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Sample records for hypersensitive response reveals

  1. Lipid Profiling of the Arabidopsis Hypersensitive Response Reveals Specific Lipid Peroxidation and Fragmentation Processes: Biogenesis of Pimelic and Azelaic Acid1[C][W

    PubMed Central

    Zoeller, Maria; Stingl, Nadja; Krischke, Markus; Fekete, Agnes; Waller, Frank; Berger, Susanne; Mueller, Martin J.

    2012-01-01

    Lipid peroxidation (LPO) is induced by a variety of abiotic and biotic stresses. Although LPO is involved in diverse signaling processes, little is known about the oxidation mechanisms and major lipid targets. A systematic lipidomics analysis of LPO in the interaction of Arabidopsis (Arabidopsis thaliana) with Pseudomonas syringae revealed that LPO is predominantly confined to plastid lipids comprising galactolipid and triacylglyceride species and precedes programmed cell death. Singlet oxygen was identified as the major cause of lipid oxidation under basal conditions, while a 13-lipoxygenase (LOX2) and free radical-catalyzed lipid oxidation substantially contribute to the increase upon pathogen infection. Analysis of lox2 mutants revealed that LOX2 is essential for enzymatic membrane peroxidation but not for the pathogen-induced free jasmonate production. Despite massive oxidative modification of plastid lipids, levels of nonoxidized lipids dramatically increased after infection. Pathogen infection also induced an accumulation of fragmented lipids. Analysis of mutants defective in 9-lipoxygenases and LOX2 showed that galactolipid fragmentation is independent of LOXs. We provide strong in vivo evidence for a free radical-catalyzed galactolipid fragmentation mechanism responsible for the formation of the essential biotin precursor pimelic acid as well as of azelaic acid, which was previously postulated to prime the immune response of Arabidopsis. Our results suggest that azelaic acid is a general marker for LPO rather than a general immune signal. The proposed fragmentation mechanism rationalizes the pathogen-induced radical amplification and formation of electrophile signals such as phytoprostanes, malondialdehyde, and hexenal in plastids. PMID:22822212

  2. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

    Stern, M.L.; Brown, T.A.; Brown, R.D.; Munson, A.E. )

    1989-09-01

    Isophorone diisocyanate was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 0.1, 0.3, and 1.0% isophorone diisocyanate and challenged with 3.0% isophorone diisocyanate. Doses of isophorone diisocyanate were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of complete Freund's adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity responses to isophorone diisocyanate with or without adjuvant pretreatment.

  3. Hypersensitivity Responses in the Central Nervous System

    PubMed Central

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen; Berg, Carsten Tue; Owens, Trevor

    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. Antibodies and complement have been associated to demyelinating pathology in multiple sclerosis (MS) lesions, where macrophages predominate among infiltrating myeloid cells. Serum-derived autoantibodies with predominant specificity for the astrocyte water channel aquaporin-4 (AQP4) are implicated as inducers 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 with CD4+ T cells, but not with antibodies. By contrast, NMO-like astrocyte and myelin pathology can be transferred to mice with AQP4–IgG from NMO patients. This is dependent on complement, and does not require T cells. Consistent with clinical observations that interferon-beta is ineffective 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 injection of antibody and complement to the CNS, or experimental manipulations to induce BBB breakdown. We here review studies in MS and NMO that elucidate roles for IgG and complement in the induction of BBB breakdown, astrocytopathy, and demyelinating pathology. These studies point to significance of T-independent effector mechanisms in neuroinflammation. PMID:26500654

  4. Hypersensitive response – A biophysical phenomenon of producers

    PubMed Central

    Bashir, Zoobia; Shafique, Sobiya; Anjum, Tehmina; Shafique, Shazia; Akram, Waheed

    2013-01-01

    Hypersensitive response/reaction is a form of the cellular demise frequently linked alongside plant resistance against pathogen infection. Main transducers for this reaction are the intermediates of reactive oxygen and ion fluxes which are plausibly needed for hypersensitive response (Hpr Sen Rsp). An immediate and enormous energy production and its intra-cellular biochemical conduction are imperative for an Hpr Sen Rsp to be occurred. A number of studies proved that there are such diverse types of factors involved in triggering of Hpr Sen Rsp that morphologies of dead cells have become a vast topic of study. Hpr Sen Rsp could play a frolic role in plants as certain programmed cellular disintegrations in other organisms, to restrict pathogen growth. In fact, Hpr Sen Rsp can be involved in all types of tissues and most of the developmental stages. PMID:24265926

  5. Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis

    SciTech Connect

    Zipser, R.D.; Patterson, J.B.; Kao, H.W.; Hauser, C.J.; Locke, R.

    1985-10-01

    Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after ( UC)arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2, PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of UC-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.

  6. Markers for hypersensitive response and senescence show distinct patterns of expression.

    PubMed

    Pontier, D; Gan, S; Amasino, R M; Roby, D; Lam, E

    1999-04-01

    Controlled cellular suicide is an important process that can be observed in various organs during plant development. From the generation of proper sexual organs in monoecious plants to the hypersensitive response (HR) that occurs during incompatible pathogen interactions, programmed cell death (PCD) can be readily observed. Although several biochemical and morphological parameters have been described for various types of cell death in plants, the relationships existing between those different types of PCD events remain unclear. In this work, we set out to examine if two early molecular markers of HR cell death (HIN1 and HSR203J) as well as a senescence marker (SAG12) are coordinately induced during these processes. Our result indicates that although there is evidence of some cross-talk between both cell death pathways, spatial and temporal characteristics of activation for these markers during hypersensitive response and senescence are distinct. These observations indicate that these markers are relatively specific for different cell death programs. Interestingly, they also revealed that a senescence-like process seems to be triggered at the periphery of the HR necrotic lesion. This suggests that cells committed to die during the HR might release a signal able to induce senescence in the neighboring cells. This phenomenon could correspond to the establishment of a second barrier against pathogens. Lastly, we used those cell death markers to better characterize cell death induced by copper and we showed that this abiotic induced cell death presents similarities with HR cell death. PMID:10380810

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

    PubMed

    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. PMID:26708389

  8. Hypersensitivity pneumonitis.

    PubMed Central

    Kaltreider, H B

    1993-01-01

    Although the cause and development of most inflammatory and fibrotic interstitial lung diseases are unknown, both the antigenic stimuli and the immunopathogenic mechanisms that produce the syndrome of hypersensitivity pneumonitis have been well described. Hypersensitivity pneumonitis is a group of related inflammatory and fibrotic interstitial lung diseases that result from hypersensitivity immune reactions to the repeated inhalation of antigens derived from fungal, bacterial, animal protein, and reactive chemical sources. Immune complex-induced inflammatory reactions initiate acute lung injury; T cell-mediated hypersensitivity reactions perpetuate it and induce chronic inflammatory, granulomatous, and fibrotic responses in the interstitium of the lungs. Because the natural history of many interstitial lung diseases of unknown causes involves the progressive evolution through these same phases, knowledge about immune pathogenesis gained from studies of hypersensitivity pneumonitis may provide a way to understand the causes and development of other interstitial lung diseases. Images PMID:8279154

  9. Hypersensitive response of beans to Apion godmani (Coleoptera: Curculionidae).

    PubMed

    Garza, R; Vera, J; Cardona, C; Barcenas, N; Singh, S P

    2001-08-01

    High levels of resistance to Apion godinani Wagner have been reported in bean, Phaseolus vulgaris L., landraces from Mexico. We report on the role of hypersensitivity to A. godmani in five resistant and three susceptible bean genotypes. In susceptible genotypes (cultivars 'Canario 107','Jamapa', and 'Zacatecas 45'), the eggs and first instars of A. godmani were embedded in the pod mesocarp and usually were surrounded by healthy tissue. In contrast, in resistant landraces ('Amarillo 154', 'Amarillo 155', 'J-117', 'Puebla 36', and 'Pinto 168'), necrotic tissues developed concentrically around the oviposition site, encapsulating eggs and dead larvae. An inverse relationship between percentage egg and larval encapsulation at the early immature pod stages and percentage of damaged seeds at harvest was found. Results indicate that hypersensitivity in developing pods plays an important role in antibiosis to A. godmani in beans. This information will facilitate future genetic and biochemical research and provide much needed information concerning the phenotypic basis of resistance to A. godmani in bean. PMID:11561858

  10. Progressively Increased M50 Responses to Repeated Sounds in Autism Spectrum Disorder with Auditory Hypersensitivity: A Magnetoencephalographic Study

    PubMed Central

    Matsuzaki, Junko; Kagitani-Shimono, Kuriko; Sugata, Hisato; Hirata, Masayuki; Hanaie, Ryuzo; Nagatani, Fumiyo; Tachibana, Masaya; Tominaga, Koji; Mohri, Ikuko; Taniike, Masako

    2014-01-01

    The aim of this study was to investigate the differential time-course responses of the auditory cortex to repeated auditory stimuli in children with autism spectrum disorder (ASD) showing auditory hypersensitivity. Auditory-evoked field values were obtained from 21 boys with ASD (12 with and 9 without auditory hypersensitivity) and 15 age-matched typically developing controls. M50 dipole moments were significantly increased during the time-course study only in the ASD with auditory hypersensitivity compared with those for the other two groups. The boys having ASD with auditory hypersensitivity also showed more prolonged response duration than those in the other two groups. The response duration was significantly related to the severity of auditory hypersensitivity. We propose that auditory hypersensitivity is associated with decreased inhibitory processing, possibly resulting from an abnormal sensory gating system or dysfunction of inhibitory interneurons. PMID:25054201

  11. USE OF THE RIBONUCLEASE PROTECTION ASSAY FOR IDENTIFYING CHEMICALS WHICH ELLICIT HYPERSENSITIVITY RESPONSES

    EPA Science Inventory

    Use of the Ribonuclease Protection Assay (RPA) for Identifying Chemicals that Elicit Hypersensitivity Responses. L.M. Plitnick, 1, D.M. Sailstad, 2, and R.J. Smialowicz, 2 1UNC, Curriculum in Toxicology, Chapel Hill, NC and 2USEPA, NHEERL, RTP, NC.

    The incidence of aller...

  12. Influence of Pseudomonas syringae culture conditions on initiation of the hypersensitive response of culture tobacco cells.

    PubMed Central

    Yucel, I; Xiao, Y X; Hutcheson, S W

    1989-01-01

    The inhibitor sensitivity and timing of the ionic response of suspension-cultured tobacco cells were used as a bioassay for the Pseudomonas syringae signal that elicits the hypersensitive response in resistant plants. The ionic response of tobacco cell suspensions inoculated with P. syringae pv. syringae 61 and P. syringae pv. pisi grown in rich media was inhibited by rifampin, tetracycline, and streptomycin during a 2- to 2.5-h induction stage. Coculturing the bacteria with tobacco cells for 3 h or more before inoculating fresh tobacco cells specifically abolished the sensitivity of the ionic response to these inhibitors and reduced the response time of the tobacco cells from 3 to 1 h. The apparent activation of the bacteria during coculture was not dependent on the plant cells and could be achieved by incubating the bacteria in a nitrogen-deficient medium containing a metabolizable carbon source. Addition of proteose peptone and Casamino Acids to this medium suppressed activation of the bacteria. The results suggest that the hypersensitive response-eliciting signal forms late in the induction stage, perhaps as a result of the derepression of some of the P. syringae genes functional in elicitation of the hypersensitive response. The nature of the activated state remains elusive but is consistent with the accumulation of protein(s) whose activity indirectly elicits the ionic response. PMID:2764576

  13. Changes in blastogenic responses of lymphocytes and delayed type hypersensitivity responses after vaccination in dogs.

    PubMed

    Miyamoto, T; Taura, Y; Une, S; Yoshitake, M; Nakama, S; Watanabe, S

    1992-10-01

    To clarify the immunologic effects of vaccination in dogs, we monitored total leukocyte and lymphocyte counts, humoral antibody responses, blastogenic responses of lymphocyte, and delayed type hypersensitivity (DTH) responses after vaccination. Mixed vaccines were administered on day 0 except for canine parvovirus (CPV) vaccine which was readministered on day 21. The puppy and adult dogs had a significant decrease in leukocyte and lymphocyte counts on day 7. The puppies showed a significant increase in the blastogenesis of lymphocytes after each vaccination, whereas the adult dogs had no significant changes. However, the adult dogs were divided into two groups, high responders and low responders in blastogenesis of lymphocytes. The dogs with higher or lower response in SI values on day 0 tended to show decrease or increase after the first vaccination, respectively. Since almost all dogs developed high titers of humoral antibody, it is considered that vaccination acts in an immunomodulative fashion. DTH responses to phytohemagglutinin (PHA) and CPV vaccine monitored at 0, 3, and 8 weeks after the first vaccination produced strong reactions, in particular those to CPV vaccine rose significantly after vaccination and maintained the higher responses for at least 2 months. These results suggest that DTH responses to PHA and CPV vaccine are helpful to monitoring non-specific and specific immune functions in vivo, therefore, DTH could be used as simple and rapid immunologic tests in canine practice. PMID:1420577

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

    PubMed Central

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

    2013-01-01

    Background and Aims 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. Methods 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. Key Results 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 stress hormones, oxidative membrane damage and stomatal closure. Conclusions Necrotic lesion formation triggered by ipt activation closely resembles the hypersensitive response. Cytokinins may thus act as signals and/or mediators in plant defence against pathogen attack. PMID:23644362

  15. Inhibition by Agrobacterium tumefaciens and Pseudomonas savastanoi of development of the hypersensitive response elicited by Pseudomonas syringae pv. phaseolicola.

    PubMed Central

    Robinette, D; Matthysse, A G

    1990-01-01

    Injection into tobacco leaves of biotype 1 Agrobacterium tumefaciens or of Pseudomonas savastanoi inhibited the development of a visible hypersensitive response to the subsequent injection at the same site of Pseudomonas syringae pv. phaseolicola. This interference with the hypersensitive response was not seen with injection of bacterial growth medium or Escherichia coli cells. Live A. tumefaciens cells were required for the inhibitory effect. Various mutants and strains of A. tumefaciens were examined to determine the genes involved. Known chromosomal mutations generally had no effect on the ability of A. tumefaciens to inhibit the hypersensitive response, except for chvB mutants which showed a reduced (but still significant) inhibition of the hypersensitive response. Ti plasmid genes appeared to be required for the inhibition of the hypersensitive response. The bacteria did not need to be virulent in order to inhibit the hypersensitive response. Deletion of the vir region from pTi had no effect on the inhibition. However, the T region of the Ti plasmid was required for inhibition. Studies of transposon mutants suggested that the tms but not tmr or ocs genes were required. These genes were not acting after transfer to plant cells since they were effective in strains lacking vir genes and thus unable to transfer DNA to plant cells. The results suggest that the expression of the tms genes in the bacteria may inhibit the development of the hypersensitive response by the plant. An examination of the genes required in P. savastanoi for the inhibition of the hypersensitive response suggested that bacterial production of auxin was also required for the inhibition of the hypersensitive response by these bacteria. Images PMID:2211508

  16. Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response

    PubMed Central

    Delledonne, Massimo; Zeier, Jrgen; Marocco, Adriano; Lamb, Chris

    2001-01-01

    Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles in the activation of disease resistance mechanisms both in animals and plants. In animals NO cooperates with ROIs to kill tumor cells and for macrophage killing of bacteria. Such cytotoxic events occur because unregulated NO levels drive a diffusion-limited reaction with O2? to generate peroxynitrite (ONOO?), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after interaction of NO not with O2? but with H2O2 generated from O2? by superoxide dismutase. Increasing the level of O2? reduces NO-mediated toxicity, and ONOO? is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O2? dismutation to H2O2 to minimize the loss of NO by reaction with O2? and to trigger hypersensitive cell death through NO/H2O2 cooperation. However, O2? rather than H2O2 is the primary ROI signal for pathogen induction of glutathione S-transferase, and the rates of production and dismutation of O2? generated during the oxidative burst play a crucial role in the modulation and integration of NO/H2O2 signaling in the HR. Thus although plants and animals use a similar repertoire of signals in disease resistance, ROIs and NO are deployed in strikingly different ways to trigger host cell death. PMID:11606758

  17. Studies of delayed hypersensitivity responses in children in an industrialized region of Italy

    SciTech Connect

    La Rosa, M.; Mancuso, G.R.; Greco, D.; Di Paola, M.; Schiliro, G.; Bagnato, G.F.; Bellanti, J.A. )

    1991-06-01

    The purpose of the present study was to evaluate the effects of chronic exposure to chemical pollutants on cell mediated immune responses in a pediatric population living in Priolo, an industrialized area of Italy, by means of skin test (Multitest CMI). The results suggest that children living in Priolo display significantly lower delayed type hypersensitivity (DTH) response than those seen in an age-matched and socioeconomically similar group of children living in Taormina, a nonindustrialized area. The lowered incidence of DTH scores in Priolo is not due to the number of positive skin test responses to individual antigens, but rather to the size of individual reactions.

  18. Sphingolipids as New Biomarkers for Assessment of Delayed-Type Hypersensitivity and Response to Triptolide

    PubMed Central

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

    2012-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:23300675

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

    PubMed

    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 ?rip36 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. PMID:24745046

  20. Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats

    PubMed Central

    Gao, Jun; Wu, Xiaoyin; Owyang, Chung; Li, Ying

    2006-01-01

    The anterior cingulate cortex (ACC) is critically involved in processing the affective component of pain sensation. Visceral hypersensitivity is a characteristic of irritable bowel syndrome. Electrophysiological activity of the ACC with regard to visceral sensitization has not been characterized. Single ACC neuronal activities in response to colorectal distension (CRD) were recorded in control, sham-treated rats and viscerally hypersensitive (EA) rats (induced by chicken egg albumin injection, i.p). The ACC neurones of controls failed to respond to 10 or 30 mmHg CRD; only 22% were activated by 50 mmHg CRD. Among the latter, 16.4% exhibited an excitatory response to CRD and were labelled CRD-excited neurones. In contrast, CRD (10, 30 and 50 mmHg) markedly increased ACC neuronal responses of EA rats (10%, 28% and 47%, respectively). CRD produced greater pressure-dependent increases in ACC spike firing rates in EA rats compared with controls. Splanchnicectomy combined with pelvic nerve section abolished ACC responses to CRD in EA rats. Spontaneous activity in CRD-excited ACC neurones was significantly higher in EA rats than in controls. CRD-excited ACC neurones in control and EA rats (7 of 16 (42%) and 8 of 20 (40%), respectively) were activated by transcutaneous electrical and thermal stimuli. However, ACC neuronal activity evoked by noxious cutaneous stimuli did not change significantly in EA rats. This study identifies CRD-responsive neurones in the ACC and establishes for the first time that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization, characterized by increased spontaneous activity of CRD-excited neurones, decreased CRD pressure threshold, and increased response magnitude. Enhanced ACC nociceptive transmission in viscerally hypersensitive rats is restricted to visceral afferent input. PMID:16239277

  1. Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity.

    PubMed

    Wilson, A D

    2014-11-01

    Horses are affected by a wide variety of arthropod ectoparasites, ranging from lice which spend their entire life on the host, through ticks which feed over a period of days, to numerous biting insects that only transiently visit the host to feed. The presence of ectoparasites elicits a number of host responses including innate inflammatory responses, adaptive immune reactions and altered behaviour; all of which can reduce the severity of the parasite burden. All of these different responses are linked through immune mechanisms mediated by mast cells and IgE antibodies which have an important role in host resistance to ectoparasites, yet immune responses also cause severe pathological reactions. One of the best described examples of such pathological sequelae is insect bite hypersensitivity (IBH) of horses; an IgE-mediated type 1 hypersensitivity to the salivary proteins of Culicoides spp. associated with T-helper-2 production of IL4 and IL13. Importantly, all horses exposed to Culicoides have an expanded population of Culicoides antigen-specific T cells with this pattern of cytokine production, but in those which remain healthy, the inflammatory reaction is tempered by the presence of FoxP3+ CD4+ regulatory T cells that express IL10 and TGF-beta, which suppresses the IL4 production by Culicoides antigen-activated T cells. PMID:25180696

  2. Transcriptomic Analysis of Prunus domestica Undergoing Hypersensitive Response to Plum Pox Virus Infection

    PubMed Central

    Rodamilans, Bernardo; San Len, David; Mhlberger, Louisa; Candresse, Thierry; Neumller, Michael; Oliveros, Juan Carlos; Garca, 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. PMID:24959894

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

    PubMed

    Rodamilans, Bernardo; San Len, David; Mhlberger, Louisa; Candresse, Thierry; Neumller, Michael; Oliveros, Juan Carlos; Garca, 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. PMID:24959894

  4. ROLE FOR MIP-2, MIP-1 AND IL-1 IN DELAYED TYPE HYPERSENSITIVITY RESPONSE TO VIRAL ANTIGEN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Balb/c mice sensitized to HSV-1 develop a vigorous delayed type hypersensitivity (DTH) response upon intradermal virus antigen challenge. Although CD4+ T cells are a key mediator of this response, neutrophils are the most abundant cells at the antigen challenge site both initially and at the peak o...

  5. Sternotomy infection: poor prediction by acute phase response and delayed hypersensitivity.

    PubMed

    Ulicny, K S; Hiratzka, L F; Williams, R B; Grunkemeier, G L; Flege, J B; Wright, C B; Callard, G M; Mitts, D L; Dunn, E J

    1990-12-01

    Two hundred twenty-one consecutive adult cardiac surgical patients were examined prospectively for nutritional protein state, acute phase protein response, and delayed hypersensitivity reaction in an attempt to identify patients at high risk for the development of sternal wound infection, which occurred in 6 patients (2.7%). There was no significant correlation between preoperative nutritional protein concentrations (retinol-binding protein, prealbumin, and transferrin) and acute phase protein levels (C-reactive protein, alpha 1-acid glycoprotein, and complements B and C3), nor a statistically significant relationship between nutritional state or acute phase protein response and the development of sternal infection. Preoperative complement C3 levels were elevated, however, in 80.0% of those in whom sternal infections developed compared with 30.6% of those with well-healed wounds. Similarly, postoperative concentrations of alpha 1-acid glycoprotein were elevated in 80.0% of those in whom sternal infections developed compared with 28.6% of those with well-healed wounds. There was no correlation between delayed hypersensitivity and the risk of sternal infection, nor between preoperative nutritional protein and acute phase protein values. Seventy-three percent of patients were anergic on postoperative day 2. Stepwise logistic regression showed that age, body weight, preoperative intensive care unit stay, repeat median sternotomy, internal mammary artery grafting, postoperative hemorrhage, and postoperative cardiac arrest correlated with the development of sternal infection, whereas transfusion requirement, reexploration for bleeding, and the operation performed did not. We conclude that routine delayed hypersensitivity testing is of no value in predicting high-risk cardiac surgical patients when the anergy battery is placed on the preoperative day. Although statistically insignificant, possibly due to the small number of patients in whom sternal infection developed in this study (type II error), a larger study might find preoperative complement C3 and post-operative alpha 1-acid glycoprotein levels to be predictive of patients at risk for the development of sternal wound infection. The final logistic model for the predicted risk 2%) of sternal wound infection is: PREDSWC = exp(EQ)/1 + exp(EQ) where EQ = (0.38 x age) + (0.24 x weight) + (5.42 x preop ICU) + (4.39 x redo) + (7.14 x IMA) + (4.49 x hemorrhage) + (8.81 x arrest) - 62.72, and where preop ICU, redo, hemorrhage, and arrest are defined as yes (1) or no (0), IMA-is defined as 0, 1, or 2, age is in years, and weight is in kilograms. PMID:1700683

  6. Interleukin-12 reverses the inhibitory impact of photodynamic therapy (PDT) on the murine contact hypersensitivity response

    NASA Astrophysics Data System (ADS)

    Simkin, Guillermo O.; Levy, Julia G.; Hunt, David W. C.

    1998-05-01

    Treatment of mice with certain photosensitizers combined with exposure to visible light limits the development of the immunologically-mediated contact hypersensitivity (CHS) response against topically-applied chemical haptens. Understanding of the inhibitory action of photosensitizers upon the CHS response is incomplete. Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin), a photosensitizer with immunomodulatory activity, strongly depressed CHS responses to the hapten dinitrofluorobenzene (DNFB). However, if mice were administered 1 (mu) g of a recombinant preparation of the pro- inflammatory cytokine interleukin-12 (rIL-12), full-fledged CHS responses to DNFB ensued in animals treated with BPD-MA and light. In contrast, when rIL-12 was given in combination with an anti-IL-12 antibody the restorative effect of rIL-12 on the CHS response of PDT-treated mice was blocked. Evaluation of the cytokine status of spleen and draining lymph node cells showed for DNFB painted animals, that the release of the immunosuppressive cytokine IL-10 was increased by PDT and rIL-12 counter-acted the increase in IL-10 liberation associated with PDT. These studies indicate that IL-10 formation is upregulated and the availability of IL-12 may be limited in mice treated with PDT. These features may contribute to deficient CHS responses observed with PDT.

  7. A connected set of genes associated with programmed cell death implicated in controlling the hypersensitive response in maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rp1-D21 is a maize auto-active resistance gene that confers a spontaneous hypersensitive response (HR). Depending on the genetic background in which it operates; variable levels of HR are observed. This offers a convenient system to identify alleles that modulate HR and genes involved in disease res...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. The Diamine Oxidase Gene Is Associated with Hypersensitivity Response to Non-Steroidal Anti-Inflammatory Drugs

    PubMed Central

    Agndez, Jos A. G.; Ayuso, Pedro; Cornejo-Garca, Jos A.; Blanca, Miguel; Torres, Mara J.; Doa, Inmaculada; Salas, Mara; Blanca-Lpez, Natalia; Canto, Gabriela; Rondon, Carmen; Campo, Paloma; Laguna, Jos J.; Fernndez, Javier; Martnez, Carmen; Garca-Martn, Elena

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR ?=?1.7 (95% CI ?=?1.32.1; Pc ?=?0.0003) with a gene-dose effect (P?=?0.0001). The association was replicated in two populations from different geographic areas (Pc ?=?0.008 and Pc ?=?0.004, respectively). Conclusions and implications The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response. PMID:23152756

  10. Disruption of Microtubular Cytoskeleton Induced by Cryptogein, an Elicitor of Hypersensitive Response in Tobacco Cells1

    PubMed Central

    Binet, Marie-Noëlle; Humbert, Claude; Lecourieux, David; Vantard, Marylin; Pugin, Alain

    2001-01-01

    The dynamics of microtubular cytoskeleton were studied in tobacco (Nicotiana tabacum cv Xanthi) cells in response to two different plant defense elicitors: cryptogein, a protein secreted by Phytophthora cryptogea and oligogalacturonides (OGs), derived from the plant cell wall. In tobacco plants cryptogein triggers a hypersensitive-like response and induces systemic resistance against a broad spectrum of pathogens, whereas OGs induce defense responses, but fail to trigger cell death. The comparison of the microtubule (MT) dynamics in response to cryptogein and OGs in tobacco cells indicates that MTs appear unaffected in OG-treated cells, whereas cryptogein treatment caused a rapid and severe disruption of microtubular network. When hyperstabilized by the MT depolymerization inhibitor, taxol, the MT network was still disrupted by cryptogein treatment. On the other hand, the MT-depolymerizing agent oryzalin and cryptogein had different and complementary effects. In addition to MT destabilization, cryptogein induced the death of tobacco cells, whereas OG-treated cells did not die. We demonstrated that MT destabilization and cell death induced by cryptogein depend on calcium influx and that MT destabilization occurs independently of active oxygen species production. The molecular basis of cryptogein-induced MT disruption and its potential significance with respect to cell death are discussed. PMID:11161014

  11. PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity

    SciTech Connect

    Nelson, T.A.; Holmes, S.; Alekseyenko, A.V.; Shenoy, M.; DeSantis, T.; Wu, C.H.; Andersen, G.L.; Winston, J.; Sonnenburg, J.; Pasricha, P.J.; Spormann, A.

    2010-12-01

    Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.

  12. Putative Serine Protease Effectors of Clavibacter michiganensis Induce a Hypersensitive Response in the Apoplast of Nicotiana Species.

    PubMed

    Lu, You; Hatsugai, Noriyuki; Katagiri, Fumiaki; Ishimaru, Carol A; Glazebrook, Jane

    2015-11-01

    Clavibacter michiganensis subspp. michiganensis and sepedonicus cause diseases on solanaceous crops. The genomes of both subspecies encode members of the pat-1 family of putative serine proteases known to function in virulence on host plants and induction of hypersensitive responses (HR) on nonhosts. One gene of this family in C. michiganensis subsp. sepedonicus, chp-7, is required for triggering HR in Nicotiana tabacum. Here, further investigation revealed that mutation of the putative catalytic serine residue at position 232 to threonine abolished the HR induction activity of Chp-7, suggesting that enzymatic activity is required. Purified Chp-7 triggered an HR in N. tabacum leaves in the absence of the pathogen, indicating Chp-7 itself is the HR elicitor from C. michiganensis subsp. sepedonicus. Ectopic expression of chp-7 constructs in N. tabacum leaves revealed that Chp-7 targeted to the apoplast triggered an HR while cytoplasmic Chp-7 did not, indicating that Chp-7 induces the HR in the apoplast of N. tabacum leaves. Chp-7 also induced HR in N. sylvestris, a progenitor of N. tabacum, but not in other Nicotiana species tested. ChpG, a related protein from C. michiganensis subsp. michiganensis, also triggered HR in N. tabacum and N. sylvestris. Unlike Chp-7, ChpG triggered HR in N. clevelandii and N. glutinosa. PMID:26075829

  13. Does electromagnetic hypersensitivity originate from nocebo responses? Indications from a qualitative study.

    PubMed

    Dieudonné, Maël

    2016-01-01

    Idiopathic Environmental Intolerance attributed to Electromagnetic Fields (IEI-EMF) is a condition in which symptoms are attributed to electromagnetic field (EMF) exposure. As electro-hypersensitive (EHS) people have repeatedly been observed, during provocation trials, to report symptoms following perceived rather than actual exposure, the hypothesis has been put forward that IEI-EMF originates from psychological mechanisms, especially nocebo responses. This paper examines this hypothesis, using data from a qualitative study aimed at understanding how EHS people come to regard themselves as such. Forty self-diagnosed EHS people were interviewed. A typified model of their attribution process was then elaborated, inductively, from their narratives. This model is linear and composed of seven stages: (1) onset of symptoms; (2) failure to find a solution; (3) discovery of EHS; (4) gathering of information about EHS; (5) implicit appearance of conviction; (6) experimentation; (7) conscious acceptance of conviction. Overall, symptoms appear before subjects start questioning effects of EMF on their health, which is not consistent with the hypothesis that IEI-EMF originates from nocebo responses to perceived EMF exposure. However, such responses might occur at the sixth stage of the process, potentially reinforcing the attribution. It remains possible that some cases of IEI-EMF originate from other psychological mechanisms. Bioelectromagnetics. 37:14-24, 2016. © 2015 Wiley Periodicals, Inc. PMID:26369906

  14. Pathogen-induced elicitin production in transgenic tobacco generates a hypersensitive response and nonspecific disease resistance.

    PubMed Central

    Keller, H; Pamboukdjian, N; Ponchet, M; Poupet, A; Delon, R; Verrier, J L; Roby, D; Ricci, P

    1999-01-01

    The rapid and effective activation of disease resistance responses is essential for plant defense against pathogen attack. These responses are initiated when pathogen-derived molecules (elicitors) are recognized by the host. We have developed a strategy for creating novel disease resistance traits whereby transgenic plants respond to infection by a virulent pathogen with the production of an elicitor. To this end, we generated transgenic tobacco plants harboring a fusion between the pathogen-inducible tobacco hsr 203J gene promoter and a Phytophthora cryptogea gene encoding the highly active elicitor cryptogein. Under noninduced conditions, the transgene was silent, and no cryptogein could be detected in the transgenic plants. In contrast, infection by the virulent fungus P. parasitica var nicotianae stimulated cryptogein production that coincided with the fast induction of several defense genes at and around the infection sites. Induced elicitor production resulted in a localized necrosis that resembled a P. cryptogea-induced hypersensitive response and that restricted further growth of the pathogen. The transgenic plants displayed enhanced resistance to fungal pathogens that were unrelated to Phytophthora species, such as Thielaviopsis basicola, Erysiphe cichoracearum, and Botrytis cinerea. Thus, broad-spectrum disease resistance of a plant can be generated without the constitutive synthesis of a transgene product. PMID:9927640

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

    PubMed Central

    Gustavsson, Mikael B.; Backhaus, Thomas; Andersson, Mats X.

    2015-01-01

    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. PMID:26734506

  16. Serotonin attenuates biotic stress and leads to lesion browning caused by a hypersensitive response to Magnaporthe oryzae penetration in rice.

    PubMed

    Hayashi, Keiko; Fujita, Yoshikatsu; Ashizawa, Taketo; Suzuki, Fumihiko; Nagamura, Yoshiaki; Hayano-Saito, Yuriko

    2016-01-01

    The hypersensitive response (HR) of plants is one of the earliest responses to prevent pathogen invasion. A brown dot lesion on a leaf is visual evidence of the HR against the blast fungus Magnaporthe oryzae in rice, but tracking the browning process has been difficult. In this study, we induced the HR in rice cultivars harboring the blast resistance gene Pit by inoculation of an incompatible M. oryzae strain, which generated a unique resistance lesion with a brown ring (halo) around the brown fungal penetration site. Inoculation analysis using a plant harboring Pit but lacking an enzyme that catalyzes tryptamine to serotonin showed that high accumulation of the oxidized form of serotonin was the cause of the browning at the halo and penetration site. Our analysis of the halo browning process in the rice leaf revealed that abscisic acid enhanced biosynthesis of serotonin under light conditions, and serotonin changed to the oxidized form via hydrogen peroxide produced by light. The dramatic increase in serotonin, which has a high antioxidant activity, suppressed leaf damage outside the halo, blocked expansion of the browning area and attenuated inhibition of plant growth. These results suggest that serotonin helps to reduce biotic stress in the plant by acting as a scavenger of oxygen radicals to protect uninfected tissues from oxidative damage caused by the HR. The deposition of its oxide at the HR lesion is observed as lesion browning. PMID:26603141

  17. Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses.

    PubMed

    Sawada, Yu; Honda, Tetsuya; Hanakawa, Sho; Nakamizo, Satoshi; Murata, Teruasa; Ueharaguchi-Tanada, Yuri; Ono, Sachiko; Amano, Wataru; Nakajima, Saeko; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Kitoh, Akihiko; Dainichi, Teruki; Ogawa, Narihito; Kobayashi, Yuichi; Yokomizo, Takehiko; Arita, Makoto; Nakamura, Motonobu; Miyachi, Yoshiki; Kabashima, Kenji

    2015-10-19

    Resolvin E1 (RvE1) is a lipid mediator derived from ?3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID:26438363

  18. Highly sensitive determination of transient generation of biophotons during hypersensitive response to cucumber mosaic virus in cowpea.

    PubMed

    Kobayashi, Masaki; Sasaki, Kensuke; Enomoto, Masaru; Ehara, Yoshio

    2007-01-01

    The hypersensitive response (HR) is one mechanism of the resistance of plants to pathogen infection. It involves the generation of reactive oxygen species (ROS) which have crucial roles in signal transduction or as toxic agents leading to cell death. Often, ROS generation is accompanied by an ultraweak photon emission resulting from radical reactions that are initiated by ROS through the oxidation of living materials such as lipids, proteins, and DNA. This photon emission, referred to as 'biophotons', is extremely weak, but, based on the technique of photon counting imaging, a system has been developed to analyse the spatiotemporal properties of photon emission. Using this system, the dynamics of photon emission which might be associated with the oxidative burst, which promotes the HR, have been determined. Here, the transient generation of biophotons is demonstrated during the HR process in cowpea elicited by cucumber mosaic virus. The distinctive dynamics in spatiotemporal properties of biophoton emission during the HR expression on macroscopic and microscopic levels are also described. This study reveals the involvement of ROS generation in biophoton emission in the process of HR through the determination of the inhibitory effect of an antioxidant (Tiron) on biophoton emission. PMID:17158510

  19. Highly sensitive determination of transient generation of biophotons during hypersensitive response to cucumber mosaic virus in cowpea.

    TOXLINE Toxicology Bibliographic Information

    Kobayashi M; Sasaki K; Enomoto M; Ehara Y

    2007-01-01

    The hypersensitive response (HR) is one mechanism of the resistance of plants to pathogen infection. It involves the generation of reactive oxygen species (ROS) which have crucial roles in signal transduction or as toxic agents leading to cell death. Often, ROS generation is accompanied by an ultraweak photon emission resulting from radical reactions that are initiated by ROS through the oxidation of living materials such as lipids, proteins, and DNA. This photon emission, referred to as 'biophotons', is extremely weak, but, based on the technique of photon counting imaging, a system has been developed to analyse the spatiotemporal properties of photon emission. Using this system, the dynamics of photon emission which might be associated with the oxidative burst, which promotes the HR, have been determined. Here, the transient generation of biophotons is demonstrated during the HR process in cowpea elicited by cucumber mosaic virus. The distinctive dynamics in spatiotemporal properties of biophoton emission during the HR expression on macroscopic and microscopic levels are also described. This study reveals the involvement of ROS generation in biophoton emission in the process of HR through the determination of the inhibitory effect of an antioxidant (Tiron) on biophoton emission.

  20. Structural basis of metal hypersensitivity

    PubMed Central

    Wang, Yang

    2014-01-01

    Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). ?? T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific ?? T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101, DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells. PMID:22983897

  1. Molecular characterization of Pvr9 that confers a hypersensitive response to Pepper mottle virus (a potyvirus) in Nicotiana benthamiana.

    PubMed

    Tran, Phu-Tri; Choi, Hoseong; Choi, Doil; Kim, Kook-Hyung

    2015-07-01

    There are some R genes against potyviruses which were mapped in pepper. However, none of them has been characterized at the molecular level. In this study, we characterized Pvr9 which is an Rpi-blb2 ortholog from pepper and confers a hypersensitive response to Pepper mottle virus (PepMoV) in a transient expression system in Nicotiana benthamiana. This gene putatively encoded for 1298 amino acids and is located on pepper chromosome 6. PepMoV NIb was the elicitor of the Pvr9-mediated hypersensitive response. NIb from several other potyviruses also elicited the hypersensitive response. Inoculation of pepper with PepMoV resulted in a minor increase in Pvr9 transcription in the resistant cultivar CM334 and a slight down-regulation in the susceptible cultivar Floral Gem. The 5' upstream region of Pvr9 from cultivar CM334 had higher transcription activity than the region from cultivar Floral Gem. The cultivars CM334 and Floral Gem had non-functional Pvr9 homologs with loss-of-function mutations. PMID:25776758

  2. Glutathione and tryptophan metabolism are required for Arabidopsis immunity during the hypersensitive response to hemibiotrophs.

    PubMed

    Hiruma, Kei; Fukunaga, Satoshi; Bednarek, Pawel; Pislewska-Bednarek, Mariola; Watanabe, Satoshi; Narusaka, Yoshihiro; Shirasu, Ken; Takano, Yoshitaka

    2013-06-01

    The hypersensitive response (HR) is a type of strong immune response found in plants that is accompanied by localized cell death. However, it is unclear how HR can block a broad range of pathogens with different infective modes. In this study, we report that ?-glutamylcysteine synthetase GSH1, which is critical for glutathione biosynthesis, and tryptophan (Trp) metabolism contribute to HR and block development of fungal pathogens with hemibiotrophic infective modes. We found that GSH1 is involved in the penetration2 (PEN2)-based entry control of the nonadapted hemibiotroph Colletotrichum gloeosporioides. However, Arabidopsis mutants specifically defective in entry control terminated further growth of the pathogen in the presence of HR cell death, whereas gsh1 mutants supported pathogen invasive growth in planta, demonstrating the requirement of GSH1 for postinvasive nonhost resistance. Remarkably, on the basis of the phenotypic and metabolic analysis of Arabidopsis mutants defective in Trp metabolism, we showed that biosynthesis of Trp-derived phytochemicals is also essential for resistance to C. gloeosporioides during postinvasive HR. By contrast, GSH1 and these metabolites are likely to be dispensable for the induction of cell death during postinvasive HR. Furthermore, the resistance to Ralstonia solanacearum 1/resistance to Pseudomonas syringae 4 dual Resistance gene-dependent immunity of Arabidopsis to the adapted hemibiotroph shared GSH1 and cytochromes P450 CYP79B2/CYP79B3 with postinvasive nonhost resistance, whereas resistance to P. syringae pv. maculicola 1 and resistance to P. syringae 2-based Resistance gene resistance against bacterial pathogens did not. These data suggest that the synthesis of glutathione and Trp-derived metabolites during HR play crucial roles in terminating the invasive growth of both nonadapted and adapted hemibiotrophs. PMID:23696664

  3. Nitrate efflux is an essential component of the cryptogein signaling pathway leading to defense responses and hypersensitive cell death in tobacco.

    PubMed

    Wendehenne, David; Lamotte, Olivier; Frachisse, Jean-Marie; Barbier-Brygoo, Hlne; Pugin, Alain

    2002-08-01

    There is much interest in the transduction pathways by which avirulent pathogens or derived elicitors activate plant defense responses. However, little is known about anion channel functions in this process. The aim of this study was to reveal the contribution of anion channels in the defense response triggered in tobacco by the elicitor cryptogein. Cryptogein induced a fast nitrate (NO(3)(-)) efflux that was sensitive to anion channel blockers and regulated by phosphorylation events and Ca(2+) influx. Using a pharmacological approach, we provide evidence that NO(3)(-) efflux acts upstream of the cryptogein-induced oxidative burst and a 40-kD protein kinase whose activation seems to be controlled by the duration and intensity of anion efflux. Moreover, NO(3)(-) efflux inhibitors reduced and delayed the hypersensitive cell death triggered by cryptogein in tobacco plants. This was accompanied by a delay or a complete suppression of the induction of several defense-related genes, including hsr203J, a gene whose expression is correlated strongly with programmed cell death in plants. Our results indicate that anion channels are involved intimately in mediating defense responses and hypersensitive cell death. PMID:12172032

  4. Glucocorticoid effects on contact hypersensitivity and on the cutaneous response to ultraviolet light in the mouse

    SciTech Connect

    Ross, P.M.; Walberg, J.A.; Bradlow, H.L.

    1988-03-01

    A single exposure to 254 nm ultraviolet irradiation (UV) can systemically suppress experimental sensitization to the simple allergen 2,4-dinitro, 1-chlorobenzene (DNCB) in the mouse. We show here that topical application at the site of irradiation of the 21-oic acid methyl ester derivative of the synthetic glucocorticoid triamcinolone acetonide (TAme) prevents UV suppression of sensitization. That is, mice painted with TAme at the site of UV exposure developed normal contact hypersensitivity (CH); mice exposed to UV only, like mice treated with the parent compound triamcinolone acetonide (TA), failed to be sensitized by DNCB applied to a distal site. TAme is inactivated rapidly by plasma esterases, so its effect is thought to be confined to the skin. Apparently, TAme blocked the cutaneous signal(s) for systemic suppression of CH. Histologically, irradiated skin exhibited mild inflammation and hyperproliferation, but these effects were greatly exaggerated and prolonged in the UV + TAme-treated skin, independent of sensitization at the distal site. The infiltrate consisted mostly of neutrophils and lacked the round cells characteristic of cell-mediated immunity. Apparently, normal immune suppression by UV prevented this vigorous reaction to irradiated skin. Applied together with DNCB. TAme blocked sensitization. It also prevented response to challenge by DNCB in previously sensitized animals. However, unlike the parent compound triamcinolone acetonide (TA), Budesonide or Beclomethasone diproprionate, each of which can penetrate the epidermis in active form, TAme had no effect on sensitization when applied at a distal site. Likewise, TAme did not affect plasma B (17-desoxycortisol) levels, whereas the other three compounds reduced plasma B tenfold, as expected of compounds causing adrenal-pituitary suppression.

  5. Context of action of Proline Dehydrogenase (ProDH) in the Hypersensitive Response of Arabidopsis

    PubMed Central

    2014-01-01

    Background Proline (Pro) dehydrogenase (ProDH) potentiates the oxidative burst and cell death of the plant Hypersensitive Response (HR) by mechanisms not yet elucidated. ProDH converts Pro into ?1 pyrroline-5-carboxylate (P5C) and can act together with P5C dehydrogenase (P5CDH) to produce Glu, or with P5C reductase (P5CR) to regenerate Pro and thus stimulate the Pro/P5C cycle. To better understand the effects of ProDH in HR, we studied the enzyme at three stages of the defense response differing in their ROS and cell death levels. In addition, we tested if ProDH requires P5CDH to potentiate HR. Results Control and infected leaves of wild type and p5cdh plants were used to monitor ProDH activity, in vivo Pro catabolism, amino acid content, and gene expression. Wild type plants activated ProDH at all HR stages. They did not consume Pro during maximal ROS accumulation, and maintained almost basal P5C levels at all conditions. p5cdh mutants activated ProDH as wild type plants. They achieved maximum oxidative burst and cell death levels producing normal HR lesions, but evidenced premature defense activation. Conclusion ProDH activation has different effects on HR. Before the oxidative burst it leads to Pro consumption involving the action of P5CDH. During the oxidative burst, ProDH becomes functionally uncoupled to P5CDH and apparently works with P5CR. The absence of P5CDH does not reduce ROS, cell death, or pathogen resistance, indicating this enzyme is not accompanying ProDH in the potentiation of these defense responses. In contrast, p5cdh infected plants displayed increased ROS burst and earlier initiation of HR cell death. In turn, our results suggest that ProDH may sustain HR by participating in the Pro/P5C cycle, whose action on HR must be formally evaluated in a future. PMID:24410747

  6. ?2?-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

    PubMed Central

    Patel, Ryan; Bauer, Claudia S.; Nieto-Rostro, Manuela; Margas, Wojciech; Ferron, Laurent; Chaggar, Kanchan; Crews, Kasumi; Ramirez, Juan D.; Bennett, David L. H.; Schwartz, Arnold; Dickenson, Anthony H.

    2013-01-01

    The ?2?-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and is also the therapeutic target of gabapentinoid drugs. It is therefore likely to play a key role in the development of neuropathic pain. In this study, we have examined mice in which ?2?-1 gene expression is disrupted, to determine whether ?2?-1 is involved in various modalities of nociception, and for the development of behavioral hypersensitivity after partial sciatic nerve ligation (PSNL). We find that naive ?2?-1?/? mice show a marked behavioral deficit in mechanical and cold sensitivity, but no change in thermal nociception threshold. The lower mechanical sensitivity is mirrored by a reduced in vivo electrophysiological response of dorsal horn wide dynamic range neurons. The CaV2.2 level is reduced in brain and spinal cord synaptosomes from ?2?-1?/? mice, and ?2?-1?/? DRG neurons exhibit lower calcium channel current density. Furthermore, a significantly smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL, ?2?-1?/? mice show delayed mechanical hypersensitivity, which only develops at 11 d after surgery, whereas in wild-type littermates it is maximal at the earliest time point measured (3 d). There is no compensatory upregulation of ?2?-2 or ?2?-3 after PSNL in ?2?-1?/? mice, and other transcripts, including neuropeptide Y and activating transcription factor-3, are upregulated normally. Furthermore, the ability of pregabalin to alleviate mechanical hypersensitivity is lost in PSNL ?2?-1?/? mice. Thus, ?2?-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. PMID:24133248

  7. ?2?-1 gene deletion affects somatosensory neuron function and delays mechanical hypersensitivity in response to peripheral nerve damage.

    PubMed

    Patel, Ryan; Bauer, Claudia S; Nieto-Rostro, Manuela; Margas, Wojciech; Ferron, Laurent; Chaggar, Kanchan; Crews, Kasumi; Ramirez, Juan D; Bennett, David L H; Schwartz, Arnold; Dickenson, Anthony H; Dolphin, Annette C

    2013-10-16

    The ?2?-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and is also the therapeutic target of gabapentinoid drugs. It is therefore likely to play a key role in the development of neuropathic pain. In this study, we have examined mice in which ?2?-1 gene expression is disrupted, to determine whether ?2?-1 is involved in various modalities of nociception, and for the development of behavioral hypersensitivity after partial sciatic nerve ligation (PSNL). We find that naive ?2?-1(-/-) mice show a marked behavioral deficit in mechanical and cold sensitivity, but no change in thermal nociception threshold. The lower mechanical sensitivity is mirrored by a reduced in vivo electrophysiological response of dorsal horn wide dynamic range neurons. The CaV2.2 level is reduced in brain and spinal cord synaptosomes from ?2?-1(-/-) mice, and ?2?-1(-/-) DRG neurons exhibit lower calcium channel current density. Furthermore, a significantly smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL, ?2?-1(-/-) mice show delayed mechanical hypersensitivity, which only develops at 11 d after surgery, whereas in wild-type littermates it is maximal at the earliest time point measured (3 d). There is no compensatory upregulation of ?2?-2 or ?2?-3 after PSNL in ?2?-1(-/-) mice, and other transcripts, including neuropeptide Y and activating transcription factor-3, are upregulated normally. Furthermore, the ability of pregabalin to alleviate mechanical hypersensitivity is lost in PSNL ?2?-1(-/-) mice. Thus, ?2?-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. PMID:24133248

  8. Prevention of the induction of allospecific cytotoxic T lymphocyte and delayed-type hypersensitivity responses by ultraviolet irradiation of corneal allografts

    SciTech Connect

    Niederkorn, J.Y.; Callanan, D.; Ross, J.R. )

    1990-08-01

    The effect of ultraviolet radiation (UVR) on the immunogenicity of corneal allografts was examined in a mouse model. Corneal allografts differing from the host at the entire MHC and multiple minor H loci were subjected to 200 mJ/cm2 of UVB irradiation immediately prior to heterotropic transplantation. Analysis of cytotoxic T lymphocyte and delayed-type hypersensitivity responses revealed that UVR treated corneal grafts failed to induce either CTL or DTH responses in C57BL/6 recipients. UVB treatment abolished the immunogenicity of highly immunogenic corneal grafts containing either resident or infiltrating donor-specific Langerhans cells. Sequential grafting experiments demonstrated that UVB-treated grafts rendered the hosts anergic to subsequent immunization with highly immunogenic corneal limbus grafts that contained dense concentrations of Ia+ Langerhans cells of donor origin. The results indicate that UV treatment not only reduces the immunogenicity of the corneal allograft but may also render it tolerogenic.

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

    PubMed Central

    Plessis, Anne; Cournol, Raphal; Effroy, Delphine; Silva Prez, Viridiana; Botran, Lucy; Kraepiel, Yvan; Frey, Anne; Sotta, Bruno; Cornic, Gabriel; Leung, Jeffrey; Giraudat, Jrme; 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

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

    PubMed Central

    2012-01-01

    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 (110?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 (110?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 (30300??M) 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. Conclusions Taken together, these results suggest that a brief treatment with oxaliplatin or its metabolite oxalate is sufficient to enhance the responsiveness of TRPA1 but not that of TRPM8 and TRPV1 expressed by DRG neurons, which may contribute to the characteristic acute peripheral neuropathy induced by oxaliplatin. PMID:22839205

  11. Purification and Characterization of a Novel Hypersensitive Response-Inducing Elicitor from Magnaporthe oryzae that Triggers Defense Response in Rice

    PubMed Central

    Chen, Mingjia; Zeng, Hongmei; Qiu, Dewen; Guo, Lihua; Yang, Xiufen; Shi, Huaixing; Zhou, Tingting; Zhao, Jing

    2012-01-01

    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. PMID:22624059

  12. Laryngeal hypersensitivity in chronic cough.

    PubMed

    Hull, J H; Menon, A

    2015-12-01

    Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. Patients with cough and laryngeal hypersensitivity frequently report features that overlap other laryngeal dysfunction syndromes, including a tendency for the vocal cords to inappropriately adduct. The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field. PMID:26325433

  13. Hypersensitivity pneumonitis

    PubMed Central

    Lacasse, Yves; Cormier, Yvon

    2006-01-01

    Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the subject has been previously sensitized. The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 30:100,000 and HP accounted for less than 2% of these cases. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence respectively, using simple diagnostic criteria. Chest X-rays may be normal in active HP; High Resolution Computed Tomography is sensitive but not specific for the diagnosis of HP. The primary use of pulmonary function tests is to determine the physiologic abnormalities and the associated impairment. Despite the pitfalls of false positive and false negatives, antigen-specific IgG antibodies analysis can be useful as supportive evidence for HP. Bronchoalveolar lavage plays an important role in the investigation of patients suspected of having HP. A normal number of lymphocytes rules out all but residual disease. Surgical lung biopsy should be reserved for rare cases with puzzling clinical presentation or for verification the clinical diagnosis when the clinical course or response to therapy is unusual. Being an immune reaction in the lung, the most obvious treatment of HP is avoidance of contact with the offending antigen. Systemic corticosteroids represent the only reliable pharmacologic treatment of HP but do not alter the long-term outcome. The use of inhaled steroids is anecdotal. Treatment of chronic or residual disease is supportive. PMID:16817954

  14. Role of dendritic cell-mediated abnormal immune response in visceral hypersensitivity

    PubMed Central

    Li, Meng; Zhang, Lu; Lu, Bin; Chen, Zhe; Chu, Li; Meng, Lina; Fan, Yihong

    2015-01-01

    The role of dendritic cells (DCs) in irritable bowel syndrome (IBS) is unclear. This study tested the hypothesis that intestinal DCs induced visceral hypersensitivity in IBS rats through mast cell (MC) activation. The IBS rat model was established by combining colorectal distension with restraint stress. The number of CD103-positive cells in colon was higher in the IBS group. Expression of PAR-2, IL-4 and IL-9 in the colonic mucosa was higher in the IBS group. Mesenteric lymph node DCs (MLNDCs) and splenic CD4+/CD8+ T cells were isolated and purified by a magnetic labeling-based technique; they were cultured alone or co-cultured (T4+DC/T8+DC). The coculture of MLNDCs and CD4+ T cells had the highest IL-4 secretion in the IBS group, while IL-9 expression was higher in the cultures containing CD8+ T cells. Our findings indicate that an increased number of DCs in the colon stimulated CD4+ T cells to secrete high levels of IL-4, which led to the activation of MCs and subsequently resulted in visceral hypersensitivity. PMID:26550249

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

    PubMed

    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. PMID:23291850

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. CgDN3: an essential pathogenicity gene of colletotrichum gloeosporioides necessary to avert a hypersensitive-like response in the host Stylosanthes guianensis.

    PubMed

    Stephenson, S A; Hatfield, J; Rusu, A G; Maclean, D J; Manners, J M

    2000-09-01

    A gene of Colletotrichum gloeosporioides that is induced by nitrogen starvation in axenic culture and is expressed at the early stages of infection of the host Stylosanthes guianensis has been identified and its role in pathogenicity tested. The sequence of this gene, named CgDN3, indicated that it encodes a protein of 74 amino acids that contains a predicted 18 amino acid signal sequence for secretion of a basic 54 amino acid mature protein with weak homology to an internal region of plant wall-associated receptor kinases. Mutants of C. gloeosporioides were produced by homologous recombination in which part of the coding sequence and promoter region of the CgDN3 gene was replaced with a hygromycin-resistance gene cassette. Mutations in the CgDN3 gene were confirmed in two independent transformants and Northern (RNA) analysis demonstrated the disrupted CgDN3 gene was not expressed. The mutants had faster mycelial growth rates in vitro but produced spores that germinated to form appressoria normally on the leaf surface. However, the CgDN3 mutants were unable to infect and reproduce on intact host leaves. Microscopic analysis revealed small clusters of necrotic host cells at inoculation sites on leaves, suggesting that these mutants elicited a localized, host hypersensitive-like response. The mutants were able to grow necrotrophically and reproduce on leaves when conidia were inoculated directly onto wound sites. The putative promoter region of the CgDN3 gene was fused to a gene encoding a modified jellyfish green fluorescent protein and introduced into the fungus. Following inoculation, strong expression of green fluorescent protein was observed in primary infection vesicles in infected epidermal cells with weaker expression evident in hyphae growing within infected leaf tissue. These findings indicate that CgDN3 encodes a novel pathogenicity determinant associated with the biotrophic phase of primary infection and required to avert a hypersensitive-like response by a compatible host. PMID:10975650

  18. Hypersensitivity pneumonitis.

    PubMed

    Ando, M; Suga, M

    1997-09-01

    There are 30 or more groups of hypersensitivity pneumonitis (HP), such as farmer's lung, bird fancier's disease, humidifier lung, air-conditioner disease, and summer-type HP. Regardless of the causative agent or its environmental setting, the pathogenesis and clinical manifestations of the groups are similar. Immune-complex formation and complement activation might play a role during the early inflammatory phase of the disease. Much evidence, however, supports a more important role of T-cell-mediated delayed-type hypersensitivity reaction than humoral hyperresponsiveness in the development of the disease. High-resolution CT findings, a striking increase in the number of T cells in bronchoalveolar lavage fluids, and the presence of specific IgG and IgA antibodies to the causative antigens in the patient's serum samples are helpful in differentiating HP from other interstitial lung diseases. Management and treatment involve avoidance of antigen exposure and occasional use of corticosteroid therapy. PMID:9331543

  19. Capsaicin-sensitive cough receptors in lower airway are responsible for cough hypersensitivity in patients with upper airway cough syndrome

    PubMed Central

    Yu, Li; Xu, Xianghuai; Wang, Lan; Yang, Zhongmin; L, Hanjing; Qiu, Zhongmin

    2013-01-01

    Background Cough hypersensitivity may be related to the pathogenesis of upper airway cough syndrome (UACS). The purpose of the study was to investigate the role of capsaicin-sensitive cough receptors on the laryngopharynx and lower airway in the cough hypersensitivity of patients with UACS. Material/Methods 59 patients with UACS, 33 patients with rhinitis/sinusitis without cough, and 39 healthy volunteers were recruited for the study. Cough threshold C5, defined as the lowest concentration of capsaicin required for the induction of ?5 coughs upon esposure to capsaicin, were determined at baseline and after laryngopharngeal anesthesia with lidocaine in all the subjects. After induced sputum cytology, the concentrations of histamine, prostaglandin E2 (PGE2), and calcitonin-gene-related peptide (CGPR) in the induced sputum were measured by ELISA. In 15 patients with UACS, sputum cytology and measurement of the above mediators were repeated after successful therapy. Results C5 response to capsaicin was significantly lower in the UACS group than in the rhinitis/sinusitis group and healthy control groups [3.9 (0.98, 7.8) ?mol/L vs. 7.8 (3.9, 93.75) ?mol/L vs. 31.2 (15.6, 62.5) ?mol/L, H=40.12, P=0.000]. Laryngopharngeal anesthesia with lidocaine dramatically increased C5 to capsaicin in the subjects of all 3 groups by a similar degree, but the increase in the UACS group was still the lowest, with an increased level of histamine, PGE2, and CGRP in the induced sputum. When cough resolved with the treatment of cetirizine alone or in combination with erythromycin, the levels of CGRP and histamine in the induced sputum decreased significantly in 15 patients with UACS, with no obvious change in cell differential or concentration of PGE2 in the induced sputum. Conclusions Laryngeal TRPV1 plays an important role in cough sensitivity, but sensitization of capsaicin-sensitive cough receptors in the lower airway may be more responsible for the cough hypersensitivity in patients with UACS. PMID:24296694

  20. Irisflorentin modifies properties of mouse bone marrow-derived dendritic cells and reduces the allergic contact hypersensitivity responses.

    PubMed

    Fu, Ru-Huei; Tsai, Chia-Wen; Tsai, Rong-Tzong; Liu, Shih-Ping; Chan, Tzu-Min; Ho, Yu-Chen; Lin, Hsin-Lien; Chen, Yue-Mi; Hung, Huey-Shan; Chiu, Shao-Chih; Tsai, Chang-Hai; Wang, Yu-Chi; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2015-01-01

    Irisflorentin is an isoflavone component derived from the roots of Belamcanda chinensis (L.) DC. In traditional Chinese medicine, this herb has pharmacological properties to treat inflammatory disorders. Dendritic cells (DCs) are crucial modulators for the development of optimal T-cell immunity and maintenance of tolerance. Aberrant activation of DCs can induce harmful immune responses, and so agents that effectively improve DC properties have great clinical value. We herein investigated the effects of irisflorentin on lipopolysaccharide (LPS)-stimulated maturation of mouse bone marrow-derived DCs in vitro and in the contact hypersensitivity response (CHSR) in vivo. Our results demonstrated that treatment with up to 40 ?M irisflorentin does not cause cellular toxicity. Irisflorentin significantly lessened the proinflammatory cytokine production (tumor necrosis factor-?, interleukin-6, and interleukin-12p70) by LPS-stimulated DCs. Irisflorentin also inhibited the expression of LPS-induced major histocompatibility complex class II and costimulatory molecules (CD40 and CD86) on LPS-stimulated DCs. In addition, irisflorentin diminished LPS-stimulated DC-elicited allogeneic T-cell proliferation. Furthermore, irisflorentin significantly interfered with LPS-induced activation of I?B kinase, c-Jun N-terminal kinase, and p38, as well as the nuclear translocation of NF-?B p65. Subsequently, treatment with irisflorentin obviously weakened 2,4-dinitro-1-fluorobenzene-induced delayed-type hypersensitivity. These findings suggest new insights into the role of irisflorentin as an immunotherapeutic adjuvant through its capability to modulate the properties of DCs. PMID:25654487

  1. Use of Mutant-Assisted Gene Identification and Characterization (MAGIC) to identify novel genetic loci that modify the maize hypersensitive response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The partially-dominant, autoactive maize disease resistance gene Rp1-D21 causes hypersensitive response (HR) lesions to form spontaneously on the leaves and stem in the absence of pathogen recognition. The maize nested association mapping (NAM) population consists of 25 200-line subpopulations each...

  2. If photoinhibition of soybean photosystem II enhances the hypersensitive response, it is not solely due to blockage of electron transfer flow at D1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have suggested that photoinhibition, through inactivation of photosystem II (PSII), could be beneficial to plants during defense to pathogens through enhanced reactive oxygen (ROS), especially during the hypersensitive response (HR). In this study, we addressed this question by focu...

