important HR...

  6. FACILITATING RADICAL FRONT-END INNOVATION THROUGH TARGETED HR PRACTICES

    DEFF Research Database (Denmark)

    Aagaard, Annabeth

    2017-01-01

    This study examines how radical front end innovation can be actively facilitated through selected and targeted HR practices and bundles of HR practices. The empirical field is an explorative case study of front end innovation and HR practices in the pharmaceutical industry, with an in-depth case...... study of the Danish pharmaceutical company, H. Lundbeck A/S, and explorative studies of seven European and American pharmaceutical and biotech companies. The study aims to show how companies can apply HR practices in ways that actively supports the development of radical front end innovation. The value...... added and the contribution of this article to the existing FEI and HR literature therefore lies in the exploration and mapping of how radical front end innovation is and can be facilitated through targeted HR practices; and in identifying the unique opportunities and challenges of innovation...

  7. Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

    Science.gov (United States)

    Ampere, Alexandre; Delhaes, Laurence; Soots, Jacques; Bart, Frederic; Wallaert, Benoit

    2012-08-01

    Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account.

  8. Hypersensitivity and nanoparticles: update and research trends.

    Science.gov (United States)

    Mocan, Teodora; Matea, Cristian T; Iancu, Cornel; Agoston-Coldea, Lucia; Mocan, Lucian; Orasan, Remus

    2016-01-01

    Nanotechnology holds a great promise for a wide range of medical-intent applications (diagnostic, treatment and prophylaxis of various diseases). Their advantages are due to their size, versatility and potential for multiple simultaneous applications. However, concerns have been formulated by scientific world due to insufficient data on toxicity of nanomaterials. One area of interest is represented by the interactions between nanoparticles and the components of the immune system. We review herein reported data on hypersensitivity reactions. The role exerted by nanoparticles in both immunostimulation and immunosuppression in allergen-driven mechanisms was studied, as well as future trends in worldwide research.

  9. 7th Drug hypersensitivity meeting: part two

    OpenAIRE

    Elera, Javier Dionicio; Boteanu, Cosmin; Blanco, Maria Aranzazu Jimenez; Gonzalez-Mendiola, Rosario; García, Irene Carrasco; Alvarez, Antonio; Martinez, Jose Julio Laguna; Garrido, Jaume Martí; Barona, Carla Torán; Chorda, Carolina Perales; Salgueiro, Ramón López; Palacios, Miguel Díaz; Rojas,Dolores Hernández Fernández de; Acar, Emre Ali; Aktas, Ayse

    2016-01-01

    Table of contents Poster walk 11: miscellaneous drug hypersensitivity 2 (P92–P94, P96–P101) P92 16 years of experience with proton pump inhibitors (PPIs) Javier Dionicio Elera, Cosmin Boteanu, Maria Aranzazu Jimenez Blanco, Rosario Gonzalez-Mendiola, Irene Carrasco García, Antonio Alvarez, Jose Julio Laguna Martinez P93 Allergy evaluation of quinolone induced adverse reactions Jaume Martí Garrido, Carla Torán Barona, Carolina Perales Chorda, Ramón López Salgueiro, Miguel Díaz Palacios, Dolore...

  10. [Hypersensitivity reactions to use of mebeverine].

    Science.gov (United States)

    in 't Veld, B A; van Puyenbroek, E; Stricker, B H

    1997-07-12

    Twenty-one cases of adverse reactions to mebeverine use were reported to the Inspectorate for Health Care in the Netherlands since 1978. In 12 patients (five men and seven women) this was an immunological hypersensitivity reaction. All patients recovered after drug withdrawal. The time between start and onset of symptoms varied from several minutes to 14 days. Most reactions consisted of urticaria or maculopapular rash, sometimes accompanied by fever, polyarthritis, thrombopenia or angioedema. In contradiction to the manufacturer's claims adverse reactions to the use of mebeverine do occur.

  11. Pain hypersensitivity mechanisms at a glance.

    Science.gov (United States)

    Gangadharan, Vijayan; Kuner, Rohini

    2013-07-01

    There are two basic categories of pain: physiological pain, which serves an important protective function, and pathological pain, which can have a major negative impact on quality of life in the context of human disease. Major progress has been made in understanding the molecular mechanisms that drive sensory transduction, amplification and conduction in peripheral pain-sensing neurons, communication of sensory inputs to spinal second-order neurons, and the eventual modulation of sensory signals by spinal and descending circuits. This poster article endeavors to provide an overview of how molecular and cellular mechanisms underlying nociception in a physiological context undergo plasticity in pathophysiological states, leading to pain hypersensitivity and chronic pain.

  12. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands.

    Science.gov (United States)

    Schurink, Anouk; Wolc, Anna; Ducro, Bart J; Frankena, Klaas; Garrick, Dorian J; Dekkers, Jack C M; van Arendonk, Johan A M

    2012-10-30

    Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case-control design. Cases and controls were matched on various factors (e.g. region, sire) to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb) were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. The genome-wide association study identified several genomic regions associated with insect bite

  13. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    Directory of Open Access Journals (Sweden)

    Schurink Anouk

    2012-10-01

    Full Text Available Abstract Background Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. Results The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. Conclusions The genome-wide association

  14. Dendritic cell populations in patients with self-reported food hypersensitivity

    Directory of Open Access Journals (Sweden)

    Lied GA

    2011-05-01

    Full Text Available Gülen A Lied1,3,4,*, Petra Vogelsang2,*, Arnold Berstad1,4, Silke Appel2 1Institute of Medicine, 2Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway; 3Division of Gastroenterology, Department of Medicine; 4Section of Clinical Allergology, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway *These authors contributed equally to this workAbstract: Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.Keywords: food hypersensitivity, atopy, dendritic cells, CD38

  15. Fasting mitigates immediate hypersensitivity: a pivotal role of endogenous D-beta-hydroxybutyrate.

    Science.gov (United States)

    Nakamura, Shigeru; Hisamura, Ryuji; Shimoda, Sachiko; Shibuya, Izumi; Tsubota, Kazuo

    2014-01-01

    Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca(2+)]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24 hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca(2+)]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in

  16. Frequency, treatment, and functional outcome in children with hypersensitivity pneumonitis

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Petersen, Bodil Laub; Pedersen, Karen Damgaard

    2011-01-01

    Hypersensitivity pneumonitis is a rare interstitial lung disease and very few data regarding frequency, treatment and outcome exist for children. Children identified with hypersensitivity pneumonia from a Danish national cohort with diffuse interstitial lung disease form the basis of this study...

  17. [Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs].

    Science.gov (United States)

    Chalabianloo, Fatemeh

    2012-09-18

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered to be the second most frequent cause of adverse drug reactions, including drug hypersensitivity, after beta-lactam antibiotics. An understanding of the underlying mechanisms and clinical characteristics of hypersensitivity reactions to NSAIDs is necessary for the diagnosis and management of these undesirable reactions in the clinical setting.

  18. Central Hypersensitivity in Chronic Hemiplegic Shoulder Pain

    Science.gov (United States)

    Hoo, Jennifer Soo; Paul, Tracy; Chae, John; Wilson, Richard

    2013-01-01

    Objective This study aimed to examine the association of hemiplegic shoulder pain with central hypersensitivity through pressure-pain thresholds (PPT) at healthy, distant tissues. Design This study is a cross-sectional study. A total of 40 patients (n=20 hemiplegic shoulder pain (HSP), n=20 stroke without HSP) were enrolled in this study. Pressure-pain thresholds were measured at the affected deltoid and contralateral deltoid and tibialis anterior using a handheld algometer. Differences in PPTs were analyzed by Wilcoxon Rank Sum test and with linear regression analysis controlling for gender, a known confounder of PPTs. Results Subjects with hemiplegic shoulder pain had lower local PPTs than stroke control subjects when comparing the painful to dominant shoulders and comparing the non-painful shoulder and tibialis anterior to the non-dominant side controls. Similarly, those with hemiplegic shoulder pain had lower PPTs when comparing to controls in contralesional-to-contralesional comparisons as well as ipsilesional-to-ipsilesional comparisons. Conclusions Subjects with hemiplegic shoulder pain have lower local and distal PPTs than subjects without hemiplegic shoulder pain. Our study suggests that chronic shoulder pain may be associated with widespread central hypersensitivity, which has been previously found to be associated with other chronic pain syndromes. This further understanding can then help develop better treatment options for those with this hemiplegic shoulder pain. PMID:23255268

  19. Hypersensitivity reaction to nonanimal stabilized hyaluronic acid.

    Science.gov (United States)

    Matarasso, Seth L; Herwick, Robert

    2006-07-01

    Soft tissue augmentation has become a cornerstone of facial rejuvenation. The bovine collagens were historically considered the "gold standard" as they had an extensive safety history and were effective. However, because of their brief duration and the approximate 1.0% to 3.0% incidence of hypersensitivity, alternatives were sought. A new class of agents, the hyaluronans, was recently granted approval by the Food and Drug Administration. The hyaluronans are indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (eg, the nasolabial folds). The hyaluronans have two derivations: nonanimal stabilized hyaluronic acid (NASHA) and an additional formulation of avian origin. Both are considered major advancements as they are not species specific and therefore theoretically do not elicit humoral or cell-mediated immune reactions. To date there have been a few reports of allergic reactions to the NASHA hyaluronans, primarily to Restylane. We report what to our knowledge is the first hypersensitivity reaction to the second brand of NASHA, Captique.

  20. Specific Aspects of Drug Hypersensitivity in Children.

    Science.gov (United States)

    Bergmann, Marcel; Caubet, Jean-Christoph

    2016-01-01

    Suspicion for drug hypersensitivity (DH) is a common reason for children's referral to an allergy department, with β-lactam antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) as the most frequently involved drugs. The prevalence of DH in children remains not well defined as epidemiologic studies in children are lacking, and the most of those take into account adverse drug reactions (ADR) without a systematic allergy work-up to confirm or exclude hypersensitivity. The clinical history is mandatory in order to classify the reaction as being immediate or non-immediate and then to subsequently adapt the allergy work-up. Mainly due to the lack of studies, the same guidelines used for diagnosis of drug allergy in adults are generally used in the pediatric population, and the diagnosis is based mainly on in vivo tests (i.e. skin tests and/or drug provocation test) and rarely on in vitro tests. However, specific aspects of management of DH in children have been recently highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    Science.gov (United States)

    Quirce, S; Vandenplas, O; Campo, P; Cruz, M J; de Blay, F; Koschel, D; Moscato, G; Pala, G; Raulf, M; Sastre, J; Siracusa, A; Tarlo, S M; Walusiak-Skorupa, J; Cormier, Y

    2016-06-01

    The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Cough reflex hypersensitivity: A role for neurotrophins.

    Science.gov (United States)

    El-Hashim, Ahmed Z; Jaffal, Sahar M

    2017-03-01

    Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs). NTs belong to a family of trophic factors and are critical for the development and maintenance of neurons in the central and peripheral nervous system including sympathetic efferents, sensory neuron afferents, and immune cells. Nerve growth factor (NGF) was the first member of the NT family to be discovered, with wide ranging actions associated with synapse formation, survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression and activity of functionally important proteins such as ion channels, receptors, and neurotransmitters. In addition, NGF has been implicated in several disease states particularly neuropathic pain and most recently in the sensitization of the cough reflex. This review will briefly address the peripheral and central sensitization mechanisms of airway neurons and will then focus on NGF signaling and its role in cough hypersensitivity.

  3. A novel patatin-like protein from cotton plant, GhPat1, is co-expressed with GhLox1 during Xanthomonas campestris-mediated hypersensitive cell death.

    Science.gov (United States)

    Cacas, Jean-Luc; Marmey, Philippe; Montillet, Jean-Luc; Sayegh-Alhamdia, Majd; Jalloul, Aida; Rojas-Mendoza, Ana; Clérivet, Alain; Nicole, Michel

    2009-01-01

    In cotton plant, Xanthomonas-induced hypersensitive response (HR) is accompanied by a lipid peroxidation process involving a 9-lipoxygenase (LOX), GhLox1. Initiation of this oxidative metabolism implies the release of the LOX substrates, or polyunsaturated fatty acids. Since patatin-like proteins (PLPs) are likely candidates for mediating the latter step, we searched for genes encoding such enzymes, identified and cloned one of them that we named GhPat1. Biochemical and molecular studies showed that GhPat1 expression was up-regulated during the incompatible interaction, prior to the onset of the corresponding galactolipase activity and cell death symptoms in tissues. Protein sequence analysis and modelling also revealed that GhPat1 catalytic amino acids and fold were conserved across plant PLPs. Based on these results and our previous work (Jalloul et al. in Plant J 32:1-12, 2002), a role for GhPat1, in synergy with GhLox1, during HR-specific lipid peroxidation is discussed.

  4. African American Accounting Majors and the 150-hr Requirement

    Science.gov (United States)

    Booker, Quinton; Hill, Cecil L.; Wright, Carl

    2010-01-01

    The study provides information on African American accounting majors' views regarding 150-hr issues. The authors collected data from 152 students at two schools. Students at one school supported the requirement while those at the other school did not. However, students believed that the 150-hr requirement enhances the quality of certified public…

  5. Managing (Sales)People towards Performance: HR Strategy, Leadership & Teamwork

    NARCIS (Netherlands)

    H.M.S. Dietz (Bart)

    2009-01-01

    textabstractManaging people towards performance is one of the most critical priorities for managers in practice. This dissertation focuses on this important issue and explores how HR Strategy, Leaders, and Teams, impact performance. It addresses respectively how HR as a system of coherent

  6. Outsourcing HR Services: The Role of Human Resource Intermediaries

    Science.gov (United States)

    Kock, Henrik; Wallo, Andreas; Nilsson, Barbro; Hoglund, Cecilia

    2012-01-01

    Purpose: In this article, the area of interest is an emerging type of organisation called human resource intermediaries (HRIs), which focus on delivering human resource (HR) services to public sector organisations and private companies. The purpose of this article is, thus, to explore HRIs as deliverers of HR services. More specifically, the…

  7. HR - arbejdet i små og mellemstore virksomheder

    DEFF Research Database (Denmark)

    Madsen, Svend Ole

    2012-01-01

    En undersøgelse af implementeringsmæssige udfordringer som følge af HR - medarbejderes kursusdeltagelse......En undersøgelse af implementeringsmæssige udfordringer som følge af HR - medarbejderes kursusdeltagelse...

  8. Value creation through HR shared services: towards a conceptual framework

    NARCIS (Netherlands)

    Meijerink, Jeroen Gerard; Bondarouk, Tatiana; Looise, Jan C.

    2013-01-01

    Purpose – The purpose of this paper is to derive a measure for the performance of human resource shared service providers (HR SSPs) and then to develop a theoretical framework that conceptualises their performance. Design/methodology/approach – This conceptual paper starts from the HR shared

  9. Mast cells: a possible link between psychological stress, enteric infection, food allergy and gut hypersensitivity in the irritable bowel syndrome.

    Science.gov (United States)

    Gui, X Y

    1998-10-01

    Intestinal mast cell activation (degranulation), which results from previous enteric infection and/or intestinal allergy, may play a central role in the gut hypersensitivity in both motor response and visceral perception in the Irritable Bowel syndrome. This occurs through various mediators acting on enteric neurons and smooth muscle cells. Psychological stress may trigger this sensitive alarm system via the brain-gut axis.

  10. IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity

    NARCIS (Netherlands)

    Girard-Madoux, Mathilde J. H.; Kel, Junda M.; Reizis, Boris; Clausen, Björn E.

    2012-01-01

    Background: IL-10 is a pleiotropic cytokine and potent negative regulator of both innate and adaptive immune responses. Consequently, IL-10-deficient (IL-10(-/-)) mice have enhanced contact hypersensitivity (CHS) to topical hapten. Objective: Although the importance of IL-10 production by

  11. Peripheral and central P2X3 receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse

    Science.gov (United States)

    Shinoda, Masamichi; Feng, Bin; Gebhart, G. F.

    2009-01-01

    Background & Aims Irritable bowel syndrome is characterized by altered sensory qualities, namely discomfort/pain and colorectal hypersensitivity. In mice, we examined the role of P2X3 receptors in colon mechanosensitivity and intracolonic zymosan-produced hypersensitivity, a model of persistent colon hypersensitivity without colon inflammation. Methods The visceromotor response (VMR) to colon distension (15 – 60 mmHg) was determined before and after intracolonic saline or zymosan (30 mg/mL, 0.1 mL, daily for 3 days) treatment. Colon pathology and intracolonic ATP release was assessed in parallel experiments. To examine P2X3 receptor contributions to colon mechanosensation and hypersensitivity, electrophysiological experiments were performed using an in vitro colon-pelvic nerve preparation. Results VMRs to distension were significantly reduced in P2X3+/−and P2X3−/− mice relative to wildtype mice. Colon hypersensitivity produced by zymosan was virtually absent in P2X3−/− relative to wildtype or P2X3+/− mice. Intralumenal release of the endogenous P2X receptor ligand ATP did not differ between wildtype and P2X3−/− mice or change after intracolonic zymosan treatment. Responses of muscular and muscular-mucosal pelvic nerve afferents to mechanical stretch did not differ between P2X3−/− and wildtype mice. Both muscular and muscular-mucosal afferents in wildtype mice sensitized to application of an inflammatory soup, whereas only muscular-mucosal afferents did so in P2X3−/− mice. Conclusions These results suggest differential roles for peripheral and central P2X3 receptors in colon mechanosensory transduction and hypersensitivity. PMID:19549524

  12. Multiple hypersensitivities including recurrent airway obstruction, insect bite hypersensitivity, and urticaria in 2 warmblood horse populations.

    Science.gov (United States)

    Kehrli, D; Jandova, V; Fey, K; Jahn, P; Gerber, V

    2015-01-01

    Multiple hypersensitivities (MHS) have been described in humans, cats, and dogs, but not horses. Horses suffering from recurrent airway obstruction (RAO), insect bite hypersensitivity (IBH), or urticaria (URT) will have an increased risk of also being affected by another one of these hypersensitivities. This predisposition for MHS also will be associated with decreased shedding of strongylid eggs in feces and with a single nucleotide polymorphism (SNP BIEC2-224511), previously shown to be associated with RAO. The first population (P1) included 119 randomly sampled horses representative of the Swiss sporthorse population; the replication population (P2) included 210 RAO-affected Warmblood horses and 264 RAO-unaffected controls. All horses were Warmbloods, 14 years or older. Associations between disease phenotypes (RAO, IBH, URT, MHS) fecal egg counts, the SNP BIEC2-224511 as well as management and environmental factors were investigated. In P1, RAO-affected horses had a 13.1 times higher odds ratio (OR) of also suffering from IBH (P = .004). In P2, the respective OR was 7.4 (P = .002) and IBH-affected horses also showed a 7.1 times increased OR of concomitantly suffering from URT (P < .001). IBH, URT, and MHS phenotypes were significantly associated with the absence of nematode eggs in the feces. This is the first report of MHS in horses. Specifically, an increased risk for IBH should be expected in RAO-affected horses. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  13. Aquifer test plan for the 100-HR-3 Operable Unit

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, L.C.; Hartman, M.J.

    1994-03-28

    This test plan directs hydrologic testing activities planned at three existing Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) wells in the 100-HR-3 Operable Unit of the Hanford Site. Three additional wells will be installed near these existing wells and used as additional testing arid observation points during the field activities. Figure 1 shows the locations of the three test sites. A primary objective of the testing program is to provide more detailed hydraulic characterization information for the unconfined aquifer and targeted test sites than provided by the initial reconnaissance-level slug testing of Vukelich. A second objective is to evaluate the applicability of slug interference and dipole flow tests for detailed hydraulic characterization in an unconfined aquifer. This aquifer testing program will also be useful for substantiating hydraulic conductivities reported from previous slug tests and evaluating the effects of filter pack volume/configuration on slug test data. Vukelich recommended additional testing to address the latter two issues.

  14. THE CHANGING ROLE OF HR: VALUES AND CONTRIBUTION

    DEFF Research Database (Denmark)

    Andersen, Torben; Krogager, Per

    2011-01-01

    This paper illustrates, through a case-study of one of the old life sciences and diagnostics companies in Denmark, Radiometer Medical Plc. (now part of the Danaher Corporation), how the HR-department starts to work in a much more systematic way with effectiveness and efficiency, in the attempt...... to ‘deliver results’. Through the development of consecutive measures of the HR contribution, developed as part of a larger restructuring of the function, HR has now acquired a more central position in the company. The function has taken the initiative to frequently monitor activities and its ability...... with a stronger emphasis on core values and rationalizing the function itself....

  15. Predicting maximal HR in heart failure patients on β-blockade therapy.

    Science.gov (United States)

    Keteyian, Steven J; Kitzman, Dalane; Zannad, Faiez; Landzberg, Joel; Arnold, J Malcolm; Brubaker, Peter; Brawner, Clinton A; Bensimhon, Daniel; Hellkamp, Anne S; Ewald, Greg

    2012-03-01

    Standards for estimating maximal HR are important when interpreting the adequacy of physiologic stress during exercise testing, assessing chronotropic response, and prescribing an exercise training regimen. The equation 220 - age is used to estimate maximum HR; however, it overestimates measured maximal HR in patients taking β-adrenergic blockade (βB) therapy. This study developed and validated a practical equation to predict maximal HR in patients with heart failure (HF) taking βB therapy. Data from symptom-limited exercise tests completed on patients with systolic HF participating in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial and taking a βB agent were used to develop a simplified equation, which was validated using bootstrapping. The simplified derived equation was 119 + 0.5 (resting HR) - 0.5 (age) - (0, if test was completed using a treadmill; 5, if using a stationary bike). The R2 and SEE were 0.28 and 18 beats·min(-1), respectively. Validation of this equation yielded a mean R and SEE of 0.28 and 18 beats·min(-1), respectively. For the equation 220 - age, the R2 was -2.93, and the SEE was 43 beats·min(-1). We report a valid and simple population-specific equation for estimating peak HR in patients with HF taking βB therapy. This equation should be helpful when evaluating chronotropic response or assessing if a maximum effort was provided during exercise testing. We caution, however, that the magnitude of the variation (SEE = 18 beats·min(-1)) associated with this prediction equation may make it impractical when prescribing exercise intensity.

  16. Ceftriaxone Induced Hypersensitivity Reactions Following Intradermal Skin Test: Case Series

    Directory of Open Access Journals (Sweden)

    Sereen Rose Thomson

    2017-10-01

    Full Text Available The incidence of cephalosporin induced hypersensitivity reactions in non-penicillin allergic patients is about 1.7% and in penicillin allergic patients it is about 3-5%. Infact, cephalosporins are considered as the first choice in penicillin allergic patients who need antibiotic therapy intraoperatively. Prompt identification of patients with beta-lactam allergy would lead to an improved utilization of antibiotics and reduced occurrence of resistant strains. We hereby attempt to present a series of cases where ceftriaxone has been implicated in the manifestation of various hypersensitivity reactions. We have also tried to highlight some of the errors, risk factors and other drugs that precipitate a hypersensitivity reaction.

  17. Understanding the effectiveness of precursor reductions in lowering 8-hr ozone concentrations--Part II. The eastern United States.

    Science.gov (United States)

    Reynolds, Steven D; Blanchard, Charles L; Ziman, Stephen D

    2004-11-01

    Analyses of ozone (O3) measurements in conjunction with photochemical modeling were used to assess the feasibility of attaining the federal 8-hr O3 standard in the eastern United States. Various combinations of volatile organic compound (VOC) and oxides of nitrogen (NOx) emission reductions were effective in lowering modeled peak 1-hr O3 concentrations. VOC emissions reductions alone had only a modest impact on modeled peak 8-hr O3 concentrations. Anthropogenic NOx emissions reductions of 46-86% of 1996 base case values were needed to reach the level of the 8-hr standard in some areas. As NOx emissions are reduced, O3 production efficiency increases, which accounts for the less than proportional response of calculated 8-hr O3 levels. Such increases in O3 production efficiency also were noted in previous modeling work for central California. O3 production in some urban core areas, such as New York City and Chicago, IL, was found to be VOC-limited. In these areas, moderate NOx emissions reductions may be accompanied by increases in peak 8-hr O3 levels. The findings help to explain differences in historical trends in 1- and 8-hr O3 levels and have serious implications for the feasibility of attaining the 8-hr O3 standard in several areas of the eastern United States.

  18. HR-Cloud-Transformation – Vorgehen und Erfolgsfaktoren

    National Research Council Canada - National Science Library

    Ziebell, Robert-Christian; Schultz, Martin; Albors Garrigós, José; Schoeneberg, Klaus-Peter

    2016-01-01

    ... Lösungen. Diese Lösungen bieten nicht nur technologische, sondern vor allem fachliche Vorteile, denn Prozesssilos werden aufgebrochen und durch eine gesamtheitlich abgebildete HR-Prozesswelt ersetzt. Dies...

  19. THE CHANGING ROLE OF HR: VALUES AND CONTRIBUTION

    DEFF Research Database (Denmark)

    Andersen, Torben; Krogager, Per

    2011-01-01

    This paper illustrates, through a case-study of one of the old life sciences and diagnostics companies in Denmark, Radiometer Medical Plc. (now part of the Danaher Corporation), how the HR-department starts to work in a much more systematic way with effectiveness and efficiency, in the attempt...... to ‘deliver results’. Through the development of consecutive measures of the HR contribution, developed as part of a larger restructuring of the function, HR has now acquired a more central position in the company. The function has taken the initiative to frequently monitor activities and its ability...... to support the operations and progress of the business organization. The case study is an empirical example of how a local HR-unit (in a large global corporation), without any tradition in this domain, successfully managed to simultaneous develop capacities to pursue effectiveness and efficiency, ending up...

  20. Equine insect bite hypersensitivity: what do we know?

    Science.gov (United States)

    Schaffartzik, A; Hamza, E; Janda, J; Crameri, R; Marti, E; Rhyner, C

    2012-06-30

    Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin and with stimulated peripheral blood mononuclear cells. Various studies have shown IBH to be associated with IgE-mediated reactions against salivary antigens from Culicoides spp. However, until recently, the causative allergens had not been characterized at the molecular level. A major advance has now been made, as 11 Culicoides salivary gland proteins have been identified as relevant allergens for IBH. Currently, there is no satisfactory treatment of IBH. Characterization of the main allergens for IBH and understanding what mechanisms induce a healthy or allergic immune response towards these allergens may help to develop new treatment strategies, such as immunotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity.