  3. A MYB Transcription Factor Regulates Very-Long-Chain Fatty Acid Biosynthesis for Activation of the Hypersensitive Cell Death Response in Arabidopsis[W][OA

    PubMed Central

    Raffaele, Sylvain; Vailleau, Fabienne; Lger, Amandine; Joubs, Jrme; Miersch, Otto; Huard, Carine; Ble, Elisabeth; Mongrand, Sbastien; Domergue, Frdric; Roby, Dominique

    2008-01-01

    Plant immune responses to pathogen attack include the hypersensitive response (HR), a form of programmed cell death occurring at invasion sites. We previously reported on Arabidopsis thaliana MYB30, a transcription factor that acts as a positive regulator of a cell death pathway conditioning the HR. Here, we show by microarray analyses of Arabidopsis plants misexpressing MYB30 that the genes encoding the four enzymes forming the acyl-coA elongase complex are putative MYB30 targets. The acyl-coA elongase complex synthesizes very-long-chain fatty acids (VLCFAs), and the accumulation of extracellular VLCFA-derived metabolites (leaf epidermal wax components) was affected in MYB30 knockout mutant and overexpressing lines. In the same lines, a lipid extraction procedure allowing high recovery of sphingolipids revealed changes in VLCFA contents that were amplified in response to inoculation. Finally, the exacerbated HR phenotype of MYB30-overexpressing lines was altered by the loss of function of the acyl-ACP thioesterase FATB, which causes severe defects in the supply of fatty acids for VLCFA biosynthesis. Based on these findings, we propose a model in which MYB30 modulates HR via VLCFAs by themselves, or VLCFA derivatives, as cell death messengers in plants. PMID:18326828

  4. Delayed hypersensitivity responses to human IgG and methylated bovine serum albumin are regulated by different mechanisms.

    PubMed Central

    Clark, C; Dalmasso, A P

    1982-01-01

    We found marked differences in in vitro and in vivo delayed hypersensitivity (DH) responses to human IgG (human gamma-globulin, HGG) and methylated bovine serum albumin (MeBSA). Lymph node cells (LNC) from cyclophosphamide (CY) pretreated, antigen-adjuvant immunized mice exhibited increased HGG-induced and decreased MeBSA-induced proliferative responses in vitro compared with LNC from similarly immunized but non-CY-pretreated animals. These effects were antigen-specific. Further, treatment of CY-HGG-adjuvant immunized mice with aqueous (aq) HGG either before or after immunization markedly suppressed HGG-specific in vitro proliferation and in vivo DH responses. Therefore, induction of suppression by aqHGG did not appear to depend on CY-sensitive cells either as a possible source of suppressor cell precursors or as participants in the regulatory events. In contrast, in vivo DH reactivity to MeBSA was unaffected by administration of aqMeBSA either before or after mice were immunized with CY-MeBSA-adjuvant. Our results suggest that DH responses to HGG and MeBSA are regulated by distinct mechanisms which influence the induction and the development of sensitivity. PMID:7118159

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

    PubMed Central

    stn, Suayib; Bartetzko, Verena; Brnke, Frederik

    2015-01-01

    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. PMID:26284106

  6. Adducts of Oxylipin Electrophiles to Glutathione Reflect a 13 Specificity of the Downstream Lipoxygenase Pathway in the Tobacco Hypersensitive Response

    PubMed Central

    Davoine, Cline; Falletti, Olivier; Douki, Thierry; Iacazio, Gilles; Ennar, Najla; Montillet, Jean-Luc; Triantaphylids, Christian

    2006-01-01

    The response to reactive electrophile species (RES) is now considered as part of the plant response to pathogen and insect attacks. Thanks to a previously established high-performance liquid chromatography tandem mass spectrometry methodology, we have investigated the production of oxylipin RES adducts to glutathione (GSH) during the hypersensitive response (HR) of plants. We have observed that RES conjugation to GSH in tobacco (Nicotiana tabacum) leaves is facile and nonspecific. In cryptogein-elicited tobacco leaves, we show that the oxylipin RES adducts to GSH are produced in correlation with GSH consumption, increase in glutathione S-transferase activity, and the appearance of the cell death symptoms. In this model, the adducts arise mainly from the downstream 13 lipoxygenase (LOX) metabolism, although the induced 9 LOX pathway leads massively to the accumulation of upstream metabolites. The main adducts were obtained from 2-hexenal and 12-oxo-phytodienoic acid. They accumulate transiently as 1-hexanol-3-GSH, a reduced adduct, and 12-oxo-phytodienoic acid-GSH, respectively. RES conjugation does not initiate cell death but explains part of the GSH depletion that accompanies HR cell death. The nature of these GSH conjugates shows the key role played by the 13 LOX pathway in RES signaling in the tobacco HR. PMID:16500992

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

    PubMed

    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, the early phase, the late phase and the chronic phase and these three phases correspond temporally with early (acute and sub acute), late and very late stent thrombosis. Bioabsorbable allergy free poly lactic acid self expanding stents, nickel free stainless steel materials, stent coverage with nitric oxide donors and antibodies with endothelial progenitor cell capturing abilities as well as stents eluting anti-inflammatory and anti-allergic agents might be the solution of this so feared and devastating stent complication. PMID:21700348

  8. Gene expression in Brassica campestris showing a hypersensitive response to the incompatible pathogen Xanthomonas campestris pv. vitians.

    PubMed

    Collinge, D B; Milligan, D E; Dow, J M; Scofield, G; Daniels, M J

    1987-09-01

    Xanthomonas campestris pv. vitians, a pathogen of lettuce, elicits a hypersensitive response within 12 hours of inoculation into Brassica leaves, characterized by tissue collapse, loss of membrane integrity, vein blockage and melanin production. In contrast, the compatible pathogen, X. c. pv. campestris, has no visible effects on leaves for 48 hours, after which inoculated areas show chlorosis which eventually spreads, followed by rotting.mRNA was prepared from leaves inoculated with suspensions of both pathovars or with sterile medium up to 24 hours following inoculation. In vitro translation of total and poly A(+) RNA in rabbit reticulocyte lysate in the presence of (35)S methionine followed by separation of the polypeptide products by 2D-PAGE, allowed comparison of the effects of these treatments on plant gene expression. Major changes in gene expression were observed as a consequence of the inoculation technique. In addition, after inoculation with X. c. vitians, up to fifteen additional major polypeptides appeared or greatly increased by four hours. Some of these had disappeared by nine hours and several more had appeared. No major polypeptides disappeared or decreased greatly in intensity following inoculation with X. c. vitians. PMID:24301262

  9. A Connected Set of Genes Associated with Programmed Cell Death Implicated in Controlling the Hypersensitive Response in Maize

    PubMed Central

    Olukolu, Bode A.; Negeri, Adisu; Dhawan, Rahul; Venkata, Bala P.; Sharma, Pankaj; Garg, Anshu; Gachomo, Emma; Marla, Sandeep; Chu, Kevin; Hasan, Anna; Ji, Jiabing; Chintamanani, Satya; Green, Jason; Shyu, Chi-Ren; Wisser, Randall; Holland, James; Johal, Guri; Balint-Kurti, Peter

    2013-01-01

    Rp1-D21 is a maize auto-active resistance gene conferring a spontaneous hypersensitive response (HR) of variable severity depending on genetic background. We report an association mapping strategy based on the Mutant Assisted Gene Identification and Characterization approach to identify naturally occurring allelic variants associated with phenotypic variation in HR. Each member of a collection of 231 diverse inbred lines of maize constituting a high-resolution association mapping panel were crossed to a parental stock heterozygous for Rp1-D21, and the segregating F1 generation testcrosses were evaluated for phenotypes associated with lesion severity for 2 years at two locations. A genome-wide scan for associations with HR was conducted with 47,445 SNPs using a linear mixed model that controlled for spurious associations due to population structure. Since the ability to identify candidate genes and the resolution of association mapping are highly influenced by linkage disequilibrium (LD), we examined the extent of genome-wide LD. On average, marker pairs separated by >10 kbp had an r2 value of <0.1. Genomic regions surrounding SNPs significantly associated with HR traits were locally saturated with additional SNP markers to establish local LD structure and precisely identify candidate genes. Six significantly associated SNPs at five loci were detected. At each locus, the associated SNP was located within or immediately adjacent to candidate causative genes predicted to play significant roles in the control of programmed cell death and especially in ubiquitin pathway-related processes. PMID:23222653

  10. Genetics of resistance to the geminivirus, Bean dwarf mosaic virus, and the role of the hypersensitive response in common bean.

    PubMed

    Seo, Y-S; Gepts, P; Gilbertson, R L

    2004-03-01

    Bean dwarf mosaic virus (BDMV) is a single-stranded DNA virus (genus: Begomovirus, family: Geminiviridae) that infects common bean ( Phaseolus vulgaris L.) and causes stunted plant growth, and mosaic and mottle symptoms in leaves. BDMV shows differential pathogenicity in common bean, infecting germplasm of the Andean gene pool (e.g., the snap bean cultivar Topcrop), but not that of the Middle American gene pool (e.g., the pinto bean cultivar Othello). Resistance to BDMV in Othello is associated with development of a hypersensitive response (HR) in vascular (phloem) tissues. In this study, Middle American germplasm representing the four recognized races (i.e., Durango, Guatemala, Jalisco, and Mesoamerica) and the parents of Othello were inoculated with BDMV and a BDMV-green fluorescent protein (GFP) reporter. All genotypes showed partial or complete resistance to BDMV and BDMV-GFP, indicating the widespread distribution of resistance in the Middle American gene pool. A number of BDMV-resistant germplasm did not show the HR, indicating it is not correlated with resistance. In the F(1), F(2), and F(3) of reciprocal crosses between Othello and Topcrop, a single dominant allele, Bdm, conferred BDMV resistance. PMID:14625673

  11. Constitutively active Pto induces a Prf-dependent hypersensitive response in the absence of avrPto.

    PubMed Central

    Rathjen, J P; Chang, J H; Staskawicz, B J; Michelmore, R W

    1999-01-01

    Resistance in tomato to Pseudomonas syringae pv tomato (avrPto) is conferred by the gene Pto in a gene-for-gene relationship. A hypersensitive disease resistance response (HR) is elicited when Pto and avrPto are expressed experimentally within the same plant cell. The kinase capability of Pto was required for AvrPto-dependent HR induction. Systematic mutagenesis of the activation segment of Pto kinase confirmed the homologous P+1 loop as an AvrPto-binding determinant. Specific amino acid substitutions in this region led to constitutive induction of HR upon expression in the plant cell in the absence of AvrPto. Constitutively active Pto mutants required kinase capability for activity, and were unable to interact with proteins previously shown to bind to wild-type Pto. The constitutive gain-of-function phenotype was dependent on a functional Prf gene, demonstrating activation of the cognate disease resistance pathway and precluding a role for Prf upstream of Pto. PMID:10369664

  12. Hypersensitive response and acyl?homoserine lactone production of the fire blight antagonists Erwinia tasmaniensis and Erwinia billingiae

    PubMed Central

    Jakovljevic, Vladimir; Jock, Susanne; Du, Zhiqiang; Geider, Klaus

    2008-01-01

    Summary Fire blight caused by the Gram?negative bacterium Erwinia amylovora can be controlled by antagonistic microorganisms. We characterized epiphytic bacteria isolated from healthy apple and pear trees in Australia, named Erwinia tasmaniensis, and the epiphytic bacterium Erwinia billingiae from England for physiological properties, interaction with plants and interference with growth of E. amylovora. They reduced symptom formation by the fire blight pathogen on immature pears and the colonization of apple flowers. In contrast to E. billingiae, E. tasmaniensis strains induced a hypersensitive response in tobacco leaves and synthesized levan in the presence of sucrose. With consensus primers deduced from lsc as well as hrpL, hrcC and hrcR of the hrp region of E. amylovora and of related bacteria, these genes were successfully amplified from E. tasmaniensis DNA and alignment of the encoded proteins to other Erwinia species supported a role for environmental fitness of the epiphytic bacterium. Unlike E. tasmaniensis, the epiphytic bacterium E. billingiae produced an acyl?homoserine lactone for bacterial cell?to?cell communication. Their competition with the growth of E. amylovora may be involved in controlling fire blight. PMID:21261861

  13. A Genome-Wide Association Study of the Maize Hypersensitive Defense Response Identifies Genes That Cluster in Related Pathways

    PubMed Central

    Venkata, Bala P.; Marla, Sandeep; Ji, Jiabing; Gachomo, Emma; Chu, Kevin; Negeri, Adisu; Benson, Jacqueline; Nelson, Rebecca; Bradbury, Peter; Nielsen, Dahlia; Holland, James B.; Balint-Kurti, Peter J.; Johal, Gurmukh

    2014-01-01

    Much remains unknown of molecular events controlling the plant hypersensitive defense response (HR), a rapid localized cell death that limits pathogen spread and is mediated by resistance (R-) genes. Genetic control of the HR is hard to quantify due to its microscopic and rapid nature. Natural modifiers of the ectopic HR phenotype induced by an aberrant auto-active R-gene (Rp1-D21), were mapped in a population of 3,381 recombinant inbred lines from the maize nested association mapping population. Joint linkage analysis was conducted to identify 32 additive but no epistatic quantitative trait loci (QTL) using a linkage map based on more than 7000 single nucleotide polymorphisms (SNPs). Genome-wide association (GWA) analysis of 26.5 million SNPs was conducted after adjusting for background QTL. GWA identified associated SNPs that colocalized with 44 candidate genes. Thirty-six of these genes colocalized within 23 of the 32 QTL identified by joint linkage analysis. The candidate genes included genes predicted to be in involved programmed cell death, defense response, ubiquitination, redox homeostasis, autophagy, calcium signalling, lignin biosynthesis and cell wall modification. Twelve of the candidate genes showed significant differential expression between isogenic lines differing for the presence of Rp1-D21. Low but significant correlations between HR-related traits and several previously-measured disease resistance traits suggested that the genetic control of these traits was substantially, though not entirely, independent. This study provides the first system-wide analysis of natural variation that modulates the HR response in plants. PMID:25166276

  14. Chronic hypersensitivity pneumonitis caused by Saccharopolyspora rectivirgula is not associated with a switch to a Th2 response.

    PubMed

    Andrews, Kelly; Ghosh, Manik C; Schwingshackl, Andreas; Rapalo, Gabriel; Luellen, Charlean; Waters, Christopher M; Fitzpatrick, Elizabeth A

    2016-03-01

    Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease results in alveolitis and granuloma formation and may progress to a chronic form associated with fibrosis; a greater understanding of the immunopathogenic mechanisms leading to chronic HP is needed. We used the Saccharopolyspora rectivirgula (SR) mouse model of HP to determine the extent to which a switch to a Th2-type immune response is associated with chronic HP. Exposure of wild-type (WT) and tlr2/9(-/-) mice to SR for 14 wk resulted in neutrophilic and lymphocytic alveolitis that was not dependent on Toll-like receptors (TLRs) 2 and 9. Long-term exposure of WT mice to SR resulted in a significant increase in collagen deposition, protein leakage, and IL-1? accompanied by a decrease in quasistatic compliance and total lung capacity compared with unexposed mice. This was associated with an increase in IL-17 but not IL-4 production or recruitment of Th2 cells. tlr2/9(-/-) mice exhibited an increase in protein leakage but less IL-1? and collagen deposition in the lungs compared with WT mice, yet they still displayed a decrease in quasistatic compliance, although total lung capacity was not affected. These mice exhibited an increase in both IL-13 and IL-17, which suggests that IL-13 may ameliorate some of the lung damage caused by long-term SR exposure. Our results suggest that lung pathology following long-term SR exposure in WT mice is associated with the IL-17 response and that TLRs 2 and 9 may inhibit the development of the IL-13/Th2 response. PMID:26719148

  15. Delayed-type hypersensitivity.

    PubMed

    Luo, Y; Dorf, M E

    2001-05-01

    Delayed-type hypersensitivity (DTH) is an in vivo assay of cell-mediated immune function. DTH reactions are often divided into two phases: the sensitization phase, referring to the initial immunization with specific antigen, and the efferent or challenge phase of the DTH response, which usually follows 6 to 14 days after sensitization. This unit details the protocol for stimulating DTH responses in mice to the O-succinimide ester of the hapten 4-hydroxy-3-nitrophenyl acetyl (abbreviated NP-O-Su). PMID:18432796

  16. Genes at Human Chromosome 5q31.1 Regulate Delayed Type Hypersensitivity Responses Associated with Leishmania chagasi Infection

    PubMed Central

    Jeronimo, Selma M. B.; Holst, Ashlee K. B.; Jamieson, Sarra E.; Francis, Richard; Martins, Daniella R. A.; Ettinger, Nicholas; Nascimento, Eliana T.; Miller, E. Nancy; Cordell, Heather J.; Duggal, Priya; Beaty, Terri H.; Blackwell, Jenefer M.; Wilson, Mary E.

    2008-01-01

    Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to disease, clusters in families, and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3-q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH?; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analysed for association with DTH+/? status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH+ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P=0.005; 95% CI=1.28-3.97) and TGFBI (OR 1.94; P=0.003; 95% CI=1.24-3.03). VL child/parent trios gave no evidence of linkage and association, but the DTH? phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P=0.006; 95% CI=1.38-7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P=0.042; 95% CI=1.04-8.65). These results indicate several genes in the immune response gene cluster at 5q23.3-q31.1 influence outcomes of L. chagasi infection in this region of Brazil. PMID:17713557

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

    PubMed Central

    Lee, Seonghee; Ishiga, Yasuhiro; Clermont, Kristen

    2013-01-01

    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. PMID:23638370

  18. Hypersensitive response to Potato virus Y in potato cultivar Srpo Mira is conferred by the Ny-Smira gene located on the long arm of chromosome IX.

    PubMed

    Tomczy?ska, Iga; Jupe, Florian; Hein, Ingo; Marczewski, Waldemar; Sliwka, Jadwiga

    2014-01-01

    Potato virus Y (PVY, Potyvirus) is the fifth most important plant virus worldwide in terms of economic and scientific impact. It infects members of the family Solanaceae and causes losses in potato, tomato, tobacco, pepper and petunia production. In potato and its wild relatives, two types of resistance genes against PVY have been identified. While Ry genes confer symptomless extreme resistance, Ny genes cause a hypersensitive response visible as local necrosis that may also be able to prevent the virus from spreading under certain environmental conditions. The potato cultivar Srpo Mira originates from Hungary and is highly resistant to PVY, although the source of this resistance remains unknown. We show that cv. Srpo Mira reacts with a hypersensitive response leading to necrosis after PVY(NTN) infection in detached leaf, whole plant and grafting assays. The hypersensitivity to PVY(NTN) segregated amongst 140 individuals of tetraploid progeny of cvs. Srpo MiraנMaris Piper in a 1:1 ratio, indicating that it was conferred by a single, dominant gene in simplex. Moreover, we identified five DNA markers linked to this trait and located the underlying locus (Ny-Smira) to the long arm of potato chromosome IX. This position corresponds to the location of the Ry chc and Ny-1 genes for PVY resistance. A simple PCR marker, located 1cM from the Ny-Smira gene, can be recommended for selection of PVY-resistant progeny of cv. Srpo Mira. PMID:25076838

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

    PubMed

    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. PMID:25187258

  20. A conserved proline residue in Dothideomycete Avr4 effector proteins is required to trigger a Cf-4-dependent hypersensitive response.

    PubMed

    Mesarich, Carl H; Stergiopoulos, Ioannis; Beenen, Henriek G; Cordovez, Viviane; Guo, Yanan; Karimi Jashni, Mansoor; Bradshaw, Rosie E; de Wit, Pierre J G M

    2016-01-01

    CfAvr4, a chitin-binding effector protein produced by the Dothideomycete tomato pathogen Cladosporium fulvum, protects the cell wall of this fungus against hydrolysis by secreted host chitinases during infection. However, in the presence of the Cf-4 immune receptor of tomato, CfAvr4 triggers a hypersensitive response (HR), which renders the pathogen avirulent. Recently, several orthologues of CfAvr4 have been identified from phylogenetically closely related species of Dothideomycete fungi. Of these, DsAvr4 from Dothistroma septosporum also triggers a Cf-4-dependent HR, but CaAvr4 and CbAvr4 from Cercospora apii and Cercospora beticola, respectively, do not. All, however, bind chitin. To identify the region(s) and specific amino acid residue(s) of CfAvr4 and DsAvr4 required to trigger a Cf-4-dependent HR, chimeric and mutant proteins, in which specific protein regions or single amino acid residues, respectively, were exchanged between CfAvr4 and CaAvr4 or DsAvr4 and CbAvr4, were tested for their ability to trigger an HR in Nicotiana benthamiana plants transgenic for the Cf-4 immune receptor gene. Based on this approach, a single region common to CfAvr4 and DsAvr4 was determined to carry a conserved proline residue necessary for the elicitation of this HR. In support of this result, a Cf-4-dependent HR was triggered by mutant CaAvr4 and CbAvr4 proteins carrying an arginine-to-proline substitution at this position. This study provides the first step in deciphering how Avr4 orthologues from different Dothideomycete fungi trigger a Cf-4-dependent HR. PMID:25845605

  1. PS3, a semisynthetic beta-1,3-glucan sulfate, diminishes contact hypersensitivity responses through inhibition of L- and P-selectin functions.

    PubMed

    Alban, Susanne; Ludwig, Ralf J; Bendas, Gerd; Schn, Michael P; Oostingh, Gertie J; Radeke, Heinfried H; Fritzsche, Juliane; Pfeilschifter, Josef; Kaufmann, Roland; Boehncke, Wolf-Henning

    2009-05-01

    Leukocyte extravasation is initiated by an interaction of selectin adhesion molecules and appropriate carbohydrate ligands. Targeting those interactions seems a promising approach to treat chronic inflammation. We developed a beta-1, 3-glucan sulfate (PS3) with inhibitory activity toward L and P-selectins under static conditions. Here, detailed investigation showed inhibition of P- and L-selectins, but not E-selectin under flow conditions (relative reduction of interaction with appropriate ligands to 34.4+/-16.6, 8.5+/-3.6, or 99.5+/-9.9%, respectively, by PS3 for P-, L- or E-selectin). Intravital microscopy revealed reduction of leukocyte rolling in skin microvasculature from 22.7+/-5.0 to 12.6+/-4.0% after injection of PS3. In the next experiments, mice were sensitized with 2,4,-dinitrofluorobenzene (DNFB), and lymphocytes were transferred into syngeneic recipients, which were challenged by DNFB. Inflammatory responses were reduced when immunity was generated in mice treated with PS3 or in L-selectin-deficient mice. No effect was observed when L-selectin-deficient donor mice were treated with PS3, further suggesting that PS3 acted primarily through inhibition of L-selectin. Elicitation of a contact hypersensitivity response was reduced in P-selectin-deficient and in PS3-treated mice. Again, PS3 had no effect in P-selectin-deficient mice. PS3 is a potent P- and L-selectin inhibitor that may add to the therapy of inflammatory diseases. PMID:19052560

  2. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein.

    PubMed

    Morrison, R P; Belland, R J; Lyng, K; Caldwell, H D

    1989-10-01

    Chlamydia trachomatis infection of humans is commonly a localized inflammation that can result in infertility, blindness, and perhaps arthritis. The pathogenic process(es) that cause these sequelae are thought to be immunological. A 57-kD protein that is common among Chlamydia elicits ocular inflammation when introduced onto the conjunctivae of guinea pigs or nonhuman primates previously sensitized by chlamydial infection. This protein is thought to mediate the immunopathology that follows chlamydial infection. To more thoroughly characterize this chlamydial component, we cloned its gene from a C. psittaci strain and identified a particular recombinant that produced the 57-kD polypeptide. The recombinant gene product was immunoreactive with a monospecific anti-57-kD serum, and elicited an ocular inflammation similar to that produced by the 57-kD antigen isolated from chlamydiae. Sequencing identified two ORFs that encode polypeptides of 11.2 and 58.1 kD and are co-transcribed. These two polypeptides show homology with Escherichia coli groE and Coxiella burnetii htp heat-shock proteins. Striking homology (greater than 50%) was found between the 57-kD protein and the HtpB, GroEL, 65-k Mycobacterium tuberculosis and Hsp60 proteins. Thus, the 57-kD chlamydial protein, previously implicated as mediating a deleterious immunologic response to chlamydial infections, is a stress-induced protein similar to those that occur universally in both prokaryotic and eukaryotic organisms. PMID:2571668

  3. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein

    PubMed Central

    1989-01-01

    Chlamydia trachomatis infection of humans is commonly a localized inflammation that can result in infertility, blindness, and perhaps arthritis. The pathogenic process(es) that cause these sequelae are thought to be immunological. A 57-kD protein that is common among Chlamydia elicits ocular inflammation when introduced onto the conjunctivae of guinea pigs or nonhuman primates previously sensitized by chlamydial infection. This protein is thought to mediate the immunopathology that follows chlamydial infection. To more thoroughly characterize this chlamydial component, we cloned its gene from a C. psittaci strain and identified a particular recombinant that produced the 57-kD polypeptide. The recombinant gene product was immunoreactive with a monospecific anti-57-kD serum, and elicited an ocular inflammation similar to that produced by the 57-kD antigen isolated from chlamydiae. Sequencing identified two ORFs that encode polypeptides of 11.2 and 58.1 kD and are co-transcribed. These two polypeptides show homology with Escherichia coli groE and Coxiella burnetii htp heat-shock proteins. Striking homology (greater than 50%) was found between the 57-kD protein and the HtpB, GroEL, 65-k Mycobacterium tuberculosis and Hsp60 proteins. Thus, the 57-kD chlamydial protein, previously implicated as mediating a deleterious immunologic response to chlamydial infections, is a stress-induced protein similar to those that occur universally in both prokaryotic and eukaryotic organisms. PMID:2571668

  4. Detection of reactive oxygen species can be used to distinguish ToxA-induced cell death from the hypersensitive response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unlike the situation of resistance (R) gene mediated cell death, the biochemical mechanism for the fungal toxin ToxA-caused cell death is not well-defined. Resistance associated with the gene-for-gene interaction is usually manifested in a form of programmed cell death termed the hypersensitive resp...

  5. Suppression of urushiol-induced delayed-type hypersensitivity responses in mice with serum IgG immunoglobulin from human hyposensitized donors.

    PubMed

    Stampf, J L; Castagnoli, N; Epstein, W; Baldwin, R W; Byers, V

    1990-09-01

    Serum IgG immunoglobulin fractions from human subjects hyposensitized to poison ivy/oak by oral administration of urushiol suppressed the induction of delayed-type hypersensitivity (DTH) responses in mice to this hapten. This suppressive activity was hapten specific because it did not modify DTH responses to dinitrofluorobenzene (DNFB). Absorption of human serum with lymph node cells from urushiolsensitized but not DNFB-sensitized mice removed the suppressive activity, suggesting that anti-idiotypic antibodies reacting with T-cell receptors are involved. PMID:2384694

  6. DOLICHOL PHOSPHATE MANNOSE SYNTHASE1 Mediates the Biogenesis of Isoprenyl-Linked Glycans and Influences Development, Stress Response, and Ammonium Hypersensitivity in Arabidopsis[W

    PubMed Central

    Jadid, Nurul; Mialoundama, Alexis Samba; Heintz, Dimitri; Ayoub, Daniel; Erhardt, Mathieu; Mutterer, Jérôme; Meyer, Denise; Alioua, Abdelmalek; Van Dorsselaer, Alain; Rahier, Alain; Camara, Bilal; Bouvier, Florence

    2011-01-01

    The most abundant posttranslational modification in nature is the attachment of preassembled high-mannose-type glycans, which determines the fate and localization of the modified protein and modulates the biological functions of glycosylphosphatidylinositol-anchored and N-glycosylated proteins. In eukaryotes, all mannose residues attached to glycoproteins from the luminal side of the endoplasmic reticulum (ER) derive from the polyprenyl monosaccharide carrier, dolichol P-mannose (Dol-P-Man), which is flipped across the ER membrane to the lumen. We show that in plants, Dol-P-Man is synthesized when Dol-P-Man synthase1 (DPMS1), the catalytic core, interacts with two binding proteins, DPMS2 and DPMS3, that may serve as membrane anchors for DPMS1 or provide catalytic assistance. This configuration is reminiscent of that observed in mammals but is distinct from the single DPMS protein catalyzing Dol-P-Man biosynthesis in bakers’ yeast and protozoan parasites. Overexpression of DPMS1 in Arabidopsis thaliana results in disorganized stem morphology and vascular bundle arrangements, wrinkled seed coat, and constitutive ER stress response. Loss-of-function mutations and RNA interference–mediated reduction of DPMS1 expression in Arabidopsis also caused a wrinkled seed coat phenotype and most remarkably enhanced hypersensitivity to ammonium that was manifested by extensive chlorosis and a strong reduction of root growth. Collectively, these data reveal a previously unsuspected role of the prenyl-linked carrier pathway for plant development and physiology that may help integrate several aspects of candidate susceptibility genes to ammonium stress. PMID:21558543

  7. The purification and characterization of a novel hypersensitive-like response-inducing elicitor from Verticillium dahliae that induces resistance responses in tobacco.

    PubMed

    Wang, Bingnan; Yang, Xiufen; Zeng, Hongmei; Liu, Hua; Zhou, Tingting; Tan, Beibei; Yuan, Jingjing; Guo, Lihua; Qiu, Dewen

    2012-01-01

    PevD1, a novel protein elicitor from the pathogenic cotton verticillium wilt fungus, Verticillium dahliae, induced a hypersensitive response in tobacco plants. In this paper, the elicitor was purified and analyzed using de novo sequencing. The protein-encoding pevD1 gene consists of a 468-bp open reading frame that produces a polypeptide of 155 amino acids, with a theoretical molecular weight of 16.23 kDa. The sequence of elicitor protein PevD1 was matched to the genomic sequence (GenBank accession no. ABJE 01000445.1) of a putative protein from V. dahliae strain vdls.17, but a function had not yet been reported. The pevD1 gene was expressed in Escherichia coli, and the recombinant protein was characterized for its ability to confer systemic acquired resistance to tobacco mosaic virus (TMV). Recombinant PevD1-treated plants exhibited enhanced systemic resistance compared to control, including a significant reduction in the number and size of TMV lesions on tobacco leaves. The elicitor protein-induced hydrogen peroxide production, extracellular-medium alkalization, callose deposition, phenolics metabolism, and lignin synthesis in tobacco. Our results demonstrate that elicitor-PevD1 triggers defense responses in intact tobacco plants. PMID:21691787

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

    PubMed

    Huitema, Edgar; Vleeshouwers, Vivianne G A A; Cakir, Cahit; Kamoun, Sophien; Govers, Francine

    2005-03-01

    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 canonical elicitins (class I), such as INF1 of the potato and tomato pathogen Phytophthora infestans. Two genes, inf2A and inf2B, encoding a distinct class (class III) of elicitin-like proteins, also occur in P. infestans. Unlike secreted class I elicitins, class III elicitins are thought to be cell-surface-anchored polypeptides. Molecular characterization of the inf2 genes indicated that they are widespread in Phytophthora spp. and occur as a small gene family. In addition, Southern blot and Northern blot hybridizations using gene-specific probes showed that inf2A and inf2B genes and transcripts can be detected in 17 different P. infestans isolates. Functional secreted expression in plant cells of the elicitin domain of the infl and inf2 genes was conducted using a binary Potato virus X (PVX) vector (agroinfection) and Agrobacterium tumefaciens transient transformation assays (agroinfiltration), and resulted in HR-like necrotic symptoms and induction of defense response genes in tobacco. However, comparative analyses of elicitor activity of INF1, INF2A, and INF2B revealed significant differences in intensity, specificity, and consistency of HR induction. Whereas INF1 induced the HR in Nicotiana benthamiana, INF2A induced weak symptoms and INF2B induced no symptoms on this plant. Nonetheless, similar to INF1, HR induction by INF2A in N. benthamiana required the ubiquitin ligase-associated protein SGT1. Overall, these results suggest that variation in the resistance of Nicotiana spp. to P. infestans is shadowed by variation in the response to INF elicitins. The ability of tobacco, but not N. benthamiana, to respond to INF2B could explain differences in resistance to P. infestans observed for these two species. PMID:15782632

  9. Relationship between delayed hypersensitivity response and acquired cell-mediated immunity in C57BL/6J mice infected with Leishmania donovani.

    PubMed Central

    Fahey, J R; Herman, R

    1985-01-01

    The relationship between the development of acquired cell-mediated immunity and the concomitant level of specific delayed hypersensitivity (DH) in C57BL/6J mice infected with the intracellular protozoan parasite Leishmania donovani was studied. It was determined that the intradermal injection of Leishmania antigen (heat- or phenol-killed flagellated forms of L. donovani) could elicit a DH response as early as day 10 and as late as day 120 postinfection in mice infected by the intravenous route. Dose-response studies showed that there is an inverse relationship between the size of the infecting dose of parasites and the magnitude of the DH response. Thus, increasing the degree of infection depressed the DH response. This depression, however, could be abrogated by treatment of mice with cyclophosphamide (201 mg/kg) before intradermal injection of antigen. PMID:4018876

  10. Mutational analysis of the Verticillium dahliae protein elicitor PevD1 identifies distinctive regions responsible for hypersensitive response and systemic acquired resistance in tobacco.

    PubMed

    Liu, Wenxian; Zeng, Hongmei; Liu, Zhipeng; Yang, Xiufen; Guo, Lihua; Qiu, Dewen

    2014-01-01

    In our previous study, PevD1 was characterized as a novel protein elicitor produced by Verticillium dahliae inducing hypersensitive response (HR) and systemic acquired resistance (SAR) in tobacco plants; however, the detailed mechanisms of PevD1's elicitor activity remain unclear. In this study, five mutant fragments of PevD1 were generated by polymerase chain reaction-based mutagenesis and the truncated proteins expressed in Escherichia coli were used to test their elicitor activities. Biological activity analysis showed that the N-terminal and C-terminal of PevD1 had distinct influence on HR and SAR elicitation. Fragment PevD1?N98, which spans the C-terminal 57 amino acids of PevD1, was critical for the induction of HR in tobacco plants. In contrast, fragment PevD1?C57, the N-terminal of 98 amino acids of PevD1, retained the ability to induce SAR against tobacco mosaic virus (TMV) but not induction of HR, suggesting that the induction of HR is not essential for SAR mediated by PevD1. Our results indicated that fragment PevD1?C57 could be a candidate peptide for plant protection against pathogens without causing negative effects. PMID:24080193

  11. Hypersensitivity reactions to corticosteroids.

    PubMed

    Vatti, Rani R; Ali, Fatima; Teuber, Suzanne; Chang, Christopher; Gershwin, M Eric

    2014-08-01

    Hypersensitivity reactions to corticosteroids (CS) are rare in the general population, but they are not uncommon in high-risk groups such as patients who receive repeated doses of CS. Hypersensitivity reactions to steroids are broadly divided into two categories: immediate reactions, typically occurring within 1 h of drug administration, and non-immediate reactions, which manifest more than an hour after drug administration. The latter group is more common. We reviewed the literature using the search terms "hypersensitivity to steroids, adverse effects of steroids, steroid allergy, allergic contact dermatitis, corticosteroid side effects, and type I hypersensitivity" to identify studies or clinical reports of steroid hypersensitivity. We discuss the prevalence, mechanism, presentation, evaluation, and therapeutic options in corticosteroid hypersensitivity reactions. There is a paucity of literature on corticosteroid allergy, with most reports being case reports. Most reports involve non-systemic application of corticosteroids. Steroid hypersensitivity has been associated with type I IgE-mediated allergy including anaphylaxis. The overall prevalence of type I steroid hypersensitivity is estimated to be 0.3-0.5%. Allergic contact dermatitis (ACD) is the most commonly reported non-immediate hypersensitivity reaction and usually follows topical CS application. Atopic dermatitis and stasis dermatitis of the lower extremities are risk factors for the development of ACD from topical CS. Patients can also develop hypersensitivity reactions to nasal, inhaled, oral, and parenteral CS. A close and detailed evaluation is required for the clinician to confirm the presence of a true hypersensitivity reaction to the suspected drug and choose the safest alternative. Choosing an alternative CS is not only paramount to the patient's safety but also ameliorates the worry of developing an allergic, and potentially fatal, steroid hypersensitivity reaction. This evaluation becomes especially important in high-risk groups where steroids are a life-saving treatment. The assessment should be done when the patient's underlying condition is in a quiescent state. PMID:23567983

  12. Investigation of the role of delayed-type-hypersensitivity responses to myelin in the pathogenesis of Theiler's virus-induced demyelinating disease.

    PubMed Central

    Borrow, P; Welsh, C J; Tonks, P; Dean, D; Blakemore, W F; Nash, A A

    1998-01-01

    The contribution of autoimmune responses to the pathogenesis of Theiler's virus-induced demyelinating disease was investigated. Delayed-type hypersensitivity responses to myelin were examined in both symptomatic and asymptomatic mice at different times post-infection, in order to determine whether autoreactivity correlates with the development of demyelination. The results indicate that although autoimmune responses probably do not play a major role in the initiation of demyelination at early times post-infection, autoreactivity to myelin antigens dose eventually develop in symptomatic animals, perhaps through the mechanism of epitope spreading. Autoimmunity to myelin components is therefore an additional factor that may contribute to lesion progression in chronically diseased animals. Images Figure 2 PMID:9659218

  13. Delayed hypersensitivity responses in mice and guinea pigs to Mycobacterium leprae, Mycobacterium vaccae, and Mycobacterium nonchromogenicum cytoplasmic proteins.

    PubMed

    Watson, S R; Morrison, N E; Collins, F M

    1979-07-01

    Antigenic relationships between Mycobacterium vaccae, M. nonchromogenicum, and M. leprae were examined in mice and guinea pigs injected with M. vaccae or M. nonchromogenicum suspensions. The growth of both organisms in outbred ICR and four inbred mouse strains was followed up to 30 days. M. nonchromogenicum persisted in the livers and spleens of the inbred mice substantially better than did the M. vaccae population in the same mouse strains. A translucent colony variant of M. vaccae isolated from the opossum survived in vivo better than the opaque colony isolated from opossums and cattle. Persistence of M. vaccae and M. nonchromogenicum was not markedly increased in T-cell-depleted (nude) mice. Normal mice infected with increasing numbers of M. vaccae did not develop delayed-type hypersensitivity to the homologous M. vaccae cytoplasmic protein antigen. When heat-killed M. vaccae were incorporated into Freund adjuvant, both mice and guinea pigs developed delayed hypersensitivity to cytoplasmic antigens prepared from M. vaccae, M. nonchromogenicum and M. vaccae vaccines cross-sensitized guinea pigs to the M. leprae cytoplasmic antigens. PMID:383613

  14. The prevalence of dentine hypersensitivity in Chinese adults.

    PubMed

    Ye, W; Feng, X-P; Li, R

    2012-03-01

    Dentine hypersensitivity is a common oral problem. This study investigated the prevalence of dentine hypersensitivity in the adult population of Shanghai, China. A multi-stage, stratified, random sampling method was used to investigate the study population. A total of 2120 subjects were examined at 10 investigation points in Shanghai City. Subjects were divided into age groups (10 years per age group) and included the same number of male and female subjects in each group. Participants completed a dentine hypersensitivity questionnaire and underwent clinical examination. The diagnosis of dentine hypersensitivity was confirmed clinically as a sharp well-localised pain in response to administration of a blast of cold air from a triple syringe. Gingival recession of sensitive teeth was measured by a Williams periodontal probe. Among 2120 participants, 723 were diagnosed as having dentine hypersensitivity, indicating a prevalence of 34·1%. The male to female ratio of dentine hypersensitivity was 1:1·5. The prevalence of dentine hypersensitivity was highest in the 40- to 49-year age group at 43·9%. The number of teeth with dentine hypersensitivity was 3·2 per patient. Dentine hypersensitivity occurred predominantly in the premolars (49·6%), followed by the anterior teeth (30·5%). A total of 84·3% of dentine hypersensitive patients had gingival recession. The prevalence of dentine hypersensitivity in Shanghai adults was 34·1%, indicating that it is a common condition. Therefore, public education about the condition and effective treatment of dentine hypersensitivity are required. PMID:21902706

  15. An Induced Hypersensitive-Like Response Limits Expression of Foreign Peptides via a Recombinant TMV-Based Vector in a Susceptible Tobacco

    PubMed Central

    Li, Mangmang; Li, Ping; Song, Rentao; Xu, Zhengkai

    2010-01-01

    Background By using tobacco mosaic virus (TMV)-based vectors, foreign epitopes of the VP1 protein from food-and-month disease virus (FMDV) could be fused near to the C-terminus of the TMV coat protein (CP) and expressed at high levels in susceptible tobacco plants. Previously, we have shown that the recombinant TMV vaccines displaying FMDV VP1 epitopes could generate protection in guinea pigs and swine against the FMDV challenge. Recently, some recombinant TMV, such as TMVFN20 that contains an epitope FN20 from the FMDV VP1, were found to induce local necrotic lesions (LNL) on the inoculated leaves of a susceptible tobacco, Nicotiana tabacum Samsun nn. This hypersensitive-like response (HLR) blocked amplification of recombinant TMVFN20 in tobacco and limited the utility of recombinant TMV vaccines against FMDV. Methodology/Principal Findings Here we investigate the molecular mechanism of the HLR in the susceptible Samsun nn. Histochemical staining analyses show that these LNL are similar to those induced in a resistant tobacco Samsun NN inoculated with wild type (wt) TMV. The recombinant CP subunits are specifically related to the HLR. Interestingly, this HLR in Samsun nn (lacking the N/N′-gene) was able to be induced by the recombinant TMV at both 25°C and 33°C, whereas the hypersensitive response (HR) in the resistant tobacco plants induced by wt TMV through the N/N′-gene pathways only at a permissive temperature (below 30°C). Furthermore, we reported for the first time that some of defense response (DR)-related genes in tobacco were transcriptionally upregulated during HLR. Conclusions Unlike HR, HLR is induced in the susceptible tobacco through N/N′-gene independent pathways. Induction of the HLR is associated with the expression of the recombinant CP subunits and upregulation of the DR-related genes. PMID:21124743

  16. A single gene, AIN, in Medicago truncatula mediates a hypersensitive response to both bluegreen aphid and pea aphid, but confers resistance only to bluegreen aphid

    PubMed Central

    Klingler, John P.; Nair, Ramakrishnan M.; Edwards, Owain R.; Singh, Karam B.

    2009-01-01

    Biotic stress in plants frequently induces a hypersensitive response (HR). This distinctive reaction has been studied intensively in several pathosystems and has shed light on the biology of defence signalling. Compared with microbial pathogens, relatively little is known about the role of the HR in defence against insects. Reference genotype A17 of Medicago truncatula Gaertn., a model legume, responds to aphids of the genus Acyrthosiphon with necrotic lesions resembling a HR. In this study, the biochemical nature of this response, its mode of inheritance, and its relationship with defence against aphids were investigated. The necrotic lesion phenotype and resistance to the bluegreen aphid (BGA, Acyrthosiphon kondoi Shinji) and the pea aphid (PA, Acyrthosiphon pisum (Harris)) were analysed using reference genotypes A17 and A20, their F2 progeny and recombinant inbred lines. BGA-induced necrotic lesions co-localized with the production of H2O2, consistent with an oxidative burst widely associated with hypersensitivity. This HR correlated with stronger resistance to BGA in A17 than in A20; these phenotypes cosegregated as a semi-dominant gene, AIN (Acyrthosiphon-induced necrosis). In contrast to BGA, stronger resistance to PA in A17, compared with A20, did not cosegregate with a PA-induced HR. The AIN locus resides in a cluster of sequences predicted to encode the CC-NBS-LRR subfamily of resistance proteins. AIN-mediated resistance presents a novel opportunity to use a model plant and model aphid to study the role of the HR in defence responses to phloem-feeding insects. PMID:19690018

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

    PubMed

    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. PMID:25968478

  18. Pepper suppressor of the G2 allele of skp1 interacts with the receptor-like cytoplasmic kinase1 and type III effector AvrBsT and promotes the hypersensitive cell death response in a phosphorylation-dependent manner.

    PubMed

    Kim, Nak Hyun; Kim, Dae Sung; Chung, Eui Hwan; Hwang, Byung Kook

    2014-05-01

    Xanthomonas campestris pv vesicatoria type III effector protein, AvrBsT, triggers hypersensitive cell death in pepper (Capsicum annuum). Here, we have identified the pepper SGT1 (for suppressor of the G2 allele of skp1) as a host interactor of AvrBsT and also the pepper PIK1 (for receptor-like cytoplasmic kinase1). PIK1 specifically phosphorylates SGT1 and AvrBsT in vitro. AvrBsT specifically binds to the CHORD-containing protein and SGT1 domain of SGT1, resulting in the inhibition of PIK1-mediated SGT1 phosphorylation and subsequent nuclear transport of the SGT1-PIK1 complex. Liquid chromatography-tandem mass spectrometry of the proteolytic peptides of SGT1 identified the residues serine-98 and serine-279 of SGT1 as the major PIK1-mediated phosphorylation sites. Site-directed mutagenesis of SGT1 revealed that the identified SGT1 phosphorylation sites are responsible for the activation of AvrBsT-triggered cell death in planta. SGT1 forms a heterotrimeric complex with both AvrBsT and PIK1 exclusively in the cytoplasm. Agrobacterium tumefaciens-mediated coexpression of SGT1 and PIK1 with avrBsT promotes avrBsT-triggered cell death in Nicotiana benthamiana, dependent on PIK1. Virus-induced silencing of SGT1 and/or PIK1 compromises avrBsT-triggered cell death, hydrogen peroxide production, defense gene induction, and salicylic acid accumulation, leading to the enhanced bacterial pathogen growth in pepper. Together, these results suggest that SGT1 interacts with PIK1 and the bacterial effector protein AvrBsT and promotes the hypersensitive cell death associated with PIK1-mediated phosphorylation in plants. PMID:24686111

  19. SUPERNATANTS FROM THE ULTRAVIOLET-IRRADIATED KERATINOCYTES DECREASE THE RESISTANCE AND DELAYED-TYPE HYPERSENSITIVITY RESPONSE TO MYCOBACTERIUM BOVIS BACILLUS CALMETTE-GUERIN IN MICE AND IMPAIR THE PHAGOCYTIC ABILITY OF MACROPHAGES

    EPA Science Inventory

    Recently, we demonstrated that exposure of mice to a single high does or to multiple smaller doses of ultraviolet (UV) radiation decreased the induction of the delayed type hypersensitivity (DTH) response to Mycobacterium bovis-BCG injected into unexposed sites. In view of the li...

  20. Alveolar Macrophage Innate Response to Mycobacterium immunogenum, the Etiological Agent of Hypersensitivity Pneumonitis: Role of JNK and p38 MAPK Pathways

    PubMed Central

    Yadav, Jagjit S.

    2013-01-01

    Mycobacterium immunogenum is an emerging pathogen of the immune-mediated lung disease hypersensitivity pneumonitis (HP) reported in machinists occupationally exposed to contaminated metal working fluid (MWF). However, the mechanism of its interaction with the host lung is unclear. Considering that alveolar macrophages play a central role in host defense in the exposed lung, understanding their interaction with the pathogen could provide initial insights into the underlying immunopathogenesis events and mechanisms. In the current study, M. immunogenum 700506, a predominant genotype isolated from HP-linked fluids, was shown to multiply intracellularly, induce proinflammatory mediators (TNF-?, IL-1?, IL-1?, IL-6, GM-CSF, NO) and cause cytotoxicity/cell death in the cultured murine alveolar macrophage cell line MH-S in a dose- and time-dependent manner. The responses were detected as early as 3h post-infection. Comparison of this and four additional genotypes of M. immunogenum (MJY-3, MJY-4, MJY-12, MJY-14) using an effective dose-time combination (100 MOI for 24h) showed these macrophage responses in the following order (albeit with some variations for individual response indicators). Inflammatory: MJY-3 ? 700506 > MJY-4 ? MJY-14 ? MJY-12; Cytotoxic: 700506 ? MJY-3 > MJY-4 ? MJY-12 ? MJY-14. In general, 700506 and MJY-3 showed a more aggressive response than other genotypes. Chemical blocking of either p38 or JNK inhibited the induction of proinflammatory mediators (cytokines, NO) by 700506. However, the cellular responses showed a somewhat opposite effect. This is the first report on M. immunogenum interactions with alveolar macrophages and on the identification of JNK- and p38- mediated signaling and its role in mediating the proinflammatory responses during these interactions. PMID:24349452

  1. DNaseI Hypersensitivity and Ultraconservation Reveal Novel, Interdependent Long-Range Enhancers at the Complex Pax6 Cis-Regulatory Region

    PubMed Central

    McBride, David J.; Buckle, Adam; van Heyningen, Veronica; Kleinjan, Dirk A.

    2011-01-01

    The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS) analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP) shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR), allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing visualisation of migratory defects in both pathways in Pax6Sey/Sey mice. PMID:22220192

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

    PubMed

    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 ?-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 ?-arrestin2 (?Arr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of ?Arr2 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 G?i inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the G?s 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 ?Arr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs. PMID:25123018

  3. IREN, a novel EF-hand motif-containing nuclease, functions in the degradation of nuclear DNA during the hypersensitive response cell death in rice.

    PubMed

    Ootsubo, Yuka; Hibino, Takanori; Wakazono, Takahito; Mukai, Yukio; Che, Fang-Sik

    2016-04-01

    The hypersensitive response (HR), a type of programmed cell death that is accompanied by DNA degradation and loss of plasma membrane integrity, is a common feature of plant immune responses. We previously reported that transcription of IREN which encodes a novel EF-hand containing plant nuclease is controlled by OsNAC4, a key positive regulator of HR cell death. Transient overexpression of IREN in rice protoplasts also led to rapid DNA fragmentation, while suppression of IREN using RNA interference showed remarkable decrease of DNA fragmentation during HR cell death. Maximum DNA degradation associated with the recombinant IREN was observed in the presence of Ca(2+) and Mg(2+) or Ca(2+) and Mn(2+). Interestingly, DNA degradation mediated by the recombinant IREN was completely abolished by Zn(2+), even when Ca(2+), Mg(2+), or Mn(2+) were present in the reaction buffer. These data indicate that IREN functions in the degradation of nuclear DNA during HR cell death. PMID:26766411

  4. Elicitin-like proteins Oli-D1 and Oli-D2 from Pythium oligandrum trigger hypersensitive response in Nicotiana benthamiana and induce resistance against Botrytis cinerea in tomato.

    PubMed

    Ouyang, Zhigang; Li, Xiaohui; Huang, Lei; Hong, Yongbo; Zhang, Yafen; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2015-04-01

    The biocontrol agent Pythium oligandrum and its elicitin-like proteins oligandrins have been shown to induce disease resistance in a range of plants. In the present study, the ability of two oligandrins, Oli-D1 and Oli-D2, to induce an immune response and the possible molecular mechanism regulating the defence responses in Nicotiana benthamiana and tomato were investigated. Infiltration of recombinant Oli-D1 and Oli-D2 proteins induced a typical immune response in N.?benthamiana including the induction of a hypersensitive response (HR), accumulation of reactive oxygen species and production of autofluorescence. Agrobacterium-mediated transient expression assays revealed that full-length Oli-D1 and Oli-D2 were required for full HR-inducing activity in N.?benthamiana, and virus-induced gene silencing-mediated knockdown of some of the signalling regulatory genes demonstrated that NbSGT1 and NbNPR1 were required for Oli-D1 and Oli-D2 to induce HR in N.?benthamiana. Subcellular localization analyses indicated that both Oli-D1 and Oli-D2 were targeted to the plasma membrane of N.?benthamiana. When infiltrated or transiently expressed in leaves, Oli-D1 and Oli-D2 induced resistance against Botrytis cinerea in tomato and activated the expression of a set of genes involved in the jasmonic acid/ethylene (JA/ET)-mediated signalling pathway. Our results demonstrate that Oli-D1 and Oli-D2 are effective elicitors capable of inducing immune responses in plants, probably through the JA/ET-mediated signalling pathway, and that both Oli-D1 and Oli-D2 have potential for the development of bioactive formulae for crop disease control in practice. PMID:25047132

  5. Oligomerization, Conformational Stability and Thermal Unfolding of Harpin, HrpZPss and Its Hypersensitive Response-Inducing C-Terminal Fragment, C-214-HrpZPss

    PubMed Central

    Tarafdar, Pradip K.; Vedantam, Lakshmi Vasudev; Sankhala, Rajeshwer S.; Purushotham, Pallinti; Podile, Appa Rao; Swamy, Musti J.

    2014-01-01

    HrpZa harpin from Pseudomonas syringaeis a highly thermostable protein that exhibits multifunctional abilities e.g., it elicits hypersensitive response (HR), enhances plant growth, acts as a virulence factor, and forms pores in plant plasma membranes as well as artificial membranes. However, the molecular mechanism of its biological activity and high thermal stability remained poorly understood. HR inducing abilities of non-overlapping short deletion mutants of harpins put further constraints on the ability to establish structure-activity relationships. We characterized HrpZPss from Pseudomonas syringae pv. syringae and its HR inducing C-terminal fragment with 214 amino acids (C-214-HrpZPss) using calorimetric, spectroscopic and microscopic approaches. Both C-214-HrpZPss and HrpZPss were found to form oligomers. We propose that leucine-zipper-like motifs may take part in the formation of oligomeric aggregates, and oligomerization could be related to HR elicitation. CD, DSC and fluorescence studies showed that the thermal unfolding of these proteins is complex and involves multiple steps. The comparable conformational stability at 25C (?10.0 kcal/mol) of HrpZPss and C-214-HrpZPss further suggest that their structures are flexible, and the flexibility allows them to adopt proper conformation for multifunctional abilities. PMID:25502017

  6. Hypersensitivity pneumonitis induced by Penicillium species.

    PubMed

    Solley, G O; Hyatt, R E

    1980-01-01

    An entomologist developed an illness with typical features of hypersensitivity pneumonitis. On-site investigations indicated that on the days of his attacks he was exposed to dust laden with several species of mold, especially Penicillium spp., as well as to mists generated by reservoir-type humidifiers. Serologic tests to more than 40 antigens prepared from organisms and sources known to cause hypersensitivity pneumonitis showed strong reactions to Penicillium and to antigens prepared from the scum of a large industrial humidifier and from his laboratory humidifier. PFTs revealed a significant reduction in DLCO, Following a 4-mo period without laboratory exposure, he experienced no further episodes, a return to his previous exercise tolerance, and a normal DLCO, BP studies with extracts of Penicillium casei and humidifier water from his laboratory (H1) resulted in objective evidence, both clinically and by hematologic and pulmonary function testing, of hypersensitivity to Penicillium spp. and possibly also to the H1 preparation. PMID:7350206

  7. Hypersensitivity pneumonitis from ordinary residential exposures.

    PubMed Central

    Apostolakos, M J; Rossmoore, H; Beckett, W S

    2001-01-01

    A previously healthy woman developed hypersensitivity pneumonitis of such severity that she required chronic systemic corticosteroid therapy for symptom control. Detailed investigation of her workplace and home environments revealed fungi in her typical suburban home, to which she had specific serum precipitating antibodies. Efforts to remove mold from the home were unsuccessful in relieving symptoms, and moving to another residence was the only intervention that allowed her to be withdrawn from corticosteroid therapy. Hypersensitivity pneumonitis is commonly associated with occupational or avocational exposures, such as moldy hay in farmers or bird antigen in bird breeders. We propose that hypersensitivity pneumonitis may occur in North America, as it does in Japan, from domestic exposures alone. PMID:11673130

  8. Anandamide Attenuates Th-17 Cell-Mediated Delayed-Type Hypersensitivity Response by Triggering IL-10 Production and Consequent microRNA Induction

    PubMed Central

    Jackson, Austin R.; Nagarkatti, Prakash; Nagarkatti, Mitzi

    2014-01-01

    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. PMID:24699635

  9. Inhibition of the Redox Function of APE1/Ref-1 in Myeloid Leukemia Cell Lines Results in a Hypersensitive Response to Retinoic Acid-induced Differentiation and Apoptosis

    PubMed Central

    Fishel, Melissa L.; Colvin, E. Scott; Luo, Meihua; Kelley, Mark R.; Robertson, Kent A.

    2010-01-01

    Objective The standard of care for promyelocytic leukemia includes use of the differentiating agent all-trans retinoic acid (RA) and chemotherapy. RA induces cell differentiation through retinoic acid receptor (RAR) transcription factors. Because redox mechanisms influence how readily transcription factors bind to DNA response elements (RARE), the impact of small molecule (E3330) inhibition of the redox regulatory protein, apurinic-apyrimidinic endonuclease/redox effector factor (APE1/Ref-1) on RAR DNA binding and function in RA-induced myeloid leukemia cell differentiation and apoptosis was investigated. Materials and Methods The redox function of APE1 was studied using the small molecule inhibitor E3330 in HL-60 and PLB acute myeloid leukemia cells. Electrophoretic mobility shift assays (EMSA) were employed to determine effect of inhibitor on APE1/Ref-1 redox signaling function. Trypan blue assays, Annexin-V/PI and CD11b staining, and real time PCR analyses were employed to determine survival, apoptosis and differentiation status of cells in culture. Results RAR? binds to its RARE in a redox-dependent manner mediated by APE1/Ref-1 redox regulation. Redox-dependent RAR-RARE binding is blocked by E3330, a small molecule redox inhibitor of APE1/Ref-1. Combination treatment of RA + E3330 results in a profound hypersensitivity of myeloid leukemia cells to RA-induced differentiation and apoptosis. Additionally, redox inhibition by E3330 results in enhanced RAR target gene, BLR-1, expression in myeloid leukemia cells. Conclusion The redox function of APE1/Ref-1 regulates RAR binding to its DNA RAREs influencing the response of myeloid leukemia cells to RA-induced differentiation. Targeting of APE1/Ref-1 redox function may allow manipulation of the retinoid response with therapeutic implications. PMID:20826193

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

    PubMed Central

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

    2014-01-01

    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-nave 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 (01) 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/?L, interquartile range (IQR) 315517 vs. 373 cells/?L, IQR 228487; p=0.104) and VL (4.3 log10 copies/mL, IQR 3.44.9 vs. 4.4 log10 copies/mL, IQR 3.65.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/?L, IQR 115358) and anergic groups (246 cells/?L, IQR 136358; 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=0.283). Conclusions DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre-HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL-suppressive HAART. PMID:24499779

  11. Morin inhibits Fyn kinase in mast cells and IgE-mediated type I hypersensitivity response in vivo.

    PubMed

    Kim, Jie Wan; Lee, Jun Ho; Hwang, Bang Yeon; Mun, Se Hwan; Ko, Na Young; Kim, Do Kyun; Kim, Bokyung; Kim, Hyung Sik; Kim, Young Mi; Choi, Wahn Soo

    2009-05-01

    Mast cells are responsible for IgE-mediated allergic responses. Although dietary flavonoid morin has been known to suppress mast cell activation, its in vivo anti-allergic activity and the underlying mechanisms remain are largely unknown. In this study, we determine whether morin suppresses IgE-mediated allergic responses in an animal model and its mechanism of action. Morin suppressed IgE-mediated PCA in mice (ED50 23.9 mg/kg) and inhibited degranulation and production of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4 in antigen (Ag)-stimulated mast cells. The mechanism of action was a follows. Morin inhibited the activating phosphorylation of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT) in rat basophilic leukemia (RBL)-2H3 cells and bone marrow-derived mast cells (BMMCs). Akt and the mitogen-activated protein (MAP) kinases, p38, extracellular signal-regulated kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK) were inhibited as well. In vitro kinase assay indicated that Fyn kinase, not Lyn and Syk, was inhibited by morin in a dose-dependent manner (IC50 5.7 microM). In conclusion, the results suggest that morin suppresses the IgE-mediated allergic response by primarily inhibiting Fyn kinase in mast cells. PMID:19426688

  12. High dose dietary pyridoxine induces T-helper type 1 polarization and decreases contact hypersensitivity response to fluorescein isothiocyanate in mice.

    PubMed

    Kobayashi, Chie; Kurohane, Kohta; Imai, Yasuyuki

    2012-01-01

    Pyridoxine (vitamin B(6)) is commonly used as a dietary supplement and beneficial effects of it are expected. However, excess ingestion of pyridoxine has been shown to cause a severe sensory neuropathy in humans and experimental animals. We have been studying the linkage between the nervous and immune systems using a fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse model. We have found that activation of transient receptor potential ankyrin 1 (TRPA1), which is expressed on sensory neurons, enhances skin sensitization to FITC. Another feature of FITC-induced CHS is its dependence on T helper 2 (Th2) type responses. We hypothesized that the excess intake of pyridoxine may affect sensitization to FITC and influence helper T-cell polarization. We examined FITC-induced CHS in BALB/c mice fed a diet containing excess pyridoxine (120 mg/kg diet) for 3 weeks. We found that mice fed on the excess-pyridoxine diet exhibited a lower response as to FITC-induced CHS compared with ones fed on a diet with a standard pyridoxine content (6.0 mg/kg diet). Moreover, the interferon (IFN)-?/interleukin (IL)-4 ratio produced by draining lymph node cells was significantly higher with the excess-pyridoxine diet. This suggested that the cytokine balance was shifted toward Th1 with the excess-pyridoxine diet. Consistently, Th1-dependent oxazolone-induced CHS was enhanced with the excess-pyridoxine diet. These results suggested that an excess pyridoxine intake actively influences the immune system by altering helper T cell polarization. PMID:22466557

  13. Two phenotypically distinct T cells are involved in ultraviolet-irradiated urocanic acid-induced suppression of the efferent delayed-type hypersensitivity response to herpes simplex virus, type 1 in vivo

    SciTech Connect

    Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.

    1987-09-01

    When UVB-irradiated urocanic acid, the putative photoreceptor/mediator for UVB suppression, is administered to mice it induces a dose-dependent suppression of the delayed-type hypersensitivity response to herpes simplex virus, type 1 (HSV-1), of similar magnitude to that induced by UV irradiation of mice. In this study, the efferent suppression of delayed-type hypersensitivity by UV-irradiated urocanic acid is demonstrated to be due to 2 phenotypically distinct T cells, (Thy1+, L3T4-, Ly2+) and (Thy1+, L3T4+, Ly2-). The suppression is specific for HSV-1. This situation parallels the generation of 2 distinct T-suppressor cells for HSV-1 by UV irradiation of mice and provides further evidence for the involvement of urocanic acid in the generation of UVB suppression.

  14. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

    Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as StevensJohnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

  15. Novel Antibodies Reactive with Sialyl Lewis X in Both Humans and Mice Define Its Critical Role in Leukocyte Trafficking and Contact Hypersensitivity Responses.

    PubMed

    Matsumura, Ryuji; Hirakawa, Jotaro; Sato, Kaori; Ikeda, Toshiaki; Nagai, Motoe; Fukuda, Minoru; Imai, Yasuyuki; Kawashima, Hiroto

    2015-06-12

    Sialyl Lewis X (sLe(x)) antigen functions as a common carbohydrate determinant recognized by all three members of the selectin family. However, its expression and function in mice remain undefined due to the poor reactivity of conventional anti-sLe(x) monoclonal antibodies (mAbs) with mouse tissues. Here, we developed novel anti-sLe(x) mAbs, termed F1 and F2, which react well with both human and mouse sLe(x), by immunizing fucosyltransferase (FucT)-IV and FucT-VII doubly deficient mice with 6-sulfo-sLe(x)-expressing cells transiently transfected with an expression vector encoding CMP-N-acetylneuraminic acid hydroxylase. F1 and F2 specifically bound both the N-acetyl and the N-glycolyl forms of sLe(x) as well as 6-sulfo-sLe(x), a major ligand for L-selectin expressed in high endothelial venules, and efficiently blocked physiological lymphocyte homing to lymph nodes in mice. Importantly, both of the mAbs inhibited contact hypersensitivity responses not only when administered in the L-selectin-dependent sensitization phase but also when administered in the elicitation phase in mice. When administered in the latter phase, F1 and F2 efficiently blocked rolling of mouse leukocytes along blood vessels expressing P- and E-selectin in the auricular skin in vivo. Consistent with these findings, the mAbs blocked P- and E-selectin-dependent leukocyte rolling in a flow chamber assay. Taken together, these results indicate that novel anti-sLe(x) mAbs reactive with both human and mouse tissues, with the blocking ability against leukocyte trafficking mediated by all three selectins, have been established. These mAbs should be useful in determining the role of sLe(x) antigen under physiological and pathological conditions. PMID:25944902

  16. A suppressor of the menadione-hypersensitive phenotype of a Xanthomonas campestris pv. phaseoli oxyR mutant reveals a novel mechanism of toxicity and the protective role of alkyl hydroperoxide reductase.

    PubMed

    Vattanaviboon, Paiboon; Whangsuk, Wirongrong; Mongkolsuk, Skorn

    2003-03-01

    We isolated menadione-resistant mutants of Xanthomonas campestris pv. phaseoli oxyR (oxyR(Xp)). The oxyRR2(Xp) mutant was hyperresistant to the superoxide generators menadione and plumbagin and was moderately resistant to H(2)O(2) and tert-butyl hydroperoxide. Analysis of enzymes involved in oxidative-stress protection in the oxyRR2(Xp) mutant revealed a >10-fold increase in AhpC and AhpF levels, while the levels of superoxide dismutase (SOD), catalase, and the organic hydroperoxide resistance protein (Ohr) were not significantly altered. Inactivation of ahpC in the oxyRR2(Xp) mutant resulted in increased sensitivity to menadione killing. Moreover, high levels of expression of cloned ahpC and ahpF in the oxyR(Xp) mutant complemented the menadione hypersensitivity phenotype. High levels of other oxidant-scavenging enzymes such as catalase and SOD did not protect the cells from menadione toxicity. These data strongly suggest that the toxicity of superoxide generators could be mediated via organic peroxide production and that alkyl hydroperoxide reductase has an important novel function in the protection against the toxicity of these compounds in X. campestris. PMID:12591894

  17. Management Strategies for Clopidogrel Hypersensitivity.

    PubMed

    Beavers, Craig J; Carris, Nicolas W; Ruf, Kathryn M

    2015-06-01

    Clopidogrel is a cornerstone of dual antiplatelet therapy. Hypersensitivity reactions potentially limit the use of this treatment and present a significant clinical challenge. The authors have developed recommendations for the management of clopidogrel hypersensitivity with consideration for the etiology, pathophysiology, and critical evaluation of potential management strategies. The clopidogrel hypersensitivity reaction is complex in mechanism and presents generally around day 5 of treatment. Generalized reactions are most common, but the reaction may also be localized or systemic. Screening patients for hypersensitivity is not always possible because the type IV delayed reaction is not detected reliably by conventional skin prick, intradermal challenge, or patch testing. Proposed strategies for management of clopidogrel hypersensitivity include treatment of the reaction with corticosteroids, clopidogrel desensitization, substituting an alternative P2Y12 inhibitor, or clopidogrel avoidance. The safety, efficacy, and cost of each potential strategy must be considered when managing a patient with clopidogrel hypersensitivity. PMID:26056028

  18. Targeting a Cross-Reactive Gly m 5 Soy Peptide as Responsible for Hypersensitivity Reactions in a Milk Allergy Mouse Model

    PubMed Central

    Curciarello, Renata; Smaldini, Paola L.; Candreva, Angela M.; Gonzlez, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A.

    2014-01-01

    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 (?), a truncated fragment containing the C-terminal domain (?-T) and peptides of ?-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 ? and ?-T reacted with the different CMP-specific antibodies. ?-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 ?-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 ?-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. PMID:24416141

  19. Therapeutic effects of a fermented soy product on peanut hypersensitivity is associated with modulation of Th1 and Th2 responses

    PubMed Central

    Zhang, Tengfei; Pan, Weijun; Takebe, Minoru; Schofield, Brian; Sampson, Hugh; Li, Xiu-Min

    2008-01-01

    Background 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. Objective To assess possible therapeutic effects of ImmuBalance on peanut hypersensitivity using a murine model of peanut allergy (PNA). Methods Peanut (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 peanut specific-IgE levels and splenocyte cytokine profiles were determined. Results While 100 % of sham-treated peanut-allergic mice developed anaphylactic reactions with a median score of 3.3 following peanut 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 to sham-treated mice, whereas IFN-? production was moderately increased. TGF-? and TNF-? production were similar. Conclusions ImmuBalance protects against peanut-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 peanut allergy. PMID:18705693

  20. Hypersensitive pneumonitis: a case report.

    PubMed

    Reyes, Libertad I Ruscalleda; Román, Vélez Jesús M

    2013-01-01

    Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis, constitutes a spectrum of granulomatous, interstitial, bronchiolar, and alveolar-filling lung diseases resulting from repeated inhalation and sensitization to a wide variety of organic aerosols and low-molecular-weight chemical antigens. We report a case of a 57 year-old-female with hypersensitive pneumonitis due to pigeon droppings. Early diagnosis during the acute phase of hypersensitive pneumonitis is important due to the irreversible damages caused by this chronic disease. PMID:23882989

  1. Chronic hypersensitivity pneumonitis.

    PubMed

    Costabel, Ulrich; Bonella, Francesco; Guzman, Josune

    2012-03-01

    Hypersensitivity pneumonitis (HP) is a complex syndrome caused by the inhalation of environmental antigens. Chronic HP may mimic other fibrotic lung diseases, such as idiopathic pulmonary fibrosis. Recognition of the antigen is important for diagnosis; avoidance of further exposure is critical for treatment. Fibrosis on biopsy or high-resolution computed tomography is a predictor of increased mortality. Additional research is needed to understand why the disease develops only in a minority of exposed individuals and why cases of chronic HP may progress without further antigen exposure. PMID:22365252

  2. Azathioprine hypersensitivity syndrome: a case report.

    PubMed

    Fenaux, S; Tintillier, M; Cuvelier, Ch; Migali, G; Pochet, J M

    2013-01-01

    We report here the case of a 51-year-old man presenting to the Emergency Department with a febrile cutaneous eruption with diffuse arthralgia 10 days after the onset of azathioprine therapy. The clinical examination did not reveal any inflammatory syndrome and the results of all bacteriological tests were negative. A skin biopsy was performed, which revealed a granulocytary pustula with superficial dermal oedema and a neutrophil infiltration without sign of vasculitis. A side effect of azathioprine was suspected, and treatment was discontinued. Fortunately, the patient recovered within a few days. Azathioprine hypersensitivity syndrome is a rare side effect of azathioprine. Hypersensitivity syndrome is an idiosyncratic, non-IgE-mediated reaction that appears to be unrelated to thiopurine methyltransferase levels. Diagnosis is mainly clinical and requires an exclusion of other processes. The only treatment option available is to stop azathioprine intake. PMID:24156226

  3. Immediate-type hypersensitivity drug reactions

    PubMed Central

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

    2014-01-01

    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. PMID:24286446

  4. Domain Swapping and Gene Shuffling Identify Sequences Required for Induction of an Avr-Dependent Hypersensitive Response by the Tomato Cf-4 and Cf-9 Proteins

    PubMed Central

    Wulff, Brande B. H.; Thomas, Colwyn M.; Smoker, Matthew; Grant, Murray; Jones, Jonathan D. G.

    2001-01-01

    The tomato Cf-4 and Cf-9 genes confer resistance to infection by the biotrophic leaf mold pathogen Cladosporium. Their protein products induce a hypersensitive response (HR) upon recognition of the fungus-encoded Avr4 and Avr9 peptides. Cf-4 and Cf-9 share >91% sequence identity and are distinguished by sequences in their N-terminal domains A and B, their N-terminal leucine-rich repeats (LRRs) in domain C1, and their LRR copy number (25 and 27 LRRs, respectively). Analysis of Cf-4/Cf-9 chimeras, using several different bioassays, has identified sequences in Cf-4 and Cf-9 that are required for the Avr-dependent HR in tobacco and tomato. A 10–amino acid deletion within Cf-4 domain B relative to Cf-9 was required for full Avr4-dependent induction of an HR in most chimeras analyzed. Additional sequences required for Cf-4 function are located in LRRs 11 and 12, a region that contains only eight of the 67 amino acids that distinguish it from Cf-9. One chimera, with 25 LRRs that retained LRR 11 of Cf-4, induced an attenuated Avr4-dependent HR. The substitution of Cf-9 N-terminal LRRs 1 to 9 with the corresponding sequences from Cf-4 resulted in attenuation of the Avr9-induced HR, as did substitution of amino acid A433 in LRR 15. The amino acids L457 and K511 in Cf-9 LRRs 16 and 18 are essential for induction of the Avr9-dependent HR. Therefore, important sequence determinants of Cf-9 function are located in LRRs 10 to 18. This region contains 15 of the 67 amino acids that distinguish it from Cf-4, in addition to two extra LRRs. Our results demonstrate that sequence variation within the central LRRs of domain C1 and variation in LRR copy number in Cf-4 and Cf-9 play a major role in determining recognition specificity in these proteins. PMID:11226184

  5. Hypersensitivity reactions from taxol.

    PubMed

    Weiss, R B; Donehower, R C; Wiernik, P H; Ohnuma, T; Gralla, R J; Trump, D L; Baker, J R; Van Echo, D A; Von Hoff, D D; Leyland-Jones, B

    1990-07-01

    Taxol is an antitumor agent in clinical trial that has been shown to have activity against advanced ovarian carcinoma and melanoma. Hypersensitivity reactions (HSRs) have been one of the toxicities observed with administration of this drug. Of 301 patients treated, 32 patients have had definite (27 patients) or possible (five patients) hypersensitivity reactions to taxol. All but one patient had the reaction from the first or second exposure to this agent. Reactions occurred at a variety of doses and were characterized most frequently by dyspnea, hypotension, bronchospasm, urticaria, and erythematous rashes. Thirteen (41%) patients had received premedication designed to prevent such toxicity; nevertheless, they sustained HSRs. Prolonging the drug infusion appears to have somewhat reduced, but not obviated, the risk of HSRs. The cause (taxol itself or its excipient Cremophor EL; Badische Anilin und Soda-Fabrik AG [BASF], Ludwigshafen, Federal Republic of Germany) and the mechanism of these reactions to taxol are unknown. We provide guidelines to prevent or minimize such toxicity and treat reactions if they still occur. PMID:1972736

  6. Hypersensitivity Pneumonitis in a Housewife Exposed to Aspergillus flavus in Poor Living Conditions: A Case Report

    PubMed Central

    Estibeiro, Anita Sandhya Mendonca; Mesquita, Anthony Menezes

    2016-01-01

    Hypersensitivity Pneumonitis (HP) or Extrinsic Allergic Alveolitis (EAA) is a disease resulting from immunologically induced inflammation in response to inhalation of a wide variety of airborne allergens. The condition develops mainly in non atopic individuals sensitized to organic dust due to repeated exposures. It is a relatively rare disease constituting upto 2% of interstitial lung diseases. Knowledge of classical High Resolution Computed Tomography (HRCT) of lung findings aid in early diagnosis. We report a case of subacute hypersensitivity pneumonitis in a housewife who despite being symptomatic remained undiagnosed for two years. She showed a good response to therapy, but soon relapsed. Visit to her home revealed that she lived in a damp house full of moldy walls. PMID:26894116

  7. Hypersensitivity Pneumonitis in a Housewife Exposed to Aspergillus flavus in Poor Living Conditions: A Case Report.

    PubMed

    Fernandes, Lalita; Estibeiro, Anita Sandhya Mendonca; Mesquita, Anthony Menezes

    2016-01-01

    Hypersensitivity Pneumonitis (HP) or Extrinsic Allergic Alveolitis (EAA) is a disease resulting from immunologically induced inflammation in response to inhalation of a wide variety of airborne allergens. The condition develops mainly in non atopic individuals sensitized to organic dust due to repeated exposures. It is a relatively rare disease constituting upto 2% of interstitial lung diseases. Knowledge of classical High Resolution Computed Tomography (HRCT) of lung findings aid in early diagnosis. We report a case of subacute hypersensitivity pneumonitis in a housewife who despite being symptomatic remained undiagnosed for two years. She showed a good response to therapy, but soon relapsed. Visit to her home revealed that she lived in a damp house full of moldy walls. PMID:26894116

  8. Chromatin studies reveal that an ERE is located far upstream of a vitellogenin gene and that a distal tissue-specific hypersensitive site is conserved for two coordinately regulated vitellogenin genes.

    PubMed Central

    Burch, J B; Fischer, A H

    1990-01-01

    Estrogen induces the expression of three vitellogenin genes in chicken hepatocytes. To survey the vitellogenin III (VTGIII) gene region for possible distal regulatory sequences, we identified tissue-specific hypersensitive (HS) sites within a 45 kb chromatin region spanning this gene. Five constitutive HS sites were found to mark the VTGIII gene region in hormone-naive hepatocytes. Strikingly, the constitutive HS site located 5.5 kb upstream of the VTGIII gene and a previously identified HS site located within the coordinately regulated VTGII gene mapped to nearly identical copies of a 72 bp sequence. Moreover, it would appear that there has been evolutionary pressure to retain specifically this 72 bp of VTGII-like sequence near the VTGIII gene subsequent to the VTGIII and VTGII genes becoming unlinked approximately 16 Myr ago. Two additional sets of HS sites were induced in the VTGIII gene region in response to estrogen. One set mapped immediately upstream of the gene in the vicinity of what we show to be a functional estrogen response element (ERE). The other induced HS site mapped 7.5 kb upstream of the gene. This far-upstream region was sequenced and was found to contain two imperfect ERE consensus sequences spaced 88 bp apart. In transient expression assays neither of these individual imperfect ERE sequences was functional, but a fragment spanning both sequences behaved as a strong ERE. In contrast to this synergism between imperfect ERE sequences, the presence of an NF-1 binding site 23 bp away from the more distal imperfect ERE sequence was not sufficient to render the latter a functional ERE in our assays. Images PMID:2377458

  9. Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.

    PubMed

    Suda, T; Sato, A; Ida, M; Gemma, H; Hayakawa, H; Chida, K

    1995-03-01

    We describe five patients with hypersensitivity pneumonitis (HP) that was related to using home ultrasonic humidifiers. All patients had micronodular infiltrates on their chest radiograph, and their lung biopsy specimens revealed alveolitis with or without epithelioid cell granulomas. Challenge tests were performed on two patients with the humidifier water and three patients using the humidifier. All patients tested exhibited a positive response. Tests for precipitating antibodies against an extract of the humidifier water gave strongly positive reactions in all patients tested. Precipitins to Cephalosporium acremonium and Candida albicans were also present in all cases, whereas precipitins to thermophilic actinomycetes were not detected. Although cultures of the water grew a variety of fungal and bacterial organisms, thermophilic actinomycetes could not be detected. These findings suggest that thermophilic organisms may not be the causative antigens of HP associated with ultrasonic humidifiers. All five patients had an increase in the bronchoalveolar lavage (BAL) lymphocytes that were predominantly CD4+ lymphocytes. The T helper cell count (CD4) to suppressor T cell count (CD8) ratio was significantly higher than that observed in summer-type HP, and lower than that observed in bird fancier's lung, indicating that the phenotypes of the BAL lymphocytes may vary with the type of HP. PMID:7874942

  10. Hypersensitivity pneumonitis due to an ultrasonic humidifier.

    PubMed

    Alvarez-Fernndez, J A; Quirce, S; Calleja, J L; Cuevas, M; Losada, E

    1998-02-01

    We describe a woman with hypersensitivity pneumonitis that was related to using a home ultrasonic humidifier. A micronodular infiltrate was seen in her chest radiograph. The inhalation challenge test was performed with the humidifier, and she exhibited a positive response. The cultures of the humidifier water grew Candida albicans, Rhodotorula spp., and Aspergillus spp. The test for precipitating antibodies against the humidifier water gave a positive response, and specific IgG, IgM, and IgA antibodies against extracts of A. fumigatus, C. albicans, and Rhodotorula spp. were demonstrated in the patient's serum by ELISA. A strong, dose-dependent inhibition of Rhodotorula IgG-ELISA by humidifier water was observed, suggesting that Rhodotorula might be the cause of hypersensitivity pneumonitis in this patient. PMID:9534923

  11. Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength

    PubMed Central

    Paskin, Taylor R.; Jellies, John; Bacher, Jessica; Beane, Wendy S.

    2014-01-01

    Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli), planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian behavioral assay to test responses to small ranges of visible wavelengths (red, blue, green), as well as ultraviolet (UV) and infrared (IR) which have not previously been examined. Our data show that planarians display behavioral responses across a range of wavelengths. These responses occur in a hierarchy, with the shortest wavelengths (UV) causing the most intense photophobic responses while longer wavelengths produce no effect (red) or an apparent attraction (IR). In addition, our data reveals that planarian photophobia is comprised of both a general photophobic response (that drives planarians to escape the light source regardless of wavelength) and wavelength-specific responses that encompass specific behavioral reactions to individual wavelengths. Our results serve to improve the understanding of planarian phototaxis and suggest that behavioral studies performed with white light mask a complex behavioral interaction with the environment. PMID:25493551

  12. The C2 protein of tomato yellow leaf curl Sardinia virus acts as a pathogenicity determinant and a 16-amino acid domain is responsible for inducing a hypersensitive response in plants.

    PubMed

    Matić, Slavica; Pegoraro, Mattia; Noris, Emanuela

    2016-04-01

    The role of the C2 protein in the pathogenicity of tomato yellow leaf curl Sardinia virus (TYLCSV) was investigated. Here we report that Agrobacterium-mediated transient expression of TYLCSV C2 resulted in a strong hypersensitive response (HR) in Nicotiana benthamiana, N. tabacum, and Arabidopsis thaliana, with induction of plant cell death and production of H2O2. Since HR is not evident in plants infected by TYLCSV, it is expected that TYLCSV encodes a gene (or genes) that counters this response. HR was partially counteracted by co-agroinfiltration of TYLCSV V2 and Rep, leading to chlorotic reaction, with no HR development. Considering that the corresponding C2 protein of the closely related tomato yellow leaf curl virus (TYLCV) did not induce HR, alignment of the C2 proteins of TYLCSV and TYLCV were carried out and a hypervariable region of 16 amino acids was identified. Its role in the induction of HR was demonstrated using TYLCSV-TYLCV C2 chimeric genes, encoding two TYLCSV C2 variants with a complete (16 aa) or a partial (10 aa only) swap of the corresponding sequence of TYLCV C2. Furthermore, using NahG transgenic N. benthamiana lines compromised in the accumulation of salicylic acid (SA), a key regulator of HR, only a chlorotic response occurred in TYLCSV C2-infiltrated tissue, indicating that SA participates in such plant defense process. These findings demonstrate that TYLCSV C2 acts as a pathogenicity determinant and induces host defense responses controlled by the SA pathway. PMID:26826600

  13. Prolonged stimulus exposure reveals prolonged neurobehavioral response patterns.

    PubMed

    Johnson, Brett A; Woo, Cynthia C; Zeng, Yu; Xu, Zhe; Hingco, Edna E; Ong, Joan; Leon, Michael

    2010-05-15

    Although it has been shown repeatedly that minimum response times in sensory systems can be quite short, organisms more often continue to respond to sensory stimuli over considerably longer periods of time. The continuing response to sensory stimulation may be a more realistic assessment of natural sensory responses, so we determined for how long a stimulus would evoke a response in nave, freely moving animals. Specifically, we determined for how long such rats responded to odorants during continuous passive exposures by monitoring their sniffing with whole-body plethysmography. We found that nave rats continue to sniff odorants vigorously for up to 3 minutes, much longer than what has been reported for highly trained, highly motivated rats. Patterns of 2-deoxyglucose (2-DG) uptake in the glomerular layer of the rat olfactory bulb also were seen after only 1-5 minutes of odorant exposure, overlapping with the period of increased respiration to odorants. Moreover, these 2-DG uptake patterns closely resembled the patterns that emerge from prolonged odorant exposures, suggesting that activity mapping over prolonged periods can identify areas of activity that are present when rats are still attending and responding to odorant stimuli. Given these findings, it seems important to consider the possibility that prolonged exposure to other sensory stimuli will reveal more realistic neural response patterns. PMID:20232477

  14. Arabidopsis thaliana natural variation reveals connections between UV radiation stress and plant pathogen-like defense responses.

    PubMed

    Piofczyk, Thomas; Jeena, Ganga; Pecinka, Ales

    2015-08-01

    UV radiation is a ubiquitous component of solar radiation that affects plant growth and development. Here we studied growth related traits of 345 Arabidopsis thaliana accessions in response to UV radiation stress. We analyzed the genetic basis of this natural variation by genome-wide association studies, which suggested a specific candidate genomic region. RNA-sequencing of three sensitive and three resistant accessions combined with mutant analysis revealed five large effect genes. Mutations in PHE ammonia lyase 1 (PAL1) and putative kinase At1g76360 rendered Arabidopsis hypersensitive to UV stress, while loss of function from putative methyltransferase At4g22530, novel plant snare 12 (NPSN12) and defense gene activated disease resistance 2 (ADR2) conferred higher UV stress resistance. Three sensitive accessions showed strong ADR2 transcriptional activation, accumulation of salicylic acid (SA) and dwarf growth upon UV stress, while these phenotypes were much less affected in resistant plants. The phenotype of sensitive accessions resembles autoimmune reactions due to overexpression of defense related genes, and suggests that natural variation in response to UV radiation stress is driven by pathogen-like responses in Arabidopsis. PMID:25656510

  15. TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus.

    PubMed

    Yu, Shaoyong; Ouyang, Ann

    2009-02-01

    Bradykinin (BK) activates sensory nerves and causes hyperalgesia. Transient receptor potential A1 (TRPA1) is expressed in sensory nerves and mediates cold, mechanical, and chemical nociception. TRPA1 can be activated by BK. TRPA1 knockout mice show impaired responses to BK and mechanical nociception. However, direct evidence from sensory nerve terminals is lacking. This study aims to determine the role of TRPA1 in BK-induced visceral mechanical hypersensitivity. Extracellular recordings of action potentials from vagal nodose and jugular neurons are performed in an ex vivo guinea pig esophageal-vagal preparation. Peak frequencies of action potentials of afferent nerves evoked by esophageal distension and chemical perfusion are recorded and compared. BK activates most nodose and all jugular C fibers. This activation is repeatable and associated with a significant increase in response to esophageal distension, which can be prevented by the B2 receptor antagonist WIN64338. TRPA1 agonist allyl isothiocyanate (AITC) activates most BK-positive nodose and jugular C fibers. This is associated with a transient loss of response to mechanical distensions and desensitization to a second AITC perfusion. Desensitization with AITC and pretreatment with TRPA1 inhibitor HC-030031 both inhibit BK-induced mechanical hypersensitivity but do not affect BK-evoked activation in nodose and jugular C fibers. In contrast, esophageal vagal afferent Adelta fibers do not respond to BK or AITC and fail to show mechanical hypersensitivity after BK perfusion. This provides the first evidence directly from visceral sensory afferent nerve terminals that TRPA1 mediates BK-induced mechanical hypersensitivity. This reveals a novel mechanism of visceral peripheral sensitization. PMID:19033534

  16. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota

    PubMed Central

    Rawls, John F.; Samuel, Buck S.; Gordon, Jeffrey I.

    2004-01-01

    Animals have developed the means for supporting complex and dynamic consortia of microorganisms during their life cycle. A transcendent view of vertebrate biology therefore requires an understanding of the contributions of these indigenous microbial communities to host development and adult physiology. These contributions are most obvious in the gut, where studies of gnotobiotic mice have disclosed that the microbiota affects a wide range of biological processes, including nutrient processing and absorption, development of the mucosal immune system, angiogenesis, and epithelial renewal. The zebrafish (Danio rerio) provides an opportunity to investigate the molecular mechanisms underlying these interactions through genetic and chemical screens that take advantage of its transparency during larval and juvenile stages. Therefore, we developed methods for producing and rearing germ-free zebrafish through late juvenile stages. DNA microarray comparisons of gene expression in the digestive tracts of 6 days post fertilization germ-free, conventionalized, and conventionally raised zebrafish revealed 212 genes regulated by the microbiota, and 59 responses that are conserved in the mouse intestine, including those involved in stimulation of epithelial proliferation, promotion of nutrient metabolism, and innate immune responses. The microbial ecology of the digestive tracts of conventionally raised and conventionalized zebrafish was characterized by sequencing libraries of bacterial 16S rDNA amplicons. Colonization of germ-free zebrafish with individual members of its microbiota revealed the bacterial species specificity of selected host responses. Together, these studies establish gnotobiotic zebrafish as a useful model for dissecting the molecular foundations of host-microbial interactions in the vertebrate digestive tract. PMID:15070763

  17. Metabolomics reveals insect metabolic responses associated with fungal infection.

    PubMed

    Xu, Yong-Jiang; Luo, Feifei; Gao, Qiang; Shang, Yanfang; Wang, Chengshu

    2015-06-01

    The interactions between insects and pathogenic fungi are complex. We employed metabolomic techniques to profile insect metabolic dynamics upon infection by the pathogenic fungus Beauveria bassiana. Silkworm larvae were infected with fungal spores and microscopic observations demonstrated that the exhaustion of insect hemocytes was coupled with fungal propagation in the insect body cavity. Metabolomic analyses revealed that fungal infection could significantly alter insect energy and nutrient metabolisms as well as the immune defense responses, including the upregulation of carbohydrates, amino acids, fatty acids, and lipids, but the downregulation of eicosanoids and amines. The insect antifeedant effect of the fungal infection was evident with the reduced level of maclurin (a component of mulberry leaves) in infected insects but elevated accumulations in control insects. Insecticidal and cytotoxic mycotoxins like oosporein and beauveriolides were also detected in insects at the later stages of infection. Taken together, the metabolomics data suggest that insect immune responses are energy-cost reactions and the strategies of nutrient deprivation, inhibition of host immune responses, and toxin production would be jointly employed by the fungus to kill insects. The data obtained in this study will facilitate future functional studies of genes and pathways associated with insect-fungus interactions. PMID:25895944

  18. Tolerant and Susceptible Sesame Genotypes Reveal Waterlogging Stress Response Patterns.

    PubMed

    Wang, Linhai; Li, Donghua; Zhang, Yanxin; Gao, Yuan; Yu, Jingyin; Wei, Xin; Zhang, Xiurong

    2016-01-01

    Waterlogging is a common adverse environmental condition that limits plant growth. Sesame (Sesamum indicum) is considered a drought-tolerant oil crop but is typically susceptible to harmful effects from waterlogging. The present study used comparative analysis to explore the waterlogging stress response associated with two sesame genotypes. The RNA-seq dataset generated during a time course of 0, 3, 9 and 15 h of waterlogging as well as 20 h post-drainage indicated that stress gradually suppressed the expression of sesame genes, with 9 h as the critical time point for the response of sesame to waterlogging stress. Of the 19,316 genes expressed during waterlogging, 72.1% were affected significantly. Sesame of both tolerant and susceptible genotypes showed decreased numbers of upregulated differentially expressed genes (DEGs) but increased numbers of downregulated DEGs at the onset of waterlogging. However, the tolerant-genotype sesame exhibited 25.5% more upregulated DEGs and 29.7% fewer downregulated DEGs than those of the susceptible-genotype strain between 3 and 15 h. The results indicated that the tolerant sesame displayed a more positive gene response to waterlogging. A total of 1,379 genes were significantly induced and commonly expressed in sesame under waterlogging conditions from 3 to 15 h regardless of tolerance level; of these genes, 98 are known homologous stress responsive genes, while the remaining 1,281 are newly reported here. This gene set may represent the core genes that function in response to waterlogging, including those related mainly to energy metabolism and phenylpropanoid biosynthesis. Furthermore, a set of 3,016 genes functioning in energy supply and cell repair or formation was activated in sesame recovery from waterlogging stress. A comparative analysis between sesame of the tolerant and susceptible genotypes revealed 66 genes that may be candidates for improving sesame tolerance to waterlogging. This study provided a comprehensive picture of the sesame gene expression pattern in response to waterlogging stress. These results will help dissect the mechanism of the sesame response to waterlogging and identify candidate genes to improve its tolerance. PMID:26934874

  19. Tolerant and Susceptible Sesame Genotypes Reveal Waterlogging Stress Response Patterns

    PubMed Central

    Wang, Linhai; Li, Donghua; Zhang, Yanxin; Gao, Yuan; Yu, Jingyin; Wei, Xin; Zhang, Xiurong

    2016-01-01

    Waterlogging is a common adverse environmental condition that limits plant growth. Sesame (Sesamum indicum) is considered a drought-tolerant oil crop but is typically susceptible to harmful effects from waterlogging. The present study used comparative analysis to explore the waterlogging stress response associated with two sesame genotypes. The RNA-seq dataset generated during a time course of 0, 3, 9 and 15 h of waterlogging as well as 20 h post-drainage indicated that stress gradually suppressed the expression of sesame genes, with 9 h as the critical time point for the response of sesame to waterlogging stress. Of the 19,316 genes expressed during waterlogging, 72.1% were affected significantly. Sesame of both tolerant and susceptible genotypes showed decreased numbers of upregulated differentially expressed genes (DEGs) but increased numbers of downregulated DEGs at the onset of waterlogging. However, the tolerant-genotype sesame exhibited 25.5% more upregulated DEGs and 29.7% fewer downregulated DEGs than those of the susceptible-genotype strain between 3 and 15 h. The results indicated that the tolerant sesame displayed a more positive gene response to waterlogging. A total of 1,379 genes were significantly induced and commonly expressed in sesame under waterlogging conditions from 3 to 15 h regardless of tolerance level; of these genes, 98 are known homologous stress responsive genes, while the remaining 1,281 are newly reported here. This gene set may represent the core genes that function in response to waterlogging, including those related mainly to energy metabolism and phenylpropanoid biosynthesis. Furthermore, a set of 3,016 genes functioning in energy supply and cell repair or formation was activated in sesame recovery from waterlogging stress. A comparative analysis between sesame of the tolerant and susceptible genotypes revealed 66 genes that may be candidates for improving sesame tolerance to waterlogging. This study provided a comprehensive picture of the sesame gene expression pattern in response to waterlogging stress. These results will help dissect the mechanism of the sesame response to waterlogging and identify candidate genes to improve its tolerance. PMID:26934874

  20. Central and peripheral hypersensitivity in the irritable bowel syndrome

    PubMed Central

    Zhou, QiQi; Fillingim, Roger B.; Riley, Joseph L.; Malarkey, William B.; Verne, G. Nicholas

    2010-01-01

    Previous investigations of somatic hypersensitivity in IBS patients have typically involved only a single stimulus modality, and little information exists regarding whether patterns of somatic pain perception vary across stimulus modalities within a group of patients with IBS. Therefore, the current study was designed to characterize differences in perceptual responses to a battery of noxious somatic stimuli in IBS patients compared to controls. A total of 78 diarrhea-predominant and 57 controls participated in the study. We evaluated pain threshold and tolerance and sensory and affective ratings of contact thermal, mechanical pressure, ischemic stimuli, and cold pressor stimuli. In addition to assessing perceptual responses, we also evaluated differences in neuroendocrine and cardiovascular responses to these experimental somatic pain stimuli. A subset of IBS patients demonstrated the presence of somatic hypersensitivity to thermal, ischemic, and cold pressor nociceptive stimuli. The somatic hypersensitivity in IBS patients was somatotopically organized in that the lower extremities that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. There were also changes in ACTH, cortisol, and systolic blood pressure in response to the ischemic pain testing in IBS patients when compared to controls. The results of this study suggest that a more widespread alteration in central pain processing in a subset of IBS patients may be present as they display hypersensitivity to heat, ischemic, and cold pressor stimuli. PMID:20074857

  1. Phenological sequences reveal aggregate life history response to climatic warming.

    PubMed

    Post, Eric S; Pedersen, Christian; Wilmers, Christopher C; Forchhammer, Mads C

    2008-02-01

    Climatic warming is associated with organisms breeding earlier in the season than is typical for their species. In some species, however, response to warming is more complex than a simple advance in the timing of all life history events preceding reproduction. Disparities in the extent to which different components of the reproductive phenology of organisms vary with climatic warming indicate that not all life history events are equally responsive to environmental variation. Here, we propose that our understanding of phenological response to climate change can be improved by considering entire sequences of events comprising the aggregate life histories of organisms preceding reproduction. We present results of a two-year warming experiment conducted on 33 individuals of three plant species inhabiting a low-arctic site. Analysis of phenological sequences of three key events for each species revealed how the aggregate life histories preceding reproduction responded to warming, and which individual events exerted the greatest influence on aggregate life history variation. For alpine chickweed (Cerastium alpinum), warming elicited a shortening of the duration of the emergence stage by 2.5 days on average, but the aggregate life history did not differ between warmed and ambient plots. For gray willow (Salix glauca), however, all phenological events monitored occurred earlier on warmed than on ambient plots, and warming reduced the aggregate life history of this species by 22 days on average. Similarly, in dwarf birch (Betula nana), warming advanced flower bud set, blooming, and fruit set and reduced the aggregate life history by 27 days on average. Our approach provides important insight into life history responses of many organisms to climate change and other forms of environmental variation. Such insight may be compromised by considering changes in individual phenological events in isolation. PMID:18409426

  2. Emotional face discrimination as revealed by electrophysiological periodic visual responses.

    PubMed

    Dzhelyova, Milena; Rossion, Bruno

    2015-01-01

    Being able to read social information is vital for an individual. A wealth of social cues is provided by the face, in particular emotional expressions. To address the question of how the brain discriminates emotional faces, we recorded electroencephalogram from 18 participants during a fast periodic oddball paradigm, which provides an objective, implicit and robust quantifiable measure of visual discrimination. The same face with a neutral expression was presented at a rate of 5.88 Hz during an 80 sec sequence. Every five faces, the same face displaying an emotional expression of fear, disgust or happiness (in different sequences), was presented, thus resulting in a sequence NNNNFNNNNFNNNNF (e.g., neutral-fear oddball sequence). The oddball 1.18Hz (5.88Hz/5) response and its harmonics (e.g., 2f = 2.36 Hz) were used to measure emotional face discrimination. This emotional face discrimination response was observed bilaterally at occipito-temporal sites. Furthermore, inverting the faces significantly reduced the brain response over the occipito-temporal regions for the oddball frequency, suggesting that it reflected high level processes related to the emotional faces. The response to happy faces was characterised with more dorsal distribution than angry and disgusted faces. The latter face type was characterised with more anterior scalp topography than the angry faces. An additional analysis confirmed the topographical differences and hinted at partly distinct neural generators. A complementary time domain analysis revealed several components discriminating neutral from emotional faces and an additional experiment comparing the mode of stimulus presentation - sine vs. square wave - suggested that these 3 components peaked at 120 ms (positive); 170 ms (negative) and 250 ms (positive) after stimulus onset. These observations provide new insights into the temporal dynamics of facial expression processing and show that the fast periodic oddball paradigm can be successfully employed to address processes underlying social perception. Meeting abstract presented at VSS 2015. PMID:26326379

  3. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    PubMed

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. PMID:26454262

  4. Metabolic Phenotyping Reveals a Lipid Mediator Response to Ionizing Radiation

    PubMed Central

    2015-01-01

    Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to ? radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to ? radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine. PMID:25126707

  5. Pepper Suppressor of the G2 Allele of skp1 Interacts with the Receptor-Like Cytoplasmic Kinase1 and Type III Effector AvrBsT and Promotes the Hypersensitive Cell Death Response in a Phosphorylation-Dependent Manner1[C][W][OPEN

    PubMed Central

    Kim, Nak Hyun; Kim, Dae Sung; Chung, Eui Hwan; Hwang, Byung Kook

    2014-01-01

    Xanthomonas campestris pv vesicatoria type III effector protein, AvrBsT, triggers hypersensitive cell death in pepper (Capsicum annuum). Here, we have identified the pepper SGT1 (for suppressor of the G2 allele of skp1) as a host interactor of AvrBsT and also the pepper PIK1 (for receptor-like cytoplasmic kinase1). PIK1 specifically phosphorylates SGT1 and AvrBsT in vitro. AvrBsT specifically binds to the CHORD-containing protein and SGT1 domain of SGT1, resulting in the inhibition of PIK1-mediated SGT1 phosphorylation and subsequent nuclear transport of the SGT1-PIK1 complex. Liquid chromatography-tandem mass spectrometry of the proteolytic peptides of SGT1 identified the residues serine-98 and serine-279 of SGT1 as the major PIK1-mediated phosphorylation sites. Site-directed mutagenesis of SGT1 revealed that the identified SGT1 phosphorylation sites are responsible for the activation of AvrBsT-triggered cell death in planta. SGT1 forms a heterotrimeric complex with both AvrBsT and PIK1 exclusively in the cytoplasm. Agrobacterium tumefaciens-mediated coexpression of SGT1 and PIK1 with avrBsT promotes avrBsT-triggered cell death in Nicotiana benthamiana, dependent on PIK1. Virus-induced silencing of SGT1 and/or PIK1 compromises avrBsT-triggered cell death, hydrogen peroxide production, defense gene induction, and salicylic acid accumulation, leading to the enhanced bacterial pathogen growth in pepper. Together, these results suggest that SGT1 interacts with PIK1 and the bacterial effector protein AvrBsT and promotes the hypersensitive cell death associated with PIK1-mediated phosphorylation in plants. PMID:24686111

  6. Hypersensitivity to chironomid larvae.

    PubMed

    Galindo, P A; Feo, F; Gmez, E; Borja, J; Melero, R; Lombardero, M; Barber, D; Garca Rodrguez, R

    1998-01-01

    Chironomid larvae (red midge larvae) are often used by aquarists as fish food. Their hemoglobins can cause IgE-mediated allergic diseases in exposed and unexposed people. The aim of this study was to find out the prevalence of positive skin tests to chironomids in patients suffering from rhinitis and/or bronchial asthma in Ciudad Real (Spain). A total of 465 patients were submitted to skin prick tests with chironomids in addition to common inhalant allergens. The patients with positive skin prick test (wheal > or = 3 mm) to these larvae answered a questionnaire. Skin prick tests with Acarus siro, shrimp, cockroach and mosquito (Culex pipiens) were carried out. Serum levels of total IgE and anti-Chironommus thummi, anti-Dermatophagoides pteronyssinus, anti-shrimp, and anti-mosquito (Aedes communis) IgE were determined. Conjunctival or nasal provocation tests were carried out with chironomids. Of the 465 patients skin tested, 19 showed a positive skin prick test with chironomids, corresponding to 4.1% of all patients and 6% of the atopic patients. None were monosensitized. Significant correlations were found between skin prick test results with chironomids and mites (p < 0.005). Of the 19 patients, 15 had positive skin prick test with the common mosquito C. pipiens. Seven patients showed elevated anti-D. pteronyssinus IgE, six elevated anti-shrimp IgE, and 10 showed elevated anti-A. communis IgE. Provocation tests with chironomids were positive in 14 patients (four nasal and 10 conjunctival tests). Conjunctival provocation tests were carried out in 16 controls and were positive in three; all three showed positive skin prick test with chironomids. One patient had occupational allergy from the larvae (aquarist). After mosquito bites, five patients showed immediate wheal reactions and one patient suffered an anaphylactic reaction after several mosquito bites. Only two patients remembered having been in contact with chironomids as fish food. We found hypersensitivity to these larvae in patients without apparent contact to them. These patients could have become sensitized in various ways, including: 1) inhaling particles of chironomids or others that are cross-reactive with them; 2) exposure to products used as fish food containing chironomids; and, 3) through cross-reactivity with other allergens such as mites, shrimp or mosquitoes. PMID:9777536

  7. Isolation of ABA hypersensitive mutants in allhexaploid breadwheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The plant hormone abscisic acid (ABA) stimulates seed dormancy during embryo maturation, inhibits germination of mature seed, and stimulates stress responses such as stomatal closure in response to drought stress. Arabidopsis mutants isolated for ABA hypersensitive (ABH) seed germination showed incr...

  8. Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

    PubMed

    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 36.6C 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. PMID:22329454

  9. [CT findings of hypersensitivity pneumonitis].

    PubMed

    Kobayashi, H; Matsuoka, R; Mieno, T; Kitamura, S

    1989-04-01

    CT findings of 22 cases of hypersensitivity pneumonitis (HP) were evaluated on 1 cm slices. All cases were diagnosed by transbronchial lung biopsy and clinical information. The study population included 8 men and 14 women with a mean age of 43 years. The causative antigens were considered to be so-called summer type in 17 cases, air humidifier in 1, pigeon in 1 and paint spray (isocyanate was suspected) in 3. CT examination were performed at a mean of 1.5 weeks after admission. In conclusion, characteristic CT findings of HP include combination of small nodular shadows and slight elevation of lung density. The size of nodular shadows was usually within 1 cm diameter, and their distribution was considered to be a centrilobular pattern, representing alveolitis and granuloma formation in a secondary lobule. It was though that the slight elevation of lung density developed when the disease extended all over the secondary lobule and the nodules developed when the disease was limited to the centrilobular lesion. In most cases, significant changes in proximal bronchi and pulmonary vasculatures could not be detected. The presence of segmental or lobar distribution of the shadows was also suggested. In addition to the typical findings, various other findings were also revealed; irregular shaped dense shadows, subpleural curvilinear shadow and honeycombing formation, especially in chronic cases. These findings have caused some difficulty in distinguishing HP from other interstitial diseases. More precise information can probably be obtained by thin slice CT than by 1 cm slice thicknesses, nevertheless, the standard method of CT should yield a useful diagnostic imaging. PMID:2796055

  10. Phenylalanine ammonia-lyase in tobacco. Molecular cloning and gene expression during the hypersensitive reaction to tobacco mosaic virus and the response to a fungal elicitor.

    PubMed Central

    Pellegrini, L; Rohfritsch, O; Fritig, B; Legrand, M

    1994-01-01

    A tobacco (Nicotiana tabacum L. cv Samsun NN) cDNA clone coding the enzyme phenylalanine ammonia-lyase (PAL) was isolated from a cDNA library made from polyadenylated RNA purified from tobacco mosaic virus (TMV)-infected leaves. Southern analysis indicated that, in tobacco, PAL is encoded by a small family of two to four unclustered genes. Northern analysis showed that PAL genes are weakly expressed under normal physiological conditions, they are moderately and transiently expressed after wounding, but they are strongly induced during the hypersensitive reaction to TMV or to a fungal elicitor. Ribonuclease protection experiments confirmed this evidence and showed the occurrence of two highly homologous PAL messengers originating from a single gene or from two tightly co-regulated genes. By in situ RNA-RNA hybridization PAL transcripts were shown to accumulate in a narrow zone of leaf tissue surrounding necrotic lesions caused by TMV infection or treatment with the fungal elicitor. In this zone, no cell specificity was observed and there was a decreasing gradient of labeling from the edge of necrosis. Some labeling was also found in various cell types of young, healthy stems and was shown to accumulate in large amounts in the same cell types after the deposition of an elicitor solution at the top of the decapitated plant. PMID:7824656

  11. Hypersensitivity reaction associated with phenytoin

    PubMed Central

    Indu, T. H.; Basutkar, Roopa Satyanarayan

    2015-01-01

    Hypersensitivity reactions with antiepileptic drugs (AEDs) are generally associated with aromatic AEDs. We present a case of hypersensitivity reactions followed by administration of phenytoin with diazepam and ranitidine in a patient with generalized tonic-clonic seizures. Antigen-antibody reactions or decreased levels of epoxide hydrolase are well known with phenytoin. Increased level of serum phenytoin causing toxicities due to competitive inhibition with diazepam on co-administration was also reported in the literature. Prevention of the adverse effects with AEDs is a multi-stage process, which requires implementation of preventive measures through careful monitoring and prompts interventions. PMID:26692739

  12. Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation

    PubMed Central

    Tague, Sarah E.; Clarke, Gwenalle L.; Winter, Michelle K.; McCarson, Kenneth E.; Wright, Douglas E.; Smith, Peter G.

    2012-01-01

    Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin D deficient. Previous findings demonstrated that putative nociceptors (pain-sensing nerves) express vitamin D receptors (VDRs), suggesting responsiveness to 1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient diets for 2 4 weeks showed mechanical deep muscle hypersensitivity, but not cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance deficits and occurred before onset of overt muscle or bone pathology. Hypersensitivity was not due to hypocalcemia and was actually accelerated by increased dietary calcium. Morphometry of skeletal muscle innervation showed increased numbers of presumptive nociceptor axons (peripherin-positive axons containing calcitonin gene-related peptide), without changes in sympathetic or skeletal muscle motor innervation. Similarly, there was no change in epidermal innervation. In culture, sensory neurons displayed enriched VDR expression in growth cones, and sprouting was regulated by VDR-mediated rapid response signaling pathways, while sympathetic outgrowth was not affected by different concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D deficiency can lead to selective alterations in target innervation, resulting in presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is likely to contribute to muscular hypersensitivity and pain. PMID:21957236

  13. Suppressive subtraction hybridization reveals that rice gall midge attack elicits plant-pathogen-like responses in rice.

    PubMed

    Rawat, Nidhi; Himabindu, Kudapa; Neeraja, Chiruvuri Naga; Nair, Suresh; Bentur, Jagadish S

    2013-02-01

    The Asian rice gall midge, Orseolia oryzae (Diptera: Cecidomyiidae), is the third most destructive insect pest of rice (Oryza sativa L.). Till date, 11 gall midge resistance gene loci have been characterized in different rice varieties. To elucidate molecular basis of incompatible (hypersensitive response plus [HR+] type) and compatible rice-gall midge interactions, two suppressive subtraction hybridization cDNA libraries were constructed. These were enriched for differentially expressed transcripts after gall midge infestation in two rice varieties (resistant Suraksha and susceptible TN1). In total, 2784 ESTs were generated and sequenced from the two libraries, of which 1536 were from the resistant Suraksha and 1248 were from the susceptible TN1. Majority (80%) of the ESTs was non-redundant sequences with known functions and was classified into three principal gene ontology (GO) categories and 12 groups. Upregulation of NBS-LRR, Cytochrome P450, heat shock proteins, phenylalanine ammonia lyase and OsPR10α genes from the Suraksha library, as revealed by real-time PCR, indicated that R gene mediated, salicylic acid related defense pathway is likely to be involved in gall midge resistance. Present study suggested that resistance in Suraksha against gall midge is similar in nature to the resistance observed in plants against pathogens. However, in TN1, genes related to primary metabolism and redox were induced abundantly. Results suggested that genes encoding translationally controlled tumor protein and NAC domain proteins are likely to be involved in the gall midge susceptibility. PMID:23257077

  14. TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHAEL (IT) EXPOSURES

    EPA Science Inventory

    ABSTRACT for 2001 DMS213

    TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN
    MICE AFTER DERMAL AND INTRATRACHEAL (IT) EXPOSURES. E Boykin, M Ward, MJ Selgrade, and D Sailstad. NHEERL, ORD, US EPA, RTP, NC, USA.
    TMA causes respiratory hypersensitivity (RH) responses. W...

  15. TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER MULTIPLE INTRATRACHAEL (IT) EXPOSURE

    EPA Science Inventory

    SOT 2001 DMS214

    TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN
    MICE AFTER MULTIPLE INTRATRACHEAL (IT) EXPOSURES. D Sailstad, E Boykin, M Ward, and MJ Selgrade. NHEERL, ORD, US EPA, RTP, NC, USA.
    TMA causes Th2 related respiratory hypersensitivity (RH) responses. W...

  16. Chlorhexidine and hypersensitivity reactions in dentistry.

    PubMed

    Pemberton, M N; Gibson, J

    2012-12-01

    Immunological reactions to chlorhexidine, including allergy (Type I hypersensitivity) and allergic contact dermatitis/stomatitis (Type IV hypersensitivity), have been recognised for many years. This potential safety issue, however, is not well known within dentistry. The purpose of this paper is to alert dentists and dental care professionals to the potential of chlorhexidine in causing hypersensitivity reactions and to consider this possibility if unexplained hypersensitivity reactions occur. PMID:23222325

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

    PubMed

    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. PMID:25738554

  18. Antibody and delayed-type hypersensitivity responses to Ochrobactrum anthropi cytosolic and outer membrane antigens in infections by smooth and rough Brucella spp.

    PubMed Central

    Velasco, J; Daz, R; Grill, M J; Barbern, M; Marn, C; Blasco, J M; Moriyn, I

    1997-01-01

    Immunological cross-reactions between Brucella spp. and Ochrobactrum anthropi were investigated in animals and humans naturally infected by Brucella spp. and in experimentally infected rams (Brucella ovis infected), rabbits (Brucella melitensis infected), and mice (B. melitensis and Brucella abortus infected). In the animals tested, O. anthropi cytosolic proteins evoked a delayed-type hypersensitivity reaction of a frequency and intensity similar to that observed with B. melitensis brucellin. O. anthropi cytosolic proteins also reacted in gel precipitation tests with antibodies in sera from Brucella natural hosts with a frequency similar to that observed with B. melitensis proteins, and absorption experiments and immunoblotting showed antibodies to both Brucella-specific proteins and proteins common to Brucella and O. anthropi. No antibodies to O. anthropi cytosolic proteins were detected in the sera of Brucella-free hosts. Immunoblotting with sera of Brucella-infected sheep and goats showed immunoglobulin G (IgG) to Brucella group 3 outer membrane proteins and to O. anthropi proteins of similar molecular weight. No IgG to the O-specific polysaccharide of O. anthropi lipopolysaccharide was detected in the sera of Brucella-infected hosts. The sera of sheep, goats, and rabbits infected with B. melitensis contained IgG to O. anthropi rough lipopolysaccharide and lipid A, and B. ovis and O. anthropi rough lipopolysaccharides showed equal reactivities with IgG in the sera of B. ovis-infected rams. The findings show that the immunoresponse of Brucella-infected hosts to protein antigens is not necessarily specific for brucellae and suggest that the presence of O. anthropi or some related bacteria explains the previously described reactivities to Brucella rough lipopolysaccharide and outer membrane proteins in healthy animals. PMID:9144364

  19. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    SciTech Connect

    Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-03-01

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with /sup 14/C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A/sub 2/ (TXA/sub 2/) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more /sup 14/C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p < 0.001; /sup 14/C release: 1.5 +/- 0.5%, p < 0.002) in response to thrombin (0.075 U/ml). Thus, a pathway independent of released ADP or TXA/sub 2/ formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of /sup 125/I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA/sub 2/ formation, the action of released ADP or increased thrombin binding.

  20. Modulation of Th1/Th2 immune responses by killed Propionibacterium acnes and its soluble polysaccharide fraction in a type I hypersensitivity murine model: induction of different activation status of antigen-presenting cells.

    PubMed

    Squaiella-Baptisto, Carla Cristina; Teixeira, Daniela; Mussalem, Juliana Sekeres; Ishimura, Mayari Eika; Longo-Maugri, Ieda Maria

    2015-01-01

    Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model. PMID:25973430

  1. Modulation of Th1/Th2 Immune Responses by Killed Propionibacterium acnes and Its Soluble Polysaccharide Fraction in a Type I Hypersensitivity Murine Model: Induction of Different Activation Status of Antigen-Presenting Cells

    PubMed Central

    Mussalem, Juliana Sekeres; Ishimura, Mayari Eika; Longo-Maugéri, Ieda Maria

    2015-01-01

    Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model. PMID:25973430

  2. Management of hypersensitivity reactions to anti-D immunoglobulin preparations.

    PubMed

    Rutkowski, K; Nasser, S M

    2014-11-01

    RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh isoimmunization. Its use has significantly reduced the incidence of haemolytic disease of the foetus and newborn previously responsible for one death in every 2200 births. In pregnancy, acute drug-induced hypersensitivity reactions including anaphylaxis can have serious deleterious effects on the mother and foetus/neonate. Women can be erroneously labelled as drug allergic as the investigation of hypersensitivity reactions in pregnancy is complex and drug challenges are usually contraindicated. We present three cases of suspected anti-D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion-related reaction. We also propose a new algorithm for the investigations of such reaction. It relies on detailed history, cautious interpretation of skin tests, foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges. This is not to deprive women of anti-D which might put their future pregnancies at risk. PMID:25066207

  3. Central hypersensitivity in chronic musculoskeletal pain.

    PubMed

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-05-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold 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 level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity. PMID:25952059

  4. Immunosuppressive effects of transforming growth factor beta: inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response.

    PubMed

    Epstein, S P; Baer, R L; Thorbecke, G J; Belsito, D V

    1991-06-01

    Recent reports show that transforming growth factor (TGF)-beta exerts a variety of immunosuppressive activities. The present study focuses on the effects of TGF-beta 1 on expression of Ia antigen by Langerhans cells. Although TGF-beta 1, in concentrations from 0.001 to 100 micrograms/ml, has no effect on constitutive expression of Ia antigen on these cells, the in vitro up-regulation of Ia antigen on the surface of LC by interleukin (IL)-1, tumor necrosis factor-alpha, interferon-gamma, IL-3, and granulocyte/macrophage-colony stimulating factor is inhibited by the concomitant addition of 1 microgram/ml TGF-beta 1. In contrast, TGF-beta 1 has no effect on the up-regulation induced by IL-2 or IL-6. In this report, the activity of TGF-beta closely resembles that of Cyclosporine A (CsA). Similar results are seen in vivo when either TGF-beta 1 (5 micrograms, intraperitoneally [ip], daily on days 0-3) or CsA (1 mg, subcutaneously [sc], twice daily on days 0-3) are given together with IL-2 (500 U, intraperitoneally [ip], twice daily on days 1-3) or interferon-gamma (4,000 U, ip, twice daily on days 1-3). Given the important role of Ia expression in cell-mediated immune reactions, the effect of TGF-beta on contact sensitivity was next investigated. In doses of 5 micrograms, ip, daily on days 6-8, TGF-beta inhibits the expression of contact reactivity in animals sensitized on day 0 and challenged on day 7. In contrast, no effect is observed on the induction of contact sensitivity in mice given TGF-beta 1 on days--1 to 2, sensitized on day 0, and challenged on day 7. The possible importance of antagonism between TGF-beta and other cytokines, especially IFN-gamma, involved in the elicitation of contact hypersensitivity reactions is discussed. PMID:2045671

  5. CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity.

    PubMed

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

    2015-12-01

    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) ?(+) 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(+)Ly6C(hi)) 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

  6. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/interferon gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity1

    PubMed Central

    Lu, Thomas X.; Hartner, Jochen; Lim, Eun-Jin; Fabry, Victoria; Mingler, Melissa K.; Cole, Eric T.; Orkin, Stuart H.; Aronow, Bruce J.; Rothenberg, Marc E.

    2011-01-01

    An altered balance between Th1 and Th2 cytokines is responsible for a variety of immuno-inflammatory disorders such as asthma, yet the role of post-transcriptional mechanisms, such as those mediated by microRNAs, in adjusting the relative magnitude and balance of Th cytokine expression have been largely unexplored. Here we show that miR-21 has a central role in setting a balance between Th1 and Th2 responses to antigens. Targeted ablation of miR-21 in mice led to reduced lung eosinophilia after allergen challenge, with a broadly reprogrammed immunoactivation transcriptome, and significantly increased levels of the Th1 cytokine IFN?. Biological network-based transcriptome analysis of OVA-challenged miR-21-/-mice identified an unexpected prominent dysregulation of IL-12/IFN? pathways as the most significantly affected in the lungs with a key role for miR-21 in IFN? signaling and T-cell polarization, consistent with a functional miR-21 binding site in IL-12p35. In support of these hypotheses, miR-21 deficiency led dendritic cells to produce more IL-12 after LPS stimulation, and OVA-challenged CD4+ T lymphocytes to produce increased IFN? and decreased IL-4. Further, loss of miR-21 significantly enhanced the Th1-associated delayed-type hypersensitivity cutaneous responses. Thus, our results define miR-21 as a major regulator of Th1 vs. Th2 responses, defining a new mechanism for regulating polarized immuno-inflammatory responses. PMID:21849676

  7. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity.

    PubMed

    Lu, Thomas X; Hartner, Jochen; Lim, Eun-Jin; Fabry, Victoria; Mingler, Melissa K; Cole, Eric T; Orkin, Stuart H; Aronow, Bruce J; Rothenberg, Marc E

    2011-09-15

    An altered balance between Th1 and Th2 cytokines is responsible for a variety of immunoinflammatory disorders such as asthma, yet the role of posttranscriptional mechanisms, such as those mediated by microRNAs (miRs), in adjusting the relative magnitude and balance of Th cytokine expression have been largely unexplored. In this study, we show that miR-21 has a central role in setting a balance between Th1 and Th2 responses to Ags. Targeted ablation of miR-21 in mice led to reduced lung eosinophilia after allergen challenge, with a broadly reprogrammed immunoactivation transcriptome and significantly increased levels of the Th1 cytokine IFN-?. Biological network-based transcriptome analysis of OVA-challenged miR-21(-/-) mice identified an unexpected prominent dysregulation of IL-12/IFN-? pathways as the most significantly affected in the lungs, with a key role for miR-21 in IFN-? signaling and T cell polarization, consistent with a functional miR-21 binding site in IL-12p35. In support of these hypotheses, miR-21 deficiency led dendritic cells to produce more IL-12 after LPS stimulation and OVA-challenged CD4(+) T lymphocytes to produce increased IFN-? and decreased IL-4. Further, loss of miR-21 significantly enhanced the Th1-associated delayed-type hypersensitivity cutaneous responses. Thus, our results define miR-21 as a major regulator of Th1 versus Th2 responses, defining a new mechanism for regulating polarized immunoinflammatory responses. PMID:21849676

  8. Flower Development under Drought Stress: Morphological and Transcriptomic Analyses Reveal Acute Responses and Long-Term Acclimation in Arabidopsis[C][W

    PubMed Central

    Su, Zhao; Ma, Xuan; Guo, Huihong; Sukiran, Noor Liyana; Guo, Bin; Assmann, Sarah M.; Ma, Hong

    2013-01-01

    Drought dramatically affects plant growth and crop yield, but previous studies primarily examined responses to drought during vegetative development. Here, to study responses to drought during reproductive development, we grew Arabidopsis thaliana plants with limited water, under conditions that allowed the plants to initiate and complete reproduction. Drought treatment from just after the onset of flowering to seed maturation caused an early arrest of floral development and sterility. After acclimation, plants showed reduced fertility that persisted throughout reproductive development. Floral defects included abnormal anther development, lower pollen viability, reduced filament elongation, ovule abortion, and failure of flowers to open. Drought also caused differential expression of 4153 genes, including flowering time genes FLOWERING LOCUS T, SUPPRESSOR OF OVEREXPRESSION OF CO1, and LEAFY, genes regulating anther and pistil development, and stress-related transcription factors. Mutant phenotypes of hypersensitivity to drought and fewer differentially expressed genes suggest that DEHYDRATION RESPONSE ELEMENT B1A may have an important function in drought response in flowers. A more severe filament elongation defect under drought in myb21 plants demonstrated that appropriate stamen development requires MYB DOMAIN PROTEIN 21 under drought conditions. Our study reveals a regulatory cascade in reproductive responses and acclimation under drought. PMID:24179129

  9. 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.

    PubMed

    Sueldo, Daniela J; Shimels, Mahdere; Spiridon, Laurentiu N; Caldararu, Octav; Petrescu, Andrei-Jose; Joosten, Matthieu H A J; Tameling, Wladimir I L

    2015-10-01

    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 Required for HR-Associated Cell Death-1) is a tomato (Solanum lycopersicum) NB-LRR protein that participates in the signalling cascade leading to resistance to the pathogens Cladosporium fulvum and Verticillium dahliae. To identify mutations in NRC1 that cause increased signalling activity, we generated a random library of NRC1 variants mutated in their nucleotide-binding domain and screened them for the ability to induce an elicitor-independent HR in Nicotiana tabacum. Screening of 1920 clones retrieved 11 gain-of-function mutants, with 10 of them caused by a single amino acid substitution. All substitutions are located in or very close to highly conserved motifs within the nucleotide-binding domain, suggesting modulation of the signalling activity of NRC1. Three-dimensional modelling of the nucleotide-binding domain of NRC1 revealed that the targeted residues are centred around the bound nucleotide. Our mutational approach has generated a wide set of novel gain-of-function mutations in NRC1 and provides insight into how the activity of this NB-LRR is regulated. PMID:26009937

  10. Regulation of delayed-type hypersensitivity-like responses in the mouse lung, determined with histological procedures: serotonin, T-cell suppressor-inducer factor and high antigen dose tolerance regulate the magnitude of T-cell dependent inflammatory reactions.