    Science.gov (United States)

    Suckow, Shelby K; Caudle, Robert M

    2009-09-22

    Visceral hypersensitivity is a clinical observation made when diagnosing patients with functional bowel disorders. The cause of visceral hypersensitivity is unknown but is thought to be attributed to inflammation. Previously we demonstrated that a unique set of enteric neurons, colospinal afferent neurons (CANs), co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor. The aim of this study was to determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral hypersensitivity following inflammation. Recently, work has suggested that dorsal root ganglion (DRG) neurons expressing the transient receptor potential vanilloid-1 (TRPV1) receptor mediate inflammation induced visceral hypersensitivity. Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX) prior to inflammation and behavioural testing. CANs do not express the TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment resulted in a significant decrease in TRPV1 expressing neurons in the colon and immunohistochemical analysis revealed no change in peptide or receptor expression in CANs following RTX lesioning as compared to control data. Behavioral studies determined that both inflamed non-RTX and RTX animals showed a decrease in balloon pressure threshold as compared to controls. Immunohistochemical analysis demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were up-regulated following inflammation. Furthermore, inflammation resulted in the activation of the PAR2 receptors expressed on CANs. Our data show that inflammation causes an up-regulation of the NMDA receptor and the activation of the PAR2 receptor expressed on CANs. These changes are associated with a decrease in balloon pressure in response to colorectal distension in non-RTX and RTX lesioned animals. Therefore, these data suggest that CANs

  2. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs during inflammation induced visceral hypersensitivity

    Directory of Open Access Journals (Sweden)

    Caudle Robert M

    2009-09-01

    Full Text Available Abstract Background Visceral hypersensitivity is a clinical observation made when diagnosing patients with functional bowel disorders. The cause of visceral hypersensitivity is unknown but is thought to be attributed to inflammation. Previously we demonstrated that a unique set of enteric neurons, colospinal afferent neurons (CANs, co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor. The aim of this study was to determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral hypersensitivity following inflammation. Recently, work has suggested that dorsal root ganglion (DRG neurons expressing the transient receptor potential vanilloid-1 (TRPV1 receptor mediate inflammation induced visceral hypersensitivity. Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX prior to inflammation and behavioural testing. Results CANs do not express the TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment resulted in a significant decrease in TRPV1 expressing neurons in the colon and immunohistochemical analysis revealed no change in peptide or receptor expression in CANs following RTX lesioning as compared to control data. Behavioral studies determined that both inflamed non-RTX and RTX animals showed a decrease in balloon pressure threshold as compared to controls. Immunohistochemical analysis demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were up-regulated following inflammation. Furthermore, inflammation resulted in the activation of the PAR2 receptors expressed on CANs. Conclusion Our data show that inflammation causes an up-regulation of the NMDA receptor and the activation of the PAR2 receptor expressed on CANs. These changes are associated with a decrease in balloon pressure in response to colorectal distension in non-RTX and RTX lesioned

  3. Unpacking social hypersensitivity: vulnerability to the absence of positive feedback.

    Science.gov (United States)

    Cikara, Mina; Girgus, Joan S

    2010-10-01

    Navigating social life requires accurately calibrated sensitivity to external feedback, thus extreme sensitivity to external feedback may be maladaptive. Using a daily diary design, the authors investigated whether the relationship between social hypersensitivity and daily events predicted level, lability, and reactivity of both self-esteem and affect. Relative to their less sensitive peers, socially hypersensitive people exhibited lower levels of self-esteem and greater negative affect and experienced greater fluctuations in self-esteem and negative affect. Although most people were negatively reactive to the presence of negative feedback, socially hypersensitive people were negatively reactive to the absence of positive feedback as well. The authors argue that reactivity to the absence of positive feedback is a fundamental, heretofore untested aspect of what makes social hypersensitivity a pernicious orientation.

  4. Innovations for combating dentin hypersensitivity: current state of the art.

    Science.gov (United States)

    Li, Yiming

    2012-06-01

    Dentin hypersensitivity is a common dental complaint, and in severe cases it can impair eating, drinking, and even speaking, thus interfering with the normal daily life of an individual. Throughout years of research, there has been significant advancement in understanding dentin hypersensitivity, and various treatment regimens have been developed for combating the problem. The continued efforts have recently resulted in a novel technology that uses 8% arginine and calcium carbonate for treating dentin hypersensitivity. Formulations of oral care products using this technology--including toothpaste and prophylactic pastes--have demonstrated not only their effectiveness but also their ability to provide instant relief. This paper provides an overview of the etiology of dentin hypersensitivity, the discovery and development of measures for combating the problem, and the available data on the clinical efficacy of products based on 8% arginine and calcium carbonate.

  5. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  6. The role for decorin in delayed-type hypersensitivity

    National Research Council Canada - National Science Library

    Seidler, Daniela G; Mohamed, Negia A; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V; Zarbock, Alexander; Götte, Martin

    2011-01-01

    ... (oxazolone-mediated delayed-type hypersensitivity [DTH]) in decorin-deficient (Dcn(-/-)) and wild-type mice. Dcn(-/-) mice showed a reduced ear swelling 24 h after oxazolone treatment with a concurrent attenuation of leukocyte infiltration...

  7. Comparison of Hypersensitivity in Metal Ceramic Crowns cemented with Zinc Phosphate and Self-adhesive Resin: A Prospective Study.

    Science.gov (United States)

    Shankar, Thatapudi; Garhnayak, Mirna; Garhnayak, Lokanath; Dhal, Angurbala; Kar, Aswini K

    2017-10-01

    Luting agents used to fix artificial prostheses, such as fixed partial denture (FPD) to tooth are basically viscous in nature and show chemical reaction for fixation. Postcementation hypersensitivity is a frequent complaint of patients. The present study was conducted to compare postcementation hypersensitivity with zinc phosphate and self-adhesive resin in complete coverage crown. This study included 30 patients in which 60 porcelein fused to metal crowns was placed. Two metal crowns were placed in each patient in nonantagonis-tic contralateral quadrants. First crown was cemented with zinc phosphate cement, while the other was cemented with self-adhesive resin. Hypersensitivity was evaluated by visual analog scale (VAS) score and by clinical test. For clinical evaluation of sensitivity, hot and cold water was applied to the cervical margin of restoration for 5 seconds and response was recorded. This study consisted of 30 patients in which 60 crowns were given. There was no statistical difference in VAS score of mastication in zinc phosphate cement recorded at baseline, 1 week, 4 weeks, 6 months, 1 year, and 2 years (p > 0.05). Cold response also did not show a significant difference at six time points. Warm response showed slight decrease in subsequent time points but was nonsignificant (p > 0.05). Similarly, with self-adhesive resin cement, VAS score during mastication, hot and cold response was statistically nonsignificant (p > 0.05). Postcementation hypersensitivity is a frequent complaint that patient may experience. However, we found no statistically significant difference in both cements tested. Postcementation hypersensitivity is an unpleasant sensation experienced by patients. This may affect the success of any prosthesis. Thus, selection of luting agent for cementation plays an important role to eliminate this symptom.

  8. Role of TRPV1 in inflammation-induced airway hypersensitivity

    OpenAIRE

    Lee, Lu-Yuan; Gu, Qihai

    2009-01-01

    Airway hypersensitivity is a common pathophysiological feature in various airway inflammatory diseases. Increasing evidence suggests that activation of the transient receptor potential vanilloid type 1 receptor (TRPV1) plays an important part in the manifestation of various symptoms of airway hypersensitivity. This mini-review focuses on recent studies that have revealed several potential contributing factors to the increase in TRPV1 sensitivity in pulmonary sensory neurons during airway infl...

  9. A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene

    OpenAIRE

    Kim, Young Jae; Hwang, Eu Dong; Leem, Ah Young; Kang, Beo Deul; Chang, Soo Yun; Kim, Ho Keun; Park, In Kyu; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon

    2014-01-01

    Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man w...

  10. A Rare Diabetic Autonomic Neuropathy: Carotid Sinus Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ahmet Kaya

    2016-03-01

    Full Text Available Carotid sinus hypersensitivity is a common cause of fainting and falls in the elderly, and can be diagnosed by carotid sinus massage. We present a 67-year-old diabetic man who was admitted with hyperglycemia. During thyroid examination, clouding of consciousness occurred with unilateral palpation. Asystole was documented for 4.8 seconds and suspected for 7 seconds upon carotid sinus massage. A cardioverter defibrillator was implanted. Carotid sinus hypersensitivity should be kept in mind when examining diabetic patients.

  11. Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update

    OpenAIRE

    Luis González-Aveledo; Arnaldo Capriles-Hulett; Fernan Caballero-Fonseca; Mario Sánchez-Borges

    2010-01-01

    After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal antiinflammatory drugs are the second cause of hypersensitivity to drugs. Acute manifestations affect the respiratory tract (aspirin exacerbated respiratory disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis). Correct diagnosis and treatment in order to prevent unnecessary morbidity and the potential risk of death from these severe reactions, and to provide proper medical advice on future dru...

  12. Hyaluronidase hypersensitivity: A rare complication of peribulbar block

    Directory of Open Access Journals (Sweden)

    A R Rajalakshmi

    2016-01-01

    Full Text Available Peribulbar block, though safe, can cause serious complications such as globe perforation and peribulbar hemorrhage. Hyaluronidase is an enzyme that is used as an adjuvant in peribulbar anesthesia, and it helps in rapid penetration of the anesthetic agent. Hypersensitivity to hyaluronidase is a rare but potentially sight-threatening complication. We report a case of hyaluronidase hypersensitivity following peribulbar injection for cataract surgery mimicking as peribulbar hematoma in the immediate postinjection phase and as orbital cellulitis 48 h later.

  13. A world allergy organization international survey on diagnostic procedures and therapies in drug allergy/hypersensitivity.

    Science.gov (United States)

    Thong, Bernard Yu-Hor; Mirakian, Rita; Castells, Mariana; Pichler, Werner; Romano, Antonino; Bonadonna, Patrizia; Diana, Deleanu; Kowalski, Marek; Yanez, Anahi; Lleonart, Ramon; Sanchez-Borges, Mario; Demoly, Pascal

    2011-12-01

    To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009. Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro-specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens-Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies.

  14. Activation of spinal glucagon-like peptide-1 receptors specifically suppresses pain hypersensitivity.

    Science.gov (United States)

    Gong, Nian; Xiao, Qi; Zhu, Bin; Zhang, Chang-Yue; Wang, Yan-Chao; Fan, Hui; Ma, Ai-Niu; Wang, Yong-Xiang

    2014-04-09

    This study aims to identify the inhibitory role of the spinal glucagon like peptide-1 receptor (GLP-1R) signaling in pain hypersensitivity and its mechanism of action in rats and mice. First, GLP-1Rs were identified to be specifically expressed on microglial cells in the spinal dorsal horn, and profoundly upregulated after peripheral nerve injury. In addition, intrathecal GLP-1R agonists GLP-1(7-36) and exenatide potently alleviated formalin-, peripheral nerve injury-, bone cancer-, and diabetes-induced hypersensitivity states by 60-90%, without affecting acute nociceptive responses. The antihypersensitive effects of exenatide and GLP-1 were completely prevented by GLP-1R antagonism and GLP-1R gene knockdown. Furthermore, exenatide evoked β-endorphin release from both the spinal cord and cultured microglia. Exenatide antiallodynia was completely prevented by the microglial inhibitor minocycline, β-endorphin antiserum, and opioid receptor antagonist naloxone. Our results illustrate a novel spinal dorsal horn microglial GLP-1R/β-endorphin inhibitory pathway in a variety of pain hypersensitivity states.

  15. Anisakis simplex: from obscure infectious worm to inducer of immune hypersensitivity.

    Science.gov (United States)

    Audicana, M Teresa; Kennedy, Malcolm W

    2008-04-01

    Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites ("gastroallergic anisakiasis"), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.

  16. A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Feng; Tang, Yijun; Gao, Zhe [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

    2010-06-25

    Naringenin, a flavonoid in grapefruits and citrus fruits, has been reported to exhibit anti-inflammatory and anti-oxidative activities. Contact hypersensitivity (CHS) is a T cell-mediated immune reaction, and the factors released from macrophages also contribute to this response. Previous studies showed that naringenin suppressed CHS by inhibiting activation and migration of macrophages. However, little is known about naringenin's effects on T lymphocytes. Our study indicated that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment. Furthermore, naringenin reduced CD69 (the protein level) and cytokines such as IL-2, TNF-{alpha}, and IFN-{gamma} (the mRNA level) expressions which highly expressed by activated T cells. Meanwhile, naringenin also induced T cell apoptosis by upregulation of Bax, Bad, PARP, cleaved-caspase 3 and downregulation of phosphorylated Akt, Bcl-2. These findings suggest that, besides its anti-inflammatory activities in macrophages, naringenin also showed inhibitory effects on the activation and proliferation of T cells to alleviate symptoms of contact hypersensitivity.

  17. Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

    Science.gov (United States)

    Bonamichi-Santos, Rafael; Castells, Mariana

    2016-01-01

    Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Sulfasalazine-Related Hypersensitivity Reactions in Patients With Rheumatic Diseases.

    Science.gov (United States)

    Cildag, Songul; Senturk, Taskin

    2017-03-01

    Sulfasalazine (SSZ), which has an arylamine sulfonamide structure, is an anti-inflammatory drug used in the treatment of many rheumatic diseases. Various adverse effects have been reported related to SSZ. In the present study, we aimed to define the frequency of SSZ-related hypersensitivity reaction in patients with rheumatoid arthritis and ankylosing spondylitis. A total of 136 patients were included in this study. During follow-ups, reaction type, reaction duration, and drug doses were recorded in patients who developed hypersensitivity reactions. Drugs were discontinued in patients who developed reactions, and they were treated with antihistaminics and/or corticosteroids, according to requirements. Drug provocation tests with the drugs and aminosalicylic acid were performed in patients with negative skin prick test individually. A total of 136 patients, with ages ranging from 19 to 71 years (mean, 41.97 [SD, 12.04] years), were included in the study. Hypersensitivity reactions according to the drug provocation test were found against SSZ in 12 patients (8.8%). The SSZ-related hypersensitivity reaction types were urticaria in 7 patients, urticaria and angioedema in 4 patients, and pruritus in 1 patient. Sulfasalazine is widely used by rheumatologists in the treatment of rheumatic diseases. Whereas the frequency of sulfonamide-related hypersensitivity reactions was reported as 3.0% in the population, we detected hypersensitivity reactions to be 8.8% with SSZ usage in rheumatic diseases.

  19. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Chun-Bing Chen

    2018-01-01

    Full Text Available Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS/drug-induced hypersensitivity syndrome (DIHS, or Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN. Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs. The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.

  20. The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity

    Directory of Open Access Journals (Sweden)

    Andersson David A

    2010-01-01

    Full Text Available Abstract Background The cooling agents menthol and icilin act as agonists at TRPM8 and TRPA1. In vitro, activation of TRPM8 by icilin and cold, but not menthol, is dependent on the activity of a sub-type of phospholipase A2, iPLA2. Lysophospholipids (e.g. LPC produced by PLA2 activity can also activate TRPM8. The role of TRPA1 as a primary cold sensor in vitro is controversial, although there is evidence that TRPA1 plays a role in behavioural responses to noxious cold stimuli. In this study, we have investigated the roles of TRPM8 and TRPA1 and the influence of iPLA2 on noxious cold sensitivities in naïve animals and after local administration of menthol, icilin and LPC. The roles of the channels in cold sensitivity were investigated in mice lacking either TRPM8 (Trpm8-/- or TRPA1 (Trpa1-/-. Results Intraplantar administration of icilin evoked a dose-dependent increase in sensitivity to a 10°C stimulus that was inhibited by iPLA2 inhibition with BEL. In contrast the cold hypersensitivities elicited by intraplantar menthol and LPC were not inhibited by BEL treatment. BEL had no effect on basal cold sensitivity and mechanical hypersensitivities induced by the TRPV1 agonist, capsaicin, and the P2X3 agonist α,β-methylene ATP. Both Trpm8-/- and Trpa1-/- mice showed longer latencies for paw withdrawal from a 10°C stimulus than wild-type littermates. Cold hypersensitivities induced by either icilin or LPC were absent in Trpm8-/- mice but were retained in Trpa1-/- mice. In contrast, cold hypersensitivity evoked by menthol was present in Trpm8-/- mice but was lost in Trpa1-/- mice. Conclusions The findings that iPLA2 inhibition blocked the development of cold hypersensitivity after administration of icilin but failed to affect menthol-induced hypersensitivity agree well with our earlier in vitro data showing a differential effect of iPLA2 inhibition on the agonist activities of these agents. The ability of LPC to induce cold hypersensitivity

  1. Are They Fit For Purpose? Exploring Managers' Experiences of UK HR Graduates & Employability Implications: A Pilot Study

    OpenAIRE

    Mullen, Emma

    2014-01-01

    The purpose of this research is to expand on existing understandings of graduate employability through exploring the lived experiences and perceptions of key informants, in this case, those with direct line management responsibilities for graduates. The context of this research is focused on Human Resources (HR) graduates, a discipline that has seen little qualitative inquiry across the Higher Education (HE), employability and HR literature, and which is currently dominated by skills-led appr...

  2. Involvement of the Electrophilic Isothiocyanate Sulforaphane in Arabidopsis Local Defense Responses1

    Science.gov (United States)

    Andersson, Mats X.; Nilsson, Anders K.; Johansson, Oskar N.; Boztaş, Gülin; Adolfsson, Lisa E.; Pinosa, Francesco; Petit, Christel Garcia; Aronsson, Henrik; Mackey, David; Tör, Mahmut; Hamberg, Mats; Ellerström, Mats

    2015-01-01

    Plants defend themselves against microbial pathogens through a range of highly sophisticated and integrated molecular systems. Recognition of pathogen-secreted effector proteins often triggers the hypersensitive response (HR), a complex multicellular defense reaction where programmed cell death of cells surrounding the primary site of infection is a prominent feature. Even though the HR was described almost a century ago, cell-to-cell factors acting at the local level generating the full defense reaction have remained obscure. In this study, we sought to identify diffusible molecules produced during the HR that could induce cell death in naive tissue. We found that 4-methylsulfinylbutyl isothiocyanate (sulforaphane) is released by Arabidopsis (Arabidopsis thaliana) leaf tissue undergoing the HR and that this compound induces cell death as well as primes defense in naive tissue. Two different mutants impaired in the pathogen-induced accumulation of sulforaphane displayed attenuated programmed cell death upon bacterial and oomycete effector recognition as well as decreased resistance to several isolates of the plant pathogen Hyaloperonospora arabidopsidis. Treatment with sulforaphane provided protection against a virulent H. arabidopsidis isolate. Glucosinolate breakdown products are recognized as antifeeding compounds toward insects and recently also as intracellular signaling and bacteriostatic molecules in Arabidopsis. The data presented here indicate that these compounds also trigger local defense responses in Arabidopsis tissue. PMID:25371552

  3. News from HR: a word from Anne-Sylvie Catherin

    CERN Multimedia

    2016-01-01

    Anne-Sylvie Catherin, head of HR Department, looks back over her years at CERN before taking up her new position at the European Central Bank.   At the end of July, I will be leaving CERN on a special leave of absence to take up a new position at the European Central Bank. This is a new chapter in my career, in a new context with its own challenges, and as I prepare for it, I would like to take a little time to look back over my years at CERN and share with you the enriching journey it has been, both for myself and for HR. It has always been my strong belief that any organisation’s greatest asset is its people. When an HR professional believes that, it’s only a short step to the conclusion that the best way to nurture those people is by adopting a professional approach to HR. In this respect, I arrived at a very fortuitous time. Enrico Chiaveri was head of HR and, although his background is in physics, we shared that same conviction. Enrico was the icebreaker in driving change, a...

  4. [Aspirin hypersensitivity: characteristics and diagnostic approach].

    Science.gov (United States)

    Baudrand, H; Zaouche, S; Dubost, R; Carsin, A; Chatte, G; Freymond, N; Piperno, D; Dubreuil, C; Froehlich, P; Pacheco, Y; Devouassoux, G

    2015-03-01

    In routine medical practice, the diagnosis of aspirin hypersensitivity (AH) remains difficult. No clinical feature or biomarker is available to reliably confirm this diagnosis and oral provocation tests (OPT) are rarely performed. To compare asthmatics with and without AH. The clinical characteristics of 21 asthmatics with and 24 without AH respectively were determined. AH was defined by a positive OPT. A full blood count was done before and 24 hours after the OPT. The medical history was associated with a weak sensitivity (52%) and a good specificity (96%) for assessing the diagnosis of AH. There was a higher prevalence of AH in women, and a higher frequency of allergic rhinitis in AH, but no characteristic was useful to facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate higher values of platelets in AH patients. Following OPT, in AH patients only, a decrease in blood eosinophils and an increase in neutrophils was observed. These results confirm that the diagnosis of AH is challenging, with the history having only weak sensitivity. The observation that fluctuations in eosinophils and neutrophils occur following OPT in AH patients only warrants further investigations and suggests a rapid pro-inflammatory role for aspirin. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  5. Nonimmediate hypersensitivity reactions to iodinated contrast media.

    Science.gov (United States)

    Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J

    2013-08-01

    To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.

  6. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    Science.gov (United States)

    Farmer, A D; Aziz, Q

    2009-01-01

    Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

  7. Peripheral neuropathy induces cutaneous hypersensitivity in chronically spinalized rats.

    Science.gov (United States)

    Pitcher, Graham M; Ritchie, Jennifer; Henry, James L

    2013-07-01

    The present study was aimed at the issue of whether peripheral nerve injury-induced chronic pain is maintained by supraspinal structures governing descending facilitation to the spinal dorsal horn, or whether altered peripheral nociceptive mechanisms sustain central hyperexcitability and, in turn, neuropathic pain. We examined this question by determining the contribution of peripheral/spinal mechanisms, isolated from supraspinal influence(s), in cutaneous hypersensitivity in an animal model of peripheral neuropathy. Adult rats were spinalized at T8-T9; 8 days later, peripheral neuropathy was induced by implanting a 2-mm polyethylene cuff around the left sciatic nerve. Hind paw withdrawal responses to mechanical or thermal plantar stimulation were evaluated using von Frey filaments or a heat lamp, respectively. Spinalized rats without cuff implantation exhibited a moderate decrease in mechanical withdrawal threshold on ~day 10 (P day 18 (P day 4; P day 10; P neuropathy may have a pathologically relevant role in both inducing and sustaining neuropathic pain. Wiley Periodicals, Inc.

  8. Occupational asthma due to esparto hypersensitivity in a building worker.

    Science.gov (United States)

    Ruiz-Hornillos, Francisco Javier; De Barrio Fernández, Manuel; Molina, Pilar Tornero; Marcén, Itziar Sánchez; Fernandez, Galicia Davila; Sotés, María Rubio; de Ocariz, María Luisa Baeza Ochoa

    2007-01-01

    Esparto is a gramineous plant that has multiple applications in today's industry. Several cases of hypersensitivity pneumonitis (HP) caused by esparto inhalation have been reported, but only one case of asthma caused by Aspergillus fumigatus contaminating esparto has been communicated. We report a case of asthma induced by esparto inhalation in a 58-year-old man, who is a building industry worker, with subclinical sensitization to grass pollen. The relation between clinical symptoms and work activities was supported by peak expiratory flow (PEF) monitorization; PEF values decreased by 20% the days he handled esparto. Prick test with esparto was positive. Immunoblot analysis revealed several allergens in the esparto extract, some of them present in Lolium and A. fumigatus extracts. IgE immunoblot inhibition revealed a complete inhibition of lolium and A. fumigatus IgE reactive bands by esparto proteins. The patient then avoided the exposure to esparto at work and has remained asymptomatic for the last 2 years. In conclusion, this is a case of occupational asthma caused by esparto dust mediated by IgE antibodies. Proteins of A. fumigatus as well as proteins from this gramineous plant, which cross-reacted with esparto allergens, were responsible for the disease.

  9. Evaluation of the hypersensitivity potential of alternative butter flavorings.

    Science.gov (United States)

    Anderson, Stacey E; Franko, Jennifer; Wells, J R; Lukomska, Ewa; Meade, B Jean

    2013-12-01

    Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3=17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25-50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. Published by Elsevier Ltd.

  10. HDAC4 is required for inflammation-associated thermal hypersensitivity.

    Science.gov (United States)

    Crow, Megan; Khovanov, Nikita; Kelleher, Jayne H; Sharma, Simone; Grant, Andrew D; Bogdanov, Yury; Wood, John N; McMahon, Stephen B; Denk, Franziska

    2015-08-01

    Transcriptional alterations are characteristic of persistent pain states, but the key regulators remain elusive. HDAC4 is a transcriptional corepressor that has been linked to synaptic plasticity and neuronal excitability, mechanisms that may be involved in peripheral and central sensitization. Using a conditional knockout (cKO) strategy in mice, we sought to determine whether the loss of HDAC4 would have implications for sensory neuron transcription and nociception. HDAC4 was found to be largely unnecessary for transcriptional regulation of naïve sensory neurons but was essential for appropriate transcriptional responses after injury, with Calca and Trpv1 expression consistently down-regulated in HDAC4 cKO compared to levels in the littermate controls (0.2-0.44-fold change, n = 4 in 2 separate experiments). This down-regulation corresponded to reduced sensitivity to 100 nM capsaicin in vitro (IC50 = 230 ± 20 nM, 76 ± 4.4% wild-type capsaicin responders vs. 56.9 ± 4.7% HDAC4 cKO responders) and to reduced thermal hypersensitivity in the complete Freund's adjuvant (CFA) model of inflammatory pain (1.3-1.4-fold improvement over wild-type controls; n = 5-12, in 2 separate experiments). These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors. © The Author(s).

  11. Presumed hydrochlorothiazide-associated immunologic-hypersensitivity-induced pericardial effusion

    Directory of Open Access Journals (Sweden)

    Michael J Chaskes

    2013-08-01

    Full Text Available A 50-year-old Caucasian female presented for a second opinion regarding a newly diagnosed pericardial effusion. Seven months previously, hydrochlorothiazide was introduced into her pharmacologic regimen to aid in the management of her hypertension. A routine echocardiogram indicated a large pericardial effusion with signs of early cardiac tamponade. The patient subsequently underwent successful pericardiocentesis with complete drainage of the pericardial effusion. The effusion was empirically attributed to a viral etiology. Repeat echocardiograms showed recurrence of the pericardial effusion. Prior to undergoing a second pericardiocentesis with pericardial biopsy, as her physicians recommended, the patient sought a second opinion. While obtaining the patient’s history, an allergy to sulfa was elicited. The possibility that the pericardial effusion may be secondary to an immunologic-hypersensitivity reaction was considered. It was recommended the patient discontinue the use of hydrochlorothiazide. Nine days following discontinuation of hydrochlorothiazide and without any other intervention, an echocardiogram was reported to show the size of the pericardial effusion had subsided substantially. Nine weeks following discontinuation, almost complete resolution of the pericardial effusion was reported. It is hypothesized that when treated with hydrochlorothiazide, the patient had an immune response leading to the pericardial effusion.