    PubMed Central

    Garssen, J; Nijkamp, F P; Wagenaar, S S; Zwart, A; Askenase, P W; Van Loveren, H

    1989-01-01

    We have studied delayed-type hypersensitivity (DTH) responses to picryl chloride (PCl) in the lungs of mice. Intranasal challenge with 0.6% picryl sulphonic acid (PSA), a water soluble form of PCl, of BALB/c mice, sensitized with PCl epicutaneously 1 week earlier, induced an accumulation of mononuclear inflammatory cells around bronchioli and blood vessels. Maximal inflammatory responses were seen 48 hr after challenge. These responses were antigen-specific, and also T-cell dependent, since athymic nude mice failed to show this reaction. A role for mast cells in the responses was studied using two strains of mast cell-deficient mice. In one of these (W/Wv) lung DTH responses to PCl were reduced severely. In the other strain (S1/S1d) the responses around vessels were decreased slightly, whereas the responses in the interstitial tissue and around bronchioli were similar to those in +/+ littermate controls. Involvement of serotonin was investigated using two serotonin receptor antagonists, i.e. methysergide and ketanserin. Treatment of mice with either of the antagonists prevented occurrence of the DTH-like reaction in the lung after intranasal antigen challenge. In the lungs of sensitized mice, significantly increased permeability was established 2 hr after antigen challenge. It was concluded that release of serotonin in the lung may provide an environment that comprises local vascular permeability and that facilitates the local recruitment and possibly the activation of DTH effector T cells, leading to subsequent attraction of mononuclear leucocytes into the lung. Immunological regulation of the DTH-like reactions in the lung was similar to that of contact sensitivity in the skin, since intravenous injection of an antigen-specific T-cell suppressor inducer factor prior to sensitization or pretreatment with a high dose of picryl sulphonic acid intravenously both resulted in reduction of the DTH-like lung histological response to picryl sulphonic acid. From these findings it was concluded that DTH-like lung responses are similar to DTH responses in the skin. Images Figure 1 Figure 3 PMID:2807371

  11. [Hypersensitivity pneumonitis caused by Trichoderma viride].

    PubMed

    Enrquez-Matas, Alicia; Quirce, Santiago; Cubero, Noelia; Sastre, Joaqun; Melchor, Rosario

    2009-06-01

    Hypersensitivity pneumonitis (HP) can be induced by exposure to indoor molds contaminating humidifiers and heating or ventilation systems. A 54-year-old woman with dyspnea, cough, chest pain, and fever was seen in the emergency room. A chest radiograph revealed interstitial infiltrates and blood tests showed leukocytosis with neutrophilia and severe hypoxemia. A diagnosis of HP was made by a combination of clinical, radiologic, physiologic, and immunologic studies. Trichoderma viride was isolated in cultures of water samples from an ultrasonic humidifier installed in the patient's home a year earlier. Precipitating immunoglobulin G antibodies to T viride were detected in the patient's serum by enzyme-linked immunosorbent assay. The patient remained symptom free after the humidifier was removed from her home. Our findings strongly suggest that the patient developed HP due to T viride from the humidifier. To our knowledge, this is the first report of such a case. PMID:19442428

  12. Role of the zinc-finger and basic motifs of chrysanthemum virus B p12 protein in nucleic acid binding, protein localization and induction of a hypersensitive response upon expression from a viral vector.

    PubMed

    Lukhovitskaya, N I; Ignatovich, I V; Savenkov, E I; Schiemann, J; Morozov, S Yu; Solovyev, A G

    2009-03-01

    The genomes of carlaviruses encode cysteine-rich proteins (CRPs) of unknown function. The 12 kDa CRP of chrysanthemum virus B (CVB), p12, has been shown previously to induce a hypersensitive response (HR) when expressed from potato virus X (PVX). This study demonstrated that a p12-induced HR was preceded by induction of a number of genes related to pathogenesis, stress and systemic acquired resistance. p12 localized predominantly to the nucleus. Interestingly, it was found that p12 bound both RNA and DNA in vitro, but notably exhibited a preference for DNA in the presence of Zn(2+) ions. Mutational analysis of the p12 conserved sequence motifs demonstrated that the basic motif is required for p12 translocation to the nucleus, thus representing part of the protein nuclear localization signal, whereas the predicted zinc finger motif is needed for both Zn(2+)-dependent DNA binding and eliciting an HR in PVX-infected leaves. Collectively, these results link, for the first time, nuclear localization of the protein encoded by a cytoplasmically replicating virus and its DNA-binding capacity with HR induction. Furthermore, these data suggest that p12 may mediate induction of the host genes by binding to the plant genomic DNA, and emphasize that CVB p12 is functionally distinct from other known nuclear-localized proteins encoded by the plant positive-stranded RNA viruses. PMID:19218219

  13. Divergent responses of Pygoscelis penguins reveal a common environmental driver.

    PubMed

    Hinke, Jefferson T; Salwicka, Kasia; Trivelpiece, Susan G; Watters, George M; Trivelpiece, Wayne Z

    2007-10-01

    The responses of predators to environmental variability in the Antarctic Peninsula region have exhibited divergent patterns owing to variation in the geographic settings of colonies and predator life-history strategies. Five breeding colonies of Pygoscelis penguins from King George Island and Livingston Island, South Shetland Islands, Antarctica, were examined to (1) compare the responses of sympatric congeners to recent changes in their Antarctic ecosystem and (2) assess underlying causes for such responses. We used linear regression and correlation analyses to compare indices of abundance, recruitment, and summer breeding performance of the Adlie (P. adeliae), gentoo (P. papua), and chinstrap penguins (P. antarctica). Breeding colonies of Adlie and chinstrap penguins have declined by roughly 50% since the mid-1970s, and recruitment indices of Adlie penguins have declined by roughly 80%, but no such patterns are evident for gentoo penguins. Fledging success, however, has remained stable at all breeding colonies. The different trends in abundance and recruitment indices for each species, despite generally similar indices of summer performance, suggest that winter conditions contribute to the divergent responses among the penguins. In particular, strong correlations between indices of penguin and krill recruitment suggest that penguins in the South Shetland Islands may live under an increasingly krill-limited system that has disproportionate effects on the survival of juvenile birds. PMID:17566778

  14. Hypersensitivity pneumonitis in a high school teacher.

    PubMed

    Moniodis, A; Hamilton, T; Racila, E; Cockrill, B; McCunney, R

    2015-10-01

    Hypersensitivity pneumonitis (HP) is an inflammatory lung disease mediated by an immunological response to an inhaled antigen. Outbreaks of HP have been reported in industrial settings where manufacturing workers are exposed to water-based metalworking fluids (MWFs). Water-based MWFs promote growth of microorganisms and can be easily aerosolized and are thus potential aetiological agents of HP. We present a case of HP caused by exposure to water-based MWF in a vocational high school teacher. Culture of MWF used at his school grew Pseudomonas pseudoalcaligenes. This is the first known report of MWF-induced HP outside an industrial setting. The growth of Pseudomonas spp in this case recalls the earliest reports of the microbiology of MWF-induced HP and suggests that routine bacterial culture may be useful in the diagnosis of HP in workplaces without standard cleaning and biocide regulations. PMID:26136595

  15. Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty

    PubMed Central

    Mihalko, William M.; Grupp, Thomas M.; Manning, Blaine T.; Dennis, Douglas A.; Goodman, Stuart B.; 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. PMID:25883940

  16. Mediated amperometry reveals different modes of yeast responses to sugars.

    PubMed

    Garjonyte, Rasa; Melvydas, Vytautas; Malinauskas, Albertas

    2016-02-01

    Menadione-mediated amperometry at carbon paste electrodes modified with various yeasts (Saccharomyces cerevisiae, Candida pulcherrima, Pichia guilliermondii and Debaryomyces hansenii) was employed to monitor redox activity inside the yeast cells induced by glucose, fructose, sucrose, maltose or galactose. Continuous measurements revealed distinct modes (transient or gradually increasing) of the current development during the first 2 to 3 min after subjection to glucose, fructose and sucrose at electrodes containing S. cerevisiae and non-Saccharomyces strains. Different modes (increasing or decreasing) of the current development after yeast subjection to galactose at electrodes with S. cerevisiae or D. hansenii and at electrodes with C. pulcherrima and P. guilliermondii suggested different mechanisms of galactose assimilation. PMID:26523505

  17. [Medicine hypersensitivity--case report].

    PubMed

    Zdziarski, Przemys?aw

    2004-04-01

    In this paper a case of good tolerance to benzathine benzylpenicillin, but benzylpenicillin potassium allergy in subject with history of multidrug hypersensitivity was described. The same therapeutic agent is contained in both commercial drugs and dosage formulation can cause the unpredictable adverse drug reactions (ADRs). This thesis was confirmed by positive intradermal test with the same, but negative with other commercial product of benzylpenicillin potassium. Later chromatographic analysis shows drug contaminations. Thus an exclusion of allergy to drug impurities (and additives) is necessary for correct diagnosis benzylpenicillin allergy (and any active constituent). Furthermore, allergy to drug impurities (and additives) closely resemble cross-reactions or multiple chemical sensitivity syndrome (MCSS). PMID:15517938

  18. The appearance of DNase I hypersensitive sites at the 5' end of the late SV40 genes is correlated with the transcriptional switch.

    PubMed Central

    Cremisi, C

    1981-01-01

    DNase I digestion of the SV40 nuclear chromosome late in infection reveals three hypersensitive sites on the late side of the Bg1 I site. Two of these sites at bp 370, 270 correspond to the 5' side of the late transcripts while the third at bp 190, to a region that is required for early transcription. Early in infection, as well as in an SV40 transformed cell line and a T-Ag negative revertant (deleted in the coding region for T-Ag) only one of these sites is present - the one associated with early transcription. Thus, the positions of these major hypersensitive sites are related to the differential expression of the early and late genes. The presence of the characteristic hypersensitive site corresponding to "early" region expression in the revertant, where large T antigen is not synthesized, but where the early "promotor" is intact, indicates that large T antigen is not responsible for this particular hypersensitive site. Additional minor specific DNase I cuts were found on the early genes, at early times only, at 300, 550, 850 bp from Bg1 I site. In the transformed cell line, one of these minor cuts is found about 350-400 bp from the Bg1 I site and in the revertant, where this region is deleted, a new site is created at 100 bp. Images PMID:6273814

  19. Radiobiological Response of Cervical Cancer Cell Line in Low Dose Region: Evidence of Low Dose Hypersensitivity (HRS) and Induced Radioresistance (IRR)

    PubMed Central

    Singh, Rabiraja; George, Daicy; Vijaykumar, T.S.; John, Subhashini

    2015-01-01

    Background Purpose of the present study was to examine the response of cervical cancer cell line (HeLa cell line) to low dose radiation using clonogenic assay and mathematical modeling of the low dose response by Joiners induced repair model. Materials and Methods Survival of HeLa cells following exposure to single and fractionated low doses of ? (gamma)-ray, 6 MV, and 15 MV photon was measured by clonogenic assay. Results HeLa cell line demonstrated marked low dose response consisting of an area of HRS and IRR in the dose region of <1 Gy. The two gradients of the low dose region (?s and ?r) were distinctly different with a transition dose (Dc) of 0.28-0.40 cGy. Conclusion HeLa cell line demonstrates marked HRS and IRR with distinct transition dose. This may form the biological basis of the clinical study to investigate the chemo potentiating effect of low dose radiation in cervical cancer. PMID:26266200

  20. Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast

    PubMed Central

    Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara; Dodgson, Stacie E; Gygi, Steven P; Amon, Angelika; Torres, Eduardo M

    2014-01-01

    Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms. DOI: http://dx.doi.org/10.7554/eLife.03023.001 PMID:25073701

  1. Global response of M-I coulping revealed by AMPERE

    NASA Astrophysics Data System (ADS)

    Waters, C. L.; Anderson, B. J.; Korth, H.

    2014-12-01

    The Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) provides one of the few in-situ datasets that allows studies of global properties of magnetosphere-ionosphere (M-I) interactions. The characterisation of the Birkeland currents, sensed by the Iridium constellation of satellites for both hemispheres simultaneously, is possible particularly for storm-time events. Other data sets (e.g. HF radar) that provide large spatial coverage may also be combined with AMPERE data in order to understand hemisphere differences in power input. In this presentation, we focus on the ability of AMPERE data to provide details of M-I coupling in both hemispheres simultaneously. The presentation will be illustrated using examples showing comparisons from north and south hemisphere Birkeland current configurations and Poynting flux.

  2. Desensitizing Agent Reduces Dentin Hypersensitivity During Ultrasonic Scaling: A Pilot Study

    PubMed Central

    Suda, Tomonari; Akiyama, Toshiharu; Takano, Takuya; Gokyu, Misa; Sudo, Takeaki; Khemwong, Thatawee; Izumi, Yuichi

    2015-01-01

    Background Dentin hypersensitivity can interfere with optimal periodontal care by dentists and patients. The pain associated with dentin hypersensitivity during ultrasonic scaling is intolerable for patient and interferes with the procedure, particularly during supportive periodontal therapy (SPT) for patients with gingival recession. Aim This study proposed to evaluate the desensitizing effect of the oxalic acid agent on pain caused by dentin hypersensitivity during ultrasonic scaling. Materials and Methods This study involved 12 patients who were incorporated in SPT program and complained of dentin hypersensitivity during ultrasonic scaling. We examined the availability of the oxalic acid agent to compare the degree of pain during ultrasonic scaling with or without the application of the dentin hypersensitivity agent. Evaluation of effects on dentin hypersensitivity was determined by a questionnaire and visual analog scale (VAS) pain scores after ultrasonic scaling. The statistical analysis was performed using the paired Student t-test and Spearman rank correlation coefficient. Results The desensitizing agent reduced the mean VAS pain score from 69.33 16.02 at baseline to 26.08 27.99 after application. The questionnaire revealed that >80% patients were satisfied and requested the application of the desensitizing agent for future ultrasonic scaling sessions. Conclusion This study shows that the application of the oxalic acid agent considerably reduces pain associated with dentin hypersensitivity experienced during ultrasonic scaling. This pain control treatment may improve patient participation and treatment efficiency. PMID:26501012

  3. Hypersensitivity reactions to HIV therapy

    PubMed Central

    Chaponda, Mas; Pirmohamed, Munir

    2011-01-01

    Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions. PMID:21480946

  4. Transcript and protein profiling analysis of OTA-induced cell death reveals the regulation of the toxicity response process in Arabidopsis thaliana

    PubMed Central

    Wang, Yan; Peng, Xiaoli; Xu, Wentao; Luo, YunBo; Zhao, Weiwei; Hao, Junran; Liang, Zhihong; Zhang, Yu; Huang, Kunlun

    2012-01-01

    Ochratoxin A (OTA) is a toxic isocoumarin derivative produced by various species of mould which mainly grow on grain, coffee, and nuts. Recent studies have suggested that OTA induces cell death in plants. To investigate possible mechanisms of OTA phytotoxicity, both digital gene expression (DGE) transcriptomic and two-dimensional electrophoresis proteomic analyses were used, through which 3118 genes and 23 proteins were identified as being up- or down-regulated at least 2-fold in Arabidopsis leaf in response to OTA treatment. First, exposure of excised Arabidopsis thaliana leaves to OTA rapidly causes the hypersensitive reponse, significantly accelerates the increase of reactive oxygen species and malondialdehyde, and enhances antioxidant enzyme defence responses and xenobiotic detoxification. Secondly, OTA stimulation causes dynamic changes in transcription factors and activates the membrane transport system dramatically. Thirdly, a concomitant persistence of compromised photosynthesis and photorespiration is indicative of a metabolic shift from a highly active to a weak state. Finally, the data revealed that ethylene, salicylic acid, jasmonic acid, and mitogen-activated protein kinase signalling molecules mediate the process of toxicity caused by OTA. Profiling analyses on Arabidopsis in response to OTA will provide new insights into signalling transduction that modulates the OTA phytotoxicity mechanism, facilitate mapping of regulatory networks, and extend the ability to improve OTA tolerance in Arabidopsis. PMID:22207617

  5. Hypersensitivity to azathioprine in myasthenia gravis.

    PubMed Central

    Watts, G. F.; Corston, R.

    1984-01-01

    A patient with myasthenia gravis is described who exhibited hypersensitivity including an apparent acute exacerbation of the underlying disorder when treated with azathioprine. 6-mercaptoprine (6-MP) also produced hypersensitivity which, in contrast, did not manifest as a myasthenic exacerbation. PMID:6539914

  6. Development and validation of the Newcastle laryngeal hypersensitivity questionnaire

    PubMed Central

    2014-01-01

    Background Laryngeal hypersensitivity may be an important component of the common disorders of laryngeal motor dysfunction including chronic refractory cough, pdoxical vocal fold movement (vocal cord dysfunction), muscle tension dysphonia, and globus pharyngeus. Patients with these conditions frequently report sensory disturbances, and an emerging concept of the irritable larynx suggests common features of a sensory neuropathic dysfunction as a part of these disorders. The aim of this study was to develop a Laryngeal Hypersensitivity Questionnaire for patients with laryngeal dysfunction syndromes in order to measure the laryngeal sensory disturbance occurring in these conditions. Methods The 97 participants included 82 patients referred to speech pathology for behavioural management of laryngeal dysfunction and 15 healthy controls. The participants completed a 21 item self administered questionnaire regarding symptoms of abnormal laryngeal sensation. Factor analysis was conducted to examine correlations between items. Discriminant analysis and responsiveness to change were evaluated. Results The final questionnaire comprised 14 items across three domains: obstruction, pain/thermal, and irritation. The questionnaire demonstrated significant discriminant validity with a mean difference between the patients with laryngeal disorders and healthy controls of 5.5. The clinical groups with laryngeal hypersensitivity had similar abnormal scores. Furthermore the Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) showed improvement following behavioural speech pathology intervention with a mean reduction in LHQ score of 2.3. Conclusion The Newcastle Laryngeal Hypersensitivity Questionnaire is a simple, non-invasive tool to measure laryngeal pesthesia in patients with laryngeal conditions such as chronic cough, pdoxical vocal fold movement (vocal cord dysfunction), muscle tension dysphonia, and globus pharyngeus. It can successfully differentiate patients from healthy controls and measure change following intervention. It is a promising tool for use in clinical research and practice. PMID:24552215

  7. Reduced 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity response in IL-15 receptor alpha-deficient mice correlates with diminished CCL5/RANTES and CXCL10/IP-10 expression.

    PubMed

    Chen, Jia-Perng; Liao, Nan-Shih; Lai, Szu-Liang; Hsu, Lilan; Mao, Wan-Yu; Ku, Min-Chi; Liao, Fang

    2005-03-01

    Using a model of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity (CHS) we found that, as compared with wild-type mice, IL-15 receptor alpha chain (IL-15Ralpha)-deficient mice showed significantly less ear swelling. This decreased response was associated with diminished expression of CCL5/RANTES and CXCL10/IP-10, chemokines critical for effector cell recruitment, in the inflamed tissue. We determined that both the number of CD8(+) T cells infiltrating the affected skin and the production of CCL5/RANTES by antigen-stimulated CD8(+) T cells were decreased in IL-15Ralpha(-/-) mice. The lower levels of CXCL10/IP-10 suggested that the IL-15Ralpha(-/-) mice had reduced production of IFN-gamma, the primary inducer of CXCL10/IP-10, which was in fact the case. However, by contrast with CCL5/RANTES, the diminished levels of IFN-gamma were likely due to the decreased number of skin-infiltrating CD8(+) T cells, since IFN-gamma production by antigen-stimulated CD8(+) T cells was comparable between wild-type and IL-15Ralpha(-/-) mice. Our data suggest a positive, pro-inflammatory feedback loop involving CCL5/RANTES, IFN-gamma and CXCL10/IP-10 that underlies the CHS reaction and that is disrupted, likely primarily by a defect in CCL5/RANTES production, in mice lacking IL-15Ralpha, resulting in impaired leukocyte recruitment and inflammation. Moreover, it is particularly noteworthy that the defect in CCL5/RANTES expression in CD8(+) T cells is intrinsic to the absence of IL-15Ralpha, indicating that IL-15Ralpha is critical for CCL5/RANTES expression in CD8(+) T cells. PMID:15719370

  8. Summer-type hypersensitivity pneumonitis.

    PubMed

    Ando, M; Suga, M; Nishiura, Y; Miyajima, M

    1995-08-01

    Summer-type hypersensitivity pneumonitis (SHP), the most prevalent type of HP in Japan, is caused by seasonal mold contamination in the home environment. The causative agent of the disease is Trichosporon cutaneum. The fungus grows in warm, moldy, decaying organic matter, and scatters in the air from the colonizing places. The inhaled fungi sensitize susceptible patients intratracheally and induce the disease. Glucuronoxylomannan of the fungus has a potent antigenicity that causes granulomatous alveolitis. Assay of anti-T. cutaneum antibody is very useful to establish the diagnosis of the disease because the antibody activity is virtually positive in all cases of the disease. Elimination of T. cutaneum from the colonizing places prevents recrudescence. SHP, a new form of HP, had been considered to be peculiar to Japan, but the first case of SHP outside Japan was identified in Korea last year. Soon it will be recognized in many countries of temperate and tropical clime. PMID:8563107

  9. Severe type IV hypersensitivity to 'black henna' tattoo.

    PubMed

    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

  10. Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece.

    PubMed

    Rahiotis, C; Polychronopoulou, A; Tsiklakis, K; Kakaboura, A

    2013-12-01

    The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21·3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38·6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non-carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21·3% to 38·6% depending on the type of stimuli. Cervical non-carious lesions and gingival recessions were determined as significant predictors of dentin hypersensitivity. PMID:24180256

  11. Correlation between the Constitution of Sasang and Sexual Difference in the Hypersensitive Reaction of Sweet Bee Venom

    PubMed Central

    Lee, Kwangho

    2012-01-01

    Objectives: The aim of this study is to investigate the correlation between the constitution of Sasang and the bee venom hypersensitive reaction, as well as the hypersensitive reaction occurrence ratio between males and females, for patients treated with sweet bee venom (SBV) and who had undergone an examination of the constitution of the Sasang. Methods: All 81 patients enrolled in the study were treated with SBV and underwent an examination of the constitution of Sasang from January 2010 to July 2012. We divided them into two groups for the hypersensitive reaction and no response and compared the distributions of the Sasang-constitution types for the two groups as well as the hypersensitive reaction occurrence ratio between males and females. Results: No significant differences were found between the hypersensitive-reaction group and the no-response group (p= 0.390), but the hypersensitive-reaction occurrence ratio was statistically higher in females than in males (p= 0.001). Conclusions: Hypersensitive reactions do not seem to be related to the Sasang-constitution types, but the possibility of hypersensitive reactions among females seems to be higher than it is among males. PMID:25780647

  12. Environmental Hypersensitivity Disorder, Total Allergy and 20th Century Disease

    PubMed Central

    Stewart, D.E.

    1987-01-01

    Environmental hypersensitivity disorder is reputed to cause multiple allergic responses in susceptible people after exposure to common substances in the environment. The seriously afflicted, who believe themselves to be unable to live in the modern world, often become severely disabled. After a careful search of the literature, I am unable to find any scientific evidence for the validity of the theories, testing methods, or treatments given to these patients by clinical ecologists. This paper critically examines the concepts of environmental hypersensitivity and reviews scientific studies on this subject. It concludes that these patients are a heterogeneous group, and that many of them suffer from treatable psychiatric disorders. Guidelines are given for their management. PMID:21263833

  13. Expert opinion on the cough hypersensitivity syndrome in respiratory medicine.

    PubMed

    Morice, Alyn H; Millqvist, Eva; Belvisi, Maria G; Bieksiene, Kristina; Birring, Surinder S; Chung, Kian Fan; Dal Negro, Roberto W; Dicpinigaitis, Peter; Kantar, Ahmad; McGarvey, Lorcan P; Pacheco, Adalberto; Sakalauskas, Raimundas; Smith, Jaclyn A

    2014-11-01

    In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area. PMID:25142479

  14. Sympathoinhibition and hypotension in carotid sinus hypersensitivity

    NASA Technical Reports Server (NTRS)

    Smith, M. L.; Ellenbogen, K. A.; Eckberg, D. L.

    1992-01-01

    Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position.

  15. Where Asthma and Hypersensitivity Pneumonitis Meet and Differ

    PubMed Central

    Bogaert, Pieter; Tournoy, Kurt G.; Naessens, Thomas; Grooten, Johan

    2009-01-01

    Asthma is a type-I allergic airway disease characterized by Th2 cells and IgE. Episodes of bronchial inflammation, eosinophilic in nature and promoting bronchoconstriction, may become chronic and lead to persistent respiratory symptoms and irreversible structural airway changes. Representative mostly of mild to moderate asthma, this clinical definition fails to account for the atypical and often more severe phenotype found in a considerable proportion of asthmatics who have increased neutrophil cell counts in the airways as a distinguishing trait. Neutrophilic inflammation is a hallmark of another type of allergic airway pathology, hypersensitivity pneumonitis. Considered as an immune counterpart of asthma, hypersensitivity pneumonitis is a prototypical type-III allergic inflammatory reaction involving the alveoli and lung interstitium, steered by Th1 cells and IgG and, in its chronic form, accompanied by fibrosis. Although pathologically very different and commonly approached as separate disorders, as discussed in this review, clinical studies as well as data from animal models reveal undeniable parallels between both airway diseases. Danger signaling elicited by the allergenic agent or by accompanying microbial patterns emerges as critical in enabling immune sensitization and in determining the type of sensitization and ensuing allergic disease. On this basis, we propose that asthma allergens cause severe noneosinophilic asthma because of sensitization in the presence of hypersensitivity pneumonitis-promoting danger signaling. PMID:19074616

  16. Electrical hypersensitivity in humans--fact or fiction?

    PubMed

    Silny, J

    1999-08-01

    The phenomenon of the so-called electrical hypersensitivity in the weak electromagnetic fields of everyday life, potentially causing different health symptoms, is reviewed under consideration of current results from in-vivo and in-vitro investigations as well as of statistical data. Electrical hypersensitivity cannot be explained by means of the known and validated influence mechanisms of electromagnetic fields in humans, as their thresholds are at least 50 times higher for harmless effects, and more than 1000 times higher for adverse effects than the strengths of the environmental fields. Present statistical data reveal clear inconsistencies in many respects. The prevalence varies by a factor 1000 although the reporting countries have comparable field and exposure situations. Neither the apparently random combination of symptoms on the side of the suffering patients nor the problematic attribution of the symptoms to certain electromagnetic field situations do support the hypothesis of a electrical hypersensitivity. On the other hand, the statistical data must be considered unsubstantiated because of the small number of cases and the procedures of survey. Consequently, there is a need for additional, systematic investigations of this group of patients under participation of different medical and biomedical disciplines. PMID:10507130

  17. Hazards of the 'hard cash': hypersensitivity pneumonitis.

    PubMed

    Kupeli, Elif; Karnak, Demet; Sak, Serpil Dizbay; Kayacan, Oya

    2010-01-01

    Hypersensitivity pneumonitis (HP) is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors' knowledge, the present report is the first to describe 'hard cash HP', possibly caused by chipping dust or printing dye. PMID:21038004

  18. Genetic Variation Associated with Hypersensitivity to Mercury

    PubMed Central

    Austin, David William; Spolding, Briana; Gondalia, Shakuntla; Shandley, Kerrie; Palombo, Enzo A.; Knowles, Simon; Walder, Ken

    2014-01-01

    Objectives: Very little is known about mechanisms of idiosyncratic sensitivity to the damaging effects of mercury (Hg); however, there is likely a genetic component. The aim of the present study was to search for genetic variation in genes thought to be involved in Hg metabolism and transport in a group of individuals identified as having elevated Hg sensitivity compared to a normal control group. Materials and Methods: Survivors of pink disease (PD; infantile acrodynia) are a population of clinically identifiable individuals who are Hg sensitive. In the present study, single nucleotide polymorphisms in genes thought to be involved in Hg transport and metabolism were compared across two groups: (i) PD survivors (n = 25); and (ii) age- and sex-matched healthy controls (n = 25). Results: Analyses revealed significant differences between groups in genotype frequencies for rs662 in the gene encoding paraoxanase 1 (PON1) and rs1801131 in the gene encoding methylenetetrahydrofolate reductase (MTHFR). Conclusions: We have identified two genetic polymorphisms associated with increased sensitivity to Hg. Genetic variation in MTHFR and PON1 significantly differentiated a group formerly diagnosed with PD (a condition of Hg hypersensitivity) with age- and gender-matched healthy controls. PMID:25948960

  19. Drug Induced Hypersensitivity and the HLA Complex

    PubMed Central

    Alfirevic, Ana; Pirmohamed, Munir

    2011-01-01

    Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated by a wide range of structurally diverse chemical compounds. The pathophysiological mechanisms underlying hypersensitivity reactions are not well understood, but it is thought that they are immune mediated. MHC region on Chromosome 6 contains many genes with immune function. Classical MHC molecules are highly polymorphic cell surface glycoproteins whose function is to present peptide antigens to T cells. In addition to conferring protection from some diseases, HLA alleles are also associated with an increased risk of other diseases, including drug-induced hypersensitivity. Pharmacogenetic approach to predict the risk of drug-induced hypersensitivity has been established for several drugs. We will discuss the progress of hypersensitivity pharmacogenetics over the last few years and focus on current efforts of the international community to develop consortia which aim to standardize disease phenotypes and to identify affected individuals through international collaborations. In addition, we will discuss the clinical utility of HLA typing as predictive or diagnostic testing for drug-induced hypersensitivity.

  20. Genome-wide analysis links NFATC2 with asparaginase hypersensitivity.

    PubMed

    Fernandez, Christian A; Smith, Colton; Yang, Wenjian; Mullighan, Charles G; Qu, Chunxu; Larsen, Eric; Bowman, W Paul; Liu, Chengcheng; Ramsey, Laura B; Chang, Tamara; Karol, Seth E; Loh, Mignon L; Raetz, Elizabeth A; Winick, Naomi J; Hunger, Stephen P; Carroll, William L; Jeha, Sima; Pui, Ching-Hon; Evans, William E; Devidas, Meenakshi; Relling, Mary V

    2015-07-01

    Asparaginase is used to treat acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions can lead to suboptimal asparaginase exposure. Our objective was to use a genome-wide approach to identify loci associated with asparaginase hypersensitivity in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols Total XIIIA (n = 154), Total XV (n = 498), and Total XVI (n = 271), or Children's Oncology Group protocols POG 9906 (n = 222) and AALL0232 (n = 2163). Germline DNA was genotyped using the Affymetrix 500K, Affymetrix 6.0, or the Illumina Exome BeadChip array. In multivariate logistic regression, the intronic rs6021191 variant in nuclear factor of activated T cells 2 (NFATC2) had the strongest association with hypersensitivity (P = 4.1 10(-8); odds ratio [OR] = 3.11). RNA-seq data available from 65 SJCRH ALL tumor samples and 52 Yoruba HapMap samples showed that samples carrying the rs6021191 variant had higher NFATC2 expression compared with noncarriers (P = 1.1 10(-3) and 0.03, respectively). The top ranked nonsynonymous polymorphism was rs17885382 in HLA-DRB1 (P = 3.2 10(-6); OR = 1.63), which is in near complete linkage disequilibrium with the HLA-DRB1*07:01 allele we previously observed in a candidate gene study. The strongest risk factors for asparaginase allergy are variants within genes regulating the immune response. PMID:25987655

  1. Type I hypersensitivity reaction as a complication of lepa

    PubMed Central

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

    2015-01-01

    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. PMID:26792959

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

    PubMed

    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. PMID:26792959

  3. Dentinal hypersensitivity: A comparative clinical evaluation of CPP-ACP F, sodium fluoride, propolis, and placebo

    PubMed Central

    Madhavan, Souparna; Nayak, Moksha; Shenoy, Amarnath; Shetty, Rajesh; Prasad, Krishna

    2012-01-01

    Background: Dentine hypersensitivity is a transient condition that often resolves with the natural sclerotic obturation of dentinal tubules. A potent topically applied in-office desensitizing treatment is indicated as the choice of treatment when dentine hypersensitivity is localized to one or two teeth. Aim: The present study aimed to evaluate and compare the clinical efficiency of CPP-ACP F, sodium fluoride, propolis, and distilled water that was used as placebo in treating dentinal hypersensitivity. Materials and Methods: 120 patients aged 2040 years reporting with dentinal hypersensitivity in relation to canine, premolar and molars with erosion, abrasion, and gingival recession were randomly assigned to four groups of 30 patients each. Response to air jet and tactile stimuli were measured using visual analogue scale initially on 1st, 7th, 15th, 28th, 60th, and final assessment was done on the 90th day. Statistical Analysis: A statistical analysis was done using Anova test (Fischer's test) and Tukey HSD test for multicomparison. Results: The teeth treated with the test group showed decrease in the mean hypersensitivity values compared to control group, over a period of three months. The results showed propolis to be most efficient in treating dentinal hypersensitivity and CPP- ACPF showed to be the least efficient. Conclusion: All test groups were effective in reducing dentinal hypersensitivity, although they differed in rapidity of action over the period of 3 months. Further studies can be done using advanced materials and techniques. Multiple therapeutic modalities have been developed to treat dentinal hypersensitivity including products that impede nerve conduction of pain stimulus, products that mechanically occlude dentinal tubules, and calcium containing products designed to create plugs in the tubules utilizing a demineralization mechanism. PMID:23112475

  4. [Overdose or hypersensitivity to vitamin D?].

    PubMed

    Hmami, F; Oulmaati, A; Amarti, A; Kottler, M-L; Bouharrou, A

    2014-10-01

    Vitamin D intoxication with severe hypercalcemia is rare in the neonatal and infancy period. Through nine cases of hypercalcemia, secondary to taking 600,000 units of vitamin D (Sterogyl(®)), a review of vitamin D requirements and possible mechanisms of toxicity including hypersensitivity to this vitamin will be discussed. We report nine cases of babies admitted to our department between the ages of 25 and 105 days for treatment of severe dehydration. The pregnancies were normal, with no incidents at delivery. Clinical signs were dominated by weight loss, vomiting, and fever. Examination on admission revealed dehydration whose degree ranged from 8 to 15% with preserved diuresis and loss weight between 100 and 1100 g. Laboratory tests objectified hypercalcemia between 113 and 235mg/L, hypercalciuria (urinary calcium/creatinine mmol/mmol >0.5), and a low-level of parathyroid hormone. The vitamin D values in nine patients were toxic (344-749 nmol/L; normal >50 nmol/L; toxicity if >250 nmol/L). Abdominal ultrasound objectified renal nephrocalcinosis in seven patients. The DNA study, performed in eight patients, did not reveal a mutation of the vitamin D 24-hydroxylase gene (CYP24A1). The treatment consisted of intravenous rehydration with treatment of hypercalcemia (diuretics and corticosteroids). Serum calcium returned to the normal range within 4-50 days, with weight gain progressively over the following weeks. The follow-up (2 years for the oldest case) showed the persistence of images of nephrocalcinosis. Genetic susceptibility and metabolic differences appear to modulate the threshold of vitamin D toxicity. However, respect for recommended doses, recognized as safe in a large study population, reduces the risk of toxicity. PMID:25129320

  5. Hypersensitivity manifestations to the fruit mango

    PubMed Central

    Sareen, Richa

    2011-01-01

    The objectives of this study are 1) To review the published data and document the current knowledge on allergic manifestations to the fruit mango 2) To highlight the two distinct clinical presentations of hypersensitivity reactions caused by mango 3) To discuss the role of cross-reactivity 4) To increase awareness of potentially life threatening complications that can be caused by allergy to mango. An extensive search of the literature was performed in Medline/PubMed with the key terms "mango", "anaphylaxis", "contact dermatitis", "cross-reactivity", "food hypersensitivity", "oral allergy syndrome" and "urticaria". The bibliographies of all papers thus located were searched for further relevant articles. A total of 17 reports describing 22 patients were documented, including ten patients with immediate hypersensitivity reaction and twelve patients with delayed hypersensitivity reaction to mango. Ten of these patients (four with immediate reaction; six with delayed reaction) were from geographical areas cultivating mango, whereas twelve patients (six with immediate reaction; six with delayed reaction) were from the countries where large scale mango cultivation does not occur. The clinical features, pathogenesis and diagnostic modalities of both these presentations are highlighted. The fruit mango can cause immediate and delayed hypersensitivity reactions, as also "oral allergy syndrome". Although rare, it can even result in a life threatening event. Reactions may even occur in individuals without prior exposure to mango, owing to cross reactivity. It is imperative to recognize such a phenomenon early so as to avoid potentially severe clinical reactions in susceptible patients. PMID:22053296

  6. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology.

    PubMed

    Selman, Moiss; Pardo, Annie; King, Talmadge E

    2012-08-15

    Hypersensitivity pneumonitis (HP) is a complex syndrome resulting from repeated exposure to a variety of organic particles. HP may present as acute, subacute, or chronic clinical forms but with frequent overlap of these various forms. An intriguing question is why only few of the exposed individuals develop the disease. According to a two-hit model, antigen exposure associated with genetic or environmental promoting factors provokes an immunopathological response. This response is mediated by immune complexes in the acute form and by Th1 and likely Th17 T cells in subacute/chronic cases. Pathologically, HP is characterized by a bronchiolocentric granulomatous lymphocytic alveolitis, which evolves to fibrosis in chronic advanced cases. On high-resolution computed tomography scan, ground-glass and poorly defined nodules, with patchy areas of air trapping, are seen in acute/subacute cases, whereas reticular opacities, volume loss, and traction bronchiectasis superimposed on subacute changes are observed in chronic cases. Importantly, subacute and chronic HP may mimic several interstitial lung diseases, including nonspecific interstitial pneumonia and usual interstitial pneumonia, making diagnosis extremely difficult. Thus, the diagnosis of HP requires a high index of suspicion and should be considered in any patient presenting with clinical evidence of interstitial lung disease. The definitive diagnosis requires exposure to known antigen, and the assemblage of clinical, radiologic, laboratory, and pathologic findings. Early diagnosis and avoidance of further exposure are keys in management of the disease. Corticosteroids are generally used, although their long-term efficacy has not been proved in prospective clinical trials. Lung transplantation should be recommended in cases of progressive end-stage illness. PMID:22679012

  7. Contact hypersensitivity in hand dermatitis.

    PubMed

    Li, Lin-feng; Wang, Jing

    2002-10-01

    Contact hypersensitivity (CHS) in hand dermatitis (HD) was studied by patch testing (PT) 105 consecutive adult HD patients and 361 cases of suspected non-hand allergic contact dermatitis (NHD). The suspected offending agents were also investigated by a questionnaire. Age and sex distribution was no different between the 2 groups. The total positivity rate of PT in the HD group was much lower than in the control group (46.7% versus 63.2%, p < 0.01, chi2-test). The most common allergens in HD were rubber mix(17.1%), p-phenylenediamine (PPD) (14.3%), fragrance mix (9.5%), nickel (9.5%), colophonium (6.7%) and potassium dichromate (2.9%), while those in the control group, in sequence, were nickel (20.5%), rubber mix (16.9%), PPD (14.1%), fragrance mix (12.7%), potassium dichromate (5.5%) and colophonium (5.0%). The positivity rate to nickel was lower in the HD group (9.5% versus 20.5%, p < 0.05, chi2-test), while there was no significant difference for the other allergens. HD was divided arbitrarily into 5 groups: (1) vesicular form, in which fine papules and vesicles can be detected. 65.7% of the HD was vesicular form and 55.1% of them were PT positive; (2) fissured form, in which dry skin with fine fissures or desquamation is seen. 8.6% of the HD was fissured form and 30% of them were PT positive; (3) hyperkeratotic form, in which the lesions are thick, hyperkeratotic plaques - 6.7% of the HD was this form and no positive reaction was found; (4) hand and foot dermatitis (HFD) - 12.4% of HD was HFD and 53.8% of them were PT positive; (5) pompholyx - 6.7% of the patients had pompholyx and one positive result to nickel was detected. The suspected offending agents were reported in only 13 (12.4%) patients. These results suggest that CHS is less common in HD than in NHD and that other factors, such as skin irritation, may play more of a role in HD. Nickel allergy is less common in HD than in NHD. CHS may play a role in more than 1/2 of vesicular form HD, HFD and in some fissured HD also, but is less common in hyperkeratotic HD and pompholyx. Only a small proportion of the HD patients could report the suspected offending agents and PT should be performed in all patients with chronic HD. PMID:12492518

  8. Involvement of protein kinase ? in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity

    PubMed Central

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin

    2015-01-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ? (PKM?) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKM? is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ?-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKM? (p-PKM?) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.52 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKM? might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity. PMID:25761958

  9. Involvement of protein kinase ? in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.

    PubMed

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin; Lin, Chun

    2015-05-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ? (PKM?) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKM? is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ?-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKM? (p-PKM?) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5-2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKM? might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity. PMID:25761958

  10. Physiological and Transcriptional Analyses Reveal Differential Phytohormone Responses to Boron Deficiency in Brassica napus Genotypes.

    PubMed

    Zhou, Ting; Hua, Yingpeng; Huang, Yupu; Ding, Guangda; Shi, Lei; Xu, Fangsen

    2016-01-01

    Phytohormones play pivotal roles in the response of plants to various biotic and abiotic stresses. Boron (B) is an essential microelement for plants, and Brassica napus (B. napus) is hypersensitive to B deficiency. However, how auxin responds to B deficiency remained a dilemma for many years and little is known about how other phytohormones respond to B deficiency. The identification of B-efficient/inefficient B. napus indicates that breeding might overcome these constraints in the agriculture production. Here, we seek to identify phytohormone-related processes underlying B-deficiency tolerance in B. napus at the physiological and gene expression levels. Our study indicated low-B reduced indole-3-acetic acid (IAA) concentration in both the shoots and roots of B. napus, and affected the expression of the auxin biosynthesis gene BnNIT1 and the efflux gene BnPIN1 in a time-dependent manner. Low-B increased the jasmonates (JAs) and abscisic acid (ABA) concentrations and induced the expression of the ABA biosynthesis gene BnNCED3 and the ABA sensor gene BnPYL4 in the shoot. In two contrasting genotypes, the auxin concentration decreased more drastically in the B-inefficient genotype 'W10,' and together the expression of BnNIT1 and BnPIN1 also decreased more significantly in 'W10' under long-term B deficiency. While the JAs concentration was considerably higher in this genotype, and the ABA concentration was induced in 'W10' compared with the B-efficient genotype 'QY10.' Digital gene expression (DGE) profiling confirmed the differential expression of the phytohormone-related genes, indicating more other phyohormone differences involving in gene regulation between 'QY10' and 'W10' under low-B stress. Additionally, the activity of DR5:GFP was reduced in the root under low-B in Arabidopsis, and the application of exogenous IAA could partly restore the B-defective phenotype in 'W10.' Overall, our data suggested that low-B disturbed phytohormone homeostasis in B. napus, which originated from the change of transcriptional regulation of phytohormones-related genes, and the differences between genotypes may partly account for their difference in tolerance (B-efficiency) to low-B. PMID:26952137

  11. Physiological and Transcriptional Analyses Reveal Differential Phytohormone Responses to Boron Deficiency in Brassica napus Genotypes

    PubMed Central

    Zhou, Ting; Hua, Yingpeng; Huang, Yupu; Ding, Guangda; Shi, Lei; Xu, Fangsen

    2016-01-01

    Phytohormones play pivotal roles in the response of plants to various biotic and abiotic stresses. Boron (B) is an essential microelement for plants, and Brassica napus (B. napus) is hypersensitive to B deficiency. However, how auxin responds to B deficiency remained a dilemma for many years and little is known about how other phytohormones respond to B deficiency. The identification of B-efficient/inefficient B. napus indicates that breeding might overcome these constraints in the agriculture production. Here, we seek to identify phytohormone-related processes underlying B-deficiency tolerance in B. napus at the physiological and gene expression levels. Our study indicated low-B reduced indole-3-acetic acid (IAA) concentration in both the shoots and roots of B. napus, and affected the expression of the auxin biosynthesis gene BnNIT1 and the efflux gene BnPIN1 in a time-dependent manner. Low-B increased the jasmonates (JAs) and abscisic acid (ABA) concentrations and induced the expression of the ABA biosynthesis gene BnNCED3 and the ABA sensor gene BnPYL4 in the shoot. In two contrasting genotypes, the auxin concentration decreased more drastically in the B-inefficient genotype ‘W10,’ and together the expression of BnNIT1 and BnPIN1 also decreased more significantly in ‘W10’ under long-term B deficiency. While the JAs concentration was considerably higher in this genotype, and the ABA concentration was induced in ‘W10’ compared with the B-efficient genotype ‘QY10.’ Digital gene expression (DGE) profiling confirmed the differential expression of the phytohormone-related genes, indicating more other phyohormone differences involving in gene regulation between ‘QY10’ and ‘W10’ under low-B stress. Additionally, the activity of DR5:GFP was reduced in the root under low-B in Arabidopsis, and the application of exogenous IAA could partly restore the B-defective phenotype in ‘W10.’ Overall, our data suggested that low-B disturbed phytohormone homeostasis in B. napus, which originated from the change of transcriptional regulation of phytohormones-related genes, and the differences between genotypes may partly account for their difference in tolerance (B-efficiency) to low-B. PMID:26952137

  12. Unusual formaldehyde-induced hypersensitivity in two schoolgirls

    SciTech Connect

    Gammage, R.B. ); Hanna, W.T.; Painter, P.B. )

    1990-01-01

    Two schoolgirls developed a syndrome resembling Henoch-Schonlein purpura while attending a recently opened school insulated with urea-formaldehyde foam (UFFI). Skin rashes and swellings were accompanied by bizarre, blue-green discoloration of the skin. Subsequent investigations by county, state and federal authorities, and low measured concentrations of formaldehyde, prompted initial conclusions that in-school formaldehyde exposures were not responsible for the girls' problems. Subsequent controlled exposures to UFFI and formaldehyde while in hospital elicited the whole cascade of symptoms. The chronology of the onset and amplification of systems make it probable that the formaldehyde exposures precipitating the girls' hypersensitivity, occurred in the school. 3 refs.

  13. Hypersensitivity pneumonitis in a technician using Pauli's reagent.

    PubMed Central

    Evans, W V; Seaton, A

    1979-01-01

    A technician working in a medical laboratory used a spray of sodium diazobenzenesulphate (Pauli's reagent) in chromatography. She developed a respiratory illness with both airways obstruction and radiographic and physiological evidence of interstitial pneumonitis. An occupational type of challenge test was followed by both immediate and late bronchial obstructive responses, by a fall in arterial oxygen tension, and by increased radiographic shadowing. Histology of a lung biopsy specimen, a low serum C3, and a postive skin prick test to the reagent suggested that the illness was a hypersensitivity reaction to Pauli's reagent. Images PMID:542917

  14. Chemotherapy hypersensitivity reactions in ovarian cancer.

    PubMed

    Picard, Matthieu; Matulonis, Ursula A; Castells, Mariana

    2014-03-01

    Ovarian cancer is the fifth leading cause of cancer death among women in the United States. Chemotherapy using a taxane and platinum combination is key in improving survival in patients with newly diagnosed advanced ovarian cancer and is also used to treat recurrent platinum-sensitive disease. However, hypersensitivity reactions (HSRs) to chemotherapeutic agents are increasingly common and can greatly limit their use. Moreover, because of the frequent lack of equally effective alternative agents, chances of survival can be compromised. Therefore, physicians caring for these patients must be familiar with the management of HSRs to chemotherapy, and major advancements have recently been made in this field. Most HSRs implicate mast cell and basophil activation either through an IgE-mediated (ie, platinum agents) or nonspecific (ie, taxanes) mechanism. Therefore, these reactions have the potential to lead to anaphylaxis, at which time they should be treated with intramuscular epinephrine. Serum tryptase, which is released alongside histamine after mast cell activation, may be measured after an acute HSR to document mast cell involvement. After an HSR, the decision to re-treat with the same agent or a closely related one will vary depending on the causative drug, the type of HSR, and its severity. Drug desensitization has emerged as a safe and effective way of reintroducing a chemotherapeutic agent or monoclonal antibody responsible for an HSR in a patient who is expected to benefit from its continued use and for whom alternatives are considered less effective and/or more toxic. Currently, candidates for desensitization are preferably evaluated in academic settings with expertise in those procedures, because their use is still limited. Efforts are now needed to increase awareness about desensitization procedures so that more patients may benefit. This challenge will require the close collaboration of patients, nurses, oncologists, and allergists. PMID:24616544

  15. [Pathogenesis and treatment of hypersensitivity pneumonitis].

    PubMed

    Ando, M

    2000-01-01

    Hypersensitivity pneumonitis (HP) is a granulomatous interstitial lung disease resulting from an immunologic reaction to the repeated inhalation of organic dusts and active chemicals. There are 50 or more groups of HP, but the prevalence varies from country to country, and even within a country, depending on a variety of occupational or environmental inhalants. In Western coutries farmer's lung, bird fancier's disease, humidifier lung, and air-conditioner disease are common, but in Japan summer-type HP is the most prevalent group. Summer-type HP is a house-related illnes induced by Trichosporon asahii and Trichosporon mucoides which contaminate the patients' home environments in hot and humid conditions. The polysaccharide antigen contains mannan backbone attached with short side chains consi-sting of mannose, xylose, and glucuronic acid residues. Both immune complex-mediated and T cell-mediated immune responses to the yeast are involved in the induction and development of the disease. Host factors such as HLA-DQw3 and cigarette smoking also play an important role in the develop-ment or suppression of the disease. An assay for serum anti-Trichosporon antibody by a Triko Kit is very useful for the serodiagnosis, and sanitization by cleaning, disinfecting, and removing from the colonizing location of Trichosporon prevents recurrence of the disease. Summer-type HP induced by Trichosporon is a new type of HP. It can be found in other countries including most Western countries, because Trichosporon asahii and Trichosporon mucoides distribute in the temperate and subtropical areas of the world. PMID:10938513

  16. PERSISTENT SUPPRESSION OF CONTACT HYPERSENSITIVITY, AND ALTERED T-CELL PARAMETERS IN F344 RATS EXPOSED PERINATALLY TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

    EPA Science Inventory

    Abstract
    The outcome of perinatal low-level TCDD exposure on the T cell-mediated contact hypersensitivity response (CHS) in adult F344 rats was investigated. Suppression of the 2,4- dinitrofluorobenzene (DNFB)-specific contact hypersensitivity reponse occurred in mature off...

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

    PubMed Central

    2010-01-01

    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 so that it is more prone to HR and hence can react more promptly to limit the invading pathogens' spread from the infection sites. PMID:21192820

  18. Heat-rekindling in UVB-irradiated skin above NGF-sensitized muscle: experimental models of prolonged mechanical hypersensitivity.

    PubMed

    Vecchio, Silvia Lo; Finocchietti, Sara; Gazerani, Parisa; Petersen, Lars J; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

    2014-01-01

    Experimental models of prolonged pain hypersensitivity in humans are desirable for screening novel analgesic compounds. In this study, heat stimuli were applied in ultraviolet-B (UVB)-irradiated skin and in the UVB-irradiated skin combined with nerve growth factor (NGF)-injected muscle to investigate 1) whether the evoked mechanical hypersensitivity by UVB irradiation would be prolonged or enhanced following heat rekindling, and 2) whether the combination between cutaneous and muscle hypersensitivity may influence the rekindling effects. Skin sensitization was induced in 25 volunteers by UVB irradiation in areas above the upper-trapezius muscle, low-back or forearm. Muscle sensitization was induced in the low back by bilateral injections of NGF. The area of cutaneous hyperalgesia was evaluated 3 days after the irradiation by mechanical pin-prick stimulation whereas the areas of allodynia were evaluated 1, 2 and 3 days after irradiation by von Frey hair assessments. Cutaneous heat stimulation (40°C for 5 min) was performed on the 3(rd) day to investigate its effect on the areas of cutaneous allodynia and hyperalgesia. Findings revealed that 1) allodynia and hyperalgesia developed following UVB irradiation, 2) heat stimulation of the UVB-irradiated skin enlarged both hyperalgesic and allodynic areas (P < 0.01), and 3) muscle sensitization did not influence the effect of UVB on allodynia or the response to heat rekindling. These data suggest that heat rekindling applied to an UVB-sensitized skin can maintain or facilitate allodynia and hyperalgesia for a longer period offering a suitable model for testing analgesic compounds when sufficient duration of time is needed for investigation of drug efficacy. PMID:25349637

  19. Heat-rekindling in UVB-irradiated skin above NGF-sensitized muscle: experimental models of prolonged mechanical hypersensitivity

    PubMed Central

    Vecchio, Silvia Lo; Finocchietti, Sara; Gazerani, Parisa; Petersen, Lars J; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

    2014-01-01

    Experimental models of prolonged pain hypersensitivity in humans are desirable for screening novel analgesic compounds. In this study, heat stimuli were applied in ultraviolet-B (UVB)-irradiated skin and in the UVB-irradiated skin combined with nerve growth factor (NGF)-injected muscle to investigate 1) whether the evoked mechanical hypersensitivity by UVB irradiation would be prolonged or enhanced following heat rekindling, and 2) whether the combination between cutaneous and muscle hypersensitivity may influence the rekindling effects. Skin sensitization was induced in 25 volunteers by UVB irradiation in areas above the upper-trapezius muscle, low-back or forearm. Muscle sensitization was induced in the low back by bilateral injections of NGF. The area of cutaneous hyperalgesia was evaluated 3 days after the irradiation by mechanical pin-prick stimulation whereas the areas of allodynia were evaluated 1, 2 and 3 days after irradiation by von Frey hair assessments. Cutaneous heat stimulation (40C for 5 min) was performed on the 3rd day to investigate its effect on the areas of cutaneous allodynia and hyperalgesia. Findings revealed that 1) allodynia and hyperalgesia developed following UVB irradiation, 2) heat stimulation of the UVB-irradiated skin enlarged both hyperalgesic and allodynic areas (P < 0.01), and 3) muscle sensitization did not influence the effect of UVB on allodynia or the response to heat rekindling. These data suggest that heat rekindling applied to an UVB-sensitized skin can maintain or facilitate allodynia and hyperalgesia for a longer period offering a suitable model for testing analgesic compounds when sufficient duration of time is needed for investigation of drug efficacy. PMID:25349637

  20. Delayed hypersensitivity reactions following allergic and irritant inflammation.

    PubMed

    Hindsn, M; Christensen, O B

    1992-01-01

    Delayed hypersensitivity retest reaction 3 and 6 weeks after induction of allergic and irritant inflammation, was studied in 13 females with known hypersensitivity to nickel. An increased retest reaction compared to controls was observed only in sites of earlier specific allergic inflammation. Also a general down-regulation of the degree of hypersensitivity was observed at retesting. PMID:1357866

  1. Metal Hypersensitivity and Total Knee Arthroplasty.

    PubMed

    Lachiewicz, Paul F; Watters, Tyler Steven; Jacobs, Joshua J

    2016-02-01

    Metal hypersensitivity in patients with a total knee arthroplasty (TKA) is a controversial topic. The diagnosis is difficult, given the lack of robust clinical validation of the utility of cutaneous and in vitro testing. Metal hypersensitivity after TKA is quite rare and should be considered after eliminating other causes of pain and swelling, such as low-grade infection, instability, component loosening or malrotation, referred pain, and chronic regional pain syndrome. Anecdotal observations suggest that two clinical presentations of metal hypersensitivity may occur after TKA: dermatitis or a persistent painful synovitis of the knee. Patients may or may not have a history of intolerance to metal jewelry. Laboratory studies, including erythrocyte sedimentation rate, C-reactive protein level, and knee joint aspiration, are usually negative. Cutaneous and in vitro testing have been reported to be positive, but the sensitivity and specificity of such testing has not been defined. Some reports suggest that, if metal hypersensitivity is suspected and nonsurgical measures have failed, then revision to components fabricated of titanium alloy or zirconium coating can be successful in relieving symptoms. Revision should be considered as a last resort, however, and patients should be informed that no evidence-based medicine is available to guide the management of these conditions, particularly for decisions regarding revision. Given the limitations of current testing methods, the widespread screening of patients for metal allergies before TKA is not warranted. PMID:26752739

  2. Pustular drug hypersensitivity syndrome due to allopurinol.

    PubMed

    Ben Salem, Chaker; Saidi, Wafa; Larif, Sofiene; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2015-01-01

    Allopurinol hypersensitivity syndrome (AHS) is a severe drug reaction. It is characterized by rash, fever, and internal organ involvement. It may present in different clinical forms. We present a case of acute generalized exanthematous pustulosis occurring as a manifestation of AHS. PMID:25821326

  3. Severe Hyperacusis, Photophobia, and Skin Hypersensitivity

    PubMed Central

    Fioretti, Alessandra Barbara; Varakliotis, Theodoros; Poli, Otello; Cantagallo, Manuela; Eibenstein, Alberto

    2016-01-01

    We report a case of a patient with severe hyperacusis, photophobia, and skin hypersensitivity. The patient was initially treated with sound therapy and medical therapy for 4 months and successfully with a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy which improved her mood and the tolerance for sounds and light. PMID:26981300

  4. Dissecting a Role for Melanopsin in Behavioural Light Aversion Reveals a Response Independent of Conventional Photoreception

    PubMed Central

    Semo, Ma'ayan; Gias, Carlos; Ahmado, Ahmad; Sugano, Eriko; Allen, Annette E.; Lawrence, Jean M.; Tomita, Hiroshi; Coffey, Peter J.; Vugler, Anthony A.

    2010-01-01

    Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA) is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT), melanopsin knockout (Opn4?/?) and rd/rd cl (melanopsin only (MO)) mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO) mice, lacking three elements deemed essential for conventional photoreception (Opn4?/? Gnat1?/? Cnga3?/?). Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice. PMID:21124784

  5. Comparative transcriptomics of rice reveals an ancient pattern of response to microbial colonization

    PubMed Central

    Gimil, Sonia; Chang, Hur-Song; Zhu, Tong; Sesma, Ane; Osbourn, Anne; Roux, Christophe; Ioannidis, Vassilios; Oakeley, Edward J.; Docquier, Mylne; Descombes, Patrick; Briggs, Steven P.; Paszkowski, Uta

    2005-01-01

    Glomalean fungi induce and colonize symbiotic tissue called arbuscular mycorrhiza on the roots of most land plants. Other fungi also colonize plants but cause disease not symbiosis. Whole-transcriptome analysis using a custom-designed Affymetrix Gene-Chip and confirmation with real-time RT-PCR revealed 224 genes affected during arbuscular mycorrhizal symbiosis. We compared these transcription profiles with those from rice roots that were colonized by pathogens (Magnaporthe grisea and Fusarium moniliforme). Over 40% of genes showed differential regulation caused by both the symbiotic and at least one of the pathogenic interactions. A set of genes was similarly expressed in all three associations, revealing a conserved response to fungal colonization. The responses that were shared between pathogen and symbiont infection may play a role in compatibility. Likewise, the responses that are different may cause disease. Some of the genes that respond to mycorrhizal colonization may be involved in the uptake of phosphate. Indeed, phosphate addition mimicked the effect of mycorrhiza on 8% of the tested genes. We found that 34% of the mycorrhiza-associated rice genes were also associated with mycorrhiza in dicots, revealing a conserved pattern of response between the two angiosperm classes. PMID:15905328

  6. Adult-onset temporal lobe epilepsy, cognitive decline, multi-antiepileptic drug hypersensitivity, and Hashimoto's encephalopathy: Two case studies?

    PubMed Central

    Sadan, Ofer; Seyman, Estelle; Ash, Elissa L.; Kipervasser, Svetlana; Neufeld, Miri Y.

    2013-01-01

    Hashimoto's encephalopathy is defined by the coexistence of encephalopathy and antithyroid antibodies. We report two cases of adult-onset temporal lobe epilepsy with subacute cognitive decline, high titers of antithyroid antibodies, multi-antiepileptic drug hypersensitivity, and good response to immunomodulatory treatment. The relevance of multidrug hypersensitivity in the setting of adult-onset epilepsy and the importance of searching for autoimmune causes for epilepsy are discussed. PMID:25667846

  7. Treatments for hypersensitive noncarious cervical lesions

    PubMed Central

    Veitz-Keenan, Analia; Barna, Julie Ann; Strober, Brad; Matthews, Abigail G.; Collie, Damon; Vena, Donald; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant. Methods Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly. Evaluations were conducted at baseline and at one, three and six months thereafter. Primary outcomes were the reduction or elimination of hypersensitivity as measured clinically and by means of patient-reported outcomes. Results Lesion depth and pretreatment sensitivity (mean, 5.3 on a 0- to 10-point scale) were balanced across treatments, as was sleep bruxism (present in 42.2 percent of participants). The six-month participant recall rate was 99 percent. Treatments significantly reduced mean sensitivity (P < .01), with the sealant and restoration groups displaying a significantly higher reduction (P < .01) than did the dentifrice group. The dentifrice group’s mean (standard deviation) sensitivity at six months was 2.1 (2.1); those of the sealant and restoration groups were 1.0 (1.6) and 0.8 (1.4), respectively. Patient-reported sensitivity (to cold being most pronounced) paralleled clinical measurements at each evaluation. Conclusions Sealing and restoration treatments were effective overall in reducing NCCL hypersensitivity. The potassium nitrate dentifrice reduced sensitivity with increasing effectiveness through six months but not to the degree offered by the other treatments. Practical Implications Sealant or restoration placement is an effective method of immediately reducing NCCL sensitivity. Although a potassium nitrate dentifrice did reduce sensitivity slowly across six months, at no time was the reduction commensurate with that of sealants or restorations. PMID:23633698

  8. A case of chlorpheniramine maleate-induced hypersensitivity with aspirin intolerance.

    PubMed

    Kim, Min-Hye; Lee, Sang-Min; Lee, So-Hee; Kwon, Hyouk-Soo; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

    2011-01-01

    Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines. PMID:21217928

  9. Random monocyte migration: an in vitro correlation with the delayed hypersensitivity skin reaction.

    PubMed Central

    Hawes, C S; Kemp, A S; Jones, W R

    1979-01-01

    The in vitro random migration and chemotactic activity of peripheral blood monocytes and neutrophils was compared with the delayed hypersensitivity skin test to streptokinase-streptodornase in fourteen normal subjects. A significant positive correlation (P less than 0.001) was observed between the random migration of monocytes and the size of the skin test reaction. No significant correlation was found with random neutrophil migration or monocyte and neutrophil chemotactic responses. These results indicate that the in vitro random mobility of monocytes is related to the in vivo expression of a delayed-type hypersensitivity skin reaction. PMID:509784

  10. Aberrant neural signatures of decision-making: Pathological gamblers display cortico-striatal hypersensitivity to extreme gambles.

    PubMed

    Gelskov, Sofie V; Madsen, Kristoffer H; Ramsøy, Thomas Z; Siebner, Hartwig R

    2016-03-01

    Pathological gambling is an addictive disorder characterized by an irresistible urge to gamble despite severe consequences. One of the hallmarks of pathological gambling is maladaptive and highly risky decision-making, which has been linked to dysregulation of reward-related brain regions such as the ventral striatum. However, previous studies have produced contradictory results regarding the implication of this network, revealing either hypo- or hypersensitivity to monetary gains and losses. One possible explanation is that the gambling brain might be misrepresenting the benefits and costs when weighting the potential outcomes, and not the gains and losses per se. To address this issue, we investigated whether pathological gambling is associated with abnormal brain activity during decisions that weight the utility of possible gains against possible losses. Pathological gamblers and healthy human subjects underwent functional magnetic resonance imaging while they accepted or rejected mixed gain/loss gambles with fifty-fifty chances of winning or losing. Contrary to healthy individuals, gamblers showed a U-shaped response profile reflecting hypersensitivity to the most appetitive and most aversive bets in an executive cortico-striatal network including the dorsolateral prefrontal cortex and caudate nucleus. This network is concerned with the evaluation of action-outcome contingencies, monitoring recent actions and anticipating their consequences. The dysregulation of this specific network, especially for extreme bets with large potentials consequences, offers a novel understanding of the neural basis of pathological gambling in terms of deficient associations between gambling actions and their financial impact. PMID:26780575

  11. Evaluation of Dentifrice Containing Nano-hydroxyapatite for Dentinal Hypersensitivity: A Randomized Controlled Trial

    PubMed Central

    Gopinath, Nithin Manchery; John, Joseph; Nagappan, N; Prabhu, S; Kumar, E Senthil

    2015-01-01

    Background: This randomized, double-blind, parallel arm study was carried out to evaluate and compare the effectiveness between nano-hydroxyapatite (HAP) and a benchmark dentifrice in reducing dentin hypersensitivity. Materials and Methods: About 36 patients were selected, randomly divided into two groups and was evaluated clinically using three different stimuli, i.e., tactile, air blast, and cold water test. The patient’s responses to various stimuli were recorded using a visual analog scale at baseline and after 4 weeks. Results: Statistical analysis was done using unpaired and paired t-tests. It was seen that patients treated in both groups showed significant reductions scores across all sensitivity measures at the end of 4 weeks. Conclusion: The HAP containing toothpaste was effective in reducing dentin hypersensitivity with pre-existing benchmark toothpaste tested and hence can be advocated in the management of hypersensitivity. PMID:26464553

  12. LACK OF ANALGESIC EFFICACY OF SPINAL ONDANSETRON ON THERMAL AND MECHANICAL HYPERSENSITIVITY FOLLOWING SPINAL NERVE LIGATION IN THE RAT

    PubMed Central

    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 and neurochemical alterations in spinal serotonergic system have not been thoroughly investigated following spinal nerve ligation in the rat. To test this, we acutely injected intrathecal ondansetron in rats between 14 and 30 days after SNL and assessed effects on thermal and mechanical hypersensitivity. We also determined the density of serotonergic nerve fibers, serotonin content and the levels of 5-HT3 receptors within the spinal cord at this time point. Intrathecal ondansetron (1, 3, 10, 30, and 100 ?g) produced no effect on behavioral measures of thermal or mechanical hypersensitivity whereas intrathecal morphine (1?g) and gabapentin (200 ?g) partially reversed thermal and mechanical hypersensitivity following SNL. In addition, SNL did not alter the density of serotonergic fibers or 5-HT3 receptor immunoreactivity or spinal tissue content of 5-HT within the dorsal horn. These results do not support anatomic plasticity of descending serotonergic pathways or tonic 5-HT3 receptor activity in maintaining hypersensitivity after nerve injury and in contrast to previous studies fail to demonstrate an anti-hypersensitivity effect of intrathecal injection of the 5-HT3 receptor antagonist ondansetron following peripheral nerve injury. Importantly, behavioral measures of mechanical hypersensitivity assess threshold responses whereas physiological studies of mechanically evoked neuronal responses involve application of suprathreshold stimuli. Thus, suprathreshold or more intense stimuli may be necessary to recruit descending serotonergic facilitatory drive required to observe the inhibitory effects of ondansetron on spinal neuronal excitability and behavioral hypersensitivity. PMID:20637741

  13. Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles

    PubMed Central

    Varn, Frederick S.; Andrews, Erik H.; Mullins, David W.; Cheng, Chao

    2016-01-01

    Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these results allow for a detailed and personalized assessment of the patient immune response to a tumour. When combined with routinely collected patient biopsy genomic data, this method can enable a richer understanding of the complex interplay between the host immune system and cancer. PMID:26725977

  14. Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles.

    PubMed

    Varn, Frederick S; Andrews, Erik H; Mullins, David W; Cheng, Chao

    2016-01-01

    Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these results allow for a detailed and personalized assessment of the patient immune response to a tumour. When combined with routinely collected patient biopsy genomic data, this method can enable a richer understanding of the complex interplay between the host immune system and cancer. PMID:26725977

  15. Interaction Analyses of Genes Required for Resistance Responses to Powdery Mildew in Barley Reveal Distinct Pathways Leading to Leaf Cell Death.

    PubMed Central

    Peterhansel, C.; Freialdenhoven, A.; Kurth, J.; Kolsch, R.; Schulze-Lefert, P.

    1997-01-01

    Race-specific resistance in barley to the powdery mildew fungus (Erysiphe graminis f sp hordei) is associated with a cell death reaction (hypersensitive response [HR]). Genetically, it is dependent on dominant resistance genes (Mlx), and in most cases, it is also dependent on Rar1 and Rar2. Non-race-specific resistance to the fungus, which is due to the lack of the Mlo wild-type allele, is dependent on Ror1 and Ror2 and is not associated with an HR in the region of pathogen attack. However, the absence of the Mlo wild-type allele stimulates a spontaneous cell death response in foliar tissue. This response is also controlled by Ror1 and Ror2, as indicated by trypan blue staining patterns. Lack of Mlo enhances transcript accumulation of pathogenesis-related genes upon fungal challenge, and this response is diminished by mutations in Ror genes. Using DNA marker-assisted selection of genotypes, we provide evidence, via gene interaction studies, that Ror1 and Ror2 are not essential components of race-specific resistance and do not compromise hypersensitive cell death. Reciprocal experiments show that neither is Rar1 a component of mlo-controlled resistance nor does it affect spontaneous cell death. We show that mlo- and Ror-dependent resistance is active when challenged with E. g. f sp tritici, a nonhost pathogen of barley. Our observations suggest separate genetic pathways operating in race-specific and non-race-specific resistance; they indicate also a separate genetic control of hypersensitive and spontaneous cell death in foliar tissue. PMID:12237388

  16. Time-Course Proteome Analysis Reveals the Dynamic Response of Cryptococcus gattii Cells to Fluconazole

    PubMed Central

    Chong, Hin Siong; Campbell, Leona; Padula, Matthew P.; Hill, Cameron; Harry, Elizabeth; Li, Simone S.; Wilkins, Marc R.; Herbert, Ben; Carter, Dee

    2012-01-01

    Cryptococcus gattii is an encapsulated fungus capable of causing fatal disease in immunocompetent humans and animals. As current antifungal therapies are few and limited in efficacy, and resistance is an emerging issue, the development of new treatment strategies is urgently required. The current study undertook a time-course analysis of the proteome of C. gattii during treatment with fluconazole (FLC), which is used widely in prophylactic and maintenance therapies. The aims were to analyze the overall cellular response to FLC, and to find fungal proteins involved in this response that might be useful targets in therapies that augment the antifungal activity of FLC. During FLC treatment, an increase in stress response, ATP synthesis and mitochondrial respiratory chain proteins, and a decrease in most ribosomal proteins was observed, suggesting that ATP-dependent efflux pumps had been initiated for survival and that the maintenance of ribosome synthesis was differentially expressed. Two proteins involved in fungal specific pathways were responsive to FLC. An integrative network analysis revealed co-ordinated processes involved in drug response, and highlighted hubs in the network representing essential proteins that are required for cell viability. This work demonstrates the dynamic cellular response of a typical susceptible isolate of C. gattii to FLC, and identified a number of proteins and pathways that could be targeted to augment the activity of FLC. PMID:22880118

  17. Integrated metabolomic and proteomic analysis reveals systemic responses of Rubrivivax benzoatilyticus JA2 to aniline stress.

    PubMed

    Mujahid, Md; Prasuna, M Lakshmi; Sasikala, Ch; Ramana, Ch Venkata

    2015-02-01

    Aromatic amines are widely distributed in the environment and are major environmental pollutants. Although degradation of aromatic amines is well studied in bacteria, physiological adaptations and stress response to these toxic compounds is not yet fully understood. In the present study, systemic responses of Rubrivivax benzoatilyticus JA2 to aniline stress were deciphered using metabolite and iTRAQ-labeled protein profiling. Strain JA2 tolerated high concentrations of aniline (30 mM) with trace amounts of aniline being transformed to acetanilide. GC-MS metabolite profiling revealed aniline stress phenotype wherein amino acid, carbohydrate, fatty acid, nitrogen metabolisms, and TCA (tricarboxylic acid cycle) were modulated. Strain JA2 responded to aniline by remodeling the proteome, and cellular functions, such as signaling, transcription, translation, stress tolerance, transport and carbohydrate metabolism, were highly modulated. Key adaptive responses, such as transcription/translational changes, molecular chaperones to control protein folding, and efflux pumps implicated in solvent extrusion, were induced in response to aniline stress. Proteo-metabolomics indicated extensive rewiring of metabolism to aniline. TCA cycle and amino acid catabolism were down-regulated while gluconeogenesis and pentose phosphate pathways were up-regulated, leading to the synthesis of extracellular polymeric substances. Furthermore, increased saturated fatty acid ratios in membranes due to aniline stress suggest membrane adaptation. The present study thus indicates that strain JA2 employs multilayered responses: stress response, toxic compound tolerance, energy conservation, and metabolic rearrangements to aniline. PMID:25388363

  18. Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease.

    PubMed

    Funke, M; Fellrath, J-M

    2008-08-01

    Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient's environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema. PMID:18669792

  19. Cellular hypersensitivity in Guillain-Barr syndrome

    PubMed Central

    Sheremata, William A.; Rocklin, Ross E.; David, John

    1974-01-01

    The Guillain-Barr syndrome is hypothesized to be secondary to cellular hypersensitivity to peripheral nerve antigens. To test this theory lymphocytes from 100 subjects were studied using the macrophage-migration-inhibition factor (MIF) assay. Thirty-four normal controls gave a mean migration of 100.4 9%. Of 34 patients with peripheral nervous system disease, only those with the Guillain-Barr syndrome showed hypersensitivity with a mean migration of 72 11%. Of 34 patients with central nervous system disease only three with multiple sclerosis and two with stroke gave similar results. Positive results in the Guillain-Barr syndrome were found only in patients presenting with classical disease and who were ill at the time of study. PMID:4366128

  20. Hypersensitivity pneumonitis associated with environmental mycobacteria.

    PubMed

    Beckett, William; Kallay, Michael; Sood, Akshay; Zuo, Zhengfa; Milton, Donald

    2005-06-01

    A previously healthy man working as a machine operator in an automotive factory developed respiratory symptoms. Medical evaluation showed abnormal pulmonary function tests, a lung biopsy showed hypersensitivity pneumonitis, and his illness was traced to his work environment. His physician asked the employer to remove him from exposure to metalworking fluids. Symptoms reoccurred when he was later reexposed to metalworking fluids, and further permanent decrement in his lung function occurred. Investigation of his workplace showed that five of six large reservoirs of metalworking fluids (cutting oils) grew Mycobacterium chelonae (or Mycobacterium immunogenum), an organism previously associated with outbreaks of hypersensitivity pneumonitis in automaking factories. His lung function remained stable after complete removal from exposure. The employer, metalworking fluid supplier, union, and the National Institute for Occupational Safety and Health were notified of this sentinel health event. No further cases have been documented in this workplace. PMID:15929902

  1. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

    Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

    2011-01-01

    Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

  2. Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.

    PubMed

    Kreiss, K; Cox-Ganser, J

    1997-10-01

    A workshop discussing eight clusters of hypersensitivity pneumonitis in the automotive industry among metalworking fluid-exposed workers concluded that a risk exists for this granulomatous lung disease where water-based fluids are used and unusual microbial contaminants predominate. Strong candidates for microbial etiology are nontuberculous mycobacteria and fungi. Cases of hypersensitivity pneumonitis occur among cases with other work-related respiratory symptoms and chest diseases. Reversibility of disease has occurred in many cases with exposure cessation, allowing return to work to jobs without metalworking fluid exposures or, in some situations, to jobs without the same metalworking fluid exposures. Cases have been recognized with metalworking fluid exposures generally less than 0.5 mg/m3. The workshop participants identified knowledge gaps regarding risk factors, exposure-response relationships, intervention efficacy, and natural history, as well as surveillance needs to define the extent of the problem in this industry. In the absence of answers to these questions, guidance for prevention is necessarily limited. PMID:9258399

  3. Hypersensitivity reactions during treatment with biological agents.

    PubMed

    Puxeddu, Ilaria; Caltran, Elena; Rocchi, Valeria; Del Corso, Isabella; Tavoni, Antonio; Migliorini, Paola

    2016-01-01

    The recent development of biological agents, namely, anti-tumour necrosis factor alpha (TNF-?) agents (infliximab, adalimumab and etanercept), anti- CD20 monoclonal antibody (rituximab) and anti-interleukin 6 receptor (IL-6R) monoclonal antibody (tocilizumab), represents a major breakthrough for the treatment of immune-mediated disorders. Given their structural and functional differences, distinct safety profiles can be expected for each of these agents. Evidence in the literature indicates that patients treated with anti-TNF-? agents and tocilizumab are at increased risk for bacterial infections. However, an increased therapeutic use of these biological agents has disclosed other side-effects, including immediate hypersensitivity reactions, such as anaphylaxis and urticaria. Both under-diagnosis and over-diagnosis of hypersensitivity reactions to biological agents are potential problems. Thus, it is important to identify these reactions and to adopt the right approach to manage them. This article reviews the general aspects of adverse events during biologic treatment, focusing on IgE-mediated hypersensitivity reactions to anti-TNF-? agents, rituximab and tocilizumab, and on the tools for the diagnosis of these life-threatening reactions. PMID:26751942

  4. Drug Hypersensitivity: Pharmacogenetics and Clinical Syndromes

    PubMed Central

    Phillips, Elizabeth J.; Chung, Wen-Hung; Mockenhaupt, Maja; Roujeau, Jean-Claude; Mallal, Simon A.

    2011-01-01

    Severe cutaneous adverse reactions (SCARs) include syndromes such as drug reaction, eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes including abacavir hypersensitivity reaction, allopurinol DRESS/DIHS and SJS/TEN and SJS/TEN associated with aromatic amine anticonvulsants. These HLA associations have created the promise for prevention through screening and have additionally shed further light on the immunopathogenesis of SCARs. The roll-out of HLA-B*5701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs. Numerous hurdles exist in the widespread translation of several other drugs such as carbamazepine where the positive predictive value of HLA-B*1502 is low and the negative predictive value of HLA-B*1502 for SJS/TEN may not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotype standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes. PMID:21354501

  5. Global Transcription Profiling Reveals Comprehensive Insights into Hypoxic Response in Arabidopsis1[w

    PubMed Central

    Liu, Fenglong; VanToai, Tara; Moy, Linda P.; Bock, Geoffrey; Linford, Lara D.; Quackenbush, John

    2005-01-01

    Plants have evolved adaptation mechanisms to sense oxygen deficiency in their environments and make coordinated physiological and structural adjustments to enhance their hypoxic tolerance. To gain insight into how plants respond to low-oxygen stress, gene expression profiling using whole-genome DNA amplicon microarrays was carried out at seven time points over 24 h, in wild-type and transgenic PSAG12:ipt Arabidopsis (Arabidopsis thaliana) plants under normoxic and hypoxic conditions. Transcript levels of genes involved in glycolysis and fermentation pathways, ethylene synthesis and perception, calcium signaling, nitrogen utilization, trehalose metabolism, and alkaloid synthesis were significantly altered in response to oxygen limitation. Analysis based on gene ontology assignments suggested a significant down-regulation of genes whose functions are associated with cell walls, nucleosome structures, water channels, and ion transporters and a significant up-regulation of genes involved in transcriptional regulation, protein kinase activity, and auxin responses under conditions of oxygen shortage. Promoter analysis on a cluster of up-regulated genes revealed a significant overrepresentation of the AtMYB2-binding motif (GT motif), a sugar response element-like motif, and a G-box-related sequence, and also identified several putative anaerobic response elements. Finally, quantitative real-time polymerase chain reactions using 29 selected genes independently verified the microarray results. This study represents one of the most comprehensive analyses conducted to date investigating hypoxia-responsive transcriptional networks in plants. PMID:15734912

  6. Condition-specific role of colonic inflammatory molecules in persistent functional colorectal hypersensitivity in the mouse

    PubMed Central

    La, Jun-Ho; Gebhart, G. F.

    2014-01-01

    Background A low-level inflammation has been hypothesized to mediate visceral hypersensitivity in functional bowel disorders that persist after or even in the absence of gut inflammation. We aimed to test the efficacy of a steroidal anti-inflammatory treatment, and identify local inflammatory molecules mediating post- and non-inflammatory colorectal hypersensitivity using two mouse models. Methods Visceromotor responses to colorectal distension were quantified as a measure of colorectal sensitivity. On day 1, mice received intracolonic saline (control), trinitrobenzenesulfonic acid (post-inflammatory on day 15), or acidified hypertonic saline (non-inflammatory). Colorectal sensitivity before (day 10) and after (day 15) four-day dexamethasone treatment was compared, and colonic gene expression of inflammatory molecules was quantified. Results Dexamethasone effectively inhibited gene expression of inflammatory molecules such as interleukin (IL)-1? and mast cell protease-1 in the colon, but did not attenuate colorectal hypersensitivity in either model. Gene expression of inflammatory molecules in the colon did not differ between control and the non-inflammatory model, but the post-inflammatory model showed increased IL-10 and tight junction protein 2, and decreased IL-6, transforming growth factor (TGF)-?, a precursor of ?-endorphin, occludin, and mucin 2. While no common molecule explained colorectal hypersensitivity in these models, hypersensitivity was positively correlated with TGF-?2 mRNA in control, and with IL-1?, inhibin ?A and prostaglandin E2 synthase in the dexamethasone-treated post-inflammatory model. In the non-inflammatory model, cyclooxygenase-2 mRNA was negatively correlated with colorectal sensitivity. Conclusion These results suggest that persistent functional colorectal hypersensitivity is mediated by condition-specific mediators whose gene expression in the colon is not inevitably sensitive to steroidal anti-inflammatory treatment. PMID:25307695

  7. Structure of the 'Escherichia Coli' Leucine-Responsive Regulatory Protein Lrp Reveals a Novel Octameric Assembly

    SciTech Connect

    de los Rios, S.; Perona, J.J.; /UC, Santa Barbara

    2007-07-09

    The structure of Escherichia coli leucine-responsive regulatory protein (Lrp) cocrystallized with a short duplex oligodeoxynucleotide reveals a novel quaternary assembly in which the protein octamer forms an open, linear array of four dimers. In contrast, structures of the Lrp homologs LrpA, LrpC and AsnC crystallized in the absence of DNA show that these proteins instead form highly symmetrical octamers in which the four dimers form a closed ring. Although the DNA is disordered within the Lrp crystal, comparative analyses suggest that the observed differences in quaternary state may arise from DNA interactions during crystallization. Interconversion of these conformations, possibly in response to DNA or leucine binding, provides an underlying mechanism to alter the relative spatial orientation of the DNA-binding domains. Breaking of the closed octamer symmetry may be a common essential step in the formation of active DNA complexes by all members of the Lrp/AsnC family of transcriptional regulatory proteins.

  8. Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

    PubMed

    Zhang, Lingling; Hou, Rui; Su, Hailin; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2012-01-01

    Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes. PMID:22530030

  9. Eye Tracking Reveals Impaired Attentional Disengagement Associated with Sensory Response Patterns in Children with Autism.

    PubMed

    Sabatos-DeVito, Maura; Schipul, Sarah E; Bulluck, John C; Belger, Aysenil; Baranek, Grace T

    2016-04-01

    This study used a gap-overlap paradigm to examine the impact of distractor salience and temporal overlap on the ability to disengage and orient attention in 50 children (4-13 years) with ASD, DD and TD, and associations between attention and sensory response patterns. Results revealed impaired disengagement and orienting accuracy in ASD. Disengagement was impaired across all groups during temporal overlap for dynamic stimuli compared to static, but only ASD showed slower disengagement from multimodal relative to unimodal dynamic stimuli. Attentional disengagement had differential associations with distinct sensory response patterns in ASD and DD. Atypical sensory processing and temporal binding appear to be intertwined with development of disengagement in ASD, but longitudinal studies are needed to unravel causal pathways. PMID:26816345

  10. Natural grouping of neural responses reveals spatially segregated clusters in prearcuate cortex.

    PubMed

    Kiani, Roozbeh; Cueva, Christopher J; Reppas, John B; Peixoto, Diogo; Ryu, Stephen I; Newsome, William T

    2015-03-18

    A fundamental challenge in studying the frontal lobe is to parcellate this cortex into "natural" functional modules despite the absence of topographic maps, which are so helpful in primary sensory areas. Here we show that unsupervised clustering algorithms, applied to 96-channel array recordings from prearcuate gyrus, reveal spatially segregated subnetworks that remain stable across behavioral contexts. Looking for natural groupings of neurons based on response similarities, we discovered that the recorded area includes at least two spatially segregated subnetworks that differentially represent behavioral choice and reaction time. Importantly, these subnetworks are detectable during different behavioral states and, surprisingly, are defined better by "common noise" than task-evoked responses. Our parcellation process works well on "spontaneous" neural activity, and thus bears strong resemblance to the identification of "resting-state" networks in fMRI data sets. Our results demonstrate a powerful new tool for identifying cortical subnetworks by objective classification of simultaneously recorded electrophysiological activity. PMID:25728571

  11. [A case of hypersensitivity pneumonitis caused by zinc fume].

    PubMed

    Miyazaki, Hiroo; Hirata, Takeo; Shimane, Shoko; Morita, Sumihito; Chihara, Koji; Enomoto, Noriyuki; Suda, Takafumi; Chida, Kingo

    2006-12-01

    A 55-year-old man with a 3-year occupational history of welding was admitted for repeated episodes of fever, cough and dyspnea after inhalation of smoke while welding galvanized steel. A computed tomography (CT) showed diffuse centrilobular nodules, panlobular ground-glass opacity and interlobular septal thickening in both lung fields, and he suffered from hypoxemia (PaO2 = 55.3Torr) while breathing room air. Percentage of lymphocytes in bronchoalveolar lavage fluid increased, and lung biopsy specimens at thoracoscopy revealed lymphocytic alveolitis and organization in air spaces. His symptoms and signs disappeared spontaneously only when he ceased welding. Panlobular ground-glass opacity and interlobular septal thickening improved immediately with oral corticosteroids. Patch tests using metal series gave positive reactions to zinc. We diagnosed this case as hypersensitivity pneumonitis caused by zinc fumes. PMID:17233399

  12. Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.

    PubMed

    Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars

    2009-01-01

    Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints. PMID:18375180

  13. Global Analysis of Neutrophil Responses to Neisseria gonorrhoeae Reveals a Self-Propagating Inflammatory Program

    PubMed Central

    Sintsova, Anna; Sarantis, Helen; Islam, Epshita A.; Sun, Chun Xiang; Amin, Mohsen; Chan, Carlos H. F.; Stanners, Clifford P.; Glogauer, Michael; Gray-Owen, Scott D.

    2014-01-01

    An overwhelming neutrophil-driven response causes both acute symptoms and the lasting sequelae that result from infection with Neisseria gonorrhoeae. Neutrophils undergo an aggressive opsonin-independent response to N. gonorrhoeae, driven by the innate decoy receptor CEACAM3. CEACAM3 is exclusively expressed by human neutrophils, and drives a potent binding, phagocytic engulfment and oxidative killing of Opa-expressing bacteria. In this study, we sought to explore the contribution of neutrophils to the pathogenic inflammatory process that typifies gonorrhea. Genome-wide microarray and biochemical profiling of gonococcal-infected neutrophils revealed that CEACAM3 engagement triggers a Syk-, PKCδ- and Tak1-dependent signaling cascade that results in the activation of an NF-κB-dependent transcriptional response, with consequent production of pro-inflammatory cytokines. Using an in vivo model of N. gonorrhoeae infection, we show that human CEACAM-expressing neutrophils have heightened migration toward the site of the infection where they may be further activated upon Opa-dependent binding. Together, this study establishes that the role of CEACAM3 is not restricted to the direct opsonin-independent killing by neutrophils, since it also drives the vigorous inflammatory response that typifies gonorrhea. By carrying the potential to mobilize increasing numbers of neutrophils, CEACAM3 thereby represents the tipping point between protective and pathogenic outcomes of N. gonorrhoeae infection. PMID:25188454

  14. NMR Metabolomic Profiling Reveals New Roles of SUMOylation in DNA Damage Response

    PubMed Central

    Cano, Kristin E.; Li, Yi-Jia; Chen, Yuan

    2010-01-01

    Post-translational modifications by the Small Ubiquitin-like Modifier (SUMO) family of proteins have been established as critical events in the cellular response to a wide range of DNA damaging reagents and radiation; however, the detailed mechanism of SUMOylation in DNA damage response is not well understood. In this study, we used nuclear magnetic resonance (NMR) spectroscopy based metabolomics approach to examine the effect of an inhibitor of SUMO-mediated protein-protein interactions on MCF7 breast cancer cell response to radiation. Metabolomics is sensitive to changes in cellular functions, and thus provides complementary information to other biological studies. The peptide inhibitor (SUMO interaction motif mimic, SIM) and a control peptide were stably expressed in MCF-7 cell line. Metabolite profiles of the cell lines before and after radiation were analyzed using solution NMR methods. Various statistical methods were used to isolate significant changes. Differences in the amounts of glutamine, aspartate, malate, alanine, glutamate and NADH between the SIM-expressing and control cells suggest a role for SUMOylation in regulating mitochondrial function. This is also further verified following the metabolism of 13C-labeled glutamine. The inability of the cells expressing the SIM peptide to increase production of the antioxidants carnosine and glutathione after radiation damage suggests an important role of SUMOylation in regulating the levels of antioxidants that protect cells from free radicals and reactive oxygen species generated by radiation. This study reveals previously unknown roles of SUMOylation in DNA damage response. PMID:20695451

  15. NMR metabolomic profiling reveals new roles of SUMOylation in DNA damage response.

    PubMed

    Cano, Kristin E; Li, Yi-Jia; Chen, Yuan

    2010-10-01

    Post-translational modifications by the Small Ubiquitin-like Modifier (SUMO) family of proteins have been established as critical events in the cellular response to a wide range of DNA damaging reagents and radiation; however, the detailed mechanism of SUMOylation in DNA damage response is not well understood. In this study, we used a nuclear magnetic resonance (NMR) spectroscopy-based metabolomics approach to examine the effect of an inhibitor of SUMO-mediated protein-protein interactions on MCF7 breast cancer cell response to radiation. Metabolomics is sensitive to changes in cellular functions and thus provides complementary information to other biological studies. The peptide inhibitor (SUMO interaction motif mimic, SIM) and a control peptide were stably expressed in MCF-7 cell line. Metabolite profiles of the cell lines before and after radiation were analyzed using solution NMR methods. Various statistical methods were used to isolate significant changes. Differences in the amounts of glutamine, aspartate, malate, alanine, glutamate and NADH between the SIM-expressing and control cells suggest a role for SUMOylation in regulating mitochondrial function. This is also further verified following the metabolism of (13)C-labeled glutamine. The inability of the cells expressing the SIM peptide to increase production of the antioxidants carnosine and glutathione after radiation damage suggests an important role of SUMOylation in regulating the levels of antioxidants that protect cells from free radicals and reactive oxygen species generated by radiation. This study reveals previously unknown roles of SUMOylation in DNA damage response. PMID:20695451

  16. Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots.

    PubMed

    Aubry-Hivet, D; Nziengui, H; Rapp, K; Oliveira, O; Paponov, I A; Li, Y; Hauslage, J; Vagt, N; Braun, M; Ditengou, F A; Dovzhenko, A; Palme, K

    2014-01-01

    Plant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1-g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation-related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella-located PIN3 were stronger than in those deprived of the epidermis and cortex cell-specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up-regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis. PMID:24373012

  17. Predicting invasive species impacts: a community module functional response approach reveals context dependencies.

    PubMed

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2015-03-01

    Predatory functional responses play integral roles in predator-prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator-prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. PMID:25265905

  18. Predicting invasive species impacts: a community module functional response approach reveals context dependencies

    PubMed Central

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2015-01-01

    Summary Predatory functional responses play integral roles in predator–prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator–prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. PMID:25265905

  19. Immediate and Delayed Hypersensitivity Reactions to Corticosteroids: Evaluation and Management.

    PubMed

    Otani, Iris M; Banerji, Aleena

    2016-03-01

    Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids have been described, the occurrence of immediate hypersensitivity reactions and delayed contact dermatitis due to corticosteroids remains under-recognized. Hypersensitivity reactions can occur to a corticosteroid itself, or to the additives and vehicles in corticosteroid preparations. Skin testing and oral graded challenge can help confirm the suspected culprit agent in immediate hypersensitivity reactions and help identify an alternative tolerated corticosteroid. Patch testing can help identify the culprit agents in delayed hypersensitivity contact dermatitis. Cross-reactivity patterns have not been observed for immediate hypersensitivity reactions as they have been for delayed contact dermatitis. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. We review the current understanding regarding the clinical presentation, evaluation, and management of immediate and delayed hypersensitivity reactions to corticosteroids. PMID:26857016

  20. Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions.

    PubMed

    Brown, L F; Olbricht, S M; Berse, B; Jackman, R W; Matsueda, G; Tognazzi, K A; Manseau, E J; Dvorak, H F; Van de Water, L

    1995-03-15

    Delayed hypersensitivity (DH) is a T cell-mediated form of immune response characterized by a predominantly perivascular, mononuclear cell infiltrate. The venules in DH reactions are hyperpermeable to plasma proteins, leading to extravasation of plasma fibrinogen and its extravascular clotting to form a fibrin gel that promotes induration and angiogenesis. The mechanisms responsible for microvascular hyperpermeability in DH are unknown. Recently, a cytokine named vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF) has been implicated in the chronic vascular hyperpermeability and angiogenesis of solid and ascites tumors, healing wounds, rheumatoid arthritis, and psoriasis. These findings suggested that VPF/VEGF might also have a role in the pathogenesis of DH. Two model systems were studied: allergic contact dermatitis to poison ivy in human volunteers and classical tuberculin hypersensitivity in rats. In both, in situ hybridization revealed that the mRNAs encoding VPF/VEGF were strikingly overexpressed in keratinocytes of the epidermis; scattered mononuclear cells infiltrating the dermis also overexpressed VPF/VEGF mRNA, to a greater extent in rat tuberculin than in human contact reactions. In contact reactions, mRNAs for two VPF/VEGF vascular endothelial cell receptors, flt-1 and KDR, were also strikingly overexpressed. Abundant fibrin deposition in both models confirmed that dermal microvessels were indeed hyperpermeable to plasma fibrinogen. These results implicate VPF/VEGF as a potentially important mediator in the pathogenesis of cell-mediated immunity and provide further evidence that products of epithelial cells may regulate the inflammatory response. PMID:7876550

  1. Hypersensitivity Pneumonitis Caused by Cephalosporins With Identical R1 Side Chains.

    PubMed

    Lee, Sang Hee; Kim, Mi Hyun; Lee, Kwangha; Jo, Eun Jung; Park, Hye Kyung

    2015-09-01

    Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient's hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins. PMID:25749765

  2. Transgenic Zebrafish Reveal Tissue-Specific Differences in Estrogen Signaling in Response to Environmental Water Samples

    PubMed Central

    Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki S.; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. Results: We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ER? was expressed in developing heart valves but not in the liver, whereas ER?2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves. Citation: Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. 2014. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples. Environ Health Perspect 122:356362;?http://dx.doi.org/10.1289/ehp.1307329 PMID:24425189

  3. Differential Gene Expression Reveals Candidate Genes for Drought Stress Response in Abies alba (Pinaceae)

    PubMed Central

    Ziegenhagen, Birgit; Liepelt, Sascha

    2015-01-01

    Increasing drought periods as a result of global climate change pose a threat to many tree species by possibly outpacing their adaptive capabilities. Revealing the genetic basis of drought stress response is therefore implemental for future conservation strategies and risk assessment. Access to informative genomic regions is however challenging, especially for conifers, partially due to their large genomes, which puts constraints on the feasibility of whole genome scans. Candidate genes offer a valuable tool to reduce the complexity of the analysis and the amount of sequencing work and costs. For this study we combined an improved drought stress phenotyping of needles via a novel terahertz water monitoring technique with Massive Analysis of cDNA Ends to identify candidate genes for drought stress response in European silver fir (Abies alba Mill.). A pooled cDNA library was constructed from the cotyledons of six drought stressed and six well-watered silver fir seedlings, respectively. Differential expression analyses of these libraries revealed 296 candidate genes for drought stress response in silver fir (247 up- and 49 down-regulated) of which a subset was validated by RT-qPCR of the twelve individual cotyledons. A majority of these genes code for currently uncharacterized proteins and hint on new genomic resources to be explored in conifers. Furthermore, we could show that some traditional reference genes from model plant species (GAPDH and eIF4A2) are not suitable for differential analysis and we propose a new reference gene, TPC1, for drought stress expression profiling in needles of conifer seedlings. PMID:25924061

  4. Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata.

    PubMed

    Miyazaki, Taiga; Nakayama, Hironobu; Nagayoshi, Yohsuke; Kakeya, Hiroshi; Kohno, Shigeru

    2013-01-01

    Proper protein folding in the endoplasmic reticulum (ER) is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR), is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata ?ire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata. PMID:23382685

  5. Dissection of Ire1 Functions Reveals Stress Response Mechanisms Uniquely Evolved in Candida glabrata

    PubMed Central

    Miyazaki, Taiga; Nakayama, Hironobu; Nagayoshi, Yohsuke; Kakeya, Hiroshi; Kohno, Shigeru

    2013-01-01

    Proper protein folding in the endoplasmic reticulum (ER) is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR), is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata. PMID:23382685

  6. The Transcriptome and Proteome of the Diatom Thalassiosira pseudonana Reveal a Diverse Phosphorus Stress Response

    PubMed Central

    Dyhrman, Sonya T.; Mercier, Melissa L.; Alexander, Harriet; Whitney, LeAnn P.; Drzewianowski, Andrea; Bulygin, Vladimir V.; Bertrand, Erin M.; Wu, Zhijin; Benitez-Nelson, Claudia; Heithoff, Abigail

    2012-01-01

    Phosphorus (P) is a critical driver of phytoplankton growth and ecosystem function in the ocean. Diatoms are an abundant class of marine phytoplankton that are responsible for significant amounts of primary production. With the control they exert on the oceanic carbon cycle, there have been a number of studies focused on how diatoms respond to limiting macro and micronutrients such as iron and nitrogen. However, diatom physiological responses to P deficiency are poorly understood. Here, we couple deep sequencing of transcript tags and quantitative proteomics to analyze the diatom Thalassiosira pseudonana grown under P-replete and P-deficient conditions. A total of 318 transcripts were differentially regulated with a false discovery rate of <0.05, and a total of 136 proteins were differentially abundant (p<0.05). Significant changes in the abundance of transcripts and proteins were observed and coordinated for multiple biochemical pathways, including glycolysis and translation. Patterns in transcript and protein abundance were also linked to physiological changes in cellular P distributions, and enzyme activities. These data demonstrate that diatom P deficiency results in changes in cellular P allocation through polyphosphate production, increased P transport, a switch to utilization of dissolved organic P through increased production of metalloenzymes, and a remodeling of the cell surface through production of sulfolipids. Together, these findings reveal that T. pseudonana has evolved a sophisticated response to P deficiency involving multiple biochemical strategies that are likely critical to its ability to respond to variations in environmental P availability. PMID:22479440

  7. The transcriptome and proteome of the diatom Thalassiosira pseudonana reveal a diverse phosphorus stress response.

    PubMed

    Dyhrman, Sonya T; Jenkins, Bethany D; Rynearson, Tatiana A; Saito, Mak A; Mercier, Melissa L; Alexander, Harriet; Whitney, Leann P; Drzewianowski, Andrea; Bulygin, Vladimir V; Bertrand, Erin M; Wu, Zhijin; Benitez-Nelson, Claudia; Heithoff, Abigail

    2012-01-01

    Phosphorus (P) is a critical driver of phytoplankton growth and ecosystem function in the ocean. Diatoms are an abundant class of marine phytoplankton that are responsible for significant amounts of primary production. With the control they exert on the oceanic carbon cycle, there have been a number of studies focused on how diatoms respond to limiting macro and micronutrients such as iron and nitrogen. However, diatom physiological responses to P deficiency are poorly understood. Here, we couple deep sequencing of transcript tags and quantitative proteomics to analyze the diatom Thalassiosira pseudonana grown under P-replete and P-deficient conditions. A total of 318 transcripts were differentially regulated with a false discovery rate of <0.05, and a total of 136 proteins were differentially abundant (p<0.05). Significant changes in the abundance of transcripts and proteins were observed and coordinated for multiple biochemical pathways, including glycolysis and translation. Patterns in transcript and protein abundance were also linked to physiological changes in cellular P distributions, and enzyme activities. These data demonstrate that diatom P deficiency results in changes in cellular P allocation through polyphosphate production, increased P transport, a switch to utilization of dissolved organic P through increased production of metalloenzymes, and a remodeling of the cell surface through production of sulfolipids. Together, these findings reveal that T. pseudonana has evolved a sophisticated response to P deficiency involving multiple biochemical strategies that are likely critical to its ability to respond to variations in environmental P availability. PMID:22479440

  8. Transcriptional profiling of Petunia seedlings reveals candidate regulators of the cold stress response.

    PubMed

    Li, Bei; Ning, Luyun; Zhang, Junwei; Bao, Manzhu; Zhang, Wei

    2015-01-01

    Petunias are important ornamentals with the capacity for cold acclimation. So far, there is limited information concerning gene regulation and signaling pathways associated with the cold stress response in petunias. A custom-designed petunia microarray representing 24816 genes was used to perform transcriptome profiling in petunia seedlings subjected to cold at 2C for 0.5 h, 2 h, 24 h, and 5 d. A total of 2071 transcripts displayed differential expression patterns under cold stress, of which 1149 were up-regulated and 922 were down-regulated. Gene ontology enrichment analysis demarcated related biological processes, suggesting a possible link between flavonoid metabolism and plant adaptation to low temperatures. Many novel stress-responsive regulators were revealed, suggesting that diverse regulatory pathways may exist in petunias in addition to the well-characterized CBF pathway. The expression changes of selected genes under cold and other abiotic stress conditions were confirmed by real-time RT-PCR. Furthermore, weighted gene co-expression network analysis divided the petunia genes on the array into 65 modules that showed high co-expression and identified stress-specific hub genes with high connectivity. Our identification of these transcriptional responses and groups of differentially expressed regulators will facilitate the functional dissection of the molecular mechanism in petunias responding to environment stresses and extend our ability to improve cold tolerance in plants. PMID:25784921

  9. Transcriptional profiling of Petunia seedlings reveals candidate regulators of the cold stress response

    PubMed Central

    Li, Bei; Ning, Luyun; Zhang, Junwei; Bao, Manzhu; Zhang, Wei

    2015-01-01

    Petunias are important ornamentals with the capacity for cold acclimation. So far, there is limited information concerning gene regulation and signaling pathways associated with the cold stress response in petunias. A custom-designed petunia microarray representing 24816 genes was used to perform transcriptome profiling in petunia seedlings subjected to cold at 2°C for 0.5 h, 2 h, 24 h, and 5 d. A total of 2071 transcripts displayed differential expression patterns under cold stress, of which 1149 were up-regulated and 922 were down-regulated. Gene ontology enrichment analysis demarcated related biological processes, suggesting a possible link between flavonoid metabolism and plant adaptation to low temperatures. Many novel stress-responsive regulators were revealed, suggesting that diverse regulatory pathways may exist in petunias in addition to the well-characterized CBF pathway. The expression changes of selected genes under cold and other abiotic stress conditions were confirmed by real-time RT-PCR. Furthermore, weighted gene co-expression network analysis divided the petunia genes on the array into 65 modules that showed high co-expression and identified stress-specific hub genes with high connectivity. Our identification of these transcriptional responses and groups of differentially expressed regulators will facilitate the functional dissection of the molecular mechanism in petunias responding to environment stresses and extend our ability to improve cold tolerance in plants. PMID:25784921

  10. Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity

    PubMed Central

    Campillo-Navarro, Marcia; Chvez-Blanco, Alma D; Wong-Baeza, Isabel; Serafn-Lpez, Jeanet; Flores-Meja, Ral; Estrada-Parra, Sergio; Estrada-Garca, Iris; Chacn-Salinas, Rommel

    2014-01-01

    Lungs are indispensable organs for the respiratory process, and maintaining their homeostasis is essential for human health and survival. However, during the lifetime of an individual, the lungs suffer countless insults that put at risk their delicate organization and function. Many cells of the immune system participate to maintain this equilibrium and to keep functional lungs. Among these cells, mast cells have recently attracted attention because of their ability to rapidly secrete many chemical and biological mediators that modulate different processes like inflammation, angiogenesis, cell proliferation, etc. In this review, we focus on recent advances in the understanding of the role that mast cells play in lung protection during infections, and of the relation of mast cell responses to type I hypersensitivity-associated pathologies. Furthermore, we discuss the potential role of mast cells during wound healing in the lung and its association with lung cancer, and how mast cells could be exploited as therapeutic targets in some diseases PMID:25484639

  11. LLLT in treating dentinary hypersensitivity: new concepts

    NASA Astrophysics Data System (ADS)

    Brugnera, Aldo, Jr.; Zanin, Fatima; Ladalardo, Thereza C.; Pinheiro, Antonio; Pecora, Jesus D.

    2006-02-01

    Dental hypersensitivity has been studied for several years and it is reported as a strikingly painful condition originating from the exposition of dentinal tubuli . The exposed area is subjected to several kinds of stimuli, resulting in a rapid sharp acute pain. LLLT has been shown to have antiinflammatory, analgesic and cellular effects in both hyperemia and inflammation of the dental pulp. Our previous histological study showed that irradiated animals presented an increased production of dentine and shutting of dentinal tubuli. On the other hand, non-irradiated subjects still showed signals of intense inflammatory reaction and even necrosis at the same experimental times. Irradiated teeth did not show cell degeneration. The LLLT was shown to be efficient in the stimulation of odontoblast cells, producing reparative dentin and closing dentin tubuli. Our clinical studies with 660nm, 790nm and 830nm diode laser, and the total dose per tooth of 4J/cm was shown effective in treating dentinal hypersensitivity as it quickly reduces pain and maintains a prolonged painless status in 91.27 % to 97% of the cases. In a recent study our team observed that significant levels of dentinal desensitization were only found in patients belonging to the 25-35 age group. In conclusion, the results demonstrated indeed that LLLT, when based on the use of correct irradiations parameters is effective in treating hypersensitivity, but the age of patients is one of the factors that may alter the success of treatment due to dentinal sclerosis, which makes the penetration of light more difficult.

  12. Phenytoin-induced acute hypersensitivity pneumonitis

    PubMed Central

    Periwal, Pallavi; Joshi, Sharad; Gothi, Rajesh; Talwar, Deepak

    2015-01-01

    Lungs are target organs for toxic effects of various drugs due to many reasons. Diphenylhydantoin (DPH) is reported to have many extrapulmonary side effects. We are presenting a case of acute hypersensitivity pneumonitis (HP) secondary to DPH, presenting with respiratory failure. Acute HP with respiratory failure is an uncommon drug side effect of the DPH therapy and is a diagnosis of exclusion. It requires detailed workup and exclusion of other causes along with evidence of improvement in the patient's condition after withholding DPH. PMID:26664176

  13. Comparative Transcriptomic Analysis Reveals Similarities and Dissimilarities in Saccharomyces cerevisiae Wine Strains Response to Nitrogen Availability

    PubMed Central

    Barbosa, Catarina; Garca-Martnez, Jos; Prez-Ortn, Jos E.; Mendes-Ferreira, Ana

    2015-01-01

    Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape-musts and the development of strategies to optimize yeast performance in industrial fermentations. PMID:25884705

  14. Transcriptome analysis reveals strong and complex antiviral response in a mollusc.

    PubMed

    He, Yan; Jouaux, Aude; Ford, Susan E; Lelong, Christophe; Sourdaine, Pascal; Mathieu, Michel; Guo, Ximing

    2015-09-01

    Viruses are highly abundant in the oceans, and how filter-feeding molluscs without adaptive immunity defend themselves against viruses is not well understood. We studied the response of a mollusc Crassostrea gigas to Ostreid herpesvirus 1 µVar (OsHV-1μVar) infections using transcriptome sequencing. OsHV-1μVar can replicate extremely rapidly after challenge of C. gigas as evidenced by explosive viral transcription and DNA synthesis, which peaked at 24 and 48 h post-inoculation, respectively, accompanied by heavy oyster mortalities. At 120 h post-injection, however, viral gene transcription and DNA load, and oyster mortality, were greatly reduced indicating an end of active infections and effective control of viral replication in surviving oysters. Transcriptome analysis of the host revealed strong and complex responses involving the activation of all major innate immune pathways that are equipped with expanded and often novel receptors and adaptors. Novel Toll-like receptor (TLR) and MyD88-like genes lacking essential domains were highly up-regulated in the oyster, possibly interfering with TLR signal transduction. RIG-1/MDA5 receptors for viral RNA, interferon-regulatory factors, tissue necrosis factors and interleukin-17 were highly activated and likely central to the oyster's antiviral response. Genes related to anti-apoptosis, oxidation, RNA and protein destruction were also highly up-regulated, while genes related to anti-oxidation were down-regulated. The oxidative burst induced by the up-regulation of oxidases and severe down-regulation of anti-oxidant genes may be important for the destruction of viral components, but may also exacerbate oyster mortality. This study provides unprecedented insights into antiviral response in a mollusc. The mobilization and complex regulation of expanded innate immune-gene families highlights the oyster genome's adaptation to a virus-rich marine environment. PMID:26004318

  15. Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway

    PubMed Central

    Schmitz, Samuel; Lim, Hubert H.

    2014-01-01

    The central auditory system has traditionally been divided into lemniscal and nonlemniscal pathways leading from the midbrain through the thalamus to the cortex. This view has served as an organizing principle for studying, modeling, and understanding the encoding of sound within the brain. However, there is evidence that the lemniscal pathway could be further divided into at least two subpathways, each potentially coding for sound in different ways. We investigated whether such an interpretation is supported by the spatial distribution of response features in the central nucleus of the inferior colliculus (ICC), the part of the auditory midbrain assigned to the lemniscal pathway. We recorded responses to pure tone stimuli in the ICC of ketamine-xylazine-anesthetized guinea pigs and used three-dimensional brain reconstruction techniques to map the location of the recording sites. Compared with neurons in caudal-and-medial regions within an isofrequency lamina of the ICC, neurons in rostral-and-lateral regions responded with shorter first-spike latencies with less spiking jitter, shorter durations of spiking responses, a higher proportion of spikes occurring near the onset of the stimulus, lower thresholds, and larger local field potentials with shorter latencies. Further analysis revealed two distinct clusters of response features located in either the caudal-and-medial or the rostral-and-lateral parts of the isofrequency laminae of the ICC. Thus we report substantial differences in coding properties in two regions of the ICC that are consistent with the hypothesis that the lemniscal pathway is made up of at least two distinct subpathways from the midbrain up to the cortex. PMID:25128560

  16. Intrathecal clonidine potentiates suppression of tactile hypersensitivity by spinal cord stimulation in a model of neuropathy.

    PubMed

    Schechtmann, Gastn; Wallin, Johan; Meyerson, Bjrn A; Linderoth, Bengt

    2004-07-01

    Spinal cord stimulation (SCS) may provide pain relief in approximately 60%-70% of well selected patients with pain caused by peripheral nerve injury. We have previously demonstrated that intrathecal (IT) administration of small doses of certain drugs, both in experimental animals and in patients, significantly enhances the pain-relieving effect of SCS. The alpha2-adrenoceptor agonist, clonidine, is extensively used as an adjunct to spinal morphine and is suggested to be particularly effective for neuropathic pain, but its clinical use is limited by side effects such as sedation and hypotension. In this study, we investigated the dose-response characteristics of IT clonidine, and whether a subeffective dose of clonidine could enhance the effect of SCS in nerve-injured rats with tactile hypersensitivity (allodynia). Results showed that clonidine, in doses of 1-20 microg, reduced the hypersensitivity in a dose-dependent manner. In rats in which SCS per se failed to suppress tactile hypersensitivity, the combination of SCS and a subeffective dose of clonidine appeared to be highly synergistic and markedly attenuated the hypersensitivity. These results suggest that small doses of IT clonidine may be combined with SCS in neuropathic pain patients who do not obtain satisfactory relief with SCS alone. PMID:15281519

  17. DNase I hypersensitive sites flank the mouse class II major histocompatibility complex during B cell development.

    PubMed Central

    Carson, S

    1991-01-01

    The mouse class II major histocompatibility complex (MHC) encodes a polymorphic, multigene family important in the immune response, and is expressed mainly on mature B cells, on certain types of dendritic cells and is also inducible by gamma-interferon on antigen presenting cells. To study the regulatory elements which control this expression pattern, we have examined the chromatin structure flanking the class II MHC region, in particular during B cell differentiation. Using a panel of well-characterised mouse cell lines specific for different stages of B cell development (pre-B, B, plasma cell) as well as non-B cell lines, we have mapped the DNase I hypersensitive (DHS) sites adjacent to the mouse MHC class II region. The results presented show, for the first time that there are specific hypersensitive sites flanking the class II MHC locus during pre B cell, B cell and plasma cell stages of B cell differentiation, irrespective of the status of class II MHC expression. These hypersensitive sites are not found in T cell, fibroblast or uninduced myelomonocytic cell lines. This suggests that these DHS sites define a developmentally stable, chromatin structure, which can be used as a marker of B cell lineage commitment and may indicate that a combination of these hypersensitive sites reflect regulatory proteins involved in the immediate expression of a particular class II MHC gene or possibly control of the entire locus. Images PMID:1923768

  18. Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response

    PubMed Central

    Gao, Xing-Huang; Krokowski, Dawid; Guan, Bo-Jhih; Bederman, Ilya; Majumder, Mithu; Parisien, Marc; Diatchenko, Luda; Kabil, Omer; Willard, Belinda; Banerjee, Ruma; Wang, Benlian; Bebek, Gurkan; Evans, Charles R.; Fox, Paul L.; Gerson, Stanton L.; Hoppel, Charles L.; Liu, Ming; Arvan, Peter; Hatzoglou, Maria

    2015-01-01

    The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems. Bioinformatics analysis revealed that sulfhydrated cysteines are part of a wide range of biological functions. In pancreatic β cells exposed to endoplasmic reticulum (ER) stress, elevated H2S promotes the sulfhydration of enzymes in energy metabolism and stimulates glycolytic flux. We propose that transcriptional and translational reprogramming by the integrated stress response (ISR) in pancreatic β cells is coupled to metabolic alternations triggered by sulfhydration of key enzymes in intermediary metabolism. DOI: http://dx.doi.org/10.7554/eLife.10067.001 PMID:26595448

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

    PubMed Central

    2015-01-01

    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 does not completely eliminate the possibility of hypersensitivity and that patients who received BV treatment before may also be sensitized to SBV. Thus, a skin test should be given prior to using SBV.

  20. Transcriptome signatures of class I and III stress response deregulation in Lactobacillus plantarum reveal pleiotropic adaptation

    PubMed Central

    2013-01-01

    Background To cope with environmental challenges bacteria possess sophisticated defense mechanisms that involve stress-induced adaptive responses. The canonical stress regulators CtsR and HrcA play a central role in the adaptations to a plethora of stresses in a variety of organisms. Here, we determined the CtsR and HrcA regulons of the lactic acid bacterium Lactobacillus plantarum WCFS1 grown under reference (28C) and elevated (40C) temperatures, using ctsR, hrcA, and ctsR-hrcA deletion mutants. Results While the maximum specific growth rates of the mutants and the parental strain were similar at both temperatures (0.33??0.02h-1 and 0.34??0.03h-1, respectively), DNA microarray analyses revealed that the CtsR or HrcA deficient strains displayed altered transcription patterns of genes encoding functions involved in transport and binding of sugars and other compounds, primary metabolism, transcription regulation, capsular polysaccharide biosynthesis, as well as fatty acid metabolism. These transcriptional signatures enabled the refinement of the gene repertoire that is directly or indirectly controlled by CtsR and HrcA of L. plantarum. Deletion of both regulators, elicited transcriptional changes of a large variety of additional genes in a temperature-dependent manner, including genes encoding functions involved in cell-envelope remodeling. Moreover, phenotypic assays revealed that both transcription regulators contribute to regulation of resistance to hydrogen peroxide stress. The integration of these results allowed the reconstruction of CtsR and HrcA regulatory networks in L. plantarum, highlighting the significant intertwinement of class I and III stress regulons. Conclusions Taken together, our results enabled the refinement of the CtsR and HrcA regulatory networks in L. plantarum, illustrating the complex nature of adaptive stress responses in this bacterium. PMID:24238744

  1. Excess fertilizer responsive miRNAs revealed in Linum usitatissimum L.

    PubMed

    Melnikova, Nataliya V; Dmitriev, Alexey A; Belenikin, Maxim S; Speranskaya, Anna S; Krinitsina, Anastasia A; Rachinskaia, Olga A; Lakunina, Valentina A; Krasnov, George S; Snezhkina, Anastasiya V; Sadritdinova, Asiya F; Uroshlev, Leonid A; Koroban, Nadezda V; Samatadze, Tatiana E; Amosova, Alexandra V; Zelenin, Alexander V; Muravenko, Olga V; Bolsheva, Nadezhda L; Kudryavtseva, Anna V

    2015-02-01

    Effective fertilizer application is necessary to increase crop yields and reduce risk of plant overdosing. It is known that expression level of microRNAs (miRNAs) alters in plants under different nutrient concentrations in soil. The aim of our study was to identify and characterize miRNAs with expression alterations under excessive fertilizer in agriculturally important crop - flax (Linum usitatissimum L.). We have sequenced small RNAs in flax grown under normal and excessive fertilizer using Illumina GAIIx. Over 14 million raw reads was obtained for two small RNA libraries. 84 conserved miRNAs from 20 families were identified. Differential expression was revealed for several flax miRNAs under excessive fertilizer according to high-throughput sequencing data. For 6 miRNA families (miR395, miR169, miR408, miR399, miR398 and miR168) expression level alterations were evaluated on the extended sampling using qPCR. Statistically significant up-regulation was revealed for miR395 under excessive fertilizer. It is known that target genes of miR395 are involved in sulfate uptake and assimilation. However, according to our data alterations of the expression level of miR395 could be associated not only with excess sulfur application, but also with redundancy of other macro- and micronutrients. Furthermore expression level was evaluated for miRNAs and their predicted targets. The negative correlation between miR399 expression and expression of its predicted target ubiquitin-conjugating enzyme E2 gene was shown in flax for the first time. So we suggested miR399 involvement in phosphate regulation in L. usitatissimum. Revealed in our study expression alterations contribute to miRNA role in flax response to excessive fertilizer. PMID:25483925

  2. Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity

    PubMed Central

    Ferrusqua, Jos; Prez-Martnez, Isabel; Gmez de la Torre, Ricardo; Fernndez-Almira, Mara Luisa; de Francisco, Ruth; Rodrigo, Luis; Riestra, Sabino

    2015-01-01

    Mesalazine is a 5-aminosalicylic acid derivative that has been widely used to treat patients with inflammatory bowel disease. Accumulating evidence indicates that mesalazine has a very low rate of adverse drug reactions and is well tolerated by patients. However, a few cases of pulmonary and cardiac disease related to mesalazine have been reported in the past, though infrequently, preventing clinicians from diagnosing the conditions early. We describe the case of a 32-year-old man with ulcerative colitis who was admitted with a two-month history of persistent fever following mesalazine treatment initiated 14 mo earlier. At the time of admission, mesalazine dose was increased from 1.5 to 3.0 g/d, and antibiotic therapy was started with no improvement. Three weeks after admission, the patient developed dyspnea, non-productive cough, and chest pain. Severe eosinophilia was detected in laboratory tests, and a computed tomography scan revealed interstitial infiltrates in both lungs, as well as a large pericardial effusion. The bronchoalveolar lavage reported a CD4/CD8 ratio of 0.5, and an increased eosinophil count. Transbronchial biopsy examination showed a severe eosinophilic infiltrate of the lung tissue. Mesalazine-induced cardiopulmonary hypersensitivity was suspected after excluding other possible etiologies. Consequently, mesalazine treatment was suspended, and corticosteroid therapy was initiated, resulting in resolution of symptoms and radiologic abnormalities. We conclude that mesalazine-induced pulmonary and cardiac hypersensitivity should always be considered in the differential diagnosis of unexplained cardiopulmonary symptoms and radiographic abnormalities in patients with inflammatory bowel disease. PMID:25852295

  3. Glycerol Hypersensitivity in a Drosophila Model for Glycerol Kinase Deficiency Is Affected by Mutations in Eye Pigmentation Genes

    PubMed Central

    Wightman, Patrick J.; Jackson, George R.; Dipple, Katrina M.

    2012-01-01

    Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency. PMID:22427807

  4. Presence of corrosion products and hypersensitivity-associated reactions in periprosthetic tissue after aseptic loosening of total hip replacements with metal bearing surfaces.