  12. A single amino acid insertion in the WRKY domain of the Arabidopsis TIR-NBS-LRR-WRKY-type disease resistance protein SLH1 (sensitive to low humidity 1) causes activation of defense responses and hypersensitive cell death.

    Science.gov (United States)

    Noutoshi, Yoshiteru; Ito, Takuya; Seki, Motoaki; Nakashita, Hideo; Yoshida, Shigeo; Marco, Yves; Shirasu, Ken; Shinozaki, Kazuo

    2005-09-01

    In this study we characterized the sensitive to low humidity 1 (slh1) mutant of Arabidopsis ecotype No-0 which exhibits normal growth on agar plate medium but which on transfer to soil shows growth arrest and development of necrotic lesions. cDNA microarray hybridization and RNA gel blot analysis revealed that genes associated with activation of disease resistance were upregulated in the slh1 mutants in response to conditions of low humidity. Furthermore, the slh1 mutants accumulate callose, autofluorescent compounds and salicylic acid (SA). We demonstrate that SA is required for the slh1 phenotype but not PAD4 or NPR1. SLH1 was isolated by map-based cloning and it encodes a resistance (R)-like protein consisting of a domain with Toll and interleukin-1 receptor homology (TIR), a nucleotide-binding domain (NB), leucine-rich repeats (LRR) and a carboxy-terminal WRKY domain. SLH1 is identical to the R gene RRS1-R of the Arabidopsis ecotype Nd-1, a gene which confers resistance to the bacterial pathogen Ralstonia solanacearum GMI1000 and also functions as an R gene to this pathogen in No-0. We identified a 3 bp insertion mutation in slh1 that results in the addition of a single amino acid in the WRKY domain; thereby impairing its DNA-binding activity. Our data suggest that SLH1 disease resistance signaling may be negatively regulated by its WRKY domain in the R protein and that the constitutive defense activation conferred by the slh1 mutation is inhibited by conditions of high humidity.

  13. TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity.

    Science.gov (United States)

    Barabas, Marie E; Stucky, Cheryl L

    2013-03-04

    Mechanisms underlying postoperative pain remain poorly understood. In rodents, skin-only incisions induce mechanical and heat hypersensitivity similar to levels observed with skin plus deep incisions. Therefore, cutaneous injury might drive the majority of postoperative pain. TRPA1 and TRPV1 channels are known to mediate inflammatory and nerve injury pain, making them key targets for pain therapeutics. These channels are also expressed extensively in cutaneous nerve fibers. Therefore, we investigated whether TRPA1 and TRPV1 contribute to mechanical and heat hypersensitivity following skin-only surgical incision. Behavioral responses to mechanical and heat stimulation were compared between skin-incised and uninjured, sham control groups. Elevated mechanical responsiveness occurred 1 day post skin-incision regardless of genetic ablation or pharmacological inhibition of TRPA1. To determine whether functional changes in TRPA1 occur at the level of sensory neuron somata, we evaluated cytoplasmic calcium changes in sensory neurons isolated from ipsilateral lumbar 3-5 DRGs of skin-only incised and sham wild type (WT) mice during stimulation with the TRPA1 agonist cinnamaldehyde. There were no changes in the percentage of neurons responding to cinnamaldehyde or in their response amplitudes. Likewise, the subpopulation of DRG somata retrogradely labeled specifically from the incised region of the plantar hind paw showed no functional up-regulation of TRPA1 after skin-only incision. Next, we conducted behavior tests for heat sensitivity and found that heat hypersensitivity peaked at day 1 post skin-only incision. Skin incision-induced heat hypersensitivity was significantly decreased in TRPV1-deficient mice. In addition, we conducted calcium imaging with the TRPV1 agonist capsaicin. DRG neurons from WT mice exhibited sensitization to TRPV1 activation, as more neurons (66%) from skin-incised mice responded to capsaicin compared to controls (46%), and the sensitization

  14. Efeito da suplementação com L-alanil-L-glutamina sobre a resposta de hipersensibilidade do tipo tardio em ratos submetidos ao treinamento intenso Effect of L-glutamine and L-alanyl-L-glutamine supplementation on the response to delayed-type hypersensitivity test (DTH in rats submitted to intense training

    Directory of Open Access Journals (Sweden)

    Marcelo Macedo Rogero

    2002-12-01

    Full Text Available O treinamento intenso e o exercício exaustivo podem ocasionar imunossupressão em atletas por meio da diminuição da concentração plasmática de glutamina. O presente estudo verificou inicialmente o efeito da suplementação com L-glutamina e L-alanilL-glutamina sobre a resposta ao teste de hipersensibilidade do tipo tardio (HTT em ratos submetidos ao treinamento intenso em natação durante seis semanas. Posteriormente, foi avaliado o efeito dessas intervenções nutricionais sobre a contagem total e porcentual de leucócitos e concentração sérica de anticorpos IgG anti-albumina de soro bovino, em animais submetidos ao teste de exaustão e recuperados durante o período de 3 horas. Não houve efeito do treinamento e da suplementação sobre a resposta ao teste de HTT. Animais suplementados apresentaram maior concentração de glutamina no plasma (PIntense training and exhaustive exercise may cause immunesupression in athletes by reducing plasma glutamine concentration. Initially, this study verified the effect of L-glutamine and L-alanyl-L-glutamine supplementation on the response to delayed-type hypersensitivity test (DTH in rats submitted to intense swimming training for six weeks. Later on, we assessed the effect of these nutritional interventions on total and differential white blood cell counts and on concentration of anti-bovine serum albumin IgG antibodies, in animals submitted to exhaustion test and a three-hour recovery period. There was no effect of training and supplementation on the response to DTH. Supplemented animals presented greatest plasma glutamine concentration (p<0.05, though this increase in glutaminemia did not interfere on the serum IgG antibody concentration. The recovery period after intense exercise resulted in decreased glutaminemia as compared with the values obtained immediately after exhaustion test (p<0.05. Increase in corticosterone levels induced by strenuous exercises led to leukocytosis, neutrophilia

  15. Esprit HR mattress cover in pressure ulcer prevention.

    Science.gov (United States)

    Khoulowa, J

    Modern mattresses provide soft dense foam, which permits the redistribution of pressure on the patient over a wider area - away from bony prominences where pressure ulcers usually occur. The material used in producing multistretch covers for the new mattresses had a tendency to delaminate as a result of a combination of heat, moisture and inappropriate cleansing techniques causing the water barriers to fall. In partnership with York Health NHS Trust and the material manufacturer, STM Healthcare produced a mattress cover (Esprit HR) which was able to withstand higher pressure from heat and moisture and greatly extended the life expectancy of the Esprit HR mattress.

  16. Nifurtimox therapy for Chagas disease does not cause hypersensitivity reactions in patients with such previous adverse reactions during benznidazole treatment.

    Science.gov (United States)

    Pérez-Molina, José A; Sojo-Dorado, Jesús; Norman, Francesca; Monge-Maillo, Begoña; Díaz-Menéndez, Marta; Albajar-Viñas, Pedro; López-Vélez, Rogelio

    2013-08-01

    Currently, only two drugs are approved for treating Trypanosoma cruzi infection: benznidazole and nifurtimox. Adverse reactions are frequent with both drugs: they have chemical similarities and common metabolic pathways making cross reactions a possibility. Our objective was to describe the safety/tolerability profile of nifurtimox in patients who had previously discontinued benznidazole due to hypersensitivity reactions. We performed a prospective observational study from September 2009 to December 2011. Patients who discontinued benznidazole therapy due to hypersensitivity reactions (HR) and were later treated with nifurtimox were included. HR to benznidazole were defined as presence of a rash with or without mucosal involvement, fever or laboratory abnormalities (such as eosinophilia, leucopaenia or impaired liver function tests). The drugs were prescribed for 60 days (benznidazole) or 60-90 days (nifurtimox). The National Cancer Institute criteria (CTCAE, 2006, Version 3.0) were used for grading and reporting of adverse reactions (AR). Eighteen patients (16 females, two males, median age 35.5 years, range 15-50 years) with asymptomatic late chronic infection, were included. Median time between benznidazole interruption and start of therapy with nifurtimox was 121.5 days (IQR 72-223 days). Fifteen patients (83.3%) developed an AR to nifurtimox, gastrointestinal complaints and anorexia being the most common, and 13 patients (72%) completed the treatment schedule. Five patients interrupted therapy (27.8%) mainly because of gastrointestinal intolerance and/or nervous system toxicity. Only one patient developed skin lesions, a mild maculopapular rash not requiring specific therapy or treatment withdrawal. There was no severe AR. Nifurtimox as second line therapy in patients who discontinued benznidazole specifically due to HR appears to be safe and does not seem to be associated with a higher incidence of AR. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. CD11b+Ly6G− myeloid cells mediate mechanical inflammatory pain hypersensitivity

    Science.gov (United States)

    Ghasemlou, Nader; Chiu, Isaac M.; Julien, Jean-Pierre; Woolf, Clifford J.

    2015-01-01

    Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund’s adjuvant (CFA) as a model of adjuvant- and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G+CD11b+ neutrophils and T-cell receptor (TCR) β+ T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b+Ly6G− myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2+Ly6Chi) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b+Ly6G− myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation. PMID:26598697

  18. Multiple wavelength microwave observations of the RS Canum Venaticorum stars UX Arietis, HR 1099, HR 5110, and II Pegasi

    Science.gov (United States)

    Willson, Robert F.; Lang, Kenneth R.

    1987-01-01

    The variabilities, core size and magnetic field of the RS CVn star UX Arietis was measured with the VLA at pairs of frequencies near 1415 MHz and 4835 MHz on June 10, 1985. Data were also gathered on HR 1099, HR 5110 and II Peg. UX Arietis exhibited variability on time scales ranging from 30 sec to 1 hr at 4835 MHz, but no detectable variations at 1415 MHz. An upper limit of 900 billion cm was placed on the size of the core emitting region, which is estimated to have a magnetic field strength of 15 G. The 30 sec variations are attributed to absorption by thermal plasma between the G5 and K1 companions of the UX Arietis system.

  19. Sleep Fragmentation Exacerbates Mechanical Hypersensitivity and Alters Subsequent Sleep-Wake Behavior in a Mouse Model of Musculoskeletal Sensitization

    Science.gov (United States)

    Sutton, Blair C.; Opp, Mark R.

    2014-01-01

    Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on

  20. Anticonvulsant hypersensitivity syndrome: clinical and laboratory features.

    Science.gov (United States)

    Mansur, Ayşe Tülin; Pekcan Yaşar, Sirin; Göktay, Fatih

    2008-11-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a severe adverse drug reaction with multiorgan involvement. Aromatic anticonvulsants are the most frequently involved drugs. This study was aimed to highlight the clinical and laboratory findings of AHS. The medical records of 31 patients diagnosed as AHS in a 12-year period were evaluated retrospectively. The syndrome was related to carbamazepine in 48.38%, phenytoin in 35.48%, lamotrigine in 9.6% and cotreatment with lamotrigine and valproic acid in 6.45% of cases. Symptoms appeared 2-86 (mean: 35.96) days after ingestion of the offending agent. The type of skin rash was maculopapular and/or erythrodermic in 77.42% of patients, bullous in 19.35%, and erythematopustular in 3.22%. Fever and peripheral lymphadenopathy were detected in 61.29% and 54.82% of cases, respectively. Laboratory investigations revealed elevation of hepatic enzymes in 70.96%, leucocytosis in 43.3%, and peripheral eosinophilia in 64.3% of patients. Our analysis showed that carbamazepine and phenytoin are still the major causes of AHS, with lamotrigine being the third etiologic agent. Valproic acid and benzodiazepines are safe alternatives of the causative anticonvulsants. As there are yet no strict diagnostic criteria, the constellation of clinical and laboratory features that occur within 3 months of the associated anticonvulsant agents helps to recognize the disorder. The risk of seizure due to withdrawal or changing of the anticonvulsant drug and the potentially serious clinical features often necessitates providing care and treatment in an inpatient setting.

  1. Hypersensitivity myocarditis associated with ephedra use.

    Science.gov (United States)

    Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  2. Value-based HR practices, i-deals and clinical error control with CSR as a moderator.

    Science.gov (United States)

    Luu, Tuan; Rowley, Chris; Siengthai, Sununta; Thanh Thao, Vo

    2017-05-08

    Purpose Notwithstanding the rising magnitude of system factors in patient safety improvement, "human factors" such as idiosyncratic deals (i-deals) which also contribute to the adjustment of system deficiencies should not be neglected. The purpose of this paper is to investigate the role of value-based HR practices in catalyzing i-deals, which then influence clinical error control. The research further examines the moderating role of corporate social responsibility (CSR) on the effect of value-based HR practices on i-deals. Design/methodology/approach The data were collected from middle-level clinicians from hospitals in the Vietnam context. Findings The research results confirmed the effect chain from value-based HR practices through i-deals to clinical error control with CSR as a moderator. Originality/value The HRM literature is expanded through enlisting i-deals and clinical error control as the outcomes of HR practices.

  3. An Ounce of Prevention: The Benefits of an HR Audit

    Science.gov (United States)

    Seals, Brenda

    2011-01-01

    During her 13 years leading a school district human resources office, the author came to recognize that managing human capital is much more than recruiting, hiring, managing personnel records, and handling performance issues. In addition to implementing initiatives to increase the efficiency with which HR officers and staff perform those tasks,…

  4. “DOCTOR! Go for a course in HR Management”

    African Journals Online (AJOL)

    The best approach is through proactive leadership, emphasising ... HR Management”. Open Forum. Abstract. A key principle of family medicine is the management of resources. Human Resource Management (HRM) underpins other principles of family .... stantive vs. procedural issues, in labour jargon). An employer must ...

  5. Enrico Chiaveri: The dialogue in the HR Strategy

    CERN Multimedia

    2009-01-01

    Enrico Chiaveri has been Head of the Human Resources Department since 2005. A core part of his department’s mission with the new Management is to develop and implement a strategic HR approach for our forward-looking Organization. He explained key aspects of the HR strategy to the Bulletin. For the first time in CERN’s history, a head of the HR Department and his deputy - Anne-Sylvie Catherin - invited the staff to a general information meeting on 23 February 2009. The scope of the meeting was to present the status of a number of current initiatives that will improve and tailor CERN’s HR strategy to the needs of the Organization and its staff, and also open up dialogue. Presented for the first time in an integrated way, the initiatives include contract policy, MARS, a staff survey, CERN’s values, a performance model, recruitment & outreach, learning & development, internal mobility and the development of a code of condu...

  6. Atypical Employment Relationships and Commitment: Wishful Thinking or HR Challenge?

    NARCIS (Netherlands)

    Torka, Nicole

    2004-01-01

    Nowadays, simultaneously maintaining flexible working practices and commitment is an important topic for HR managers since they both can contribute to organisational success. However, many HRM researchers and practitioners are unsure whether these can go together as job security is often seen as a

  7. HR Manager Leadership in Quality Improvement in a College Environment

    Science.gov (United States)

    Sharabi, Moshe

    2010-01-01

    Purpose: The purpose of this paper is to present the influence of the human resource (HR) manager on the quality of service in an academic college, and the human resource management (HRM) outcomes of the process. Design/methodology/approach: The paper relates to a customer satisfaction survey. More than 120 questionnaires were completed by the…

  8. HR practices for enhancing sustainable employability : implementation, use, and outcomes

    NARCIS (Netherlands)

    Ybema, Jan Fekke; van Vuuren, Tinka; van Dam, Karen

    2017-01-01

    With the aging of the workforce, organizations need to maintain or improve the sustainable employability of their workforce throughout their working life. This raises the question which HR practices increase workers’ sustainable employability at work. The aim of this study is to investigate the

  9. The hypergiant HR 8752 evolving through the yellow evolutionary void

    NARCIS (Netherlands)

    Nieuwenhuijzen, H.; De Jager, C.; Kolka, I.; Israelian, G.; Lobel, A.; Zsoldos, E.; Maeder, A.; Meynet, G.

    2012-01-01

    Context. We study the time history of the yellow hypergiant HR 8752 based on high-resolution spectra (1973-2005), the observed MK spectral classification data, B - V- and V-observations (1918-1996) and yet earlier V-observations (1840-1918).
    Aims. Our local thermal equilibrium analysis of the

  10. FACILITATING RADICAL FRONT-END INNOVATION THROUGH TARGETED HR PRACTICES

    DEFF Research Database (Denmark)

    Aagaard, Annabeth

    2017-01-01

    study of the Danish pharmaceutical company, H. Lundbeck A/S, and explorative studies of seven European and American pharmaceutical and biotech companies. The study aims to show how companies can apply HR practices in ways that actively supports the development of radical front end innovation. The value...

  11. Can HR practices retain flexworkers with their agency?

    NARCIS (Netherlands)

    Kroon, B.; Freese, C.

    2013-01-01

    Purpose Workers have different motives to be employed at specialist contract work agencies, such as career development aspirations, or a desire for freedom and independence. The purpose of this paper is to study how these different motives relate to the appreciation of HR practices applied by

  12. Learning Culture, Line Manager and HR Professional Practice

    Science.gov (United States)

    Harrison, Patricia

    2011-01-01

    Purpose: This paper aims to focus on the role of line management and learning culture in the development of professional practice for the human resource (HR) practitioner. Design/methodology/approach: Three-year longitudinal, matched-pair study involving five participants and their line managers. Findings: Two of the five participants experienced…

  13. In-sourcing HR: shared service centres in the Netherlands

    NARCIS (Netherlands)

    Farndale, Elaine; Paauwe, Jaap; Hoeksema, Ludwig

    2009-01-01

    Due to the impact of now widely-available technologies, new logics behind the organisation of the HR function through the in- and outsourcing of HRM activities have been emerging, particularly addressing issues of integration, cost-efficiency and competitive advantage. In particular, increasing

  14. Heart Rate Variability: Effect of Exercise Intensity on Postexercise Response

    Science.gov (United States)

    James, David V. B.; Munson, Steven C.; Maldonado-Martin, Sara; De Ste Croix, Mark B. A.

    2012-01-01

    The purpose of the present study was to investigate the influence of two exercise intensities (moderate and severe) on heart rate variability (HRV) response in 16 runners 1 hr prior to (-1 hr) and at +1 hr, +24 hr, +48 hr, and +72 hr following each exercise session. Time domain indexes and a high frequency component showed a significant decrease…

  15. Immediate-type hypersensitivity to polyethylene glycols: a review.

    Science.gov (United States)

    Wenande, E; Garvey, L H

    2016-07-01

    Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate-type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross-sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEG's as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re-exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management. © 2016 John Wiley & Sons Ltd.

  16. Comparison of cellular responses to Xanthomonas perforans infection between resistant and susceptible tomato accessions.

    Science.gov (United States)

    Wang, Y Q; Zhang, X F; Li, N; Liu, X

    2017-02-01

    Bacterial spot of tomato (Solanum lycopersicum L.) caused by several Xanthomonas species is one of the most destructive diseases. Genes regulating the hypersensitive resistance and field resistance to X. perforans race T3 have been intensively investigated over the last decade. However, a comparative analysis of cellular responses to the pathogen in susceptible and resistant hosts has not been completed, which prevents the detailed understanding of the interactions between the pathogen and tomato plants. In this study, the characteristics of lesions, stomata, and pathogen colonization in hypersensitive response (HR) PI 128216, field-resistant PI 114490, and susceptible OH 88119 tomato plants after inoculation with green fluorescent protein-labeled X. perforans race T3 bacteria were investigated. Significant differences in developmental processes and the micromorphology of spot lesions among three tomato lines were observed. Our results suggested that the faster lesion development in OH 88119 plants compared with that of the other two lines was associated with a greater increase in the stomatal apertures over a longer period following bacterial inoculation. The depth of bacterial colonization and pathogen density inside infected leaves in OH 88119 were also significantly different from that of resistant tomato plants. Determination of the ultrastructural responses to X. perforans among three tomato lines revealed that cell wall defense response was the main difference between resistant and susceptible tomato lines. These results may provide fundamental information for understanding the cellular and molecular mechanisms regulating tomato responses to X. perforans race T3. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Amygdala hypersensitivity in response to emotional faces in Tourette's patients.

    Science.gov (United States)

    Neuner, Irene; Kellermann, Thilo; Stöcker, Tony; Kircher, Tilo; Habel, Ute; Shah, Jon N; Schneider, Frank

    2010-10-01

    Tourette's syndrome is characterised by motor and vocal tics as well as a high level of impulsivity and emotional dysregulation. Neuroimaging studies point to structural changes of the basal ganglia, prefrontal cortex and parts of the limbic system. However, there is no link between behavioural symptoms and the structural changes in the amygdala. One aspect of daily social interaction is the perception of emotional facial expressions, closely linked to amgydala function. We therefore investigated via fMRI the implicit discrimination of six emotional facial expressions in 19 adult Tourette's patients. In comparison to healthy control group, Tourette's patients showed significantly higher amygdala activation, especially pronounced for fearful, angry and neutral expressions. The BOLD-activity of the left amygdala correlated negatively with the personality trait extraversion. We will discuss these findings as a result of either deficient frontal inhibition due to structural changes or a desynchronization in the interaction of the cortico-striato-thalamo-cortical network within structures of the limbic system. Our data show an altered pattern of implicit emotion discrimination and emphasize the need to consider motor and non-motor symptoms in Tourette's syndrome in the choice of both behavioural and pharmacological treatment.

  18. Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

    Science.gov (United States)

    Latremoliere, Alban; Woolf, Clifford J.

    2009-01-01

    Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. Perspective In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors. PMID:19712899

  19. Getting the HR message across: The linkage between line HR consensus and commitment strength among hospital employees

    NARCIS (Netherlands)

    Dorenbosch, Luc; Reuver, Renee; Sanders, Karin

    2006-01-01

    Related to the theoretical work of Bowen and Ostroff (2004; also Ostroff/Bowen 2000), this article focuses on the features of an HRM system that help or constrain organizations to get their HR message across. At a department-level of analysis, we focus on the consensus between line managers and

  20. Current Knowledge and Management of Hypersensitivity to Aspirin and NSAIDs.

    Science.gov (United States)

    Laidlaw, Tanya M; Cahill, Katherine N

    Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most common culprits of drug-induced hypersensitivity reactions, and can lead to a wide array of adverse effects. The accurate and timely diagnosis of aspirin and NSAID-induced hypersensitivity reactions is important for both patient safety and for the initiation of appropriate disease-specific management and treatment. Because there are no reliably validated in vitro tests available, aspirin and NSAID challenges are considered to be the criterion standard for the diagnosis of these hypersensitivity reactions, though in some patients the diagnosis can be made on the basis of a clear clinical history. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial

    Directory of Open Access Journals (Sweden)

    Yoshida Y

    2015-11-01

    hypersensitivity reactions.Results: Hypersensitivity reactions occurred in three patients (4.1%; all three experienced a cutaneous reaction (grade 1 erythema. None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%.Conclusion: The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned. Keywords: oxaliplatin, dexamethasone, hypersensitivity, allergy 

  2. Visceral hypersensitivity is provoked by 2,4,6-trinitrobenzene sulfonic acid-induced ileitis in rats

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Shah

    2016-07-01

    Full Text Available Background and Aims: Crohn’s Disease (CD, a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48, an equal volume of 30% Ethanol (n = 24 and Saline (n = 24, respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR to 20, 40, 60, 80 and 100 mmHg colorectal distension pressure (CRD at day 1, 3, 7, 14, 21 and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6, and dorsal root ganglia (T11 for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05 VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05 in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusions: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral

  3. Inhibitory effect of the selective serotonin 5-HT₃ receptor antagonist ramosetron on duodenal acidification-induced gastric hypersensitivity in rats.

    Science.gov (United States)

    Nakata-Fukuda, Mari; Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Uchiyama, Yasuo

    2014-05-15

    Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are both functional gastrointestinal disorders and frequently co-occur in patients. While one cause of FD appears to be gastric hypersensitivity, whether the hypersensitivity is affected by IBS treatments remains unclear, given the lack of appropriate animal models for testing. Here, we established an experimental model of duodenal acidification-induced gastric hypersensitivity in conscious rats. The model involved duodenal acidification induced by the infusion of hydrochloric acid into the proximal duodenum, with the nociceptive response being determined as the change in mean arterial pressure (MAP) during gastric distension via an indwelling latex balloon. Using our model we evaluated the effects of duodenal acidification, increased distension pressure, and orally administered therapeutic agents for IBS with diarrhea (IBS-D). Duodenal acidification enhanced the pressor response during gastric distension, and pretreatment with the opioid κ-receptor agonist fedotozine (10mg/kg, intra-arterial) inhibited the pressor response. Pressure levels of 15-60 mm Hg increased MAP in response to gastric distension. The serotonin 5-HT3 receptor antagonist ramosetron (30 μg/kg) inhibited MAP increase induced by duodenal acidification, with no other IBS-D therapeutic agents showing any effect. In contrast, the serotonin 5-HT3 receptor agonist m-chlorophenylbiguanide (1mg/kg) significantly enhanced the pressor response during gastric distension. These findings indicate that the serotonin 5-HT3 receptor plays a key role in duodenal acidification-induced gastric hypersensitivity in rats, suggesting that ramosetron may reduce FD symptoms by ameliorating sensitized gastric perception. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Activación de celulas supresoras de la respuesta de hipersensibilidad tardía en ratones BALB/c infectados o vacunados con Leishmania mexicana pifanoi Activation of supressor cells of delayed hypersensitivity response in BALB/C mice infected or immunized with Leishmania mexicana pifanoi

    Directory of Open Access Journals (Sweden)

    Hilda A. Pérez

    1985-12-01

    Full Text Available Los ratones BALB/c inmunizados SC con promastigotes no viables de Leishmania mexicana pifanoi, desarrollaron respuestas de hipersensibilidad tardia (RHT contra el parásito. En contraposición, los ratones BALB/c infectados crónicamente con L.m. pifanoi y aquellos inmunizados IV con una dosis supraóptima de parásitos muertos, mostraron inhibición de la RHT. La supresión de la RHT en los animales infectados, estuvo precedida por un estado transitorio de inmunidad celular, manifestado durante la fase inicial del desarrollo de las lesiones (4-12 semanas. La inhibición de la RHT observada en los animales infectados o inmunizados con dosis supraóptimas, fue causada por un mecanismo activo, transferible a receptores singénicos a través de las células esplénicas de los donantes suprimidos. La población de células supresoras fue no adherente a "nylon", sensible al tratamiento con un suero anti-timocitos de ratón y C', y de acción específica sobre la RHT contra antígenos leishmánicos. Se propone que la ocurrencia de células T supresoras de la RHT en los animales infectados crónicamente o inmunizados con dosis supraóptimas, es causada por el exceso de carga antigénica. Esta última, en el caso de los animales infectados, secundaria a una falla primaria en el control inmunológico de la población parasitaria.A T suppressor cell population that specifically shut down delayed hypersensitivity responses (DHR to the parasite was found in both BALB/c mice chronically infected with Leishmania mexicana pifanoi and in naive mice which had received a single IV supraoptimal dose of killed parasites. At the early phase of infection mice exhibited a transitory state of cell-mediated immunity against the parasite that was abrogated when lesions reached their accelerated phase of growth. Results suggest that in both infected and high-dose immunized mice, the activation of T suppressor cells of DHR is related to antigen overload.