    PubMed

    Huber, Monika; Reinisch, Georg; Trettenhahn, Günter; Zweymüller, Karl; Lintner, Felix

    2009-01-01

    Aseptic loosening of articular implants is frequently associated with tissue reactions to wear particles. Some patients, who had received metal-on-metal articulations, present early symptoms including persistent pain and implant failure. These symptoms raise the suspicion about the development of an immunological response. Furthermore, the generation of rare corrosion products in association with metallic implants has been observed. Corrosion products are known to enhance third-body wear and contribute to the loss of the implant. The purpose of this study was to investigate periprosthetic tissue containing solid corrosion products after aseptic loosening of second-generation metal-on-metal total hip replacements made of low-carbon cobalt-chromium-molybdenum alloy for the presence of immunologically determined tissue changes. Periprosthetic tissue of 11 cases containing uncommon solid deposits was investigated by light microscopy. In order to confirm the presence of corrosion products, additional methods including scanning electron microscopy (SEM) investigation, energy dispersive X-ray (EDX) and Fourier transform infrared microspectroscopy (FTIR) analysis were used. All investigated cases revealed solid chromium orthophosphate corrosion products as well as metallic wear particles to a various extent. Moreover, various intense tissue reactions characteristic of immune response were observed in all cases. The simultaneous presence of corrosion products and hypersensitivity-associated tissue reaction indicates that a relationship between corrosion development and implant-related hypersensitivity may exist. PMID:18725188

  5. Upregulation of Ih expressed in IB4-negative A? nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    PubMed Central

    Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neurons ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative A?-type (IB4? A?) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- A? neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

  6. Upregulation of Ih expressed in IB4-negative A? nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain.

    PubMed

    Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron's ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative A?-type (IB4(-) A?) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4(-) A? neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

  7. Hypersensitivity reaction to nonanimal stabilized hyaluronic acid.

    PubMed

    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. PMID:16781306

  8. Comparative transcriptome analysis revealed the genotype specific cold response mechanism in tobacco.

    PubMed

    Hu, Risheng; Zhu, Xianxin; Xiang, Shipeng; Zhan, Youguo; Zhu, Mingdong; Yin, Hanqi; Zhou, Qingming; Zhu, Lieshu; Zhang, Xianwen; Liu, Zhi

    2016-01-15

    Cold stress is a major adverse environmental factor that affects plant growth, development, productivity and quality. In the present study, comparative genome-wide transcriptome analysis on two tobacco (Nicotiana tobacum L.) cultivars, cold-tolerant NC567 and cold-sensitive Taiyan8, was performed using RNA-seq technology. After the first assembly, total length of unigenes is from 101,308,644 to 123,781,795bp, the N50 length is from 1357 to 1475bp, and 152,688 unigenes in NC567 and 144,160 unigenes in Taiyan8 were identified, respectively. Functional classification of cold-responsive (COR) genes showed that the genes involved in cell wall metabolism, transcription factors, ubiquitin-proteasome system (UPS) and signaling are over-represented, and the COR genes are specifically induced during cold stress in NC567. Pathway analysis revealed the significant enrichment of the COR genes in plant circadian clock. Taken together, the present study suggested the positive roles of the highly induced expression of the COR genes and the conserved mechanism of circadian clock related genes in tobacco response to cold stress, and provided some valuable genes for crop improvement to cope with cold stress. PMID:26692485

  9. Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

    PubMed Central

    Ishino, Kousuke; Kato, Tatsuya; Kato, Mamoru; Shibata, Tatsuhiro; Watanabe, Masatoshi; Wakabayashi, Keiji; Nakagama, Hitoshi; Totsuka, Yukari

    2015-01-01

    Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome) analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA) against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC), revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice. PMID:25658799

  10. DNA barcodes reveal microevolutionary signals in fire response trait in two legume genera.

    PubMed

    Bello, Abubakar; Daru, Barnabas H; Stirton, Charles H; Chimphango, Samson B M; van der Bank, Michelle; Maurin, Olivier; Muasya, A Muthama

    2015-01-01

    Large-scale DNA barcoding provides a new technique for species identification and evaluation of relationships across various levels (populations and species) and may reveal fundamental processes in recently diverged species. Here, we analysed DNA sequence variation in the recently diverged legumes from the Psoraleeae (Fabaceae) occurring in the Cape Floristic Region (CFR) of southern Africa to test the utility of DNA barcodes in species identification and discrimination. We further explored the phylogenetic signal on fire response trait (reseeding and resprouting) at species and generic levels. We showed that Psoraleoid legumes of the CFR exhibit a barcoding gap yielding the combination of matK and rbcLa (matK + rbcLa) data set as a better barcode than single regions. We found a high score (100 %) of correct identification of individuals to their respective genera but a very low score (<50 %) in identifying them to species. We found a considerable match (54 %) between genetic species and morphologically delimited species. We also found that different lineages showed a weak but significant phylogenetic conservatism in their response to fire as reseeders or resprouters, with more clustering of resprouters than would be expected by chance. These novel microevolutionary patterns might be acting continuously over time to produce multi-scale regularities of biodiversity. This study provides the first insight into the DNA barcoding campaign of land plants in species identification and detection of the phylogenetic signal in recently diverged lineages of the CFR. PMID:26507570

  11. Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells

    PubMed Central

    Stingele, Silvia; Stoehr, Gabriele; Peplowska, Karolina; Cox, Jrgen; Mann, Matthias; Storchova, Zuzana

    2012-01-01

    Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their transcriptome and proteome in comparison with their diploid counterparts. We found that whereas transcription levels reflect the chromosome copy number changes, the abundance of some proteins, such as subunits of protein complexes and protein kinases, is reduced toward diploid levels. Furthermore, using the quantitative data we investigated the changes of cellular pathways in response to aneuploidy. This analysis revealed specific and uniform alterations in pathway regulation in cells with extra chromosomes. For example, the DNA and RNA metabolism pathways were downregulated, whereas several pathways such as energy metabolism, membrane metabolism and lysosomal pathways were upregulated. In particular, we found that the p62-dependent selective autophagy is activated in the human trisomic and tetrasomic cells. Our data present the first broad proteomic analysis of human cells with abnormal karyotypes and suggest a uniform cellular response to the presence of an extra chromosome. PMID:22968442

  12. In vivo gene manipulation reveals the impact of stress-responsive MAPK pathways on tumor progression

    PubMed Central

    Kamiyama, Miki; Naguro, Isao; Ichijo, Hidenori

    2015-01-01

    It has been widely accepted that tumor cells and normal stromal cells in the host environment coordinately modulate tumor progression. Mitogen-activated protein kinase pathways are the representative stress-responsive cascades that exert proper cellular responses to divergent environmental stimuli. Genetically engineered mouse models and chemically induced tumorigenesis models have revealed that components of the MAPK pathway not only regulate the behavior of tumor cells themselves but also that of surrounding normal stromal cells in the host environment during cancer pathogenesis. The individual functions of MAPK pathway components in tumor initiation and progression vary depending on the stimuli and the stromal cell types involved in tumor progression, in addition to the molecular isoforms of the components and the origins of the tumor. Recent studies have indicated that MAPK pathway components synergize with environmental factors (e.g. tobacco smoke and diet) to affect tumor initiation and progression. Moreover, some components play distinct roles in the course of tumor progression, such as before and after the establishment of tumors. Hence, a comprehensive understanding of the multifaceted functions of MAPK pathway components in tumor initiation and progression is essential for the improvement of cancer therapy. In this review, we focus on the reports that utilized knockout, conditional knockout, and transgenic mice of MAPK pathway components to investigate the effects of MAPK pathway components on tumor initiation and progression in the host environment. PMID:25880821

  13. Evoked amygdala responses to negative faces revealed by adaptive MEG beamformers

    PubMed Central

    Cornwell, Brian R; Carver, Frederick W; Coppola, Richard; Johnson, Linda; Alvarez, Ruben; Grillon, Christian

    2008-01-01

    Adaptive beamformer analyses of magnetoencephalograms (MEG) have shown promise as a method for functional imaging of cortical processes. Although recent evidence is encouraging, it is unclear whether these methods can both localize and reconstruct the time course of activity in subcortical structures such as the amygdala. Fourteen healthy participants (7 women) performed a perceptual matching task of negative emotional faces (angry and fearful) and geometric shapes that was designed for functional magnetic resonance imaging (fMRI) studies to maximize amygdala activation. Neuromagnetic data were collected with a 275-channel whole-head magnetometer, and event-related adaptive beamformer analyses were conducted to estimate broadband evoked responses to faces and shapes across the whole brain in 7mm steps. Group analyses revealed greater left amygdala activity to faces over shapes, both when face-matching and shape-matching trials were presented in separate blocks and when they were randomly intermixed. This finding was replicated in a second experiment with 7 new participants (3 women). Virtual sensor time series showed clear evoked responses in the left amygdala and left fusiform gyrus in both runs and experiments. We conclude that amygdala activity can be resolved from MEGs with adaptive beamformers with temporal resolution superior to other neuroimaging modalities. This demonstration should encourage use of MEG for elucidating functional networks mediating fear-related neural phenomena that likely unfold rapidly in time across cortical and subcortical structures. PMID:18930036

  14. Systems responses of rats to mequindox revealed by metabolic and transcriptomic profiling.

    PubMed

    Zhao, Xiu-Ju; Hao, Fuhua; Huang, Chongyang; Rantalainen, Mattias; Lei, Hehua; Tang, Huiru; Wang, Yulan

    2012-09-01

    Mequindox is used as an antibiotic drug in livestock; however, its toxicity remains largely unclear. Previously, we investigated metabolic responses of mice to mequindox exposure. In order to evaluate dependences of animal species in response to mequindox insult, we present the metabolic consequences of mequindox exposure in a rat model, by employing the combination of metabonomics and transcriptomics. Metabolic profiling of urine revealed that metabolic recovery is achieved for rats exposed to a low or moderate dose of mequindox, whereas high levels of mequindox exposure trigger liver dysfunction, causing no such recovery. We found that mequindox exposure causes suppression of the tricarboxylic acid cycle and stimulation of glycolysis, which is in contrast to a mouse model previously investigated. In addition, mequindox dosage induces promotion of ?-oxidation of fatty acids, which was confirmed by elevated expressions of acox1, hsd17b2, and cpt1a in liver. Furthermore, altered levels of N-methylnicotinate, 1-methylnicotinamide, and glutathione disulfide highlighted the promotion of vitamin B3 antioxidative cycle in rats exposed to mequindox. Moreover, mequindox exposure altered levels of gut microbiotal related co-metabolites, suggesting a perturbation of the gut microflora of the host. Our work provides a comprehensive view of the toxicological effects of mequindox, which is important in the usage of mequindox in animal and human food safety. PMID:22845897

  15. In vivo gene manipulation reveals the impact of stress-responsive MAPK pathways on tumor progression.

    PubMed

    Kamiyama, Miki; Naguro, Isao; Ichijo, Hidenori

    2015-07-01

    It has been widely accepted that tumor cells and normal stromal cells in the host environment coordinately modulate tumor progression. Mitogen-activated protein kinase pathways are the representative stress-responsive cascades that exert proper cellular responses to divergent environmental stimuli. Genetically engineered mouse models and chemically induced tumorigenesis models have revealed that components of the MAPK pathway not only regulate the behavior of tumor cells themselves but also that of surrounding normal stromal cells in the host environment during cancer pathogenesis. The individual functions of MAPK pathway components in tumor initiation and progression vary depending on the stimuli and the stromal cell types involved in tumor progression, in addition to the molecular isoforms of the components and the origins of the tumor. Recent studies have indicated that MAPK pathway components synergize with environmental factors (e.g. tobacco smoke and diet) to affect tumor initiation and progression. Moreover, some components play distinct roles in the course of tumor progression, such as before and after the establishment of tumors. Hence, a comprehensive understanding of the multifaceted functions of MAPK pathway components in tumor initiation and progression is essential for the improvement of cancer therapy. In this review, we focus on the reports that utilized knockout, conditional knockout, and transgenic mice of MAPK pathway components to investigate the effects of MAPK pathway components on tumor initiation and progression in the host environment. PMID:25880821

  16. Capturing Arabidopsis root architecture dynamics with ROOT-FIT reveals diversity in responses to salinity.

    PubMed

    Julkowska, Magdalena M; Hoefsloot, Huub C J; Mol, Selena; Feron, Richard; de Boer, Gert-Jan; Haring, Michel A; Testerink, Christa

    2014-11-01

    The plant root is the first organ to encounter salinity stress, but the effect of salinity on root system architecture (RSA) remains elusive. Both the reduction in main root (MR) elongation and the redistribution of the root mass between MRs and lateral roots (LRs) are likely to play crucial roles in water extraction efficiency and ion exclusion. To establish which RSA parameters are responsive to salt stress, we performed a detailed time course experiment in which Arabidopsis (Arabidopsis thaliana) seedlings were grown on agar plates under different salt stress conditions. We captured RSA dynamics with quadratic growth functions (root-fit) and summarized the salt-induced differences in RSA dynamics in three growth parameters: MR elongation, average LR elongation, and increase in number of LRs. In the ecotype Columbia-0 accession of Arabidopsis, salt stress affected MR elongation more severely than LR elongation and an increase in LRs, leading to a significantly altered RSA. By quantifying RSA dynamics of 31 different Arabidopsis accessions in control and mild salt stress conditions, different strategies for regulation of MR and LR meristems and root branching were revealed. Different RSA strategies partially correlated with natural variation in abscisic acid sensitivity and different Na(+)/K(+) ratios in shoots of seedlings grown under mild salt stress. Applying root-fit to describe the dynamics of RSA allowed us to uncover the natural diversity in root morphology and cluster it into four response types that otherwise would have been overlooked. PMID:25271266

  17. DNA barcodes reveal microevolutionary signals in fire response trait in two legume genera

    PubMed Central

    Bello, Abubakar; Daru, Barnabas H.; Stirton, Charles H.; Chimphango, Samson B. M.; van der Bank, Michelle; Maurin, Olivier; Muasya, A. Muthama

    2015-01-01

    Large-scale DNA barcoding provides a new technique for species identification and evaluation of relationships across various levels (populations and species) and may reveal fundamental processes in recently diverged species. Here, we analysed DNA sequence variation in the recently diverged legumes from the Psoraleeae (Fabaceae) occurring in the Cape Floristic Region (CFR) of southern Africa to test the utility of DNA barcodes in species identification and discrimination. We further explored the phylogenetic signal on fire response trait (reseeding and resprouting) at species and generic levels. We showed that Psoraleoid legumes of the CFR exhibit a barcoding gap yielding the combination of matK and rbcLa (matK + rbcLa) data set as a better barcode than single regions. We found a high score (100 %) of correct identification of individuals to their respective genera but a very low score (<50 %) in identifying them to species. We found a considerable match (54 %) between genetic species and morphologically delimited species. We also found that different lineages showed a weak but significant phylogenetic conservatism in their response to fire as reseeders or resprouters, with more clustering of resprouters than would be expected by chance. These novel microevolutionary patterns might be acting continuously over time to produce multi-scale regularities of biodiversity. This study provides the first insight into the DNA barcoding campaign of land plants in species identification and detection of the phylogenetic signal in recently diverged lineages of the CFR. PMID:26507570

  18. The neural response to emotional prosody, as revealed by functional magnetic resonance imaging.

    PubMed

    Mitchell, Rachel L C; Elliott, Rebecca; Barry, Martin; Cruttenden, Alan; Woodruff, Peter W R

    2003-01-01

    Prosody is an important feature of language, comprising intonation, loudness, and tempo. Emotional prosodic processing forms an integral part of our social interactions. The main aim of this study was to use bold contrast fMRI to clarify the normal functional neuroanatomy of emotional prosody, in passive and active contexts. Subjects performed six separate scanning studies, within which two different conditions were contrasted: (1) "pure" emotional prosody versus rest; (2) congruent emotional prosody versus 'neutral' sentences; (3) congruent emotional prosody versus rest; (4) incongruent emotional prosody versus rest; (5) congruent versus incongruent emotional prosody; and (6) an active experiment in which subjects were instructed to either attend to the emotion conveyed by semantic content or that conveyed by tone of voice. Data resulting from these contrasts were analysed using SPM99. Passive listening to emotional prosody consistently activated the lateral temporal lobe (superior and/or middle temporal gyri). This temporal lobe response was relatively right-lateralised with or without semantic information. Both the separate and direct comparisons of congruent and incongruent emotional prosody revealed that subjects used fewer brain regions to process incongruent emotional prosody than congruent. The neural response to attention to semantics, was left lateralised, and recruited an extensive network not activated by attention to emotional prosody. Attention to emotional prosody modulated the response to speech, and induced right-lateralised activity, including the middle temporal gyrus. In confirming the results of lesion and neuropsychological studies, the current study emphasises the importance of the right hemisphere in the processing of emotional prosody, specifically the lateral temporal lobes. PMID:12757912

  19. Yeast Transcriptome and In Vivo Hypoxia Detection Reveals Histoplasma capsulatum Response to Low Oxygen Tension.

    PubMed

    DuBois, Juwen C; Pasula, Rajamouli; Dade, Jessica E; Smulian, A George

    2016-01-01

    Although there is growing understanding of the microenvironmental conditions fungal pathogens encounter as they colonize their host, nothing is known about Histoplasma capsulatum's response to hypoxia. Here we characterized hypoxia during murine histoplasmosis using an in vivo hypoxia detection agent, Hypoxyprobe-2 (HP-2); and analyzed H. capsulatum's transcriptional profile in response to in vitro hypoxia. Immunohistopathology and flow cytometry analyses revealed distinct regions of hypoxia during infection. Granuloma cells, enriched with macrophages and T-cells isolated from infected livers were 66-76% positive for HP-2, of which, 95% of macrophages and 55% of T-cells were hypoxic. Although inhibited, H. capsulatum was able to survive under in vitro hypoxic conditions (<1% O2), and restored growth when replaced in normoxia. Next-generation sequencing (RNA-seq) analysis after 24 hours of hypoxia demonstrated a significant increase in NIT50 (swirm domain DNA binding protein), a predicted ABC transporter (ABC), NADPH oxidoreductase (NADP/FAD), and guanine nucleotide exchange factor (RSP/GEF); and other genes with no known designated function. Computational transcription factor binding site analysis predicted human sterol regulatory element binding protein (SREBP) binding sites upstream of NIT50, ABC, NADP/FAD and RSP/GEF. Hypoxia resulted in a time-dependent increase in the H. capsulatum homolog of SREBP, here named Srb1. Srb1 peaked at 8 hours and returned to basal levels by 24 hours. Our findings demonstrate that H. capsulatum encounters and survives severe hypoxia during infection. Additionally, the hypoxic response may be regulated at the level of transcription, and these studies contribute to the understanding of hypoxic regulation and adaptation in H. capsulatum. PMID:26483436

  20. Revealing Shared and Distinct Gene Network Organization in Arabidopsis Immune Responses by Integrative Analysis1

    PubMed Central

    Dong, Xiaobao; Jiang, Zhenhong; Peng, You-Liang; Zhang, Ziding

    2015-01-01

    Pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) are two main plant immune responses to counter pathogen invasion. Genome-wide gene network organizing principles leading to quantitative differences between PTI and ETI have remained elusive. We combined an advanced machine learning method and modular network analysis to systematically characterize the organizing principles of Arabidopsis (Arabidopsis thaliana) PTI and ETI at three network resolutions. At the single network node/edge level, we ranked genes and gene interactions based on their ability to distinguish immune response from normal growth and successfully identified many immune-related genes associated with PTI and ETI. Topological analysis revealed that the top-ranked gene interactions tend to link network modules. At the subnetwork level, we identified a subnetwork shared by PTI and ETI encompassing 1,159 genes and 1,289 interactions. This subnetwork is enriched in interactions linking network modules and is also a hotspot of attack by pathogen effectors. The subnetwork likely represents a core component in the coordination of multiple biological processes to favor defense over development. Finally, we constructed modular network models for PTI and ETI to explain the quantitative differences in the global network architecture. Our results indicate that the defense modules in ETI are organized into relatively independent structures, explaining the robustness of ETI to genetic mutations and effector attacks. Taken together, the multiscale comparisons of PTI and ETI provide a systems biology perspective on plant immunity and emphasize coordination among network modules to establish a robust immune response. PMID:25614062

  1. Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity.

    PubMed

    Omiya, Ryusuke; Tsushima, Fumihiko; Narazaki, Hidehiko; Sakoda, Yukimi; Kuramasu, Atsuo; Kim, Youn; Xu, Haiying; Tamura, Hideto; Zhu, Gefeng; Chen, Lieping; Tamada, Koji

    2009-12-01

    Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1-Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1-Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of naïve and memory T cells along with G(0)/G(1) cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions. PMID:19930044

  2. Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity

    PubMed Central

    Omiya, Ryusuke; Tsushima, Fumihiko; Narazaki, Hidehiko; Sakoda, Yukimi; Kuramasu, Atsuo; Kim, Youn; Xu, Haiying; Tamura, Hideto; Zhu, Gefeng; Chen, Lieping; Tamada, Koji

    2009-01-01

    Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of nave and memory T cells along with G0/G1 cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions. PMID:19930044

  3. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...

  4. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...

  5. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...

  6. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...

  7. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...

  8. Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response

    PubMed Central

    Feinerman, Ofer; Jentsch, Garrit; Tkach, Karen E; Coward, Jesse W; Hathorn, Matthew M; Sneddon, Michael W; Emonet, Thierry; Smith, Kendall A; Altan-Bonnet, Grgoire

    2010-01-01

    Understanding how the immune system decides between tolerance and activation by antigens requires addressing cytokine regulation as a highly dynamic process. We quantified the dynamics of interleukin-2 (IL-2) signaling in a population of T cells during an immune response by combining in silico modeling and single-cell measurements in vitro. We demonstrate that IL-2 receptor expression levels vary widely among T cells creating a large variability in the ability of the individual cells to consume, produce and participate in IL-2 signaling within the population. Our model reveals that at the population level, these heterogeneous cells are engaged in a tug-of-war for IL-2 between regulatory (Treg) and effector (Teff) T cells, whereby access to IL-2 can either increase the survival of Teff cells or the suppressive capacity of Treg cells. This tug-of-war is the mechanism enforcing, at the systems level, a core function of Treg cells, namely the specific suppression of survival signals for weakly activated Teff cells but not for strongly activated cells. Our integrated model yields quantitative, experimentally validated predictions for the manipulation of Treg suppression. PMID:21119631

  9. The role of MIP-1alpha in experimental hypersensitivity pneumonitis.

    PubMed

    Schuyler, M; Gott, K; French, V

    2004-01-01

    S. rectivirgula (SR) causes Farmer's Lung Disease, a classic example of hypersensitivity pneumonitis (HP). We utilized a model of experimental hypersensitivity pneumonitis (EHP), antibody to MIP-1alpha and MIP-1alpha -/- mice, to test the hypothesis that MIP-1alpha is essential in the development of EHP. Treatment of C57BI/6 mice with anti-MIP-1alpha antibody did not change the extent of pulmonary histology abnormalities, BALF cell number or characteristics, or BALF concentration of IL12p40, TNF, IL1alpha and IL6, after an i.t. challenge with SR. MIP-1alpha -/- animals responded similarly to wild-type (wt) animals in the extent and nature of pulmonary histologic changes and BALF cell number and type after a single i.t. injection of SR There was a dose-response relationship between the amount of SR and BALF IL12p40, MCP-1 and IL6 in both strains, and MIP-1alpha in wild-type animals. We next transferred SR cultured spleen cells from SR sensitized mice (both wt and MIP-1alpha -/-) to naive recipients. Lung histology and BALF characteristics after SR i.t. challenge of the recipients were used to determine if adoptive transfer had occurred. Cultured cells from MIP-1alpha -/- animals were fully capable of transferring EHP to recipients. There was no difference of BALF TNF, IL6 and IL1alpha between the strains, but there was more MCP-1 and IL12p40 in the MIP-1alpha -/- mice than in the control mice. MIP-1alpha is not necessary for the recruitment of cells into the lung and BALF after i.t. administration of SR, or the development of cells able to adoptively transfer EHP. PMID:15526753

  10. HDAC4 is required for inflammation-associated thermal hypersensitivity

    PubMed Central

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

    2015-01-01

    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 nave 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 (0.20.44-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 Freunds adjuvant (CFA) model of inflammatory pain (1.31.4-fold improvement over wild-type controls; n = 512, 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.Crow, M., Khovanov, N., Kelleher, J. H., Sharma, S., Grant, A. D., Bogdanov, Y., Wood, J. N., McMahon, S. B., Denk, F. HDAC4 is required for inflammation-associated thermal hypersensitivity. PMID:25903105

  11. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    SciTech Connect

    Fang, Liang; Zhao, Fang; Shen, Xuefeng; Ouyang, Weiming; Liu, Xinqin; Xu, Yan; Yu, Tao; Jin, Boquan; Chen, Jingyuan; Luo, Wenjing

    2012-12-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup −} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4{sup +} thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  12. The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

    PubMed

    Asgar, J; Zhang, Y; Saloman, J L; Wang, S; Chung, M-K; Ro, J Y

    2015-12-01

    Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-d-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and ?,?-methylene adenosine triphosphate (??meATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain and mechanical hyperalgesia. Mechanistic studies elucidating transcriptional or post-translational regulation of TRPA1 expression under pathological pain conditions should provide important basic information to further advance the treatment of craniofacial muscle pain conditions. PMID:26393428

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

    PubMed Central

    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 Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched casecontrol 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 study identified several genomic regions associated with insect bite hypersensitivity in Shetland pony mares and Icelandic horses. On chromosome 20, associated genomic regions in both breeds were within 2 Mb from the equine lymphocyte antigen class II region. Increased knowledge on insect bite hypersensitivity associated genes will contribute to our understanding of its biology, enabling more efficient selection, therapy and prevention to decrease insect bite hypersensitivity prevalence. PMID:23110538

  14. Clinical efficiency of a natural resin fluoride varnish (Shellac F) in reducing dentin hypersensitivity.

    PubMed

    Hoang-Dao, B-T; Hoang-Tu, H; Tran-Thi, N-N; Koubi, G; Camps, J; About, I

    2009-02-01

    Previous in vitro permeability and scanning electron microscopic studies have demonstrated the effectiveness of a new natural based-resin varnish (Shellac F) in dentin permeability reduction and effective tubule occlusion. The aim of this randomized double-blind, controlled, split mouth 8-week clinical study was to evaluate the efficiency of Shellac F in reducing dentin hypersensitivity. Ten patients (eight women: two men) completed the study. A quadrant including at least one hypersensitive tooth (Visual Analog Scale - VAS = 15 mm to air blast) was considered as a unit and randomly assigned to different groups for Shellac F, Duraphat, Isodan. Three applications of each material were completed at days 0, 1 and 7. The subjective response was assessed by tactile and thermal/evaporative methods. Data were collected at baseline and after the first application, at 15 min, 1, 7, 14, 28 and 56 days. Analysis was based on Kruskall-Wallis test, Wilcoxon signed rank test and the method of the least square means. No statistically significant difference was noted between Shellac F and the two control materials. Regardless of the type of stimulus, Shellac F showed significant immediate and progressive continuous efficiency in reducing dentin hypersensitivity until 56 days (VAS of 14 +/- 12 mm and provoking pain force of 89 +/- 12 cN, respectively, compared with 38 +/- 23 mm and 41 +/- 10 cN at baseline), corresponding to a highly effective relief dentin hypersensitivity. Shellac F reduced dentin hypersensitivity and did not differ from the two desensitizing agents used as controls. PMID:19522897

  15. Metagenomics, metatranscriptomics and single cell genomics reveal functional response of active Oceanospirillales to Gulf oil spill

    SciTech Connect

    Mason, Olivia U.; Hazen, Terry C.; Borglin, Sharon; Chain, Patrick S. G.; Dubinsky, Eric A.; Fortney, Julian L.; Han, James; Holman, Hoi-Ying N.; Hultman, Jenni; Lamendella, Regina; Mackelprang, Rachel; Malfatti, Stephanie; Tom, Lauren M.; Tringe, Susannah G.; Woyke, Tanja; Zhou, Jizhong; Rubin, Edward M.; Jansson, Janet K.

    2012-06-12

    The Deepwater Horizon oil spill in the Gulf of Mexico resulted in a deep-sea hydrocarbon plume that caused a shift in the indigenous microbial community composition with unknown ecological consequences. Early in the spill history, a bloom of uncultured, thus uncharacterized, members of the Oceanospirillales was previously detected, but their role in oil disposition was unknown. Here our aim was to determine the functional role of the Oceanospirillales and other active members of the indigenous microbial community using deep sequencing of community DNA and RNA, as well as single-cell genomics. Shotgun metagenomic and metatranscriptomic sequencing revealed that genes for motility, chemotaxis and aliphatic hydrocarbon degradation were significantly enriched and expressed in the hydrocarbon plume samples compared with uncontaminated seawater collected from plume depth. In contrast, although genes coding for degradation of more recalcitrant compounds, such as benzene, toluene, ethylbenzene, total xylenes and polycyclic aromatic hydrocarbons, were identified in the metagenomes, they were expressed at low levels, or not at all based on analysis of the metatranscriptomes. Isolation and sequencing of two Oceanospirillales single cells revealed that both cells possessed genes coding for n-alkane and cycloalkane degradation. Specifically, the near-complete pathway for cyclohexane oxidation in the Oceanospirillales single cells was elucidated and supported by both metagenome and metatranscriptome data. The draft genome also included genes for chemotaxis, motility and nutrient acquisition strategies that were also identified in the metagenomes and metatranscriptomes. These data point towards a rapid response of members of the Oceanospirillales to aliphatic hydrocarbons in the deep sea.

  16. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity

    PubMed Central

    Everard, Amandine; Lazarevic, Vladimir; Gaïa, Nadia; Johansson, Maria; Ståhlman, Marcus; Backhed, Fredrik; Delzenne, Nathalie M; Schrenzel, Jacques; François, Patrice; Cani, Patrice D

    2014-01-01

    The gut microbiota is involved in metabolic and immune disorders associated with obesity and type 2 diabetes. We previously demonstrated that prebiotic treatment may significantly improve host health by modulating bacterial species related to the improvement of gut endocrine, barrier and immune functions. An analysis of the gut metagenome is needed to determine which bacterial functions and taxa are responsible for beneficial microbiota–host interactions upon nutritional intervention. We subjected mice to prebiotic (Pre) treatment under physiological (control diet: CT) and pathological conditions (high-fat diet: HFD) for 8 weeks and investigated the production of intestinal antimicrobial peptides and the gut microbiome. HFD feeding significantly decreased the expression of regenerating islet-derived 3-gamma (Reg3g) and phospholipase A2 group-II (PLA2g2) in the jejunum. Prebiotic treatment increased Reg3g expression (by ∼50-fold) and improved intestinal homeostasis as suggested by the increase in the expression of intectin, a key protein involved in intestinal epithelial cell turnover. Deep metagenomic sequencing analysis revealed that HFD and prebiotic treatment significantly affected the gut microbiome at different taxonomic levels. Functional analyses based on the occurrence of clusters of orthologous groups (COGs) of proteins also revealed distinct profiles for the HFD, Pre, HFD-Pre and CT groups. Finally, the gut microbiota modulations induced by prebiotics counteracted HFD-induced inflammation and related metabolic disorders. Thus, we identified novel putative taxa and metabolic functions that may contribute to the development of or protection against the metabolic alterations observed during HFD feeding and HFD-Pre feeding. PMID:24694712

  17. Metagenome, metatranscriptome and single-cell sequencing reveal microbial response to Deepwater Horizon oil spill

    PubMed Central

    Mason, Olivia U; Hazen, Terry C; Borglin, Sharon; Chain, Patrick S G; Dubinsky, Eric A; Fortney, Julian L; Han, James; Holman, Hoi-Ying N; Hultman, Jenni; Lamendella, Regina; Mackelprang, Rachel; Malfatti, Stephanie; Tom, Lauren M; Tringe, Susannah G; Woyke, Tanja; Zhou, Jizhong; Rubin, Edward M; Jansson, Janet K

    2012-01-01

    The Deepwater Horizon oil spill in the Gulf of Mexico resulted in a deep-sea hydrocarbon plume that caused a shift in the indigenous microbial community composition with unknown ecological consequences. Early in the spill history, a bloom of uncultured, thus uncharacterized, members of the Oceanospirillales was previously detected, but their role in oil disposition was unknown. Here our aim was to determine the functional role of the Oceanospirillales and other active members of the indigenous microbial community using deep sequencing of community DNA and RNA, as well as single-cell genomics. Shotgun metagenomic and metatranscriptomic sequencing revealed that genes for motility, chemotaxis and aliphatic hydrocarbon degradation were significantly enriched and expressed in the hydrocarbon plume samples compared with uncontaminated seawater collected from plume depth. In contrast, although genes coding for degradation of more recalcitrant compounds, such as benzene, toluene, ethylbenzene, total xylenes and polycyclic aromatic hydrocarbons, were identified in the metagenomes, they were expressed at low levels, or not at all based on analysis of the metatranscriptomes. Isolation and sequencing of two Oceanospirillales single cells revealed that both cells possessed genes coding for n-alkane and cycloalkane degradation. Specifically, the near-complete pathway for cyclohexane oxidation in the Oceanospirillales single cells was elucidated and supported by both metagenome and metatranscriptome data. The draft genome also included genes for chemotaxis, motility and nutrient acquisition strategies that were also identified in the metagenomes and metatranscriptomes. These data point towards a rapid response of members of the Oceanospirillales to aliphatic hydrocarbons in the deep sea. PMID:22717885

  18. Calcium sodium phosphosilicate had some benefit on dentine hypersensitivity.

    PubMed

    Freda, Nicolas M; Veitz-Keenan, Analia

    2016-03-01

    Data sourcesMedline (via Pubmed), Embase, Web of Science, CENTRAL (The Cochrane Library), and the Chinese Biomedical Literature Database. Search strategy was limited to articles published in English and Chinese. No restriction applied to date of publication and a supplemental manual search was conducted by reviewing the reference lists for related paper and articles. Grey literature was also searched in ClinicalTrials.gov, the National Research Register, OpenGrey and the WHO's international clinical Trial Registry Platform.Study selectionRandomised controlled trials in humans with DH that compared topical CSPS in any modality and any concentration to a negative (placebo) control. The primary outcome was the DH pain response to routine activities or to thermal, tactile, evaporative or electrical stimuli, and the secondary outcome was the side effect of CSPS use including discomfort, oral hygiene deterioration or dental staining.Data extraction and synthesisStudy selection, data extraction and risk bias assessment were carried out in duplicate by two calibrated reviewers. Any disagreement was resolved via discussion after consulting a third reviewer. Mean differences (MDs) and standard deviations (SDs) were used to summarise data in studies with continuous outcomes. Heterogeneity was assessed using the I(2) test. Meta-analysis was performed when similarities were found among the included studies. The Grading of Recommendations Assessment Development and Evaluation (GRADE) System's Profiler was used to assess the quality of the body of the evidence.ResultsEleven trials were included comparing CSPS with a negative control. Four articles that focused on post-periodontal therapy were extracted as an independent analysis group. CSPS was used in topical administration with concentrations ranging from 2.5%-15%. Follow-up times ranged from 15 days to eight weeks. DH pain was elicited by tactile, evaporative or thermal stimuli. A 10 cm visual analogue scale (VAS) was the most commonly used for measurements. Five studies revealed a low risk of bias, one study had a high risk of bias and five studies had an unclear risk of bias. Seven of the studies were regarded as having a potential conflict of interest.For the primary outcome (DH) Subjects in the DH group (four studies) showed that toothpaste containing 5% CSPS was favoured compared with a negative control at almost every time point, however one study did not report a significant difference between these treatments at two weeks.The results from the from the grey literature (two studies) did not show significant differences between the CSPS and control groups and the results were not in agreement with the other studies.Another study observed effects of both 2.5% and 7.5% CSPS-containing toothpaste: 7.5% CSPS was more effective at relieving DH than a negative control, whereas no significant difference was found between 2.5% and the negative controls.For the secondary outcome (adverse events): six studies did not observe adverse reactions. The remaining studies reported minor adverse events, although most were not orally related.Toothpaste containing 5% CSPS versus negative control: the 5% CSPS-containing toothpaste showed a better desensitising effect at both two and six weeks regardless of the applied stimuli (evaporative, two weeks: MD = -0.68; 95% CIs = -1.15, -0. 20; I2 = 59%; evaporative, six weeks: MD = -1.69; 95% CIs = -1.86, -1.52; I2 = 42%; thermal, two weeks: MD = -0.59; 95% CIs = -1.33, 0.14; I2 = 84%; and thermal, six weeks: MD = -1.70; 95% CIs = -2.17, -1.23;I2 = 72%). The quality of evidence was categorised as 'moderate'.Prophylaxis paste containing 15% CSPS versus negative control: prophylaxis paste containing 15% CSPS showed a better desensitising effect on post-periodontal therapy DH pain than a negative control, immediately after prophylaxis and at four weeks, as determined using evaporative or tactile stimuli, and the results showed relatively low heterogeneity (evaporative, immediate: MD = -0.87; 95% CIs = -1.23, -0.51; I2 = 0%; evaporative, four weeks: MD = -0.93; 95% CIs = -1.11, -0.75; I2 = 41%; tactile, immediate: MD = -9.59; 95%CIs = -12.17, -7.01; I2 = 55%; and tactile, four weeks: MD = -8.34; 95% CIs = -10.87, -5.80; I2 =0%). The quality of evidence was classified as 'low'.The two studies that assessed patients' self-assessments of dentine sensitivity were not pooled because of clinical heterogeneity.ConclusionsThe majority of the studies included in the review found that sodium phosphosilicate was more effective than negative control at alleviating dentine hypersensitivity, used either as toothpaste to alleviate DH or as a prophylaxis paste to treat post-periodontal therapy DH. The review found moderate quality of evidence that 5% CSPS-containing toothpaste is effective for use as an at-home treatment to relieve DH. There is low quality evidence that prophylaxis paste containing 15% CSPS is favoured over a negative control at reducing post-periodontal therapy hypersensitivity. It remains unclear whether concentrations of more than 5% CSPS have increased risk of side effects. The results are based on a small number of clinical trials. Seven of the studies were industry or partially industry-sponsored. PMID:27012568

  19. Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity.

    PubMed

    Savetsky, Ira L; Albano, Nicholas J; Cuzzone, Daniel A; Gardenier, Jason C; Torrisi, Jeremy S; Garca Nores, Gabriela D; Nitti, Matthew D; Hespe, Geoffrey E; Nelson, Tyler S; Kataru, Raghu P; Dixon, J Brandon; Mehrara, Babak J

    2015-11-01

    Obesity is a major risk factor for inflammatory dermatologic diseases, including atopic dermatitis and psoriasis. In addition, recent studies have shown that obesity impairs lymphatic function. As the lymphatic system is a critical regulator of inflammatory reactions, we tested the hypothesis that obesity-induced lymphatic dysfunction is a key regulator of cutaneous hypersensitivity reactions in obese mice. We found that obese mice have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity. In addition, obese mice displayed heightened dermatitis responses to inflammatory skin stimuli, resulting in both higher peak inflammation and a delayed clearance of inflammatory responses. Injection of recombinant vascular endothelial growth factor-C remarkably increased lymphangiogenesis, lymphatic function, and lymphatic endothelial cell expression of chemokine (C-C motif) ligand 21, while decreasing inflammation and expression of inducible nitrous oxide synthase. These changes resulted in considerably decreased dermatitis responses in both lean and obese mice. Taken together, our findings suggest that obesity-induced changes in the lymphatic system result in an amplified and a prolonged inflammatory response. PMID:26176761

  20. Delayed hypersensitivity and neutrophil chemotaxis: effect of trauma.

    PubMed

    Meakins, J L; McLean, A P; Kelly, R; Bubenik, O; Pietsch, J B; MacLean, L D

    1978-04-01

    To investigate alterations in host defense produced by trauma, skin testing with five standard recall antigens was done on admission and weekly on 53 patients with blunt trauma and seven with penetrating missile injuries, who then were classified as normal (N), 2 or more positive responses; relatively anergic (RA), one positive response; or anergic (A), no response. Neutrophil chemotaxis was tested 145 times in 32 patients. Degree of injury was assessed by assigning one point to pelvic fracture, long-bone fracture, head, chest, or abdominal injury, to a maximum of five. The A and RA patients had greater trauma, 3 vs. 1.6 for N, and a significantly increased rate of sepsis (p less than 0.005) and mortality (p less than 0.05). Incidence of anergy depended upon age and extent of trauma. Neutrophil chemotaxis in A and RA patients was significantly (p less than 0.001) worse at 96.7 +/- 2.4 mu and 99.8 +/- 1.7 mu compared to N, 113.2 +/- 1.7 mu, and controls 121 +/- 4 mu. With recovery, chemotaxis returned to normal. It is concluded that failure of delayed hypersensitivity responses follows trauma, is related to the severity of injury and age of patient, and is associated with an abnormality of neutrophil chemotaxis and increased rate of sepsis. PMID:660668

  1. Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria.

    PubMed

    Tillie-Leblond, I; Grenouillet, F; Reboux, G; Roussel, S; Chouraki, B; Lorthois, C; Dalphin, J-C; Wallaert, B; Millon, L

    2011-03-01

    Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP). The aim of the present study was to identify the antigen (Ag) responsible for MWF-associated HP, and to optimise serological diagnosis by definition of a threshold allowing discrimination between HP patients and asymptomatic exposed workers. 13 patients, who were workers at a car engine manufacturing plant, were suspected of MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from 13 MWF-associated HP patients, 12 asymptomatic exposed workers and 18 healthy unexposed controls were tested to determine their immunological responses to three Ags, including Mycobacterium immunogenum. M. immunogenum was identified in 40% of used fluids by culture and confirmed by DNA sequencing. The threshold for differentiating MWF-associated HP patients from asymptomatic exposed workers was five arcs of precipitation (sensitivity 77% and specificity 92%), as determined by electrosyneresis (ES). Using ELISA methods with protein extract from M. immunogenum, a threshold leading to 92% sensitivity and 100% specificity was established. The detection of specific antibodies against M. immunogenum Ag at high levels in case sera suggests that M. immunogenum-contaminated MWF is responsible for MWF-associated HP. To discriminate MWF-associated HP patients from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a 1.6-AU threshold for ELISA methods. PMID:20693254

  2. Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

    PubMed

    Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

    2000-09-01

    Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death. PMID:11006337

  3. Genetic Interaction Landscape Reveals Critical Requirements for Schizosaccharomyces pombe Brc1 in DNA Damage Response Mutants.

    PubMed

    Sánchez, Arancha; Roguev, Assen; Krogan, Nevan J; Russell, Paul

    2015-05-01

    Brc1, which was first identified as a high-copy, allele-specific suppressor of a mutation impairing the Smc5-Smc6 holocomplex in Schizosaccharomyces pombe, protects genome integrity during normal DNA replication and when cells are exposed to toxic compounds that stall or collapse replication forks. The C-terminal tandem BRCT (BRCA1 C-terminus) domain of fission yeast Brc1 docks with phosphorylated histone H2A (γH2A)-marked chromatin formed by ATR/Rad3 checkpoint kinase at arrested and damaged replication forks; however, how Brc1 functions in relation to other genome protection modules remains unclear. Here, an epistatic mini-array profile reveals critical requirements for Brc1 in mutants that are defective in multiple DNA damage response pathways, including checkpoint signaling by Rad3-Rad26/ATR-ATRIP kinase, DNA repair by Smc5-Smc6 holocomplex, replication fork stabilization by Mrc1/claspin and Swi1-Swi3/Timeless-Tipin, and control of ubiquitin-regulated proteolysis by the COP9 signalosome (CSN). Exogenous genotoxins enhance these negative genetic interactions. Rad52 and RPA foci are increased in CSN-defective cells, and loss of γH2A increases genotoxin sensitivity, indicating a critical role for the γH2A-Brc1 module in stabilizing replication forks in CSN-defective cells. A negative genetic interaction with the Nse6 subunit of Smc5-Smc6 holocomplex indicates that the DNA repair functions of Brc1 and Smc5-Smc6 holocomplex are at least partially independent. Rtt107, the Brc1 homolog in Saccharomyces cerevisiae, has a very different pattern of genetic interactions, indicating evolutionary divergence of functions and DNA damage responses. PMID:25795664

  4. Growth and carbon isotopes of Mediterranean trees reveal contrasting responses to increased carbon dioxide and drought.

    PubMed

    Granda, Elena; Rossatto, Davi Rodrigo; Camarero, J Julio; Voltas, Jordi; Valladares, Fernando

    2014-01-01

    Forest dynamics will depend upon the physiological performance of individual tree species under more stressful conditions caused by climate change. In order to compare the idiosyncratic responses of Mediterranean tree species (Quercus faginea, Pinus nigra, Juniperus thurifera) coexisting in forests of central Spain, we evaluated the temporal changes in secondary growth (basal area increment; BAI) and intrinsic water-use efficiency (iWUE) during the last four decades, determined how coexisting species are responding to increases in atmospheric CO2 concentrations (C(a)) and drought stress, and assessed the relationship among iWUE and growth during climatically contrasting years. All species increased their iWUE (ca. +15 to +21%) between the 1970s and the 2000s. This increase was positively related to C(a) for J. thurifera and to higher C(a) and drought for Q. faginea and P. nigra. During climatically favourable years the study species either increased or maintained their growth at rising iWUE, suggesting a higher CO2 uptake. However, during unfavourable climatic years Q. faginea and especially P. nigra showed sharp declines in growth at enhanced iWUE, likely caused by a reduced stomatal conductance to save water under stressful dry conditions. In contrast, J. thurifera showed enhanced growth also during unfavourable years at increased iWUE, denoting a beneficial effect of C(a) even under climatically harsh conditions. Our results reveal significant inter-specific differences in growth driven by alternative physiological responses to increasing drought stress. Thus, forest composition in the Mediterranean region might be altered due to contrasting capacities of coexisting tree species to withstand increasingly stressful conditions. PMID:23928889

  5. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples

    USGS Publications Warehouse

    Gorelick, Daniel A.; Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EED) are exogenous chemicals that mimic endogenous hormones, such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ER) in the larval heart compared to the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit similar tissue-specific effects as BPA and genistein or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue-specificity in ER activation is due to differences in the expression of estrogen receptor subtypes. ERα is expressed in developing heart valves but not in the liver, whereas ERβ2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  6. Gene response profiles for Daphnia pulex exposed to the environmental stressor cadmium reveals novel crustacean metallothioneins

    PubMed Central

    Shaw, Joseph R; Colbourne, John K; Davey, Jennifer C; Glaholt, Stephen P; Hampton, Thomas H; Chen, Celia Y; Folt, Carol L; Hamilton, Joshua W

    2007-01-01

    Background Genomic research tools such as microarrays are proving to be important resources to study the complex regulation of genes that respond to environmental perturbations. A first generation cDNA microarray was developed for the environmental indicator species Daphnia pulex, to identify genes whose regulation is modulated following exposure to the metal stressor cadmium. Our experiments revealed interesting changes in gene transcription that suggest their biological roles and their potentially toxicological features in responding to this important environmental contaminant. Results Our microarray identified genes reported in the literature to be regulated in response to cadmium exposure, suggested functional attributes for genes that share no sequence similarity to proteins in the public databases, and pointed to genes that are likely members of expanded gene families in the Daphnia genome. Genes identified on the microarray also were associated with cadmium induced phenotypes and population-level outcomes that we experimentally determined. A subset of genes regulated in response to cadmium exposure was independently validated using quantitative-realtime (Q-RT)-PCR. These microarray studies led to the discovery of three genes coding for the metal detoxication protein metallothionein (MT). The gene structures and predicted translated sequences of D. pulex MTs clearly place them in this gene family. Yet, they share little homology with previously characterized MTs. Conclusion The genomic information obtained from this study represents an important first step in characterizing microarray patterns that may be diagnostic to specific environmental contaminants and give insights into their toxicological mechanisms, while also providing a practical tool for evolutionary, ecological, and toxicological functional gene discovery studies. Advances in Daphnia genomics will enable the further development of this species as a model organism for the environmental sciences. PMID:18154678

  7. Barcoded Pyrosequencing Reveals That Consumption of Galactooligosaccharides Results in a Highly Specific Bifidogenic Response in Humans

    PubMed Central

    Davis, Lauren M. G.; Martínez, Inés; Walter, Jens; Goin, Caitlin; Hutkins, Robert W.

    2011-01-01

    Prebiotics are selectively fermented ingredients that allow specific changes in the gastrointestinal microbiota that confer health benefits to the host. However, the effects of prebiotics on the human gut microbiota are incomplete as most studies have relied on methods that fail to cover the breadth of the bacterial community. The goal of this research was to use high throughput multiplex community sequencing of 16S rDNA tags to gain a community wide perspective of the impact of prebiotic galactooligosaccharide (GOS) on the fecal microbiota of healthy human subjects. Fecal samples from eighteen healthy adults were previously obtained during a feeding trial in which each subject consumed a GOS-containing product for twelve weeks, with four increasing dosages (0, 2.5, 5, and 10 gram) of GOS. Multiplex sequencing of the 16S rDNA tags revealed that GOS induced significant compositional alterations in the fecal microbiota, principally by increasing the abundance of organisms within the Actinobacteria. Specifically, several distinct lineages of Bifidobacterium were enriched. Consumption of GOS led to five- to ten-fold increases in bifidobacteria in half of the subjects. Increases in Firmicutes were also observed, however, these changes were detectable in only a few individuals. The enrichment of bifidobacteria was generally at the expense of one group of bacteria, the Bacteroides. The responses to GOS and the magnitude of the response varied between individuals, were reversible, and were in accordance with dosage. The bifidobacteria were the only bacteria that were consistently and significantly enriched by GOS, although this substrate supported the growth of diverse colonic bacteria in mono-culture experiments. These results suggest that GOS can be used to enrich bifidobacteria in the human gastrointestinal tract with remarkable specificity, and that the bifidogenic properties of GOS that occur in vivo are caused by selective fermentation as well as by competitive interactions within the intestinal environment. PMID:21966454

  8. Kidney tissue proteomics reveals regucalcin downregulation in response to diabetic nephropathy with reflection in urinary exosomes.

    PubMed

    Zubiri, Irene; Posada-Ayala, Maria; Benito-Martin, Alberto; Maroto, Aroa S; Martin-Lorenzo, Marta; Cannata-Ortiz, Pablo; de la Cuesta, Fernando; Gonzalez-Calero, Laura; Barderas, Maria G; Fernandez-Fernandez, Beatriz; Ortiz, Alberto; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-11-01

    Diabetic nephropathy (DN) is a major complication of diabetes mellitus and the most frequent cause of end-stage renal disease. DN progresses silently and without clinical symptoms at early stages. Current noninvasive available markers as albuminuria account with severe limitations (late response, unpredictable prognosis, and limited sensitivity). Thus, it urges the discovery of novel markers to help in diagnosis and outcome prediction. Tissue proteomics allows zooming-in where pathophysiological changes are taking place. We performed a differential analysis of renal tissue proteome in a rat model of early DN by 2-dimensional differential gel electrophoresis and mass spectrometry. Confirmation was performed by Western blot, immunohistochemistry (IHC), and selected reaction monitoring (SRM). Rat urine samples were collected and exosomes were isolated from urine to evaluate if these microvesicles reflect changes directly occurring at tissue level. The protein showing maximum altered expression in rat tissue in response to DN was further analyzed in human kidney tissue and urinary exosomes. Regucalcin protein or senescence marker protein-30 (SMP30) (Swiss-Prot Q03336) was found to be strongly downregulated in DN kidney tissue compared with healthy controls. The same trend was observed in exosomes isolated from urine of control and DN rats. These data were further confirmed in a pilot study with human samples. IHC revealed a significant decrease of regucalcin in human kidney disease tissue vs control kidney tissue, and regucalcin was detected in exosomes isolated from healthy donors' urine but not from kidney disease patients. In conclusion, regucalcin protein expression is reduced in DN kidney tissue and this significant change is reflected in exosomes isolated from urine. Urinary exosomal regucalcin represents a novel tool, which should be explored for early diagnosis and progression monitoring of diabetic kidney disease. PMID:26072307

  9. Transcriptomics Reveal Several Gene Expression Patterns in the Piezophile Desulfovibrio hydrothermalis in Response to Hydrostatic Pressure

    PubMed Central

    Amrani, Amira; Bergon, Aurlie; Holota, Hlne; Tamburini, Christian; Garel, Marc; Ollivier, Bernard; Imbert, Jean; Dolla, Alain; Pradel, Nathalie

    2014-01-01

    RNA-seq was used to study the response of Desulfovibrio hydrothermalis, isolated from a deep-sea hydrothermal chimney on the East-Pacific Rise at a depth of 2,600 m, to various hydrostatic pressure growth conditions. The transcriptomic datasets obtained after growth at 26, 10 and 0.1 MPa identified only 65 differentially expressed genes that were distributed among four main categories: aromatic amino acid and glutamate metabolisms, energy metabolism, signal transduction, and unknown function. The gene expression patterns suggest that D. hydrothermalis uses at least three different adaptation mechanisms, according to a hydrostatic pressure threshold (HPt) that was estimated to be above 10 MPa. Both glutamate and energy metabolism were found to play crucial roles in these mechanisms. Quantitation of the glutamate levels in cells revealed its accumulation at high hydrostatic pressure, suggesting its role as a piezolyte. ATP measurements showed that the energy metabolism of this bacterium is optimized for deep-sea life conditions. This study provides new insights into the molecular mechanisms linked to hydrostatic pressure adaptation in sulfate-reducing bacteria. PMID:25215865

  10. Time-series analysis reveals genetic responses to intensive management of razorback sucker (Xyrauchen texanus)

    PubMed Central

    Dowling, Thomas E; Turner, Thomas F; Carson, Evan W; Saltzgiver, Melody J; Adams, Deborah; Kesner, Brian; Marsh, Paul C

    2014-01-01

    Time-series analysis is used widely in ecology to study complex phenomena and may have considerable potential to clarify relationships of genetic and demographic processes in natural and exploited populations. We explored the utility of this approach to evaluate population responses to management in razorback sucker, a long-lived and fecund, but declining freshwater fish species. A core population in Lake Mohave (Arizona-Nevada, USA) has experienced no natural recruitment for decades and is maintained by harvesting naturally produced larvae from the lake, rearing them in protective custody, and repatriating them at sizes less vulnerable to predation. Analyses of mtDNA and 15 microsatellites characterized for sequential larval cohorts collected over a 15-year time series revealed no changes in geographic structuring but indicated significant increase in mtDNA diversity for the entire population over time. Likewise, ratios of annual effective breeders to annual census size (Nb/Na) increased significantly despite sevenfold reduction of Na. These results indicated that conservation actions diminished near-term extinction risk due to genetic factors and should now focus on increasing numbers of fish in Lake Mohave to ameliorate longer-term risks. More generally, time-series analysis permitted robust testing of trends in genetic diversity, despite low precision of some metrics. PMID:24665337

  11. Infectious diseases of marine molluscs and host responses as revealed by genomic tools.

    PubMed

    Guo, Ximing; Ford, Susan E

    2016-03-01

    More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large-scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance. PMID:26880838

  12. Brain responses in humans reveal ideal observer-like sensitivity to complex acoustic patterns.

    PubMed

    Barascud, Nicolas; Pearce, Marcus T; Griffiths, Timothy D; Friston, Karl J; Chait, Maria

    2016-02-01

    We use behavioral methods, magnetoencephalography, and functional MRI to investigate how human listeners discover temporal patterns and statistical regularities in complex sound sequences. Sensitivity to patterns is fundamental to sensory processing, in particular in the auditory system, because most auditory signals only have meaning as successions over time. Previous evidence suggests that the brain is tuned to the statistics of sensory stimulation. However, the process through which this arises has been elusive. We demonstrate that listeners are remarkably sensitive to the emergence of complex patterns within rapidly evolving sound sequences, performing on par with an ideal observer model. Brain responses reveal online processes of evidence accumulation-dynamic changes in tonic activity precisely correlate with the expected precision or predictability of ongoing auditory input-both in terms of deterministic (first-order) structure and the entropy of random sequences. Source analysis demonstrates an interaction between primary auditory cortex, hippocampus, and inferior frontal gyrus in the process of discovering the regularity within the ongoing sound sequence. The results are consistent with precision based predictive coding accounts of perceptual inference and provide compelling neurophysiological evidence of the brain's capacity to encode high-order temporal structure in sensory signals. PMID:26787854

  13. The similarity structure of distributed neural responses reveals the multiple representations of letters.

    PubMed

    Rothlein, David; Rapp, Brenda

    2014-04-01

    Most cognitive theories of reading and spelling posit modality-specific representations of letter shapes, spoken letter names, and motor plans as well as abstract, amodal letter representations that serve to unify the various modality-specific formats. However, fundamental questions remain regarding the very existence of abstract letter representations, the neuro-topography of the different types of letter representations, and the degree of cortical selectivity for orthographic information. We directly test quantitative models of the similarity/dissimilarity structure of distributed neural representations of letters using Multivariate Pattern Analysis-Representational Similarity Analysis (MVPA-RSA) searchlight methods to analyze the BOLD response recorded from single letter viewing. These analyses reveal a left hemisphere ventral temporal region selectively tuned to abstract letter representations as well as substrates tuned to modality-specific (visual, phonological and motoric) representations of letters. The approaches applied in this research address various shortcomings of previous studies that have investigated these questions and, therefore, the findings we report serve to advance our understanding of the nature and format of the representations that occur within the various sub-regions of the large-scale networks used in reading and spelling. PMID:24321558

  14. Revealing the neural response to imperceptible peripheral flicker with machine learning.

    PubMed

    Porbadnigk, Anne K; Scholler, Simon; Blankertz, Benjamin; Ritz, Arnd; Born, Matthias; Scholl, Robert; Muller, Klaus-Robert; Curio, Gabriel; Treder, Matthias S

    2011-01-01

    Lighting in modern-day devices is often discrete. The sharp onsets and offsets of light are known to induce a steady-state visually evoked potential (SSVEP) in the electroencephalogram (EEG) at low frequencies. However, it is not well-known how the brain processes visual flicker at the threshold of conscious perception and beyond. To shed more light on this, we ran an EEG study in which we asked participants (N=6) to discriminate on a behavioral level between visual stimuli in which they perceived flicker and those that they perceived as constant wave light. We found that high frequency flicker which is not perceived consciously anymore still elicits a neural response in the corresponding frequency band of EEG, con-tralateral to the stimulated hemifield. The main contribution of this paper is to show the benefit of machine learning techniques for investigating this effect of subconscious processing: Common Spatial Pattern (CSP) filtering in combination with classification based on Linear Discriminant Analysis (LDA) could be used to reveal the effect for additional participants and stimuli, with high statistical significance. We conclude that machine learning techniques are a valuable extension of conventional neurophysiological analysis that can substantially boost the sensitivity to subconscious effects, such as the processing of imperceptible flicker. PMID:22255141

  15. Genetic structure along an elevational gradient in Hawaiian honeycreepers reveals contrasting evolutionary responses to avian malaria

    PubMed Central

    2008-01-01

    Background The Hawaiian honeycreepers (Drepanidinae) are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens), the apapane (Himatione sanguinea), and the iiwi (Vestiaria coccinea) were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent. PMID:19014596

  16. Plasminogen activator urokinase expression reveals TRAIL responsiveness and supports fractional survival of cancer cells

    PubMed Central

    Pavet, V; Shlyakhtina, Y; He, T; Ceschin, D G; Kohonen, P; Perälä, M; Kallioniemi, O; Gronemeyer, H

    2014-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10/Apo2L) holds promise for cancer therapy as it induces apoptosis in a large variety of cancer cells while exerting negligible toxicity in normal ones. However, TRAIL can also induce proliferative and migratory signaling in cancer cells resistant to apoptosis induced by this cytokine. In that regard, the molecular mechanisms underlying the tumor selectivity of TRAIL and those balancing apoptosis versus survival remain largely elusive. We show here that high mRNA levels of PLAU, which encodes urokinase plasminogen activator (uPA), are characteristic of cancer cells with functional TRAIL signaling. Notably, decreasing uPA levels sensitized cancer cells to TRAIL, leading to markedly increased apoptosis. Mechanistic analyses revealed three molecular events taking place in uPA-depleted cells: reduced basal ERK1/2 prosurvival signaling, decreased preligand decoy receptor 2 (DcR2)-death receptor 5 (DR5) interaction and attenuated recruitment of DcR2 to the death-inducing signaling complex upon TRAIL challenge. These phenomena were accompanied by increased FADD and procaspase-8 recruitment and processing, thus guiding cells toward a caspase-dependent cell death that is largely independent of the intrinsic apoptosis pathway. Collectively, our results unveil PLAU mRNA levels as marker for the identification of TRAIL-responsive tumor cells and highlight a key role of uPA signaling in ‘apoptosis versus survival' decision-making processes upon TRAIL challenge. PMID:24481457

  17. Retrospective stable isotope analysis reveals ecosystem responses to river regulation over the last century.

    PubMed

    Turner, Thomas F; Krabbenhoft, Trevor I; Collyer, Michael L; Krabbenhoft, Corey A; Edwards, Melanie S; Sharp, Zachary D

    2015-12-01

    Disruption of natural flow regimes, nutrient pollution, and other consequences of human population growth and development have impacted most major rivers of the world. Alarming losses of aquatic biodiversity coincide with human-caused river alteration, but effects of biotic homogenization on aquatic ecosystem processes are not as well documented. This is because unaltered systems for comparison are scarce, and some ecosystem-wide effects may take decades to manifest. We evaluated aquatic ecosystem responses to extensive river- floodplain engineering and nutrient addition in the Rio Grande of southwestern North America as revealed by changes in trophic structure of, and resource availability to, the fish community. Stable Isotope Analysis (SIA) was conducted on museum-preserved fishes collected over a 70-year period of intensive river management and exponential human population growth. Trophic complexity and resource heterogeneity for fish consumers (measured as "isotopic niche breadth") decreased following sediment deprivation and channelization, and these effects persist into the present. Increased nutrient inputs led to ?15N enrichment in the entire fish community at all affected sites, and a shift to autochthonous sources of carbon at the most proximal site downstream of wastewater release, probably via bottom-up transfer. Overall, retrospective SIA of apex consumers suggests radical change and functional impairment of a floodplain river ecosystem already marked by significant biodiversity loss. PMID:26909427

  18. Genetic structure along an elevational gradient in Hawaiian honeycreepers reveals contrasting evolutionary responses to avian malaria

    USGS Publications Warehouse

    Eggert, L.S.; Terwilliger, L.A.; Woodworth, B.L.; Hart, P.J.; Palmer, D.; Fleischer, R.C.

    2008-01-01

    Background. The Hawaiian honeycreepers (Drepanidinae) are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens), the apapane (Himatione sanguinea), and the iiwi (Vestiaria coccinea) were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results. Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion. Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent. ?? 2008 Eggert et al; licensee BioMed Central Ltd.

  19. Responses of a bursting pacemaker to excitation reveal spatial segregation between bursting and spiking mechanisms

    PubMed Central

    Maran, Selva K; Sieling, Fred H; Demla, Kavita; Prinz, Astrid A; Canavier, Carmen C

    2011-01-01

    Central pattern generators (CPGs) frequently include bursting neurons that serve as pacemakers for rhythm generation. Phase resetting curves (PRCs) can provide insight into mechanisms underlying phase locking in such circuits. PRCs were constructed for a pacemaker bursting complex in the pyloric circuit in the stomatogastric ganglion of the lobster and crab. This complex is comprised of the Anterior Burster (AB) neuron and two Pyloric Dilator (PD) neurons that are all electrically coupled. Artificial excitatory synaptic conductance pulses of different strengths and durations were injected into one of the AB or PD somata using the Dynamic Clamp. Previously, we characterized the inhibitory PRCs by assuming a single slow process that enabled synaptic inputs to trigger switches between an up state in which spiking occurs and a down state in which it does not. Excitation produced five different PRC shapes, which could not be explained with such a simple model. A separate dendritic compartment was required to separate the mechanism that generates the up and down phases of the bursting envelope (1) from synaptic inputs applied at the soma, (2) from axonal spike generation and (3) from a slow process with a slower time scale than burst generation. This study reveals that due to the nonlinear properties and compartmentalization of ionic channels, the response to excitation is more complex than inhibition. PMID:21360137

  20. The similarity structure of distributed neural responses reveals the multiple representations of letters

    PubMed Central

    Rothlein, David; Rapp, Brenda

    2014-01-01

    Most cognitive theories of reading and spelling posit modality-specific representations of letter shapes, spoken letter names, and motor plans as well as abstract, amodal letter representations that serve to unify the various modality-specific formats. However, fundamental questions remain regarding the very existence of abstract letter representations, the neuro-topography of the different types of letter representations, and the degree of cortical selectivity for orthographic information. We directly test quantitative models of the similarity/dissimilarity structure of distributed neural representations of letters using Multivariate Pattern Analysis-Representational Similarity Analysis (MVPA-RSA) searchlight methods to analyze the BOLD response recorded from single letter viewing. These analyses reveal a left hemisphere ventral temporal region selectively tuned to abstract letter representations as well as substrates tuned to modality-specific (visual, phonological and motoric) representations of letters. The approaches applied in this research address various shortcoming of previous studies that have investigated these questions and, therefore, the findings we report serve to advance our understanding of the nature and format of the representations that occur within the various sub- regions of the large-scale networks used in reading and spelling. PMID:24321558

  1. Hypersensitivity to Ticks and Lyme Disease Risk

    PubMed Central

    Burke, Georgine; Wikel, Stephen K.; Spielman, Andrew; Telford, Sam R.; McKay, Kathleen

    2005-01-01

    Although residents of Lyme diseaseendemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%31%) reported >1 tick bites, and 17% (95% CI 13%21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.940.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease. PMID:15705320

  2. [Hypersensitivity pneumonitis caused by a home humidifier].

    PubMed

    Hagiwara, S; Ishii, Y; Sugiyama, Y; Kitamura, S

    1995-09-01

    A 33-year-old man was admitted complaining of a fever, dyspnea, and a dry cough almost every night since December of 1992. He had been using an ultrasonic humidifier at home. The chest CT scan and roentgenogram showed bilateral reticulonodular shadows. After admission, the symptoms resolved spontaneously. These findings were suggestive of hypersensitivity pneumonitis. After analysis of fluid obtained by bronchoalveolar lavage and of a specimen obtained by transbronchial biopsy, "humidifier lung" was diagnosed. Ten species of microorganisms were isolated from the water left in the patient's humidifier. On precipitation and complement fixation tests of the patients serum, the results were positive for three of those microorganisms: Flavobacterium multivorum, Yersinia pseudotuberculosis, and Aureobacterium liquefaciens. The titer on the complement fixation test increased immediately after a provocation test. The laboratory results suggest that at least one of these three microorganisms was the causative antigen in this case. PMID:8538084

  3. Revealing a latent variable: individual differences in affective response to repeated injections.

    PubMed

    Aydin, Cigdem; Frohmader, Karla; Akil, Huda

    2015-10-01

    [Correction Notice: An Erratum for this article was reported in Vol 129(5) of Behavioral Neuroscience (see record 2015-43762-001). In the article, there was an error in the abstract. The sentence "However, injections significantly increased time spent immobile in the forced swim test in LRs, while the identical regimen significantly decreased the same measure in HRs, compared with handled-controls." should be "However, injections significantly increased time spent immobile in the forced swim test in HRs, while the identical regimen significantly decreased the same measure in LRs, compared with handled-controls."] Latent variables may exist in experimental designs and may interfere with reproducibility of findings. The present study reveals 1 such variable, the individual differences in affective response to chronic injection stress, by using the novelty-seeking phenotype as a model of differential emotional reactivity. The phenotype is identified by exposing a population of experimentally nave outbred rats to the mild stress of a novel environment and classifying them as high responders (HR; upper 1/3) and low responders (LR; lower 1/3) based on their locomotor reactivity. Research has shown that HR/LR animals differ in their basal levels of anxiety- and depressive-like behavior, as well as in their response to environmental and pharmacological challenges; suggesting validity of this model in studying individual differences in stress reactivity. The present data showed that 14 daily, intraperitoneal saline injections did not alter the phenotypic differences in social behavior observed basally in HR/LR rats. However, injections significantly increased time spent immobile in the forced swim test in HRs, [corrected] while the identical regimen significantly decreased the same measure in LRs, [corrected] compared with handled-controls. These data indicate that individual differences in stress reactivity can have a significant impact on the depressive-like responses to repeated intraperitoneal injections in rats. Given that such underlying emotional variability exists within standard, outbred rat populations, this study highlights the importance of accounting for such variability in any study investigating the effects of repeated drug administration on depressive-like behavior for reliability and replicability of findings. Thus, we recommend including an uninjected control group in all studies. PMID:26191946

  4. Transcriptome Analysis of Cotton (Gossypium hirsutum L.) Genotypes That Are Susceptible, Resistant, and Hypersensitive to Reniform Nematode (Rotylenchulus reniformis)

    PubMed Central

    Li, Ruijuan; Rashotte, Aaron M.; Singh, Narendra K.; Lawrence, Kathy S.; Weaver, David B.; Locy, Robert D.

    2015-01-01

    Reniform nematode is a semi-endoparasitic nematode species causing significant yield loss in numerous crops, including cotton (Gossypium hirsutum L.). An RNA-sequencing analysis was conducted to measure transcript abundance in reniform nematode susceptible (DP90 & SG747), resistant (BARBREN-713), and hypersensitive (LONREN-1) genotypes of cotton (Gossypium hirsutum L.) with and without reniform nematode infestation. Over 90 million trimmed high quality reads were assembled into 84,711 and 80, 353 transcripts using the G. arboreum and the G. raimondii genomes as references. Many transcripts were significantly differentially expressed between the three different genotypes both prior to and during nematode pathogenesis, including transcripts corresponding to the gene ontology categories of cell wall, hormone metabolism and signaling, redox reactions, secondary metabolism, transcriptional regulation, stress responses, and signaling. Further analysis revealed that a number of these differentially expressed transcripts mapped to the G. raimondii and/or the G. arboreum genomes within 1 megabase of quantitative trait loci that had previously been linked to reniform nematode resistance. Several resistance genes encoding proteins known to be strongly linked to pathogen perception and resistance, including LRR-like and NBS-LRR domain-containing proteins, were among the differentially expressed transcripts mapping near these quantitative trait loci. Further investigation is required to confirm a role for these transcripts in reniform nematode susceptibility, hypersensitivity, and/or resistance. This study presents the first systemic investigation of reniform nematode resistance-associated genes using different genotypes of cotton. The candidate reniform nematode resistance-associated genes identified in this study can serve as the basis for further functional analysis and aid in further development of reniform a nematode resistant cotton germplasm. PMID:26571375

  5. Prediction of drug-induced immediate hypersensitivity in guinea pigs.

    PubMed

    Chazal, I; Verdier, F; Virat, M; Descotes, J

    1994-10-01

    This study was undertaken to evaluate an assay to assess the risk for drug-induced immediate hypersensitivity reactions. Groups of five to 10 guinea-pigs were given six ip injections of the test compound on days 1, 3, 5, 8, 10 and 12. Aluminium hydroxide was also given in the first injection. At day 33, the animals were given an iv injection of the test compound and the response was recorded by grading the severity of clinical symptoms. Cutaneous passive anaphylaxis was also evaluated in six naive guinea pigs using Evans blue and sera collected from treated animals on day 26. A panel of six positive model compounds (ovalbumin, aprotinin, chymopapain, tetracosactide, cyanocobalamin and procaine), and the negative compound Ribomunyl were tested. Positive systemic and/or cutaneous anaphylactic responses were observed with ovalbumin, aprotinin, chymopapain and tetracosactide whereas no responses were noted with cyanocobalamin, procaine and Ribomunyl. Our results suggest that this protocol can help differentiate positive model compounds (known to induce reactions in man) from negative model compounds, provided that their molecular weight is large enough, but that it is not applicable to substances of low molecular weight. PMID:20693069

  6. Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent.

    PubMed

    Bhan, Urvashi; Newstead, Michael J; Zeng, Xianying; Ballinger, Megan N; Standiford, Louis R; Standiford, Theodore J

    2011-12-01

    Hypersensitivity pneumonitis (HP), an inflammatory lung disease, develops after repeated exposure to inhaled particulate antigen and is characterized by a vigorous T helper type 1-mediated immune response, resulting in the release of IL-12 and interferon (IFN)-?. These T helper type 1 cytokines may participate in the pathogenesis of HP. Stachybotrys chartarum (SC) is a dimorphic fungus implicated in a number of respiratory illnesses, including HP. Here, we have developed a murine model of SC-induced HP that reproduces pathology observed in human HP and hypothesized that toll receptor-like 9 (TLR9)-mediated dendritic cell responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice sensitized and challenged with 10(6) SC spores develop granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of neutrophils and CD4(+) and CD8(+) T cells. SC sensitization and challenge resulted in robust pulmonary expression of tumor necrosis factor-?, IL-12, and IFN-?. SC-mediated granulomatous inflammation required IFN-? and was TLR9 dependent, because TLR9(-/-) mice displayed reduced peribronchial inflammation, decreased accumulation and/or activation of polymorphonuclear (PMN) and CD4(+) and CD8(+) T cells, and reduced lung expression of type 1 cytokines and chemokines. T-cell production of IFN-? was IL-12 dependent. Our studies suggest that TLR9 is critical for dendritic cell-mediated development of a type 1 granulomatous inflammation in the lung in response to SC. PMID:21982832

  7. Hypersensitivity to sound--questionnaire data, audiometry and classification.

    PubMed

    Anari, M; Axelsson, A; Eliasson, A; Magnusson, L

    1999-01-01

    This study included consecutive case histories and audiometry of 100 patients with hypersensitivity to sounds. There are several different conditions with the symptom of hypersensitivity to sounds. Hyperacusis is one of those and is seldom described in the literature. The term hyperacusis is often used synonymously with hypersensitivity to sound. We propose that there is a specific condition that could be termed hyperacusis. Hyperacusis is often elicited by loud sounds or by a number of other traumata or diseases. It is not typical of occupational noise exposure (with the exception of exposure to music). The typical patient is relatively young, the mean age being approximately 10 years less than for a population of patients with tinnitus or noise-induced hearing loss. In addition to hypersensitivity to sound, the patients often suffer from tinnitus (86%). Sounds are frequently painful and exposure to loud sounds worsens the condition for some time. The patients often have headaches. Pure tone audiograms show normal hearing or a slight high tone loss. The uncomfortable loudness level is markedly decreased, mostly less than 90 dB HL. Patients with hyperacusis may also be divided into those hypersensitive to the loudness of sounds with a decreased pure tone uncomfortable loudness level and those hypersensitive to certain specific sounds irrespective of loudness showing relatively high pure tone uncomfortable loudness levels and decreased uncomfortable loudness levels to specific sounds. With a careful history other conditions with the symptom of hypersensitivity to sound can be excluded. PMID:10572967

  8. Genome-wide association reveals the locus responsible for four-horned ruminant.

    PubMed

    Kijas, James W; Hadfield, Tracy; Naval Sanchez, Marina; Cockett, Noelle

    2016-04-01

    Phenotypic variability in horn characteristics, such as their size, number and shape, offers the opportunity to elucidate the molecular basis of horn development. The objective of this study was to map the genetic determinant controlling the production of four horns in two breeds, Jacob sheep and Navajo-Churro, and examine whether an eyelid abnormality occurring in the same populations is related. Genome-wide association mapping was performed using 125 animals from the two breeds that contain two- and four-horned individuals. A case-control design analysis of 570 712 SNPs genotyped with the ovine HD SNP Beadchip revealed a strong association signal on sheep chromosome 2. The 10 most strongly associated SNPs were all located in a region spanning Mb positions 131.9-132.6, indicating the genetic architecture underpinning the production of four horns is likely to involve a single gene. The closest genes to the most strongly associated marker (OAR2_132568092) were MTX2 and the HOXD cluster, located approximately 93 Kb and 251 Kb upstream respectively. The occurrence of an eyelid malformation across both breeds was restricted to polled animals and those carrying more than two horns. This suggests the eyelid abnormality may be associated with departures from the normal developmental production of two-horned animals and that the two conditions are developmentally linked. This study demonstrated the presence of separate loci responsible for the polled and four-horned phenotypes in sheep and advanced our understanding of the complexity that underpins horn morphology in ruminants. PMID:26767438

  9. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw

    USGS Publications Warehouse

    MacKelprang, R.; Waldrop, M.P.; Deangelis, K.M.; David, M.M.; Chavarria, K.L.; Blazewicz, S.J.; Rubin, E.M.; Jansson, J.K.

    2011-01-01

    Permafrost contains an estimated 1672????????Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 ??C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  10. Comparison of Transcriptional Changes to Chloroplast and Mitochondrial Perturbations Reveals Common and Specific Responses in Arabidopsis

    PubMed Central

    Van Aken, Olivier; Whelan, James

    2012-01-01

    Throughout the life of a plant, the biogenesis and fine-tuning of energy organelles is essential both under normal growth and stress conditions. Communication from organelle to nucleus is essential to adapt gene regulation and protein synthesis specifically to the current needs of the plant. This organelle-to-nuclear communication is termed retrograde signaling and has been studied extensively over the last decades. In this study we have used large-scale gene expression data sets relating to perturbations of chloroplast and mitochondrial function to gain further insights into plant retrograde signaling and how mitochondrial and chloroplast retrograde pathways interact and differ. Twenty seven studies were included that assess transcript profiles in response to chemical inhibition as well as genetic mutations of organellar proteins. The results show a highly significant overlap between gene expression changes triggered by chloroplast and mitochondrial perturbations. These overlapping gene expression changes appear to be common with general abiotic, biotic, and nutrient stresses. However, retrograde signaling pathways are capable of distinguishing the source of the perturbation as indicated by a statistical overrepresentation of changes in genes encoding proteins of the affected organelle. Organelle-specific overrepresented functional categories among others relate to energy metabolism and protein synthesis. Our analysis also suggests that WRKY transcription factors play a coordinating role on the interface of both organellar signaling pathways. Global comparison of the expression profiles for each experiment revealed that the recently identified chloroplast retrograde pathway using phospho-adenosine phosphate is possibly more related to mitochondrial than chloroplast perturbations. Furthermore, new marker genes have been identified that respond specifically to mitochondrial and/or chloroplast dysfunction. PMID:23269925

  11. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw.

    PubMed

    Mackelprang, Rachel; Waldrop, Mark P; DeAngelis, Kristen M; David, Maude M; Chavarria, Krystle L; Blazewicz, Steven J; Rubin, Edward M; Jansson, Janet K

    2011-12-15

    Permafrost contains an estimated 1672 Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 °C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. PMID:22056985

  12. Azathioprine hypersensitivity presenting as septic shock with encephalopathy.

    PubMed

    James, Antonia; Blagojevic, Jelena; Benham, Stuart W; Cornall, Richard; Frater, John

    2013-01-01

    We present a case of azathioprine hypersensitivity presenting as septic shock with associated encephalopathy. The patient was presented with rapid onset of fever, hypotension, confusion and a rapidly declining conscious level. He was admitted to the intensive care unit where he received numerous invasive investigations and treatments with broad-spectrum antibiotics, antivirals and antifungals. All microbial cultures were negative. The patient-consistent with azathioprine hypersensitivity-made a spontaneous recovery after 7 days. The case shows that a time line of drug initiation is a key part of the medical history and consideration of azathioprine hypersensitivity could avoid unnecessary interventions and excessive antimicrobial use. PMID:23513015

  13. Azathioprine hypersensitivity presenting as septic shock with encephalopathy

    PubMed Central

    James, Antonia; Blagojevic, Jelena; Benham, Stuart W; Cornall, Richard; Frater, John

    2013-01-01

    We present a case of azathioprine hypersensitivity presenting as septic shock with associated encephalopathy. The patient was presented with rapid onset of fever, hypotension, confusion and a rapidly declining conscious level. He was admitted to the intensive care unit where he received numerous invasive investigations and treatments with broad-spectrum antibiotics, antivirals and antifungals. All microbial cultures were negative. The patientconsistent with azathioprine hypersensitivitymade a spontaneous recovery after 7?days. The case shows that a time line of drug initiation is a key part of the medical history and consideration of azathioprine hypersensitivity could avoid unnecessary interventions and excessive antimicrobial use. PMID:23513015

  14. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity

    PubMed Central

    Meulenbroeks, Chantal; van der Lugt, Jaco J.; van der Meide, Nathalie M. A.; Willemse, Ton; Rutten, Victor P. M. G.; Zaiss, Dietmar M. W.

    2015-01-01

    The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFN? mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFN?-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder. PMID:25901733

  15. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.

    PubMed

    Meulenbroeks, Chantal; van der Lugt, Jaco J; van der Meide, Nathalie M A; Willemse, Ton; Rutten, Victor P M G; Zaiss, Dietmar M W

    2015-01-01

    The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFN? mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFN?-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder. PMID:25901733

  16. Pseudomonas corrugata crpCDE is part of the cyclic lipopeptide corpeptin biosynthetic gene cluster and is involved in bacterial virulence in tomato and in hypersensitive response in Nicotiana benthamiana.

    PubMed

    Strano, Cinzia Patricia; Bella, Patrizia; Licciardello, Grazia; Fiore, Alberto; Lo Piero, Angela Roberta; Fogliano, Vincenzo; Venturi, Vittorio; Catara, Vittoria

    2015-06-01

    Pseudomonas corrugata?CFBP 5454 produces two kinds of cyclic lipopeptides (CLPs), cormycin A and corpeptins, both of which possess surfactant, antimicrobial and phytotoxic activities. In this study, we identified genes coding for a putative non-ribosomal peptide synthetase and an ABC-type transport system involved in corpeptin production. These genes belong to the same transcriptional unit, designated crpCDE. The genetic organization of this locus is highly similar to other Pseudomonas?CLP biosynthetic clusters. Matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis revealed that transporter and synthetase genomic knock-out mutants were unable to produce corpeptins, but continued to produce cormycin A. This suggests that CrpCDE is the only system involved in corpeptin production in P.?corrugata?CFBP 5454. In addition, phylogenetic analysis revealed that the CrpE ABC transporter clustered with the transporters of CLPs with a long peptide chain. Strains depleted in corpeptin production were significantly less virulent than the wild-type strain when inoculated in tomato plants and induced only chlorosis when infiltrated into Nicotiana benthamiana leaves. Thus, corpeptins are important effectors of P.?corrugata interaction with plants. Expression analysis revealed that crpC transcription occurs at high cell density. Two LuxR transcriptional regulators, PcoR and RfiA, have a pivotal role in crpC expression and thus in corpeptin production. PMID:25231335

  17. Probabilistic independent component analysis for laser speckle contrast images reveals in vivo multi - component vascular responses to forepaw stimulation.

    PubMed

    Li, Nan; Pelled, Galit; Thakor, Nitish V

    2010-01-01

    Brain's functional response can be studied by observing the spatiotemporal dynamics of functional and structural changes in cerebral vasculature. However, very few studies explore detailed changes at the level of individual microvessels while revealing the simultaneous wide field view of microcirculation responses to functional stimulation. Here we use a high spatiotemporal resolution laser speckle contrast imaging method, in combination with probabilistic independent component analysis to reveal the changes of cerebral blood flow pattern in response to electrical forepaw stimulation in an anesthetized rat model. The proposed method is able to pick up the response of a single vessel down to approximately 20 microm diameter in a 4mm 4mm field of view, and automatically extract response from multiple vascular components. Two main vascular components, arteriolar and capillary responses respectively, show significantly different temporal dynamics. Overall, the experimental results from five rats reveal that the specific arteriole branch proximal to the activation sites dilate prior consistently to the increase of blood flow in the capillaries with a latency time 0.91 0.05s. The presented results provide novel microscopic scale evidence of the contribution of different vascular compartments in the hemodynamic response to neuronal activation. PMID:21096788

  18. Studies of migration inhibition tests in penicillin hypersensitivity.

    PubMed Central

    Warrington, R J; Sauder, P J; Rutherford, W J

    1979-01-01

    The release of the migration inhibition factors, leucocyte inhibitory factor (LIF) and macrophage migration inhibition factor (MIF) from stimulated peripheral blood lymphocytes has been compared in patients with immediate (IgE-mediated) penicillin allergy and in patients with delayed hypersensitivity to tuberculin PPD. It has been shown that in these two groups of subjects, a comparable specific proliferative response can occur following stimulation with the appropriate drug (benzylpenicillin) or antigen (PPD). By cell fractionation studies, the proliferation was found to occur in the isolated T cell population in both subject groups. However, the lymphocyte response to benzylpenicillin was rarely associated with the release of LIF or MIF, in contrast to the situation in tuberculin sensitivity where a concomitant release of LIF and MIF was found. In about one third of penicillin allergic subjects, culture supernatants from specifically stimulated lymphocyte cultures induced migration inhibition in the indirect leucocyte migration test, but the inhibitory activity apparently resulted from the presence of penicillin-specific antibody and not from LIF. PMID:393437

  19. Cytip regulates dendritic-cell function in contact hypersensitivity.

    PubMed

    Heib, Valeska; Sparber, Florian; Tripp, Christoph H; Ortner, Daniela; Stoitzner, Patrizia; Heufler, Christine

    2012-03-01

    Cytohesin-interacting protein (Cytip) is induced during dendritic cell (DC) maturation and in T cells upon activation. It has also been shown to be involved in the regulation of immune responses. Here, we evaluated the functional consequences of Cytip deficiency in DCs using Cytip knockout (KO) mice. No difference in DC subpopulations in the skin draining lymph nodes (LNs) was found between Cytip KO mice and their wild-type counterparts, excluding a role in DC development. To investigate the function of Cytip in DCs in vivo, we used 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) as a model system. In the sensitization as well as in the elicitation phase, DCs derived from Cytip KO mice induced an increased inflammatory reaction indicated by more pronounced ear swelling. Furthermore, IL-12 production was increased in Cytip KO bone marrow-derived DCs (BMDCs) after CpG stimulation. Additionally, Cytip-deficient DCs loaded with ovalbumin induced stronger proliferation of antigen-specific CD4(+) and CD8(+) T cells in vitro. Finally, migration of skin DCs was not altered after TNCB application due to Cytip deficiency. Taken together, these data suggest a suppressive function for Cytip in mouse DCs in limiting immune responses. PMID:22488362

  20. Integrin ?E(CD103) Is Involved in Regulatory T-Cell Function in Allergic Contact Hypersensitivity.

    PubMed

    Braun, Andrea; Dewert, Nadin; Brunnert, Fiona; Schnabel, Viktor; Hardenberg, Jan-Hendrik; Richter, Beatrice; Zachmann, Karolin; Cording, Sascha; Claen, Anna; Brans, Richard; Hamann, Alf; Huehn, Jochen; Schn, Michael P

    2015-12-01

    Murine contact hypersensitivity (CHS) is a dendritic cell (DC)-dependent T-cell-mediated inflammation with CD8(+) T cells as effectors and CD4(+) T cells as regulators (Treg cells) that models human allergic contact dermatitis. The integrin ?E(CD103) is expressed by some T-cell and DC subsets and has been implicated in epithelial lymphocyte localization, but its role in immune regulation remains enigmatic. We have identified a function for CD103 in the development of cutaneous allergic immune responses. CHS responses, but not irritant contact dermatitis, were significantly augmented in CD103-deficient mice in hapten-challenged skin. Phenotype and function of skin DCs during sensitization were normal, whereas adoptive transfer experiments revealed that the elevated CHS response in CD103-deficient mice is transferred by primed T cells and is independent of resident cells in recipient mice. While T-cell counts were elevated in challenged skin of CD103-deficient mice, the FoxP3 expression level of CD4(+)CD25(+) Treg cells was significantly reduced, indicating impaired functionality. Indeed, Treg cells from CD103-deficient mice were not able to suppress CHS reactions during the elicitation phase. Further, CD103 on FoxP3(+) Treg cells was involved in Treg retention to inflamed skin. These findings indicate an unexpected dichotomous functional role for CD103 on Treg cells by modulating FoxP3 expression. PMID:26203637

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

    PubMed Central

    Ostrov, David A.; Grant, Barry J.; Pompeu, Yuri A.; Sidney, John; Harndahl, Mikkel; Southwood, Scott; Oseroff, Carla; Lu, Shun; Jakoncic, Jean; de Oliveira, Cesar Augusto F.; Yang, Lun; Mei, Hu; Shi, Leming; Shabanowitz, Jeffrey; English, A. Michelle; Wriston, Amanda; Lucas, Andrew; Phillips, Elizabeth; Mallal, Simon; Grey, Howard M.; Sette, Alessandro; Hunt, Donald F.; Buus, Soren; Peters, Bjoern

    2012-01-01

    Idiosyncratic adverse drug reactions are unpredictable, dose-independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association 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 molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function; however, the mechanism by which abacavir induces this pathologic T-cell response remains unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T 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. PMID:22645359

  2. Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity

    PubMed Central

    Asnaashari, Mohammad; Moeini, Masoumeh

    2013-01-01

    Dentin hypersensitivity (DH) is a relatively common painful condition among dental problems. Although many studies have been performed regarding the diagnosis and treatment of DH, dental practitioners are still confused about the definite diagnosis and treatment.The use of lasers as a treatment for dentin hypersensitivity was first introduced in 1985.Laser treatment in dentin hypersensitivity is an interesting and controversial issue and many investigations have been done on its mechanism of action, advantages, and unclear points.The present literature review tries to go over the definition, diagnosis, etiology , predisposing factors, various laser types in the treatment of DH alone or in combination with topical desensitizing agents. Since a certain treatment has not yet introduced for dentin hypersensitivity, a combination of laser therapy and topical desensitizing factors ,can increase the success of the treatment compared with either treatments alone. PMID:25606300

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

    PubMed

    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. PMID:22774324

  4. Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.

    PubMed

    Dickson, Scott D; Salazar, Kimberly C

    2013-08-01

    Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other ?-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the ?-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure. PMID:23546989

  5. IgE-mediated food hypersensitivity disorders.

    PubMed

    Gotua, M; Lomidze, N; Dolidze, N; Gotua, T

    2008-04-01

    Food allergy has become a serious health concern especially in developed countries in the past two decades. In general population approximately 4-6% of children and 1-3% of adults experience food allergy. The article reviews IgE-mediated food hypersensitivity disorders. Epidemiology, Mechanism, Clinical manifestations, Genetically modified crops (GMOs), Diagnosis, Prevention and Treatment of IgE-mediated food allergies are discussed. The investigations show that over 90% of IgE-mediated food allergies in childhood are caused by: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish and shellfish. Also the causes of food allergy are food additives, genetically modified crops. Risk factors for food-dependent exercise-induced anaphylaxis include asthma and previous allergic reactions to the causative food. Food allergy is one of the most common causes of systematic anaphylaxis and anaphylactoid reactions, with an annual incidence of four cases per million populations and estimated 500 deaths annually. In addition to gastrointestinal symptoms, individuals may experience urticaria, angioedema, atopic dermatitis, oral syndrome, asthma, rhinitis, conjunctivitis, hypotension, shock and cardiac arrhythmias, caused by the massive release of mediators from mast cells and basophiles. Diagnosis of food allergy is based on history, detailed dietary analysis, skin testing, measuring specific IgE in blood serum and challenge tests. Treatment and prevention includes: avoidance diet, application of auto-injectable epinephrine, H1 and H2 antihistamines, corticosteroids, antileukotrienes, prostaglandin synthetase inhibitors, cromolyn sodium, etc. PMID:18487689

  6. Dentin hypersensitivity: Recent trends in management

    PubMed Central

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-01-01

    Dentinal hypersensitivity (DH) is a common clinical condition usually associated with exposed dentinal surfaces. It can affect patients of any age group and most commonly affects the canines and premolars of both the arches. This article concisely reviews the patho-physiology, mechanism and clinical management of the DH. Treatment of DH should start with an accurate diagnosis. Differential diagnosis should be made and all other probable causes should be excluded. An often neglected phase of clinical management of DH is the identification and treatment of the causative factors of DH. By removing the etiological factors, the condition can be even prevented from occurring or recurring. There are various treatment modalities available which can be used at home or may be professionally applied. The at home desensitizing agents include toothpastes, mouthwashes or chewing gums and they act by either occluding the dentinal tubules or blocking the neural transmission. This article also discusses the recent treatment options like bioglass, Portland cement, lasers and casein phosphopeptide. PMID:21217949

  7. Hypersensitivity pneumonitis: the dug-well lung.

    PubMed

    Sharma, Bharat Bhushan; Singh, Sheetu; Singh, Virendra

    2013-01-01

    Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is caused by a variety of environmental agents and may present as occult respiratory illness. HP represents a potentially curable subgroup of interstitial lung disease. This study was designed to examine a group of patients with HP due to a unique mechanism of environmental exposure. Five patients with HP were retrospectively identified, from our hospital records, admitted during the period of March 2007 to February 2011 with history of exposure to dug wells. The mode of exposure was specified as multiple entries into a dug well for different reasons. Other modes of exposure were considered as criteria of exclusion. All of the five patients had subacute HP based on available clinical, radiographic, immunologic, and supportive evidence and exposure. There were additional allergic bronchopulmonary aspergillosis-like features in one patient who did not have antecedent asthma. The evaluation of patient records indicated a fungal etiology. The air and soil from selected wells were tested for fungal organisms. Both settings grew Aspergillus as the predominant species. This novel mechanism of HP is labeled "dug-well lung" because the disease was attributed to exposure to dug wells. Lung disease may result from exposure to a dug well. Farmers or mechanics, climbing down these damp wells for a multitude of reasons, are prone to develop HP. The public health care personnel and farming community should be made aware of this potential occupation-related health hazard. PMID:24169053

  8. Descending modulation of neuropathic hypersensitivity by dopamine D2 receptors in or adjacent to the hypothalamic A11 cell group.

    PubMed

    Wei, Hong; Viisanen, Hanna; Pertovaara, Antti

    2009-05-01

    We determined the role of the dopamine D2 receptor in or adjacent to the dopaminergic A11 cell group in descending modulation of neuropathic hypersensitivity. Moreover, we determined the spinal neurotransmitter receptors mediating the modulatory effect. Neuropathy was produced by spinal nerve ligation in the rat that had a chronic cannula for drug delivery into A11 or a control site in the locus coeruleus, and a catheter for spinal drug delivery. Hypersensitivity was assessed by a withdrawal response to monofilaments. Quinpirole (a dopamine D2/D3 receptor agonist) in A11 attenuated hypersensitivity, without influencing thermal nociception in the uninjured tail. Quinpirole in the locus coeruleus failed to influence hypersensitivity. L-741,626 (a dopamine D2 receptor antagonist), raclopride (a dopamine D2/D3 receptor antagonist) and bicuculline (a GABA(A) receptor antagonist) in A11 reversed the antihypersensitivity effect of quinpirole. Raclopride or bicuculline alone in A11 had no effects, whereas muscimol (a GABA(A) receptor agonist) alone in A11 suppressed hypersensitivity. Spinal administration of atipamezole (an alpha(2)-adrenoceptor antagonist) or marginally also WAY-100635 (a 5-HT(1A) receptor antagonist), but not raclopride or bicuculline, reduced the antihypersensitivity effect induced by quinpirole in A11. Electrical stimulation of A11 produced thermal antinociception following intrathecal administration of saline but not raclopride. The results indicate that activation of the dopamine D2 receptor in A11 may selectively suppress neuropathic hypersensitivity, due to mechanisms that involve GABA(A) receptors in the hypothalamus and descending noradrenergic pathways acting on spinal alpha(2)-adrenoceptors, possibly together with a slight contribution of descending serotoninergic pathways acting on spinal 5-HT(1A) receptors. PMID:19416636

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

    PubMed Central

    Yoshida, Yoichiro; Hirata, Keiji; Matsuoka, Hiroshi; Iwamoto, Shigeyoshi; Kotaka, Masahito; Fujita, Hideto; Aisu, Naoya; Hoshino, Seiichiro; Kosaka, Takeo; Maeda, Kotaro; Kiyomi, Fumiaki; Yamashita, Yuichi

    2015-01-01

    Background Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions. Patients and methods The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of 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. PMID:26648694

  10. Rapid vs. delayed infrared responses after ischemia reveal recruitment of different vascular beds

    PubMed Central

    Chang, Ken; Yoon, Stephen; Sheth, Niral; Seidel, Miles; Antalek, Matthew; Ahad, James; Darlington, Thomas; Ikeda, Allison; Kato, Gregory J.; Ackerman, Hans; Gorbach, Alexander M.

    2015-01-01

    Continuous infrared imaging revealed transient changes in forearm temperature during arterial occlusion, reperfusion, and recovery in a healthy subject group. Processing the imaging data with the k-means algorithm further revealed reactive vascular sites in the skin with rapid or delayed temperature amplification. The observed temporal and spatial diversity of blood-flow-derived forearm temperature allow consideration of thermal-imaging guided placement of skin sensors to achieve enhanced sensitivity in monitoring of skin hemodynamics. PMID:26435756

  11. Systems Scale Interactive Exploration Reveals Quantitative and Qualitative Differences in Response to Influenza and Pneumococcal Vaccines

    PubMed Central

    Obermoser, Gerlinde; Presnell, Scott; Domico, Kelly; Xu, Hui; Wang, Yuanyuan; Anguiano, Esperanza; Thompson-Snipes, LuAnn; Ranganathan, Rajaram; Zeitner, Brad; Bjork, Anna; Anderson, David; Speake, Cate; Ruchaud, Emily; Skinner, Jason; Alsina, Laia; Sharma, Mamta; Dutartre, Helene; Cepika, Alma; Israelsson, Elisabeth; Nguyen, Phuong; Nguyen, Quynh-Anh; Harrod, A. Carson; Zurawski, Sandra M.; Pascual, Virginia; Ueno, Hideki; Nepom, Gerald T.; Quinn, Charlie; Blankenship, Derek; Palucka, Karolina; Banchereau, Jacques; Chaussabel, Damien

    2013-01-01

    SUMMARY Systems immunology approaches were employed to investigate innate and adaptive immune responses to influenza and pneumococcal vaccines. These two non-live vaccines show different magnitudes of transcriptional responses at different time points after vaccination. Software solutions were developed to explore correlates of vaccine efficacy measured as antibody titers at day 28. These enabled a further dissection of transcriptional responses. Thus, the innate response, measured within hours in the peripheral blood, was dominated by an interferon transcriptional signature after influenza vaccination and by an inflammation signature after pneumococcal vaccination. Day 7 plasmablast responses induced by both vaccines was more pronounced after pneumococcal vaccination. Together, these results suggest that comparing global immune responses elicited by different vaccines will be critical to our understanding of the immune mechanisms underpinning successful vaccination. PMID:23601689

  12. Receptor system response kinetics reveal functional subtypes of native murine and recombinant human GABAA receptors

    PubMed Central

    McClellan, Annette M L; Twyman, Roy E

    1999-01-01

    Regional distinctions in GABA type A (GABAA) miniature IPSC responses are thought to be determined by postsynaptic receptor composition. The kinetics of receptor activation and deactivation were studied using rapid exchange (100 ?s) of GABA at excised patches containing recombinant (?1?1?2 or ?2?1?2) and native (cortical) GABAA receptors.Receptors activated by brief (< 1 ms) pulses of GABA demonstrated a characteristic current response, hereby referred to as the receptor system response. System response properties included agonist concentration-dependent peak amplitudes and concentration-independent maximal rates of activation and deactivation. Receptor subtypes were characterized functionally and phenotyped using the system response characteristics.System responses obtained for ?1?1?2 receptors exhibited a single phenotype while ?2?1?2 receptors exhibited either a predominant slow deactivation (type I) or a relatively infrequent faster (type II) phenotype. Receptor system responses of ?2?1?2 receptors reached peak currents twice as fast as those of ?1?1?2 receptors (0.5 versus 1.0 ms) but decayed 2 or 6 times more slowly (?long of ?190 and 62 ms for type I and II ?2?1?2, and ?34 ms for ?1?1?2 receptors).Receptor system responses from cultured fetal mouse cortical neurons could be statistically separated and classified into five major types with little intragroup variability, primarily based on variations in the current deactivation phases.Receptors subjected to pharmacological modulation exhibited alterations in system response properties consistent with known mechanisms of action, such that distinctions between binding and gating modulations were possible.Brief agonist exposure places limits on receptor activation and deactivation response kinetics. Consequently, receptor system responses may be used to characterize and functionally phenotype an excised patch receptor population. Furthermore, since synaptic exposure to transmitter is postulated to be similarly brief, IPSC kinetics may reflect a functional fingerprint of synaptic receptors. PMID:10066899

  13. A World Allergy Organization International Survey on Diagnostic Procedures and Therapies in Drug Allergy/Hypersensitivity

    PubMed Central

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

    2011-01-01

    Objective To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). Methods 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. Results Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitrospecific 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 StevensJohnson 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%. Conclusions 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. PMID:23268453

  14. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity

    PubMed Central

    Pirmohamed, Munir; Ostrov, David A.; Park, B. Kevin

    2015-01-01

    Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions. PMID:26254050

  15. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity.

    PubMed

    Pirmohamed, Munir; Ostrov, David A; Park, B Kevin

    2015-08-01

    Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions. PMID:26254050

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

    PubMed

    Fang, Feng; Tang, Yijun; Gao, Zhe; Xu, Qiang

    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. PMID:20471963

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

    SciTech Connect

    Fang, Feng; Tang, Yijun; Gao, Zhe; Xu, Qiang

    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.

  18. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    ERIC Educational Resources Information Center

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have

  19. RNA-seq analysis reveals genetic response and tolerance mechanisms to ozone exposure in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative stress caused by ground level ozone is a major contributor to yield loss in a number of important crop plants. Soybean (Glycine max) is especially ozone sensitive, and research into its response to oxidative stress is limited. To better understand the genetic response in soybean to oxida...

  20. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    ERIC Educational Resources Information Center

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  1. Evaluation of the hypersensitivity potential of alternative butter flavorings

    PubMed Central

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

    2015-01-01

    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 2550% 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. PMID:24007741

  2. Hypersensitivity of lung vessels to catecholamines in systemic hypertension.

    PubMed Central

    Guazzi, M D; Alimento, M; Fiorentini, C; Pepi, M; Polese, A

    1986-01-01

    Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper-reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over-reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure. PMID:3089490

  3. Hypersensitivity to Aeroallergens in Patients with Nasobronchial Allergy

    PubMed Central

    Balaban, Jagoda; Bijelic, Radojka; Milicevic, Snjezana

    2014-01-01

    ABSTRACT Background: Aeroallergens are the most common causes of allergy. Aim: The aim of this study was to determine hypersensitivity to aeroallergens in patients with nasobronchial allergy. Methods: This retrospective population study included 2254 patients with nasobronchial allergy, from late adolescents to adults. Their response to aeroallergens was assessed by skin prick tests. Results: More patients had rhinitis (72.7%), than asthma (27.6%). Although majority of patients were female, allergy is more common in men than in women (p<0.05). Both groups of patients had the greatest number of positive skin prick tests for Dermatophagoides pteronyssinus (27.5%) and weed pollens (21.9%), followed by grass (18.3%) and tree pollens (10.1%). Ragweed is the most common positive weed pollen in both groups, more in patients with rhinitis (p=0.022). The cocksfoot is the most common grass pollen in rhinitis group (15.3%), but meadow grass (12.6%) in asthma patients. Birch is the most common tree allergen in the both groups. Conclusions: More patients with nasobronchial allergy have rhinitis than asthma. Skin prick tests are usually positive for Dermatophagoides pteronyssinus and weed pollens, followed by grass and tree pollens, and they are more common positive in patients with rhinitis than asthma. PMID:24937928

  4. Mining large-scale response networks reveals topmost activities in Mycobacterium tuberculosis infection

    PubMed Central

    Sambarey, Awanti; Prashanthi, Karyala; Chandra, Nagasuma

    2013-01-01

    Mycobacterium tuberculosis owes its high pathogenic potential to its ability to evade host immune responses and thrive inside the macrophage. The outcome of infection is largely determined by the cellular response comprising a multitude of molecular events. The complexity and inter-relatedness in the processes makes it essential to adopt systems approaches to study them. In this work, we construct a comprehensive network of infection-related processes in a human macrophage comprising 1888 proteins and 14,016 interactions. We then compute response networks based on available gene expression profiles corresponding to states of health, disease and drug treatment. We use a novel formulation for mining response networks that has led to identifying highest activities in the cell. Highest activity paths provide mechanistic insights into pathogenesis and response to treatment. The approach used here serves as a generic framework for mining dynamic changes in genome-scale protein interaction networks. PMID:23892477

  5. A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage.

    PubMed

    Nardo, Tiziana; Oneda, Roberta; Spivak, Graciela; Vaz, Bruno; Mortier, Laurent; Thomas, Pierre; Orioli, Donata; Laugel, Vincent; Stary, Anne; Hanawalt, Philip C; Sarasin, Alain; Stefanini, Miria

    2009-04-14

    UV-sensitive syndrome (UV(S)S) is a recently-identified autosomal recessive disorder characterized by mild cutaneous symptoms and defective transcription-coupled repair (TC-NER), the subpathway of nucleotide excision repair (NER) that rapidly removes damage that can block progression of the transcription machinery in actively-transcribed regions of DNA. Cockayne syndrome (CS) is another genetic disorder with sun sensitivity and defective TC-NER, caused by mutations in the CSA or CSB genes. The clinical hallmarks of CS include neurological/developmental abnormalities and premature aging. UV(S)S is genetically heterogeneous, in that it appears in individuals with mutations in CSB or in a still-unidentified gene. We report the identification of a UV(S)S patient (UV(S)S1VI) with a novel mutation in the CSA gene (p.trp361cys) that confers hypersensitivity to UV light, but not to inducers of oxidative damage that are notably cytotoxic in cells from CS patients. The defect in UV(S)S1VI cells is corrected by expression of the WT CSA gene. Expression of the p.trp361cys-mutated CSA cDNA increases the resistance of cells from a CS-A patient to oxidative stress, but does not correct their UV hypersensitivity. These findings imply that some mutations in the CSA gene may interfere with the TC-NER-dependent removal of UV-induced damage without affecting its role in the oxidative stress response. The differential sensitivity toward oxidative stress might explain the difference between the range and severity of symptoms in CS and the mild manifestations in UV(s)S patients that are limited to skin photosensitivity without precocious aging or neurodegeneration. PMID:19329487

  6. Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes.

    PubMed

    Rotroff, D M; Shahin, M H; Gurley, S B; Zhu, H; Motsinger-Reif, A; Meisner, M; Beitelshees, A L; Fiehn, O; Johnson, J A; Elbadawi-Sidhu, M; Frye, R F; Gong, Y; Weng, L; Cooper-DeHoff, R M; Kaddurah-Daouk, R

    2015-11-01

    Achieving hypertension (HTN) control and mitigating the adverse health effects associated with HTN continues to be a global challenge. Some individuals respond poorly to current HTN therapies, and mechanisms for response variation remain poorly understood. We used a nontargeted metabolomics approach (gas chromatography time-of-flight/mass spectrometry gas chromatography time-of-flight/mass spectrometry) measuring 489 metabolites to characterize metabolite signatures associated with treatment response to anti-HTN drugs, atenolol (ATEN), and hydrochlorothiazide (HCTZ), in white and black participants with uncomplicated HTN enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses study. Metabolite profiles were significantly different between races, and metabolite responses associated with home diastolic blood pressure (HDBP) response were identified. Metabolite pathway analyses identified gluconeogenesis, plasmalogen synthesis, and tryptophan metabolism increases in white participants treated with HCTZ (P < 0.05). Furthermore, we developed predictive models from metabolite signatures of HDBP treatment response (P < 1 × 10(-5)). As part of a quantitative systems pharmacology approach, the metabolites identified herein may serve as biomarkers for improving treatment decisions and elucidating mechanisms driving HTN treatment responses. PMID:26783503

  7. A rapid dehydration leaf assay reveals stomatal response differences in grapevine genotypes

    PubMed Central

    Hopper, Daniel W; Ghan, Ryan; Cramer, Grant R

    2014-01-01

    A simple and reliable way of phenotyping plant responses to dehydration was developed. Fully-developed leaves were detached and placed in a closed plastic box containing a salt solution to control the atmospheric water potential in the container. Three hours of dehydration (weight loss of the leaf) was optimal for measuring changes in stomatal response to dehydration. Application of the plant hormone abscisic acid (ABA) prior to leaf detachment decreased the amount of water loss, indicating that the assay was able to detect differences based on a stomatal response to dehydration. Five different Vitis genotypes (V. riparia, V. champinii, V. vinifera cv. Shiraz, V. vinifera cv. Grenache and V. vinifera cv. Cabernet Sauvignon) with known differences in drought tolerance were screened for their dehydration response and the results obtained corresponded to previous reports of stomatal responses in the vineyard. Significant differences in stomatal density along with differences in the amount and rate of water lost indicate differences in dehydration sensitivity among the genotypes screened. Differences in stomatal response to ABA were also detected. Shiraz had the lowest stomatal density and the highest ABA sensitivity among the genotypes screened, yet Shiraz lost the most amount of water, indicating that it was the least sensitive to dehydration. Despite having the highest stomatal density and intermediate stomatal sensitivity to ABA, V. riparia lost the smallest amount of water, indicating that it was the most sensitive to dehydration. The assay presented here represents a simple and reliable phenotyping method for plant responses to leaf dehydration. PMID:26504528

  8. Global transcription profiling reveals differential responses to chronic nitrogen stress and putative nitrogen regulatory components in Arabidopsis

    PubMed Central

    Bi, Yong-Mei; Wang, Rong-Lin; Zhu, Tong; Rothstein, Steven J

    2007-01-01

    Background A large quantity of nitrogen (N) fertilizer is used for crop production to achieve high yields at a significant economic and environmental cost. Efforts have been directed to understanding the molecular basis of plant responses to N and identifying N-responsive genes in order to manipulate their expression, thus enabling plants to use N more efficiently. No studies have yet delineated these responses at the transcriptional level when plants are grown under chronic N stress and the understanding of regulatory elements involved in N response is very limited. Results To further our understanding of the response of plants to varying N levels, a growth system was developed where N was the growth-limiting factor. An Arabidopsis whole genome microarray was used to evaluate global gene expression under different N conditions. Differentially expressed genes under mild or severe chronic N stress were identified. Mild N stress triggered only a small set of genes significantly different at the transcriptional level, which are largely involved in various stress responses. Plant responses were much more pronounced under severe N stress, involving a large number of genes in many different biological processes. Differentially expressed genes were also identified in response to short- and long-term N availability increases. Putative N regulatory elements were determined along with several previously known motifs involved in the responses to N and carbon availability as well as plant stress. Conclusion Differentially expressed genes identified provide additional insights into the coordination of the complex N responses of plants and the components of the N response mechanism. Putative N regulatory elements were identified to reveal possible new components of the regulatory network for plant N responses. A better understanding of the complex regulatory network for plant N responses will help lead to strategies to improve N use efficiency. PMID:17705847

  9. Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats

    SciTech Connect

    Koutouzov, S.; Remmal, A.; Marche, P.; Meyer, P.

    1987-11-01

    Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY by using /sup 32/P-labeled quiescent platelets. In unstimulated cells, both the rate and extent of /sup 32/P incorporation into individual inositol-containing phospholipids and phosphatidic acid were identical in SHR and WKY. This finding suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced phosphoinositide metabolism, when monitored as changes in (/sup 32/P)phosphatidic acid, was significantly higher in SHR than in WKY. For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more (/sup 32/P)phosphatidic acid in SHR than in WKY. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced (/sup 32/P)phosphatidic acid formation in SHR. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. Following thrombin stimulation, (/sup 32/P)phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR.

  10. Stromal Transcriptional Profiles Reveal Hierarchies of Anatomical Site, Serum Response and Disease and Identify Disease Specific Pathways

    PubMed Central

    Parsonage, Greg N.; Legault, Holly M.; OToole, Margot; Pearson, Mark J.; Thomas, Andrew M.; Scheel-Toellner, Dagmar; Raza, Karim; Buckley, Christopher D.; Falciani, Francesco

    2015-01-01

    Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through _3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts. PMID:25807374

  11. DNA Microarray Analysis of Anaerobic Methanosarcina Barkeri Reveals Responses to Heat Shock and Air Exposure

    SciTech Connect

    Zhang, Weiwen; Culley, David E.; Nie, Lei; Brockman, Fred J.

    2006-04-08

    Summary Methanosarcina barkeri can grow only under strictly anoxic conditions because enzymes in methane formation pathways of are very oxygen sensitive. However, it has been determined that M. barkeri can survive oxidative stress. To obtain further knowledge of cellular changes in M. barkeri in responsive to oxidative and other environmental stress, a first whole-genome M. barkeri oligonucleotide microarray was constructed according to the draft genome sequence that contains 5072 open reading frames (ORFs) and was used to investigate the global transcriptomic response of M. barkeri to oxidative stress and heat shock. The result showed that 552 genes in the M. barkeri genome were responsive to oxidative stress, while 177 genes responsive to heat-shock, respectively using a cut off of 2.5 fold change. Among them, 101 genes were commonly responsive to both environmental stimuli. In addition to various house-keeping genes, large number of functionally unknown genes (38-57% of total responsive genes) was regulated by both stress conditions. The result showed that the Hsp60 (GroEL) system, which was previously thought not present in archaea, was up-regulated and may play important roles in protein biogenesis in responsive to heat shock in M. barkeri. No gene encoding superoxide dismutase, catalase, nonspecific peroxidases or thioredoxin reductase was differentially expressed when subjected to oxidative stress. Instead, significant downregulation of house-keeping genes and up-regulation of genes encoding transposase was found in responsive to oxidative stress, suggesting that M. barkeri may be adopting a passive protective mechanism by slowing down cellular activities to survive the stress rather than activating a means against oxidative stress.

  12. Transgenic AEQUORIN reveals organ-specific cytosolic Ca2+ responses to anoxia and Arabidopsis thaliana seedlings.

    PubMed

    Sedbrook, J C; Kronebusch, P J; Borisy, G G; Trewavas, A J; Masson, P H

    1996-05-01

    Using the transgenic AEQUORIN system, we showed that the cotyledons and leaves of Arabidopsis thaliana seedlings developed a biphasic luminescence response to anoxia, indicating changes in cytosolic Ca2+ levels. A fast and transient luminescence peak occurred within minutes of anoxia, followed by a second, prolonged luminescence response that lasted 1.5 to 4 h. The Ca2+ channel blockers Gd3+, La3+, and ruthenium red (RR) partially inhibited the first response and promoted a larger and earlier second response, suggesting different origins for these responses. Both Gd3+ and RR also partially inhibited anaerobic induction of alcohol dehydrogenase gene expression. However, although anaerobic alcohol dehydrogenase gene induction occurred in seedlings exposed to water-agar medium and in roots, related luminescence responses were absent. Upon return to normoxia, the luminescence of cotyledons, leaves, and roots dropped quickly, before increasing again in a Gd3+, La3+, ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-, and RR-sensitive fashion. PMID:8685265

  13. Transgenic AEQUORIN reveals organ-specific cytosolic Ca2+ responses to anoxia and Arabidopsis thaliana seedlings

    NASA Technical Reports Server (NTRS)

    Sedbrook, J. C.; Kronebusch, P. J.; Borisy, G. G.; Trewavas, A. J.; Masson, P. H.

    1996-01-01

    Using the transgenic AEQUORIN system, we showed that the cotyledons and leaves of Arabidopsis thaliana seedlings developed a biphasic luminescence response to anoxia, indicating changes in cytosolic Ca2+ levels. A fast and transient luminescence peak occurred within minutes of anoxia, followed by a second, prolonged luminescence response that lasted 1.5 to 4 h. The Ca2+ channel blockers Gd3+, La3+, and ruthenium red (RR) partially inhibited the first response and promoted a larger and earlier second response, suggesting different origins for these responses. Both Gd3+ and RR also partially inhibited anaerobic induction of alcohol dehydrogenase gene expression. However, although anaerobic alcohol dehydrogenase gene induction occurred in seedlings exposed to water-agar medium and in roots, related luminescence responses were absent. Upon return to normoxia, the luminescence of cotyledons, leaves, and roots dropped quickly, before increasing again in a Gd3+, La3+, ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-, and RR-sensitive fashion.

  14. Transgenic AEQUORIN reveals organ-specific cytosolic Ca2+ responses to anoxia and Arabidopsis thaliana seedlings.

    PubMed Central

    Sedbrook, J C; Kronebusch, P J; Borisy, G G; Trewavas, A J; Masson, P H

    1996-01-01

    Using the transgenic AEQUORIN system, we showed that the cotyledons and leaves of Arabidopsis thaliana seedlings developed a biphasic luminescence response to anoxia, indicating changes in cytosolic Ca2+ levels. A fast and transient luminescence peak occurred within minutes of anoxia, followed by a second, prolonged luminescence response that lasted 1.5 to 4 h. The Ca2+ channel blockers Gd3+, La3+, and ruthenium red (RR) partially inhibited the first response and promoted a larger and earlier second response, suggesting different origins for these responses. Both Gd3+ and RR also partially inhibited anaerobic induction of alcohol dehydrogenase gene expression. However, although anaerobic alcohol dehydrogenase gene induction occurred in seedlings exposed to water-agar medium and in roots, related luminescence responses were absent. Upon return to normoxia, the luminescence of cotyledons, leaves, and roots dropped quickly, before increasing again in a Gd3+, La3+, ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-, and RR-sensitive fashion. PMID:8685265

  15. DNase I- and micrococcal nuclease-hypersensitive sites in the human apolipoprotein B gene are tissue specific

    SciTech Connect

    Levy-Wilson, B.; Fortier, C.; Blackhart, B.D.; McCarthy, B.J.

    1988-01-01

    The authors mapped the DNase I- and micrococcal nuclease-hypersensitive sites present in the 5' end of the human apolipoprotein B (apo-B) gene in nuclei from cells expressing or not expressing the gene. Four DNase I-hypersensitive sites were found in nuclei from liver-derived HepG2 cells and intestine-derived CaCo-2 cells, which express the apo-B gene, but not in HeLa cells, which do not. These sites are located near positions -120, -440, -700, and +760 base pairs relative to the transcriptional start site. Undifferentiated CaCo-2 cells exhibited another site, near position -540. Six micrococcal nuclease-hypersensitive sites were found in nuclei from HepG2 and CaCo-2 cells, but not in HeLa cells or free DNA. These sites are located near positions -120, -390, -530, -700, -850, and +210. HepG2 cells exhibited another site, near position +460. Comparison of the DNA sequence of the 5' flanking regions of the human and mouse apo-B genes revealed a high degree of evolutionary conservation of short stretches of sequences in the immediate vicinity of each of the DNase I- and most of the micrococcal nuclease-hypersensitive sites.

  16. Difference in perceptual and oculomotor responses revealed by apparent motion stimuli presented with an interstimulus interval.

    PubMed

    Nohara, Shizuka; Kawano, Kenji; Miura, Kenichiro

    2015-05-01

    To understand the mechanisms underlying visual motion analyses for perceptual and oculomotor responses and their similarities/differences, we analyzed eye movement responses to two-frame animations of dual-grating 3f5f stimuli while subjects performed direction discrimination tasks. The 3f5f stimulus was composed of two sinusoids with a spatial frequency ratio of 3:5 (3f and 5f), creating a pattern with fundamental frequency f. When this stimulus was shifted by 1/4 of the wavelength, the two components shifted 1/4 of their wavelengths and had opposite directions: the 5f forward and the 3f backward. By presenting the 3f5f stimulus with various interstimulus intervals (ISIs), two visual-motion-analysis mechanisms, low-level energy-based and high-level feature-based, could be effectively distinguished. This is because response direction depends on the relative contrast between the components when the energy-based mechanism operates, but not when the feature-based mechanism works. We found that when the 3f5f stimuli were presented with shorter ISIs (<100 ms), and 3f component had higher contrast, both perceptual and ocular responses were in the direction of the pattern shift, whereas the responses were reversed when the 5f had higher contrast, suggesting operation of the energy-based mechanism. On the other hand, the ocular responses were almost negligible with longer ISIs (>100 ms), whereas perceived directions were biased toward the direction of pattern shift. These results suggest that the energy-based mechanism is dominant in oculomotor responses throughout ISIs; however, there is a transition from energy-based to feature-tracking mechanisms when we perceive visual motion. PMID:25810485

  17. Colony-specific investigations reveal highly variable responses among individual corals to ocean acidification and warming.

    PubMed

    Kavousi, Javid; Reimer, James Davis; Tanaka, Yasuaki; Nakamura, Takashi

    2015-08-01

    As anthropogenic climate change is an ongoing concern, scientific investigations on its impacts on coral reefs are increasing. Although impacts of combined ocean acidification (OA) and temperature stress (T) on reef-building scleractinian corals have been studied at the genus, species and population levels, there are little data available on how individual corals respond to combined OA and anomalous temperatures. In this study, we exposed individual colonies of Acropora digitifera, Montipora digitata and Porites cylindrica to four pCO2-temperature treatments including 400 μatm-28 °C, 400 μatm-31 °C, 1000 μatm-28 °C and 1000 μatm-31 °C for 26 days. Physiological parameters including calcification, protein content, maximum photosynthetic efficiency, Symbiodinium density, and chlorophyll content along with Symbiodinium type of each colony were examined. Along with intercolonial responses, responses of individual colonies versus pooled data to the treatments were investigated. The main results were: 1) responses to either OA or T or their combination were different between individual colonies when considering physiological functions; 2) tolerance to either OA or T was not synonymous with tolerance to the other parameter; 3) tolerance to both OA and T did not necessarily lead to tolerance of OA and T combined (OAT) at the same time; 4) OAT had negative, positive or no impacts on physiological functions of coral colonies; and 5) pooled data were not representative of responses of all individual colonies. Indeed, the pooled data obscured actual responses of individual colonies or presented a response that was not observed in any individual. From the results of this study we recommend improving experimental designs of studies investigating physiological responses of corals to climate change by complementing them with colony-specific examinations. PMID:26009841

  18. Differential reproductive responses to stress reveal the role of life-history strategies within a species.

    PubMed

    Schultner, J; Kitaysky, A S; Gabrielsen, G W; Hatch, S A; Bech, C

    2013-11-22

    Life-history strategies describe that 'slow'- in contrast to 'fast'-living species allocate resources cautiously towards reproduction to enhance survival. Recent evidence suggests that variation in strategies exists not only among species but also among populations of the same species. Here, we examined the effect of experimentally induced stress on resource allocation of breeding seabirds in two populations with contrasting life-history strategies: slow-living Pacific and fast-living Atlantic black-legged kittiwakes. We tested the hypothesis that reproductive responses in kittiwakes under stress reflect their life-history strategies. We predicted that in response to stress, Pacific kittiwakes reduce investment in reproduction compared with Atlantic kittiwakes. We exposed chick-rearing kittiwakes to a short-term (3-day) period of increased exogenous corticosterone (CORT), a hormone that is released during food shortages. We examined changes in baseline CORT levels, parental care and effects on offspring. We found that kittiwakes from the two populations invested differently in offspring when facing stress. In response to elevated CORT, Pacific kittiwakes reduced nest attendance and deserted offspring more readily than Atlantic kittiwakes. We observed lower chick growth, a higher stress response in offspring and lower reproductive success in response to CORT implantation in Pacific kittiwakes, whereas the opposite occurred in the Atlantic. Our findings support the hypothesis that life-history strategies predict short-term responses of individuals to stress within a species. We conclude that behaviour and physiology under stress are consistent with trade-off priorities as predicted by life-history theory. We encourage future studies to consider the pivotal role of life-history strategies when interpreting inter-population differences of animal responses to stressful environmental events. PMID:24089339

  19. Differential reproductive responses to stress reveal the role of life-history strategies within a species

    PubMed Central

    Schultner, J.; Kitaysky, A. S.; Gabrielsen, G. W.; Hatch, S. A.; Bech, C.

    2013-01-01

    Life-history strategies describe that ‘slow’- in contrast to ‘fast’-living species allocate resources cautiously towards reproduction to enhance survival. Recent evidence suggests that variation in strategies exists not only among species but also among populations of the same species. Here, we examined the effect of experimentally induced stress on resource allocation of breeding seabirds in two populations with contrasting life-history strategies: slow-living Pacific and fast-living Atlantic black-legged kittiwakes. We tested the hypothesis that reproductive responses in kittiwakes under stress reflect their life-history strategies. We predicted that in response to stress, Pacific kittiwakes reduce investment in reproduction compared with Atlantic kittiwakes. We exposed chick-rearing kittiwakes to a short-term (3-day) period of increased exogenous corticosterone (CORT), a hormone that is released during food shortages. We examined changes in baseline CORT levels, parental care and effects on offspring. We found that kittiwakes from the two populations invested differently in offspring when facing stress. In response to elevated CORT, Pacific kittiwakes reduced nest attendance and deserted offspring more readily than Atlantic kittiwakes. We observed lower chick growth, a higher stress response in offspring and lower reproductive success in response to CORT implantation in Pacific kittiwakes, whereas the opposite occurred in the Atlantic. Our findings support the hypothesis that life-history strategies predict short-term responses of individuals to stress within a species. We conclude that behaviour and physiology under stress are consistent with trade-off priorities as predicted by life-history theory. We encourage future studies to consider the pivotal role of life-history strategies when interpreting inter-population differences of animal responses to stressful environmental events. PMID:24089339

  20. [Salmonella typhi vaccination response study reveals defective antibody production selective IgA deficiency patient].

    PubMed

    Pleguezuelo, Daniel E; Gianelli, Carla

    2015-01-01

    Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre-vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production. PMID:26556667

  1. Environmental Interactions and Epistasis Are Revealed in the Proteomic Responses to Complex Stimuli

    PubMed Central

    Samir, Parimal; Rahul; Slaughter, James C.; Link, Andrew J.

    2015-01-01

    Ultimately, the genotype of a cell and its interaction with the environment determine the cells biochemical state. While the cells response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well. PMID:26247773

  2. EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness.

    PubMed

    Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

    2015-01-01

    Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly "domain general" conflict processing mechanisms, instead of conflict source specific effects. PMID:26169473

  3. [Heat-responsive mechanisms in plants revealed by proteomic analysis: A review].

    PubMed

    Liu, Jun-ming; Zhao, Qi; Yin, Ze-peng; Xu, Chen-xi; Wang, Quan-hua; Dai, Shao-jun

    2015-08-01

    Heat stress is a major abiotic stress that limits plant growth and productivity. In recent years, proteomic investigations provide more information for understanding the sophisticated heat-responsive molecular mechanism in plants at systematic biological level. The heat-responsive proteomic patterns in several plants, i. e., model plants (Arabidopsis thaliana), staple food crops (soybean, rice and wheat), heat-tolerant plants (Agrostis stolonifera, Portulaca oleracea, and Carissa spinarum), grapevine, Populus euphratica, Medicago sativa, and Pinellia ternate, were reported. A total of 838 heat-responsive proteins have been identified in these studies. Among them, 534 proteins were induced and the expression of 304 proteins was reduced in plants under heat stress. In this paper, the diverse protein patterns in plants under various heat stress conditions (30-45 C for 0-10 d) were analyzed integratively. This provided new evidences and clues for further interpreting the signaling and metabolic pathways, e.g., signaling, stress and defense, carbohydrate and energy metabolism, photosynthesis, transcription, protein synthesis and fate, membrane and transport, in heat-responsive networks, and laid a foundation for a holistic understanding of the molecular regulatory mechanism in plants in response to heat stress. PMID:26685622

  4. EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness

    PubMed Central

    Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

    2015-01-01

    Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly “domain general” conflict processing mechanisms, instead of conflict source specific effects. PMID:26169473

  5. Simultaneous dual-task performance reveals parallel response selection after practice

    NASA Technical Reports Server (NTRS)

    Hazeltine, Eliot; Teague, Donald; Ivry, Richard B.