  5. Hypersensitivity to intravenous ondansetron: a case report

    Directory of Open Access Journals (Sweden)

    Mehra Karishma K

    2008-08-01

    Full Text Available Abstract Introduction Ondansetron, a 5-hydroxytryptamine3 receptor antagonist widely used in the prevention and treatment of chemotherapy-induced nausea and vomiting, is associated with various unusual adverse drug reactions. In this paper, we describe a hypersensitivity reaction to a single intravenous dose of ondansetron. Case presentation A 19-year-old woman presented to the emergency department of our institute with 3–4 episodes of nausea, vomiting and epigastric distress. She had a diagnosis of polycystic ovarian disease and had been on treatment with cyproterone acetate 2 mg, ethinyl estradiol 0.035 mg, finasteride 5 mg and metformin 500 mg for a month. She had been taking oral roxithromycin 500 mg per day for the past 3 days for treatment of a mild upper respiratory tract infection. She also occasionally took rabeprazole 10 mg for gastritis which had worsened after treatment with roxithromycin. She was treated with a single 4 mg dose of ondansetron intravenously. She immediately developed urticaria, which was treated with intravenous dexamethasone 4 mg and chlorpheniramine maleate 20 mg. The reaction abated within a few minutes and she was discharged within an hour. She was asymptomatic at 72 hours of follow-up. She had no history of ondansetron exposure, or drug or food allergies. On the Naranjo's causality assessment scale, the adverse event was 6 indicating a "probable" reaction to ondansetron. Conclusion 5-hydroxytryptamine3 receptor antagonists have been associated with life-threatening adverse reactions such as hypotension, seizures and anaphylaxis. The wide availability of these drugs in India has promoted their off label use in the treatment of gastritis, migraine and so on. Our case represents an off label use in a patient who could have been treated with a safer drug. Some authors have suggested that anaphylaxis may be a class effect while others think it may be drug specific. In our case, the reaction could be either

  6. Corticosteroid hypersensitivity studies in a skin allergy clinic.

    Science.gov (United States)

    Berbegal, L; DeLeon, F J; Silvestre, J F

    2015-12-01

    Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic. Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period. We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction. The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  7. Metal hypersensitivity after knee arthroplasty: fact or fiction?

    Science.gov (United States)

    Innocenti, Massimo; Vieri, Berti; Melani, Tommaso; Paoli, Tommaso; Carulli, Christian

    2017-06-07

    Hypersensitivity to metals in the general population has an incidence of about 15%, and in rising also for the higher number of joint replacements in the last decades. Total Knee Arthroplasty (TKA) represents the most performed orthopaedic procedure during last years, and it seems to be particularly associated with sensitization after surgery. On the other hand, there is a rising amount of patients with painful but well implanted and functioning TKAs: in certain cases, after the exclusion of the most frequent causes of failure, a condition of hypersensitivity may be found, and a revision with anallergic implants is mandatory. The present study is a review of the potential problems related to hypersensitivity in TKA, its possible diagnostic procedures, and the surgical options to date available. Medical history, patch testing, and other specific laboratory assays are useful to assess a status of metals hypersensitivity before surgery in subjects undergoing a knee replacement, or even after TKA in patients complaining pain in otherwise well implanted and aligned prostheses. However, few groups worlwide deal with such condition, and all proposed diagnostic protocols may be considered still today conjectural. On the other hand, these represent the most updated knowledge of this condition, and may be useful for both the patient and the orthopaedic surgeon. Once assessed a possible or ascertained allergy to metals, several options are available for primary andr revision knee surgery, in order to avoid the risk of hypersensitivity. A review of the recent publications on this topic and an overview of the related aspects has been made to understand a condition to date considered negligible. Hypersensitivity to metals has not to be nowadays considered a "fiction", but rather a possible preoperative risk or a postoperative cause of failure of TKA. Crucial is the information of patients and the medical history, associated in suspect cases to laboratory testings. Today in the

  8. Old, New and Hidden Causes of Perioperative Hypersensitivity.

    Science.gov (United States)

    Garvey, Lene Heise

    2016-01-01

    Perioperative hypersensitivity reactions are rare, often life-threatening events, and subsequent investigations to identify the culprit are important to avoid re-exposure. All exposures in the perioperative setting may potentially be the cause of a hypersensitivity reaction, but drugs administered intravenously such as neuromuscular blocking agents (NMBA), induction agents and antibiotics have traditionally been reported to be implicated most commonly. It has recently become apparent that there are geographical differences in sensitization patterns related to variation in exposures, referral patterns and performance and interpretation of investigations. Differences in sensitization to NMBAs are partly explained by cross sensitization to pholcodine, an ingredient in cough-medicines available in some countries. While NMBAs are the most common causes of perioperative hypersensitivity in some countries, this may not necessarily be the case in all countries. New and hidden allergens have emerged as causes of perioperative hypersensitivity such as blue dyes, chlorhexidine and excipients. Detailed knowledge of the events at the time of reaction is necessary to identify potential culprits including rare and hidden allergens. Cooperation between allergists and anaesthetists, or other staff present perioperatively, is often needed to identify hidden or even undocumented exposures. The objectives of this review are to provide an overview of the history of investigation of perioperative hypersensitivity, to describe the differences in causes of perioperative hypersensitivity emerging over time and to increase awareness about the "hidden allergens" in the perioperative setting. Some practical advice on how to approach the patient testing negative on all initial investigations is also included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Efficacy of two commercially available dentifrices in reducing dentinal hypersensitivity

    Directory of Open Access Journals (Sweden)

    Prasad KVV

    2010-01-01

    Full Text Available Objective: A parallel design clinical study evaluated reduction in hypersensitivity after brushing for 12 weeks with Anchor toothpaste (containing potassium citrate, zinc citrate, triclosan and sodium monofluorophosphate (test and Colgate Total (sodium fluoride, silica, triclosan and copolymer (control dentifrices. Materials and Methods: Sixty adults with sensitivity to hot and cold stimulus in at least two tooth surfaces were stratified at the baseline examination by tactile, hot and cold stimuli scores in two balanced groups. Subjects were randomly allocated the test and control dentifrices and evaluated after 6 and 12 weeks of dentifrice use for hypersensitivity. Results: The two teeth that were selected in each patient were designated as two different sets. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the test group showed a reduction in tooth hypersensitivity by 36.67% (P < 0.01, 20.35% (P < 0.01 and 53.64 % (P < 0.01, respectively, in the first set of teeth and 43.75% (P < 0.01, 24.48% (P < 0.01 and 59.78% (P < 0.01, respectively, in the second set of teeth. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the control group showed a reduction in tooth hypersensitivity by 42.86% (P < 0.01, 13.02% (P < 0.01 and 45.14% (P < 0.01, respectively, in the first set of teeth and 40% (P < 0.01, 16.59% (P < 0.01 and 44.16% (P < 0.01, respectively, in the second set of teeth. Conclusions: Both the products reduced dentinal hypersensitivity in the study subjects at the end of the 12-week period. However, there was no statistically significant difference in reduction in hypersensitivity between the two products.

  10. Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome

    NARCIS (Netherlands)

    Kuiken, S. D.; Lindeboom, R.; Tytgat, G. N.; Boeckxstaens, G. E.

    2005-01-01

    Visceral hypersensitivity is considered an important pathophysiological mechanism in irritable bowel syndrome, yet its relationship to symptoms is unclear. Aim: To detect possible associations between symptoms and the presence of hypersensitivity to rectal distension in patients with irritable bowel

  11. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    NARCIS (Netherlands)

    Schurink, A.; Wolc, A.; Ducro, B.J.; Frankena, K.; Garrick, D.J.; Dekkers, J.C.M.; Arendonk, van J.A.M.

    2012-01-01

    Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite

  12. Role HR business partnerství a jeho proměny

    OpenAIRE

    Lučná, Kateřina

    2011-01-01

    This thesis focuses on the HR Business Partnership Model, as introduced and continuously updated by David Ulrich. The goal of the thesis is to show the development and transformation of HR roles, and the transformation of the HR Business Partner's role. In the practical part, I attempt to answer the question of how HR fulfills the roles of HR Business Partnership in its recently defined form. Evaluators are themselves employees, managers and HR professionals.

  13. Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Liggett, S B; Christensen, N J

    1991-01-01

    by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP...... to diabetic autonomic neuropathy. Regardless of the mechanism of adrenergic denervation hypersensitivity in such patients, these data provide further evidence that measurements of cellular adrenergic receptors (and adenylate cyclase) in vitro are a fallible index of sensitivity to catecholamines in vivo....

  14. Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)

    DEFF Research Database (Denmark)

    Nissen, Christoffer V; Bindslev-Jensen, Carsten; Mørtz, Charlotte G

    2015-01-01

    BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify...... responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients. CONCLUSIONS: All but one of our patients could be classified according to the EAACI...

  15. Dapsone hypersensitivity syndrome not related to G6PD deficiency.

    Science.gov (United States)

    Schulkes, Karlijn J G; Tervaert, J W Cohen; Rijken, Feiko; Haas, Lenneke E M

    2015-12-18

    Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. We describe a 55-year-old Caucasian woman with normal glucose-6-phosphate dehydrogenase levels presenting with an extensive skin eruption, high-grade fever, pneumonitis and hepatitis, which occurred within 3 weeks after initiation of dapsone. In addition to supportive care, the patient was successfully treated with high-dose corticosteroids and antibiotics. The combination of high-grade fever, skin rash, lung and liver involvement made a dapsone hypersensitivity syndrome very likely. 2015 BMJ Publishing Group Ltd.

  16. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    LENUS (Irish Health Repository)

    Keohane, John

    2012-02-03

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  17. Contact Hypersensitivity to Topical Antimicrobial and Antifungal Agents

    Directory of Open Access Journals (Sweden)

    A K Bajaj

    1982-01-01

    Full Text Available To find out the incidence of hypersensitivity to antimicrobial drugs patch tests with various commercially available antimicrobial agents were carried out in 112 patients suspected of contact sensitivity to these substances. Eighty eight patients showed positive reaction to one or more drugs. H incidence of contact sensitivity was observed with neomycin (48%, nitrofurazone (460/o and bromsalicyl chloranilide (45%, while gentian violet gentamicin and povidone iodine were found to be the least sensitizers (5%, 6% and 70/o - respectively. Multiple hypersensitivity (four or more drugs was observed in 25 patients and a large number of them had ulcers at the time of study or in the past.

  18. Transmission electron microscopic characterization of hypersensitive human radicular dentin

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiyama, M.; Noiri, Y.; Ozaki, K.; Uchida, A.; Ishikawa, Y.; Ishida, H. (Tokushima Univ. School of Dentistry (Japan))

    1990-06-01

    Transmission electron microscopy (TEM) and x-ray microanalysis (XMA) were used for the study of the ultrastructure of the lumens of dentinal tubules in superficial layers of dentin specimens obtained by use of a new biopsy technique from both hypersensitive and naturally desensitized areas of exposed root surfaces, in vivo. The TEM images showed clearly that the lumens of most of the tubules were occluded with mineral crystals in naturally desensitized areas, but such lumens were empty and surrounded with peritubular and intertubular dentin in hypersensitive areas. Moreover, electron-dense structures that lined peritubular dentin were observed in the empty lumens of dentinal tubules.

  19. Human Resource Predictive Analytics HRPA For HR Management In Organizations

    Directory of Open Access Journals (Sweden)

    Sujeet N. Mishra

    2015-08-01

    Full Text Available Human resource predictive analytics is an evolving application field of analytics for HRM purposes. The purpose of HRM is measuring employee performance and engagement studying workforce collaboration patterns analyzing employee churn and turnover and modelling employee lifetime value. The motive of applying HRPA is to optimize performances and produce better return on investment for organizations through decision making based on data collection HR metrics and predictive models. The paper is divided into three sections to understand the emergence of HR predictive analytics for HRM. Firstly the paper introduces the concept of HRPA. Secondly the paper discusses three aspects of HRPA a Need b Approach amp Application c Impact. Lastly the paper leads to the conclusion on HRPA.

  20. Biomarkers for non-human primate type-I hypersensitivity: antigen-specific immunoglobulin E assays.

    Science.gov (United States)

    Clark, Darcey; Shiota, Faith; Forte, Carla; Narayanan, Padma; Mytych, Daniel T; Hock, M Benjamin

    2013-06-28

    Immunoglobulin E (IgE) is the least abundant immunoglobulin in serum. However, development of an IgE immune response can induce IgE receptor-expressing cells to carry out potent effector functions. A reliable antigen-specific IgE biomarker method for use in non-human primate studies would facilitate (i) confirmation of Type-I hypersensitivity reactions during safety toxicology testing, and (ii) a better understanding of non-human primate models of allergic disease. We cloned and expressed a recombinant cynomolgus monkey IgE molecule in order to screen a panel of commercially available detection reagents raised against human IgE for cross-reactivity. The reagent most reactive to cynomolgus IgE was confirmed to be specific for IgE and did not bind recombinant cynomolgus monkey IgG1-4. A drug-specific IgE assay was developed on the MSD electrochemiluminescent (ECL) platform. The assay is capable of detecting 10 ng/mL drug-specific IgE. Importantly, the assay is able to detect IgE in the presence of excess IgG, the scenario likely to be present in a safety toxicology study. Using our ECL assay, we were able to confirm that serum from cynomolgus monkeys that had experienced clinical symptoms consistent with hypersensitivity responses contained IgE specific for a candidate therapeutic antibody. In addition, a bioassay for mast cell activation was developed using CD34(+)-derived cynomolgus monkey mast cells. This assay confirmed that plasma from animals identified as positive in the drug-specific IgE immunoassay contained biologically active IgE (i.e. could sensitize cultured mast cells), resulting in histamine release after exposure to the therapeutic antibody. These sensitive assays for Type-I hypersensitivity in the NHP can confirm that secondary events are downstream of immunogenicity. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice

    Energy Technology Data Exchange (ETDEWEB)

    Connor, M.J. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Puhvel, S.M. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Sakamoto, M. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Nanthur, J. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States))

    1994-12-01

    In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 [mu]g TCDD/kg body weight on postnatal day 0. At 12 [mu]g/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 [mu]g/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice. (orig.)

  2. Teaching HR Professionals: The Classroom as a Community of Practice

    Directory of Open Access Journals (Sweden)

    Alex Avramenko

    2013-05-01

    Full Text Available This paper introduces an innovative course design incorporating both communities of practice and reflective practice as a learning strategy for part-time learners in higher education. The new design has been applied to teaching HR practitioners in a UK-based business school. Findings indicate that the suggested way of organizing teaching and learning for part-time professionals is very informative and facilitates a richer engagement with theory whilst addressing issues of practice.

  3. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    OpenAIRE

    Schurink, A.; Wolc, A.; Ducro, B.J.; Frankena, K.; Garrick, D.J.; Dekkers, J.C.M.; Arendonk, van, J.A.M.

    2012-01-01

    Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods: Da...

  4. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    OpenAIRE

    Schurink, Anouk; Wolc, Anna; Ducro, Bart J; Frankena, Klaas; Garrick, Dorian J; Dekkers, Jack CM; van Arendonk, Johan AM

    2012-01-01

    Abstract Background Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Met...

  5. Stereotypes and Prejudices in HR Industry in Romania

    Directory of Open Access Journals (Sweden)

    Simina GHERASIM-ARDELEAN

    2011-03-01

    Full Text Available In this paper we aimed to reveal the effects of the crisis in HR area, the stereotypes and prejudices clients have about Romanian HR companies, training programs and trainers and the ideal profile of a trainer. The effects of the crisis in HR are: the stagnation of the number of clients in the company’s portfolio, the decreasing in the number of contracted training, the decreasing of the training prices and project-based contracts with trainers instead of permanent job contracts. We find that two important features a trainer should have are connected with the age of the trainer and personality traits. A good trainer is expected to have an age between 30 and 50 years and a pleasant personality. Most of the correlations obtained between stereotypes and prejudices are positive. Almost all items correlated with the others. Demographic data correlated also with items. Respondent’s education correlates positively with the number of the training classes attended and stereotypes on trainer’s age. The more educated the respondent is, the more likely is to have attended a greater number of trainings and tend to prefer mature trainer to young trainer (under 30 years old. The more mature respondents tend to prefer foreign trainers and mature trainers. Age of the respondent and trainer’s country of provenience and age are positively correlated.

  6. Size-exclusion chromatographic NMR under HR-MAS.

    Science.gov (United States)

    Lucena Alcalde, Guillermo; Anderson, Natalie; Day, Iain J

    2017-05-01

    The addition of stationary phases or sample modifiers can be used to modify the separation achievable in the diffusion domain of diffusion NMR experiments or provide information on the nature of the analyte-sample modifier interaction. Unfortunately, the addition of insoluble chromatographic stationary phases can lead to line broadening and degradation in spectral resolution, largely because of differences in magnetic susceptibility between the sample and the stationary phase. High-resolution magic angle spinning (HR-MAS) techniques can be used to remove this broadening. Here, we attempt the application of HR-MAS to size-exclusion chromatographic NMR with limited success. Observed diffusion coefficients for polymer molecular weight reference standards are shown to be larger than those obtained on static samples. Further investigation reveals that under HR-MAS it is possible to obtain reasonably accurate estimates of diffusion coefficients, using either full rotor synchronisation or sophisticated pulse sequences. The requirement for restricting the sample to the centre of the MAS rotor to ensure homogeneous magnetic and RF fields is also tested. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. A novel bioactive glass-ceramic for treating dentin hypersensitivity

    Directory of Open Access Journals (Sweden)

    Camila Tirapelli

    2010-12-01

    Full Text Available Dentin hypersensitivity (DH is a painful response to stimulus applied to the open dentinal tubules of a vital tooth. It's a common oral condition, however, without an ideal treatment available yet. This work evaluated in vitro the effect of micron-sized particles from a novel bioactive glass-ceramic (Biosilicate in occluding open dentinal tubules. A dentin disc model was employed to observe comparatively, using scanning electron microscopy (SEM, dentinal tubule occlusion by different products and deposition of hydroxyl carbonate apatite (HCA on dentin surface by Biosilicate, after a single application: G1 - Dentifrice with potassium nitrate and fluoride; G2 - Two-step calcium phosphate precipitation treatment; G3 - Water-free gel containing Biosilicate particles (1%; G4 - Biosilicate particles mixed with distilled water in a 1:10 ratio; all of them after 1, 12 and 24 hours of immersion in artificial saliva. Fourier transform infrared spectroscopy (FTIR was performed to detect HCA formation on dentin discs filled with Biosilicate after 2 minutes, 30 minutes and 12 hours of immersion in artificial saliva. SEM showed a layer of HCA formed on dentin surface after 24 hours by G4. G1, G2 and G3 promoted not total occlusion of open dentinal tubules after 24 hours. FTIR showed HCA precipitation on the dentin surface induced by Biosilicate after 30 minutes. The micron-sized particles from the bioactive glass-ceramic thus were able to induce HCA deposition in open dentinal tubules in vitro. This finding suggests that Biosilicate may provide a new option for treating DH.

  8. Nav1.9 Channel Contributes to Mechanical and Heat Pain Hypersensitivity Induced by Subacute and Chronic Inflammation

    OpenAIRE

    Stéphane Lolignier; Muriel Amsalem; François Maingret; Françoise Padilla; Mélanie Gabriac; Eric Chapuy; Alain Eschalier; Patrick Delmas; Jérôme Busserolles

    2011-01-01

    Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using ...

  9. LACK OF ANALGESIC EFFICACY OF SPINAL ONDANSETRON ON THERMAL AND MECHANICAL HYPERSENSITIVITY FOLLOWING SPINAL NERVE LIGATION IN THE RAT

    OpenAIRE

    Peters, Christopher M.; Hayashida, Ken-ichiro; Ewan, Eric E.; Nakajima, Kunie; Obata, Hideaki; Xu, Qinghao; Yaksh, Tony L.; Eisenach, James C.

    2010-01-01

    The balance between descending inhibition and facilitation is thought to be disturbed in chronic pain states. Increased facilitation by spinally released serotonin has been suggested by demonstration that mechanically evoked neuronal responses of wide dynamic range neurons are inhibited by 5-HT3 receptor antagonists in rats following spinal nerve ligation (SNL) but not sham operation. Despite these physiologic data, the effects of spinal 5-HT3 receptor blockade on behavioral hypersensitivity ...

  10. TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model.

    Science.gov (United States)

    Li, Qian; Guo, Cheng-Hao; Chowdhury, Mohammed Ali; Dai, Tao-Li; Han, Wei

    2016-01-01

    The transient receptor potential ankyrin-1 (TRPA1) channel, a pain transducer and amplifier, is drawing increasing attention in the field of visceral hypersensitivity, commonly seen in irritable bowel syndrome and inflammatory bowel disease. However, the role of TRPA1 in visceral nociception during post-inflammatory states is not well defined. Here, we explore the correlation between TRPA1 expression in the spinal dorsal horn (SDH) and persistent post-inflammatory visceral hypersensitivity. We injected rats intracolonically with 2,4,6-trinitrobenzene sulfonic acid (TNBS) or vehicle (n=12 per group). Post-inflammatory visceral hypersensitivity was assessed by recording the electromyographic activity of the external oblique muscle in response to colorectal distension. TRPA1 expression and distribution in the spinal cord and colon were examined by Western blotting and immunohistochemistry. Animals exposed to TNBS had more abdominal contractions than vehicle-injected controls ( P hypersensitivity in the rat and provides insight into potential therapeutic targets for the control of persistent visceral hypersensitivity.

  11. Attenuation of myogenic orofacial nociception and mechanical hypersensitivity by viral mediated enkephalin overproduction in male and female rats.

    Science.gov (United States)

    Kramer, Phillip R; Umorin, Mikhail; Bellinger, Larry L

    2015-03-15

    Clinical studies have tested the use of an engineered herpes virus to treat pain. We hypothesized that subcutaneous injections of an engineered herpes virus that expresses enkephalin would attenuate orofacial nociception and hypersensitivity in male and female rats by a central mechanism. Herpes virus was injected subcutaneously around the mouth of male and female rats seventy-two hours before ligatures were placed on the masseter tendon, control treatment groups received either no virus or no ligature. Enkephalin expression was measured and von Frey filament testing and meal duration were utilized to measure mechanical hypersensitivity and the nociceptive response, respectively. Naloxone or naloxone methiodide was administered to rats injected with the enkephalin expressing virus to test if enkephalin was acting peripherally or centrally. Ligature significantly lengthened meal duration and reduced the threshold to von Frey filaments for 18 days. Infection with the enkephalin transgene significantly decreased this response for at least 11 days but only in male rats. Virus injection significantly increased expression of enkephalin in the mental nerve that innervates the mouth region, the trigeminal ganglia and the trigeminal nucleus caudalis but no increase was observed in the masseter nerve after virus injection. Naloxone but not naloxone methiodide reversed the response to the enkephaline expressing virus. The data suggests that sex should be a considered when using this virus and that viral transfection of the mental nerve with an enkephalin transgene can reduce nociception and hypersensitivity through a central mechanism.

  12. Comparative expression analysis of genes induced during development of bacterial rot and induction of hypersensitive cell death in lettuce.

    Science.gov (United States)

    Kiba, Akinori; Lee, Kyon-Ye; Ohnishi, Kouhei; Hikichi, Yasufumi

    2008-11-28

    The development of bacterial rot disease caused by Pseudomonas cichorii is closely associated with programmed cell death. To investigate the molecular events occurring during the development of bacterial rot, we isolated 20 P. cichorii-responsive genes (PcRGs) in lettuce by differential display. Among these PcRGs, signal transduction-, transcription/translation- and defense/stress responses-related PcRGs were subjected to a comparative expression study. We used RNA samples isolated from lettuce leaves inoculated with P. cichorii and hypersensitive response-inducing Pseudomonas syringae pv. syringae. Expression of PcRG1-5-5 (spliceosomal protein), 2-9-2 (protein kinase) and 1-6-2 (ACC oxidase), 7-5 (alternative oxidase) and BI-I (bax inhibitor I) significantly increased in lettuce leaves inoculated with both P. cichorii and P. syringae pv. syringae. Intriguingly, PcRG 1-2-6 (protein phosphatase 2C) and 4-D-5 (protein kinase) were only up-regulated in P. cichorii-inoculated lettuce, whereas expression of PcRG1-3-2 (ribonucleoprotein) was only enhanced in P. syringae pv. syringae-inoculated lettuce. Expressions of PcRG1-3-2, 1-5-5, 1-6-2, 2-9-2, 7-5 and BI-I were induced by treatments with salicylic acid and/or methyl jasmonate. However, expression of PcRG1-2-6 and 4-D-5, which were specifically up-regulated by P. cichorii, were scarcely affected by these chemicals. Pharmacological studies suggested that ethylene and alternative oxidase were commonly related to disease development and hypersensitive responses. By contrast, there may be a different role for protein synthesis and protein kinase during disease development and in hypersensitive responses. These results suggested the overall similarity of genes expressed during disease development and in hypersensitive responses. However, there were differences not only in induction kinetics and the level of gene expression but also in the signal transduction pathway between hypersensitive responses and disease development.

  13. Isotype-like suppression of T cell-mediated immunity in vivo. I. Delayed-type hypersensitivity specificity of T cell suppression induced by antigen-binding T cell factors that initiate contact sensitivity.

    Science.gov (United States)

    Ptak, W; Bereta, M; Ptak, M; Askenase, P W

    1986-03-01

    A new form of immunoregulation is described that is based on the recent suggestion that the effector phase of delayed-type hypersensitivity (DTH) responses consists of a cascade of steps that are dependent on the sequential action of two types of antigen-specific Ly-1+ effector cells. According to this formulation, which is based on analysis of contact sensitivity (CS) in mice, DTH consists of at least two T cell-dependent steps that must occur in sequence. The first of these steps occurs within 2 hr of challenge and depends on DTH-initiating, antigen-binding, antigen-specific T cell factors that sensitize the tissues for an obligatory initial vasoactive step, which allows the antigen/major histocompatibility complex (MHC)-restricted, Ly-1+ effector T cells of classic 24 to 48 hr DTH responses to enter the tissues and produce chemoattractant lymphokines. We have now found that nonspecific suppression of CS responses can be induced by i.v. injection of these antigen-binding, CS-initiating T cell factors. Injection of the antigen-binding T cell factor induces Ly-2+, I-J-, cyclophosphamide sensitive, seemingly nonspecific suppressor T cells to inhibit initiation of CS responses. These suppressor cells do not affect the late-acting lymphokine-producing T cells, but probably act by preventing production of antigen-specific factors of the type that are required to initiate DTH responses. Furthermore, injection of CS-initiating antigen-binding T cell factors also induces suppression of sheep red blood cell (SRBC)-specific DTH, but does not affect classic anti-SRBC B cell responses, which are dependent on antigen/MHC-restricted Ly-1+ helper T cells; skin allograft rejection responses are also not affected. Thus, the suppression is DTH-specific. In addition, suppression induced by antigen-binding T cell factors is Igh and not MHC/H-2 restricted. These findings and data in the companion manuscript showing that these suppressor T cells act by production of soluble suppressor

  14. Cladosporium fulvum CfHNNI1 induces hypersensitive necrosis, defence gene expression and disease resistance in both host and nonhost plants.

    Science.gov (United States)

    Cai, Xin-Zhong; Zhou, Xin; Xu, You-Ping; Joosten, Matthieu H A J; de Wit, Pierre J G M

    2007-05-01

    Nonhost resistance as a durable and broad-spectrum defence strategy is of great potential for agricultural applications. We have previously isolated a cDNA showing homology with genes encoding bZIP transcription factors from tomato leaf mould pathogen Cladosporium fulvum. Upon expression, the cDNA results in necrosis in C. fulvum host tomato and nonhost tobacco plants and is thus named CfHNNI1 (for C . f ulvum host and nonhost plant necrosis inducer 1). In the present study we report the induction of necrosis in a variety of nonhost plant species belonging to three families by the transient in planta expression of CfHNNI1 using virus-based vectors. Additionally, transient expression of CfHNNI1 also induced expression of the HR marker gene LeHSR203 and greatly reduced the accumulation of recombinant Potato virus X. Stable CfHNNI1 transgenic tobacco plants were generated in which the expression of CfHNNI1 is under the control of the pathogen-inducible hsr203J promoter. When infected with the oomycetes pathogen Phytophthora parasitica var. nicotianae, these transgenic plants manifested enhanced expression of CfHNNI1 and subsequent accumulation of CfHNNI1 protein, resulting in high expression of the HSR203J and PR genes, and strong resistance to the pathogen. The CfHNNI1 transgenic plants also exhibited induced resistance to Pseudomonas syringae pv. tabaci and Tobacco mosaic virus. Furthermore, CfHNNI1 was highly expressed and the protein was translocated into plant cells during the incompatible interactions between C. fulvum and host and nonhost plants. Our results demonstrate that CfHNNI1 is a potential general elicitor of hypersensitive response and nonhost resistance.

  15. Culicoides species attracted to horses with and without insect hypersensitivity

    NARCIS (Netherlands)

    Rijt, van der R.; Boom, van den R.; Jongema, Y.; Sloet van Oldruitenborgh-Oosterbaan, M.M.

    2008-01-01

    The aims of this study were to determine (1) which species of Culicoides is most commonly attracted to horses, (2) whether horses suffering insect hypersensitivity attract more Culicoides spp. than unaffected horses, and (3) the times when Culicoides spp. are most active. Horses affected by insect

  16. Clinical and diagnostic features of perioperative hypersensitivity to cefuroxime

    DEFF Research Database (Denmark)

    Christiansen, I S; Krøigaard, M; Mosbech, H

    2015-01-01

    INTRODUCTION: The Danish Anaesthesia Allergy Centre (DAAC) investigated 89 adult patients with suspected perioperative cefuroxime-associated hypersensitivity reactions between 2004 and 2013. The goals were to determine if the time to index reaction after cefuroxime exposure could be used to impli...

  17. In vivo approaches for immune-mediated drug hypersensitivity research

    NARCIS (Netherlands)

    Kwast, L.M.

    2017-01-01

    Drug allergies, immune-mediated drug hypersensitivity reactions (IDHRs) or drug induced liver injury (DILI) are important causes of black box warnings and drug withdrawals, and thus a major problem in the development of drugs. Also drug induced liver injury Despite the high demand for preclinical

  18. Old, new and hidden causes of perioperative hypersensitivity

    DEFF Research Database (Denmark)

    Garvey, Lene Heise

    2016-01-01

    and performance and interpretation of investigations. Differences in sensitization to NMBAs are partly explained by cross sensitization to pholcodine, an ingredient in cough-medicines available in some countries. While NMBAs are the most common causes of perioperative hypersensitivity in some countries, this may...

  19. Genetic parameters of insect bite hypersensitivity in Dutch Friesian broodmares

    NARCIS (Netherlands)

    Schurink, A.; Ducro, B.J.; Heuven, H.C.M.|info:eu-repo/dai/nl/314417818; van Arendonk, J.A.M.

    2011-01-01

    Insect bite hypersensitivity (IBH) is a seasonal allergic skin disease in horses caused by bites of certain Culicoides spp. The aim of our study was to investigate the maternal effect on IBH and to estimate the heritability and repeatability of IBH in the Dutch Friesian horse population. Data

  20. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hypersensitivity pneumonitis immunological test system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... other allergic respiratory disorders. (b) Classification. Class II (performance standards). ...

  1. Delayed-type hypersensitivity reaction against Nexplanon®.

    Science.gov (United States)

    Serati, Maurizio; Bogani, Giorgio; Kumar, Sanjeev; Cromi, Antonella; Ghezzi, Fabio

    2015-01-01

    Nexplanon® is an etonogestrel implant with a long-acting contraceptive effect. Although several studies underlined its safety profile, its implant can rarely lead to moderate or severe adverse event. Here, we presented a case of delayed-type hypersensitivity reaction against Nexplanon® that resolved after its removal. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Equine insect bite hypersensitivity : Pathogenesis, diagnosis and immunomodulation

    NARCIS (Netherlands)

    Meulenbroeks, C.|info:eu-repo/dai/nl/31400694X

    2016-01-01

    Insect bite hypersensitivity (IBH) is a seasonal allergic dermatitis primarily caused by Culicoides midges like C. obsoletus. The welfare of IBH-affected horses is compromised due to severe itch with secondary dermatitis and skin infections. Similar to most allergies, IBH can only be controlled

  3. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.

    Science.gov (United States)

    Sutton, Blair C; Opp, Mark R

    2014-03-01

    Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased

  4. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

    Science.gov (United States)

    2012-01-01

    The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT) receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT), an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 μM). Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM) within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for β2- and β3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions. PMID:22500608

  5. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions.

    Science.gov (United States)

    Blanca-López, N; Cornejo-García, J A; Plaza-Serón, M C; Doña, I; Torres-Jaén, M J; Canto, G; Padilla-España, L; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures. Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future.

  6. Hypersensitivity test to electric magnetic fields; Test de hipersensibilidad a exposiciones residenciales a campos magneticos

    Energy Technology Data Exchange (ETDEWEB)

    Ubeda Maeso, A.; Martinez Pascual, M. A.

    2004-07-01

    The so-called electromagnetic hypersensitivity (RH) syndrome includes a number of unspecific, medically unexplained symptoms attributed to exposure to electric and magnetic fields. As a whole, laboratory tests have provided inconclusive results, in part due to the fact that many individuals show nuclear, inconsistent responses to repeated experimental field-exposures. It has been proposed that such inconsistencies could be due in part to distress caused by the lab test itself. We have developed a test to be conducted at the patient's residence, allowing for long-term follow up of exposure-response assessment and avoiding the laboratory environment and the presence of the researcher as potential stressors and confounding factors. In a pilot test, EMDEX-II magnetometers were used to continuously recording power-frequency magnetic fields in the residence of a patient with perceived EH. The patient's symptoms included distress, headache and dizziness, among other ailments. Magnetographic data of a total of 123 recording days were plotted against the corresponding data on occurrence of the symptoms episodes. As a whole, the results did not show positive linear correlation between the daily occurrence of the episode and the exposures levels recorded during the day or during the day before. These preliminary results are little supportive of the hypothesis that the patient's ailments are caused or worsened by a putative hypersensitivity to residential exposure to power-frequency magnetic fields in the 0.02-4.00 {mu}T range. (Author) 29 refs.

  7. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2010.

    Science.gov (United States)

    Sicherer, Scott H; Leung, Donald Y M

    2011-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  8. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

    Directory of Open Access Journals (Sweden)

    Tsao Douglas

    2012-04-01

    Full Text Available Abstract The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT, an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 μM. Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for β2- and β3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions.

  9. Delayed-type hypersensitivity to metals in connective tissue diseases and fibromyalgia.

    Science.gov (United States)

    Bjørklund, Geir; Dadar, Maryam; Aaseth, Jan

    2017-12-12

    Rheumatic diseases include a group of autoimmune disorders with environmental and genetic etiology that are characterized as a subgroup of connective tissue diseases (CTD). Rheumatoid arthritis (RA) often involves the small joints of the hands in a symmetrical fashion that can lead to loss of joint function, and RA, as well as Sjögren's syndrome (SS) and other rheumatic diseases, are often accompanied by sensitivity to metals. Numerous investigations on metal sensitivity were evaluated in this review. A detailed metal exposure history was collected by different evaluation of studies. In all subjects, the main source of metal exposure was nickel, mercury, gold, palladium, titanium, and chromium. All of SLE (systemic lupus erythematosus), RA and SS patients appeared to have an increased frequency of metal delayed-type hypersensitivity (DTH) (Type IV allergy). As dental restorative materials release minor amounts of their metals (including mercury, gold, and nickel), many adults are commonly exposed to these metal ions by vapor or corrosion into saliva. Metal-related DTH in these patients will induce an inflammatory response. Such inflammations are important factors in CTD progress. It is hypothesized that metal-specific T cell reactivity can act as an etiological agent in the propagation and chronification of rheumatic inflammation. The key responses of metal delayed-type hypersensitivity in autoimmunity are precipitating as an appealing challenge for further investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

    Science.gov (United States)

    Qiao, H-L; Li, Z; Yang, J; Tian, X; Gao, N; Jia, L-J

    2009-06-01

    Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.

  11. Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

    Science.gov (United States)

    Audicana, M. Teresa; Kennedy, Malcolm W.

    2008-01-01

    Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive. PMID:18400801

  12. Effectiveness of a baking soda toothpaste delivering calcium and phosphate in reducing dentinal hypersensitivity.

    Science.gov (United States)

    Ghassemi, A; Hooper, W; Winston, A E; Sowinski, J; Bowman, J; Sharma, N

    2009-01-01

    The purpose of this controlled clinical trial was to determine the effectiveness and safety of a single-phase dentifrice that delivers calcium, phosphate, and fluoride to the tooth surface (Arm & Hammer Enamel Care for Sensitive Teeth toothpaste, United Kingdom) in reducing dentinal hypersensitivity. Two-hundred and eight qualifying subjects were randomly assigned to either the Enamel Care dentifrice group or a control dentifrice group, and brushed twice daily with their assigned dentifrice for eight weeks. Pain/discomfort in response to a thermal stimulus was assessed at baseline, week 4, and week 8 using a Visual Analogue Scale (VAS; primary outcome variable) and the Schiff Thermal Sensitivity Scale (STSS; secondary outcome variable). After eight weeks, volunteers from the Enamel Care group were switched to the control dentifrice and participated in a second eight-week study to determine the degree of persistence of pain reduction. Both groups had statistically significant VAS score reductions from baseline at weeks 4 and 8, with mean VAS scores in the Enamel Care group decreasing by 45.6% at week 4 and 61.1% at week 8 (p < 0.0001). Enamel Care was statistically significantly more effective than the control at weeks 4 and 8, with respective mean VAS reductions of 63% (p < 0.0001) and 33% (p = 0.0004) greater than the control. Consistent with the VAS score results, the Enamel Care group had respective statistically significant STSS score reductions of 77% and 58% greater than the control group (p < 0.0001). The reductions in dentinal hypersensitivity seen in the Enamel Care group at week 8 persisted for an additional eight weeks, during which the subjects discontinued use of Enamel Care and brushed with the control dentifrice. Enamel Care for Sensitive Teeth toothpaste (United Kingdom) is an effective dentifrice for the management of dentinal hypersensitivity, and its efficacy persists for a least eight weeks following discontinued product use.

  13. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Kim, Seung-Hyun; Sanak, Marek; Park, Hae-Sim

    2013-05-01

    Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. HR4EU--A Web-Portal for E-Learning of Croatian

    Science.gov (United States)

    Filko, Matea; Farkaš, Daša; Hriberski, Diana

    2016-01-01

    In this paper, we present the HR4EU--a web portal for e-learning of Croatian. HR4EU is the first portal that offers Croatian language courses which are free-of-charge and developed by language professionals. Moreover, HR4EU also integrates bidirectional interaction with some of the previously developed language resources for Croatian. The HR4EU…

  15. Why a well-designed HR shared service provider fails to create end-user value?

    NARCIS (Netherlands)

    Meijerink, Jeroen Gerard; Bondarouk, Tatiana; Looise, Jan C.

    2011-01-01

    Human resource shared services centres (HR SSCs) are foreseen as improving HR service delivery for their end-users: employees, line managers and decentralized HR professionals. Although the concept expects the benefits of HR SSCs to come from centralizing knowledge and decentralizing the control

  16. Acute hyperhydration reduces athlete biological passport OFF-hr score

    DEFF Research Database (Denmark)

    Bejder Rasmussen, Jacob; Hoffmann, M F; Ashenden, M

    2016-01-01

    , the subjects were crossed-over with regard to water ingestion and the procedure was repeated. OFF-hr was reduced by ∼ 4%, ∼ 3%, and ∼ 2% at 40, 60, and 80 min, respectively, after drinking 1000 mL of water, compared with normal water ingestion (P ... with atypical blood profiles (99% specificity level) before drinking 1000 mL of water, whereas 11% (n = 18), 10% and 11% (n = 18) were identified 40, 60, and 80 min, respectively, after ingestion. This was different (P 

  17. Fexofenadine Suppresses Delayed-Type Hypersensitivity in the Murine Model of Palladium Allergy

    Directory of Open Access Journals (Sweden)

    Ryota Matsubara

    2017-06-01

    Full Text Available Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical setting, glucocorticoids and antihistamine drugs are commonly used for treatment of contact dermatitis. However, the precise mechanism of immune suppression in palladium allergy remains unknown. We investigated inhibition of the immune response in palladium allergic mice by administration of prednisolone as a glucocorticoid and fexofenadine hydrochloride as an antihistamine. Compared with glucocorticoids, fexofenadine hydrochloride significantly suppressed the number of T cells by interfering with the development of antigen-presenting cells from the sensitization phase. Our results suggest that antihistamine has a beneficial effect on the treatment of palladium allergy compared to glucocorticoids.

  18. Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles

    DEFF Research Database (Denmark)

    Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.

    2017-01-01

    Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP......), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding...... specificities and binding pocket structure. We demonstrate that primary predisposition to cutaneous NVP HSR, seen across ancestral groups, can be attributed to a cluster of HLA-C alleles sharing a common binding groove F pocket with HLA-C*04:01. An independent association with a group of class II alleles which...

  19. Intradermal testing of horses with and without insect bite hypersensitivity in The Netherlands using an extract of native Culicoides species.

    Science.gov (United States)

    Sloet van Oldruitenborgh-Oosterbaan, Marianne M; van Poppel, Miriam; de Raat, Inge J; van den Boom, Robin; Savelkoul, Huub F J

    2009-10-01

    Intradermal tests using a Culicoides nubeculosus extract have proven unreliable for diagnosis of equine insect bite hypersensitivity (IBH) in the Netherlands. The aim of this study was to evaluate the diagnostic value of an extract derived from the Dutch species C. obsoletus and C. pulicaris. Thirteen pairs of horses were tested, each pair consisting of one horse with IBH and the other a healthy control. Each horse was injected intradermally with 0.1 mL of three concentrations of Culicoides whole body extract (1 : 1000 w/v, 1 : 10,000 w/v and 1 : 25,000 w/v), histamine solution (0.01 mg/mL, positive control) and phosphate-buffered saline (negative control). Skin responses were evaluated after 30 min and at 1, 4 and 24 h. At all time points the absolute wheal diameter elicited by Culicoides extract 1 : 1000 w/v was significantly larger (P equine insect hypersensitivity.

  20. Dentists' perceptions of dentine hypersensitivity and knowledge of its treatment.

    Science.gov (United States)

    Gillam, D G; Bulman, J S; Eijkman, M A J; Newman, H N

    2002-03-01

    The aim of the present investigation was to determine by questionnaire, UK dentists' perception of Dentine Hypersensitivity (DH) and knowledge of its treatment. A total of 403 questionnaires were sent to a selected group of UK dentists who had either inquired about further postgraduate education or had attended a course at the Eastman Dental Institute/Hospital. A total of 181 of 403 dentists (44.9%) (118M; 36F, 17 no response, mean age 38.2 years [s.d. 8.97]) returned the questionnaire. About 92.8% (n=168) of responding dentists claimed to see patients with DH in their practice. According to the dentists' replies at least one of four of their patients suffered from the complaint. About 71.8% (n=130) of dentists reported that DH was a severe problem in at least 10% of their patients and that pain from DH lasted no more than 4 weeks. Most of responding dentists claimed to be asked about DH by their patients and stated that they offered advice or treatment to their patients. Nearly 87.3% (n=158) of responding dentists provided a wide range of treatment options/advice which included both in-office and over-the-counter (OTC) products. Popular responses included desensitizing pastes/gels, Topical F(-) varnishes and toothpastes/rinses/gels, advice on atraumatic tooth brushing, dentine bonding agents (DBA), glass-ionomer cements (GIC) and other unspecified restorations. Of the various in-office treatments Duraphat was the most cited choice of varnish/primer options. Sensodyne toothpaste was the most popular of the specified OTC products. Most dentists appeared to understand the aetiological features associated with DH and provided a wide range of factors including the effects of incorrect tooth brushing, dietary acids as well as the possible influence on non-dental topics such as stress. Most responding dentists believed that their advice on DH was generally effective although they did highlight that certain aspects on the condition were lacking such as appropriate

  1. [Immediate hypersensitivity to fruits and vegetables and pollenosis].

    Science.gov (United States)

    Hernández, J; García Sellés, F J; Pagán, J A; Negro, J M

    1985-01-01

    Various works have been published, mainly by Scandinavian authors, in which a partial immunological identity has been found to exist between birch pollen and hazelnut and apple. However, our attention has been particularly drawn to the high proportion of people who are allergic to the apple and other fruits, which in some cases has been as much as 50 and 70%, and in whom an oral pruritus alone is considered sufficient a symptom of allergies to certain foodstuffs. However due to the fact that the incidence of allergies to fruit in patients who suffer from pollen-related allergies is much lower in this area, being in the order of 7%, and because of the absence of birch, we decided to carry out our investigation in the opposite direction to that chosen by the Scandinavian researchers. That is to say, from the point of view of patients suffering from allergies to fruits and vegetables (these being the foodstuffs which most frequently produce allergic reactions in our own particular environment) we decided to investigate: 1) which foodstuffs, according to clinical history, are most frequently responsible for producing allergies; 2) their possible co-existence with pollen related allergies; 3) which pollens are responsible for producing a higher rate of positive results in patients; 4) and finally, by means of the RAST inhibition technique, to discover it a cross-reactivity might exist between these pollens and the peanut or the pea. We chose 40 patients (19 females and 21 males), between the ages of 5 and 49 years old, whose clinical history showed beyond a shadow of a doubt that they displayed symptoms of immediate hypersensitivity after the ingestion of certain fruits and/or vegetables. The technique employed in the skin tests was that of scratch of the skin from the backs of the patients (in a prone position), systematically using fresh natural foodstuffs, and at the same time trying to ensure that they were of the same type as those that had originally produced the

  2. HR MANAGEMENT IN THE AGE OF CRISIS: THE CASE OF GREEK CIVIL ENGINEER CONSULTANT COMPANIES

    OpenAIRE

    George, Xanthakis; Marianthi, Stogiannidou

    2012-01-01

    This paper outlines and discusses an approach to HR management in Greek Civil Engineer Consultant Companies during the economical crisis of 2010-12. A discussion of the definition, the nature and anatomy of crisis, as also the determinants of crisis behavior are presented in the first part of it. The paper is integrated with two case studies, results and conclusions. The aim of this paper is to investigate the crisis process, to explore the patterns of behavior which emerge in response to cri...

  3. The 50 distal amino acids of the 2AHP homing protein of Grapevine fanleaf virus elicit a hypersensitive reaction on Nicotiana occidentalis.

    Science.gov (United States)

    Martin, Isabelle R; Vigne, Emmanuelle; Berthold, François; Komar, Véronique; Lemaire, Olivier; Fuchs, Marc; Schmitt-Keichinger, Corinne

    2017-04-07

    Avirulence factors are critical for the arm's race between a virus and its host in determining incompatible reactions. The response of plants to viruses from the genus Nepovirus in the family Secoviridae, including Grapevine fanleaf virus (GFLV), is well characterized, although the nature and characteristics of the viral avirulence factor remain elusive. By using infectious clones of GFLV strains F13 and GHu in a reverse genetics approach with wild-type, assortant and chimeric viruses, the determinant of necrotic lesions caused by GFLV-F13 on inoculated leaves of Nicotiana occidentalis was mapped to the RNA2-encoded protein 2AHP , particularly to its 50 C-terminal amino acids. The necrotic response showed hallmark characteristics of a genuine hypersensitive reaction, such as the accumulation of phytoalexins, reactive oxygen species, pathogenesis-related protein 1c and hypersensitivity-related (hsr) 203J transcripts. Transient expression of the GFLV-F13 protein 2AHP fused to an enhanced green fluorescent protein (EGFP) tag in N. occidentalis by agroinfiltration was sufficient to elicit a hypersensitive reaction. In addition, the GFLV-F13 avirulence factor, when introduced in GFLV-GHu, which causes a compatible reaction on N. occidentalis, elicited necrosis and partially restricted the virus. This is the first identification of a nepovirus avirulence factor that is responsible for a hypersensitive reaction in both the context of virus infection and transient expression. © 2017 BSPP AND JOHN WILEY & SONS LTD.

  4. Adolescents' experiences of being food-hypersensitive: a qualitative study

    Directory of Open Access Journals (Sweden)

    Wilde-Larsson Bodil

    2007-10-01

    Full Text Available Abstract Background Experiencing or being at risk of adverse reactions to certain food items is a common health issue, especially among children and adolescents. Research has shown that living with the risk of food reactions and always having to take measures to avoid certain food in one's diet has a negative impact on quality of life. The aim of this study was to illuminate adolescents' experiences of being food hypersensitive. Methods Three focus group interviews and six individual interviews were carried out with all together 17 adolescents, 14–18 years of age, who had exclusion diets at school due to food hypersensitivity. The interviews were taped and transcribed verbatim and a qualitative content analysis was carried out. Results Five categories with subcategories, and one pervading theme, emerged. The categories were: Perceiving oneself as being particular, Feeling constrained, Experiencing others' ignorance, Keeping control, and Feeling it's okay. A pervading theme was conceptualised as Striving to normalise the experience of being food-hypersensitive. The adolescents regarded themselves as competent and courageous, but also described how they avoided the extra attention it implied to ask for special food considerations taken into account. Their self-conceptions were probably essential for their management of and attitude toward the hypersensitivity condition. They felt deprived, and those at risk of severe food reactions experienced insecurity and fear. Feelings of being disregarded were expressed, as well as facing unreliability and a lack of understanding from others. The continual work of constant vigilance and decision-making was described as time-consuming and frustrating. However, the adolescents also experienced considerate and supportive surroundings and were at pains to tone down the negative experiences and consequences of being food-hypersensitive. Conclusion Food avoidance by itself, and not only the somatic food reactions

  5. Grade and speed have greater influence on HR and RPE than ability, sex, and age in alpine skiing.

    Science.gov (United States)

    Seifert, John; Stöggl, Thomas; Scheiber, Peter; Heizinger, Eva; Müller, Erich

    2017-03-01

    The purpose of this study was to investigate the influence of ski slope grade, skiing speed, skiing ability, sex, and age on HR, RPE, and energy expenditure responses during recreational alpine skiing. Thirty-eight participants were divided by age, sex, and skiing ability. Instructor- and self-paced skiing conditions were conducted on 10° and 19.8° slopes. Skiing HR was recorded, RPE collected at the end of each run, and energy expenditure calculated. The pertinent results of this study demonstrate that the interactions of grade × speed, speed × age, and grade × age and the main effects of speed and grade significantly influenced %HRmax, mean HR, RPE, and energy expenditure during skiing. When %HRmax is taken into account, the older skiers skied at a greater relative intensity than the young skiers. The sex, age, and skiing ability main effects did not have a significant influence on mean HR, RPE, and energy expenditure. These data demonstrates that increased speed and grade results in increased physiological stress. Using mean, HR data may not be the best option for assessing physiological stress during exercise in the older athlete as it does not account for the influence of the ageing process.

  6. Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder.

    Science.gov (United States)

    Bertsch, Katja; Gamer, Matthias; Schmidt, Brigitte; Schmidinger, Ilinca; Walther, Stephan; Kästel, Thorsten; Schnell, Knut; Büchel, Christian; Domes, Gregor; Herpertz, Sabine C

    2013-10-01

    Patients with borderline personality disorder are characterized by emotional hyperarousal with increased stress levels, anger proneness, and hostile, impulsive behaviors. They tend to ascribe anger to ambiguous facial expressions and exhibit enhanced and prolonged reactions in response to threatening social cues, associated with enhanced and prolonged amygdala responses. Because the intranasal administration of the neuropeptide oxytocin has been shown to improve facial recognition and to shift attention away from negative social information, the authors investigated whether borderline patients would benefit from oxytocin administration. In a randomized placebo-controlled double-blind group design, 40 nonmedicated, adult female patients with a current DSM-IV diagnosis of borderline personality disorder (two patients were excluded based on hormonal analyses) and 41 healthy women, matched on age, education, and IQ, took part in an emotion classification task 45 minutes after intranasal administration of 26 IU of oxytocin or placebo. Dependent variables were latencies and number or initial reflexive eye movements measured by eye tracking, manual response latencies, and blood-oxygen-level-dependent responses of the amygdala to angry and fearful compared with happy facial expressions. Borderline patients exhibited more and faster initial fixation changes to the eyes of angry faces combined with increased amygdala activation in response to angry faces compared with the control group. These abnormal behavioral and neural patterns were normalized after oxytocin administration. Borderline patients exhibit a hypersensitivity to social threat in early, reflexive stages of information processing. Oxytocin may decrease social threat hypersensitivity and thus reduce anger and aggressive behavior in borderline personality disorder or other psychiatric disorders with enhanced threat-driven reactive aggression.

  7. Acetyl Salicylic Acid Challenge in Children with Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs Differentiates Between Cross-Intolerant and Selective Responders.

    Science.gov (United States)

    Blanca-López, Natalia; Haroun-Diaz, Elisa; Ruano, Francisco Javier; Pérez-Alzate, Diana; Somoza, María Luisa; Vázquez de la Torre Gaspar, María; Rivas-Ruiz, Francisco; García-Martin, Elena; Blanca, Miguel; Canto, Gabriela

    2017-10-03

    Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children are becoming a great concern. Most studies have focused on adults, with noted discrepancies observed in the classification of hypersensitivity reactions to NSAIDs in children when compared with adults. To phenotype a group of children with hypersensitivity reactions to NSAIDs, including paracetamol, and analyze the degree of agreement with the entities reported in adults and how they fit the proposed classifications. The study comprised 116 children aged 0.5 to 14 years, with a clinical history indicative of hypersensitivity reactions to NSAIDs. They all underwent a single-blind oral provocation test with acetyl salicylic acid, except in those cases when this was the suspected drug, in which case the challenge was done first with ibuprofen. If positive, cross-intolerance was established and if negative, an oral provocation test with the culprit drug was performed to establish a selective response or exclude allergy. Of the 26% diagnosed as hypersensitive to NSAIDs, 83% were cross-intolerant and 17% selective reactors. The highest significant differences between reactors and nonreactors were observed in the time to reaction after drug intake and the clinical entity (P < .0001), followed by drug involved and age (P < .01). From the total number of cases confirmed with NSAID hypersensitivity, 83% were cross-intolerant. In cross-intolerant reactions, both cutaneous and respiratory manifestations are common. Acetyl salicylic acid challenge as the first approach proved to be safe and useful to establish the diagnosis. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. The flowering locus Hr colocalizes with a major QTL affecting winter frost tolerance in Pisum sativum L.

    Science.gov (United States)

    Lejeune-Hénaut, I; Hanocq, E; Béthencourt, L; Fontaine, V; Delbreil, B; Morin, J; Petit, A; Devaux, R; Boilleau, M; Stempniak, J J; Thomas, M; Lainé, A L; Foucher, F; Baranger, A; Burstin, J; Rameau, C; Giauffret, C

    2008-05-01

    An understanding of the genetic determinism of frost tolerance is a prerequisite for the development of frost tolerant cultivars for cold northern areas. In legumes, it is not known to which extent vernalization requirement or photoperiod responsiveness are necessary for the development of frost tolerance. In pea (Pisum sativum L.) however, the flowering locus Hr is suspected to influence winter frost tolerance by delaying floral initiation until after the main winter freezing periods have passed. The objective of this study was to dissect the genetic determinism of frost tolerance in pea by QTL analysis and to assess the genetic linkage between winter frost tolerance and the Hr locus. A population of 164 recombinant inbred lines (RILs), derived from the cross Champagne x Terese was evaluated both in the greenhouse and in field conditions to characterize the photoperiod response from which the allele at the Hr locus was inferred. In addition, the population was also assessed for winter frost tolerance in 11 field conditions. Six QTL were detected, among which three were consistent among the different experimental conditions, confirming an oligogenic determinism of frost tolerance in pea. The Hr locus was found to be the peak marker for the highest explanatory QTL of this study. This result supports the hypothesis of the prominent part played by the photoperiod responsiveness in the determinism of frost tolerance for this species. The consistency of three QTL makes these positions interesting targets for marker-assisted selection.

  9. The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats

    Directory of Open Access Journals (Sweden)

    Jae Goo Kim

    2014-06-01

    Full Text Available The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05. Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats.

  10. [A case of chronic hypersensitivity pneumonitis induced by shiitake mushroom spores].

    Science.gov (United States)

    Fujiwara, K; Sato, T; Yonei, T; Genba, K; Nogami, N; Yamadori, I

    2000-12-01

    A 73-year-old woman was admitted to our hospital with a low-grade fever, dry cough and dyspnea on exertion as the chief complaints. She had been a professional shiitake mushroom grower for 50 years. Three years before visiting our hospital, she had been suspected of having hypersensitivity pneumonitis as a result of chest X-ray examination, bronchoalveolar lavage and transbronchial lung biopsy performed at another clinic. No antigens were identified at that time, but prednisolone was administered. On admission to our hospital, chest radiography and chest computed tomography revealed an interstitial shadow with subpleural honey-combing in both lower lung fields. After steroid pulse therapy, dyspnea on exertion and hypoxia improved moderately. Because of recurrence of the dyspnea, however, she was admitted on four separate occasions. On the second admission, an increase in lymphocytes was found by bronchoalveolar lavage, and septal lymphocytic infiltration accompanying fibrosis was demonstrated by transbronchial lung biopsy. On the fourth admission, a detailed immunological examination and an environmental survey were performed. The environmental provocation test yielded clinical symptoms similar to those experienced at the mushroom farm. Furthermore, tests of precipitation and lymphocyte proliferation in response to shiitake mushroom extracts were positive. Finally a diagnosis of chronic hypersensitivity pneumonitis induced by shiitake mushrooms was confirmed.

  11. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect stings.

    Science.gov (United States)

    Sicherer, Scott H; Leung, Donald Y M

    2004-07-01

    This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect venom that were reported primarily in the Journal of Allergy and Clinical Immunology from 2002 through 2003. Among the topics highlighted are new insights into the pathogenesis of atopic dermatitis and potential strategies for more effective treatment of the atopic march. Patients should remain supine with raised legs during anaphylactic shock because upper body elevation could result in sudden death from loss of venous return to the heart. A major advance in food allergy was that humanized, monoclonal anti-IgE antibody showed protection against peanut-induced anaphylaxis. In addition to studies elucidating mechanisms of drug hypersensitivity, a clinical study showed patients with a history of prior penicillin allergy with negative penicillin allergy test results are unlikely to experience reactions or resensitization on subsequent oral courses of penicillin. Lastly, there are new recommendations for patients with convincing insect sting reaction histories but negative skin test responses to venom. Copyright 2004 American Academy of Allergy, Asthma and Immunology

  12. Immunoglobulin E-mediated hypersensitivity reaction after intraperitoneal administration of vancomycin

    Directory of Open Access Journals (Sweden)

    Mun-Ju Hwang

    2015-03-01

    Full Text Available Intraperitoneal (IP vancomycin is widely used to treat Gram-positive peritonitis associated with peritoneal dialysis. There have been two cases of red man syndrome (RMS, a vancomycin-specific nonimmunologic reaction, associated with IP vancomycin. However, immune-mediated hypersensitivity reaction to IP vancomycin has not yet been reported. A 49 year old woman on continuous ambulatory peritoneal dialysis developed her first peritonitis episode. The patient was treated with IP vancomycin once/wk for 4 weeks. She experienced mild itching and flushing throughout her body for 1 day after the second treatment. Whenever vancomycin was administered, generalized urticaria and a prickling sensation developed, and the intensity increased gradually; however, these symptoms improved after vancomycin was discontinued. An allergic skin test was performed 6 weeks after the previous urticarial episode, and an intradermal skin test revealed a positive response to vancomycin. To our knowledge, this is the first case report of immunoglobulin E-mediated hypersensitivity reaction to IP vancomycin administration.

  13. Role of lipid in the induction of hapten-specific delayed hypersensitivity and contact sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Dailey, M.O.; Hunter, R.L.

    1974-04-01

    Guinea pigs immunized with bovine serum albumin conjugated with dinitrophenol (BSA-DNP), in Freund's complete adjuvant, produce antibody to the DNP and delayed-type hypersensitivity (DTH) to the BSA. We report that immunization with BSA-DNP doubly conjugated with medium chain fatty acids (L-BSA-DNP) stimulates the production of DTH specific for the hapten DNP with minimal antibody to DNP and no detectable immune response to the carrier BSA. The production of hapten-specific DTH reactions was assessed by two methods. First, animals immunized with L-BSA-DNP produced typical contact sensitivity reactions to epidermal challenge with dinitrofluorobenzene. Second, they produced grossly and microscopically typical delayed hypersensitivity reactions to the intradermal injection of DNP conjugated either to BSA or to a non-cross-reacting carrier, hen egg albumin. In further experiments, DNP-specific DTH was produced by animals immunized with BSA-DNP to which lipid groups had been attached by electrostatic rather than covalent bonds. Evidence is discussed which indicates that the production of DTH to haptens and proteins is largely a function of the lipophilic nature of the entire immunogen and is not dependent upon properties of individual antigenic determinants. Autoradiographic studies with /sup 125/I-labeled material demonstrated that the lipid-rich antigens are localized in the paracortical area of lymph nodes, in close proximity to the thymus-derived cells which are stimulated in the induction of DTH.

  14. Evaluating the statistical methodology of randomized trials on dentin hypersensitivity management.

    Science.gov (United States)

    Matranga, Domenica; Matera, Federico; Pizzo, Giuseppe

    2017-12-27

    The present study aimed to evaluate the characteristics and quality of statistical methodology used in clinical studies on dentin hypersensitivity management. An electronic search was performed for data published from 2009 to 2014 by using PubMed, Ovid/MEDLINE, and Cochrane Library databases. The primary search terms were used in combination. Eligibility criteria included randomized clinical trials that evaluated the efficacy of desensitizing agents in terms of reducing dentin hypersensitivity. A total of 40 studies were considered eligible for assessment of quality statistical methodology. The four main concerns identified were i) use of nonparametric tests in the presence of large samples, coupled with lack of information about normality and equality of variances of the response; ii) lack of P-value adjustment for multiple comparisons; iii) failure to account for interactions between treatment and follow-up time; and iv) no information about the number of teeth examined per patient and the consequent lack of cluster-specific approach in data analysis. Owing to these concerns, statistical methodology was judged as inappropriate in 77.1% of the 35 studies that used parametric methods. Additional studies with appropriate statistical analysis are required to obtain appropriate assessment of the efficacy of desensitizing agents.

  15. High-risk HPV presence in cervical specimens after a large loop excision of the cervical transformation zone: significance of newly detected hr-HPV genotypes.

    Science.gov (United States)

    van Ham, Maaike A P C; van Hamont, Dennis; Bekkers, Ruud L M; Bulten, Johan; Melchers, Willem J G; Massuger, Leon F A G

    2007-03-01

    Large loop excision of the cervical transformation zone (LLETZ) is a well-established treatment for high-grade cervical intraepithelial neoplasia. It has even been postulated that LLETZ is responsible for the elimination of the infectious agent, human papillomavirus (HPV), causing the lesion. Most studies on HPV detection after LLETZ have focused on the persistence of high-risk (hr-) HPV to identify women at risk for residual or recurrent disease. Therefore, the appearance and significance of hr-HPV types newly detected after surgical treatment has not been studied extensively so far. The presence of hr-HPV in 85 high-grade squamous cervical LLETZ biopsies and in the first follow-up smear was determined. In 80 (94%) of the LLETZ biopsies hr-HPV was detected in contrast to 30 (35%) hr-HPV positive follow-up scrapes. Twenty of the 80 hr-HPV positive women (25%) had the same hr-HPV genotypes in their follow-up cervical smears as was found in the corresponding biopsies. In the follow-up smear of 13 women a new hr-HPV genotype was detected and HPV 18 was newly detected in 8 of them. The remarkably high presence of newly detected HPV 18 genotypes may argue for a release or re-activation of this virus from proximal layers of the cervical canal incised during surgery.

  16. Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates.

    Directory of Open Access Journals (Sweden)

    Franky Baatz

    Full Text Available Resistance mutations to the HIV-1 fusion inhibitor enfuvirtide emerge mainly within the drug's target region, HR1, and compensatory mutations have been described within HR2. The surrounding envelope (env genetic context might also contribute to resistance, although to what extent and through which determinants remains elusive. To quantify the direct role of the env context in resistance to enfuvirtide and in viral infectivity, we compared enfuvirtide susceptibility and infectivity of recombinant viral pairs harboring the HR1-HR2 region or the full Env ectodomain of longitudinal env clones from 5 heavily treated patients failing enfuvirtide therapy. Prior to enfuvirtide treatment onset, no env carried known resistance mutations and full Env viruses were on average less susceptible than HR1-HR2 recombinants. All escape clones carried at least one of G36D, V38A, N42D and/or N43D/S in HR1, and accordingly, resistance increased 11- to 2800-fold relative to baseline. Resistance of full Env recombinant viruses was similar to resistance of their HR1-HR2 counterpart, indicating that HR1 and HR2 are the main contributors to resistance. Strictly X4 viruses were more resistant than strictly R5 viruses, while dual-tropic Envs featured similar resistance levels irrespective of the coreceptor expressed by the cell line used. Full Env recombinants from all patients gained infectivity under prolonged drug pressure; for HR1-HR2 viruses, infectivity remained steady for 3/5 patients, while for 2/5 patients, gains in infectivity paralleled those of the corresponding full Env recombinants, indicating that the env genetic context accounts mainly for infectivity adjustments. Phylogenetic analyses revealed that quasispecies selection is a step-wise process where selection of enfuvirtide resistance is a dominant factor early during therapy, while increased infectivity is the prominent driver under prolonged therapy.

  17. Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input

    DEFF Research Database (Denmark)

    Slimani, H.; Plaghki, L.; Ptito, M.

    2016-01-01

    that congenitally blind individuals detected significantly more C-fibre–mediated stimuli than sighted controls. A decomposition analysis of the reaction times indicated that the faster response times in the congenitally blind are due to more efficient central processing of C-fibre–mediated sensations. Conclusion......Background We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. Methods To study the contribution of Aδ- and C-fibres in pain perception, we measured...... instructed to respond as quickly as possible when detecting a laser-induced sensation. We used a 650 ms cut-off criterion to distinguish fast Aδ- from slow C-fibre–mediated sensations. Results Congenitally blind participants showed significantly faster reaction times to C- but not to Aδ...

  18. Hypersensitivity to Contingent Behavior in Paranoia: A New Virtual Reality Paradigm.

    Science.gov (United States)

    Fornells-Ambrojo, Miriam; Elenbaas, Maaike; Barker, Chris; Swapp, David; Navarro, Xavier; Rovira, Aitor; Sanahuja, Josep Maria Tomàs; Slater, Mel

    2016-02-01

    Contingency in interpersonal relationships is associated with the development of secure attachment and trust, whereas paranoia arises from the overattribution of negative intentions. We used a new virtual reality paradigm to experimentally investigate the impact of contingent behavior on trust along the paranoia continuum. Sixty-one healthy participants were randomly allocated to have a social interaction with a pleasant virtual human (avatar) programmed to be highly responsive or not (high/low contingency). Perceived trustworthiness and trusting behavior were assessed alongside control variables attachment and anxiety. Higher paranoia and dismissive attachment were associated with larger interpersonal distances. Unexpectedly, extremely paranoid individuals experienced the highly contingent avatar as more trustworthy than their low contingency counterpart. Higher dismissive attachment was also associated with more subjective trust in both conditions. Extreme paranoia is associated with hypersensitivity to noncontingent behavior, which might explain experiences of mistrust when others are not highly responsive in everyday social situations.

  19. Multiple Stars Across the H-R Diagram

    CERN Document Server

    Hubrig, Swetlana; Tokovinin, Andrei; Proceedings of the ESO Workshop held in Garching, Germany, 12-15 July 2005

    2008-01-01

    Stars show a marked tendency to be in systems of different multiplicity, ranging from simple binaries and triples to globular clusters with several 10,000's of stars. The formation and evolution of multiple systems remains a challenging part of astrophysics, and the contributions in this book report on the significant progress that had been made in this research field in the last years. The reader will find a variety of research topics addressed, such as the dynamical evolution in multiple stars, the effects of the environment on multiple system parameters, stellar evolution within multiple stars, multiplicity of massive stars, pre-main sequence and intermediate mass stars, multiplicity of low-mass stars from embedded protostars to open clusters, and brown dwarfs and extrasolar planets in multiples. This book presents the proceedings of the ESO Workshop on Multiple Stars across the H-R Diagram held in the summer of 2005.

  20. Ultraviolet and radio flares from UX Arietis and HR 1099

    Science.gov (United States)

    Lang, Kenneth R.; Willson, Robert F.

    1988-01-01

    Simultaneous observations of the RS CVn systems UX Ari and HR 1099 with the IUE satellite and the VLA are presented. Flaring activity is observed at ultraviolet wavelengths with the IUE when none is detected at radio wavelengths with the VLA. Radio flares with no detectable ultraviolet activity have also been observed. Thus, flares in the two spectral regions are either uncorrelated or weakly correlated. The flaring emission probably originates in different regions at the two wavelengths. Radio flares from RS CVn stars may originate in sources that are larger than, or comparable to, a star in size. This is in sharp contrast to compact, coherent radio flares from dwarf M stars. The ultraviolet flares from RS CVn stars probably originate in sources that are smaller than a component star.

  1. STAR-BASED METHODS FOR PLEIADES HR COMMISSIONING

    Directory of Open Access Journals (Sweden)

    S. Fourest

    2012-07-01

    Full Text Available PLEIADES is the highest resolution civilian earth observing system ever developed in Europe. This imagery program is conducted by the French National Space Agency, CNES. It has been operating since 2012 a first satellite PLEIADES-HR launched on 2011 December 17th, a second one should be launched by the end of the year. Each satellite is designed to provide optical 70 cm resolution colored images to civilian and defense users. Thanks to the extreme agility of the satellite, new calibration methods have been tested, based on the observation of celestial bodies, and stars in particular. It has then been made possible to perform MTF measurement, re-focusing, geometrical bias and focal plane assessment, absolute calibration, ghost images localization, micro-vibrations measurement, etc… Starting from an overview of the star acquisition process, this paper will discuss the methods and present the results obtained during the first four months of the commissioning phase.

  2. Direct imaging of multiple planets orbiting the star HR 8799

    Energy Technology Data Exchange (ETDEWEB)

    Marois, C; Macintosh, B; Barman, T; Zuckerman, B; Song, I; Patience, J; Lafreniere, D; Doyon, R

    2008-10-14

    Direct imaging of exoplanetary systems is a powerful technique that can reveal Jupiter-like planets in wide orbits, can enable detailed characterization of planetary atmospheres, and is a key step towards imaging Earth-like planets. Imaging detections are challenging due to the combined effect of small angular separation and large luminosity contrast between a planet and its host star. High-contrast observations with the Keck and Gemini telescopes have revealed three planets orbiting the star HR 8799, with projected separations of 24, 38, and 68 astronomical units. Multi-epoch data show counter-clockwise orbital motion for all three imaged planets. The low luminosity of the companions and the estimated age of the system imply planetary masses between 5 and 13 times that of Jupiter. This system resembles a scaled-up version of the outer portion of our Solar System.

  3. [Food hypersensitivity in the population of school children in Opole].

    Science.gov (United States)

    Pawlińska-Chmara, Romana; Teul, Iwona

    2015-01-01

    The prevalence of food allergy among children is high and constantly increasing, especially in urban environments. The aim of the study was to assess the prevalence of food hypersensitivity among children living in Opole. The study included 450 children (224 girls and 216 boys), aged 7-10 years from elementary schools in Opole. A survey was conducted on the basis of the EuroPrevall international programme questionnaire and a self-designed questionnaire for collecting information. Data were analyzed with the Statistica 8 software package. The level of significance for all analyses was p chocolate (4.87%), and cocoa (4.87%). The study revealed a high reporting of food hypersensitivity among children in Opole.

  4. Severe type IV hypersensitivity to 'black henna' tattoo.

    Science.gov (United States)

    Vasilakis, Vasileios; Knight, Bernice; Lidder, Satnam; Frankton, Sarah

    2010-10-06

    A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as 'black henna', darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo.

  5. Severe type IV hypersensitivity to ‘black henna’ tattoo

    Science.gov (United States)

    Vasilakis, Vasileios; Knight, Bernice; Lidder, Satnam; Frankton, Sarah

    2010-01-01

    A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as ‘black henna’, darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo. PMID:22778139

  6. Biochemical responses during the pathogenesis of Sclerotium rolfsii ...

    African Journals Online (AJOL)

    The hypersensitive reaction (HR), one of the most efficient and visible parts of the defense mechanisms in nature against invading pathogens, is associated with a coordinated and integrated set of metabolic alterations which are instrumental in impeding further pathogen ingress or alleviating stress. It includes a variety of ...

  7. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

    Science.gov (United States)

    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

  8. Oxazolone-induced contact hypersensitivity reduces lymphatic drainage but enhances the induction of adaptive immunity.

    Directory of Open Access Journals (Sweden)

    David Aebischer

    Full Text Available Contact hypersensitivity (CHS induced by topical application of haptens is a commonly used model to study dermal inflammatory responses in mice. Several recent studies have indicated that CHS-induced skin inflammation triggers lymphangiogenesis but may negatively impact the immune-function of lymphatic vessels, namely fluid drainage and dendritic cell (DC migration to draining lymph nodes (dLNs. On the other hand, haptens have been shown to exert immune-stimulatory activity by inducing DC maturation. In this study we investigated how the presence of pre-established CHS-induced skin inflammation affects the induction of adaptive immunity in dLNs. Using a mouse model of oxazolone-induced skin inflammation we observed that lymphatic drainage was reduced and DC migration from skin to dLNs was partially compromised. At the same time, a significantly stronger adaptive immune response towards ovalbumin (OVA was induced when immunization had occurred in CHS-inflamed skin as compared to uninflamed control skin. In fact, immunization with sterile OVA in CHS-inflamed skin evoked a delayed-type hypersensitivity (DTH response comparable to the one induced by conventional immunization with OVA and adjuvant in uninflamed skin. Striking phenotypic and functional differences were observed when comparing DCs from LNs draining uninflamed or CHS-inflamed skin. DCs from LNs draining CHS-inflamed skin expressed higher levels of co-stimulatory molecules and MHC molecules, produced higher levels of the interleukin-12/23 p40 subunit (IL-12/23-p40 and more potently induced T cell activation in vitro. Immunization experiments revealed that blockade of IL-12/23-p40 during the priming phase partially reverted the CHS-induced enhancement of the adaptive immune response. Collectively, our findings indicate that CHS-induced skin inflammation generates an overall immune-stimulatory milieu, which outweighs the potentially suppressive effect of reduced lymphatic vessel function.

  9. Immediate Reactions to More Than 1 NSAID Must Not Be Considered Cross-Hypersensitivity Unless Tolerance to ASA Is Verified.

    Science.gov (United States)

    Pérez-Alzate, D; Cornejo-García, J A; Pérez-Sánchez, N; Andreu, I; García-Moral, A; Agúndez, J A; Bartra, J; Doña, I; Torres, M J; Blanca, M; Blanca-López, N; Canto, G

    Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs). Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors. Patients who attended the Allergy Service of Hospital Infanta Leonor, Madrid, Spain with DHRs to NSAIDs between January 2011 and December 2014 were evaluated. Those with 2 or more immediate reactions occurring in less than 1 hour after intake were included. After confirming tolerance to ASA, the selectivity of the response to 2 or more NSAIDs was demonstrated by in vivo and/or in vitro testing or by controlled administration. From a total of 203 patients with immediate DHRs to NSAIDs, 16 (7.9%) met the inclusion criteria. The patients presented a total of 68 anaphylactic or cutaneous reactions (mean [SD], 4.2 [2.1]). Most reactions were to ibuprofen and other arylpropionic acid derivatives and to metamizole. Two different NSAIDs were involved in 11 patients and 3 in 5 patients. Patients with NSAID-induced anaphylaxis or urticaria/angioedema should not be considered cross-hypersensitive unless tolerance to ASA is verified.

  10. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK

    Directory of Open Access Journals (Sweden)

    Shao-Jun Wang

    2012-01-01

    Full Text Available Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36 and Shangjuxu (ST37 in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.

  11. Transfection of normal human and Chinese hamster DNA corrects diepoxybutane-induced chromosomal hypersensitivity of Fanconi anemia fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Shaham, M.; Adler, B.; Ganguly, S.; Chaganti, R.S.K.

    1987-08-01

    Cultured cells from individuals affected with Fanconi anemia (FA) exhibit spontaneous chromosome breakage and hypersensitivity to the cell killing and clastogenic effects of the difunctional alkylating agent diepoxybutane (DEB). The authors report here the correction of both of these DEB-hypersensitivity phenotypes of FA cells achieved by cotransfection of normal placental of Chinese hamster lung cell DNA and the plasmid pSV2-neo-SVgpt. Transfectants were selected for clonogenic survival after treatment with DEB at a dose of 5 ..mu..gml. At this dose of DEB, the clonogenicity of normal fibroblasts was reduced to 50% and that of FA fibroblasts was reduced to zero. DEB-resistant (DEB/sup r/) colonies selected in this system exhibited a normal response to DEB-induced chromosome breakage and resistance to repeated DEB treatment. The neo and gpt sequences were detected by Southern blot analysis of DNA from one of four DEB/sup r/ colonies independently derived from transfection of human DNA and one of three DEB/sup r/ colonies independently derived from transfection of Chinese hamster DNA. The results demonstrate that DNA sequences that complement the two hallmark cellular phenotypes (cellular and chromosomal hypersensitivity to alkylating agents) of FA are present in human as well as Chinese hamster DNA. The cloning of these genes using transfection strategies can be expected to enable molecular characterization of FA

  12. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

    Science.gov (United States)

    Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

    2015-12-02

    Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

  13. Food allergens: Hypersensitivity to food and food constituents

    Directory of Open Access Journals (Sweden)

    Stanković Ivan

    2008-01-01

    Full Text Available Adverse reactions to food which occur only in susceptible individuals may result from true physical hypersensitivity to components of foods or from psychological factors. Non-allergic food hypersensitivity may be due to a metabolic defect in the affected individual, while in food allergy immune mechanism is involved. Food allergy can be further subdivided into IgE-mediated food allergy and non-IgE-mediated food allergy, depending on the underlying allergic mechanism. Most cases of confirmed food allergy involve the production of IgE antibodies and a network of interactions between various cell types and chemical mediators. This type of allergic reaction is known as an IgE-mediated allergy (or a type I hypersensitivity reaction, and it produces immediate symptoms. The most severe form of IgE-mediated allergy is systematic answer known as anaphylaxis that can be fatal in the absence of adequate medical help. Other less severe allergy manifestations are symptoms like swelling, itching, redness and heat in the mouth, gut, skin or respiratory tract. Hypersensitivity to food requires special dietary treatment, but total exclusion of some foods from the diet can be very difficult, because of the wide distribution of some foodstuffs in the diet or their presence as impurities in other foods. It is very important that producers have good systems of control, traceability and labeling of possible presence of food allergens in order to help people with food allergies to conduct their restrictive diets that are in most cases their lifelong treatment.

  14. Hypersensitivity to Etoposide in Case of Metastatic Gestational Choriocarcinoma

    Directory of Open Access Journals (Sweden)

    Biljana Lazović

    2013-09-01

    Full Text Available Etoposide is commonly used in the treatment of a variety of neoplasms. Hypersensitivity reactions to etoposide are infrequently reported and include hypotension, hypertension, flushing, diaphoresis, chest discomfort, dyspnea, bronchospasm and loss of consciousness. We report the case of a 39-year-old woman who experienced acute bronchospasm, tachycardia, hypoxia and hypotension. The symptoms resolved within an hour after administration of intravenous fluids, methylprednisolone, diphenhydramine and oxygen. Subsequently, the patient was given etoposide phosphate without incident.

  15. Development of Immunotherapy for Insect Bite Hypersensitivity in Horses

    OpenAIRE

    Jónsdóttir, Sigríður

    2017-01-01

    Insect bite hypersensitivity (IBH) is a type I allergy of horses with production of IgE and release of inflammatory mediators. It is caused by bites of midges of the genus Culicoides. The disease is a recurrent dermatitis characterized by pruritic skin and hair loss, which can result in secondary infections. All breeds of horses can be affected, but horses born in Iceland and exported are more frequently affected than Icelandic horses born abroad. Allergens have been identified at the molecul...

  16. Ceftriaxone Induced Hypersensitivity Reactions Following Intradermal Skin Test: Case Series

    OpenAIRE

    Sereen Rose Thomson; Balaji Ommurugan; Navin Patil

    2017-01-01

    The incidence of cephalosporin induced hypersensitivity reactions in non-penicillin allergic patients is about 1.7% and in penicillin allergic patients it is about 3-5%. Infact, cephalosporins are considered as the first choice in penicillin allergic patients who need antibiotic therapy intraoperatively. Prompt identification of patients with beta-lactam allergy would lead to an improved utilization of antibiotics and reduced occurrence of resistant strains. We hereby attempt to present a ser...

  17. A Case of Possible Hypersensitivity Reactions to Human Insulin

    Directory of Open Access Journals (Sweden)

    Adamescu Eduard

    2016-03-01

    Full Text Available Background: Insulin therapy is commonly used in diabetic patients. It represents the only option for patients with type 1 diabetes mellitus and could be part of the treatment plan for the patient with type 2 diabetes mellitus. Clinical appearance of hypersensitivity reactions to insulin vary significantly, depending on the immune mechanism involved. Many skin prick tests could be interpreted as positive reactions (either by using inappropriate concentrations or due to other mast cell degranulation causes.

  18. Equine insect bite hypersensitivity: What do we know?

    OpenAIRE

    Schaffartzik A; Hamza E; Janda J; Crameri R; Marti E; Rhyner C

    2012-01-01

    Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH recent studies suggest that IBH is characterized by an imbalance between...

  19. Stipatosis or hypersensitivity pneumonitis caused by esparto (Stipa tenacissima) fibers.

    Science.gov (United States)

    Hinojosa, M

    2001-01-01

    Hypersensitivity pneumonitis or extrinsic allergic alveolitis may be defined as an immunological pulmonary disease caused by a variety of antigens reaching the lungs through inhaled organic and inorganic dusts derived from different sources, although they are usually occupational. Farmer's lung and pigeon breeder's lung are probably the most well-known types of hypersensitivity pneumonitis worldwide. Esparto grass (Stipa tenacissima), which is a grammineous plant which is commonly found in the Mediterranean countries, has a wide variety of uses. Esparto fiber is used for the manufacturing of ropes, hemp sandals, rush mats and parkets; for decorative stucco plates, used on walls and ceilings. Esparto supports a large industry in Spain. The first reports referring to esparto dust as a cause of respiratory disease did not appear until the 1960s, and it was first described as a byssinosis-like disorder. The first cases reported, in which immunologic and challenge tests were used to confirm this association, were described 14 years ago and referred as hypersensitivity pneumonitis nominated as stipatosis. Later, a large number of cases of esparto dust-induced hypersensitivity pneumonitis were reported by different authors, so that esparto may be nowadays considered as the main substance causing extrinsic allergic alveolitis in Spain. Afumigatus has been revealed to be the main inducing cause of stipatosis but probably is not the only one since other microorganisms could be implicated. On the other hand esparto fibers may also cause occupational asthma. In this article the prominent clinical findings of this disease as well as the results of serologic, bronchoalveolar lavage (BAL) and specific inhalation tests are shown. A complete historical review of esparto-induced allergic respiratory disease is also described.

  20. Evolutionary Medicine: Semen Sampling and Seminal Plasma Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Gordon G. Gallup

    2014-01-01

    Full Text Available Evidence suggests that each male may have a unique semen signature, and there are reasons to consider the possibility that semen sampling (i.e., being inseminated by different prospective mates during courtship may be part of an evolved female mate assessment strategy. Here we theorize that seminal plasma hypersensitivity represents the extreme negative end of this continuum and functions as a deterrent to mating with genetically incompatible suitors.

  1. 5-HT(2B) receptors modulate visceral hypersensitivity in a stress-sensitive animal model of brain-gut axis dysfunction.

    Science.gov (United States)

    O'Mahony, S M; Bulmer, D C; Coelho, A-M; Fitzgerald, P; Bongiovanni, C; Lee, K; Winchester, W; Dinan, T G; Cryan, J F

    2010-05-01

    Irritable bowel syndrome (IBS) is associated with an enhanced perception to visceral stimuli and exaggerated stress response. The serotonergic neurotransmitter system has been strongly implicated as a key player in the manifestation of IBS symptomatology including visceral hypersensitivity. However the role of 5-HT(2B) receptors in visceral pain, although speculated, is currently unclear. Thus we assessed the impact of a selective 5-HT(2B) receptor antagonist, RS-127445, on visceral hypersensitivity in a model of brain gut axis dysfunction the Wistar Kyoto (WKY) rat. Colorectal distension (CRD) was used to assess the visceral sensitivity of the WKY rat compared to normosensitive Sprague Dawley (SD) rats. Once we verified the visceral sensitivity of the WKY rat we assessed the efficacy of RS-127445 in pain signalling from the colorectum. We administered the compound peripherally (i.p.) and centrally (i.c.v.) in order to ascertain the site of action of RS 127445. Behavioural responses to colorectal distention were then monitored. The WKY rats were more viscerally hypersensitive than the SD as previously shown. RS-127445 (5 mg kg(-1), i.p.) significantly reversed visceral hypersensitivity in WKY animals. Moreover, when administered intracerebroventricularly RS-127445 (100 nM) also decreased the number of pain behaviours during noxious CRD in the WKY animals. Taken together, blockade of 5-HT(2B) receptors offers an exciting novel therapeutic target for pain relief in stress-related gastrointestinal disorders such as IBS.

  2. Hypersensitivity in Borderline Personality Disorder during Mindreading

    OpenAIRE

    Frick, Carina; Lang, Simone; Kotchoubey, Boris; Sieswerda, Simkje; Dinu-Biringer, Ramona; Berger, Moritz; Veser, Sandra; Essig, Marco; Barnow, Sven

    2012-01-01

    BACKGROUND: One of the core symptoms of borderline personality disorder (BPD) is the instability in interpersonal relationships. This might be related to existent differences in mindreading between BPD patients and healthy individuals. METHODS: We examined the behavioural and neurophysiological (fMRI) responses of BPD patients and healthy controls (HC) during performance of the 'Reading the Mind in the Eyes' test (RMET). RESULTS: Mental state discrimination was significantly better and faster...

  3. Health-related quality of life among adolescents with allergy-like conditions – with emphasis on food hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ahlstedt Staffan

    2004-11-01

    Full Text Available Abstract Background It is known that there is an increase in the prevalence of allergy and that allergic diseases have a negative impact on individuals' health-related quality of life (HRQL. However, research in this field is mainly focused on individuals with verified allergy, i.e. leaving out those with self-reported allergy-like conditions but with no doctor-diagnosis. Furthermore, studies on food hypersensitivity and quality of life are scarce. In order to receive information about the extent to which adolescent females and males experience allergy-like conditions and the impact of these conditions on their everyday life, the present study aimed to investigate the magnitude of self-reported allergy-like conditions in adolescence and to evaluate their HRQL. Special focus was put on food hypersensitivity as a specific allergy-like condition and on gender differences. Methods In connection with lessons completed at the children's school, a study-specific questionnaire and the generic instrument SF-36 were distributed to 1488 adolescents, 13–21 years old (response rate 97%. Results Sixty-four per cent of the respondents reported some kind of allergy-like condition: 46% reported hypersensitivity to defined substances and 51% reported allergic diseases (i.e. asthma/wheezing, eczema/rash, rhino-conjunctivitis. A total of 19% reported food hypersensitivity. Females more often reported allergy-like conditions compared with males (p Conclusions The results indicate a need to consider the psychosocial impact of allergy-like conditions during school age. Further research is needed to elucidate the gender differences in this area. A team approach addressing better understanding of how allergy-like conditions impair the HRQL may improve the management of the adolescent's health problems, both in health-care services and in schools.

  4. Bringing human resources to the table: utilization of an HR balanced scorecard at Mayo Clinic.

    Science.gov (United States)

    Fottler, Myron D; Erickson, Eric; Rivers, Patrick A

    2006-01-01

    Rather than viewing HR as a critical driver of organizational strategy and outcomes, most health care organizations see HR as a drain on the organization's bottom line. Only by aligning HR with the organizational strategy will HR leaders truly get a seat at the leadership table. HR professionals can overcome impediments and gain a seat at the table by learning the language of business and the ways in which organizational leaders use data to drive their decisions. This article shows how Mayo Clinic uses the popular Balanced Scorecard approach to align its measures of HR performance to the organization's strategic plan.

  5. Cracking the egg: An insight into egg hypersensitivity.

    Science.gov (United States)

    Dhanapala, Pathum; De Silva, Chamika; Doran, Tim; Suphioglu, Cenk

    2015-08-01

    Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    Directory of Open Access Journals (Sweden)

    Kidon Mona

    2007-12-01

    Full Text Available Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

  7. A Case of Hypersensitivity Syndrome to Both Vancomycin and Teicoplanin

    Science.gov (United States)

    Kwon, Hyouk-Soo; Chang, Yoon-Seok; Jeong, Yi-Yeong; Lee, Sang-Min; Song, Woo-Jung; Kim, Hong-Bin; Kim, Yoon-Keun; Cho, Sang-Heon; Kim, You-Young

    2006-01-01

    Drug hypersensitivity syndrome to both vancomycin and teicoplanin has not been previously reported. We describe here a 50-yr-old male patient with vertebral osteomyelitis and epidural abscess who developed hypersensitivity syndrome to both vancomycin and teicoplanin. Skin rash, fever, eosinophilia, interstitial pneumonitis, and interstitial nephritis developed following the administration of each drug, and resolved after withdrawing the drugs and treating with high dose corticosteroids. The vertebral osteomyelitis was successfully treated with 6-week course of linezolid without further complications. Skin patch tests for vancomycin and teicoplanin was done 2 months after the recovery; a weak positive result for vancomycin (10% aq.,+at D2 and +at D4 with erythema and vesicles; ICDRG scale), and a doubtful result for teicoplanin (4% aq.-at D2 and±at D4 with macular erythema; ICDRG scale). We present this case to alert clinicians to the hypersensitivity syndrome that can result from vancomycin and teicoplanin, with possible cross-reactivity, which could potentially be life-threatening. PMID:17179696

  8. [Hypersensitivity to fluindione (Previscan). Positive skin patch tests].

    Science.gov (United States)

    Frouin, E; Roth, B; Grange, A; Grange, F; Tortel, M-C; Guillaume, J-C

    2005-12-01

    Fluindione (Previscan) is an oral anticoagulant belonging to the vitamin K antagonist class and is very widely used in France. While bleeding is a common complication, severe immunoallergic reactions are less frequent. The authors report a case of drug-induced hypersensitivity syndrome. A 75 year-old woman was hospitalized for diffuse erythematous papular rash associated with facial oedema. These symptoms appeared 3 weeks after the beginning of treatment with fluindione, allopurinol and perindopril. Laboratory tests showed hyperleukocytosis, mixed hepatitis and moderate renal failure, with the entire picture being evocative of drug-induced hypersensitivity reaction. The eruption was associated with eosinophilia, hepatic cytolysis with cholestasis, and acute renale failure. While allopurinol and perindopril were stopped definitively, fluindione was only suspended temporarily following overdosage. On reintroduction, rapid recurrence of clinical and biologic signs was observed with increased severity. The skin rash resolved completely on withdrawal of the drug. Patch tests performed later were positive for fluindione and negative for allopurinol and perindopril. These manifestations were consistent with the diagnosis of drug-induced hypersensitivity syndrome due to fluindione. Very few cases have been described with fluindione despite widespread prescription of the treatment is in France. While there may be no skin involvement, immunoallergic signs such as fever, hepatitis and acute tubular interstitial nephritis have been described with fluindione and these may be related to this syndrome (DRESS - Drug Reaction with Eosinophilia and Systemic Symptoms). Skin patch testing, which is easily performed, can be extremely helpful in determining a causal relationship with medication.

  9. Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis.

    Science.gov (United States)

    Malajian, Dana; Belsito, Donald V

    2013-08-01

    Literature on the relationship between atopic dermatitis (AD) and cutaneous delayed-type hypersensitivity is inconclusive. We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD, and, to assess whether atopic patients in our database were more likely to patch test positive to certain classes of allergens. A total of 2305 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reactions among patients with AD (n = 297) and without AD (n = 2008) was assessed. Statistical analysis was done using a χ(2) test with Yates continuity correction. Compared with nonatopic patients, those with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to nickel, cobalt, and chromium, but was not associated with contact sensitization to fragrances. Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City (including Kansas City, MO, Kansas City, KS, and the adjoining suburbs). Compared with nonatopics, patients with AD are significantly more likely to have at least 1 positive patch test reaction and to develop contact hypersensitivity to metal allergens. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  10. [Hypersensitivity pneumonitis in construction plasterers (espartosis): study of 20 patients].

    Science.gov (United States)

    Cruz, María Jesús; Morell, Ferran; Roger, Alex; Muñoz, Xavier; Rodrigo, María José

    2003-04-26

    Espartosis is a type of hypersensitivity pneumonitis which frequently affects construction workers handling esparto fibres used as support material inside gypsum plaster. Exactly which agents produce this disease remains under discussion. The aims of this study were: a) to assess the possible etiologic role of the fungi colonizing esparto grass fibres and esparto itself in the genesis of this disease, and b) to describe the clinical characteristics of this disease in a large series of patients. Twenty patients diagnosed of hypersensitivity pneumonitis due to esparto grass exposure were studied. Mycologic cultures of the esparto grass fibre samples provided by each patient were performed. Fungi and/or esparto were used for determination of specific IgG antibodies, specific skin tests and specific bronchial challenge tests. Most frequently isolated fungi in causal esparto samples were Aspergillus sp. (60%) and Mucor sp. (47%). Specific IgG antibody determinations and/or specific bronchial challenge tests showed antigenicity not only for Aspergillus sp. but also for non-fungi-contaminated esparto grass and other fungi such as Penicillium sp. or Mucor sp. These results were helpful for establishing a new etiologic approach to the diagnosis of this disease. Aspergillus fumigatus is recognized as a causal agent in hypersensitivity pneumonitis due to esparto grass exposure; however, other antigenic sources such as Penicillium frequentans and other fungi, as well as esparto grass fibres, also appear to play a role in the genesis of this disease.

  11. Dynamic hydrolase activities precede hypersensitive tissue collapse in tomato seedlings.

    Science.gov (United States)

    Sueldo, Daniela; Ahmed, Ali; Misas-Villamil, Johana; Colby, Tom; Tameling, Wladimir; Joosten, Matthieu H A J; van der Hoorn, Renier A L

    2014-08-01

    Hydrolases such as subtilases, vacuolar processing enzymes (VPEs) and the proteasome play important roles during plant programmed cell death (PCD). We investigated hydrolase activities during PCD using activity-based protein profiling (ABPP), which displays the active proteome using probes that react covalently with the active site of proteins. We employed tomato (Solanum lycopersicum) seedlings undergoing synchronized hypersensitive cell death by co-expressing the avirulence protein Avr4 from Cladosporium fulvum and the tomato resistance protein Cf-4. Cell death is blocked in seedlings grown at high temperature and humidity, and is synchronously induced by decreasing temperature and humidity. ABPP revealed that VPEs and the proteasome are not differentially active, but that activities of papain-like cysteine proteases and serine hydrolases, including Hsr203 and P69B, increase before hypersensitive tissue collapse, whereas the activity of a carboxypeptidase-like enzyme is reduced. Similar dynamics were observed for these enzymes in the apoplast of tomato challenged with C. fulvum. Unexpectedly, these challenged plants also displayed novel isoforms of secreted putative VPEs. In the absence of tissue collapse at high humidity, the hydrolase activity profile is already altered completely, demonstrating that changes in hydrolase activities precede hypersensitive tissue collapse. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  12. The P25 protein of potato virus X (PVX) is the main pathogenicity determinant responsible for systemic necrosis in PVX-associated synergisms.

    Science.gov (United States)

    Aguilar, Emmanuel; Almendral, David; Allende, Lucía; Pacheco, Remedios; Chung, Bong Nam; Canto, Tomás; Tenllado, Francisco

    2015-02-01

    Most plant viruses counter the RNA silencing-based antiviral defense by expressing viral suppressors of RNA silencing (VSRs). In this sense, VSRs may be regarded as virulence effectors that can be recognized by the host as avirulence (avr) factors to induce R-mediated resistance. We made use of Agrobacterium-mediated transient coexpression of VSRs in combination with Potato virus X (PVX) to recapitulate in local tissues the systemic necrosis (SN) caused by PVX-potyvirus synergistic infections in Nicotiana benthamiana. The hypersensitive response (HR)-like response was associated with an enhanced accumulation of PVX subgenomic RNAs. We further show that expression of P25, the VSR of PVX, in the presence of VSR from different viruses elicited an HR-like response in Nicotiana spp. Furthermore, the expression of P25 by a Plum pox virus (PPV) vector was sufficient to induce an increase of PPV pathogenicity that led to necrotic mottling. A frameshift mutation in the P25 open reading frame (ORF) of PVX did not lead to necrosis when coexpressed with VSRs. These findings indicate that P25 is the main PVX determinant involved in eliciting a systemic HR-like response in PVX-associated synergisms. Moreover, we show that silencing of SGT1 and RAR1 attenuated cell death in both PVX-potyvirus synergistic infection and the HR-like response elicited by P25. Our study underscores that P25 variants that have impaired ability to suppress RNA silencing cannot act as elicitors when synergized by the presence of other VSRs. These findings highlight the importance of RNA silencing suppression activity in the HR-like response elicited by VSRs in certain hosts. The work presented here describes how the activity of the PVX suppressor P25 elicits an HR-like response in Nicotiana spp. when overexpressed with other VSR proteins. This finding suggests that the SN response caused by PVX-associated synergisms is a delayed immune response triggered by P25, once it reaches a threshold level by the

  13. Activation of cannabinoid CB1 receptors suppresses the ROS-induced hypersensitivity of rat vagal lung C-fiber afferents.

    Science.gov (United States)

    Yeh, Chou-Ming; Ruan, Ting; Lin, Yu-Jung; Hsu, Tien-Huan

    2016-10-01

    Reactive oxygen species (ROS), including H2O2, have been shown to induce hypersensitivity of vagal lung C-fibers (VLCFs) mainly through receptor potential ankyrin 1 (TRPA1) and P2X receptors. Cannabinoids (CBs) exert antinociceptive effects by binding to specific CB receptors, designated CB1 and CB2 (type 2) for type 1 and type 2, respectively. We investigated whether activation of CB receptors can suppress ROS-mediated VLCF hypersensitivity and, if so, what type(s) of CB receptors are involved. Aerosolized H2O2 (0.05%) was inhaled by anesthetized spontaneously breathing rats (n = 304) to sensitize VLCFs. Airway reflex reactivity to intravenous capsaicin, a VLCF stimulant, was measured. Perivagal pretreatments with various types of agonists and antagonists, a technique that can modulate VLCF sensitivity, were made to delineate the roles of the CB receptors. Aerosolized H2O2 induced an augmented apneic response to capsaicin, which was blocked by bilateral vagotomy or by perivagal capsaicin treatment, suggesting that the response is mediated through VLCFs. Perivagal treatment with HU210 (a nonselective CB agonist) or ACPA (a selective CB1 receptor agonist), but not JWH133 (a CB2 receptor agonist), attenuated this H2O2-induced VLCF hypersensitivity. The suppressive effects of HU210 and ACPA were prevented by an additional treatment with AM251 (a selective CB1 antagonist), but not with AM630 (a selective CB2 antagonist). Perivagal treatment with a combination of ACPA, HC030031 (a TRPA1 receptor antagonist), and iso-PPADS (a P2X receptor antagonist) further attenuated the H2O2-induced VLCF hypersensitivity, as compared with treatment with a combination of HC030031 and iso-PPADS. Our results suggest that activation of CB1 receptors may suppress the ROS-mediated VLCF hypersensitivity through a mechanism that is at least partly distinct from the function of TRPA1 and P2X receptors. Copyright © 2016. Published by Elsevier Ltd.

  14. Masses, Radii, and Cloud Properties of the HR 8799 Planets

    Science.gov (United States)

    Marley, Mark S.; Saumon, Didier; Cushing, Michael; Ackerman, Andrew S.; Fortney, Jonathan J.; Freedman, Richard

    2012-01-01

    The near-infrared colors of the planets directly imaged around the A star HR 8799 are much redder than most field brown dwarfs of the same effective temperature. Previous theoretical studies of these objects have compared the photometric and limited spectral data of the planets to the predictions of various atmosphere and evolution models and concluded that the atmospheres of planets b, c, and d are unusually cloudy or have unusual cloud properties. Most studies have also found that the inferred radii of some or all of the planets disagree with expectations of standard giant planet evolution models. Here we compare the available data to the predictions of our own set of atmospheric and evolution models that have been extensively tested against field L and T dwarfs, including the reddest L dwarfs. Unlike almost all previous studies we specify mutually self-consistent choices for effective temperature, gravity, cloud properties, and planetary radius. This procedure yields plausible and self-consistent values for the masses, effective temperatures, and cloud properties of all three planets. We find that the cloud properties of the HR 8799 planets are in fact not unusual but rather follow previously recognized trends including a gravity dependence on the temperature of the L to T spectral transition, some reasons for which we discuss. We find that the inferred mass of planet b is highly sensitive to the H and K band spectrum. Solutions for planets c and particularly d are less certain but are consistent with the generally accepted constraints on the age of the primary star and orbital dynamics. We also confirm that as for L and T dwarfs and solar system giant planets, non-equilibrium chemistry driven by atmospheric mixing is also important for these objects. Given the preponderance of data suggesting that the L to T spectral type transition is gravity dependent, we present a new evolution calculation that predicts cooling tracks on the near-infrared color

  15. Type IV hypersensitivity reactions following Dermabond adhesive utilization in knee surgery: A Report of Three Cases.

    Science.gov (United States)

    Yagnatovsky, Michelle; Pham, Hien; Rokito, Andrew; Jazrawi, Laith; Strauss, Eric

    2017-05-01

    ​We retrospectively reviewed the records of 3 patients (3 knees) with a delayed type hypersensitivity reaction following Dermabond exposure after an orthopaedic knee procedure. Delayed hypersensitivity reactions are mediated by CD4+ helper T cells. The use of skin adhesives in place of traditional sutures is increasing in popularity given Dermabond's potential benefits of decreased wound infection rate and better wound approximation. However, hypersensitivity reactions to the cyanoacrylate material in Dermabond have been described. Differentiating hypersensitivity reactions from post-operative infections is important as septic arthritis is a potentially devastating complication. This case series presents the challenge of properly diagnosing and managing hypersensitivity reactions. Consultation with allergists and dermatologists may be appropriate for ascertaining the nature of the surgical site complication and proper management. The recommended management of hypersensitivity-type reactions is a course of topical steroids and infection work up if needed.

  16. Human resources business process outsourcing: transforming how HR gets its work done

    National Research Council Canada - National Science Library

    Lawler, Edward E

    2004-01-01

    ... services. HR must excel at both delivering traditional transaction services and providing high value-added strategic services. If HR stays at the transactional level, the department will become...

  17. Hypersensitivity in borderline personality disorder during mindreading.

    Directory of Open Access Journals (Sweden)

    Carina Frick

    Full Text Available BACKGROUND: One of the core symptoms of borderline personality disorder (BPD is the instability in interpersonal relationships. This might be related to existent differences in mindreading between BPD patients and healthy individuals. METHODS: We examined the behavioural and neurophysiological (fMRI responses of BPD patients and healthy controls (HC during performance of the 'Reading the Mind in the Eyes' test (RMET. RESULTS: Mental state discrimination was significantly better and faster for affective eye gazes in BPD patients than in HC. At the neurophysiological level, this was manifested in a stronger activation of the amygdala and greater activity of the medial frontal gyrus, the left temporal pole and the middle temporal gyrus during affective eye gazes. In contrast, HC subjects showed a greater activation in the insula and the superior temporal gyri. CONCLUSION: These findings indicate that BPD patients are highly vigilant to social stimuli, maybe because they resonate intuitively with mental states of others.

  18. Cyperus scariosus Chloroform Fraction Inhibits T cell Responses in ...

    African Journals Online (AJOL)

    Erah

    delayed-type hypersensitivity models employing sheep red blood cells (SRBC) as the antigen. Further, the extract was studied ... also inhibited cell-mediated delayed type hypersensitivity (DTH) immune response (45.9 %) at 600 mg/kg dose, phagocytosis ..... states of the body and auto-immune disorders such as arthritis.

  19. Butterfly Diagram and Activity Cycles in HR 1099

    Science.gov (United States)

    Berdyugina, Svetlana V.; Henry, Gregory W.

    2007-04-01

    We analyze photometric data of the active RS CVn-type star HR 1099 for the years 1975-2006 with an inversion technique and reveal the nature of two activity cycles of 15-16 yr and 5.3+/-0.1 yr duration. The 16 yr cycle is related to variations of the total spot area and is coupled with the differential rotation, while the 5.3 yr cycle is caused by the symmetric redistribution of the spotted area between the opposite stellar hemispheres (flip-flop cycle). We recover long-lived active regions comprising two active longitudes that migrate in the orbital reference frame with a variable rate because of the differential rotation along with changes in the mean spot latitudes. The migration pattern is periodic with the 16 yr cycle. Combining the longitudinal migration of the active regions with a previously measured differential rotation law, we recover the first stellar butterfly diagram without an assumption about spot shapes. We find that mean latitudes of active regions at opposite longitudes change antisymmetrically in the course of the 16 yr cycle: while one active region migrates to the pole, the other approaches the equator. This suggests a precession of the global magnetic field with respect to the stellar rotational axis.

  20. The significance of hypersensitivity to autologous sweat and serum in cholinergic urticaria: cholinergic urticaria may have different subtypes.

    Science.gov (United States)

    Kim, Jung Eun; Jung, Kwan Ho; Cho, Hyun Hee; Kang, Hoon; Park, Young Min; Park, Hyun Jeong; Lee, Jun Young

    2015-07-01

    The pathogenesis of cholinergic urticaria (ChU) has been unclear except for the involvement of acetylcholine. Attempts to classify ChU according to etiology have rarely been performed. To evaluate the significance of responsiveness to autologous sweat and serum in ChU in relation to their clinical characteristics. This study involved 18 patients diagnosed with ChU between January 2010 and April 2011 in the Catholic Medical Center-St. Paul's Hospital. History taking included symptom duration, association with atopy, decreased sweat secretions, seasonal variation, and response to treatment. Intradermal autologous serum skin test (ASST) and autologous sweat skin test (ASwST) and basophil histamine release test with sweat were done. Sweat hypersensitivity was proven by a positive ASwST and basophil histamine release test in only 37.5% of patients with ChU, and in none of the healthy controls. The weal size of ASwST correlated with percentage basophil histamine release. A positive response to autologous serum was displayed by 38.9% of patients, whereas 10% of healthy controls showed a positive ASST response. Intriguingly, patients with a positive ASwST had a negative ASST, and vice versa. Despite this, there was no difference in the clinical characteristics between positive ASST and positive ASwST groups. The frequency of hypersensitivity to autologous sweat and serum was significantly higher in patients with ChU, compared with healthy controls. This suggests that autoimmunity to an unknown serum factor as well as sweat hypersensitivity may be involved in the pathogenesis of ChU. © 2014 The International Society of Dermatology.

  1. Carboplatin hypersensitivity in children with glial tumors: a report of two cases

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

    Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798

  2. HLA-associated drug hypersensitivity and the prediction of adverse drug reactions.

    Science.gov (United States)

    Negrini, Simone; Becquemont, Laurent

    2017-10-01

    Adverse drug reactions are an important cause of morbidity and mortality and constitute the leading reason of drug withdrawal from the market. Besides classical reactions that are related to pharmacologic activity of the drug, some reactions are unpredictable, not dose dependent, and seem to occur in genetically predisposed individuals. The majority of this reaction is immunologically driven and they are referred to as hypersensitivity reactions. A growing number of studies provided evidences that specific HLA alleles increase the risk of developing hypersensitivity drug reactions. In this context, drug hypersensitivities that have more robust pharmacogenetic data include abacavir hypersensitivity syndrome and severe cutaneous adverse reactions induced by allopurinol and carbamazepine.

  3. Hypersensitivity Reaction and Tolerance Induction to Ethambutol

    Directory of Open Access Journals (Sweden)

    Josefina Rodrigues Cernadas

    2013-01-01

    Full Text Available Tuberculosis remains the leading cause of death worldwide from any infectious agent and the alarming increase in the annual incidence of new cases has been described as a global emergency. Mycobacterium infection requires simultaneous administration of multiple drugs. Although the majority of treatment courses progress with minor side effects, adverse reactions to antituberculosis drugs occur in about 5% of treated patients and can be responsible for cessation or switching the therapy. Both nonimmediate (mostly maculopapular rash and immediate reactions (urticarial reactions have been described with these drugs. The main problem is the occurrence of reactions while the patient is on treatment with multiple drugs. The diagnosis of the culprit drug is mostly based on stopping all medication, followed by the reintroduction of each drug with a time interval of four to five days. An alternative drug should be the first approach if it is equally effective. Most of the times, none of the alternative drugs are as effective as the culprit. If this is the case, a desensitization procedure should be performed. The authors describe a case of a woman with Mycobacterium avium complex (MAC infection, to whom treatment with ethambutol was crucial to recovery, and present a modified desensitization protocol to this drug.

  4. Role of probiotics in food hypersensitivity.

    Science.gov (United States)

    Isolauri, Erika; Rautava, Samuli; Kalliomäki, Marko; Kirjavainen, Pirkka; Salminen, Seppo

    2002-06-01

    The definition of probiotics has evolved concomitant with a resurgence of research interest in host-microbe crosstalk. The original definition stated that the live active culture beneficially affects the host by improving its intestinal microbial balance, while current conceptions are based on target- and site- specific effects of clearly defined strains. The establishment of normal microbiota in the intestine represents a key process whereby the intestinal milieu is kept disease-free as it performs its dual function: mounting an inflammatory response to pathogens and maintaining hyporesponsiveness to innocuous antigens. Probiotic therapy is based on this concept of a healthy well-balanced gut microbiota. The probiotic performance of strains differs, however. Different bacteria have clearly defined adherence sites and immunological effects and divergent effects in the healthy versus inflamed mucosa. Hence, notwithstanding recent demonstrations of the important immunoregulatory potential of the healthy well-balanced gut microbiota, current probiotic research is directed towards identification of specific strains with anti-allergenic potential.

  5. Towards the Identification of New Genes Involved in ABA-Dependent Abiotic Stresses Using Arabidopsis Suppressor Mutants of abh1 Hypersensitivity to ABA during Seed Germination

    Directory of Open Access Journals (Sweden)

    Iwona Szarejko

    2013-06-01

    Full Text Available Abscisic acid plays a pivotal role in the abiotic stress response in plants. Although great progress has been achieved explaining the complexity of the stress and ABA signaling cascade, there are still many questions to answer. Mutants are a valuable tool in the identification of new genes or new alleles of already known genes and in elucidating their role in signaling pathways. We applied a suppressor mutation approach in order to find new components of ABA and abiotic stress signaling in Arabidopsis. Using the abh1 (ABA hypersensitive 1 insertional mutant as a parental line for EMS mutagenesis, we selected several mutants with suppressed hypersensitivity to ABA during seed germination. Here, we present the response to ABA and a wide range of abiotic stresses during the seed germination and young seedling development of two suppressor mutants—soa2 (suppressor of abh1 hypersensitivity to ABA 2 and soa3 (suppressor of abh1 hypersensitivity to ABA 3. Generally, both mutants displayed a suppression of the hypersensitivity of abh1 to ABA, NaCl and mannitol during germination. Both mutants showed a higher level of tolerance than Columbia-0 (Col-0—the parental line of abh1 in high concentrations of glucose. Additionally, soa2 exhibited better root growth than Col-0 in the presence of high ABA concentrations. soa2 and soa3 were drought tolerant and both had about 50% fewer stomata per mm2 than the wild-type but the same number as their parental line—abh1. Taking into account that suppressor mutants had the same genetic background as their parental line—abh1, it was necessary to backcross abh1 with Landsberg erecta four times for the map-based cloning approach. Mapping populations, derived from the cross of abh1 in the Landsberg erecta background with each suppressor mutant, were created. Map based cloning in order to identify the suppressor genes is in progress.

  6. Hypersensitivity pneumonitis induced by spores of Penicillium citrinum in a worker cultivating Enoki mushroom.

    Science.gov (United States)

    Yoshikawa, Sumiko; Tsushima, Kenji; Koizumi, Tomonobu; Kubo, Keishi; Kumagai, Toshiko; Yamazaki, Yoshitaka

    2006-01-01

    A 47-year-old Japanese woman was admitted to our hospital with a 2-week history of dry cough and shortness of breath. She had been engaged in Enoki mushroom production for 22 years. Chest X-ray and chest computed tomography (CT) scan showed bilateral fine-nodular shadows and ground glass opacity. Bronchoalveolar lavage fluid demonstrated an increase of total cell counts with predominant lymphocytosis. Pathological specimens obtained by video-assisted thoracoscopic surgery revealed alveolitis and noncaseating granuloma with giant cells. Lymphocyte stimulation test showed positive responses with Enoki mushroom, culture medium, and Penicillium citrinum. On double immunodiffusion test, a precipitation line was observed between patient's serum and Penicillium citrinum antigen. She was found to have hypersensitivity pneumonitis caused by Penicillium citrinum. This is the first report of mushroom worker's lung caused by Penicillium citrinum.

  7. Fatal meningitis following lymphocytic choriomeningitis virus infection reflects delayed-type hypersensitivity rather than cytotoxicity

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Bro-Jørgensen, K; Volkert, M

    1983-01-01

    Fatal meningitis following intracerebral inoculation of lymphocytic choriomeningitis virus (LCMV) reflects an immunopathological lesion believed to be mediated by cytotoxic T cells. The results presented here demonstrate that pretreatment with cyclophosphamide (Cy; 150 mg/kg body weight) 2 days...... before intracerebral infection significantly reduced the lethality of the infection. However, this treatment did not impair the antiviral cytotoxic response as measured in the spleen. On the other hand, virus-specific delayed-type hypersensitivity (DTH) was significantly reduced. This reduction seems......-pretreated mice; and (3) inoculation of irrelevant antigen and antigen-primed spleen cells into the footpads of Cy-pretreated, infected mice resulted in a significantly reduced footpad swelling as compared with untreated, infected controls. Taken together, these results indicate that LCMV-induced meningitis does...

  8. Coronavirus escape from heptad repeat 2 (HR2)-derived peptide entry inhibition as a result of mutations in the HR1 domain of the spike fusion protein

    NARCIS (Netherlands)

    Bosch, Berend Jan; Rossen, John W. A.; Bartelink, Willem; Zuurveen, Stephanie J.; de Haan, Cornelis A. M.; Duquerroy, Stephane; Boucher, Charles A. B.; Rottier, Peter J. M.

    Peptides based on heptad repeat (HR) domains of class I viral fusion proteins are considered promising antiviral drugs targeting virus cell entry. We have analyzed the evolution of the mouse hepatitis coronavirus during multiple passaging in the presence of an HR2-based fusion inhibitor.

  9. Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Kim, Esther S; Scott, Lesley J

    2017-06-01

    Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates. Neutropenia was the most commonly reported any-grade and grade ≥ 3 adverse event. It was infrequently associated with febrile neutropenia (palbociclib dose delay, interruption or reduction, without the routine use of growth factors, and without affecting efficacy. In conclusion, oral palbociclib combination therapy is a valuable emerging option for use in patients with HR-positive, HER2-negative advanced or metastatic breast cancer.

  10. Metabolic Portraits of Breast Cancer by HR MAS MR Spectroscopy of Intact Tissue Samples

    Directory of Open Access Journals (Sweden)

    Tonje H. Haukaas

    2017-05-01

    Full Text Available Despite progress in early detection and therapeutic strategies, breast cancer remains the second leading cause of cancer-related death among women globally. Due to the heterogeneity and complexity of tumor biology, breast cancer patients with similar diagnosis might have different prognosis and response to treatment. Thus, deeper understanding of individual tumor properties is necessary. Cancer cells must be able to convert nutrients to biomass while maintaining energy production, which requires reprogramming of central metabolic processes in the cells. This phenomenon is increasingly recognized as a potential target for treatment, but also as a source for biomarkers that can be used for prognosis, risk stratification and therapy monitoring. Magnetic resonance (MR metabolomics is a widely used approach in translational research, aiming to identify clinically relevant metabolic biomarkers or generate novel understanding of the molecular biology in tumors. Ex vivo proton high-resolution magic angle spinning (HR MAS MR spectroscopy is widely used to study central metabolic processes in a non-destructive manner. Here we review the current status for HR MAS MR spectroscopy findings in breast cancer in relation to glucose, amino acid and choline metabolism.

  11. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity.

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. © 2016 S. Karger AG, Basel.

  12. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W.

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between cells in general, that then can participate, as described herein, in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells, taking into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting non-specifically, but also can proceed in an antigen-specific manner due to coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These likely will significantly diminish the risks of current allergen specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for specific delivery of therapeutic molecular instructions through easily tolerated, non-invasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. PMID:27820941

  13. Immunological mechanisms underlying delayed-type hypersensitivity reactions to glatiramer acetate.

    Science.gov (United States)

    Mayorga, Cristobalina; Blazquez, Ana B; Doña, Inmaculada; Gomez, Francisca; Chaves, Patricia; Sanchez-Quintero, Maria J; Blanca-López, Natalia; Melendez, Lidia; Blanca, Miguel; Torres, Maria Jose

    2012-07-01

    Delayed-type hypersensitivity to glatiramer acetate is rare, and the underlying immunological mechanisms are not completely understood. To study the immunologic response in 2 patients with multiple sclerosis who developed maculopapular exanthema related with the administration of glatiramer acetate. The allergologic study included general blood tests, viral serologic tests, and skin tests (patch and intradermal tests). The immunologic study was performed in skin biopsy specimens by immunohistochemistry and in the peripheral blood by flow cytometry and the lymphocyte transformation test. Skin test results were negative in both patients, and the diagnosis was confirmed by a drug provocation test. The evaluation of the acute phase showed an increase in the percentage of CD8 T lymphocytes (>50%) and the percentage of cells expressing skin-homing receptor (cutaneous lymphocyte-associated antigen) (>70%) and chemokine receptors (CCR4 and CXCR3) at T1. A positive proliferative response was observed in T lymphocytes (stimulation index [SI] = 3.5 in patient 1 and 3.59 in patient 2), especially the CD8(+) subpopulation (SI = 5.5 and 4.6 in patients 1 and 2, respectively), and NK lymphocytes (SI = 3.9 and 8.5 in patients 1 and 2, respectively) after glatiramer acetate stimulation. This study demonstrates the important role of T(H)1 cells expressing skin-homing receptors in delayed-type hypersensitivity reactions to glatiramer acetate. A lymphocyte transformation test revealed a specific glatiramer acetate recognition by T lymphocytes and NK lymphocytes. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis.

    Science.gov (United States)

    Kuo, Chuan-Hui; Collins, Andrea M; Boettner, Douglas R; Yang, YanFen; Ono, Santa J

    2017-01-15

    Molecules that are necessary for ocular hypersensitivity reactions include the receptors CCR1 and CCR3; CCL7 is a ligand for these receptors. Therefore, we explored the role of CCL7 in mast cell activity and motility in vitro and investigated the requirement for CCL7 in a murine model of IgE-mediated allergic conjunctivitis. For mast cells treated with IgE and Ag, the presence of CCL7 synergistically enhanced degranulation and calcium influx. CCL7 also induced chemotaxis in mast cells. CCL7-deficient bone marrow-derived mast cells showed decreased degranulation following IgE and Ag treatment compared with wild-type bone marrow-derived mast cells, but there was no difference in degranulation when cells were activated via an IgE-independent pathway. In vivo, CCL7 was upregulated in conjunctival tissue during an OVA-induced allergic response. Notably, the early-phase clinical symptoms in the conjunctiva after OVA challenge were significantly higher in OVA-sensitized wild-type mice than in control challenged wild-type mice; the increase was suppressed in CCL7-deficient mice. In the OVA-induced allergic response, the numbers of conjunctival mast cells were lower in CCL7-deficient mice than in wild-type mice. Our results demonstrate that CCL7 is required for maximal OVA-induced ocular anaphylaxis, mast cell recruitment in vivo, and maximal FcεRI-mediated mast cell activation in vitro. A better understanding of the role of CCL7 in mediating ocular hypersensitivity reactions will provide insights into mast cell function and novel treatments for allergic ocular diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  15. α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

    Directory of Open Access Journals (Sweden)

    Sun Y

    2017-07-01

    Full Text Available Yan Sun,1,* Pan-Pan Yang,1,* Zhen-Yuan Song,2 Yu Feng,1 Duan-Min Hu,1 Ji Hu,1 Guang-Yin Xu,3 Hong-Hong Zhang1,3 1Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Endocrinology, The East District of Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 3Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Aim: Patients with long-standing diabetes often demonstrate intestinal dysfunction, characterized as constipation or colonic hypersensitivity. Our previous studies have demonstrated the roles of voltage-gated sodium channels NaV1.7 and NaV1.8 in dorsal root ganglion (DRG in colonic hypersensitivity of rats with diabetes. This study was designed to determine roles of antioxidant α-lipoic acid (ALA on sodium channel activities and colonic hypersensitivity of rats with diabetes. Methods: Streptozotocin was used to induce diabetes in adult female rats. Colonic sensitivity was measured by behavioral responses to colorectal distention in rats. The excitability and sodium channel currents of colon projection DRG neurons labeled with DiI were measured by whole-cell patch-clamp recordings. The expressions of NaV1.7 and NaV1.8 of colon DRGs were measured by western blot analysis. Results: ALA treatment significantly increased distention threshold in responding to colorectal distension in diabetic rats compared with normal saline treatment. ALA treatment also hyperpolarized the resting membrane potentials, depolarized action potential threshold, increased rheobase, and decreased frequency of action potentials evoked by ramp current stimulation. Furthermore, ALA treatment also reduced neuronal sodium current densities of DRG neurons innervating the colon from rats with diabetes. In addition, ALA

  16. Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation.

    Directory of Open Access Journals (Sweden)

    Stéphane Lolignier

    Full Text Available Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using Nav1.9-null mice and Nav1.9 knock-down rats. In mice we found that, although the Nav1.9 channel does not contribute to basal pain thresholds, it plays an important role in heat pain hypersensitivity induced by subacute paw inflammation (intraplantar carrageenan and chronic ankle inflammation (complete Freund's adjuvant-induced monoarthritis. We showed for the first time that Nav1.9 also contributes to mechanical hypersensitivity in both models, as assessed using von Frey and dynamic weight bearing tests. Consistently, antisense-based Nav1.9 gene silencing in rats reduced carrageenan-induced heat and mechanical pain hypersensitivity. While no changes in Nav1.9 mRNA levels were detected in dorsal root ganglia (DRGs during subacute and chronic inflammation, a significant increase in Nav1.9 immunoreactivity was observed in ipsilateral DRGs 24 hours following carrageenan injection. This was correlated with an increase in Nav1.9 immunolabeling in nerve fibers surrounding the inflamed area. No change in Nav1.9 current density could be detected in the soma of retrolabeled DRG neurons innervating inflamed tissues, suggesting that newly produced channels may be non-functional at this level and rather contribute to the observed increase in axonal transport. Our results provide evidence that Nav1.9 plays a crucial role in the generation of heat and mechanical pain hypersensitivity, both in subacute and chronic inflammatory pain models, and bring new elements for the

  17. Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation.

    Science.gov (United States)

    Lolignier, Stéphane; Amsalem, Muriel; Maingret, François; Padilla, Françoise; Gabriac, Mélanie; Chapuy, Eric; Eschalier, Alain; Delmas, Patrick; Busserolles, Jérôme

    2011-01-01

    Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using Nav1.9-null mice and Nav1.9 knock-down rats. In mice we found that, although the Nav1.9 channel does not contribute to basal pain thresholds, it plays an important role in heat pain hypersensitivity induced by subacute paw inflammation (intraplantar carrageenan) and chronic ankle inflammation (complete Freund's adjuvant-induced monoarthritis). We showed for the first time that Nav1.9 also contributes to mechanical hypersensitivity in both models, as assessed using von Frey and dynamic weight bearing tests. Consistently, antisense-based Nav1.9 gene silencing in rats reduced carrageenan-induced heat and mechanical pain hypersensitivity. While no changes in Nav1.9 mRNA levels were detected in dorsal root ganglia (DRGs) during subacute and chronic inflammation, a significant increase in Nav1.9 immunoreactivity was observed in ipsilateral DRGs 24 hours following carrageenan injection. This was correlated with an increase in Nav1.9 immunolabeling in nerve fibers surrounding the inflamed area. No change in Nav1.9 current density could be detected in the soma of retrolabeled DRG neurons innervating inflamed tissues, suggesting that newly produced channels may be non-functional at this level and rather contribute to the observed increase in axonal transport. Our results provide evidence that Nav1.9 plays a crucial role in the generation of heat and mechanical pain hypersensitivity, both in subacute and chronic inflammatory pain models, and bring new elements for the understanding of its

  18. Resolved imaging of the HR 8799 Debris disk with Herschel

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, Brenda; Booth, Mark; Broekhoven-Fiene, Hannah; Marois, Christian [National Research Council of Canada Herzberg Astronomy and Astrophsyics, 5071 W. Saanich Road, Victoria, BC, V9E 2E7 (Canada); Kennedy, Grant; Wyatt, Mark [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Sibthorpe, Bruce [SRON Netherlands Institute for Space Research, P.O. Box 800, NL-9700 AV Groningen (Netherlands); Macintosh, Bruce [Lawrence Livermore National Labs, 7000 East Ave, Livermore, CA 94550 (United States)

    2014-01-01

    We present Herschel far-infrared and submillimeter maps of the debris disk associated with the HR 8799 planetary system. We resolve the outer disk emission at 70, 100, 160, and 250 μm and detect the disk at 350 and 500 μm. A smooth model explains the observed disk emission well. We observe no obvious clumps or asymmetries associated with the trapping of planetesimals that is a potential consequence of planetary migration in the system. We estimate that the disk eccentricity must be <0.1. As in previous work by Su et al., we find a disk with three components: a warm inner component and two outer components, a planetesimal belt extending from 100 to 310 AU, with some flexibility (±10 AU) on the inner edge, and the external halo that extends to ∼2000 AU. We measure the disk inclination to be 26° ± 3° from face-on at a position angle of 64° E of N, establishing that the disk is coplanar with the star and planets. The spectral energy distribution of the disk is well fit by blackbody grains whose semi-major axes lie within the planetesimal belt, suggesting an absence of small grains. The wavelength at which the spectrum steepens from blackbody, 47 ± 30 μm, however, is short compared with other A star debris disks, suggesting that there are atypically small grains likely populating the halo. The PACS longer wavelength data yield a lower disk color temperature than do MIPS data (24 and 70 μm), implying two distinct halo dust-grain populations.

  19. The Homozygote VCPR155H/R155H Mouse Model Exhibits Accelerated Human VCP-Associated Disease Pathology

    Science.gov (United States)

    Nalbandian, Angèle; Llewellyn, Katrina J.; Kitazawa, Masashi; Yin, Hong Z.; Badadani, Mallikarjun; Khanlou, Negar; Edwards, Robert; Nguyen, Christopher; Mukherjee, Jogeshwar; Mozaffar, Tahseen; Watts, Giles; Weiss, John; Kimonis, Virginia E.

    2012-01-01

    Valosin containing protein (VCP) mutations are the cause of hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia (IBMPFD). VCP gene mutations have also been linked to 2% of isolated familial amyotrophic lateral sclerosis (ALS). VCP is at the intersection of disrupted ubiquitin proteasome and autophagy pathways, mechanisms responsible for the intracellular protein degradation and abnormal pathology seen in muscle, brain and spinal cord. We have developed the homozygous knock-in VCP mouse (VCPR155H/R155H) model carrying the common R155H mutations, which develops many clinical features typical of the VCP-associated human diseases. Homozygote VCPR155H/R155H mice typically survive less than 21 days, exhibit weakness and myopathic changes on EMG. MicroCT imaging of the bones reveal non-symmetrical radiolucencies of the proximal tibiae and bone, highly suggestive of PDB. The VCPR155H/R155H mice manifest prominent muscle, heart, brain and spinal cord pathology, including striking mitochondrial abnormalities, in addition to disrupted autophagy and ubiquitin pathologies. The VCPR155H/R155H homozygous mouse thus represents an accelerated model of VCP disease and can be utilized to elucidate the intricate molecular mechanisms involved in the pathogenesis of VCP-associated neurodegenerative diseases and for the development of novel therapeutic strategies. PMID:23029473

  20. The leucine-rich repeat (LRR) protein, CaLRR1, interacts with the hypersensitive induced reaction (HIR) protein, CaHIR1, and suppresses cell death induced by the CaHIR1 protein.

    Science.gov (United States)

    Jung, Ho Won; Hwang, Byung Kook

    2007-07-01

    Leucine-rich repeat proteins (LRRs) function in a number of signal transduction pathways via protein-protein interactions. The gene encoding a small protein of pepper, CaLRR1, is specifically induced upon pathogen challenge and treatment with pathogen-associated molecular patterns (PAMPs). We identified a pepper hypersensitive induced reaction (CaHIR1) protein that interacts with the LRR domain of the CaLRR1 protein using yeast two-hybrid screening. Ectopic expression of the pepper CaHIR1 gene induces cell death in tobacco and Arabidopsis, indicating that the CaHIR1 protein may be a positive regulator of HR-like cell death. Because transformation is very difficult in pepper plants, we over-expressed CaLRR1 and CaHIR1 in Arabidopsis to determine cellular functions of the two genes. The over-expression of the CaHIR1 gene, but not the CaLRR1 gene, in transgenic Arabidopsis confers disease resistance in response to Pseudomonas syringae infection, accompanied by the strong expression of PR genes, the accumulation of both salicylic acid and H(2)O(2), and K(+) efflux in plant cells. In Arabidopsis and tobacco plants over-expressing both CaHIR1 and CaLRR1, the CaLRR1 protein suppresses not only CaHIR1-induced cell death, but also PR gene expression elicited by CaHIR1 via its association with HIR protein. We propose that the CaLRR1 protein functions as a novel negative regulator of CaHIR1-mediated cell death responses in plants.