    2002-01-01

    E. H. Schumacher, T. L. Seymour, J. M. Glass, D. E. Kieras, and D. E. Meyer (2001) reported that dual-task costs are minimal when participants are practiced and give the 2 tasks equal emphasis. The present research examined whether such findings are compatible with the operation of an efficient response selection bottleneck. Participants trained until they were able to perform both tasks simultaneously without interference. Novel stimulus pairs produced no reaction time costs, arguing against the development of compound stimulus-response associations (Experiment 1). Manipulating the relative onsets (Experiments 2 and 4) and durations (Experiments 3 and 4) of response selection processes did not lead to dual-task costs. The results indicate that the 2 tasks did not share a bottleneck after practice.

  6. Pupillary responses reveal infants' discrimination of facial emotions independent of conscious perception.

    PubMed

    Jessen, Sarah; Altvater-Mackensen, Nicole; Grossmann, Tobias

    2016-05-01

    Sensitive responding to others' emotions is essential during social interactions among humans. There is evidence for the existence of subcortically mediated emotion discrimination processes that occur independent of conscious perception in adults. However, only recently work has begun to examine the development of automatic emotion processing systems during infancy. In particular, it is unclear whether emotional expressions impact infants' autonomic nervous system regardless of conscious perception. We examined this question by measuring pupillary responses while subliminally and supraliminally presenting 7-month-old infants with happy and fearful faces. Our results show greater pupil dilation, indexing enhanced autonomic arousal, in response to happy compared to fearful faces regardless of conscious perception. Our findings suggest that, early in ontogeny, emotion discrimination occurs independent of conscious perception and is associated with differential autonomic responses. This provides evidence for the view that automatic emotion processing systems are an early-developing building block of human social functioning. PMID:26896901

  7. Metabolomics Reveals Amino Acids Contribute to Variation in Response to Simvastatin Treatment

    PubMed Central

    Wikoff, William R.; Baillie, Rebecca A.; Zeng, Zhao-Bang; Karp, Peter D.; Fiehn, Oliver; Krauss, Ronald M.; Kaddurah-Daouk, Rima

    2012-01-01

    Statins are widely prescribed for reducing LDL-cholesterol (C) and risk for cardiovascular disease (CVD), but there is considerable variation in therapeutic response. We used a gas chromatography-time-of-flight mass-spectrometry-based metabolomics platform to evaluate global effects of simvastatin on intermediary metabolism. Analyses were conducted in 148 participants in the Cholesterol and Pharmacogenetics study who were profiled pre and six weeks post treatment with 40 mg/day simvastatin: 100 randomly selected from the full range of the LDL-C response distribution and 24 each from the top and bottom 10% of this distribution (good and poor responders, respectively). The metabolic signature of drug exposure in the full range of responders included essential amino acids, lauric acid (p<0.0055, q<0.055), and alpha-tocopherol (p<0.0003, q<0.017). Using the HumanCyc database and pathway enrichment analysis, we observed that the metabolites of drug exposure were enriched for the pathway class amino acid degradation (p<0.0032). Metabolites whose change correlated with LDL-C lowering response to simvastatin in the full range responders included cystine, urea cycle intermediates, and the dibasic amino acids ornithine, citrulline and lysine. These dibasic amino acids share plasma membrane transporters with arginine, the rate-limiting substrate for nitric oxide synthase (NOS), a critical mediator of cardiovascular health. Baseline metabolic profiles of the good and poor responders were analyzed by orthogonal partial least square discriminant analysis so as to determine the metabolites that best separated the two response groups and could be predictive of LDL-C response. Among these were xanthine, 2-hydroxyvaleric acid, succinic acid, stearic acid, and fructose. Together, the findings from this study indicate that clusters of metabolites involved in multiple pathways not directly connected with cholesterol metabolism may play a role in modulating the response to simvastatin treatment. Trial Registration ClinicalTrials.gov NCT00451828 PMID:22808006

  8. Integrative "omic" analysis reveals distinctive cold responses in leaves and roots of strawberry, Fragaria ananassa 'Korona'.

    PubMed

    Koehler, Gage; Rohloff, Jens; Wilson, Robert C; Kopka, Joachim; Erban, Alexander; Winge, Per; Bones, Atle M; Davik, Jahn; Alsheikh, Muath K; Randall, Stephen K

    2015-01-01

    To assess underlying metabolic processes and regulatory mechanisms during cold exposure of strawberry, integrative "omic" approaches were applied to Fragaria ananassa Duch. 'Korona.' Both root and leaf tissues were examined for responses to the cold acclimation processes. Levels of metabolites, proteins, and transcripts in tissues from plants grown at 18C were compared to those following 1-10 days of cold (2C) exposure. When leaves and roots were subjected to GC/TOF-MS-based metabolite profiling, about 160 compounds comprising mostly structurally annotated primary and secondary metabolites, were found. Overall, 'Korona' showed a modest increase of protective metabolites such as amino acids (aspartic acid, leucine, isoleucine, and valine), pentoses, phosphorylated and non-phosphorylated hexoses, and distinct compounds of the raffinose pathway (galactinol and raffinose). Distinctive responses were observed in roots and leaves. By 2DE proteomics a total of 845 spots were observed in leaves; 4.6% changed significantly in response to cold. Twenty-one proteins were identified, many of which were associated with general metabolism or photosynthesis. Transcript levels in leaves were determined by microarray, where dozens of cold associated transcripts were quantitatively characterized, and levels of several potential key contributors (e.g., the dehydrin COR47 and GADb) to cold tolerance were confirmed by qRT-PCR. Cold responses are placed within the existing knowledge base of low temperature-induced changes in plants, allowing an evaluation of the uniqueness or generality of Fragaria responses in photosynthetic tissues. Overall, the cold response characteristics of 'Korona' are consistent with a moderately cold tolerant plant. PMID:26528299

  9. Stimuli response of cystamine-core dendrimer revealed by diffusion and NOE NMR studies.

    PubMed

    Feng, Xueyan; Cheng, Yiyun; Wu, Qinglin; Zhang, Jiahai; Xu, Tongwen

    2011-04-14

    Stimuli response behaviors of cystamine-core dendrimer in the presence of several reducing agents including vitamin C, sodium bisulfite, and DL-Dithiothreitol are described. A competitive redox cleavage and supramolecular aggregate formation model is proposed based on PFG NMR and (1)H NMR titration experiments. Furthermore, reduction-responsive release of guest molecules from interior pockets of the cystamine-core dendrimer is confirmed by NOE studies. The results suggest that cystamine-core dendrimer is a versatile scaffold or precursor in the design of reduction-sensitive polymeric nanocapsules for biomedical purposes. PMID:21417291

  10. Problem gamblers exhibit reward hypersensitivity in medial frontal cortex during gambling.

    PubMed

    Oberg, Scott A K; Christie, Gregory J; Tata, Matthew S

    2011-11-01

    Problem gambling (PG) is increasingly conceptualized as an addiction akin to substance abuse, rather than an impulse control disorder, however the mechanism of addiction remains unclear. Neuroimaging investigations have supported a "reward deficiency" hypothesis for PG by suggesting a blunted response to gambling, particularly in the striatum. Here we describe electrophysiological evidence of a hypersensitive response to gambling feedback in problem gamblers. Previous research in healthy participants has shown that feedback during gambling tasks triggers stereotypical neural responses including the Feedback-Related Mediofrontal Negativity (FRN), the feedback-related P300, and an increase in induced theta-band (4-8 Hz) power. We tested the theory that abnormal feedback processing characterizes brain activity in problem gamblers while gambling. EEG was recorded from non-gamblers and self-identified gamblers as they engaged in a computerized version of the Iowa Gambling Task. Feedback about valence (win vs. loss) triggered a FRN in both groups, but in gamblers this was preceded by an early-latency hypersensitive fronto-central difference to feedback. This early FRN was correlated with gambling severity and was localized to medial frontal cortex using distributed source imaging (CLARA). Gamblers also differed in responses to risk, showing a blunted P300 component and less EEG power in the theta band. Here we suggest that a more nuanced interpretation of reward deficiency is called for with respect to PG. For certain aspects of brain function, gamblers may exhibit hypersensitivity to reward feedback more akin to drug sensitization than reward deficiency. Our results also suggest that the neurologically normal brain employs dissociable systems in the processing of feedback from tasks involving risky decision making. PMID:21982697

  11. Trancriptomic profiling revealed the signatures of acute immune response in tilapia (Oreochromis niloticus) following Streptococcus iniae challenge.

    PubMed

    Zhu, Jiajie; Li, Chao; Ao, Qiuwei; Tan, Yun; Luo, Yongju; Guo, Yafen; Lan, Ganqiu; Jiang, Hesheng; Gan, Xi

    2015-10-01

    Streptococcus iniae is the most significant bacterial disease of tilapia throughout the world, and commonly leads to tremendous economic losses. In contrast to other important fish species, our knowledge about the molecular mechanisms of tilapia in response to bacterial infection is still limited. Here, therefore, we utilized RNA-seq to first profiling of host responses in tilapia spleen following S. iniae infection at transcriptome level. A total of 223 million reads were obtained and assembled into 192,884 contigs with average length 844 bp. Gene expression analysis between control and infected samples at 5 h, 50 h, and 7 d revealed 1475 differentially expressed genes. In particular, the differentially expressed gene set was dramatically induced as early as 5 h, and rapidly declined to basal levels at 50 h. Enrichment and pathway analysis of the differentially expressed genes revealed the centrality of the pathogen attachment and recognition, cytoskeletal rearrangement and immune activation/inflammation in the pathogen entry and host inflammatory responses. Understanding of these responses can highlight mechanisms of tilapia host defense, and expand our knowledge of teleost immunology. Our findings will set a foundation of valuable biomarkers for future individual, strain, and family-level studies to evaluate immune effect of vaccine and individual response in host defense mechanisms to S. iniae infection, to select disease resistant families and strains. PMID:26117728

  12. Total Knee Arthroplasty Failure Induced by Metal Hypersensitivity

    PubMed Central

    Gupta, Ryan; Phan, Duy; Schwarzkopf, Ran

    2015-01-01

    Patient: Female, 70 Final Diagnosis: Metal hypersensitivity Symptoms: Joint pain • swelling • instability Medication: — Clinical Procedure: Revision total knee arthroplasty Specialty: Orthopedics and Traumatology Objective: Unusual clinical course Background: Metal hypersensitivity is an uncommon complication after total knee arthroplasty (TKA) that can lead to significant functional impairment and aseptic prosthesis failure. Case Report: We describe a 70-year-old patient who presented with persistent pain, swelling, and instability 2 years after a primary TKA. The patient had a history of metal hypersensitivity following bilateral metal-on-metal total hip arthroplasty (THA) that was revised to ceramic-on-polyethylene implants. Knee radiographs showed severe osteolysis with implant loosening. Serum cobalt was elevated and serum chromium was significantly elevated, while joint aspiration and inflammatory marker levels ruled out a periprosthetic infection. Revision TKA was performed, with intraoperative tissue pathology and postoperative leukocyte transformation testing confirming metal hypersensitivity as the cause for aseptic implant failure. Conclusions: This case report demonstrates the clinical and laboratory signs that suggest metal hypersensitivity in total knee arthroplasty and the potential for joint function restoration with revision surgery. PMID:26278890

  13. Effect of Premedications in a Murine Model of Asparaginase Hypersensitivity

    PubMed Central

    Fernandez, Christian A.; Smith, Colton; Karol, Seth E.; Ramsey, Laura B.; Liu, Chengcheng; Pui, Ching-Hon; Jeha, Sima; Evans, William E.; Finkelman, Fred D.

    2015-01-01

    A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10−13) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10−3) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies. Combining triprolidine and CV-6209 was best for mitigating asparaginase-induced hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 × 10−5). However, pretreatment with oral dexamethasone was the only agent capable of mitigating the severity of the hypersensitivity (P = 0.03) and partially restoring asparaginase activity (P = 8.3 × 10−4). To rescue asparaginase activity in sensitized mice without requiring dexamethasone, a 5-fold greater dose of asparaginase was needed to restore enzyme activity to a similar concentration as in nonsensitized mice. Our results suggest a role of histamine and PAF in asparaginase-induced allergies and indicate that mast cell–derived proteases released during asparaginase allergy may be a useful marker of clinical hypersensitivity. PMID:25573198

  14. Novel TRPM8 antagonist attenuates cold hypersensitivity after peripheral nerve injury in rats.

    PubMed

    Patel, Ryan; Gonalves, Leonor; Newman, Robert; Jiang, Feng Li; Goldby, Anne; Reeve, Jennifer; Hendrick, Alan; Teall, Martin; Hannah, Duncan; Almond, Sarah; Brice, Nicola; Dickenson, Anthony H

    2014-04-01

    Abnormal cold sensitivity is a common feature of a range of neuropathies. In the murine somatosensory system, multiple aspects of cold sensitivity are dependent on TRPM8, both short term and in response to peripheral nerve injury. The specialized nature of cold-sensitive afferents and the restricted expression of TRPM8 render it an attractive target for the treatment of cold hypersensitivity. This current study examines the effect of a novel TRPM8 antagonist (M8-An) in naive and spinal nerve-ligated rats through behavioral and in vivo electrophysiological approaches. In vitro, M8-An inhibited icilin-evoked Ca(2+) currents in HEK293 cells stably expressing human TRPM8 with an IC(50) of 10.9 nM. In vivo, systemic M8-An transiently decreased core body temperature. Deep dorsal horn recordings were made in vivo from neurons innervating the hind paw. M8-An inhibited neuronal responses to innocuous and noxious cooling of the receptive field in spinal nerve-ligated rats but not in naive rats. No effect on neuronal responses to mechanical and heat stimulation was observed. In addition, M8-An also attenuated behavioral responses to cold but not mechanical stimulation after nerve ligation without affecting the uninjured contralateral response. The data presented here support a contribution of TRPM8 to the pathophysiology of cold hypersensitivity in this model and highlight the potential of the pharmacological block of TRPM8 in alleviating the associated symptoms. PMID:24472724

  15. Multimodal Stimulation of Colorado Potato Beetle Reveals Modulation of Pheromone Response by Yellow Light

    PubMed Central

    Otálora-Luna, Fernando; Dickens, Joseph C.

    2011-01-01

    Orientation of insects to host plants and conspecifics is the result of detection and integration of chemical and physical cues present in the environment. Sensory organs have evolved to be sensitive to important signals, providing neural input for higher order multimodal processing and behavioral output. Here we report experiments to determine decisions made by Colorado potato beetle (CPB), Leptinotarsa decemlineata, in response to isolated stimuli and multimodal combinations of signals on a locomotion compensator. Our results show that in complete darkness and in the absence of other stimuli, pheromonal stimulation increases attraction behavior of CPB as measured in oriented displacement and walking speed. However, orientation to the pheromone is abolished when presented with the alternative stimulation of a low intensity yellow light in a dark environment. The ability of the pheromone to stimulate these diurnal beetles in the dark in the absence of other stimuli is an unexpected but interesting observation. The predominance of the phototactic response over that to pheromone when low intensity lights were offered as choices seems to confirm the diurnal nature of the insect. The biological significance of the response to pheromone in the dark is unclear. The phototactic response will play a key role in elucidating multimodal stimulation in the host-finding process of CPB, and perhaps other insects. Such information might be exploited in the design of applications to attract and trap CPB for survey or control purposes and other insect pests using similar orientation mechanisms. PMID:21695167

  16. Drought-responsive protein profiles reveal diverse defense pathways in corn kernels under field drought atress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drought stress is a major factor which contributes to disease susceptibility and yield loss in agricultural crops. To identify drought responsive proteins and explore metabolic pathways involved in maize tolerance to drought stress, two lines (B73 and Lo964) with contrasting drought sensitivity were...

  17. Starvation stress during larval development reveals predictive adaptive response in adult worker honey bees (Apis mellifera)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A variety of organisms exhibit developmental plasticity that results in differences in adult morphology, physiology or behavior. This variation in the phenotype, called “Predictive Adaptive Response (PAR),” gives a selective advantage in an adult's environment if the adult experiences environments s...

  18. The pupil response reveals increased listening effort when it is difficult to focus attention.

    PubMed

    Koelewijn, Thomas; de Kluiver, Hilde; Shinn-Cunningham, Barbara G; Zekveld, Adriana A; Kramer, Sophia E

    2015-05-01

    Recent studies have shown that prior knowledge about where, when, and who is going to talk improves speech intelligibility. How related attentional processes affect cognitive processing load has not been investigated yet. In the current study, three experiments investigated how the pupil dilation response is affected by prior knowledge of target speech location, target speech onset, and who is going to talk. A total of 56 young adults with normal hearing participated. They had to reproduce a target sentence presented to one ear while ignoring a distracting sentence simultaneously presented to the other ear. The two sentences were independently masked by fluctuating noise. Target location (left or right ear), speech onset, and talker variability were manipulated in separate experiments by keeping these features either fixed during an entire block or randomized over trials. Pupil responses were recorded during listening and performance was scored after recall. The results showed an improvement in performance when the location of the target speech was fixed instead of randomized. Additionally, location uncertainty increased the pupil dilation response, which suggests that prior knowledge of location reduces cognitive load. Interestingly, the observed pupil responses for each condition were consistent with subjective reports of listening effort. We conclude that communicating in a dynamic environment like a cocktail party (where participants in competing conversations move unpredictably) requires substantial listening effort because of the demands placed on attentional processes. PMID:25732724

  19. Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response.

    PubMed

    Schmidt, Andreas; Trentini, Dbora Broch; Spiess, Silvia; Fuhrmann, Jakob; Ammerer, Gustav; Mechtler, Karl; Clausen, Tim

    2014-02-01

    Arginine phosphorylation is an emerging protein modification implicated in the general stress response of Gram-positive bacteria. The modification is mediated by the arginine kinase McsB, which phosphorylates and inactivates the heat shock repressor CtsR. In this study, we developed a mass spectrometric approach accounting for the peculiar chemical properties of phosphoarginine. The improved methodology was used to analyze the dynamic changes in the Bacillus subtilis arginine phosphoproteome in response to different stress situations. Quantitative analysis showed that a B. subtilis mutant lacking the YwlE arginine phosphatase accumulated a strikingly large number of arginine phosphorylations (217 sites in 134 proteins), however only a minor fraction of these sites was increasingly modified during heat shock or oxidative stress. The main targets of McsB-mediated arginine phosphorylation comprise central factors of the stress response system including the CtsR and HrcA heat shock repressors, as well as major components of the protein quality control system such as the ClpCP protease and the GroEL chaperonine. These findings highlight the impact of arginine phosphorylation in orchestrating the bacterial stress response. PMID:24263382

  20. Shadow response in the blind cavefish Astyanax reveals conservation of a functional pineal eye

    PubMed Central

    Yoshizawa, Masato; Jeffery, William R.

    2013-01-01

    SUMMARY The blind cavefish Astyanax mexicanus undergoes bilateral eye degeneration during embryonic development. Despite the absence of light in the cave environment, cavefish have retained a structurally intact pineal eye. We show here that contrary to visual degeneration in the bilateral eyes, the cavefish pineal eye has conserved the ability to detect light. Larvae of two different Astyanax cavefish populations and the con-specific sighted surface-dwelling form (surface fish) respond similarly to light dimming by shading the pineal eye. As a response to shading, cavefish larvae swim upward vertically. This behavior resembles that of amphibian tadpoles rather than other teleost larvae, which react to shadows by swimming downward. The shadow response is highest at 1.5-days post-fertilization (d.p.f.), gradually diminishes, and is virtually undetectable by 7.5 d.p.f. The shadow response was substantially reduced after surgical removal of the pineal gland from surface fish or cavefish larvae, indicating that it is based on pineal function. In contrast, removal of one or both bilateral eye primordia did not affect the shadow response. Consistent with its light detecting capacity, immunocytochemical studies indicate that surface fish and cavefish pineal eyes express a rhodopsin-like antigen, which is undetectable in the degenerating bilateral eyes of cavefish larvae. We conclude that light detection by the pineal eye has been conserved in cavefish despite a million or more years of evolution in complete darkness. PMID:18203983

  1. Arabidopsis thaliana mutant lpsi reveals impairment in the root responses to local phosphate availability.

    PubMed

    Karthikeyan, Athikkattuvalasu S; Jain, Ajay; Nagarajan, Vinay K; Sinilal, Bhaskaran; Sahi, Shivendra V; Raghothama, Kashchandra G

    2014-04-01

    Phosphate (Pi) deficiency triggers local Pi sensing-mediated inhibition of primary root growth and development of root hairs in Arabidopsis (Arabidopsis thaliana). Generation of activation-tagged T-DNA insertion pools of Arabidopsis expressing the luciferase gene (LUC) under high-affinity Pi transporter (Pht1;4) promoter, is an efficient approach for inducing genetic variations that are amenable for visual screening of aberrations in Pi deficiency responses. Putative mutants showing altered LUC expression during Pi deficiency were identified and screened for impairment in local Pi deficiency-mediated inhibition of primary root growth. An isolated mutant was analyzed for growth response, effects of Pi deprivation on Pi content, primary root growth, root hair development, and relative expression levels of Pi starvation-responsive (PSR) genes, and those implicated in starch metabolism and Fe and Zn homeostasis. Pi deprived local phosphate sensing impaired (lpsi) mutant showed impaired primary root growth and attenuated root hair development. Although relative expression levels of PSR genes were comparable, there were significant increases in relative expression levels of IRT1, BAM3 and BAM5 in Pi deprived roots of lpsi compared to those of the wild-type. Better understanding of molecular responses of plants to Pi deficiency or excess will help to develop suitable remediation strategies for soils with excess Pi, which has become an environmental concern. Hence, lpsi mutant will serve as a valuable tool in identifying molecular mechanisms governing adaptation of plants to Pi deficiency. PMID:24561248

  2. Blast cells transfer experimental hypersensitivity pneumonitis in guinea pigs

    SciTech Connect

    Schuyler, M.; Cook, C.; Listrom, M.; Fengolio-Preiser, C.

    1988-06-01

    We previously demonstrated that experimental hypersensitivity pneumonitis (HP) can be transferred by lymph node cells (LNC) cultured in vitro with antigen. The purpose of this study was to identify the cells responsible for transfer and to determine if pulmonary cells can transfer HP. We cultured LNC from sensitized Strain 2 guinea pigs with a soluble extract of Micropolyspora faeni for 72 h, separated lymphoblasts from small lymphocytes, and transferred both subpopulations intravenously to syngeneic recipients. We also transferred irradiated lymphoblasts (1,500 rads), macrophage-depleted, lymphoblast-enriched populations, and pulmonary cells either without culture or after culture with M. faeni. Control animals received an equal volume of medium. All recipient animals were challenged intratracheally (i.t.) with M. faeni 48 h after the cell transfer, and they were killed 4 days after i.t. challenge. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. This measurement was reproducible (r = 0.95 for duplicate measurements, n = 55). All guinea pigs were maintained in HEPA-filtered air. There was a low level of pulmonary response to an i.t. challenge of M. faeni in animals that received medium. Animals that received pulmonary cells, either cultured or noncultured, did not differ from those in the control group. There was a substantial increase (p less than 0.01) in the extent of pulmonary abnormalities in the recipients of the lymphoblast population, with significant correlation (r = 0.87, p less than 0.01) between the number of lymphoblasts transferred and the extent of pulmonary abnormalities.

  3. Adaptive responses reveal contemporary and future ecotypes in a desert shrub

    USGS Publications Warehouse

    Richardson, Bryce A.; Kitchen, Stanley G.; Pendleton, Rosemary L.; Pendleton, Burton K.; Germino, Matthew J.; Rehfeldt, Gerald E.; Meyer, Susan E.

    2014-01-01

    Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species–climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep clines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are needed to inform restoration and management planning. We propose four transfer zones in blackbrush that correspond to areas currently dominated by cool-adapted and warm-adapted ecotypes in each of the two ecoregions.

  4. Meta-analysis reveals profound responses of plant traits to glacial CO2 levels

    PubMed Central

    Temme, A A; Cornwell, W K; Cornelissen, J H C; Aerts, R

    2013-01-01

    A general understanding of the links between atmospheric CO2 concentration and the functioning of the terrestrial biosphere requires not only an understanding of plant trait responses to the ongoing transition to higher CO2 but also the legacy effects of past low CO2. An interesting question is whether the transition from current to higher CO2 can be thought of as a continuation of the past trajectory of low to current CO2 levels. Determining this trajectory requires quantifying the effect sizes of plant response to low CO2. We performed a meta-analysis of low CO2 growth experiments on 34 studies with 54 species. We quantified how plant traits vary at reduced CO2 levels and whether C3 versus C4 and woody versus herbaceous plant species respond differently. At low CO2, plant functioning changed drastically: on average across all species, a 50% reduction in current atmospheric CO2 reduced net photosynthesis by 38%; increased stomatal conductance by 60% and decreased intrinsic water use efficiency by 48%. Total plant dry biomass decreased by 47%, while specific leaf area increased by 17%. Plant types responded similarly: the only significant differences being no increase in SLA for C4 species and a 16% smaller decrease in biomass for woody C3 species at glacial CO2. Quantitative comparison of low CO2 effect sizes to those from high CO2 studies showed that the magnitude of response of stomatal conductance, water use efficiency and SLA to increased CO2 can be thought of as continued shifts along the same line. However, net photosynthesis and dry weight responses to low CO2 were greater in magnitude than to high CO2. Understanding the causes for this discrepancy can lead to a general understanding of the links between atmospheric CO2 and plant responses with relevance for both the past and the future. PMID:24340192

  5. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect

    Tamura, Akitoshi Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased inflammatory cells and IgE, but the others did not. • The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. • Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.

  6. Characterization of the immunogenetic basis of ultraviolet-B light effects on contact hypersensitivity induction.

    PubMed Central

    Kurimoto, I; Streilein, J W

    1994-01-01

    Ultraviolet-B (UVB) light has proven to be deleterious to the skin immune system in mice, and one major consequence is impairment of the induction of contact hypersensitivity (CH) to haptens applied to UVB-exposed skin. It has been shown recently that the damaging effects of UVB on CH are mediated primarily by tumour necrosis factor-alpha (TNF-alpha). Moreover, not all strains of mice are equally susceptible to the deleterious effects of UVB. Mice that develop CH when hapten is applied to UVB-exposed skin are termed UVB-resistant (UVB-R), whereas mice that fail to acquire CH under these circumstances are termed UVB-susceptible (UVB-S). In the present experiments, we have characterized the UVB-susceptibility of numerous, genetically disparate inbred strains of mice by applying dinitrofluorobenzene (DNFB) epicutaneously to normal and to UVB-exposed body wall skin. The results indicate that the intensities of CH responses of these different strains were distributed in a bimodal fashion, with means at 92% and 28.5% of positive control responses. Among the strains with CH values distributed around the higher mean (i.e. UVB-R mice), the intensity of CH responses after UVB irradiation was uniformly greater than 75% of the intensity found among their positive controls. By contrast, among the strains with CH values distributed around the lower mean (i.e. UVB-S mice), the intensity of CH responses after UVB exposure was uniformly less than 60% of the intensity displayed by their positive controls. The phenotypic traits of UVB-S and UVB-R appear, therefore, to be genetically determined. To that end, we provide in this report additional evidence that UVB-S is a polygenically determined trait that is dictated by polymorphisms at a locus within H-2, and at the Lps locus. Resistance to UVB radiation is a recessive trait, and requires homozygosity of resistance alleles at one or both of the two participating loci, whereas UVB-S acts as a dominant trait. Among H-2 congenic strains of mice that are lipopolysaccharide (LPS)-sensitive (Lpsn), UVB radiation impaired the induction of CH to DNFB in all mice except those of the H-2d and H-2a haplotypes. Thus, UVB-susceptibility is dictated by alleles at two, independent genetic loci that can influence transcriptional and translational activity of the Tnf-alpha gene. The potential biological and medical meaning of regulatory polymorphisms governing TNF-alpha production in the skin may be revealed by the recent demonstration that UVB-susceptibility and UVB-resistance are phenotypic traits in humans.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8206509

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

    PubMed Central

    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 subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization. Conclusions: Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved. Citation: Sutton BC; Opp MR. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization. SLEEP 2014;37(3):515-524. PMID:24587574

  8. RNA-Seq reveals complex genetic response to deepwater horizon oil release in Fundulus grandis

    PubMed Central

    2012-01-01

    Background The release of oil resulting from the blowout of the Deepwater Horizon (DH) drilling platform was one of the largest in history discharging more than 189 million gallons of oil and subject to widespread application of oil dispersants. This event impacted a wide range of ecological habitats with a complex mix of pollutants whose biological impact is still not yet fully understood. To better understand the effects on a vertebrate genome, we studied gene expression in the salt marsh minnow Fundulus grandis, which is local to the northern coast of the Gulf of Mexico and is a sister species of the ecotoxicological model Fundulus heteroclitus. To assess genomic changes, we quantified mRNA expression using high throughput sequencing technologies (RNA-Seq) in F. grandis populations in the marshes and estuaries impacted by DH oil release. This application of RNA-Seq to a non-model, wild, and ecologically significant organism is an important evaluation of the technology to quickly assess similar events in the future. Results Our de novo assembly of RNA-Seq data produced a large set of sequences which included many duplicates and fragments. In many cases several of these could be associated with a common reference sequence using blast to query a reference database. This reduced the set of significant genes to 1,070 down-regulated and 1,251 up-regulated genes. These genes indicate a broad and complex genomic response to DH oil exposure including the expected AHR-mediated response and CYP genes. In addition a response to hypoxic conditions and an immune response are also indicated. Several genes in the choriogenin family were down-regulated in the exposed group; a response that is consistent with AH exposure. These analyses are in agreement with oligonucleotide-based microarray analyses, and describe only a subset of significant genes with aberrant regulation in the exposed set. Conclusion RNA-Seq may be successfully applied to feral and extremely polymorphic organisms that do not have an underlying genome sequence assembly to address timely environmental problems. Additionally, the observed changes in a large set of transcript expression levels are indicative of a complex response to the varied petroleum components to which the fish were exposed. PMID:22971268

  9. An Unbiased Genetic Screen Reveals the Polygenic Nature of the Influenza Virus Anti-Interferon Response

    PubMed Central

    Prez-Cidoncha, Maite; Killip, Marian J.; Oliveros, Juan C.; Asensio, Vctor J.; Fernndez, Yolanda; Bengoechea, Jos A.; Randall, Richard E.

    2014-01-01

    ABSTRACT Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space. IMPORTANCE In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response. PMID:24574395

  10. The cortical analysis of speech-specific temporal structure revealed by responses to sound quilts.

    PubMed

    Overath, Tobias; McDermott, Josh H; Zarate, Jean Mary; Poeppel, David

    2015-06-01

    Speech contains temporal structure that the brain must analyze to enable linguistic processing. To investigate the neural basis of this analysis, we used sound quilts, stimuli constructed by shuffling segments of a natural sound, approximately preserving its properties on short timescales while disrupting them on longer scales. We generated quilts from foreign speech to eliminate language cues and manipulated the extent of natural acoustic structure by varying the segment length. Using functional magnetic resonance imaging, we identified bilateral regions of the superior temporal sulcus (STS) whose responses varied with segment length. This effect was absent in primary auditory cortex and did not occur for quilts made from other natural sounds or acoustically matched synthetic sounds, suggesting tuning to speech-specific spectrotemporal structure. When examined parametrically, the STS response increased with segment length up to ?500 ms. Our results identify a locus of speech analysis in human auditory cortex that is distinct from lexical, semantic or syntactic processes. PMID:25984889

  11. The cortical analysis of speech-specific temporal structure revealed by responses to sound quilts

    PubMed Central

    Overath, Tobias; McDermott, Josh H; Zarate, Jean Mary; Poeppel, David

    2016-01-01

    Speech contains temporal structure that the brain must analyze to enable linguistic processing. To investigate the neural basis of this analysis, we used sound quilts, stimuli constructed by shuffling segments of a natural sound, approximately preserving its properties on short timescales while disrupting them on longer scales. We generated quilts from foreign speech to eliminate language cues and manipulated the extent of natural acoustic structure by varying the segment length. Using functional magnetic resonance imaging, we identified bilateral regions of the superior temporal sulcus (STS) whose responses varied with segment length. This effect was absent in primary auditory cortex and did not occur for quilts made from other natural sounds or acoustically matched synthetic sounds, suggesting tuning to speech-specific spectrotemporal structure. When examined parametrically, the STS response increased with segment length up to ~500 ms. Our results identify a locus of speech analysis in human auditory cortex that is distinct from lexical, semantic or syntactic processes. PMID:25984889

  12. Genome Wide Binding Site Analysis Reveals Transcriptional Coactivation of Cytokinin-Responsive Genes by DELLA Proteins

    PubMed Central

    Marín-de la Rosa, Nora; Pfeiffer, Anne; Hill, Kristine; Locascio, Antonella; Bhalerao, Rishikesh P.; Miskolczi, Pal; Grønlund, Anne L.; Wanchoo-Kohli, Aakriti; Thomas, Stephen G.; Bennett, Malcolm J.; Lohmann, Jan U.; Blázquez, Miguel A.; Alabadí, David

    2015-01-01

    The ability of plants to provide a plastic response to environmental cues relies on the connectivity between signaling pathways. DELLA proteins act as hubs that relay environmental information to the multiple transcriptional circuits that control growth and development through physical interaction with transcription factors from different families. We have analyzed the presence of one DELLA protein at the Arabidopsis genome by chromatin immunoprecipitation coupled to large-scale sequencing and we find that it binds at the promoters of multiple genes. Enrichment analysis shows a strong preference for cis elements recognized by specific transcription factor families. In particular, we demonstrate that DELLA proteins are recruited by type-B ARABIDOPSIS RESPONSE REGULATORS (ARR) to the promoters of cytokinin-regulated genes, where they act as transcriptional co-activators. The biological relevance of this mechanism is underpinned by the necessity of simultaneous presence of DELLAs and ARRs to restrict root meristem growth and to promote photomorphogenesis. PMID:26134422

  13. A dynamic and complex monochloramine stress response in Escherichia coli revealed by transcriptome analysis.

    PubMed

    Holder, Diane; Berry, David; Dai, Dongjuan; Raskin, Lutgarde; Xi, Chuanwu

    2013-09-15

    Despite the widespread use of monochloramine in drinking water treatment, there is surprisingly little information about its mode of action. In this study, DNA microarrays were used to investigate the global gene expression of Escherichia coli cells exposed to sub-lethal concentrations of monochloramine, with a focus on temporal dynamics. Genes induced by monochloramine were associated with several stress response functions, including oxidative stress, DNA repair, multidrug efflux, biofilm formation, antibiotic resistance, and cell wall repair. The diversity of functional associations supports a model of monochloramine action involving multiple cellular targets including cell membranes, nucleic acids, and proteins. These data suggest that E. coli responds to monochloramine exposure by activating diverse defense responses rather than a single antioxidant system and the exposure may also induce biofilm formation. The induction of multidrug efflux pumps and specific antibiotic resistance genes further suggests that exposure to monochloramine may contribute to reduced susceptibility to some antibiotics. PMID:23866139

  14. Multivariate genetic analysis of plant responses to water deficit and high temperature revealed contrasting adaptive strategies

    PubMed Central

    Vasseur, Franois; Bontpart, Thibaut; Dauzat, Myriam; Granier, Christine; Vile, Denis

    2014-01-01

    How genetic factors control plant performance under stressful environmental conditions is a central question in ecology and for crop breeding. A multivariate framework was developed to examine the genetic architecture of performance-related traits in response to interacting environmental stresses. Ecophysiological and life history traits were quantified in the Arabidopsis thaliana LerCvi mapping population exposed to constant soil water deficit and high air temperature. The plasticity of the genetic variancecovariance matrix (G-matrix) was examined using mixed-effects models after regression into principal components. Quantitative trait locus (QTL) analysis was performed on the predictors of genotype effects and genotype by environment interactions (GE). Three QTLs previously identified for flowering time had antagonistic GE effects on carbon acquisition and the other traits (phenology, growth, leaf morphology, and transpiration). This resulted in a size-dependent response of water use efficiency (WUE) to high temperature but not soil water deficit, indicating that most of the plasticity of carbon acquisition and WUE to temperature is controlled by the loci that control variation of development, size, growth, and transpiration. A fourth QTL, MSAT2.22, controlled the response of carbon acquisition to specific combinations of watering and temperature irrespective of plant size and development, growth, and transpiration rate, which resulted in size-independent plasticity of WUE. These findings highlight how the strategies to optimize plant performance may differ in response to water deficit and high temperature (or their combination), and how different GE effects could be targeted to improve plant tolerance to these stresses. PMID:25246443

  15. Multivariate genetic analysis of plant responses to water deficit and high temperature revealed contrasting adaptive strategies.

    PubMed

    Vasseur, Franois; Bontpart, Thibaut; Dauzat, Myriam; Granier, Christine; Vile, Denis

    2014-12-01

    How genetic factors control plant performance under stressful environmental conditions is a central question in ecology and for crop breeding. A multivariate framework was developed to examine the genetic architecture of performance-related traits in response to interacting environmental stresses. Ecophysiological and life history traits were quantified in the Arabidopsis thaliana Ler Cvi mapping population exposed to constant soil water deficit and high air temperature. The plasticity of the genetic variance-covariance matrix (G-matrix) was examined using mixed-effects models after regression into principal components. Quantitative trait locus (QTL) analysis was performed on the predictors of genotype effects and genotype by environment interactions (G E). Three QTLs previously identified for flowering time had antagonistic G E effects on carbon acquisition and the other traits (phenology, growth, leaf morphology, and transpiration). This resulted in a size-dependent response of water use efficiency (WUE) to high temperature but not soil water deficit, indicating that most of the plasticity of carbon acquisition and WUE to temperature is controlled by the loci that control variation of development, size, growth, and transpiration. A fourth QTL, MSAT2.22, controlled the response of carbon acquisition to specific combinations of watering and temperature irrespective of plant size and development, growth, and transpiration rate, which resulted in size-independent plasticity of WUE. These findings highlight how the strategies to optimize plant performance may differ in response to water deficit and high temperature (or their combination), and how different G E effects could be targeted to improve plant tolerance to these stresses. PMID:25246443

  16. Proteomics reveals a core molecular response of Pseudomonas putida F1 to acute chromate challenge

    PubMed Central

    2010-01-01

    Background Pseudomonas putida is a model organism for bioremediation because of its remarkable metabolic versatility, extensive biodegradative functions, and ubiquity in contaminated soil environments. To further the understanding of molecular pathways responding to the heavy metal chromium(VI) [Cr(VI)], the proteome of aerobically grown, Cr(VI)-stressed P. putida strain F1 was characterized within the context of two disparate nutritional environments: rich (LB) media and minimal (M9L) media containing lactate as the sole carbon source. Results Growth studies demonstrated that F1 sensitivity to Cr(VI) was impacted substantially by nutrient conditions, with a carbon-source-dependent hierarchy (lactate > glucose >> acetate) observed in minimal media. Two-dimensional HPLC-MS/MS was employed to identify differential proteome profiles generated in response to 1 mM chromate under LB and M9L growth conditions. The immediate response to Cr(VI) in LB-grown cells was up-regulation of proteins involved in inorganic ion transport, secondary metabolite biosynthesis and catabolism, and amino acid metabolism. By contrast, the chromate-responsive proteome derived under defined minimal growth conditions was characterized predominantly by up-regulated proteins related to cell envelope biogenesis, inorganic ion transport, and motility. TonB-dependent siderophore receptors involved in ferric iron acquisition and amino acid adenylation domains characterized up-regulated systems under LB-Cr(VI) conditions, while DNA repair proteins and systems scavenging sulfur from alternative sources (e.g., aliphatic sulfonates) tended to predominate the up-regulated proteome profile obtained under M9L-Cr(VI) conditions. Conclusions Comparative analysis indicated that the core molecular response to chromate, irrespective of the nutritional conditions tested, comprised seven up-regulated proteins belonging to six different functional categories including transcription, inorganic ion transport/metabolism, and amino acid transport/metabolism. These proteins might potentially serve as indicators of chromate stress in natural microbial communities. PMID:20482812

  17. Perturbation-response scanning reveals ligand entry-exit mechanisms of ferric binding protein.

    PubMed

    Atilgan, Canan; Atilgan, Ali Rana

    2009-10-01

    We study apo and holo forms of the bacterial ferric binding protein (FBP) which exhibits the so-called ferric transport dilemma: it uptakes iron from the host with remarkable affinity, yet releases it with ease in the cytoplasm for subsequent use. The observations fit the "conformational selection" model whereby the existence of a weakly populated, higher energy conformation that is stabilized in the presence of the ligand is proposed. We introduce a new tool that we term perturbation-response scanning (PRS) for the analysis of remote control strategies utilized. The approach relies on the systematic use of computational perturbation/response techniques based on linear response theory, by sequentially applying directed forces on single-residues along the chain and recording the resulting relative changes in the residue coordinates. We further obtain closed-form expressions for the magnitude and the directionality of the response. Using PRS, we study the ligand release mechanisms of FBP and support the findings by molecular dynamics simulations. We find that the residue-by-residue displacements between the apo and the holo forms, as determined from the X-ray structures, are faithfully reproduced by perturbations applied on the majority of the residues of the apo form. However, once the stabilizing ligand (Fe) is integrated to the system in holo FBP, perturbing only a few select residues successfully reproduces the experimental displacements. Thus, iron uptake by FBP is a favored process in the fluctuating environment of the protein, whereas iron release is controlled by mechanisms including chelation and allostery. The directional analysis that we implement in the PRS methodology implicates the latter mechanism by leading to a few distant, charged, and exposed loop residues. Upon perturbing these, irrespective of the direction of the operating forces, we find that the cap residues involved in iron release are made to operate coherently, facilitating release of the ion. PMID:19851447

  18. Phosphoproteomic Analyses Reveal Early Signaling Events in the Osmotic Stress Response1[W][OPEN

    PubMed Central

    E. Stecker, Kelly; Minkoff, Benjamin B.; Sussman, Michael R.

    2014-01-01

    Elucidating how plants sense and respond to water loss is important for identifying genetic and chemical interventions that may help sustain crop yields in water-limiting environments. Currently, the molecular mechanisms involved in the initial perception and response to dehydration are not well understood. Modern mass spectrometric methods for quantifying changes in the phosphoproteome provide an opportunity to identify key phosphorylation events involved in this process. Here, we have used both untargeted and targeted isotope-assisted mass spectrometric methods of phosphopeptide quantitation to characterize proteins in Arabidopsis (Arabidopsis thaliana) whose degree of phosphorylation is rapidly altered by hyperosmotic treatment. Thus, protein phosphorylation events responsive to 5 min of 0.3 m mannitol treatment were first identified using 15N metabolic labeling and untargeted mass spectrometry with a high-resolution ion-trap instrument. The results from these discovery experiments were then validated using targeted Selected Reaction Monitoring mass spectrometry with a triple quadrupole. Targeted Selected Reaction Monitoring experiments were conducted with plants treated under nine different environmental perturbations to determine whether the phosphorylation changes were specific for osmosignaling or involved cross talk with other signaling pathways. The results indicate that regulatory proteins such as members of the mitogen-activated protein kinase family are specifically phosphorylated in response to osmotic stress. Proteins involved in 5′ messenger RNA decapping and phosphatidylinositol 3,5-bisphosphate synthesis were also identified as targets of dehydration-induced phosphoregulation. The results of these experiments demonstrate the utility of targeted phosphoproteomic analysis in understanding protein regulation networks and provide new insight into cellular processes involved in the osmotic stress response. PMID:24808101

  19. Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

    PubMed Central

    Haase, David; Rieger, Jennifer K.; Witten, Anika; Stoll, Monika; Bornberg-Bauer, Erich; Kalbe, Martin; Reusch, Thorsten B. H.

    2014-01-01

    Vertebrate innate immunity is the first line of defense against an invading pathogen and has long been assumed to be largely unspecific with respect to parasite/pathogen species. However, recent phenotypic evidence suggests that immunogenetic variation, i.e. allelic variability in genes associated with the immune system, results in host-parasite genotype-by-genotype interactions and thus specific innate immune responses. Immunogenetic variation is common in all vertebrate taxa and this reflects an effective immunological function in complex environments. However, the underlying variability in host gene expression patterns as response of innate immunity to within-species genetic diversity of macroparasites in vertebrates is unknown. We hypothesized that intra-specific variation among parasite genotypes must be reflected in host gene expression patterns. Here we used high-throughput RNA-sequencing to examine the effect of parasite genotypes on gene expression patterns of a vertebrate host, the three-spined stickleback (Gasterosteus aculeatus). By infecting naïve fish with distinct trematode genotypes of the species Diplostomum pseudospathaceum we show that gene activity of innate immunity in three-spined sticklebacks depended on the identity of an infecting macroparasite genotype. In addition to a suite of genes indicative for a general response against the trematode we also find parasite-strain specific gene expression, in particular in the complement system genes, despite similar infection rates of single clone treatments. The observed discrepancy between infection rates and gene expression indicates the presence of alternative pathways which execute similar functions. This suggests that the innate immune system can induce redundant responses specific to parasite genotypes. PMID:25254967

  20. Correlation of transcriptomic responses and metal bioaccumulation in Mytilus edulis L. reveals early indicators of stress.

    PubMed

    Poynton, Helen C; Robinson, William E; Blalock, Bonnie J; Hannigan, Robyn E

    2014-10-01

    Marine biomonitoring programs in the U.S. and Europe have historically relied on monitoring tissue concentrations of bivalves to monitor contaminant levels and ecosystem health. By integrating 'omic methods with these tissue residue approaches we can uncover mechanistic insight to link tissue concentrations to potential toxic effects. In an effort to identify novel biomarkers and better understand the molecular toxicology of metal bioaccumulation in bivalves, we exposed the blue mussel, Mytilus edulis L., to sub-lethal concentrations (0.54 μM) of cadmium, lead, and a Cd+Pb mixture. Metal concentrations were measured in gill tissues at 1, 2, and 4 weeks, and increased linearly over the 4 week duration. In addition, there was evidence that Pb interfered with Cd uptake in the mixture treatment. Using a 3025 sequence microarray for M. edulis, we performed transcriptomic analysis, identifying 57 differentially expressed sequences. Hierarchical clustering of these sequences successfully distinguished the different treatment groups demonstrating that the expression profiles were reproducible among the treatments. Enrichment analysis of gene ontology terms identified several biological processes that were perturbed by the treatments, including nucleoside phosphate biosynthetic processes, mRNA metabolic processes, and response to stress. To identify transcripts whose expression level correlated with metal bioaccumulation, we performed Pearson correlation analysis. Several transcripts correlated with gill metal concentrations including mt10, mt20, and contig 48, an unknown transcript containing a wsc domain. In addition, three transcripts directly involved in the unfolded protein response (UPR) were induced in the metal treatments at 2 weeks and were further up-regulated at 4 weeks. Overall, correlation of tissue concentrations and gene expression responses indicates that as mussels accumulate higher concentrations of metals, initial stress responses are mobilized to protect tissues. However, given the role of UPR in apoptosis, it serves as an early indicator of stress, which once overwhelmed will result in adverse physiological effects. PMID:25016106

  1. Individual plastic responses by males to rivals reveal mismatches between behaviour and fitness outcomes

    PubMed Central

    Bretman, Amanda; Westmancoat, James D.; Gage, Matthew J. G.; Chapman, Tracey

    2012-01-01

    Plasticity in behaviour is of fundamental significance when environments are variable. Such plasticity is particularly important in the context of rapid changes in the socio-sexual environment. Males can exhibit adaptive plastic responses to variation in the overall level of reproductive competition. However, the extent of behavioural flexibility within individuals, and the degree to which rapidly changing plastic responses map onto fitness are unknown. We addressed this by determining the behaviour and fitness profiles of individual Drosophila melanogaster males subjected to up to three episodes of exposure to rivals or no rivals, in all combinations. Behaviour (mating duration) was remarkably sensitive to the level of competition and fully reversible, suggesting that substantial costs arise from the incorrect expression of even highly flexible behaviour. However, changes in mating duration matched fitness outcomes (offspring number) only in scenarios in which males experienced zero then high competition. Following the removal of competition, mating duration, but not offspring production, decreased to below control levels. This indicates that the benefit of increasing reproductive investment when encountering rivals may exceed that of decreasing investment when rivals disappear. Such asymmetric fitness benefits and mismatches with behavioural responses are expected to exert strong selection on the evolution of plasticity. PMID:22438501

  2. Genomic regions associated with the nitrogen limitation response revealed in a global wheat core collection.

    PubMed

    Bordes, Jacques; Ravel, C; Jaubertie, J P; Duperrier, B; Gardet, O; Heumez, E; Pissavy, A L; Charmet, G; Le Gouis, J; Balfourier, F

    2013-03-01

    Modern wheat (Triticum aestivum L.) varieties in Western Europe have mainly been bred, and selected in conditions where high levels of nitrogen-rich fertilizer are applied. However, high input crop management has greatly increased the risk of nitrates leaching into groundwater with negative impacts on the environment. To investigate wheat nitrogen tolerance characteristics that could be adapted to low input crop management, we supplied 196 accessions of a wheat core collection of old and modern cultivars with high or moderate amounts of nitrogen fertilizer in an experimental network consisting of three sites and 2years. The main breeding traits were assessed including grain yield and grain protein content. The response to nitrogen level was estimated for grain yield and grain number per m(2) using both the difference and the ratio between performance at the two input levels and the slope of joint regression. A large variability was observed for all the traits studied and the response to nitrogen level. Whole genome association mapping was carried out using 899 molecular markers taking into account the five ancestral group structure of the collection. We identified 54 main regions involving almost all chromosomes that influence yield and its components, plant height, heading date and grain protein concentration. Twenty-three regions, including several genes, spread over 16 chromosomes were involved in the response to nitrogen level. These chromosomal regions may be good candidates to be used in breeding programs to improve the performance of wheat varieties at moderate nitrogen input levels. PMID:23192671

  3. Exposure to natural pathogens reveals costly aphid response to fungi but not bacteria.

    PubMed

    Barribeau, Seth M; Parker, Benjamin J; Gerardo, Nicole M

    2014-02-01

    Immune responses are costly, causing trade-offs between defense and other host life history traits. Aphids present a special system to explore the costs associated with immune activation since they are missing several humoral and cellular mechanisms thought important for microbial resistance, and it is unknown whether they have alternative, novel immune responses to deal with microbial threat. Here we expose pea aphids to an array of heat-killed natural pathogens, which should stimulate immune responses without pathogen virulence, and measure changes in life-history traits. We find significant reduction in lifetime fecundity upon exposure to two fungal pathogens, but not to two bacterial pathogens. This finding complements recent genomic and immunological studies indicating that pea aphids are missing mechanisms important for bacterial resistance, which may have important implications for how aphids interact with their beneficial bacterial symbionts. In general, recent exploration of the immune systems of non-model invertebrates has called into question the generality of our current picture of insect immunity. Our data highlight that taking an ecological approach and measuring life-history traits to a broad array of pathogens provides valuable information that can complement traditional approaches. PMID:24634732

  4. Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge

    PubMed Central

    Perreault, Maude; Zulyniak, Michael A.; Britz-McKibbin, Philip; Mutch, David M.

    2015-01-01

    Objective To determine if metabolically healthy obese (MHO) individuals have a different metabolic response to a standardized diet compared to lean healthy (LH) and metabolically unhealthy obese (MUO) individuals. Methods Thirty adults (35–70 yrs) were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal). Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs) and derivatives, and fatty acids (FAs). Results The postprandial response (i.e., area under the curve, AUC) for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05). Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, γ-linolenic acid, arachidonic acid) showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA) and FAs (e.g., saturated myristic and palmitic acids) were found to correlate with glucose and insulin AUC. Conclusion MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals. PMID:26274804

  5. Metabolomic and physiological responses reveal multi-phasic acclimation of Arabidopsis thaliana to chronic UV radiation.

    PubMed

    Lake, Janice A; Field, Katie J; Davey, Matthew P; Beerling, David J; Lomax, Barry H

    2009-10-01

    Biochemical changes in vivo and pathway interactions were investigated using integrated physiological and metabolic responses of Arabidopsis thaliana L. to ultraviolet (UV) radiation (280-400 nm) at 9.96 kJ m(-2) d(-1) over the entire life cycle from seed to seed (8 weeks). Columbia-0 (Col-0) and a UV-B sensitive accession (fah-1) showed significant (P < 0.001) reductions in leaf growth after 6 weeks. Col-0 recovered growth after 8 weeks, with recovery corresponding to a switch from production of phenylpropanoids to flavonoids. fah-1 failed to recover, indicating that sinapate production is an essential component of recovery. Epidermal features show that UV radiation caused significant (P < 0.001) increases in trichome density, which may act as a structural defence response. Stomatal indices showed a significant (P < 0.0001) reduction in Col-0 and a significant (P < 0.001) increase in fah-1. Epidermal cell density was significantly increased under UV radiation on the abaxial leaf surface, suggesting that that a fully functioning phenylpropanoid pathway is a requirement for cell expansion and leaf development. Despite wild-type acclimation, the costs of adaptation lead to reduced plant fitness by decreasing flower numbers and total seed biomass. A multi-phasic acclimation to UV radiation and the induction of specific metabolites link stress-induced biochemical responses to enhanced acclimation. PMID:19558413

  6. Serum Profiling of Rat Dermal Exposure to JP-8 Fuel Reveals an Acute-Phase Response.

    PubMed

    Larabee, Jason L; Hocker, James R; Cheung, John Y; Gallucci, Randle M; Hanas, Jay S

    2008-01-01

    ABSTRACT Dermal exposure to JP-8 petroleum jet fuel leads to toxicological responses in humans and rodents. Serum profiling is a molecular analysis of changes in the levels of serum proteins and other molecules in response to changes in physiology. This present study utilizes serum profiling approaches to examine biomolecular changes in the sera of rats exposed to dermal applications of JP-8 (jet propulsion fuel-8). Using gel electrophoresis and electrospray ionization (ESI) mass spectrometry (MS), levels of serum proteins as well as low-mass constituents were found to change after dermal exposures to JP-8. The serum protein levels altered included the acute-phase response proteins haptoglobin, ceruloplasmin, alpha(1)-inhibitor III, and apolipoprotein A-IV. Haptoglobin levels increased after a 1-day JP-8 dermal exposure and continued to increase through 7 days of exposure. Ceruloplasmin levels increased after 5 days of exposure. Serum alpha(1)-inhibitor III was reduced after a 1-day exposure and the depletion continued after 7 days of exposure. Apolipoprotein A-IV increased after a 1-day exposure and then returned to basal levels after 3- and 5-day exposures of JP-8. Levels of the acute-phase protein alpha(2)-macroglobulin were found to not vary over these time course studies. Using ESI-MS analysis directly on the sera from rats exposed to dermal JP-8, low-mass sera constituents were found to correlate with control (acetone) or JP-8 exposure. PMID:20020890

  7. Exposure to natural pathogens reveals costly aphid response to fungi but not bacteria

    PubMed Central

    Barribeau, Seth M; Parker, Benjamin J; Gerardo, Nicole M

    2014-01-01

    Immune responses are costly, causing trade-offs between defense and other host life history traits. Aphids present a special system to explore the costs associated with immune activation since they are missing several humoral and cellular mechanisms thought important for microbial resistance, and it is unknown whether they have alternative, novel immune responses to deal with microbial threat. Here we expose pea aphids to an array of heat-killed natural pathogens, which should stimulate immune responses without pathogen virulence, and measure changes in life-history traits. We find significant reduction in lifetime fecundity upon exposure to two fungal pathogens, but not to two bacterial pathogens. This finding complements recent genomic and immunological studies indicating that pea aphids are missing mechanisms important for bacterial resistance, which may have important implications for how aphids interact with their beneficial bacterial symbionts. In general, recent exploration of the immune systems of non-model invertebrates has called into question the generality of our current picture of insect immunity. Our data highlight that taking an ecological approach and measuring life-history traits to a broad array of pathogens provides valuable information that can complement traditional approaches. PMID:24634732

  8. A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides

    PubMed Central

    Voelz, Kerstin; Gratacap, Remi L.; Wheeler, Robert T.

    2015-01-01

    ABSTRACT Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole-animal model system will contribute greatly to the study of molecular mechanisms involved in the interaction of the host innate immune system with fungal spores during mucormycosis. PMID:26398938

  9. Atypical presentation of fever as hypersensitivity reaction to oxaliplatin.

    PubMed

    Khurana, Arushi; Mitsis, Demytra; Kowlgi, Gurukripa N; Holle, Lisa M; Clement, Jessica M

    2016-04-01

    Oxaliplatin, a third-generation, platinum-based agent is widely used, most commonly in the FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) regimen, which is the first-line therapy in metastatic colorectal adenocarcinoma and adjuvant chemotherapy in stage III colorectal cancer. Platinum-based products are well known for causing hypersensitivity reactions. Fever associated with oxaliplatin-hypersensitivity reactions typically follows a specific pattern. It usually starts during the oxaliplatin infusion or immediately after (within hours instead of days) and happens after several administrations (mean 2-25) with unpredictable clinical presentations. We report a case of oxaliplatin-induced hypersensitivity reaction manifesting as fever but with unusual presentation than the aforementioned features. PMID:25361599

  10. Dentin Hypersensitivity: Etiology, Diagnosis and Treatment; A Literature Review

    PubMed Central

    Davari, AR; Ataei, E; Assarzadeh, H

    2013-01-01

    The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms “dentin*”, “tooth”, “teeth”, “hypersensit*”, “desensitiz*”. Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used. PMID:24724135

  11. Colloidal silica-induced hypersensitivity: myth or reality.

    PubMed

    Ben Fredj, Nadia; Ben Fadhel, Najeh; Chaabane, Amel; Chadly, Zohra; Ben Romdhane, Haifa; Boughattas, Abderrazzek; Aouam, Karim

    2016-02-01

    Background Many excipients have been reported to induce drug hypersensitivity (e.g. colouring additives, preservatives). Colloidal silica has never been reported to induce drug hypersensitivity reactions. Case report We report herein a 40-year-old patient who developed a skin eruption 2 days after Voltarene(®) (diclofenac) intake, confirmed by a positive patch test. Investigation of cross reactivity, assessed by patch testing to other non steroidal anti-inflammatory drugs, have showed a positive reaction only to piroxicam (Piroxen(®)), ketoprofen (Oki(®)) and indometacin (Indocid(®)). A hypersensivity to colloidal silica, a common excipient, was suspected. A patch test to this compound was performed showing a positive reaction. Conclusion Colloidal silica, a compound widely used in drug manufacturing, could be another culprit excipient in inducing skin hypersensitivity reactions. PMID:26613737

  12. Menthol suppresses laryngeal C-fiber hypersensitivity to cigarette smoke in a rat model of gastroesophageal reflux disease: the role of TRPM8.

    PubMed

    Liu, Bi-Yu; Lin, Yu-Jung; Lee, Hung-Fu; Ho, Ching-Yin; Ruan, Ting; Kou, Yu Ru

    2015-03-01

    Patients with gastroesophageal reflux disease (GERD) display enhanced laryngeal reflex reactivity to stimuli that may be due to sensitization of the laryngeal C-fibers by acid and pepsin. Menthol, a ligand of transient receptor potential melastatin-8 (TRPM8), relieves throat irritation. However, the possibility that GERD induces laryngeal C-fiber hypersensitivity to cigarette smoke (CS) and that menthol suppresses this event has not been investigated. We delivered CS into functionally isolated larynxes of 160 anesthetized rats. Laryngeal pH 5-pepsin treatment, but not pH 5-denatured pepsin, augmented the apneic response to CS, which was blocked by denervation or perineural capsaicin treatment (a procedure that blocks the conduction of C fibers) of the superior laryngeal nerves. This augmented apnea was partially attenuated by capsazepine [an transient receptor potential vanilloid 1 (TRPV1) antagonist], SB-366791 (a TRPV1 antagonist), and HC030031 [a transient receptor potential ankyrin 1 (TRPA1) antagonist] and was completely prevented by a combination of TRPV1 and TRPA1 antagonists. Local application of menthol significantly suppressed the augmented apnea and this effect was reversed by pretreatment with AMTB (a TRPM8 antagonist). Our electrophysiological studies consistently revealed that laryngeal pH 5-pepsin treatment increased the sensitivity of laryngeal C-fibers to CS. Likewise, menthol suppressed this laryngeal C-fiber hypersensitivity and its effect could be reversed by pretreatment with AMTB. Our results suggest that laryngeal pH 5-pepsin treatment increases sensitivity to CS of both TRPV1 and TRPA1, which are presumably located at the terminals of laryngeal C-fibers. This sensory sensitization leads to enhanced laryngeal reflex reactivity and augmentation of the laryngeal C-fiber responses to CS, which can be suppressed by menthol acting via TRPM8. PMID:25539933

  13. Metagenomics reveals sediment microbial community response to Deepwater Horizon oil spill.

    PubMed

    Mason, Olivia U; Scott, Nicole M; Gonzalez, Antonio; Robbins-Pianka, Adam; Blum, Jacob; Kimbrel, Jeffrey; Bouskill, Nicholas J; Prestat, Emmanuel; Borglin, Sharon; Joyner, Dominique C; Fortney, Julian L; Jurelevicius, Diogo; Stringfellow, William T; Alvarez-Cohen, Lisa; Hazen, Terry C; Knight, Rob; Gilbert, Jack A; Jansson, Janet K

    2014-07-01

    The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ?4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences.