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Sample records for hypersensitive response reveals

  1. Early events in plant hypersensitive response leaves revealed by IR thermography

    NASA Astrophysics Data System (ADS)

    Boccara, Martine; Boue, Christine; De Paepe, Rosine; Boccara, Albert C.

    2001-10-01

    Infrared thermography is used to reveal the establishment of Erwinia amylovora harpin-induced hypersensitive response (HR) in Nicotiana sylvestris leaves. We observed a decrease in temperature (1-2 degree(s)C) in the harpin infiltrated zone, correlated with an increase in stomatal opening, strongly suggesting that the temperature decrease is due to higher transpiration rate. IRT experiments were conducted in a laboratory environment and could be widely applied for genotype screening and monitoring drug effects.

  2. Virus-induced gene silencing reveals signal transduction components required for the Pvr9-mediated hypersensitive response in Nicotiana benthamiana.

    PubMed

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

    2016-08-01

    Resistance to pathogens mediated by plant resistance (R) proteins requires different signaling transduction components and pathways. Our previous studies revealed that a potyvirus resistance gene in pepper, Pvr9, confers a hypersensitive response (HR) to pepper mottle virus in Nicotiana benthamiana. Our results show that the Pvr9-mediated HR against pepper mottle virus infection requires HSP90, SGT1, NDR1, but not EDS1. These results suggest that the Pvr9-mediated HR is possibly related to the SA pathway but not the ET, JA, ROS or NO pathways.

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

    PubMed

    Orłowska, Elzbieta; Basile, Alessio; Kandzia, Izabela; Llorente, Briardo; Kirk, Hanne Grethe; Cvitanich, Cristina

    2012-08-01

    The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots and roots grafted with the susceptible Bintje cultivar as well as non-grafted different parts of Sarpo Mira plants were inoculated with P. infestans. The progress of the infection and the number of HR lesions were monitored, and the regulation of PR genes was compared in detached and attached leaves. Additionally, the antimicrobial activity of plant extracts was assessed. The presented data show that roots are needed to achieve full pathogen resistance, that the removal of meristems in detached leaves inhibits the formation of HR lesions, that PR genes are differentially regulated in detached leaves compared with leaves of whole plants, and that antimicrobial compounds accumulate in leaves and roots of Sarpo Mira plants challenged with P. infestans. While meristems are necessary for the formation of HR lesions, the roots of Sarpo Mira plants participate in the production of defence-associated compounds that increase systemic resistance. Based on the literature and on the presented results, a model is proposed for mechanisms involved in Sarpo Mira resistance that may apply to other resistant potato cultivars.

  4. Quantitative phosphoproteomics of tomato mounting a hypersensitive response reveals a swift suppression of photosynthetic activity and a differential role for hsp90 isoforms.

    PubMed

    Stulemeijer, Iris J E; Joosten, Matthieu H A J; Jensen, Ole N

    2009-03-01

    An important mechanism by which plants defend themselves against pathogens is the rapid execution of a hypersensitive response (HR). Tomato plants containing the Cf-4 resistance gene mount an HR that relies on the activation of phosphorylation cascades, when challenged with the Avr4 elicitor secreted by the pathogenic fungus Cladosporium fulvum. Phosphopeptides were isolated from tomato seedlings expressing both Cf-4 and Avr4 using titanium dioxide columns and LC-MS/MS analysis led to the identification of 50 phosphoproteins, most of which have not been described in tomato before. Phosphopeptides were quantified using a label-free approach based on the MS peak areas. We identified 12 phosphopeptides for which the abundance changed upon HR initiation, as compared to control seedlings. Our results suggest that photosynthetic activity is specifically suppressed in a phosphorylation-dependent way during the very early stages of HR development. In addition, phosphopeptides originating from four Hsp90 isoforms exhibited altered abundances in Cf-4/Avr4 seedlings compared to control seedlings, suggesting that the isoforms of this chaperone protein have a different function in defense signaling. We show that label-free relative quantification of the phosphoproteome of complex samples is feasible, allowing extension of our knowledge on the general physiology and defense signaling of plants mounting the HR. PMID:19178300

  5. 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.

  6. 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

  7. Microtubule Polymerization Functions in Hypersensitive Response and Accumulation of H2O2 in Wheat Induced by the Stripe Rust.

    PubMed

    Wang, Juan; Wang, Yang; Liu, Xinjie; Xu, Yuanliu; Ma, Qing

    2016-01-01

    The plant cytoskeleton, including microtubules and microfilaments, is one of the important factors in determining the polarity of cell division and growth, as well as the interaction of plants with invading pathogens. In defense responses of wheat against the stripe rust (Puccinia striiformis f. sp. tritici) infection, hypersensitive response is the most crucial event to prevent the spread of pathogens. In order to reveal the effect of microtubules on the hypersensitive cell death and H2O2 accumulation in the interaction of wheat (Triticum aestivum) cv. Suwon 11 with an incompatible race, CYR23, wheat leaves were treated with microtubule inhibitor, oryzalin, before inoculation. The results showed that the frequency of infection sites with hypersensitive response occurrence was significantly reduced, and hypersensitive cell death in wheat leaves was suppressed compared to the control. In addition, the frequency and the incidence of infected cells with H2O2 accumulation were also reduced after the treatment with oryzalin. Those results indicated that microtubules are related to hypersensitive response and H2O2 accumulation in wheat induced by the stripe rust, and depolymerization of microtubules reduces the resistance of plants to pathogen infection in incompatible interaction, suggesting that microtubules play a potential role in the expression of resistance of wheat against the stripe rust fungus.

  8. Microtubule Polymerization Functions in Hypersensitive Response and Accumulation of H2O2 in Wheat Induced by the Stripe Rust.

    PubMed

    Wang, Juan; Wang, Yang; Liu, Xinjie; Xu, Yuanliu; Ma, Qing

    2016-01-01

    The plant cytoskeleton, including microtubules and microfilaments, is one of the important factors in determining the polarity of cell division and growth, as well as the interaction of plants with invading pathogens. In defense responses of wheat against the stripe rust (Puccinia striiformis f. sp. tritici) infection, hypersensitive response is the most crucial event to prevent the spread of pathogens. In order to reveal the effect of microtubules on the hypersensitive cell death and H2O2 accumulation in the interaction of wheat (Triticum aestivum) cv. Suwon 11 with an incompatible race, CYR23, wheat leaves were treated with microtubule inhibitor, oryzalin, before inoculation. The results showed that the frequency of infection sites with hypersensitive response occurrence was significantly reduced, and hypersensitive cell death in wheat leaves was suppressed compared to the control. In addition, the frequency and the incidence of infected cells with H2O2 accumulation were also reduced after the treatment with oryzalin. Those results indicated that microtubules are related to hypersensitive response and H2O2 accumulation in wheat induced by the stripe rust, and depolymerization of microtubules reduces the resistance of plants to pathogen infection in incompatible interaction, suggesting that microtubules play a potential role in the expression of resistance of wheat against the stripe rust fungus. PMID:27610380

  9. Microtubule Polymerization Functions in Hypersensitive Response and Accumulation of H2O2 in Wheat Induced by the Stripe Rust

    PubMed Central

    Liu, Xinjie; Xu, Yuanliu

    2016-01-01

    The plant cytoskeleton, including microtubules and microfilaments, is one of the important factors in determining the polarity of cell division and growth, as well as the interaction of plants with invading pathogens. In defense responses of wheat against the stripe rust (Puccinia striiformis f. sp. tritici) infection, hypersensitive response is the most crucial event to prevent the spread of pathogens. In order to reveal the effect of microtubules on the hypersensitive cell death and H2O2 accumulation in the interaction of wheat (Triticum aestivum) cv. Suwon 11 with an incompatible race, CYR23, wheat leaves were treated with microtubule inhibitor, oryzalin, before inoculation. The results showed that the frequency of infection sites with hypersensitive response occurrence was significantly reduced, and hypersensitive cell death in wheat leaves was suppressed compared to the control. In addition, the frequency and the incidence of infected cells with H2O2 accumulation were also reduced after the treatment with oryzalin. Those results indicated that microtubules are related to hypersensitive response and H2O2 accumulation in wheat induced by the stripe rust, and depolymerization of microtubules reduces the resistance of plants to pathogen infection in incompatible interaction, suggesting that microtubules play a potential role in the expression of resistance of wheat against the stripe rust fungus.

  10. Microtubule Polymerization Functions in Hypersensitive Response and Accumulation of H2O2 in Wheat Induced by the Stripe Rust

    PubMed Central

    Liu, Xinjie; Xu, Yuanliu

    2016-01-01

    The plant cytoskeleton, including microtubules and microfilaments, is one of the important factors in determining the polarity of cell division and growth, as well as the interaction of plants with invading pathogens. In defense responses of wheat against the stripe rust (Puccinia striiformis f. sp. tritici) infection, hypersensitive response is the most crucial event to prevent the spread of pathogens. In order to reveal the effect of microtubules on the hypersensitive cell death and H2O2 accumulation in the interaction of wheat (Triticum aestivum) cv. Suwon 11 with an incompatible race, CYR23, wheat leaves were treated with microtubule inhibitor, oryzalin, before inoculation. The results showed that the frequency of infection sites with hypersensitive response occurrence was significantly reduced, and hypersensitive cell death in wheat leaves was suppressed compared to the control. In addition, the frequency and the incidence of infected cells with H2O2 accumulation were also reduced after the treatment with oryzalin. Those results indicated that microtubules are related to hypersensitive response and H2O2 accumulation in wheat induced by the stripe rust, and depolymerization of microtubules reduces the resistance of plants to pathogen infection in incompatible interaction, suggesting that microtubules play a potential role in the expression of resistance of wheat against the stripe rust fungus. PMID:27610380

  11. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli

    PubMed Central

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-01-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli. PMID:25140103

  12. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli.

    PubMed

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-07-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli.

  13. 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.

  14. 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

  15. Cutaneous hypersensitivity responses to Rhipicephalus tick larval antigens in pre-sensitized cattle.

    PubMed

    Marufu, M C; Chimonyo, M; Mans, B J; Dzama, K

    2013-06-01

    Nguni cattle are known to be more resistant to ticks than Bonsmara cattle, even if the immunological mechanisms responsible for this phenomenon are not fully understood. Cutaneous hypersensitivity responses to unfed larval extracts (ULE) of the ticks Rhipicephalus decoloratus and Rhipicephalus microplus were investigated in Nguni and Bonsmara cattle to improve knowledge on the immunity to ticks. Hypersensitivity reactions were induced by intradermal inoculation of 0.1ml of ULE of R. decoloratus and R. microplus ticks (50μg protein) in the right and left ear, respectively, of 8-9-month-old Nguni (n=11) and Bonsmara (n=9) heifers. Ear thickness was measured using callipers before and 0.5, 1, 6, 24, 48, and 72h post inoculation (PI). Bonsmara cattle showed a more intense immediate reaction with maximum response at 1h PI and no delayed hypersensitivity reaction. Nguni heifers, conversely, presented a less intense immediate reaction with maximum response at 1h PI, and a delayed hypersensitivity reaction at 72h PI. Reactions to R. decoloratus ULE produced a more intense skin response than to R. microplus in both breeds at all time intervals. Nguni cattle showed lower tick infestation indicating higher tick resistance than Bonsmara cattle. Delayed hypersensitivity reaction could be associated with superior tick resistance in the Nguni breed, while immediate hypersensitivity reaction could be associated with increased tick susceptibility in the Bonsmara breed. This study indicates the need for further investigations on the correlation of tick resistance and cellular immune responses to tick infestation in Nguni cattle. PMID:23453577

  16. Isolation, identification, and characterization of clones encoding antigens responsible for peanut hypersensitivity.

    PubMed

    Burks, A W; Cockrell, G; Stanley, J S; Helm, R M; Bannon, G A

    1995-01-01

    Peanut allergy is a significant health problem because of the frequency, the potential severity, and the chronicity of the allergic sensitivity. Serum IgE from patients with documented peanut hypersensitivity reactions and a peanut cDNA expression library were used to identify clones that encode peanut allergens. One of the major peanut allergens, Ara h I, was selected from these clones using Ara h I-specific oligonucleotides and polymerase chain reaction technology. The Ara h I clone identified a 2.3-kb mRNA species on a Northern blot containing peanut poly A+RNA. DNA sequence analysis of the cloned inserts revealed that the Ara h I allergen has significant homology with the vicilin seed storage protein family found in most higher plants. The isolation of the Ara h I clones allowed the synthesis of this protein in Escherichia coli cells and subsequent recognition of this recombinant protein in immunoblot analysis using serum IgE from patients with peanut hypersensitivity. With the production of the recombinant peanut protein it will now be possible to address the pathophysiologic and immunologic mechanisms regarding peanut hypersensitivity reactions specifically and food hypersensitivity in general.

  17. Primary generalized glucocorticoid resistance and hypersensitivity: the end-organ involvement in the stress response.

    PubMed

    Charmandari, Evangelia

    2012-10-01

    Primary generalized glucocorticoid resistance (PGGR or Chrousos syndrome) and primary generalized glucocorticoid hypersensitivity (PGGH) are rare genetic disorders characterized by generalized, partial target-tissue insensitivity or hypersensitivity to glucocorticoids, respectively, while also causing compensatory alterations in the activity of the hypothalamic-pituitary-adrenal axis. The molecular basis of Chrousos syndrome and PGGH has been ascribed to mutations in the gene encoding the human glucocorticoid receptor (hGR), which impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. Alterations in hGR action may have important implications for many critical biological processes, such as the behavioral and physiologic responses to stress, immune responses, growth, and reproduction. This Presentation summarizes the pathophysiology, clinical manifestations, and molecular mechanisms of the PGGR and PGGH states.

  18. 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 Δrip36 and rip36E149A mutants lost the ability to induce HR in S. torvum. An E149A mutation had no effect on the translocation of Rip36 into plant cells. These results indicate that Rip36 is an avirulent factor that induces HR in S. torvum and that a putative Zn-dependent protease motif is essential for this activity.

  19. 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.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Widana Gamage, Shirani M. K.; McGrath, Desmond J.; Persley, Denis M.

    2016-01-01

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

  2. [Dentinal hypersensitivity].

    PubMed

    Steinkeller-Dekel, M; Smidt, A; Pilo, R

    2010-01-01

    Dentinal hypersensitivity is defined as short and transient painful response of exposed dentin, usually cervical, to different stimuli, such as thermal, mechanical osmotic or chemical. The etiology of dentinal hypersensitivity is open tubules (because of enamel loss or gingival recession), allowing painful stimulus to reach the pulp. The hydrodynamic theory explains the mechanism through which pain is aroused. When treating dentinal hypersensitivity, dentists always have to rule out other pathologies, such as carries, leakage, postoperative sensitivity, cracked tooth etc., and only then assess pain intensity and treat the tooth. Treatment always starts with prevention of both stimulus and exposure of dentin, and reducing predisposing factors. The treatment options include OTC products, such as fluoride and/or potassium enriched mouth washes and dentifrices, or in-office treatments, such as high content fluoride varnishes and gels, potassium oxalate chelating agents, Glutaraldehyde containing tissue fixating agents, bonding materials, low viscosity glass ionomers and even non-conservative treatments such as root canal therapy or mucogingival surgical interventions.

  3. [Dentinal hypersensitivity].

    PubMed

    Steinkeller-Dekel, M; Smidt, A; Pilo, R

    2010-01-01

    Dentinal hypersensitivity is defined as short and transient painful response of exposed dentin, usually cervical, to different stimuli, such as thermal, mechanical osmotic or chemical. The etiology of dentinal hypersensitivity is open tubules (because of enamel loss or gingival recession), allowing painful stimulus to reach the pulp. The hydrodynamic theory explains the mechanism through which pain is aroused. When treating dentinal hypersensitivity, dentists always have to rule out other pathologies, such as carries, leakage, postoperative sensitivity, cracked tooth etc., and only then assess pain intensity and treat the tooth. Treatment always starts with prevention of both stimulus and exposure of dentin, and reducing predisposing factors. The treatment options include OTC products, such as fluoride and/or potassium enriched mouth washes and dentifrices, or in-office treatments, such as high content fluoride varnishes and gels, potassium oxalate chelating agents, Glutaraldehyde containing tissue fixating agents, bonding materials, low viscosity glass ionomers and even non-conservative treatments such as root canal therapy or mucogingival surgical interventions. PMID:20597258

  4. Identification of a Maize Locus that Modulates the Hypersensitive Defense Response, Using Mutant-Assisted Gene Identification and Characterization (MAGIC)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The hypersensitive response (HR) is the most visible and arguably the most important defense response in plants, although the details of how it is controlled and executed remain patchy. In this paper a novel genetic technique called MAGIC (Mutant-Assisted Gene Identification and Characterization) i...

  5. Localisation of hydrogen peroxide accumulation during Solanum tuberosum cv. Rywal hypersensitive response to Potato virus Y.

    PubMed

    Otulak, Katarzyna; Garbaczewska, Grazyna

    2010-06-01

    The reactive oxygen species hydrogen peroxide (H(2)O(2)) was detected cytochemically in Solanum tuberosum cv. Rywal tissues as a hypersensitive response (HR) 24 and 48 h after a Potato virus Y (PVY) infection. Hydrogen peroxide was detected in vivo by its reaction with 3.3-diaminobenzidine, producing a reddish-brown staining in contact with H(2)O(2). Hydrogen peroxide was detected in the necrotic area of the epidermal and mesophyll cells 24 and 48 h after the PVY infection. Highly localised accumulations of H(2)O(2) were found within xylem tracheary elements, and this was much more intensive than in non-infected leaves. Hydrogen peroxide was detected cytochemically in HR also by its reaction with cerium chloride, producing electron-dense deposits of cerium perhydroxides. Inoculation with PVY(NTN) and also PVY(N) Wi induced a rapid hypersensitive response during which highly localised accumulations of H(2)O(2) was detected in plant cell walls. The most intensive accumulation was present in the bordering cell walls of necrotic mesophyll cells and the adjacent non-necrotic mesophyll cells. Intensive electron-dense deposits of cerium perhydroxide were found along ER cistrenae and chloroplast envelopes connected with PVY particles. The precipitates of hydrogen peroxide were detected in the nuclear envelope and along tracheary elements, especially when virus particles were present inside. The intensive accumulation of H(2)O(2) at the early stages of potato-PVY interaction is consistent with its role as an antimicrobial agent and for this reason it has been regarded as a signalling molecule.

  6. 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...

  7. A genome-wide association study of the maize hypersensitive defense response identifies genes that cluster in related pathways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Much remains unknown of molecular events controling the plant hypersensitive response (HR), a rapid localized cell death that limits pathogen spread and is mediated by resistance (R-) genes. Natural modifiers of the ectopic HR phenotype induced by an aberrant auto-active R-gene (Rp1-D21), were mappe...

  8. Reduced sleep, stress responsivity, and female sex contribute to persistent inflammation-induced mechanical hypersensitivity in rats.

    PubMed

    Page, Gayle G; Opp, Mark R; Kozachik, Sharon L

    2014-08-01

    Studies in humans suggest that female sex, reduced sleep opportunities and biological stress responsivity increase risk for developing persistent pain conditions. To investigate the relative contribution of these three factors to persistent pain, we employed the Sciatic Inflammatory Neuritis (SIN) model of repeated left sciatic perineurial exposures to zymosan, an inflammatory stimulus, to determine their impact upon the development of persistent mechanical hypersensitivity. Following an initial moderate insult, a very low zymosan dose was infused daily for eight days to model a sub-threshold inflammatory perturbation to which only susceptible animals would manifest or maintain mechanical hypersensitivity. Using Sprague Dawley rats, maintaining wakefulness throughout the first one-half of the 12-h light phase resulted in a bilateral reduction in paw withdrawal thresholds (PWTs); zymosan infusion reduced ipsilateral PWTs in all animals and contralateral PWTs only in females. This sex difference was validated in Fischer 344, Lewis and Sprague Dawley rats, suggesting that females are the more susceptible phenotype for both local and centrally driven responses to repeated low-level inflammatory perturbations. Hypothalamic-pituitary-adrenal (HPA) axis hyporesponsive Lewis rats exhibited the most robust development of mechanical hypersensitivity and HPA axis hyperresponsive Fischer 344 rats matched the Lewis rats' mechanical hypersensitivity throughout the latter four days of the protocol. If HPA axis phenotype does indeed influence these findings, the more balanced responsivity of Sprague Dawley rats would seem to promote resilience in this paradigm. Taken together, these findings are consistent with what is known regarding persistent pain development in humans.

  9. Skeleton photoperiods alter delayed-type hypersensitivity responses and reproductive function of Siberian hamsters (Phodopus sungorus).

    PubMed

    Gatien, M L; Hotchkiss, A K; Dhabhar, F S; Nelson, R J

    2005-11-01

    Photoperiod (day length) can modulate immune function. Whether these photoperiodic effects on immune function are mediated directly by a circadian photoperiodic time measurement system or indirectly by nonspecific (e.g. stressful) effects of light is unknown. To discriminate between these two possibilities, Siberian hamsters (Phodopus sungorus) were housed in either long or short photoperiods (LD 16 : 8 h or LD 8 : 16 h) or in 'skeleton' long or short photoperiods (LD 1 : 14 h: LD 1 : 8 h or LD 1 : 6 h: LD 1 : 16 h). In the skeleton photoperiods, both long- and short-day animals received 2 h of light per day. After 10 weeks in their respective photoperiods, hamsters were tested for an antigen specific immune response using a delayed type hypersensitivity (DTH) model. Reproductive and endocrine responses of hamsters in each of the skeleton photoperiods were equivalent to those in standard long or short days, respectively. Hamsters in skeleton short days and LD 8 : 16 increased DTH responses compared to hamsters in both long-day groups. DTH responses were equivalent in both long-day groups. These results suggest that the influences of day length on immune function potentially are due to circadian photoperiodic time measurement systems.

  10. Delayed-type hypersensitivity response in experimental autoimmune neuritis treated with peptide-coupled spleen cells.

    PubMed

    Gregorian, S K; Rostami, A

    1994-04-01

    Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune inflammatory disease of the peripheral nervous system that is characterized by demyelination and mononuclear cell infiltration. It is induced in Lewis rats by administration of myelin P2 protein or a synthetic peptide (SP-26) corresponding to amino acid residues 53-78 of bovine P2 protein. Recently, we showed that SP-26, when coupled to syngeneic spleen cells and administered intravenously, provided an effective means of inducing tolerance by inhibiting the clinical signs, decreased proliferative response of lymphoid cells to SP-26 and histological changes of EAN. However, our current data indicate that, despite tolerance induction in these Lewis rats, the antigen-specific delayed-type hypersensitivity (DTH) response to SP-26 remained intact. Furthermore, interferon (IFN)-gamma production by spleen cells of tolerized rats were unchanged as compared to EAN rats. The in vitro proliferation of T lymphocytes from tolerized rats stimulated by SP-26 was reduced as compared to EAN controls but was enhanced upon addition of exogenous interleukin-2. Thus, reduction in EAN clinical signs does not necessarily indicate a decrease in DTH response and IFN-gamma production in EAN Lewis rats. The implication of this finding in regard to immunoregulatory mechanism of DTH response is discussed. PMID:7512578

  11. Delayed-type hypersensitivity response in experimental autoimmune neuritis treated with peptide-coupled spleen cells.

    PubMed

    Gregorian, S K; Rostami, A

    1994-04-01

    Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune inflammatory disease of the peripheral nervous system that is characterized by demyelination and mononuclear cell infiltration. It is induced in Lewis rats by administration of myelin P2 protein or a synthetic peptide (SP-26) corresponding to amino acid residues 53-78 of bovine P2 protein. Recently, we showed that SP-26, when coupled to syngeneic spleen cells and administered intravenously, provided an effective means of inducing tolerance by inhibiting the clinical signs, decreased proliferative response of lymphoid cells to SP-26 and histological changes of EAN. However, our current data indicate that, despite tolerance induction in these Lewis rats, the antigen-specific delayed-type hypersensitivity (DTH) response to SP-26 remained intact. Furthermore, interferon (IFN)-gamma production by spleen cells of tolerized rats were unchanged as compared to EAN rats. The in vitro proliferation of T lymphocytes from tolerized rats stimulated by SP-26 was reduced as compared to EAN controls but was enhanced upon addition of exogenous interleukin-2. Thus, reduction in EAN clinical signs does not necessarily indicate a decrease in DTH response and IFN-gamma production in EAN Lewis rats. The implication of this finding in regard to immunoregulatory mechanism of DTH response is discussed.

  12. Comprehensive transcriptional and functional analyses of melatonin synthesis genes in cassava reveal their novel role in hypersensitive-like cell death

    PubMed Central

    Wei, Yunxie; Hu, Wei; Wang, Qiannan; Liu, Wei; Wu, Chunjie; Zeng, Hongqiu; Yan, Yu; Li, Xiaolin; He, Chaozu; Shi, Haitao

    2016-01-01

    Melatonin is a widely known hormone in animals. Since melatonin was discovered in plants, more and more studies highlight its involvement in a wide range of physiological processes including plant development and stress responses. Many advances have been made in the terms of melatonin-mediated abiotic stress resistance and innate immunity in plants, focusing on model plants such as rice and Arabidopsis. In this study, 7 melatonin synthesis genes were systematically analyzed in cassava. Quantitative real-time PCR showed that all these genes were commonly regulated by melatonin, flg22, Xanthomonas axonopodis pv manihotis (Xam) and hydrogen peroxide (H2O2). Transient expression in Nicotiana benthamiana revealed the subcellular locations and possible roles of these melatonin synthesis genes. Notably, we highlight novel roles of these genes in hypersensitive-like cell death, as confirmed by the results of several physiological parameters. Moreover, transient expression of these genes had significant effects on the transcripts of reactive oxygen species (ROS) accumulation and defense-related genes, and triggered the burst of callose depositions and papillae-associated plant defense, indicating the possible role of them in plant innate immunity. Taken together, this study reveals the comprehensive transcripts and putative roles of melatonin synthesis genes as well as melatonin in immune responses in cassava. PMID:27739451

  13. 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.

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

    PubMed Central

    Chen, Hsin-Chun; Chang, Wen-Te; Hseu, You-Cheng; Chen, Hsing-Yu; Chuang, Cheng Hsuan; Lin, Chi-Chen; Lee, Meng-Shiou; Lin, Ming-Kuem

    2016-01-01

    Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO) and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) with direct injection (DI/GC) or headspace-solid phase microextraction (HS-SPME/GC). In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial). An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs) which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS) responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases. PMID:27529236

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

    PubMed

    Chen, Hsin-Chun; Chang, Wen-Te; Hseu, You-Cheng; Chen, Hsing-Yu; Chuang, Cheng Hsuan; Lin, Chi-Chen; Lee, Meng-Shiou; Lin, Ming-Kuem

    2016-01-01

    Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO) and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) with direct injection (DI/GC) or headspace-solid phase microextraction (HS-SPME/GC). In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial). An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs) which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS) responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases. PMID:27529236

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

    PubMed

    Johansson, Oskar N; Nilsson, Anders K; Gustavsson, Mikael B; Backhaus, Thomas; Andersson, Mats X; Ellerström, Mats

    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 (33)PO4. PMID:26734506

  18. System-Wide Hypersensitive Response-Associated Transcriptome and Metabolome Reprogramming in Tomato1[W][OA

    PubMed Central

    Etalo, Desalegn W.; Stulemeijer, Iris J.E.; Peter van Esse, H.; de Vos, Ric C.H.; Bouwmeester, Harro J.; Joosten, Matthieu H.A.J.

    2013-01-01

    The hypersensitive response (HR) is considered to be the hallmark of the resistance response of plants to pathogens. To study HR-associated transcriptome and metabolome reprogramming in tomato (Solanum lycopersicum), we used plants that express both a resistance gene to Cladosporium fulvum and the matching avirulence gene of this pathogen. In these plants, massive reprogramming occurred, and we found that the HR and associated processes are highly energy demanding. Ubiquitin-dependent protein degradation, hydrolysis of sugars, and lipid catabolism are used as alternative sources of amino acids, energy, and carbon skeletons, respectively. We observed strong accumulation of secondary metabolites, such as hydroxycinnamic acid amides. Coregulated expression of WRKY transcription factors and genes known to be involved in the HR, in addition to a strong enrichment of the W-box WRKY-binding motif in the promoter sequences of the coregulated genes, point to WRKYs as the most prominent orchestrators of the HR. Our study has revealed several novel HR-related genes, and reverse genetics tools will allow us to understand the role of each individual component in the HR. PMID:23719893

  19. 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

  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). αβ 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 αβ 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. Treatment of dentin hypersensitivity.

    PubMed

    Trushkowsky, Richard D; Oquendo, Anabella

    2011-07-01

    Dentinal hypersensitivity is exemplified by brief, sharp, well-localized pain in response to thermal, evaporative, tactile, osmotic, or chemical stimuli that cannot be ascribed to any other form of dental defect or pathology. Pulpal pain is usually more prolonged, dull, aching, and poorly localized and lasts longer than the applied stimulus. Up to 30% of adults have dentinal hypersensitivity at some time. Current techniques for treatment may be only transient in nature and results are not always predictable. Two methods of treatment of dentin hypersensitivity are tubular occlusion and blockage of nerve activity. A differential diagnosis needs to be accomplished before any treatment. PMID:21726693

  2. 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.

  3. Asymmetrical hypersensitivity to bovine collagen.

    PubMed

    Somerville, P; Wray, R C

    1993-05-01

    We report a unique patient with true asymmetrical hypersensitivity to bovine collagen. Hypersensitivity is the development of an inflammatory response at a treatment site after a negative skin test. She developed an inflammatory response in only one of two simultaneously injected sites. About 1.5% of patients with a negative skin test have a hypersensitivity reaction consisting of firmness, erythema, and swelling. The signs and symptoms generally resolve spontaneously in a few months.

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

    PubMed Central

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

    2012-01-01

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

  5. The antagonistic effect of hydroxyl radical on the development of a hypersensitive response in tobacco.

    PubMed

    Deng, Sheng; Yu, Mina; Wang, Ying; Jia, Qin; Lin, Ling; Dong, Hansong

    2010-12-01

    Reactive oxygen species (ROS) are important signalling molecules in living cells. It is believed that ROS molecules are the main triggers of the hypersensitive response (HR) in plants. In the present study of the effect of riboflavin, which is excited to generate ROS in light, on the development of the HR induced by the elicitin protein ParA1 in tobacco (Nicotiana tabacum), we found that the extent of the ParA1-induced HR was diminished by hydroxyl radical (OH•), a type of ROS. As compared with the zones treated with ParA1 only, the HR symptom in the zones that were infiltrated with ParA1 plus riboflavin was significantly diminished when the treated plants were placed in the light. However, this did not occur when the plants were maintained in the dark. Trypan blue staining and the ion leakage measurements confirmed HR suppression in the light. Further experiments proved that HR suppression is attributed to the involvement of the photoexcited riboflavin, and that the suppression can be eliminated with the addition of hydrogen peroxide scavengers or OH• scavengers. Fenton reagent treatment and EPR measurements demonstrated that it is OH• rather than hydrogen peroxide that contributes to HR suppression. Accompanying the endogenous OH• formation, suppression of the ParA1-induced HR occurred in the tobacco leaves that had been treated with high-level abscisic acid, and that suppression was also removed by OH• scavengers. These results offer evidence that OH•, an understudied and little appreciated ROS, participates in and modulates biologically relevant signalling in plant cells. PMID:21073656

  6. 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.

  7. Protection against UV-induced suppression of contact hypersensitivity responses by sunscreens in humans.

    PubMed

    Cooper, K D; Baron, E D; LeVee, G; Stevens, S R

    2002-01-01

    Both in vivo skin immune responses and the skin's reaction to sun exposure integrate a complex interplay of biologic responses. The complexity and multiplicity of events that occur in the skin during an immune response make it a sensitive indication of both UVB and UVA-induced changes in the skin by sun damage, as well as those changes that are prevented by various sunscreens. Sunscreens are the most effective and widely available intervention for sun damage, other than sun avoidance or clothing. However, sunscreens vary widely in their relative ability to screen various UV waveband components, and their testing has been variably applied to outcomes other than for erythema to determine the sunburn protection factor (SPF), a measure primarily of UVB filtration only. Determination of an immune protection factor (IPF) has been proposed as an alternative or adjunctive measure to SPF, and recent studies show IPF can indeed detect added in vivo functionality of sunscreens, such as high levels of UVA protection, that SPF cannot. Clarification of the definition of IPF, however, is required. Excellent data are available on quantification of the IPF for restoring the afferent or induction arm of contact sensitivity, but other immune parameters have also been measured. Proposed here is nomenclature for whether the IPF is measured using contact sensitivity induction (IPF-CS-I), contact sensitivity elicitation (IPF-CS-E), delayed-type hypersensitivity elicitation (IPF-DTH-E), antigen-presenting cell function (IPF-APC-FXN) or numbers (IPF-APC-#), and cytokine modification such as IL-10 (i.e. IPF-cyto-IL-10). Similar nomenclatures could be used for other measures of skin function protection (i.e. DNA damage, p53 induction, oxidation products, etc.). A review of in vivo human studies, in which sunscreens are used to intervene in a UV-induced modulation of immune response, cells or cytokines, highlights the technical variables and statistical approaches which must also be

  8. 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

  9. α2δ-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 α2δ-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 α2δ-1 gene expression is disrupted, to determine whether α2δ-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 α2δ-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 α2δ-1−/− mice, and α2δ-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, α2δ-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 α2δ-2 or α2δ-3 after PSNL in α2δ-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 α2δ-1−/− mice. Thus, α2δ-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. PMID:24133248

  10. Hypersensitivity pneumonitis

    MedlinePlus

    Hypersensitivity pneumonitis usually occurs in people who work in places where there are high levels of organic dusts, fungus, or molds. Long-term exposure can lead to lung inflammation and acute lung disease . ...

  11. Hypersensitivity Pneumonitis

    MedlinePlus

    ... Hypersensitivity Pneumonitis Also known as extrinsic allergic alveolitis, bird fancier’s lung, farmer’s lung, hot tub lung, and ... May 27, 2016 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA OIG CONTACT US National ...

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

    PubMed

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

    2012-12-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Artificial light at night alters delayed-type hypersensitivity reaction in response to acute stress in Siberian hamsters.

    PubMed

    Bedrosian, Tracy A; Aubrecht, Taryn G; Kaugars, Katherine E; Weil, Zachary M; Nelson, Randy J

    2013-11-01

    Several physiological and behavioral processes rely on precisely timed light information derived from the natural solar cycle. Using this information, traits have adapted to allow individuals within specific niches to optimize survival and reproduction, but urbanization by humans has significantly altered natural habitats. Nighttime light exposure alters immune function in several species, which could lead to decreased fitness or survival, particularly in the face of an environmental challenge. We exposed male Siberian hamsters (Phodopus sungorus) to five lux of light at night for four weeks, and then administered six hours of acute restraint stress. Delayed-type hypersensitivity (DTH) response was assessed immediately following stress. Acute restraint increased the DTH reaction in dark nights, but exposure to nighttime light prevented this response. Exposure to light at night prolonged the DTH response in non-stressed control hamsters. These results suggest that light pollution may significantly alter physiological responses in Siberian hamsters, particularly in response to a salient environmental challenge such as stress.

  15. 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.

  16. Hypersensitivity Pneumonitis.

    PubMed

    Wysong, Kristi; Phillips, Jennan A; Hammond, Stephanie

    2016-06-01

    Chronic exposure to a broad array of antigens after workers inhale aerosolized organic dust particles from mold, animal dander, bird droppings, and chemicals, especially pesticides or herbicides, increases risk for hypersensitivity pneumonitis. Several demographic characteristics of immigrant workers in farming, poultry processing, construction, and landscaping increase this worker population's risk. PMID:27067273

  17. Hypersensitivity Pneumonitis.

    PubMed

    Wysong, Kristi; Phillips, Jennan A; Hammond, Stephanie

    2016-06-01

    Chronic exposure to a broad array of antigens after workers inhale aerosolized organic dust particles from mold, animal dander, bird droppings, and chemicals, especially pesticides or herbicides, increases risk for hypersensitivity pneumonitis. Several demographic characteristics of immigrant workers in farming, poultry processing, construction, and landscaping increase this worker population's risk.

  18. Delayed-type hypersensitivity responses in infected mice elicited by cytoplasmic fractions of Cryptococcus neoformans.

    PubMed Central

    Hay, R J; Reiss, E

    1978-01-01

    Four subcellular fractions of Cryptococcus neoformans prepared by differential centrifugation of disrupted whole yeast and a 3-day culture filtrate were examined for their ability to elicit delayed-type hypersensitivity in sensitized animals. The methods used to detect sensitization were (i) the footpad swelling test and inhibition of peritoneal macrophage migration in mice and (ii) skin testing in guinea pigs. Two entities, the post-mitochondrial supernatant and the culture filtrate, showed considerable activity in the footpad test, with 26- and 30-microliter 24-h swellings, respectively, at 6 weeks after infection. With the latter there was interference from a strong antibody-mediated 4-h skin reaction. The post-mitochondrial supernatant produced strong delayed-type hypersensitivity in guinea pigs at a dose of 69 microgram, and there was no demonstrable cross-reactivity in animals sensitized with heterologous fungi. The footpad swelling in mice correlated well with the macrophage migration inhibition test, with 71% inhibition in mice infected subcutaneously with C. neoformans at 6 weeks. However, mice infected intravenously developed poorer cell-mediated immunity than the subcutaneously infected mice. The post-mitochondrial supernatant was found to contain detectable amounts of cryptococcal capsular polysaccharide. Images PMID:365751

  19. 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...

  20. Dentine hypersensitivity.

    PubMed

    West, Nicola; Seong, Joon; Davies, Maria

    2014-01-01

    Dentine hypersensitivity is a common oral pain condition affecting many individuals. The aetiology is multifactorial; however, over recent years the importance of erosion has become more evident. For dentine hypersensitivity to occur, the lesion must first be localised on the tooth surface and then initiated to exposed dentine tubules which are patent to the pulp. The short, sharp pain symptom is thought to be derived from the hydrodynamic pain theory and, although transient, is arresting, affecting quality of life. This episodic pain condition is likely to become a more frequent dental complaint in the future due to the increase in longevity of the dentition and the rise in tooth wear, particularly amongst young adults. Many efficacious treatment regimens are now available, in particular a number of over-the-counter home use products. The basic principles of treatment are altering fluid flow in the dentinal tubules with tubule occlusion or modifying or chemically blocking the pulpal nerve. PMID:24993261

  1. Carmine hypersensitivity masquerading as azithromycin hypersensitivity.

    PubMed

    Greenhawt, Matthew; McMorris, Marc; Baldwin, James

    2009-01-01

    Macrolide hypersensitivity is a rarely reported event. However, carmine dye has become increasingly important as a provocative agent. We present a case of a woman with documented carmine hypersensitivity, who reported anaphylaxis 90 minutes after ingestion of a generic azithromycin. Our investigations revealed that this was an allergy to the carmine dye in the tablet's coating rather than to the antibiotic. Seven extracts were prepared including carmine dye, crushed dried female cochineal insects, crushed tablets of Zithromax (Pfizer Inc.) and generic azithromycin (Teva Pharmaceuticals), and the crushed colored coatings from both tablets. These were suspended in preservative-free normal saline, and then applied as a skin-prick test and read at 30 minutes. The skin-prick skin test results were 4+ to histamine and carmine dye, but negative to cochineal insect extract, Pfizer crushed tablets, and negative control. The patient was 1+ to the Teva crushed tablet, but was 4+ to the Teva brand coating and negative to the Pfizer brand coating, which did not contain carmine. The patient subsequently ingested Pfizer Zithromax without any sequelae. To our knowledge, this is the first reported case of carmine anaphylaxis attributed to carmine-containing medication. Careful history and skin-prick testing to the appropriate agents allowed elucidation of the subtlety of the true offending agent without unnecessary avoidance of the medication class. Patients with a carmine hypersensitivity should actively check with their pharmacy or prescribing physician to verify their medications are free of this offending agent. PMID:19331724

  2. Comparison of the hypersensitive response induced by the tomato Cf-4 and Cf-9 genes in Nicotiana spp.

    PubMed

    Thomas, C M; Tang, S; Hammond-Kosack, K; Jones, J D

    2000-04-01

    We have previously shown that tomato Cf-9 induces an Avr9-dependent hypersensitive response (HR) in Nicotiana tabacum and potato. We show here that Cf-4 also induces an Avr4-dependent HR in two tobacco species (N. tabacum and N. benthamiana). The HR induced by Cf-4 and Cf-9 was compared in stable tobacco transgenics by a seedling lethal assay and resistance to recombinant Potato virus X expressing Avr4 or Avr9. We also compared HR induction with Agrobacterium-mediated transient expression. The Cf-4/Avr4 combination induced a more rapid HR than Cf-9/Avr9. Sensitive assays for Cf-9 and Cf-4 function should prove useful for structure/function analyses of these resistance proteins in tobacco. PMID:10755310

  3. 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...

  4. 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...

  5. Role of ATF7-TAF12 interactions in the vitamin D response hypersensitivity of osteoclast precursors in Paget's disease.

    PubMed

    Teramachi, Jumpei; Hiruma, Yuko; Ishizuka, Seiichi; Ishizuka, Hisako; Brown, Jacques P; Michou, Laëtitia; Cao, Huiling; Galson, Deborah L; Subler, Mark A; Zhou, Hua; Dempster, David W; Windle, Jolene J; Roodman, G David; Kurihara, Noriyoshi

    2013-06-01

    Osteoclast (OCL) precursors from many Paget's disease (PD) patients express measles virus nucleocapsid protein (MVNP) and are hypersensitive to 1,25-dihydroxyvitamin D₂ (1,25-(OH)₂D₃; also know as calcitriol). The increased 1,25-(OH)₂D₃ sensitivity is mediated by transcription initiation factor TFIID subunit 12 (TAF12), a coactivator of the vitamin D receptor (VDR), which is present at much higher levels in MVNP-expressing OCL precursors than normals. These results suggest that TAF12 plays an important role in the abnormal OCL activity in PD. However, the molecular mechanisms underlying both 1,25-(OH)₂D₃'s effects on OCL formation and the contribution of TAF12 to these effects in both normals and PD patients are unclear. Inhibition of TAF12 with a specific TAF12 antisense construct decreased OCL formation and OCL precursors' sensitivity to 1,25-(OH)₂D₃ in PD patient bone marrow samples. Further, OCL precursors from transgenic mice in which TAF12 expression was targeted to the OCL lineage (tartrate-resistant acid phosphatase [TRAP]-TAF12 mice), formed OCLs at very low levels of 1,25-(OH)₂D₃, although the OCLs failed to exhibit other hallmarks of PD OCLs, including receptor activator of NF-κB ligand (RANKL) hypersensitivity and hypermultinucleation. Chromatin immunoprecipitation (ChIP) analysis of OCL precursors using an anti-TAF12 antibody demonstrated that TAF12 binds the 24-hydroxylase (CYP24A1) promoter, which contains two functional vitamin D response elements (VDREs), in the presence of 1,25-(OH)₂D₃. Because TAF12 directly interacts with the cyclic adenosine monophosphate-dependent activating transcription factor 7 (ATF7) and potentiates ATF7-induced transcriptional activation of ATF7-driven genes in other cell types, we determined whether TAF12 is a functional partner of ATF7 in OCL precursors. Immunoprecipitation of lysates from either wild-type (WT) or MVNP-expressing OCL with an anti-TAF12 antibody, followed by blotting with an

  6. The 2a protein of Cucumber mosaic virus induces a hypersensitive response in cowpea independently of its replicase activity.

    PubMed

    Hu, Zhongze; Zhang, Tianqi; Yao, Min; Feng, Zhike; Miriam, Karwitha; Wu, Jianyan; Zhou, Xueping; Tao, Xiaorong

    2012-12-01

    Resistance in cowpea to infection with strains of Cucumber mosaic virus (CMV) involves a local hypersensitive response (HR), and previous studies indicated that the 2a replicase of CMV is involved in HR induction. In this study, we confirmed and extended this observation by demonstrating that the nonviral expression of the 2a protein encoded by CMV is able to induce a cell death response in cowpea plants, whereas no other CMV-encoded proteins elicits such response. The 2a single-amino acid mutant, F631Y, no longer induces the necrosis response, yet the A641S mutant still induces cell death. The 2a double mutant, F631Y and A641S, does not induce HR. However, the three 2a mutants have comparable replicase activities in a fluorescence reporter assay. The 2a(D610A) mutant that alters the highly conserved GDD motif abolishes the replicase activity, however it does not affect HR induction in cowpea. The 2a(301-778aa) fragment introduced with the same D610A mutation in the GDD motif is also capable of inducing HR in cowpea. Collectively, these findings suggest that the 2a protein of CMV is sufficient to induce HR in cowpea independently of its replicase activity.

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

    PubMed

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

    2009-10-01

    Aim of this study was to investigate the intensity and timing of the ROS formation, lipid peroxidation and expression of antioxidant enzymes as initial responses of calli of Sesamum prostratum (SP) against Fusarium oxysporum f. sesame crude toxin metabolite of varying concentrations. 2,4 dichlorophenoxy acetic acid (2,4-D) / coconut milk combinations were found to be more efficient among different hormonal regimes (2,4 -D, 2,4-D/casein hydrosylate and 2,4-D/ coconut milk). The concentration of hydrogen peroxide and lipid peroxidation were higher (13.2 and 5.7-folds, respectively) after 6 h in the treated callus confirmed the oxidative stress. An increase in total phenolics was also detected in inoculated callus. Increased activity of antioxidative enzymes viz., NADPH oxidase and superoxide dismutase (SOD) corroborate with the high level of ROSs, such as O2*- and H2O2. The poor activity of catalase confirmed the oxidative burst in the callus leading to necrosis. Activity of peroxidase was at par with total phenolics. Similarly, phenylalanine ammonia lyase (PAL) also showed high activity revealing the active phase in the synthesis of secondary metabolites in the plant. The oxidative burst generated in the interaction between Sesamum and F. oxysporum f. sesame toxin might be the first line of defense by the host mounted against the invading necrotrophic pathogen. The results suggested that the rapid production of reactive oxygen species in the callus in response to fungal toxin had been proposed to orchestrate the establishment of different defensive barriers against the pathogens. PMID:20112812

  8. Delayed type hypersensitivity response to recall antigens does not accurately reflect immune competence in advanced stage breast cancer patients.

    PubMed

    Schiffman, Kathy; Rinn, Kristine; Disis, Mary L

    2002-07-01

    The development of delayed-type hypersensitivity (DTH) response to recall antigens has long been utilized as a measure of immune competence. It is assumed that because patients with advanced stage cancers exhibit multiple immune system defects they may not be responsive to immunization. We pre-selected patients with advanced HER-2/neu (HER2) overexpressing breast and ovarian cancers for enrolment into a phase I trial designed to evaluate the immunogenicity of a HER2 peptide vaccine based on the patient's immune competence as assessed by DTH skin testing to common recall antigens (Multitest CMI, Institut Merieux, Lyon, France). At the time of a positive DTH response to tetanus toxoid (tt) peripheral blood was obtained to measure T cell responses to tt. Of 53 patients evaluated, 38 (72%) were not anergic. Among the 15 (28%) who were, seven patients with advanced stage breast cancer were re-tested a median of 26 days (range 12-150 days) after receiving a tt bopster vaccination. Five of the seven had positive DTH responses when re-challenged with tt and six had peripheral blood tetanus specific T cell response with stimulation index >2.0. Thus, the majority of patients studied with advanced stage breast or ovarian cancer were able to mount a DTH response to common recall antigens. Moreover, a negative response by DTH testing to a battery of common recall antigens was not a reflection of the breast cancer patient's ability to mount a cell-mediated immune response to a vaccinated antigen, tt.

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

    PubMed Central

    Davoine, Céline; Falletti, Olivier; Douki, Thierry; Iacazio, Gilles; Ennar, Najla; Montillet, Jean-Luc; Triantaphylidès, 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

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

    PubMed

    Üstün, Suayib; Bartetzko, Verena; Börnke, 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.

  11. TaAbc1, a member of Abc1-like family involved in hypersensitive response against the stripe rust fungal pathogen in wheat.

    PubMed

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

    2013-01-01

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

  12. Involvement of plasma membrane calcium influx in bacterial induction of the K sup + /H sup + and hypersensitive responses in tobacco. [Pseudomonas syringae pv syringae

    SciTech Connect

    Atkinson, M.M.; Keppler, L.D.; Orlandi, E.W.; Baker, C.J.; Mischke, C.F. Univ. of Maryland, College Park )

    1990-01-01

    An early event in the hypersensitive response of tobacco to Pseudomonas syringae pv syringae is the initiation of a K{sup +}/H{sup +} response characterized by specific plasma membrane K{sup +} efflux, extracellular alkalinization, and intracellular acidification. We investigated the role of calcium in induction of these host responses. Suspension-cultured tobacco cells exhibited a baseline Ca{sup 2+} influx of 0.02 to 0.06 micromole per gram per hour as determined from {sup 45}Ca{sup 2+} uptake. Following bacterial inoculation, uptake rates began to increase coincidently with onset of the K{sup +}/H{sup +} response. Rates increased steadily for 2 to 3 hours, reaching 0.5 to 1 micromole per gram per hour. This increased Ca{sup 2+} influx was prevented by EGTA and calcium channel blockers such as La{sup 3+}, Co{sup 2+}, and Cd{sup 2+} but not by verapamil and nifedipine. Lanthanum, cobalt, cadmium, and EGTA inhibited the K{sup +}/H{sup +} response in both suspension-cultured cells and leaf discs and prevented hypersensitive cell death in leaf discs. We conclude that increase plasmalemma Ca{sup 2+} influx is required for the K{sup +}/H{sup +} and hypersensitive responses in tobacco.

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

    PubMed

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

    1993-11-01

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

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

    PubMed

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

    2016-09-15

    Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. PMID:27473013

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

    PubMed

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

    2016-09-15

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

  16. Differential expression of the TMV resistance gene N prevents a hypersensitive response in seeds and during germination.

    PubMed

    Niemeyer, Julia; Ruhe, Jonas; Machens, Fabian; Hehl, Reinhard

    2013-03-01

    The dominant tobacco mosaic virus (TMV) resistance gene N confers a hypersensitive response (HR) at the site of TMV infection and protects tobacco against systemic spread of the virus. To study N gene activity in seeds and early seedling development, the avirulence gene of N, the helicase domain (p50) of the TMV replicase, was constitutively expressed in a tobacco genotype without N (nn). Transgenic F1 expressing N and p50 were generated by crossing with an NN genotype. Surprisingly, Nn F1 seeds expressing p50 are viable and germinate. Only about 5 days after sowing, seedlings started to show an HR. This paralleled the upregulation of several pathogenesis-related and HR genes. The timing of the HR is consistent with the upregulation of N gene transcript 4-6 days after sowing. The expression of p50 has a stimulating effect on the N gene transcript level during germination. These results show that tobacco seeds and very young seedlings do not express a functional N gene product.

  17. Differential expression of the TMV resistance gene N prevents a hypersensitive response in seeds and during germination.

    PubMed

    Niemeyer, Julia; Ruhe, Jonas; Machens, Fabian; Hehl, Reinhard

    2013-03-01

    The dominant tobacco mosaic virus (TMV) resistance gene N confers a hypersensitive response (HR) at the site of TMV infection and protects tobacco against systemic spread of the virus. To study N gene activity in seeds and early seedling development, the avirulence gene of N, the helicase domain (p50) of the TMV replicase, was constitutively expressed in a tobacco genotype without N (nn). Transgenic F1 expressing N and p50 were generated by crossing with an NN genotype. Surprisingly, Nn F1 seeds expressing p50 are viable and germinate. Only about 5 days after sowing, seedlings started to show an HR. This paralleled the upregulation of several pathogenesis-related and HR genes. The timing of the HR is consistent with the upregulation of N gene transcript 4-6 days after sowing. The expression of p50 has a stimulating effect on the N gene transcript level during germination. These results show that tobacco seeds and very young seedlings do not express a functional N gene product. PMID:23291787

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

    PubMed

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

    2008-09-01

    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.

  19. Glutathione Deficiency of the Arabidopsis Mutant pad2-1 Affects Oxidative Stress-Related Events, Defense Gene Expression, and the Hypersensitive Response1[C][W][OA

    PubMed Central

    Dubreuil-Maurizi, Carole; Vitecek, Jan; Marty, Laurent; Branciard, Lorelise; Frettinger, Patrick; Wendehenne, David; Meyer, Andreas J.; Mauch, Felix; Poinssot, Benoît

    2011-01-01

    The Arabidopsis (Arabidopsis thaliana) phytoalexin-deficient mutant pad2-1 displays enhanced susceptibility to a broad range of pathogens and herbivorous insects that correlates with deficiencies in the production of camalexin, indole glucosinolates, and salicylic acid (SA). The pad2-1 mutation is localized in the GLUTAMATE-CYSTEINE LIGASE (GCL) gene encoding the first enzyme of glutathione biosynthesis. While pad2-1 glutathione deficiency is not caused by a decrease in GCL transcripts, analysis of GCL protein level revealed that pad2-1 plants contained only 48% of the wild-type protein amount. In contrast to the wild type, the oxidized form of GCL was dominant in pad2-1, suggesting a distinct redox environment. This finding was corroborated by the expression of GRX1-roGFP2, showing that the cytosolic glutathione redox potential was significantly less negative in pad2-1. Analysis of oxidative stress-related gene expression showed a higher transcript accumulation in pad2-1 of GLUTATHIONE REDUCTASE, GLUTATHIONE-S-TRANSFERASE, and RESPIRATORY BURST OXIDASE HOMOLOG D in response to the oomycete Phytophthora brassicae. Interestingly, oligogalacturonide elicitation in pad2-1 revealed a lower plasma membrane depolarization that was found to act upstream of an impaired hydrogen peroxide production. This impaired hydrogen peroxide production was also observed during pathogen infection and correlated with a reduced hypersensitive response in pad2-1. In addition, a lack of pathogen-triggered expression of the ISOCHORISMATE SYNTHASE1 gene, coding for the SA-biosynthetic enzyme isochorismate synthase, was identified as the cause of the SA deficiency in pad2-1. Together, our results indicate that the pad2-1 mutation is related to a decrease in GCL protein and that the resulting glutathione deficiency negatively affects important processes of disease resistance. PMID:22007023

  20. A genome-wide association study of the maize hypersensitive defense response identifies genes that cluster in related pathways.

    PubMed

    Olukolu, Bode A; Wang, Guan-Feng; Vontimitta, Vijay; 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

    2014-08-01

    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.

  1. 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

  2. Avocado hypersensitivity.

    PubMed

    Blanco, C; Carrillo, T; Castillo, R; Quiralte, J; Cuevas, M

    1994-07-01

    The avocado (Av) is a fruit that belongs to the Lauraceae family. We report 17 patients with immediate hypersensitivity to avocado. Clinical manifestations in relation to avocado ingestion were as follows: systemic anaphylaxis in seven patients, angioedema/urticaria in six, vomiting in two, bronchial asthma in one, and rhinoconjunctivitis in one. Skin prick test (SPT) with fresh avocado was positive in all patients with the Strong avocado variety (SAv) and in 14 patients with the Hass avocado variety (HAv). Our patient-associated sensitizations were as follows: 10 to latex, eight to chestnut, eight to banana, four to kiwi, and four to walnut. Avocado-sensitized patients with latex allergy were typically middle-aged women, professionally exposed to latex, who also exhibited frequent associated sensitizations to chestnut, banana, and other fruits. Specific IgE against avocado was demonstrated in 11 of our patients, by both commercial CAP and RAST with avocado extract coupled to nitrocellulose disks. Despite its lower protein content, SAv seems to be more allergenic than HAv, both in vivo and in vitro. On incubating a pool of sera from our patients with avocado, latex, chestnut, and banana extracts, a progressive RAST inhibition was obtained, with SAv- and chestnut-marked disks. This suggests the existence of common antigenic determinants among these allergens.

  3. Whiplash-like facet joint loading initiates glutamatergic responses in the DRG and spinal cord associated with behavioral hypersensitivity

    PubMed Central

    Dong, Ling; Quindlen, Julia C.; Lipschutz, Daniel E.; Winkelstein, Beth A.

    2012-01-01

    The cervical facet joint and its capsule are a common source of neck pain from whiplash. Mechanical hyperalgesia elicited by painful facet joint distraction is associated with spinal neuronal hyperexcitability that can be induced by transmitter/receptor systems that potentiate the synaptic activation of neurons. This study investigated the temporal response of a glutamate receptor and transporters in the dorsal root ganglia (DRG) and spinal cord. Bilateral C6/C7 facet joint distractions were imposed in the rat either to produce behavioral sensitivity or without inducing any sensitivity. Neuronal metabotropic glutamate receptor-5 (mGluR5) and protein kinase C-epsilon (PKCε) expression in the DRG and spinal cord were evaluated on days 1 and 7. Spinal expression of a glutamate transporter, excitatory amino acid carrier 1 (EAAC1), was also quantified at both time points. Painful distraction produced immediate behavioral hypersensitivity that was sustained for 7 days. Increased expression of mGluR5 and PKCε in the DRG was not evident until day 7 and only following painful distraction; this increase was observed in small-diameter neurons. Only painful facet joint distraction produced a significant increase (p<0.001) in neuronal mGluR5 over time, and this increase also was significantly elevated (p ≤ 0.05) over responses in the other groups at day 7. However, there were no differences in spinal PKCε expression on either day or between groups. Spinal EAAC1 expression was significantly increased (p<0.03) only in the nonpainful groups on day 7. Results from this study suggest spinal glutamatergic plasticity is selectively modulated in association with facet-mediated pain. PMID:22578356

  4. Pseudomonas syringae pv. tomato cells encounter inhibitory levels of water stress during the hypersensitive response of Arabidopsis thaliana

    PubMed Central

    Wright, Catherine A.; Beattie, Gwyn A.

    2004-01-01

    During plant defense against bacterial pathogens, the hypersensitive response (HR) functions to restrict pathogen growth and spread. The mechanisms driving this growth restriction are poorly understood. We used a water stress-responsive transcriptional fusion to quantify the water potential sensed by individual Pseudomonas syringae pv. tomato DC3000 cells during infection of Arabidopsis thaliana leaves. A nonpathogenic DC3000 hrcC mutant defective in type III secretion, as well as the saprophyte Pseudomonas fluorescens A506, sensed water potentials of -0.3 to -0.4 MPa at 48 h postinfiltration (hpi). During pathogenesis, DC3000 sensed lower water potentials (-0.4 to -0.9 MPa), demonstrating that it can modify the intercellular environment, and these water potentials were associated with optimal DC3000 growth in culture. During the HR, DC3000 cells sensed water potentials (-1.6 to -2.2 MPa) that were low enough to prevent cell division in the majority of cells in culture. This water potential decrease occurred within only 4 hpi and was influenced by avirulence gene expression, with avrRpm1 expression associated with lower water potentials than avrRpt2 or avrB expression at 48 hpi. The population sizes of the DC3000 variants tested were significantly correlated with the apoplastic water potential at 48 hpi, with a decrease of -0.9 MPa associated with a 10-fold decrease in cells per gram of leaf. These results suggest that the apoplastic water potential is a determinant of endophytic bacterial population size, and water stress, resulting from high osmolarity or tissue desiccation, is at least one factor restricting bacterial growth during the HR. PMID:14981249

  5. 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.

  6. An atypical PMR2 locus is responsible for hypersensitivity to sodium and lithium cations in the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D.

    PubMed

    Daran-Lapujade, Pascale; Daran, Jean-Marc; Luttik, Marijke A H; Almering, Marinka J H; Pronk, Jack T; Kötter, Peter

    2009-08-01

    Saccharomyces cerevisiae strains belonging to the CEN.PK family are widely used in fundamental and applied yeast research. These strains have been reported to be hypersensitive to sodium ions and a previous microarray-based genotyping study indicated an atypical organization of the PMR2 locus. In other S. cerevisiae strains, this locus harbours one to five ENA genes that encode plasma membrane sodium-pumping ATPases. Sequence analysis of the PMR2 locus in S. cerevisiae CEN.PK113-7D revealed the presence of a new ENA gene that showed substantial sequence differences, both at the nucleotide level and at the predicted amino acid sequence level, with previously described ENA genes. The presence of this single and atypical ENA gene correlated with hypersensitivity to sodium and, in particular, to lithium ions. The native ENA6 gene was transcriptionally induced by sodium and lithium ions, but, apparently, the capacity for sodium export upon full induction was insufficient to achieve the levels of sodium and lithium ion tolerance observed in other S. cerevisiae strains. The sodium and lithium hypersensitivity of CEN.PK strains, which is potentially detrimental during cultivation in sodium-rich media, could, however, be suppressed by overexpression of ENA6.

  7. 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

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

    PubMed

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

    2015-11-01

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

  9. Natural variation in the Arabidopsis response to the avirulence gene hopPsyA uncouples the hypersensitive response from disease resistance.

    PubMed

    Gassmann, Walter

    2005-10-01

    The plant hypersensitive response (HR) is tightly associated with gene-for-gene resistance and has been proposed to function in containing pathogens at the invasion site. This tight association has made it difficult to unequivocally evaluate the importance of HR for plant disease resistance. Here, hopPsyA from Pseudomonas syringae pv. syringae 61 is identified as a new avirulence gene for Arabidopsis that triggers resistance in the absence of macroscopic HR. Resistance to P. syringae pv. tomato DC3000 expressing hopPsyA was EDS1-dependent and NDR1-independent. Intriguingly, several Arabidopsis accessions were resistant to DC3000(hopPsyA) in the absence of HR. This is comparable to the Arabidopsis response to avrRps4, but it is shown that hopPsyA does not signal through RPS4. In a cross between two hopPsyA-resistant accessions that differ in their HR response, the HR segregated as a recessive phenotype regulated by a single locus. This locus, HED1 (HR regulator in EDS1 pathway), is proposed to encode a protein whose activity can cause suppression of the EDS1-dependent HR signaling pathway. HED1-regulated symptomless gene-for-gene resistance responses may explain some cases of Arabidopsis resistance to bacteria that are classified as nonhost resistance.

  10. Electromobility Shift Assay Reveals Evidence in Favor of Allele-Specific Binding of RUNX1 to the 5' Hypersensitive Site 4-Locus Control Region.

    PubMed

    Dehghani, Hossein; Ghobakhloo, Sepideh; Neishabury, Maryam

    2016-08-01

    In our previous studies on the Iranian β-thalassemia (β-thal) patients, we identified an association between the severity of the β-thal phenotype and the polymorphic palindromic site at the 5' hypersensitive site 4-locus control region (5'HS4-LCR) of the β-globin gene cluster. Furthermore, a linkage disequilibrium was observed between this region and XmnI-HBG2 in the patient population. Based on this data, it was suggested that the well-recognized phenotype-ameliorating role assigned to positive XmnI could be associated with its linked elements in the LCR. To investigate the functional significance of polymorphisms at the 5'HS4-LCR, we studied its influence on binding of transcription factors. Web-based predictions of transcription factor binding revealed a binding site for runt-related transcription factor 1 (RUNX1), when the allele at the center of the palindrome (TGGGG(A/G)CCCCA) was A but not when it was G. Furthermore, electromobility shift assay (EMSA) presented evidence in support of allele-specific binding of RUNX1 to 5'HS4. Considering that RUNX1 is a well-known regulator of hematopoiesis, these preliminary data suggest the importance of further studies to confirm this interaction and consequently investigate its functional and phenotypical relevance. These studies could help us to understand the molecular mechanism behind the phenotype modifying role of the 5'HS4-LCR polymorphic palindromic region (rs16912979), which has been observed in previous studies. PMID:27492765

  11. The N-terminal fragment of the tomato torrado virus RNA1-encoded polyprotein induces a hypersensitive response (HR)-like reaction in Nicotiana benthamiana.

    PubMed

    Wieczorek, Przemysław; Obrępalska-Stęplowska, Aleksandra

    2016-07-01

    The hypersensitive response (HR) is a defence reaction observed during incompatible plant-pathogen interactions in plants infected with a wide range of fungi, bacteria and viruses. Here, we show that an N-terminal polyprotein fragment encoded by tomato torrado virus RNA1, located between the first ATG codon and the protease cofactor (ProCo) motif, induces an HR-like reaction in Nicotiana benthamiana. Agrobacterium tumefaciens-mediated transient expression of the first 105 amino acids (the calculated molecular weight of the fragment was ca. 11.33 kDa, hereafter refered to as the 11K domain) from ToTV RNA1 induced an HR-like phenotype in infiltrated leaves. To investigate whether the 11K domain could influence the virulence and pathogenicity of a recombinant virus, we created a potato virus X (PVX) with the 11K coding sequence inserted under a duplicated coat protein promoter. We found that 11K substantially increased the virulence of the recombinant virus. Disease phenotype induced in N. benthamiana by PVX-11K was characterized by strong local and systemic necrosis. This was not observed when the 11K domain was expressed from PVX in an antisense orientation. Further analyses revealed that the 11K domain could not suppress posttranscriptional gene silencing (PTGS) of green fluorescent protein (GFP) in the N. benthamiana 16c line. In silico analysis of the predicted secondary structure of the 11K domain indicated the presence of two putative helices that are highly conserved in tomato-infecting representatives of the genus Torradovirus. PMID:27072852

  12. Ectopically expressed sweet pepper ferredoxin PFLP enhances disease resistance to Pectobacterium carotovorum subsp. carotovorum affected by harpin and protease-mediated hypersensitive response in Arabidopsis.

    PubMed

    Ger, Mang-Jye; Louh, Guan-Yu; Lin, Yi-Hsien; Feng, Teng-Yung; Huang, Hsiang-En

    2014-12-01

    Plant ferredoxin-like protein (PFLP) is a photosynthesis-type ferredoxin (Fd) found in sweet pepper. It contains an iron-sulphur cluster that receives and delivers electrons between enzymes involved in many fundamental metabolic processes. It has been demonstrated that transgenic plants overexpressing PFLP show a high resistance to many bacterial pathogens, although the mechanism remains unclear. In this investigation, the PFLP gene was transferred into Arabidopsis and its defective derivatives, such as npr1 (nonexpresser of pathogenesis-related gene 1) and eds1 (enhanced disease susceptibility 1) mutants and NAHG-transgenic plants. These transgenic plants were then infected with the soft-rot bacterial pathogen Pectobacterium carotovorum subsp. carotovorum (Erwinia carotovora ssp. carotovora, ECC) to investigate the mechanism behind PFLP-mediated resistance. The results revealed that, instead of showing soft-rot symptoms, ECC activated hypersensitive response (HR)-associated events, such as the accumulation of hydrogen peroxide (H2 O2 ), electrical conductivity leakage and expression of the HR marker genes (ATHSR2 and ATHSR3) in PFLP-transgenic Arabidopsis. This PFLP-mediated resistance could be abolished by inhibitors, such as diphenylene iodonium (DPI), 1-l-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (E64) and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), but not by myriocin and fumonisin. The PFLP-transgenic plants were resistant to ECC, but not to its harpin mutant strain ECCAC5082. In the npr1 mutant and NAHG-transgenic Arabidopsis, but not in the eds1 mutant, overexpression of the PFLP gene increased resistance to ECC. Based on these results, we suggest that transgenic Arabidopsis contains high levels of ectopic PFLP; this may lead to the recognition of the harpin and to the activation of the HR and other resistance mechanisms, and is dependent on the protease-mediated pathway.

  13. Delayed drug hypersensitivity reactions - new concepts.

    PubMed

    Posadas, S J; Pichler, W J

    2007-07-01

    Immune reactions to small molecular compounds such as drugs can cause a variety of diseases mainly involving skin, but also liver, kidney, lungs and other organs. In addition to the well-known immediate, IgE-mediated reactions to drugs, many drug-induced hypersensitivity reactions appear delayed. Recent data have shown that in these delayed reactions drug-specific CD4(+) and CD8(+) T cells recognize drugs through their T cell receptors (TCR) in an MHC-dependent way. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthems revealed that distinct T cell functions lead to different clinical phenotypes. Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T cell reactions, which by releasing certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4(+) or CD8(+) T cells (type IVc) seem to participate in all type IV reactions. Drugs are not only immunogenic because of their chemical reactivity, but also because they may bind in a labile way to available TCRs and possibly MHC-molecules. This seems to be sufficient to stimulate certain, probably preactivated T cells. The drug seems to bind first to the fitting TCR, which already exerts some activation. For full activation, an additional interaction of the TCR with the MHC molecules is needed. The drug binding to the receptor structures is reminiscent of a pharmacological interaction between a drug and its (immune) receptor and was thus termed the p-i concept. In some patients with drug hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. The T cell reaction to the drug might thus not be due to a classical, primary response, but is due to peptide-specific T cells which happen to be stimulated by a drug. This new concept has major implications

  14. A gene cluster in Agrobacterium vitis homologous to polyketide synthase operons is associated with grape necrosis and hypersensitive response induction on tobacco.

    PubMed

    Carle, Sigrid A; Hao, Guixia; Zheng, Desen; Sanni-Sanoussi, Tamira; Talarico, Michael J; Hilton, Joshua S; Burr, Thomas J

    2008-12-01

    Here, we identify a cluster of eight genes on chromosome 2 of Agrobacterium vitis that is associated with the ability of the bacterium to cause a hypersensitive response on tobacco and a necrosis of grape shoot explants. Three of these genes share a high level of structural and sequence similarity to clusters of genes in other bacteria that encode the enzymes for biosynthesis of polyketides and long-chain polyunsaturated fatty acids. No similar gene clusters were discovered in sequenced genomes of other members of Rhizobiales. PMID:19054098

  15. 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

  16. Hypersensitivity reactions to synthetic haemodialysis membranes.

    PubMed

    Sánchez-Villanueva, Rafael J; González, Elena; Quirce, Santiago; Díaz, Raquel; Alvarez, Laura; Menéndez, David; Rodríguez-Gayo, Lucía; Bajo, M Auxiliadora; Selgas, Rafael

    2014-01-01

    Undergoing a haemodialysis (HD) session poses a certain risk of hypersensitivity adverse reactions as large quantities of blood are in contact with various synthetic materials. Hypersensitivity reactions to ethylene oxide and non-biocompatible membranes, such as cuprophane, have been described in HD. Cases of hypersensitivity with biocompatible membranes, such as polysulfone, and even polysulfone-polyvinylpyrrolidone, have also been reported. In this article we describe six cases of mostly early-stage hypersensitivity reactions to HD occurring in our department, characterised by malaise, desaturation, bronchospasm and arterial hypotension, with good response to the session’s temporary suspension and with reappearance in subsequent sessions that used a synthetic dialyser. No hypersensitivity reactions reappeared in successive observations when the sessions were carried out using a cellulose membrane.

  17. A simple method for screening of plant NBS-LRR genes that confer a hypersensitive response to plant viruses and its application for screening candidate pepper genes against Pepper mottle virus.

    PubMed

    Tran, Phu-Tri; Choi, Hoseong; Kim, Saet-Byul; Lee, Hyun-Ah; Choi, Doil; Kim, Kook-Hyung

    2014-06-01

    Plant NBS-LRR genes are abundant and have been increasingly cloned from plant genomes. In this study, a method based on agroinfiltration and virus inoculation was developed for the simple and inexpensive screening of candidate R genes that confer a hypersensitive response to plant viruses. The well-characterized resistance genes Rx and N, which confer resistance to Potato virus X (PVX) and tobamovirus, respectively, were used to optimize a transient expression assay for detection of hypersensitive response in Nicotiana benthamiana. Infectious sap of PVX and Tobacco mosaic virus were used to induce hypersensitive response in Rx- and N-infiltrated leaves, respectively. The transient expression of the N gene induced local hypersensitive response upon infection of another tobamovirus, Pepper mild mottle virus, through both sap and transcript inoculation. When this method was used to screen 99 candidate R genes from pepper, an R gene that confers hypersensitive response to the potyvirus Pepper mottle virus was identified. The method will be useful for the identification of plant R genes that confer resistance to viruses.

  18. 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 PevD1ΔN98, which spans the C-terminal 57 amino acids of PevD1, was critical for the induction of HR in tobacco plants. In contrast, fragment PevD1ΔC57, 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 PevD1ΔC57 could be a candidate peptide for plant protection against pathogens without causing negative effects.

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

    PubMed

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

    2016-01-01

    Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stressinduced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome. PMID:27385724

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

    PubMed Central

    Cao, Dong-Yuan; Bai, Guang; Ji, Yaping; Karpowicz, Jane

    2016-01-01

    Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stress-induced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome. PMID:27385724

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

    A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction. PMID:22911741

  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

    2016-01-01

    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.

  4. Delayed drug hypersensitivity reactions.

    PubMed

    Pichler, Werner J

    2003-10-21

    Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate T cells if they act as haptens and bind covalently to peptides or if they have structural features that allow them to interact with certain T-cell receptors directly. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthema reveal that distinct T-cell functions lead to different clinical phenotypes. In maculopapular exanthema, perforin-positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while a large number of cytotoxic CD8+ T cells in the epidermis is associated with formation of vesicles and bullae. Drug-specific T cells also orchestrate inflammatory skin reactions through the release of various cytokines (for example, interleukin-5, interferon) and chemokines (such as interleukin-8). Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema). Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T-cell reactions, which through the release of certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4+ or CD8+ T cells (type IVc) seem to participate in all type IV reactions.

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

    PubMed Central

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

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the distal colorectum with the pelvic nerve attached was removed for single-fiber electrophysiological recordings. Colorectal afferent endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. Intracolonic zymosan produced persistent colorectal hypersensitivity (>24 days) associated with brief colorectal inflammation. Pelvic nerve muscular-mucosal but not muscular mechanosensitive afferents recorded from mice with colorectal hypersensitivity exhibited persistent sensitization. In addition, the proportion of MIAs (relative to control) was significantly reduced from 27% to 13%, whereas the proportion of serosal afferents was significantly increased from 34% to 53%, suggesting that MIAs acquired mechanosensitivity. PGP9.5 immunostaining revealed no significant loss of colorectal nerve fiber density, suggesting that the reduction in MIAs is not due to peripheral fiber loss after intracolonic zymosan. These results indicate that colorectal MIAs and sensitized muscular-mucosal afferents that respond to stretch contribute significantly to the afferent input that sustains hypersensitivity to CRD, suggesting that targeted management of colorectal afferent input could significantly reduce patients' complaints of pain and hypersensitivity. PMID:22268098

  6. Identification of early-responsive genes associated with the hypersensitive response to tobacco mosaic virus and characterization of a WRKY-type transcription factor in tobacco plants.

    PubMed

    Yoda, H; Ogawa, M; Yamaguchi, Y; Koizumi, N; Kusano, T; Sano, H

    2002-04-01

    In order to identify genes that are involved in the defense reaction against pathogen attack, we screened for examples that are regulated during the hypersensitive response (HR) to infection by tobacco mosaic virus (TMV) of tobacco ( Nicotiana tabacum cv. Xanthi nc) carrying the N gene, which confers resistance to TMV. Among seven genes initially identified by fluorescent differential display, one clone was further characterized because its transcripts accumulated rapidly and transiently after the onset of HR. Its full-length cDNA of 1346 bp encoded a polypeptide consisting of 258 amino acids. The deduced protein contained a single WRKY domain, a Cys(2)His(2) zinc-finger motif and a leucine-zipper motif, showing high similarity to WIZZ, a member of the family of WRKY transcription factors in tobacco. The gene was thus designated TIZZ. A GFP-TIZZ fusion protein was found to localize to the nucleus upon introduction into epidermal cells of onion. Bacterially expressed TIZZ was able to bind to the W-box (TTGAC) element that is recognized by other WRKY proteins, but transactivation assays showed it to be unable to activate reporter gene expression by itself. TIZZ transcripts were induced in TMV-infected nahG transgenic tobacco plants, in which salicylic acid fails to accumulate. Neither exogenously applied salicylic acid nor mechanical wounding induced TIZZ transcript accumulation. These results indicate the presence of salicylic acid-independent pathways for HR signal transduction, in which a novel type of WRKY protein(s) may play a critical role for the activation of defense. PMID:11976958

  7. Drug hypersensitivity reactions involving skin.

    PubMed

    Hausmann, Oliver; Schnyder, Benno; Pichler, Werner J

    2010-01-01

    Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit

  8. 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

    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 F(2) progeny and recombinant inbred lines. BGA-induced necrotic lesions co-localized with the production of H(2)O(2), 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

  9. Food hypersensitivity to lamb in a cat.

    PubMed

    Reedy, L M

    1994-04-01

    Severe facial pruritus in a cat was caused by food hypersensitivity to lamb. The cat had been fed an exclusive diet of lamb for 2 years after it had been diagnosed to have food hypersensitivity to fish. Signs, including erythema, alopecia, and excoriations of the head and neck, were poorly responsive to corticosteroid administration, but resolved within a few weeks after removal of the suspected allergen.

  10. 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.

  11. Estrogen-dependent visceral hypersensitivity following stress in rats

    PubMed Central

    Hubbard, Catherine S; Karpowicz, Jane M; Furman, Andrew J; da Silva, Joyce Teixeira; Traub, Richard J

    2016-01-01

    We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress. Stress was induced via a forced-swim paradigm. In a separate group of ovariectomized rats, E2 treatment induced visceral hypersensitivity at the 2 days post-stress time point, and this hypersensitivity returned to baseline at the 18 days post-stress time point. Vehicle-treated rats show no hypersensitivity following stress. During the MRI scans, rats were exposed to noxious colorectal distention. Across groups and time points, noxious visceral stimulation led to activations in the insula, anterior cingulate, and left amygdala, parabrachial nuclei, and cerebellum. A group-by-time interaction was seen in the right amygdala, ventral striatum-pallidum, cerebellum, hippocampus, mediodorsal thalamus, and pontine nuclei. Closer inspection of the data revealed that vehicle-treated rats showed consistent activations and deactivations across time, whereas estrogen-treated animals showed minimal deactivation with noxious visceral stimulation. This unexpected finding suggests that E2 may dramatically alter visceral nociceptive processing in the brain following an acute stressor. This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control

  12. Wheat hypersensitive-induced reaction genes TaHIR1 and TaHIR3 are involved in response to stripe rust fungus infection and abiotic stresses.

    PubMed

    Duan, Yinghui; Guo, Jun; Shi, Xuexia; Guan, Xiangnan; Liu, Furong; Bai, Pengfei; Huang, Lili; Kang, Zhensheng

    2013-02-01

    KEY MESSAGE : TaHIR1 and TaHIR3 play positive roles in resistance to the stripe rust fungus via inducing HR and regulating defense-related genes, but are negatively regulated by various abiotic stimuli. Plant hypersensitive-induced reaction (HIR) genes are known to be associated with the hypersensitive response and disease defense. In wheat, two HIR genes, TaHIR1 and TaHIR3, have been identified and found to be up-regulated after infection with the stripe rust fungus. Here, we further determined their roles in defense against abiotic stresses and the stripe rust pathogen, Puccinia striiformis f. sp. tritici. TaHIR1 and TaHIR3 proteins were localized in the plasma membrane of tobacco cells. The expression of TaHIR1 and TaHIR3 was reduced by the environmental stimuli, including low temperature, drought, and high salinity stresses. In addition, the expression of TaHIR1 and TaHIR3 was down-regulated by exogenously applied ethrel and abscisic acid, whereas expression was not affected by treatments with salicylic acid and methyl jasmonate. Furthermore, barley stripe mosaic virus-induced gene silencing of TaHIR1 and TaHIR3 reduced resistance in wheat cultivar Suwon11 against an avirulent stripe rust pathotype CYR23 and area of necrotic cells neighboring the infection sites, and altered the expression levels of defense-related genes. These results suggest that TaHIR1 and TaHIR3 function positively in the incompatible interaction of wheat-stripe rust fungus, but exhibit negative transcriptional response to abiotic stresses.

  13. Platinum hypersensitivity and desensitization.

    PubMed

    Miyamoto, Shingo; Okada, Rika; Ando, Kazumichi

    2015-09-01

    Platinum agents are drugs used for various types of cancer. With increased frequency of administration of platinum agents, hypersensitivity reactions appear more frequently, occurring in over 25% of cases from the seventh cycle or second line onward. It then becomes difficult to conduct treatment using these agents. Various approaches have been investigated to address hypersensitivity reactions to platinum agents. Desensitization, which gradually increases the concentration of the anticancer drug considered to be the antigen until the target dosage, has been reported as being particularly effective, with a success rate of 80-100%. The aims of this paper are to present the current findings regarding hypersensitivity reactions to platinum agents and to discuss attempts of using desensitization against hypersensitivity reactions worldwide.

  14. Hall viscosity revealed via density response

    NASA Astrophysics Data System (ADS)

    Huang, Biao

    2015-06-01

    Quantum Hall systems have recently been shown to possess a quantity sensitive to the spatial geometry and topology of the system, dubbed the Hall viscosity ηH. Despite the extensive theoretical discussions on its properties, the question of how to measure ηH still poses a challenge. In this paper, we present a general relation between Hall viscosity and susceptibility for systems with Galilean invariance. Thus, it allows for determination of ηH through density response signatures. The relations are verified in the integer quantum Hall example and are further illustrated in an effective hydrodynamic analysis. Since the derivation is based on Kubo formulas and assumes no more than conservation laws and translational symmetry, the results are applicable to a wide range of systems.

  15. Tomato 26S Proteasome subunit RPT4a regulates ToLCNDV transcription and activates hypersensitive response in tomato.

    PubMed

    Sahu, Pranav Pankaj; Sharma, Namisha; Puranik, Swati; Chakraborty, Supriya; Prasad, Manoj

    2016-01-01

    Involvement of 26S proteasomal subunits in plant pathogen-interactions, and the roles of each subunit in independently modulating the activity of many intra- and inter-cellular regulators controlling physiological and defense responses of a plant were well reported. In this regard, we aimed to functionally characterize a Solanum lycopersicum 26S proteasomal subunit RPT4a (SlRPT4) gene, which was differentially expressed after Tomato leaf curl New Delhi virus (ToLCNDV) infection in tolerant cultivar H-88-78-1. Molecular analysis revealed that SlRPT4 protein has an active ATPase activity. SlRPT4 could specifically bind to the stem-loop structure of intergenic region (IR), present in both DNA-A and DNA-B molecule of the bipartite viral genome. Lack of secondary structure in replication-associated gene fragment prevented formation of DNA-protein complex suggesting that binding of SlRPT4 with DNA is secondary structure specific. Interestingly, binding of SlRPT4 to IR inhibited the function of RNA Pol-II and subsequently reduced the bi-directional transcription of ToLCNDV genome. Virus-induced gene silencing of SlRPT4 gene incited conversion of tolerant attributes of cultivar H-88-78-1 into susceptibility. Furthermore, transient overexpression of SlRPT4 resulted in activation of programmed cell death and antioxidant enzymes system. Overall, present study highlights non-proteolytic function of SlRPT4 and their participation in defense pathway against virus infection in tomato. PMID:27252084

  16. Tomato 26S Proteasome subunit RPT4a regulates ToLCNDV transcription and activates hypersensitive response in tomato

    PubMed Central

    Sahu, Pranav Pankaj; Sharma, Namisha; Puranik, Swati; Chakraborty, Supriya; Prasad, Manoj

    2016-01-01

    Involvement of 26S proteasomal subunits in plant pathogen-interactions, and the roles of each subunit in independently modulating the activity of many intra- and inter-cellular regulators controlling physiological and defense responses of a plant were well reported. In this regard, we aimed to functionally characterize a Solanum lycopersicum 26S proteasomal subunit RPT4a (SlRPT4) gene, which was differentially expressed after Tomato leaf curl New Delhi virus (ToLCNDV) infection in tolerant cultivar H-88-78-1. Molecular analysis revealed that SlRPT4 protein has an active ATPase activity. SlRPT4 could specifically bind to the stem-loop structure of intergenic region (IR), present in both DNA-A and DNA-B molecule of the bipartite viral genome. Lack of secondary structure in replication-associated gene fragment prevented formation of DNA-protein complex suggesting that binding of SlRPT4 with DNA is secondary structure specific. Interestingly, binding of SlRPT4 to IR inhibited the function of RNA Pol-II and subsequently reduced the bi-directional transcription of ToLCNDV genome. Virus-induced gene silencing of SlRPT4 gene incited conversion of tolerant attributes of cultivar H-88-78-1 into susceptibility. Furthermore, transient overexpression of SlRPT4 resulted in activation of programmed cell death and antioxidant enzymes system. Overall, present study highlights non-proteolytic function of SlRPT4 and their participation in defense pathway against virus infection in tomato. PMID:27252084

  17. Chronic loss of noradrenergic tone produces β-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 β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs.

  18. Chronic loss of noradrenergic tone produces β-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 β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs. PMID:25123018

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

    PubMed

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

    2015-01-01

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

  20. Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase

    PubMed Central

    Huang, Lei; Ou, Rong; Rabelo de Souza, Guilherme; Cunha, Thiago M.; Lemos, Henrique; Mohamed, Eslam; Li, Lingqian; Pacholczyk, Gabriela; Randall, Janice; Munn, David H.; Mellor, Andrew L.

    2016-01-01

    Increased pain sensitivity is a comorbidity associated with many clinical diseases, though the underlying causes are poorly understood. Recently, chronic pain hypersensitivity in rodents treated to induce chronic inflammation in peripheral tissues was linked to enhanced tryptophan catabolism in brain mediated by indoleamine 2,3 dioxygenase (IDO). Here we show that acute influenza A virus (IAV) and chronic murine leukemia retrovirus (MuLV) infections, which stimulate robust IDO expression in lungs and lymphoid tissues, induced acute or chronic pain hypersensitivity, respectively. In contrast, virus-induced pain hypersensitivity did not manifest in mice lacking intact IDO1 genes. Spleen IDO activity increased markedly as MuLV infections progressed, while IDO1 expression was not elevated significantly in brain or spinal cord (CNS) tissues. Moreover, kynurenine (Kyn), a tryptophan catabolite made by cells expressing IDO, incited pain hypersensitivity in uninfected IDO1-deficient mice and Kyn potentiated pain hypersensitivity due to MuLV infection. MuLV infection stimulated selective IDO expression by a discreet population of spleen cells expressing both B cell (CD19) and dendritic cell (CD11c) markers (CD19+ DCs). CD19+ DCs were more susceptible to MuLV infection than B cells or conventional (CD19neg) DCs, proliferated faster than B cells from early stages of MuLV infection and exhibited mature antigen presenting cell (APC) phenotypes, unlike conventional (CD19neg) DCs. Moreover, interactions with CD4 T cells were necessary to sustain functional IDO expression by CD19+ DCs in vitro and in vivo. Splenocytes from MuLV-infected IDO1-sufficient mice induced pain hypersensitivity in uninfected IDO1-deficient recipient mice, while selective in vivo depletion of DCs alleviated pain hypersensitivity in MuLV-infected IDO1-sufficient mice and led to rapid reduction in splenomegaly, a hallmark of MuLV immune pathogenesis. These findings reveal critical roles for CD19+ DCs

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

    PubMed

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

    2005-01-14

    Cutaneous exposure to the pyrethroid insecticide permethrin significantly suppresses contact hypersensitivity (CH) response to oxazolone in C57BL/6N mice. Additionally, cis-urocanic acid (cUCA), an endogenous cutaneous chromophore isomerized to its active form following exposure to ultraviolet radiation, modulates cell-mediated cutaneous immune responses. This study describes cutaneous immune alterations following combined topical permethrin and intradermal cUCA exposure. Female C57BL/6N mice were administered 5, 50 or 100 microg cUCA daily for 5 consecutive days. CH was then evaluated by the mouse ear swelling test (MEST) response to oxazolone. Decreased responses of 52.3%, 76.3% and 76.3%, respectively, as compared to controls were observed. Then, mice were co-exposed to 5 microg cUCA daily for 5 days and 1.5, 5, 15, or 25 microL permethrin, on either day 1, 3 or 5 of the cUCA treatment to evaluate combined immunomodulatory effects of the two chemicals, or cUCA daily for 5 days followed by permethrin on day 3, 5, or 7 after the last cUCA injection to demonstrate prolonged immunosuppressive effects. Two days after final treatment, mice were sensitized with oxazolone and MEST was performed. Mice receiving five cUCA injections and permethrin topically on cUCA injection day 1 showed up to 93.3% suppression of MEST compared to vehicle control. CH was suppressed by 87.5%, 86.6% and 74.2% in mice treated with 25 muL permethrin on days 3, 5 and 7 after cUCA, respectively, compared to vehicle control. Taken together, these data indicate co-exposure to cUCA and permethrin profoundly suppresses cell-mediated cutaneous immunity. PMID:15629246

  2. In vitro evidence of delayed-type hypersensitivity to hydrocortisone.

    PubMed

    Wilkinson, S M; English, J S; Mattey, D L

    1993-11-01

    Hypersensitivity to topical hydrocortisone is becoming increasingly recognized. We present further evidence that this is mediated via a delayed-type hypersensitivity reaction. A hydrocortisone: albumin complex was able to induce a proliferative response in the peripheral blood mononuclear cells of patients allergic to hydrocortisone. Protein binding of hydrocortisone or a degradation product may be important in the development of corticosteroid allergy.

  3. 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

    HrpZ—a harpin from Pseudomonas syringae—is 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 25°C (∼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

  4. Capsicum annuum basic transcription factor 3 (CaBtf3) regulates transcription of pathogenesis-related genes during hypersensitive response upon Tobacco mosaic virus infection.

    PubMed

    Huh, Sung Un; Kim, Ki-Jeong; Paek, Kyung-Hee

    2012-01-13

    Hypersensitive response (HR) cell death upon plant virus infection is an excellent plant strategy for inhibiting viral movement and obtaining systemic acquired resistance (SAR) against further infection. Various host factors are involved in these HR processes, either directly as viral resistance proteins or indirectly. We characterized a gene encoding the CaBtf3 [β-nascent polypeptide-associated complex (NAC) subunit] of NAC from the hot pepper plant. NAC contacts nascent polypeptides to prevent aggregation and degradation of newly synthesized proteins by controlling cotranslational protein folding. CaBtf3 protein fused to green fluorescent protein predominantly localized to the nucleus. Silencing phenotype of CaBtf3 upon the Tobacco mosaic virus (TMV)-P(0) inoculation exhibited reduced HR cell death and decreased expression of some HR-associated genes, but increased TMV coat protein levels compared with TRV2 control plants. Furthermore, silencing of NbBtf3, a highly homologous gene of CaBtf3, also led to the reduced Bax- and Pto-mediated cell death. The results indicate that CaBtf3 might be involved in HR cell death and could function as a transcription factor in the nucleus by transcriptional regulation of HR-related gene expression.

  5. Maternal and postnatal dietary probiotic supplementation enhances splenic regulatory T helper cell population and reduces peanut allergen-induced hypersensitivity responses in mice.

    PubMed

    Toomer, Ondulla T; Ferguson, Martine; Pereira, Marion; Do, Andrew; Bigley, Elmer; Gaines, Dennis; Williams, Kristina

    2014-09-01

    Neonatal to early childhood is the critical period for establishing a balance of T helper 1 (Th1) versus T helper 2 (Th2) cellular immunity within the gut, which is strongly influenced by the source and establishment of gut microflora. Probiotic administration has been shown to attenuate Th2-biased cellular immunity and predisposition to food allergies. To test this hypothesis we provided ad libitum a probiotic-supplemented (Primalac 454 Feed Grade Microbials) or control diet to lactating dams with suckling pups and weaned pups until 10 weeks of age. Weaned mice were sensitized/challenged with peanut extract, saline or adjuvant at 6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected for microbial analysis, while blood samples were analyzed for total plasma IgE levels. At termination (10 weeks of age), splenic T lymphocyte population subtypes were determined using FACS analysis and Th1/Th2/Th17 gene expression by PCR array. Mice given the probiotic-supplemented diet had significantly enhanced probiotic fecal counts compared to controls at 3, 6, 8 and 10 weeks. Moreover, mice fed the probiotic-supplemented diet had enhanced splenic naturally occurring T regulatory cell populations, and reduced splenic gene expression of allergic mediator IL-13 compared to controls. These results provide evidence that early probiotic supplementation may provide host protection to hypersensitivity reactions to food allergens by attenuating food allergen inflammatory responses.

  6. Pepino mosaic virus RNA-Dependent RNA Polymerase POL Domain Is a Hypersensitive Response-Like Elicitor Shared by Necrotic and Mild Isolates.

    PubMed

    Sempere, Raquel N; Gómez-Aix, Cristina; Ruíz-Ramón, Fabiola; Gómez, Pedro; Hasiów-Jaroszewska, Beata; Sánchez-Pina, María Amelia; Aranda, Miguel A

    2016-04-01

    Pepino mosaic virus (PepMV) is an emerging pathogen that represents a serious threat to tomato production worldwide. PepMV-induced diseases manifest with a wide range of symptoms, including systemic necrosis. Our results showed that PepMV accumulation depends on the virus isolate, tomato cultivar, and environmental conditions, and associates with the development of necrosis. Substitution of lysine for glutamic acid at position 67 in the triple gene block 3 (TGB3) protein, previously described as a necrosis determinant, led to increased virus accumulation and was necessary but not sufficient to induce systemic necrosis. Systemic necrosis both in tomato and Nicotiana benthamiana shared hypersensitive response (HR) features, allowing the assessment of the role of different genomic regions on necrosis induction. Overexpression of both TGB3 and the polymerase domain (POL) of the RNA-dependent RNA polymerase (RdRp) resulted in necrosis, although only local expression of POL triggered HR-like symptoms. Our results also indicated that the necrosis-eliciting activity of POL resides in its highly conserved "palm" domain, and that necrosis was jasmonic acid-dependent but not salicylic acid-dependent. Altogether, our data suggest that the RdRp-POL domain plays an important role in PepMV necrosis induction, with necrosis development depending on the virus accumulation level, which can be modulated by the nature of TGB3, host genotype and environmental conditions. PMID:26667188

  7. Pepino mosaic virus RNA-Dependent RNA Polymerase POL Domain Is a Hypersensitive Response-Like Elicitor Shared by Necrotic and Mild Isolates.

    PubMed

    Sempere, Raquel N; Gómez-Aix, Cristina; Ruíz-Ramón, Fabiola; Gómez, Pedro; Hasiów-Jaroszewska, Beata; Sánchez-Pina, María Amelia; Aranda, Miguel A

    2016-04-01

    Pepino mosaic virus (PepMV) is an emerging pathogen that represents a serious threat to tomato production worldwide. PepMV-induced diseases manifest with a wide range of symptoms, including systemic necrosis. Our results showed that PepMV accumulation depends on the virus isolate, tomato cultivar, and environmental conditions, and associates with the development of necrosis. Substitution of lysine for glutamic acid at position 67 in the triple gene block 3 (TGB3) protein, previously described as a necrosis determinant, led to increased virus accumulation and was necessary but not sufficient to induce systemic necrosis. Systemic necrosis both in tomato and Nicotiana benthamiana shared hypersensitive response (HR) features, allowing the assessment of the role of different genomic regions on necrosis induction. Overexpression of both TGB3 and the polymerase domain (POL) of the RNA-dependent RNA polymerase (RdRp) resulted in necrosis, although only local expression of POL triggered HR-like symptoms. Our results also indicated that the necrosis-eliciting activity of POL resides in its highly conserved "palm" domain, and that necrosis was jasmonic acid-dependent but not salicylic acid-dependent. Altogether, our data suggest that the RdRp-POL domain plays an important role in PepMV necrosis induction, with necrosis development depending on the virus accumulation level, which can be modulated by the nature of TGB3, host genotype and environmental conditions.

  8. Role of calcium in signal transduction during the hypersensitive response caused by basidiospore-derived infection of the cowpea rust fungus

    PubMed

    Xu; Heath

    1998-04-01

    The hypersensitive response (HR) of disease-resistant plant cells to fungal invasion is a rapid cell death that has some features in common with programmed cell death (apoptosis) in animals. We investigated the role of cytosolic free calcium ([Ca2+]i) in the HR of cowpea to the cowpea rust fungus. By using confocal laser scanning microscopy in conjunction with a calcium reporter dye, we found a slow, prolonged elevation of [Ca2+]i in epidermal cells of resistant but not susceptible plants as the fungus grew through the cell wall. [Ca2+]i levels declined to normal levels as the fungus entered and grew within the cell lumen. This elevation was related to the stage of fungal growth and not to the speed of initiation of subsequent cell death. Elevated [Ca2+]i levels also represent the first sign of the HR detectable in this cowpea-cowpea rust fungus system. The increase in [Ca2+]i was prevented by calcium channnel inhibitors. This effect was consistent with pharmacological tests in which these inhibitors delayed the HR. The data suggest that elevation of [Ca2+]i is involved in signal transduction leading to the HR during rust fungal infection.

  9. 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

  10. DNase I hypersensitivity sites and nuclear protein binding on the fatty acid synthase gene: identification of an element with properties similar to known glucose-responsive elements.

    PubMed Central

    Foufelle, F; Lepetit, N; Bosc, D; Delzenne, N; Morin, J; Raymondjean, M; Ferré, P

    1995-01-01

    We have shown previously that fatty acid synthase (FAS) gene expression is positively regulated by glucose in rat adipose tissue and liver. In the present study, we have identified in the first intron of the gene a sequence closely related to known glucose-responsive elements such as in the L-pyruvate kinase and S14 genes, including a putative upstream stimulatory factor/major late transcription factor (USF/MLTF) binding site (E-box) (+ 292 nt to + 297 nt). Location of this sequence corresponds to a site of hypersensitivity to DNase I which is present in the liver but not in the spleen. Moreover, using this information from a preliminary report of the present work, others have shown that a + 283 nt to + 303 nt sequence of the FAS gene can confer glucose responsiveness to a heterologous promoter. The protein binding to this region has been investigated in vitro by a combination of DNase I footprinting and gel-retardation experiments with synthetic oligonucleotides and known nuclear proteins. DNase I footprinting experiments using a + 161 nt to + 405 nt fragment of the FAS gene demonstrate that a region from + 290 nt to + 316 nt is protected by nuclear extracts from liver and spleen. This region binds two ubiquitous nuclear factors, USF/MLTF and the CAAT-binding transcription factor/nuclear factor 1 (CTF/NF1). Binding of these factors is similar in nuclear extracts from liver which does or does not express the FAS gene as observed for glucose-responsive elements in the L-pyruvate kinase and S14 genes. This suggests a posttranslational modification of a factor of the complex after glucose stimulation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7772036

  11. DNase I hypersensitivity sites and nuclear protein binding on the fatty acid synthase gene: identification of an element with properties similar to known glucose-responsive elements.

    PubMed

    Foufelle, F; Lepetit, N; Bosc, D; Delzenne, N; Morin, J; Raymondjean, M; Ferré, P

    1995-06-01

    We have shown previously that fatty acid synthase (FAS) gene expression is positively regulated by glucose in rat adipose tissue and liver. In the present study, we have identified in the first intron of the gene a sequence closely related to known glucose-responsive elements such as in the L-pyruvate kinase and S14 genes, including a putative upstream stimulatory factor/major late transcription factor (USF/MLTF) binding site (E-box) (+ 292 nt to + 297 nt). Location of this sequence corresponds to a site of hypersensitivity to DNase I which is present in the liver but not in the spleen. Moreover, using this information from a preliminary report of the present work, others have shown that a + 283 nt to + 303 nt sequence of the FAS gene can confer glucose responsiveness to a heterologous promoter. The protein binding to this region has been investigated in vitro by a combination of DNase I footprinting and gel-retardation experiments with synthetic oligonucleotides and known nuclear proteins. DNase I footprinting experiments using a + 161 nt to + 405 nt fragment of the FAS gene demonstrate that a region from + 290 nt to + 316 nt is protected by nuclear extracts from liver and spleen. This region binds two ubiquitous nuclear factors, USF/MLTF and the CAAT-binding transcription factor/nuclear factor 1 (CTF/NF1). Binding of these factors is similar in nuclear extracts from liver which does or does not express the FAS gene as observed for glucose-responsive elements in the L-pyruvate kinase and S14 genes. This suggests a posttranslational modification of a factor of the complex after glucose stimulation.

  12. Electrosensibility and electromagnetic hypersensitivity.

    PubMed

    Leitgeb, Norbert; Schröttner, Jörg

    2003-09-01

    Electromagnetic sensibility, the ability to perceive electric and electromagnetic exposure, and electromagnetic hypersensitivity (EHS), developing health symptoms due to exposure to environmental electromagnetic fields, need to be distinguished. Increased electrosensibility is a necessary, however, not a sufficient condition for electromagnetic hypersensitivity. At an extended sample of the general population of 708 adults, including 349 men and 359 women aged between 17 and 60 years, electrosensibility was investigated and characterized by perception threshold and its standard deviation. By analyzing the probability distributions of the perception threshold of electric 50 Hz currents, evidence could be found for the existence of a subgroup of people with significantly increased electrosensibility (hypersensibility) who as a group could be differentiated from the general population. The presented data show that the variation of the electrosensibility among the general population is significantly larger than has yet been estimated by nonionizing radiation protection bodies, but much smaller than claimed by hypersensitivity self-aid groups. These quantitative results should contribute to a less emotional discussion of this problem. The investigation method presented, is capable of exclusion diagnostics for persons suffering from the hypersensitivity syndrome. PMID:12929157

  13. Hypersensitivity to hypercapnia: definition/(s).

    PubMed

    Vickers, Kristin

    2012-05-15

    Empirical evidence indicates that panic disorder (PD) patients experience hypersensitivity to hypercapnia, a condition in which the blood level of carbon dioxide exceeds the normal value. The importance of this research line is substantial and indeed, hypercapnic hypersensitivity has been advanced as a possible endophenotype of panic. Definitions of "hypersensitivity," however, have varied. The purpose of this brief review is to delineate and critique different definitions of hypercapnic hypersensitivity. Several definitions - panic attack rate, panic symptoms including dyspnea, subjective anxiety, and respiratory disturbance - are explored. The review concludes that although no ideal definition has emerged, marked anxiety post-hypercapnia has substantial support as a putative trait marker of PD. The term "subjective hypersensitivity" (Coryell et al., 2001) is re-introduced to denote pronounced anxiety post-hypercapnia and recommended for use along with its previous definition: increased self-reported anxiety measured on a continuous visual analog scale, already widely in use. Due to the well-established link between panic and respiration, definitional candidates focusing on aberrant respiratory response - less investigated as trait markers of PD in high risk studies - warrant scrutiny as well. Several reasons why definitional clarity might be beneficial are presented, along with ideas for future research.

  14. luxR homolog avhR in Agrobacterium vitis affects the development of a grape-specific necrosis and a tobacco hypersensitive response.

    PubMed

    Hao, Guixia; Zhang, Hongsheng; Zheng, Desen; Burr, Thomas J

    2005-01-01

    The luxR homolog aviR in Agrobacterium vitis strain F2/5 was recently shown to be associated with induction of a hypersensitive response (HR) on tobacco and necrosis on grape plants, indicating that the responses are regulated by quorum sensing. We now report a second luxR homolog, avhR, whose disruption (mutant M1320) results in HR-negative and reduced grape necrosis phenotypes. The deduced AvhR protein has characteristic autoinducer binding and DNA binding domains and is unique among reported functional LuxR homologs in having substitutions at highly conserved Asp70, Trp57, and Trp85 residues, which are predicted to play important roles in autoinducer binding in TraR. M1320 was fully complemented with cloned avhR. The same array of N-acylhomoserine lactones (AHL) from F2/5, M1320, and complemented M1320 were observed; however, the signal strength from extracts of 6-day-old M1320 cultures was stronger than that of F2/5. Cultures of F2/5 amended with AHL extracts from overnight and 6-day cultures of F2/5 and M1320 were not affected in ability to cause HR or necrosis. A region of about 14 kb flanking avhR was sequenced and compared with homologous regions of A. tumefaciens C58 and Sinorhizobium meliloti Rm1021 genomes. Gene order and homology are conserved between the species. A site-directed mutation in a putative gene that resides downstream of avhR and that has homology to genes belonging to the ATP-binding cassette transporter family did not affect HR or necrosis phenotypes. It was determined that avhR and aviR are expressed independently and that neither regulates the expression of a clpA homolog in F2/5. PMID:15601702

  15. An Elicitor from Botrytis cinerea Induces the Hypersensitive Response in Arabidopsis thaliana and Other Plants and Promotes the Gray Mold Disease.

    PubMed

    Govrin, Eri M; Rachmilevitch, Shimon; Tiwari, Budhi Sagar; Solomon, Mazal; Levine, Alex

    2006-03-01

    ABSTRACT Botrytis cinerea is a necrotrophic fungus that infects over 200 plant species. Previous studies showed that host cells collapse in advance of the hyphae, suggesting secretion of toxins or elicitors. We have partially characterized elicitor activity from intercellular fluid extracted from Arabidopsis thaliana leaves infected with B. cinerea. Treatment of intact leaves or cell cultures with either intercellular fluid from infected leaves or medium from inoculated A. thaliana cell culture induced generation of reactive oxygen species, resulting in reduced photosynthesis, electrolyte leakage, and necrotic lesions that resembled the hypersensitive response (HR). The necrosis was inhibited by diphenyleneiodonium, a specific inhibitor of NADPH oxidase, and by chelating free iron, suggesting the involvement of hydroxyl radicals. The necrosis was also suppressed in dnd1 mutants that are compromised in HR. In contrast, increased cell death was observed in acd2 mutants, indicating the involvement of the host defense signaling pathways. Treatment with the intercellular fluid from infected leaves also induced transcription of pathogenesis-related (PR) genes, such as PR-1, PR-5, HSR203J, and of senescence-associated gene SAG-13. Moreover, rapid transcription of the ethylene-dependent AtEBP gene was detected, indicating induction of ethylene production. The inter-cellular fluid from infected A. thaliana induced cell death in other plants, in line with the lack of B. cinerea specificity. In summary, the intercellular fluid mimicked a range of molecular and physiological host responses that are observed during infection with a live fungus. Moreover, it accelerated the B. cinerea infection, suggesting that the elicitor may act as a pathogenicity factor in the progression of gray mold disease.

  16. Glucocorticoid hypersensitivity syndrome--a case report.

    PubMed

    Krysiak, R; Okopien, B

    2012-11-01

    Glucocorticoid hypersensitivity syndrome has been reported to date only in several patients. This article describes a unique case of this syndrome in a 24-year old female admitted to hospital because of arterial hypertension and obesity. Although her clinical picture suggested Cushing's syndrome, she had low adrenocorticotropic hormone (ACTH) and cortisol levels with a poor response to corticotrophin-releasing hormone and Synacthen. In turn, an overnight dexamethasone suppression test with 0.25 mg of dexamethasone led to a dramatic decrease in morning cortisol. A diagnosis of glucocorticoid hypersensitivity was made and the patient started treatment with ketoconazole and cabergoline, which resulted in some clinical improvement. This case illustrates the need for clinical awareness of glucocorticoid hypersensitivity in patients suspected of Cushing's syndrome.

  17. Cognitive and physiological responses in humans exposed to a TETRA base station signal in relation to perceived electromagnetic hypersensitivity.

    PubMed

    Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

    2012-01-01

    Terrestrial Trunked Radio (TETRA) technology ("Airwave") has led to public concern because of its potential interference with electrical activity in the brain. The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses. Participants were exposed to a 420 MHz TETRA signal at a power flux density of 10 mW/m(2) as well as sham (no signal) under double-blind conditions. Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study. Forty-eight sensitive and 132 control participants completed all three sessions. Measures of short-term memory, working memory, and attention were administered while physiological responses (blood volume pulse, heart rate, skin conductance) were monitored. After applying exclusion criteria based on task performance for each aforementioned cognitive measure, data were analyzed for 36, 43, and 48 sensitive participants for these respective tasks and, likewise, 107,125, and 129 controls. We observed no differences in cognitive performance between sham and TETRA exposure in either group; physiological response also did not differ between the exposure conditions. These findings are similar to previous double-blind studies with other mobile phone signals (900-2100 MHz), which could not establish any clear evidence that mobile phone signals affect health or cognitive function.

  18. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice.

    PubMed

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

    2012-10-01

    Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15-60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil- and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14-28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14-28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs.

  19. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice

    PubMed Central

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

    2012-01-01

    Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15–60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil- and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14–28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14–28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs. PMID:22859364

  20. 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.

  1. An Sfp-type PPTase and associated polyketide and nonribosomal peptide synthases in Agrobacterium vitis are essential for induction of tobacco hypersensitive response and grape necrosis.

    PubMed

    Zheng, Desen; Burr, Thomas J

    2013-07-01

    An Sfp-type phosphopantetheinyl transferase (PPTase) encoding gene F-avi5813 in Agrobacterium vitis F2/5 was found to be required for the induction of a tobacco hypersensitive response (HR) and grape necrosis. Sfp-type PPTases are post-translation modification enzymes that activate acyl-carry protein (ACP) domains in polyketide synthases (PKS) and peptidyl-carrier protein (PCP) domains of nonribosomal peptide synthases (NRPS). Mutagenesis of PKS and NRPS genes in A. vitis led to the identification of a PKS gene (F-avi4330) and NRPS gene (F-avi3342) that are both required for HR and necrosis. The gene immediately downstream of F-avi4330 (F-avi4329) encoding a predicted aminotransferase was also found to be required for HR and necrosis. Regulation of F-avi4330 and F-avi3342 by quorum-sensing genes avhR, aviR, and avsR and by a lysR-type regulator, lhnR, was investigated. It was determined that F-avi4330 expression is positively regulated by avhR, aviR, and lhnR and negatively regulated by avsR. F-avi3342 was found to be positively regulated by avhR, aviR, and avsR and negatively regulated by lhnR. Our results suggest that a putative hybrid peptide-polyketide metabolite synthesized by F-avi4330 and F-avi3342 is associated with induction of tobacco HR and grape necrosis. This is the first report that demonstrates that NRPS and PKS play essential roles in conferring the unique ability of A. vitis to elicit a non-host-specific HR and host-specific necrosis.

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

    PubMed

    Moyal, D D; Fourtanier, A M

    2003-04-01

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

  3. 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 Stevens–Johnson 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

  4. [Electromagnetic fields hypersensitivity].

    PubMed

    Sobiczewska, Elzbieta; Szmigielski, Stanisław

    2009-01-01

    The development of industry, particularly of new technologies in communication systems, gives rise to the number and diversty of electromagnetic field (EMF) sources in the environment. These sources, including power-frequent, radiofrequent and microwaves, make human life richer, safer and easier. But at the same time, there is growing concern about possible health risks connected with EMF exposure. An increasing number of persons have recently reported on a variety of health problems induced, in their opinion, by exposure to EMF. It is important to note that EMF levels to which these individuals are exposed are generally well below the recommended exposure limits and are certainly far below those known to produce any adverse effects. These persons call themselves "electromagnetic hypersensitivity individuals" And complain about experiencing various types of non-specific symptoms, including dermatological, neurological and vegetative. In the present paper, the problem of electromagnetic hypersensitivity phenomenon is discussed based on the recently published literature.

  5. Dentin Hypersensitivity and Oxalates

    PubMed Central

    Cunha-Cruz, J.; Stout, J.R.; Heaton, L.J.; Wataha, J.C.

    2011-01-01

    Treatment of dentin hypersensitivity with oxalates is common, but oxalate efficacy remains unclear. Our objective was to systematically review clinical trials reporting an oxalate treatment compared with no treatment or placebo with a dentin hypersensitivity outcome. Risk-of-bias assessment and data extraction were performed independently by two reviewers. Standardized mean differences (SMD) were estimated by random-effects meta-analysis. Of 677 unique citations, 12 studies with high risk-of-bias were included. The summary SMD for 3% monohydrogen-monopotassium oxalate (n = 8 studies) was -0.71 [95% Confidence Interval: -1.48, 0.06]. Other treatments, including 30% dipotassium oxalate (n = 1), 30% dipotassium oxalate plus 3% monohydrogen monopotassium oxalate (n = 3), 6% monohydrogen monopotassium oxalate (n = 1), 6.8% ferric oxalate (n = 1), and oxalate-containing resin (n = 1), also were not statistically significantly different from placebo treatments. With the possible exception of 3% monohydrogen monopotassium oxalate, available evidence currently does not support the recommendation of dentin hypersensitivity treatment with oxalates. PMID:21191127

  6. [Food hypersensitivity in children].

    PubMed

    Kolacek, Sanja

    2011-01-01

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

  7. Teenagers' experiences of living with food hypersensitivity: a qualitative study.

    PubMed

    MacKenzie, Heather; Roberts, Graham; van Laar, Darren; Dean, Taraneh

    2010-06-01

    Teenagers are a high-risk group for food-hypersensitivity fatalities, engage in risk-taking behaviours and may experience impaired quality of life. Understanding their experience is important to inform their care. This study aimed to describe the lived experiences of teenagers with food hypersensitivity. Individual semi-structured interviews were conducted with 21 teenagers (13-18 yr) with food hypersensitivity to a variety of foods and analysed using a phenomenological approach. Teenagers described living with (or coming to know) food hypersensitivity (FHS) as a way of life but still found living with food hypersensitivity to be burdensome. A necessary part of living with food hypersensitivity was coping with associated burden; a variety of coping strategies were employed to this effect. Teenagers described ways in which the burden of living with food hypersensitivity was alleviated or exacerbated by others. Management of food hypersensitivity was based on an assessment of acceptable risk resulting in varying levels of precaution taking. Teenagers' understanding of their FHS and ability to cope with it needs to be regularly assessed. Educational support may be required to ensure they take an appropriate level of precautions to minimize the chance of future reactions while not over compromising their quality of life. Psychological support may be required to help them to utilize healthy adaptive strategies to cope with the stresses of living with FHS. This approach is also likely to facilitate the smooth handover of responsibility from parent to teenager.

  8. 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.; González, 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 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Results Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Conclusions Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide. PMID:24416141

  9. [Nonallergic hypersensitivity to environmental factors].

    PubMed

    Rakhmanin, Iu A; Fedoseeva, V N; Makovetskaia, A K; Fedoskova, T G

    2013-01-01

    The prevalence and severity of manifestations of non-allergic hypersensitivity to chemical environmental factors pose the question about the need to study the mechanisms of its formation in population. It should be borne in mind that, in the absence of immunological mechanisms of formation of the mentioned state, the term "chemical sensitization" must be replaced by the term "non-allergic hypersensitivity." The investigation of this problem should permit to reduce the risk of formation of different types of hypersensitivity in population.

  10. Hypersensitivity reactions to vaccine components.

    PubMed

    Heidary, Noushin; Cohen, David E

    2005-09-01

    Vaccines are responsible for the control of many infectious diseases that were once common in the United States, including polio, measles, diphtheria, pertussis (whooping cough), rubella (German measles), mumps, tetanus, and Haemophilus influenzae type b. National efforts to generate collaboration between federal, state, and local governments and public and private health care providers have resulted in record high levels of vaccination coverage in the United States. The high rate of US vaccinations is paralleled by growing concerns about the safety of their delivery. The variety of substances used in vaccines sometimes causes the development of cutaneous reactions in susceptible adults and children. This article will review adverse cutaneous events consistent with hypersensitivity reactions to the following ingredients in vaccines: aluminum, thimerosal, 2-phenoxyethanol, formaldehyde, and neomycin.

  11. [STATE OF NONALLERGIC HYPERSENSITIVITY UNDER THE EXPOSURE TO ADVERSE ENVIRONMENTAL FACTORS].

    PubMed

    Fedoseeva, V N; Makovetskaya, A K; Fedoskova, T G; Mislavskiy, O V; Stomakhina, N V

    2015-01-01

    Now a number of allergopatologies is shown to be formed as non-allergic hypersensitivity. Research of this state is especially important when studying a question of formation of a condition of a chemical sensitization in response to the contact of a human body with chemical pollutants. For diagnostics of reactions of non-allergic hypersensitivity the test was developed for an assessment of activation of basophiles by specific allergens (the test of activation of basophiles by method of a flowing cytometry Flow Cast® (BD FACSCalibur)). It is possible to judge by activation on an expression of some receptors on a surface of these cages (CD63). Examination of a group of persons, having continuous contact with means of household chemicals was performed. In 54.5% of the examined persons the percent of CD63-of nonspecific activated cages was revealed to be at the level of 16-65% that gives the grounds to assume existence of a condition of not allergic hypersensitivity. Thus, the test of activation of basophiles by method of a flowing cytometry can be used for a differentiation of an IgE-dependent allergy from a condition of non-allergic hypersensitivity.

  12. [STATE OF NONALLERGIC HYPERSENSITIVITY UNDER THE EXPOSURE TO ADVERSE ENVIRONMENTAL FACTORS].

    PubMed

    Fedoseeva, V N; Makovetskaya, A K; Fedoskova, T G; Mislavskiy, O V; Stomakhina, N V

    2015-01-01

    Now a number of allergopatologies is shown to be formed as non-allergic hypersensitivity. Research of this state is especially important when studying a question of formation of a condition of a chemical sensitization in response to the contact of a human body with chemical pollutants. For diagnostics of reactions of non-allergic hypersensitivity the test was developed for an assessment of activation of basophiles by specific allergens (the test of activation of basophiles by method of a flowing cytometry Flow Cast® (BD FACSCalibur)). It is possible to judge by activation on an expression of some receptors on a surface of these cages (CD63). Examination of a group of persons, having continuous contact with means of household chemicals was performed. In 54.5% of the examined persons the percent of CD63-of nonspecific activated cages was revealed to be at the level of 16-65% that gives the grounds to assume existence of a condition of not allergic hypersensitivity. Thus, the test of activation of basophiles by method of a flowing cytometry can be used for a differentiation of an IgE-dependent allergy from a condition of non-allergic hypersensitivity. PMID:26856160

  13. 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

  14. Anticonvulsant hypersensitivity syndrome.

    PubMed

    Morkunas, A R; Miller, M B

    1997-10-01

    Anticonvulsant hypersensitivity syndrome (AHS) is an uncommon but potentially fatal adverse effect that can occur from exposure to phenytoin, carbamazepine, or phenobarbital. It has diverse clinical features and a variable presentation which results in a delay in making the diagnosis. The syndrome commonly begins within 3 weeks after initiation of an anticonvulsant. Patients typically present with a constellation of fever, usually followed by the development of a rash of variable severity and type, and lymphadenopathy. In patients presenting with these features, the clinician should have a high index of suspicion for AHS. PMID:9330838

  15. Chronic hypersensitivity pneumonitis

    PubMed Central

    Pereira, Carlos AC; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. PMID:27703382

  16. 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

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

    PubMed

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

    2015-01-01

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

  18. 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

  19. Drought-Responsive Mechanisms in Plant Leaves Revealed by Proteomics

    PubMed Central

    Wang, Xiaoli; Cai, Xiaofeng; Xu, Chenxi; Wang, Quanhua; Dai, Shaojun

    2016-01-01

    Plant drought tolerance is a complex trait that requires a global view to understand its underlying mechanism. The proteomic aspects of plant drought response have been extensively investigated in model plants, crops and wood plants. In this review, we summarize recent proteomic studies on drought response in leaves to reveal the common and specialized drought-responsive mechanisms in different plants. Although drought-responsive proteins exhibit various patterns depending on plant species, genotypes and stress intensity, proteomic analyses show that dominant changes occurred in sensing and signal transduction, reactive oxygen species scavenging, osmotic regulation, gene expression, protein synthesis/turnover, cell structure modulation, as well as carbohydrate and energy metabolism. In combination with physiological and molecular results, proteomic studies in leaves have helped to discover some potential proteins and/or metabolic pathways for drought tolerance. These findings provide new clues for understanding the molecular basis of plant drought tolerance. PMID:27763546

  20. Drug hypersensitivity syndrome.

    PubMed

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

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

  1. 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

  2. Case of immediate hypersensitivity to beer.

    PubMed

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

    2016-06-01

    We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. PMID:26661797

  3. STUDIES ON HYPERSENSITIVITY

    PubMed Central

    Gell, P. G. H.; Benacerraf, B.

    1961-01-01

    In earlier observations with the picryl system, it was concluded that contact sensitivity was a form of delayed (cellular) hypersensitivity to conjugates of sensitizer with autologous proteins indistinguishable in its immunological mechanism from other classical forms of delayed hypersensitivity to proteins. This conclusion has been confirmed and extended with the picryl and chlorbenzoyl chloride systems. 1. It is shown that to induce a state of contact sensitivity, the minimal necessary amounts of hapten are of the same order of magnitude, whether this hapten is conjugated with protein or the free reactive chemical itself. From this, it is evident that contamination of conjugates with small amounts of unreacted sensitizer plays no part in the induction of contact reactivity by the conjugate. With the dinitrophenyl system, no contact sensitivity could be induced by the conjugates used; possible reasons for this discrepancy are discussed. 2. Animals sensitized to contact by homologous conjugate can be completely desensitized by injections of such a conjugate in large amount; a similar injection schedule has no effect on the contact sensitivity of animals sensitized with the free reactive sensitizer. 3. The capacity of heterologous (ovalbumin) conjugates to evoke anti-hapten antibodies is shown to be greater than that of homologous (guinea pig seralbumin) conjugates: the reverse is true of their capacity to induce delayed reactivity. 4. Evidence is brought forward to suggest that in animals sensitized with homologous albumin conjugates, the specificity of the delayed reaction involves more than the hapten alone, even though the carrier protein is non-antigenic on its own. The contrast with the apparent lesser specificity of the antibodies later produced is discussed. PMID:13704282

  4. Sequential analysis of the numerical Stroop effect reveals response suppression.

    PubMed

    Cohen Kadosh, Roi; Gevers, Wim; Notebaert, Wim

    2011-09-01

    Automatic processing of irrelevant stimulus dimensions has been demonstrated in a variety of tasks. Previous studies have shown that conflict between relevant and irrelevant dimensions can be reduced when a feature of the irrelevant dimension is repeated. The specific level at which the automatic process is suppressed (e.g., perceptual repetition, response repetition), however, is less understood. In the current experiment we used the numerical Stroop paradigm, in which the processing of irrelevant numerical values of 2 digits interferes with the processing of their physical size, to pinpoint the precise level of the suppression. Using a sequential analysis, we dissociated perceptual repetition from response repetition of the relevant and irrelevant dimension. Our analyses of reaction times, error rates, and diffusion modeling revealed that the congruity effect is significantly reduced or even absent when the response sequence of the irrelevant dimension, rather than the numerical value or the physical size, is repeated. These results suggest that automatic activation of the irrelevant dimension is suppressed at the response level. The current results shed light on the level of interaction between numerical magnitude and physical size as well as the effect of variability of responses and stimuli on automatic processing.

  5. 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

  6. An unexpected positive hypersensitive reaction to eugenol.

    PubMed

    Tammannavar, Praveen; Pushpalatha, C; Jain, Shrenik; Sowmya, S V

    2013-09-18

    Eugenol is an active, principal aromatic liquid responsible for several pharmacological activities. It is widely used in dental practice to relieve pain arising from various sources, such as pulpitis and dentinal hypersensitivity. As a primary irritant and sensitiser, it is known to cause contact urticaria as well as chronic urticaria. However, eugenol causes allergic contact dermatitis, possibly because it can react directly with proteins to form conjugate and reactive haptens. It is found that eugenol in various dental preparations-especially in the case of some zinc oxide-contains preparations such as periodontal dressings and root canal cements. This can cause hypersensitivity when it comes in contact with gingiva or teeth. This article presents a case of immediate allergic contact urticaria to eugenol during dental treatment.

  7. Hypersensitivity vasculitis associated with leuprolide (Lupron).

    PubMed

    Gnanaraj, Joseph; Saif, Muhammad Wasif

    2010-09-01

    Leuprolide (Lupron) is a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH). Leuprolide is used as a hormonal antagonist in the treatment of advanced prostatic cancer, and as hormonal therapy in the treatment of endometriosis. Off-label, it is also used in premenopausal or perimenopausal women with hormone-responsive breast cancer for the purpose of ovarian ablation. Ever since its FDA approval in 1985, many adverse reactions have been reported in association with leuprolide ranging from local skin irritation to severe anaphylactoid reactions. In this case report, we present a case of hypersensitivity vasculitis (serum sickness) in a patient who received leuprolide for his prostate cancer. Serum sickness has never been reported as a side-effect of leuprolide. Our case is the first case of serum sickness associated with leuprolide. We emphasize that physicians using leuprolide should be wary of signs and symptoms of hypersensitivity vasculitis or serum sickness.

  8. An unexpected positive hypersensitive reaction to eugenol

    PubMed Central

    Tammannavar, Praveen; C, Pushpalatha; Jain, Shrenik; SV, Sowmya

    2013-01-01

    Eugenol is an active, principal aromatic liquid responsible for several pharmacological activities. It is widely used in dental practice to relieve pain arising from various sources, such as pulpitis and dentinal hypersensitivity. As a primary irritant and sensitiser, it is known to cause contact urticaria as well as chronic urticaria. However, eugenol causes allergic contact dermatitis, possibly because it can react directly with proteins to form conjugate and reactive haptens. It is found that eugenol in various dental preparations-especially in the case of some zinc oxide–contains preparations such as periodontal dressings and root canal cements. This can cause hypersensitivity when it comes in contact with gingiva or teeth. This article presents a case of immediate allergic contact urticaria to eugenol during dental treatment. PMID:24049087

  9. Chapter 28: Classification of hypersensitivity reactions.

    PubMed

    Uzzaman, Ashraf; Cho, Seong H

    2012-01-01

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

  10. Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis.

    PubMed

    Hariri, Lida P; Mino-Kenudson, Mari; Shea, Barry; Digumarthy, Subba; Onozato, Maristela; Yagi, Yukako; Fraire, Armando E; Matsubara, Osamu; Mark, Eugene J

    2012-05-01

    Hypersensitivity pneumonitis is an inflammatory lung disease that develops in response to exposure to antigen. Cases can be stratified by the duration of exposure and speed of symptom progression into acute, subacute, and chronic hypersensitivity pneumonitis. Although the pathologic features of subacute hypersensitivity pneumonitis are well established and those of chronic hypersensitivity pneumonitis have been reported, little is known about the histopathology of acute hypersensitivity pneumonitis. We evaluated the pathologic features of 5 patients with clinically confirmed hypersensitivity pneumonitis and rapid onset of symptoms and 3 patients with subacute or chronic hypersensitivity pneumonitis with symptom exacerbation. Histopathologic features assessed in each case included those characteristic of subacute hypersensitivity pneumonitis (bronchiolocentric chronic inflammation, histiocytic aggregates, and bronchiolitis obliterans), those associated with acute inflammation (fibrin deposition and neutrophilic infiltrate), and fibrosis. The classic features of hypersensitivity pneumonitis were identified in all 8 cases, with 1 also exhibiting fixed fibrosis confirming underlying chronic hypersensitivity pneumonitis. Fibrin deposition was present in 8 (100%) of 8 cases, and its extent was significant (28% surface area fibrin deposition/total disease area on average). Two had intra-alveolar fibrin so marked that it resembled acute fibrinous and organizing pneumonia. In addition, prominent interstitial neutrophilic infiltrate (≥5 cells/high-power field) was seen in all cases. These features have not been reported as characteristics of subacute or chronic hypersensitivity pneumonitis. Increased fibrin deposition and neutrophilic infiltrate may characterize acute hypersensitivity pneumonitis or abrupt exacerbation of hypersensitivity pneumonitis, and these along with characteristic features of subacute hypersensitivity pneumonitis (granulomatous inflammation and

  11. Sulfite hypersensitivity. A critical review

    SciTech Connect

    Gunnison, A.F.; Jacobsen, D.W.

    1987-01-01

    Sulfiting agents (sulfur dioxide and the sodium and potassium salts of bisulfite, sulfite, and metabisulfite) are widely used as preservatives in foods, beverages, and pharmaceuticals. Within the past 5 years, there have been numerous reports of adverse reactions to sulfiting agents. This review presents a comprehensive compilation and discussion of reports describing reactions to ingested, inhaled, and parenterally administered sulfite. Sulfite hypersensitivity is usually, but not exclusively, found within the chronic asthmatic population. Although there is some disagreement on its prevalence, a number of studies have indicated that 5 to 10% of all chronic asthmatics are sulfite hypersensitive. This review also describes respiratory sulfur dioxide sensitivity which essentially all asthmatics experience. Possible mechanisms of sulfite hypersensitivity and sulfur dioxide sensitivity are discussed in detail. Sulfite metabolism and the role of sulfite oxidase in the detoxification of exogenous sulfite are reviewed in relationship to the etiology of sulfite hypersensitivity. 147 references.

  12. Quantification of the stapedial reflex reveals delayed responses in autism.

    PubMed

    Lukose, Richard; Brown, Kevin; Barber, Carol M; Kulesza, Randy Joseph

    2013-10-01

    Autism is a developmental disorder characterized, in part, by sensory abnormalities. It is well established that most if not all patients with autism have problems with auditory processing, ranging from deafness to hyperacusis, and physiological testing of auditory function (i.e. auditory brain stem responses) implicates brain stem dysfunction in autism. Additionally, previous research from this lab has revealed significantly fewer auditory brain stem neurons in autistic subjects as young as 2 years of age. These observations have led us to hypothesize that objective, noninvasive measures of auditory function can be used as an early screening tool to identify neonates with an elevated risk of carrying a diagnosis of autism. Here, we provide a detailed quantitative investigation of the acoustic stapedial reflex (ASR), a three- or four-neuron brain stem circuit, in young autistic subjects and normal developing controls. Indeed, we find significantly lower thresholds, responses occurring at significantly longer latency and right-left asymmetry in autistic subjects. The results from this investigation support deficits in auditory function as a cardinal feature of autism and suggest that individuals with autism can be identified by their ASR responses. PMID:23825093

  13. 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

  14. Hypersensitivity reactions to iodinated contrast media.

    PubMed

    Guéant-Rodriguez, Rosa-Maria; Romano, Antonino; Barbaud, Annick; Brockow, Knut; Guéant, Jean-Louis

    2006-01-01

    Adverse reactions after iodinate contrast media (ICM) administration have been observed, which can be classified as immediate (i.e., occurring within one hour after administration) and delayed or non-immediate (i.e., occurring more than one hour after administration). Even though the incidence of ICM adverse reactions has been significantly reduced by the introduction of non-ionic compounds, immediate reactions still occur in about 3% of administrations. Different pathogenic mechanisms have been suggested for ICM reactions, including immunologic ones. Basophils and mast cells participate in immediate reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most non-immediate reactions, particularly maculopapular rashes. Skin tests and specific IgE assays are carried out to diagnose immediate hypersensitivity reactions, while both delayed-reading intradermal tests and patch tests are usually performed to evaluate non-immediate reactions. However, in vitro specific IgE assays are not commercially available. As far as in vitro tests are concerned, a response involving ICM-related T-cell activity may be assessed by the lymphocyte transformation test. Allergologic evaluation appears to be indicated in hypersensitivity reactions to ICM, although the sensitivity, specificity, and predictive values of allergologic tests have not yet been established. This paper summarizes the current state of the art and addresses the research that is still needed on the pathogenic mechanisms, diagnosis, and prevention of ICM-induced hypersensitivity reactions.

  15. The immune response to infection with vaccinia virus in mice. II. Appearance of hypersensitivity, production of macrophage migration inhibitory factor and transformation of spleen cells in response to virus antigens.

    PubMed Central

    Hutt, L. M.

    1975-01-01

    The appearance of specific hypersensitivity to virus antigens was examined in mice infected intravenously with vaccinia virus. Both immediate hypersensitivity, transferable by serum, and delayed-type hypersensitivity, transferable only by cells, were apparent 8 days after infection and demonstrable for at least a further 130 days. Production of macrophage migration inhibitory factor by lymphocytes from infected mice was measured directly in terms of inhibition of migration by antigen or indirectly by determining the effect of soluble factors elaborated by the stimulated lymphocytes. The irregular results may have been the resultants of antigen-mediated macrophage stimulation, toxicity and induction of migration inhibitory factor. Transformation of spleen cells - presumably lymphocytes - from infected mice could be induced in vitro by virus antigens for at least 139 days after infection. Virus/lymphocyte interaction appears to be a particularly fruitful area for further study. PMID:1056960

  16. 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

  17. Hypersensitivity to fluoroquinolones

    PubMed Central

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

    2016-01-01

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

  18. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs. PMID:18991707

  19. Zeta Inhibitory Peptide as a Novel Therapy to Control Chronic Visceral Hypersensitivity in a Rat Model

    PubMed Central

    Chen, Yu; Guo, Lixia; Dai, Hengfen; Huang, Yang; Chen, Qianqian; Lin, Chun

    2016-01-01

    Background The pathogenesis of multiple chronic visceral pain syndromes, such as irritable bowel syndrome (IBS), is not well known, and as a result current therapies are ineffective. The objective of this study was to investigate the effect of spinal protein kinase M zeta (PKMζ) on visceral pain sensitivity in rats with IBS to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide (ZIP) as a therapy for chronic visceral pain. Methods Visceral hypersensitivity rats were produced by neonatal maternal separation (NMS). Visceral pain sensitivity was assessed by electromyographic (EMG) responses of abdominal muscles to colorectal distention (CRD). Spinal PKMζ and phosphorylated PKMζ (p-PKMζ) were detected by western blot. Varying doses of ZIP were intrathecally administered to investigate the role of spinal PKMζ in chronic visceral hypersensitivity. The open field test was used to determine if ZIP therapy causes spontaneous motor activity side effects. Results Graded CRD pressure significantly increased EMG responses in NMS rats compared to control rats (p < 0.05). p-PKMζ expression increased in the thoracolumbar and lumbosacral spinal cord in the IBS-like rats with notable concomitant chronic visceral pain compared to control rats (p < 0.05). EMG data revealed that intrathecal ZIP injection (1, 5, and 10 μg) dose-dependently attenuated visceral pain hypersensitivity in IBS-like rats. Conclusions Phosphorylated PKMζ may be involved in the spinal central sensitization of chronic visceral hypersensitivity in IBS, and administration of ZIP could effectively treat chronic visceral pain with good outcomes in rat models. PMID:27776136

  20. Delayed hypersensitivity to a corticosteroid suspension containing methylprednisolone. Two cases of conjunctival inflammation after retrobulbar injection.

    PubMed

    Mathias, C G; Robertson, D B

    1985-02-01

    Two patients with chronic iridocyclitis had a delayed hypersensitivity reaction, characterized by severe conjunctival inflammation, after retrobulbar injections with a commercial suspension of methylprednisolone acetate. Although patch test reactions to methylprednisolone at enhanced concentrations were negative, delayed hypersensitivity could be easily demonstrated by intradermal testing with this corticosteroid. Both patients also had concomitant delayed hypersensitivity to a proprietary preservative (myristyl gamma-picolinium chloride) in the commercial corticosteroid suspension, which was confirmed by intradermal testing. These observations (negative patch test reactions, positive intradermal test reactions) suggest that the route of administration may be an important determinant of antigenic hapten-protein complex formation and subsequent delayed hypersensitivity responses involving cutaneous or mucocutaneous tissue.

  1. Immediate hypersensitivity reaction with mango.

    PubMed

    Shah, Ashok; Gera, Kamal

    2014-01-01

    Hypersensitivity to the fruit mango is extremely rare and can exhibit either as immediate or delayed reactions. Since 1939, only 22 patients (10 with immediate type I reactions and 12 with delayed) have been documented with allergy to mango. History of atopy and geographical region may influence the type of reaction. Immediate reactions occurred most often in patients with history of atopy, while delayed reactions developed in non-atopic individuals. Clustering of delayed hypersensitivity reports from Australia and immediate reactions from Europe has been documented. We report a 50-year-old man with immediate type I hypersensitivity to mango, who developed cough, wheezing dyspnoea, generalised itching and abdominal discomfort after ingestion of mango. Life threatening event can also happen making it imperative to diagnose on time, so as to prevent significant morbidity and potential mortality. PMID:25133813

  2. Dentin hypersensitivity and its management.

    PubMed

    Chu, C H; Lam, Anty; Lo, Edward C M

    2011-01-01

    Dentin hypersensitivity is a common patient complaint that is more prevalent than the profession realizes. It is important for dentists to diagnose dentin hypersensitivity by exclusion and provide appropriate treatment recommendations for patients. Various treatment methods have been proposed but no universally accepted desensitizing agent or treatment has been identified. When a patient has symptoms that can be attributed to dentin hypersensitivity, a thorough clinical examination should be carried out to rule out other likely causes prior to diagnosis and treatment. Depending on the identified cause, a combination of individualized instructions on proper oral health behaviors, use of at-home products, and professional treatment may be required to manage the problem. PMID:21903521

  3. [Hypersensitivity pneumonitis after exposure to Candida spp].

    PubMed

    Serrano, Carlos; Torrego, Alfonso; Loosli, Alfonso; Valero, Antonio; Picado, César

    2010-05-01

    Hypersensitivity pneumonitis (HP) is a lung disease caused by heavy and recurrent inhalation of antigens. We describe the case of a patient with HP caused by domestic exposure to Candida spp. The diagnosis was made by taking into consideration the, clinical presentation, exposure history, radiological findings, bronchoalveolar lavage, lung function and the immuno-allergy study. The diagnosis was definitively confirmed by performing a specific bronchial provocation test. It has been shown that there is cross-reactivity between different Candida species, and despite making the diagnosis in this case with Candida albicans, we were unable to define exactly which species was responsible for the HP.

  4. Hypersensitivity and pain induced by operative procedures and the "cracked tooth" syndrome.

    PubMed

    Seltzer, S; Boston, D

    1997-01-01

    Various dental conditions are responsible for tooth hypersensitivity and pain. They include hypersensitive dentin; the "cracked tooth" syndrome; pulp and periapical irritation, inflammation and/or degeneration; barodontalgia (aerodontalgia); and periodontal pathoses, particularly the pulpal-periodontal syndrome. Each operative condition is reviewed with respect to its etiology, symptomatology, and diagnosis. Some treatment recommendations are made to prevent or reduce symptoms.

  5. 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...

  6. 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

  7. 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; Díaz, R; Grilló, M J; Barberán, M; Marín, C; Blasco, J M; Moriyón, 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

  8. 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.

  9. 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.

  10. 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-Baptistão, Carla Cristina; Teixeira, Daniela; 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

  11. 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

  12. 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

  13. Lymphocyte transformation studies in drug hypersensitivity

    PubMed Central

    Warrington, R.J.; Tse, K.S.

    1979-01-01

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents. Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects. For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test. It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs. PMID:445303

  14. The P25 pathogenicity factor of Beet necrotic yellow vein virus targets the sugar beet 26S proteasome involved in the induction of a hypersensitive resistance response via interaction with an F-box protein.

    PubMed

    Thiel, Heike; Hleibieh, Kamal; Gilmer, David; Varrelmann, Mark

    2012-08-01

    P25, a Beet necrotic yellow vein virus (BNYVV) pathogenicity factor, interacts with a sugar beet protein with high homology to Arabidopsis thaliana kelch repeat containing F-box family proteins (FBK) of unknown function in yeast. FBK are members of the Skp1-Cullin-F-box (SCF) complex that mediate protein degradation. Here, we confirm this sugar beet FBK-P25 interaction in vivo and in vitro and provide evidence for in planta interaction and similar subcellular distribution in Nicotiana tabacum leaf cells. P25 even interacts with an FBK from A. thaliana, a BNYVV nonhost. FBK functional classification was possible by demonstrating the interaction with A. thaliana orthologs of Skp1-like (ASK) genes, a member of the SCF E3 ligase. By means of a yeast two-hybrid bridging assay, a direct effect of P25 on SCF-complex formation involving ASK1 protein was demonstrated. FBK transient Agrobacterium tumefaciens-mediated expression in N. benthamiana leaves induced a hypersensitive response. The full-length F-box protein consists of one F-box domain followed by two kelch repeats, which alone were unable to interact with P25 in yeast and did not lead to cell-death induction. The results support the idea that P25 is involved in virus pathogenicity in sugar beet and suggest suppression of resistance response. PMID:22512382

  15. Hemolysate-mediated renal vasoconstriction and hypersensitization.

    PubMed

    Burke, T J; Falk, S; Conger, J D; Voelkel, N F

    1999-01-01

    The present studies measured vessel diameter, before and after addition of hemolysate, in isolated afferent arterioles (AA) and efferent arterioles (EA) obtained from the rat kidney. Human red blood cells (RBC) were hemolyzed in distilled water and membranes were discarded after centrifugation. Hemolysate added to the bath solution caused vigorous AA and EA contraction and, after washout, hypersensitized the AA and EA to doses of angiotensin II (AII) which would normally only elicit 50% contraction (EC50). Neither the contraction nor the hypersensitization were mimicked by pure human hemoglobin. The vasoconstrictive responses in the AA and EA were accompanied by increased cytosolic-free calcium concentration. Further purification (desalting) of the hemolysate to remove substance of < or = 1000 Da (which include ATP) did not eliminate the vasoconstrictive component from the hemolysate. Finally, cultured rat aortic vascular smooth muscle cells also demonstrated a rapid increase in (Ca2+i) when exposed to hemolysate. This increase in (Ca2+i) was, in part, dependent on Ca2+ influx since it could be attenuated with diltiazem (10(-5) M). In conclusion, hemolysate contains a factor which induces contractions of the isolated rat kidney AA and EA and rapid elevations in (Ca2+i). This factor, from hemolyzed RBC, is not hemoglobin itself. PMID:10048115

  16. 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

  17. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2010.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2011-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year.

  18. Food hypersensitivity in a cat.

    PubMed

    Medleau, L; Latimer, K S; Duncan, J R

    1986-09-15

    Food hypersensitivity was diagnosed in a 4-year-old Siamese cat. Clinical signs included intense erythema, with alopecia, excoriations, erosions, and crusts involving the ventral portion of the abdomen, inguinal region, medial aspect of each thigh, and cranial and lateral aspects of all 4 limbs. The cat was intensely pruritic. Histologically, there was cutaneous mast cell hyperplasia and diffuse infiltration of eosinophils in the dermis. Blood eosinophilia also was found. Clinical signs resolved after exclusive feeding of a hypoallergenic diet.

  19. Hypersensitivity pneumonitis during minocycline treatment.

    PubMed

    Kloppenburg, M; Dijkmans, B A; Breedveld, F C

    1994-06-01

    A patient is reported who developed dyspnoea, fever, pleuritic chest pain and a non-productive cough following treatment with minocycline for 9 days. The chest radiograph showed an interstitial pattern and there was a peripheral eosinophilia. A diagnosis of hypersensitivity pneumonitis attributable to minocycline was made. The disease responded quickly to withdrawal of the drug. This observation shows that minocycline, despite its mild toxicity profile, can give rise to serious adverse effects.

  20. Genotyping for Severe Drug Hypersensitivity

    PubMed Central

    Karlin, Eric; Phillips, Elizabeth

    2014-01-01

    Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety. PMID:24429903

  1. [Phenytoin hypersensitivity syndrome].

    PubMed

    García-Samaniego, J; Soriano, V; Soto, J; Muñoz, F

    1994-11-01

    Diphenylhydantoine is a drug frequently used in the treatment of epilepsia. In rare occasions, it produces a mulsisystemic manifestation characterized by fever, lymphadenopathy, hepatitis, eosinophilia and desquamative cutaneous eruption, which typically develops within 4-8 weeks after the beginning of the treatment. Mortality rates may reach up to 40% in patients with severe hepatic affection, although the response to steroid therapy is usually frequent. We present the case of a patient which developed a syndrome of hypersensibility to diphenylhydantoine with mononucleosic manifestations, icteric hepatitis and exfoliative dermatitis, who completely recovered a few days after his hospitalization. PMID:7654902

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

    PubMed

    Yu, Chuan-Hang; Chang, Yu-Chao

    2014-06-01

    Dentin hypersensitivity is a common symptomatic condition that causes discomfort and sometimes severe pain. The purpose of this study was to evaluate the clinical efficacy of the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser treatment on cervically exposed hypersensitive dentin. Twenty patients with dentin hypersensitivity of caries-free teeth were selected. A visual analog scale (VAS) was used to measure dentin sensitivity in response to air stimulus. A 2-minute Er:YAG laser (energy level: 60 mJ/pulse; repetition rate: 2 Hz) was applied to cervically exposed hypersensitive dentin. After 4 weeks, the hypersensitive teeth were examined again, and the VAS score was measured again and recorded. No complications such as detrimental pulpal effects were observed. Eighteen participants reported significantly reduced dentin hypersensitivity 4 weeks after the laser desensitization treatment. The VAS scores measured 4 weeks after the Er:YAG laser desensitization treatment were significantly decreased as compared with those measured at the baseline (p < 0.05). In conclusion, the Er:YAG laser desensitization treatment can effectively reduce hypersensitivity of cervically exposed hypersensitive dentin. PMID:23602018

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

    PubMed

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

    2007-01-01

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

  4. Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice.

    PubMed

    Kripke, M L; Morison, W L

    1986-05-01

    Exposing mice to UV radiation in the UVB range (280-320 nm) causes a selective immune suppression that contributes to the development of UVB-induced skin cancers. Among the immune responses suppressed by UVB irradiation are contact and delayed hypersensitivity reactions to haptens administered at unexposed sites. In these studies we provide evidence that delayed and contact hypersensitivity to the same hapten are not equivalent reactions and that they are suppressed in UVB-irradiated mice by 2 different mechanisms. This conclusion is based on the findings that: suppression of contact hypersensitivity could not be overcome by immunizing UVB-irradiated mice with hapten-coupled antigen-presenting cells derived from normal donors; and treatment of UVB-irradiated mice with methylprednisolone before immunization prevented the suppression of delayed hypersensitivity but had no effect on the suppression of contact hypersensitivity. The decreased ability to induce contact hypersensitivity in UVB-irradiated mice could be transferred to x-irradiated mice by reconstituting them with spleen cells from UVB-irradiated donors. The induction of hapten-specific suppressor cells, however, required both UVB irradiation and priming with hapten. Based on these results, we postulate that UVB irradiation induces a population of suppressor-inducer cells with specificity for a modified skin antigen and that this antigen serves as a carrier molecule for haptens that induce contact hypersensitivity and for tumor-specific transplantation antigens on UVB-induced tumors. PMID:3745963

  5. 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.

  6. Biochemical Analyses of Sorghum Varieties Reveal Differential Responses to Drought

    PubMed Central

    Ogbaga, Chukwuma C.; Stepien, Piotr; Dyson, Beth C.; Rattray, Nicholas J. W.; Ellis, David I.; Goodacre, Royston; Johnson, Giles N.

    2016-01-01

    We have examined the biochemical responses of two sorghum cultivars of differing drought tolerance, Samsorg 17 (more drought tolerant) and Samsorg 40 (less drought tolerant), to sustained drought. Plants were exposed to different degrees of drought and then maintained at that level for five days. Responses were examined in terms of metabolic changes and the expression of drought induced proteins—Heat Shock Proteins (HSPs) and dehydrins (DHNs). Generalised phenotypic changes were studied using Fourier transform infrared (FT-IR) Spectroscopy and non-targeted Gas Chromatography Mass Spectrometry (GC-MS) was employed to detect changes in metabolites, while changes in protein expression were examined using Western blot analysis. Different response profiles of metabolites, HSPs and DHNs were observed in the two cultivars. Metabolic changes involved variation in amino acids, polysaccharides and their derivatives. A total of 188 compounds, with 142 known metabolites and 46 unknown small molecules, were detected in the two sorghum varieties. Under water deficit conditions, Samsorg 17 accumulated sugars and sugar alcohols, while in Samsorg 40 amino acids increased in concentration. This study suggest that the two Sorghum varieties adopt distinct approaches in response to drought, with Samsorg 17 being better able to maintain leaf function under severe drought conditions. PMID:27153323

  7. 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 Adélie (P. adeliae), gentoo (P. papua), and chinstrap penguins (P. antarctica). Breeding colonies of Adélie and chinstrap penguins have declined by roughly 50% since the mid-1970s, and recruitment indices of Adélie 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.

  8. Compensatory islet response to insulin resistance revealed by quantitative proteomics

    SciTech Connect

    El Ouaamari, Abdelfattah; Zhou, Jian -Ying; Liew, Chong Wee; Shirakawa, Jun; Dirice, Ercument; Gedeon, Nicholas; Kahraman, Sevim; De Jesus, Dario F.; Bhatt, Shweta; Kim, Jong -Seo; Clauss, Therese R. W.; Camp, II, David G.; Smith, Richard D.; Qian, Wei -Jun; Kulkarni, Rohit N.

    2015-07-07

    Compensatory islet response is a distinct feature of the pre-diabetic insulin resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from five-month-old male control, high-fat diet fed (HFD) or obese ob/ob mice by LC-MS(/MS) and quantified ~1,100 islet proteins (at least two peptides) with a false discovery rate <1%. Significant alterations in abundance were observed for ~350 proteins between groups. A majority of alterations were common to both models, and the changes of a subset of ~40 proteins and 12 proteins were verified by targeted quantification using selected reaction monitoring and Western blots, respectively. The insulin resistant islets in both groups exhibited reduced expression of proteins controlling energy metabolism, oxidative phosphorylation, hormone processing, and secretory pathways. Conversely, an increased expression of molecules involved in protein synthesis and folding suggested effects in endoplasmic reticulum stress response, cell survival, and proliferation in both insulin resistant models. In conclusion, we report a unique comparison of the islet proteome that is focused on the compensatory response in two insulin resistant rodent models that are not overtly diabetic. In conclusion, these data provide a valuable resource of candidate proteins to the scientific community to undertake further studies aimed at enhancing β-cell mass in patients with diabetes. The data are available via the MassIVE repository, with accession MSV000079093.

  9. Compensatory islet response to insulin resistance revealed by quantitative proteomics

    DOE PAGES

    El Ouaamari, Abdelfattah; Zhou, Jian -Ying; Liew, Chong Wee; Shirakawa, Jun; Dirice, Ercument; Gedeon, Nicholas; Kahraman, Sevim; De Jesus, Dario F.; Bhatt, Shweta; Kim, Jong -Seo; et al

    2015-07-07

    Compensatory islet response is a distinct feature of the pre-diabetic insulin resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from five-month-old male control, high-fat diet fed (HFD) or obese ob/ob mice by LC-MS(/MS) and quantified ~1,100 islet proteins (at least two peptides) with a false discovery rate <1%. Significant alterations in abundance were observed for ~350 proteins between groups. A majority of alterations were common to both models, and the changes of a subset of ~40 proteins and 12 proteins were verified by targeted quantification using selectedmore » reaction monitoring and Western blots, respectively. The insulin resistant islets in both groups exhibited reduced expression of proteins controlling energy metabolism, oxidative phosphorylation, hormone processing, and secretory pathways. Conversely, an increased expression of molecules involved in protein synthesis and folding suggested effects in endoplasmic reticulum stress response, cell survival, and proliferation in both insulin resistant models. In conclusion, we report a unique comparison of the islet proteome that is focused on the compensatory response in two insulin resistant rodent models that are not overtly diabetic. In conclusion, these data provide a valuable resource of candidate proteins to the scientific community to undertake further studies aimed at enhancing β-cell mass in patients with diabetes. The data are available via the MassIVE repository, with accession MSV000079093.« less

  10. Biochemical Analyses of Sorghum Varieties Reveal Differential Responses to Drought.

    PubMed

    Ogbaga, Chukwuma C; Stepien, Piotr; Dyson, Beth C; Rattray, Nicholas J W; Ellis, David I; Goodacre, Royston; Johnson, Giles N

    2016-01-01

    We have examined the biochemical responses of two sorghum cultivars of differing drought tolerance, Samsorg 17 (more drought tolerant) and Samsorg 40 (less drought tolerant), to sustained drought. Plants were exposed to different degrees of drought and then maintained at that level for five days. Responses were examined in terms of metabolic changes and the expression of drought induced proteins-Heat Shock Proteins (HSPs) and dehydrins (DHNs). Generalised phenotypic changes were studied using Fourier transform infrared (FT-IR) Spectroscopy and non-targeted Gas Chromatography Mass Spectrometry (GC-MS) was employed to detect changes in metabolites, while changes in protein expression were examined using Western blot analysis. Different response profiles of metabolites, HSPs and DHNs were observed in the two cultivars. Metabolic changes involved variation in amino acids, polysaccharides and their derivatives. A total of 188 compounds, with 142 known metabolites and 46 unknown small molecules, were detected in the two sorghum varieties. Under water deficit conditions, Samsorg 17 accumulated sugars and sugar alcohols, while in Samsorg 40 amino acids increased in concentration. This study suggest that the two Sorghum varieties adopt distinct approaches in response to drought, with Samsorg 17 being better able to maintain leaf function under severe drought conditions. PMID:27153323

  11. Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

    PubMed

    Ellero-Simatos, S; Lewis, J P; Georgiades, A; Yerges-Armstrong, L M; Beitelshees, A L; Horenstein, R B; Dane, A; Harms, A C; Ramaker, R; Vreeken, R J; Perry, C G; Zhu, H; Sànchez, C L; Kuhn, C; Ortel, T L; Shuldiner, A R; Hankemeier, T; Kaddurah-Daouk, R

    2014-01-01

    While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 ± 8 vs. 61 ± 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 × 10(-4), N = 12). These results suggest that serotonin is implicated in aspirin response variability. PMID:25029353

  12. 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.

  13. What boxing-related stimuli reveal about response behaviour.

    PubMed

    Ottoboni, Giovanni; Russo, Gabriele; Tessari, Alessia

    2015-01-01

    When two athletes meet inside the ropes of the boxing ring to fight, their cognitive systems have to respond as quickly as possible to a manifold of stimuli to assure victory. In the present work, we studied the pre-attentive mechanisms, which form the basis of an athlete's ability in reacting to an opponent's punches. Expert boxers, beginner boxers and people with no experience of boxing performed a Simon-like task where they judged the colour of the boxing gloves worn by athletes in attack postures by pressing two lateralised keys. Although participants were not instructed to pay attention to the direction of the punches, beginner boxers' responses resembled a defence-related pattern, expert boxers' resembled counterattacks, whereas non-athletes' responses were not influenced by the unrelated task information. Results are discussed in the light of an expertise-related action simulation account. PMID:25385452

  14. [Epidemiology of teeth hypersensitivity].

    PubMed

    Lutskaia, I K; Zinovenko, O G; Kovalenko, I P

    2015-01-01

    A clinical examination of 98 patients aged 20 to 75 years was carried out to identifyclinical and epidemiological features of hard tooth tissueshypersensitivity. The survey found out what stimuli (cold, hot, sour, mechanical, chemical) cause the appearance of dental hyperesthesia. The detailed survey of the affected area aimed to determine the presence of dental caries, gingival recession, wedge-shaped defects, erosions, microcracks and chipped enamel, as well as wear of the tooth crown. Forty-threepatients of 98 (43.88%) had tooth sensitivity. Most affected age group was 25-34 years (33%). Among patients studied with hyperesthesia 86% complained of pain. It was establishedthat dental hyperesthesia most often causes an intense, but quickly passing pain response, wherein upon exposure of several types of stimuli. Teeth with high sensitivity showed signs of abrasion (74.1%), most often--on the vestibular surface (44.4%). Patients under 45 years had notable cracks and wedge-shaped defects. In patients 45 years and older cracks and increased abrasion of hard dental tissues was seen. PMID:26271696

  15. HYPERSENSITIVE RESPONSE-LIKE LESIONS 1 Codes for AtPPT1 and Regulates Accumulation of ROS and Defense Against Bacterial Pathogen Pseudomonas syringae in Arabidopsis thaliana

    PubMed Central

    Dutta, Aditya; Chan, Samuel H.P.; Pauli, Noel T.

    2015-01-01

    Abstract Aims: Plants employ both basal and resistance gene (R gene)-mediated defenses in response to pathogens. Reactive oxygen species (ROS) are widely reported to play a central role in both basal and R gene-mediated defense; however, the nature of ROS has been less well established for basal defense. In addition, spatial distribution of redox moieties and mechanisms of plant responses during basal defense are poorly understood. We investigated redox signaling in Arabidopsis thaliana in response to virulent bacterial pathogen, focusing on the role of the mitochondria in balancing energy demands against generation of physiologically relevant ROS. Results: Positional cloning of an Arabidopsis lesion mimic mutant identified a polyprenyl transferase involved in the biosynthesis of Coenzyme Q10 (CoQ), which leads to novel insights into physiological ROS levels and their role in basal resistance. Gain- and loss-of-function studies identified Coenzyme Q10 redox state to be a key determinant of ROS levels. These Coenzyme Q10 redox state-mediated ROS levels had a direct bearing on both response against pathogen and ability to thrive in high oxidative stress environments. Innovation: We demonstrate that Coenzyme Q10 redox state generates an ROS threshold for a successful basal resistance response. Perturbation of the Coenzyme Q10 redox state has the potential to disrupt plant defense responses against bacterial pathogens. Conclusions: Coenzyme Q10 redox state is a key regulator of Arabidopsis basal resistance against bacterial pathogens. Antioxid. Redox Signal. 22, 785–796. PMID:25557512

  16. Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols.

    PubMed

    Katiyar, S K; Elmets, C A; Agarwal, R; Mukhtar, H

    1995-11-01

    Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a polyphenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280-320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. Topical application of GTP (1-6 mg/animal), 30 min prior to or 30 min after exposure to a single dose of UVB (2 kJ/m2) resulted in significant protection against local (25-90%) and systemic suppression (23-95%) of CHS and inflammation in mouse dorsal skin (70-80%). These protective effects were dependent on the dose of GTP employed; increasing the dose (1-6 mg/animal) resulted in an increased protective effect (25-93%). The protective effects were also dependent on the dose of UVB (2-32 kJ/m2). Among the four major epicatechin derivatives present in GTP, (-)-epigallocatechin-3-gallate, the major constituent in GTP, was found to be the most effective in affording protection against UVB-caused CHS and inflammatory responses. Our study suggests that green tea, specifically polyphenols present therein, may be useful against inflammatory dermatoses and immunosuppression caused by solar radiation.

  17. 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

  18. 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

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

    PubMed

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

    2015-01-01

    The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected. PMID:25883940

  20. Hypersensitivity syndrome caused by amitriptyline administration

    PubMed Central

    Milionis, H.; Skopelitou, A.; Elisaf, M.

    2000-01-01

    Adverse cutaneous manifestations are among the most common side effects associated with psychotropic drugs. Skin reactions due to amitriptyline (a tricyclic antidepressant agent) include rashes and hypersensitivity reactions (for example, urticaria and photosensitivity) as well as hyperpigmentation. Hypersensitivity syndrome is a specific severe idiosyncratic reaction causing skin, liver, joint, and haematological abnormalities, which usually resolve after the discontinuation of the implicated drug. A case of a 24 year old woman who experienced hypersensitivity syndrome three weeks after the initiation of amitriptyline is reported.


Keywords: tricyclic antidepressant drugs; amitriptyline; adverse cutaneous reactions; hypersensitivity syndrome PMID:10824052

  1. 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

  2. Network deconstruction reveals network structure in responsive microgels.

    PubMed

    Smith, Michael H; Herman, Emily S; Lyon, L Andrew

    2011-04-14

    Detailed characterization of hydrogel particle erosion revealed critical physicochemical differences between spheres, where network decomposition was informative of network structure. Real-time, in situ monitoring of the triggered erosion of colloidal hydrogels (microgels) was performed via multiangle light scattering. The solution-average molar mass and root-mean-square radii of eroding particles were measured as a function of time for microgels prepared from N-isopropylacrylamide (NIPAm) or N-isopropylmethacrylamide (NIPMAm), copolymerized with a chemically labile cross-linker (1,2-dihydroxylethylene)bisacrylamide (DHEA). Precipitation polymerization was employed to yield particles of comparable dimensions but with distinct topological features. Heterogeneous cross-linker incorporation resulted in a heterogeneous network structure for pNIPAm microgels. During the erosion reaction, mass loss proceeded from the exterior toward the interior of the polymer. In contrast, pNIPMAm microgels had a more homogeneous network structure, which resulted in a more uniform mass loss throughout the particle during erosion. Although both particle types degraded into low molar mass products, pNIPAm microgels were incapable of complete dissolution due to the presence of nondegradable cross-links arising from chain transfer and branching during particle synthesis. The observations described herein provide insight into key design parameters associated with the synthesis of degradable hydrogel particles, which may be of use in various biotechnological applications. PMID:21425815

  3. [Delayed hypersensitivity to protamine and immediate hypersensitivity to insulin].

    PubMed

    Köllner, A; Senff, H; Engelmann, L; Kalveram, K J; Velcovsky, H G; Haneke, E

    1991-08-16

    A 63-year-old female, with type II diabetes mellitus, diagnosed in 1967, was started on combination therapy with sulphonylureas and human depot insulin in May 1989, because of inadequate blood sugar control with sulphonylureas alone. Within 3 months she began to develop nodular skin reactions at the site of injection, 12-24 hours after insulin injections. Intradermal testing demonstrated delayed (Gell and Coombs type IV) hypersensitivity to protamine. No specific IgE or IgG antibodies were demonstrable. She was changed to protamine-free human delayed action insulin. After an initial reaction-free period, red urticarial lesions, attributable to immediate (Gell and Coombs type I) hypersensitivity to human insulin, appeared at the injection sites. There were no other complications with continued insulin therapy, and after about 6 weeks no further local reactions were detectable. When an allergic reaction to an insulin preparation is suspected, careful immunological investigation should be performed, to ensure adequate treatment without risk to the patient.

  4. Antigenic specificities of delayed hypersensitivity in mice to dinitrophenylated proteins

    PubMed Central

    Yonemasu, K.; Crowle, A. J.

    1973-01-01

    Humoral antibodies capable of suppressing induction of delayed hypersensitivity to dinitrophenylated proteins in mice were tested for specific absorbability onto chemically insolubilized antigen and for the antigenic determinant specificities of their immunosuppressive (i.e. contrasensitizing) effects. The activity of an antiserum could be completely removed by absorption with homologous antigen, and it could be recovered by dissociating the absorbed antibodies at low pH and high salt concentration. The immunosuppressive antibodies therefore are specific for determinants on the native antigen, and non-antibody serum constituents are non-essential. By selective immunoabsorptions and elutions, antibodies specific for carrier protein, for dinitrophenyl hapten, and for new determinants unique to the hapten—protein complexes were prepared and were compared with unfractionated antiserum for contrasensitizing activity. Nearly all activity could be accounted for by the anti-hapten antibodies, although anti-carrier antibodies also had some. Despite this evidence that immunosuppressiveness was hapten-specific, the delayed hypersensitivity being suppressed by these antibodies was shown to be directed against hapten—carrier complexes or against carrier but not against hapten alone. Hence, humoral antibodies against a portion of an antigen molecule can suppress induction of delayed hypersensitivity specific for other sometimes unrelated parts of this same molecule, and it is possible to induce antibody-mediated tolerance to a multi-determinant antigen with an antibody response against just a part of the antigen. The theoretical and practical implications of these findings are discussed. Notable theoretically is the observation that although determinant specificities of humoral antibody and delayed hypersensitivity responses to one antigen usually differ, the former can regulate the latter for a given species of antigen molecule. Most important practically is the implication

  5. Supernatants from 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.

    PubMed

    Jeevan, A; Ullrich, S E; Dizon, V V; Kripke, M L

    1991-12-01

    We recently demonstrated that exposure of mice to a single high dose or multiple smaller doses of ultraviolet (UV) radiation decreased the induction of the delayed-type hypersensitivity (DTH) response to bacillus Calmette-Guerin (BCG) from Mycobacterium bovis injected into unexposed sites. In view of the limited ability of UV radiation to penetrate beyond the epidermis and upper layers of the dermis, it is not entirely clear how exposing the dorsal skin of mice to UV radiation causes systemic impairment of the immune response to BCG. In this study we report that mice injected with supernatants from keratinocyte cultures exposed to UV radiation in vitro impaired host resistance to BCG. Both induction and elicitation of the DTH reaction were suppressed after the intravenous injection of supernatants from UV-irradiated keratinocytes. Furthermore, these supernatants interfered with the elimination of viable bacteria from the lymphoid organs. To determine whether macrophages were the target of the UV-induced, keratinocyte-derived, suppressive cytokine, macrophages were isolated from mice injected with the suppressive cytokine or treated in vitro with the supernatants and tested for their ability to ingest and kill BCG in vitro. Injection of the suppressive factor significantly reduced the phagocytosis of BCG by the macrophages but did not alter the rate of intracellular killing. Similarly, phagocytosis was reduced when normal macrophages were treated in vitro with the suppressive factor. These findings suggest that the suppressive cytokine interferes with the elimination of bacteria in vivo by inhibiting the initial step in bacterial clearance, the uptake of the bacteria by host macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1823151

  6. Mold-induced hypersensitivity pneumonitis.

    PubMed

    Greenberger, Paul A

    2004-01-01

    Mold-induced hypersensitivity pneumonitis results from macrophage- and lymphocyte-driven inflammation, which may be attributable to contaminated humidifiers or heating-ventilation systems or sources in homes, schools, or workplaces. A case may be suspected when there is water intrusion or inadequate drainage. Some fungal causes include species of Alternaria, Aspergillus, Cryptostroma, Penicillium, Pullularia, Rhodotorula, and Trichosporon. The differential diagnosis includes mold-induced asthma, sick building syndrome, mass psychogenic illness (epidemic hysteria), unjustified fears of "toxic" molds, and conditions causing recurrent pneumonitis. PMID:15510579

  7. Angioneurotic edema: a rare case of hypersensitivity to metoclopramide

    PubMed Central

    Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

    2013-01-01

    The case of a 30-year-old woman who had already experienced two incidents of angioneurotic edema and urticaria caused by drugs during the acute gastroenteritis. The allergological workup revealed hypersensitivity to metoclopramide. This case documents that metoclopramide, a drug commonly used to inhibit the vomiting, may cause not only bronchospastic reaction in an asthmatic patient but also angioneurotic edema of the tongue and larynx as well as urticaria. No similar cases in the literature were found. PMID:24278059

  8. Paediatric feather duvet hypersensitivity pneumonitis.

    PubMed

    Jordan, Louise E; Guy, Emma

    2015-01-01

    A previously well 12-year-old boy was admitted with a second insidious episode of dyspnoea, dry cough, anorexia, weight loss and chest pain. At admission, he had an oxygen requirement, significantly impaired lung function and reduced exercise tolerance. Initial forced expiratory volume in 1 s was 26%; a 3 min exercise test stopped at 1 min 50 when saturations dropped to 85%. CT scan showed ground-glass nodularity with lymphadenopathy. Bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia and viruses were negative, and microbiology results for the BAL were reported in the absence of histology. This is because at the time the BAL samples were collected, a lung biopsy was performed. The biopsy was consistent with hypersensitivity pneumonitis. Echo was normal and CT pulmonary angiography negative. After taking a thorough history, exposure to feather duvets prior to each episode was elicited. IgG of avian precipitants was raised at 10.6 mgA/L (normal <10 mgA/L). Clinical improvement began with avoidance of exposure, while the boy was an inpatient. Antigen avoidance continued on discharge. He continues to improve since discharge. The condition was diagnosed as hypersensitivity pneumonitis secondary to exposure to antigens from feather duvets. PMID:26113584

  9. Paediatric feather duvet hypersensitivity pneumonitis.

    PubMed

    Jordan, Louise E; Guy, Emma

    2015-01-01

    A previously well 12-year-old boy was admitted with a second insidious episode of dyspnoea, dry cough, anorexia, weight loss and chest pain. At admission, he had an oxygen requirement, significantly impaired lung function and reduced exercise tolerance. Initial forced expiratory volume in 1 s was 26%; a 3 min exercise test stopped at 1 min 50 when saturations dropped to 85%. CT scan showed ground-glass nodularity with lymphadenopathy. Bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia and viruses were negative, and microbiology results for the BAL were reported in the absence of histology. This is because at the time the BAL samples were collected, a lung biopsy was performed. The biopsy was consistent with hypersensitivity pneumonitis. Echo was normal and CT pulmonary angiography negative. After taking a thorough history, exposure to feather duvets prior to each episode was elicited. IgG of avian precipitants was raised at 10.6 mgA/L (normal <10 mgA/L). Clinical improvement began with avoidance of exposure, while the boy was an inpatient. Antigen avoidance continued on discharge. He continues to improve since discharge. The condition was diagnosed as hypersensitivity pneumonitis secondary to exposure to antigens from feather duvets.

  10. Hypersensitivity reactions to titanium: diagnosis and management.

    PubMed

    Wood, Megan M; Warshaw, Erin M

    2015-01-01

    Titanium is notable for its biocompatibility and is used as biologic implant material across surgical specialties, especially in metal-sensitive individuals. However, rare cases of titanium hypersensitivity reactions are reported in the literature. This article discusses the properties and biological behavior of titanium and provides a thorough review of the literature on reported cases, diagnostic techniques, and approach to management of titanium hypersensitivity.

  11. Management of dentinal hypersensitivity: a review.

    PubMed

    Parolia, Abhishek; Kundabala, M; Mohan, Mandakini

    2011-03-01

    Dentinal hypersensitivity is a very common clinical finding that can cause considerable concern for the patient. Clinicians must understand the various etiological factors, their complexities, and numerous treatment options available. This article reviews the etiology, management, and prevention of dentinal hypersensitivity. PMID:21563596

  12. Genetic factors in the predisposition to drug-induced hypersensitivity reactions.

    PubMed

    Pirmohamed, Munir

    2006-02-03

    Drug hypersensitivity reactions can occur with most drugs, although the frequency, severity, and clinical manifestations vary. Case reports have suggested that there may be familial clustering of drug hypersensitivity suggesting a genetic predisposition. As with most other forms of drug response, predisposition to drug hypersensitivity reactions is likely to be multifactorial and multigenic. Given the immune pathogenesis of these reactions, it is perhaps not surprising that the most significant genetic associations have been identified in the major histocompatibility complex for drugs such as abacavir, carbamazepine, and allopurinol. For abacavir, it has been suggested that preprescription genotyping for HLA-B*5701 in whites may reduce the incidence of hypersensitivity. It is likely that as our knowledge of variation in the human genome improves, coupled with improvements in technology, many more significant genetic predisposing factors for drug hypersensitivity are likely to be identified in the next decade. However, as we search for these genetic factors, it is important that we do not forget environmental predisposition, and to bear in mind that a genetic marker for drug hypersensitivity in one population may not necessarily be relevant for another population. Notwithstanding the advances in genetic technologies, the ultimate determinant of success in this area of research will be the identification and careful phenotyping of patients with drug hypersensitivity reactions. As we progress to whole genome scanning, in order to satisfy the requirements for adequate statistical power, the identification of large numbers of carefully phenotyped patients will be feasible only through international collaborations.

  13. Cutting Edge: Redox Signaling Hypersensitivity Distinguishes Human Germinal Center B Cells.

    PubMed

    Polikowsky, Hannah G; Wogsland, Cara E; Diggins, Kirsten E; Huse, Kanutte; Irish, Jonathan M

    2015-08-15

    Differences in the quality of BCR signaling control key steps of B cell maturation and differentiation. Endogenously produced H2O2 is thought to fine tune the level of BCR signaling by reversibly inhibiting phosphatases. However, relatively little is known about how B cells at different stages sense and respond to such redox cues. In this study, we used phospho-specific flow cytometry and high-dimensional mass cytometry (CyTOF) to compare BCR signaling responses in mature human tonsillar B cells undergoing germinal center (GC) reactions. GC B cells, in contrast to mature naive B cells, memory B cells, and plasmablasts, were hypersensitive to a range of H2O2 concentrations and responded by phosphorylating SYK and other membrane-proximal BCR effectors in the absence of BCR engagement. These findings reveal that stage-specific redox responses distinguish human GC B cells.

  14. Studies of the quenching phenomenon in delayed contact hypersensitivity reactions.

    PubMed

    Basketter, D A; Allenby, C F

    1991-09-01

    Studies in guinea pig and man have shown that eugenol can quench non-specifically contact urticarial responses, whereas limonene seems largely ineffective. In a comprehensive series of studies, there was little evidence of quenching of delayed contact hypersensitivity reactions to cinnamic aldehyde or citral, including in 'pre-quenched' material supplied by a perfume/flavour company, and in a similar mixture prepared in this laboratory, in the guinea pig model. In addition, there was no evidence of the quenching by eugenol of allergic reactions to cinnamic aldehyde in a panel of human subjects with a proven history of cinnamic-aldehyde-induced allergic contact dermatitis. Overall, the results lend little credibility to earlier literature reports of quenching phenomena in delayed contact hypersensitivity responses.

  15. Nucleotide excision repair-induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response.

    PubMed

    Marteijn, Jurgen A; Bekker-Jensen, Simon; Mailand, Niels; Lans, Hannes; Schwertman, Petra; Gourdin, Audrey M; Dantuma, Nico P; Lukas, Jiri; Vermeulen, Wim

    2009-09-21

    Chromatin modifications are an important component of the of DNA damage response (DDR) network that safeguard genomic integrity. Recently, we demonstrated nucleotide excision repair (NER)-dependent histone H2A ubiquitination at sites of ultraviolet (UV)-induced DNA damage. In this study, we show a sustained H2A ubiquitination at damaged DNA, which requires dynamic ubiquitination by Ubc13 and RNF8. Depletion of these enzymes causes UV hypersensitivity without affecting NER, which is indicative of a function for Ubc13 and RNF8 in the downstream UV-DDR. RNF8 is targeted to damaged DNA through an interaction with the double-strand break (DSB)-DDR scaffold protein MDC1, establishing a novel function for MDC1. RNF8 is recruited to sites of UV damage in a cell cycle-independent fashion that requires NER-generated, single-stranded repair intermediates and ataxia telangiectasia-mutated and Rad3-related protein. Our results reveal a conserved pathway of DNA damage-induced H2A ubiquitination for both DSBs and UV lesions, including the recruitment of 53BP1 and Brca1. Although both lesions are processed by independent repair pathways and trigger signaling responses by distinct kinases, they eventually generate the same epigenetic mark, possibly functioning in DNA damage signal amplification. PMID:19797077

  16. Nucleotide excision repair–induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response

    PubMed Central

    Marteijn, Jurgen A.; Bekker-Jensen, Simon; Mailand, Niels; Lans, Hannes; Schwertman, Petra; Gourdin, Audrey M.; Dantuma, Nico P.; Lukas, Jiri

    2009-01-01

    Chromatin modifications are an important component of the of DNA damage response (DDR) network that safeguard genomic integrity. Recently, we demonstrated nucleotide excision repair (NER)–dependent histone H2A ubiquitination at sites of ultraviolet (UV)-induced DNA damage. In this study, we show a sustained H2A ubiquitination at damaged DNA, which requires dynamic ubiquitination by Ubc13 and RNF8. Depletion of these enzymes causes UV hypersensitivity without affecting NER, which is indicative of a function for Ubc13 and RNF8 in the downstream UV–DDR. RNF8 is targeted to damaged DNA through an interaction with the double-strand break (DSB)–DDR scaffold protein MDC1, establishing a novel function for MDC1. RNF8 is recruited to sites of UV damage in a cell cycle–independent fashion that requires NER-generated, single-stranded repair intermediates and ataxia telangiectasia–mutated and Rad3-related protein. Our results reveal a conserved pathway of DNA damage–induced H2A ubiquitination for both DSBs and UV lesions, including the recruitment of 53BP1 and Brca1. Although both lesions are processed by independent repair pathways and trigger signaling responses by distinct kinases, they eventually generate the same epigenetic mark, possibly functioning in DNA damage signal amplification. PMID:19797077

  17. Analysis of Magnaporthe oryzae Genome Reveals a Fungal Effector, Which Is Able to Induce Resistance Response in Transgenic Rice Line Containing Resistance Gene, Pi54

    PubMed Central

    Ray, Soham; Singh, Pankaj K.; Gupta, Deepak K.; Mahato, Ajay K.; Sarkar, Chiranjib; Rathour, Rajeev; Singh, Nagendra K.; Sharma, Tilak R.

    2016-01-01

    Rice blast caused by Magnaporthe oryzae is one of the most important diseases of rice. Pi54, a rice gene that imparts resistance to M. oryzae isolates prevalent in India, was already cloned but its avirulent counterpart in the pathogen was not known. After decoding the whole genome of an avirulent isolate of M. oryzae, we predicted 11440 protein coding genes and then identified four candidate effector proteins which are exclusively expressed in the infectious structure, appresoria. In silico protein modeling followed by interaction analysis between Pi54 protein model and selected four candidate effector proteins models revealed that Mo-01947_9 protein model encoded by a gene located at chromosome 4 of M. oryzae, interacted best at the Leucine Rich Repeat domain of Pi54 protein model. Yeast-two-hybrid analysis showed that Mo-01947_9 protein physically interacts with Pi54 protein. Nicotiana benthamiana leaf infiltration assay confirmed induction of hypersensitive response in the presence of Pi54 gene in a heterologous system. Genetic complementation test also proved that Mo-01947_9 protein induces avirulence response in the pathogen in presence of Pi54 gene. Here, we report identification and cloning of a new fungal effector gene which interacts with blast resistance gene Pi54 in rice. PMID:27551285

  18. Analysis of Magnaporthe oryzae Genome Reveals a Fungal Effector, Which Is Able to Induce Resistance Response in Transgenic Rice Line Containing Resistance Gene, Pi54.

    PubMed

    Ray, Soham; Singh, Pankaj K; Gupta, Deepak K; Mahato, Ajay K; Sarkar, Chiranjib; Rathour, Rajeev; Singh, Nagendra K; Sharma, Tilak R

    2016-01-01

    Rice blast caused by Magnaporthe oryzae is one of the most important diseases of rice. Pi54, a rice gene that imparts resistance to M. oryzae isolates prevalent in India, was already cloned but its avirulent counterpart in the pathogen was not known. After decoding the whole genome of an avirulent isolate of M. oryzae, we predicted 11440 protein coding genes and then identified four candidate effector proteins which are exclusively expressed in the infectious structure, appresoria. In silico protein modeling followed by interaction analysis between Pi54 protein model and selected four candidate effector proteins models revealed that Mo-01947_9 protein model encoded by a gene located at chromosome 4 of M. oryzae, interacted best at the Leucine Rich Repeat domain of Pi54 protein model. Yeast-two-hybrid analysis showed that Mo-01947_9 protein physically interacts with Pi54 protein. Nicotiana benthamiana leaf infiltration assay confirmed induction of hypersensitive response in the presence of Pi54 gene in a heterologous system. Genetic complementation test also proved that Mo-01947_9 protein induces avirulence response in the pathogen in presence of Pi54 gene. Here, we report identification and cloning of a new fungal effector gene which interacts with blast resistance gene Pi54 in rice. PMID:27551285

  19. 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

  20. 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

  1. Heat resistance and salt hypersensitivity in Lactococcus lactis due to spontaneous mutation of llmg_1816 (gdpP) induced by high-temperature growth.

    PubMed

    Smith, William M; Pham, Thi Huong; Lei, Lin; Dou, Junchao; Soomro, Aijaz H; Beatson, Scott A; Dykes, Gary A; Turner, Mark S

    2012-11-01

    During construction of several gene deletion mutants in Lactococcus lactis MG1363 which involved a high-temperature (37.5°C) incubation step, additional spontaneous mutations were observed which resulted in stable heat resistance and in some cases salt-hypersensitive phenotypes. Whole-genome sequencing of one strain which was both heat resistant and salt hypersensitive, followed by PCR and sequencing of four other mutants which shared these phenotypes, revealed independent mutations in llmg_1816 in all cases. This gene encodes a membrane-bound stress signaling protein of the GdpP family, members of which exhibit cyclic dimeric AMP (c-di-AMP)-specific phosphodiesterase activity. Mutations were predicted to lead to single amino acid substitutions or protein truncations. An independent llmg_1816 mutant (Δ1816), created using a suicide vector, also displayed heat resistance and salt hypersensitivity phenotypes which could be restored to wild-type levels following plasmid excision. L. lactis Δ1816 also displayed improved growth in response to sublethal concentrations of penicillin G. High-temperature incubation of a wild-type industrial L. lactis strain also resulted in spontaneous mutation of llmg_1816 and heat-resistant and salt-hypersensitive phenotypes, suggesting that this is not a strain-specific phenomenon and that it is independent of a plasmid integration event. Acidification of milk by the llmg_1816-altered strain was inhibited by lower salt concentrations than the parent strain. This study demonstrates that spontaneous mutations can occur during high-temperature growth of L. lactis and that inactivation of llmg_1816 leads to temperature resistance and salt hypersensitivity.

  2. Severe hypersensitivity reaction to minocycline.

    PubMed

    de Paz, S; Pérez, A; Gómez, M; Trampal, A; Domínguez Lázaro, A

    1999-01-01

    Minocycline is a tetracycline derivative mainly used in the treatment of acne vulgaris in young persons. Adverse events have been reported with minocycline, although it can be considered a safe drug. We report a case of severe hypersensitivity reaction to minocycline in a young patient. Laboratory examinations, chest X-ray, skin test and skin biopsy were performed. Oral challenge test with minocycline was not carried out as it can be hazardous. A case of severe reaction to minocycline is described in this article. The clinical and laboratory findings may be helpful in diagnosing similar reactions for which the immunological mechanisms are unknown. Moreover, this type of reaction must be recognized early due to the potential fatal outcome.

  3. Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat.

    PubMed

    Wei, Hong; Koivisto, Ari; Saarnilehto, Marja; Chapman, Hugh; Kuokkanen, Katja; Hao, Bin; Huang, Jin-Lu; Wang, Yong-Xiang; Pertovaara, Antti

    2011-03-01

    The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed on nociceptive primary afferent neurons. On the proximal nerve ending within the spinal dorsal horn, TRPA1 regulates transmission to spinal interneurons, and thereby pain hypersensitivity. Here we assessed whether the contribution of the spinal TRPA1 channel to pain hypersensitivity varies with the experimental pain model, properties of test stimulation or the behavioral pain response. The antihypersensitivity effect of intrathecally (i.t.) administered Chembridge-5861528 (CHEM; a selective TRPA1 channel antagonist; 5-10μg) was determined in various experimental models of pain hypersensitivity in the rat. In spinal nerve ligation and rapid eye movement (REM) sleep deprivation models, i.t. CHEM attenuated mechanical hypersensitivity. Capsaicin-induced secondary (central) but not primary (peripheral) mechanical hypersensitivity was also reduced by i.t. administration of CHEM or A-967079, another TRPA1 channel antagonist. Formalin-induced secondary mechanical hypersensitivity, but not spontaneous pain, was suppressed by i.t. CHEM. Moreover, mechanical hypersensitivity induced by cholekystokinin in the rostroventromedial medulla was attenuated by i.t. pretreatment with CHEM. Independent of the model, the antihypersensitivity effect induced by i.t. CHEM was predominant on responses evoked by low-intensity stimuli (⩽6g). CHEM (10μg i.t.) failed to attenuate pain behavior in healthy controls or mechanical hypersensitivities induced by i.t. administrations of a GABA(A) receptor antagonist, or NMDA or 5-HT(3) receptor agonists. Conversely, i.t. administration of a TRPA1 channel agonist, cinnamon aldehyde, induced mechanical hypersensitivity. The results indicate that the spinal TRPA1 channel exerts an important role in secondary (central) pain hypersensitivity to low-intensity mechanical stimulation in various pain hypersensitivity conditions. The spinal TRPA1 channel provides a promising target

  4. Testing for Drug Hypersensitivity Syndromes

    PubMed Central

    Rive, Craig M; Bourke, Jack; Phillips, Elizabeth J

    2013-01-01

    Adverse drug reactions are a common cause of patient morbidity and mortality. Type B drug reactions comprise only 20% of all drug reactions but they tend to be primarily immunologically mediated and less dependent on the drug’s pharmacological action and dose. Common Type B reactions seen in clinical practice are those of the immediate, IgE, Gell-Coombs Type I reactions, and the delayed, T-cell mediated, Type IV reactions. Management of these types of reactions, once they have occurred, requires careful consideration and recognition of the utility of routine diagnostic tests followed by ancillary specialised diagnostic testing. For Type I, IgE mediated reactions this includes prick/intradermal skin testing and oral provocation. For Type IV, T-cell mediated reactions this includes a variety of in vivo (patch testing) and ex vivo tests, many of which are currently mainly used in highly specialised research laboratories. The recent association of many serious delayed (Type IV) hypersensitivity reactions to specific drugs with HLA class I and II alleles has created the opportunity for HLA screening to exclude high risk populations from exposure to the implicated drug and hence prevent clinical reactions. For example, the 100% negative predictive value of HLA-B*5701 for true immunologically mediated abacavir hypersensitivity and the development of feasible, inexpensive DNA-based molecular tests has led to incorporation of HLA-B*5701 screening in routine HIV clinical practice. The mechanism by which drugs specifically interact with HLA has been recently characterised and promises to lead to strategies for pre-clinical screening to inform drug development and design. PMID:23592889

  5. Azuki bean cells are hypersensitive to cadmium and do not synthesize phytochelatins.

    PubMed

    Inouhe, M; Ito, R; Ito, S; Sasada, N; Tohoyama, H; Joho, M

    2000-07-01

    Suspension-cultured cells of azuki bean (Vigna angularis) as well as the original root tissues were hypersensitive to Cd (<10 microM). Repeated subculturings with a sublethal level of Cd (1-10 microM) did not affect the subsequent response of cells to inhibitory levels of Cd (10-100 microM). The azuki bean cells challenged to Cd did not contain phytochelatin (PC) peptides, unlike tomato (Lycopersicon esculentum) cells that have a substantial tolerance to Cd (>100 microM). Both of the cell suspensions contained a similar level of reduced glutathione (GSH) when grown in the absence of Cd. Externally applied GSH to azuki bean cells recovered neither Cd tolerance nor PC synthesis of the cells. Furthermore, enzyme assays in vitro revealed that the protein extracts of azuki bean cells had no activity converting GSH to PCs, unlike tomato. These results suggest that azuki bean cells are lacking in the PC synthase activity per se, hence being Cd hypersensitive. We concluded that the PC synthase has an important role in Cd tolerance of suspension-cultured cells. PMID:10889252

  6. 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

  7. 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.

  8. Objective clinical and laboratory studies of immediate hypersensitivity reactions to foods in asthmatic children.

    PubMed

    May, C D

    1976-10-01

    Clinical and laboratory observations were made with 38 children afflicted with chronic severe asthma (reversible obstructive airway disease) in which hypersensitivity to food was incriminated in the histories. Symptoms were evoked in double-blind food challenges in only 11/38 children and 14/70 challenges, and were characteristic of immediate-type hypersensitivity and were chiefly gastrointestinal, even though asthma was the common presenting complaint. There were no delayed reactions. Peanut was responsible for 8 reactions, egg for 5, and cow's milk for 1. The feature that most successfully identified those having positive reactions in challenges was a significant wheal reaction in a skin test by puncture technique using a verified extract of 1:20 W/V concentration. No subject with clinically significant, symptomatic hypersensitivity to food had a negative puncture test, and puncture tests were positive in only 10/56 instances of negative reactions in food challenges. Laboratory observations included release of histamine and enzymes from leukocytes and the levels of neutrophil enzymes in serum before and after food provocation tests. While these determinations were of interest with respect to the immunochemical basis of reactions to foods, they did not prove useful for practical clinical diagnosis. The outstanding laboratory findings was the occurrence of "spontaneous" release of 25% to 100% of the histamine from leukocytes in all cases proved clinically hypersensitive by food challenges, which suggests that this may be an indicator of immediate-type hypersensitivity to food. From the findings in the study, a general approach to food hypersensitivity was developed in which the immunologic components coupled with quantitative concentration-response relationships serve to render comprehensible the distinction between asymptomatic (immunologic) hypersensitivity and symptomatic (clinical) hypersensitivity.

  9. [In vitro immunologic diagnosis of hypersensitivity to vegetables].

    PubMed

    Carrillo Díaz, T; Cuevas Agustín, M; Luz Díez Gómez, M; Losada Cosme, E; Moneo Goiri, I

    1986-01-01

    Acute reaction to food allergens is a fairly common problem that is often seen in the allergist's office, its incidence being specially high in childhood. Milk and eggs are the most common sensitizing foods, but usually the type of food allergens responsible for these reactions varies according to food habits in different countries. Legumes occupy an important role in the Spanish diet, being responsible for a large number of allergic reactions. It has been shown that legumes occupy the fourth place in importance among the food allergens, inducing hypersensitivity reactions in Spanish children. This article describes five patients with clinical features suggestive of being mediated by IgE antibodies specific for different legumes. In all the cases, disorders appeared immediately after the ingestion or even the inhalation of vapours from cooked legumes (lentil, bean or chick-pea). Clinical features consisted of: urticaria, angioedema, abdominal symptoms and rhinoconjunctivitis and/or asthma. The five patients required hospital emergency care on several occasions. Two patients suffered also from seasonal pollinosis with rhinoconjunctivitis and asthma. All the patients complained of these type of disorders with any legume, but lentil was found to induce the most severe reactions and it was therefore selected for this study. The presence of specific IgE antibodies was demonstrated in vivo in all the patients by means of skin prick-test. It was performed using a lentil extract prepared in our laboratory. Negative controls were also included. A reverse enzymeimmunoassay (REIA) revealed the presence of specific IgE antibodies in the sera of the five subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. 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.

  11. Multicolor fluorescence imaging for early detection of the hypersensitive reaction to tobacco mosaic virus.

    PubMed

    Chaerle, Laury; Lenk, Sándor; Hagenbeek, Dik; Buschmann, Claus; Van Der Straeten, Dominique

    2007-03-01

    The physiological status of plants can nowadays be promptly monitored with non-invasive methods. This opens the possibility to continuously follow-up plant performance and permits to detect stress-induced deviations presymptomatically. Upon stress, plants may synthesize specific compounds, depending on the causal agent. Such compounds may alter the absorption of the light impinging on plant leaves, hence the spectrum of reflected, re-emitted, and transmitted light changes. UV-excited fluorescence imaging specifically allows visualization of the accumulation of phenolic compounds, e.g. those associated with the hypersensitive response to pathogens. By using imaging at regular intervals (time-lapse series) of tobacco mosaic virus (TMV) infection in resistant tobacco we aimed at the description and quantification of the kinetics of blue-green fluorescence compared to the visual development of the disease. Presymptomatic responses to TMV infection were observed with a multicolor fluorescence and reflectance imaging setup. The onset of increases in blue-green and chlorophyll fluorescence were comparable in timing, although further symptom development was strikingly different. Compounds known to accumulate during the hypersensitive response and displaying blue-green fluorescence revealed different dynamics of fluorescence evolution in time. The multichannel imaging system permitted to discern the key components salicylic acid and scopoletin. In contrast, for the compatible interaction between TMV and non-resistant tobacco, no presymptomatic responses were detected on inoculated leaves. This work proves the potential of multispectral imaging to unveil stress-associated signatures, and the power of blue-green fluorescence imaging to monitor accumulation of secondary compounds.

  12. 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

  13. Drug-Hypersensitivity Syndrome: Diagnosis and Treatment

    PubMed Central

    Hamm, Rose L.

    2012-01-01

    Drug-induced hypersensitivity syndrome is a systemic autoimmune disorder that results in mucocutaneous symptoms ranging in severity from mild pruritus to life-threatening skin and mucosal loss, with different nomenclature depending on the severity of the symptoms. The purpose of this article is to review the recent advances in understanding the pathology of drug-induced hypersensitivity syndrome, as well as current recommendations for both medical and wound management. PMID:24527369

  14. Recent advances in hypersensitivity pneumonitis.

    PubMed

    Lacasse, Yves; Girard, Mélissa; Cormier, Yvon

    2012-07-01

    Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an allergen to which the subject has been previously sensitized. The diagnosis of HP most often relies on an array of nonspecific clinical symptoms and signs developed in an appropriate setting, with the demonstration of interstitial markings on chest radiographs, serum precipitating antibodies against offending antigens, a lymphocytic alveolitis on BAL, and/or a granulomatous reaction on lung biopsies. The current classification of HP in acute, subacute, and chronic phases is now challenged, and a set of clinical predictors has been proposed. Nonspecific interstitial pneumonitis, usual interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia may be the sole histologic expression of the disease. Presumably, like in idiopathic interstitial pneumonia, acute exacerbations of chronic HP may occur without further exposure to the offending antigen. New offending antigens, such as mycobacteria causing hot tub lung and metalworking fluid HP, have recently been identified and have stimulated further research in HP. PMID:22796841

  15. Chlamydial disease pathogenesis. Ocular hypersensitivity elicited by a genus-specific 57-kD protein

    PubMed Central

    1989-01-01

    Recurrent or persistent infections with Chlamydia trachomatis are thought to provide the antigenic stimulus for the chronic inflammation associated with blinding trachoma. We used the guinea pig model of inclusion conjunctivitis to identify chlamydial antigens that may be involved in this deleterious immune response. We purified from chlamydial elementary bodies a genus-specific 57-kD protein that elicited an ocular hypersensitivity response when placed topically onto the conjunctiva of ocular immune guinea pigs. This response was characterized by a predominantly mononuclear macrophage and lymphocyte cellular infiltrate of the submucosal epithelium. The clinical and histological findings were consistent with those of a delayed hypersensitivity response. These data demonstrated that the 57-kD chlamydial protein was a potent stimulator of ocular delayed hypersensitivity. Our findings may be critical to understanding the pathogenesis of the debilitating chlamydial diseases associated with chronic inflammation, such as trachoma and many urogenital syndromes. PMID:2926323

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

    PubMed

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

    2011-09-01

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

  17. Periaqueductal Grey EP3 Receptors Facilitate Spinal Nociception in Arthritic Secondary Hypersensitivity

    PubMed Central

    Drake, R.A.R.; Leith, J.L.; Almahasneh, F.; Martindale, J.; Wilson, A.W.; Lumb, B.

    2016-01-01

    Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase–prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown. In naive rats, PG EP3 receptor (EP3R) antagonism in vlPAG modulated noxious withdrawal reflex (EMG) thresholds to preferential C-nociceptor, but not A-nociceptor, activation and raised thermal withdrawal thresholds in awake animals. In rats with inflammatory arthritis, secondary mechanical and thermal hypersensitivity of the hindpaw developed and was associated with spinal sensitization to A-nociceptor inputs alone. In arthritic rats, blockade of vlPAG EP3R raised EMG thresholds to C-nociceptor activation in the area of secondary hypersensitivity to a degree equivalent to that evoked by the same manipulation in naive rats. Importantly, vlPAG EP3R blockade also affected responses to A-nociceptor activation, but only in arthritic animals. We conclude that vlPAG EP3R activity exerts an equivalent facilitation on the spinal processing of C-nociceptor inputs in naive and arthritic animals, but gains in effects on spinal A-nociceptor processing from a region of secondary hypersensitivity. Therefore, the spinal sensitization to A-nociceptor inputs associated with secondary hypersensitivity is likely to be at least partly dependent on descending prostanergic facilitation from the vlPAG. SIGNIFICANCE STATEMENT After tissue damage, sensitivity to painful stimulation develops in undamaged areas (secondary

  18. Hypersensitivity to pain in congenital blindness.

    PubMed

    Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano; Pietrini, Pietro; Ptito, Maurice; Kupers, Ron

    2013-10-01

    Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants' attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects, congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing. PMID:24040972

  19. Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride

    PubMed Central

    Anderson, Stacey E.; Shane, Hillary; Long, Carrie; Lukomska, Ewa; Meade, B. Jean; Marshall, Nikki B.

    2016-01-01

    Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. PMID:27216637

  20. Lung Transplantation for Hypersensitivity Pneumonitis

    PubMed Central

    Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

    2015-01-01

    BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

  1. Hypersensitivity reactions associated with oxaliplatin.

    PubMed

    Saif, M Wasif

    2006-09-01

    The reported incidence of hypersensitivity reactions (HSRs) associated with oxaliplatin in patients with colorectal cancer (CRC) is approximately 12%, with 1 - 2% of patients developing grade 3 or 4 in severity. However, the recent rising incidence of HSR to oxaliplatin observed is the result of increasing clinical use. HSR to oxaliplatin may manifest as facial flushing, rash/hives, tachycardia, dyspnoea, erythema, pruritus, fever, tongue swelling, headache, chills, weakness, vomiting, burning sensations, dizziness and oedema. Anaphylactic shock is rare but serious, and must be considered in the event of hypotension. No definitive approaches to prevent and treat HSR associated with oxaliplatin are available; however, few successful strategies have been reported. Such strategies include: slowing the infusion rate, use of steroids and antagonists of type 1 and 2 histamine receptors, and desensitisation. Successful implementation of oxaliplatin desensitisation protocols based on other platinum-containing compounds have been reported, which could enable a small number of patients who experience severe HSR to further receive an effective therapy for CRC. However, reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitisation strategies are still missing. Recently, subcutaneous adrenaline has also been utilised as an alternative approach to manage HSR to oxaliplatin. Knowledge of this rare but real toxicity of oxaliplatin is paramount because the use of this drug continues to increase not only for the treatment of patients with stage II-IV CRC, but also other solid malignancies. In this article, the author discusses the incidence, clinical presentation, pathogenesis, risk factors and current strategies of management of HSR associated with oxaliplatin. PMID:16907658

  2. Hypersensitivity pneumonitis and exposure to zirconium silicate in a young ceramic tile worker.

    PubMed

    Liippo, K K; Anttila, S L; Taikina-Aho, O; Ruokonen, E L; Toivonen, S T; Tuomi, T

    1993-10-01

    We describe a nonsmoking ceramic tile worker 25 yr of age who developed a worsening dry cough and dyspnea after 3.5 yr as a sorter and glazer of tiles. Open lung biopsy revealed an intense granulomatous interstitial pneumonia with mild fibrosis, compatible with hypersensitivity pneumonitis, and numerous very small birefringent crystals around the terminal airways and occasionally in granulomas. Pulmonary particle analysis revealed an inhaled dust burden nearly 100-fold the normal background level, mainly consisting of clay minerals and zirconium silicate. The patient had no history or clinical or laboratory findings suggesting any organic etiologic agent. A sarcoid granulomatosis type of chronic pulmonary hypersensitivity reaction is known after long-term exposure to zirconium, but this case demonstrates that zirconium can also cause an acute and fulminant allergic alveolitislike hypersensitivity reaction.

  3. 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

  4. Power toothbrushes, gender, and dentin hypersensitivity.

    PubMed

    Hefti, A F; Stone, C

    2000-06-01

    Power toothbrushes require less force for plaque removal than manual brushes. In addition, in vitro studies have indicated that brushing with low force could occlude patent dentin tubules by formation of a smear layer. Hence, lessening the force necessary to remove plaque may reduce dentin hypersensitivity. However, it was recently suggested that the use of an oscillating/rotating power toothbrush could decrease tooth sensitivity as compared to a sonic power toothbrush. Therefore, the objective of the present research was to compare the effect on dentin hypersensitivity of two different types of power brushes, the Optiva Sonicare and the Braun Oral B Ultra Plaque Remover. The null hypothesis was tested in an 8-week, randomized, parallel group, examiner-blind clinical trial. Fifty-nine subjects with a history of dentin hypersensitivity participated. Dentin hypersensitivity-associated pain was elicited using tactile and evaporative stimuli and assessed using a visual analog scale (VAS) instrument. Clinical examinations were carried out at screening and baseline and repeated after 8 weeks of twice daily use of the power brushes. Data analysis was performed on VAS scores obtained at the final visit following adjustment for group differences at baseline. A 35% to 40% reduction in pain as compared to baseline was observed in both treatment groups. Treatment-related differences were not statistically significant. A gender-related effect on dentin hypersensitivity was observed using the tactile stimulus and may merit further investigation.

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

    ERIC Educational Resources Information Center

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

    2016-01-01

    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.…

  6. A naturally hypersensitive glucocorticoid receptor elicits a compensatory reduction of hypothalamus–pituitary–adrenal axis activity early in ontogeny

    PubMed Central

    Muráni, Eduard; Ponsuksili, Siriluck; Jaeger, Alexandra; Görres, Andreas; Tuchscherer, Armin; Wimmers, Klaus

    2016-01-01

    We comprehensively characterized the effects of a unique natural gain-of-function mutation in the glucocorticoid receptor (GR), GRAla610Val, in domestic pigs to expand current knowledge of the phenotypic consequences of GR hypersensitivity. Cortisol levels were consistently reduced in one-week-old piglets, at weaning and in peripubertal age, probably due to a reduced adrenal capacity to produce glucocorticoids (GC), which was indicated by an adrenocortical thinning in GRAla610Val carriers. Adrenocorticotrophic hormone (ACTH) levels were significantly reduced in one-week-old piglets only. Expression analyses in peripubertal age revealed significant downregulation of hypothalamic expression of CRH and AVP, the latter only in females, and upregulation of hepatic expression of SERPINA6, by GRAla610Val. Transcriptional repression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) from GRAla610Val carriers was more sensitive to dexamethasone treatment ex vivo. However, no significant effects on growth, body composition, blood chemistry or cell counts were observed under baseline conditions. These results suggest that GRAla610Val-induced GR hypersensitivity elicits a compensatory reduction in endogenous, bioactive glucocorticoid levels via readjustment of the hypothalamus–pituitary–adrenal (HPA) axis early in ontogeny to maintain an adequate response, but carriers are more sensitive to exogenous GC. Therefore, GRAla610Val pigs represent a valuable animal model to explore GR-mediated mechanisms of HPA axis regulation and responses to glucocorticoid-based drugs. PMID:27440422

  7. Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response

    PubMed Central

    Brucklacher, Robert M; Patel, Kruti M; VanGuilder, Heather D; Bixler, Georgina V; Barber, Alistair J; Antonetti, David A; Lin, Cheng-Mao; LaNoue, Kathryn F; Gardner, Thomas W; Bronson, Sarah K; Freeman, Willard M

    2008-01-01

    Background Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes. Results Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals. Conclusion These changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics. PMID:18554398

  8. TRPA1 Contributes to Cold Hypersensitivity

    PubMed Central

    Camino, Donato del; Murphy, Sarah; Heiry, Melissa; Barrett, Lee B.; Earley, Taryn J.; Cook, Colby A.; Petrus, Matt J.; Zhao, Michael; D'Amours, Marc; Deering, Nate; Brenner, Gary J.; Costigan, Michael; Hayward, Neil J.; Chong, Jayhong A.; Fanger, Christopher M.; Woolf, Clifford J.; Patapoutian, Ardem; Moran, Magdalene M.

    2010-01-01

    TRPA1 is a non-selective cation channel expressed by nociceptors. While it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions where reactive oxygen species and pro-inflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1-/- mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain. PMID:21068322

  9. 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.

  10. Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief.

    PubMed

    Cummins, Diane

    2009-01-01

    This paper provides an overview of the current knowledge of diagnosis, epidemiology, etiology, and clinical management of dentin hypersensitivity. It summarizes technical approaches to relieve sensitivity in professional and home-use products, with emphasis on the clinical evidence for the efficacy of desensitizing toothpaste, and introduces a new innovative dentifrice technology containing 8% arginine, calcium carbonate, and 1450 ppm fluoride. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli which cannot be ascribed to any other form of dental defect or disease. The hydrodynamic theory proposes that pain-producing stimuli cause a change in dentin fluid flow that activates intra-dental nerve fibers, via a mechanoreceptor response, to cause pain. To be hypersensitive, dentin must be exposed and dentin tubules must be open to external stimuli and patent at the pulp. Gingival recession is the primary cause of dentin exposure, and a major predisposing factor for dentin hypersensitivity. Dentin hypersensitivity is a prevalent condition. It has been reported to afflict 15-20% of the adult population, typically 20 to 50-year-olds, with peak incidence between 30 and 39 years. Some studies have reported higher prevalence levels of up to 57%. The incidence of dentin hypersensitivity is expected to rise with changing diets, and as caries and periodontal disease prevention result in improved oral health status, and retention and functionality of the dentition. Treatments to relieve dentin hypersensitivity are based on interruption of the neural response to pain stimuli or occlusion of open tubules to block the hydrodynamic mechanism. Effective and robust dentin occlusion offers the greatest prospect for instant and lasting relief of dentin hypersensitivity. In particular, materials which can coat exposed dentin surfaces, in addition to plugging and sealing open dentin tubules, offer the intriguing

  11. Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief.

    PubMed

    Cummins, Diane

    2009-01-01

    This paper provides an overview of the current knowledge of diagnosis, epidemiology, etiology, and clinical management of dentin hypersensitivity. It summarizes technical approaches to relieve sensitivity in professional and home-use products, with emphasis on the clinical evidence for the efficacy of desensitizing toothpaste, and introduces a new innovative dentifrice technology containing 8% arginine, calcium carbonate, and 1450 ppm fluoride. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli which cannot be ascribed to any other form of dental defect or disease. The hydrodynamic theory proposes that pain-producing stimuli cause a change in dentin fluid flow that activates intra-dental nerve fibers, via a mechanoreceptor response, to cause pain. To be hypersensitive, dentin must be exposed and dentin tubules must be open to external stimuli and patent at the pulp. Gingival recession is the primary cause of dentin exposure, and a major predisposing factor for dentin hypersensitivity. Dentin hypersensitivity is a prevalent condition. It has been reported to afflict 15-20% of the adult population, typically 20 to 50-year-olds, with peak incidence between 30 and 39 years. Some studies have reported higher prevalence levels of up to 57%. The incidence of dentin hypersensitivity is expected to rise with changing diets, and as caries and periodontal disease prevention result in improved oral health status, and retention and functionality of the dentition. Treatments to relieve dentin hypersensitivity are based on interruption of the neural response to pain stimuli or occlusion of open tubules to block the hydrodynamic mechanism. Effective and robust dentin occlusion offers the greatest prospect for instant and lasting relief of dentin hypersensitivity. In particular, materials which can coat exposed dentin surfaces, in addition to plugging and sealing open dentin tubules, offer the intriguing

  12. 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...

  13. Immune cell populations in cutaneous delayed-type hypersensitivity

    PubMed Central

    1983-01-01

    Delayed-type hypersensitivity (DTH) is a prototypic T lymphocyte- mediated response to antigenic challenge. In this study, mononuclear cells infiltrating the skin during cutaneous response to tuberculin in presensitized human subjects (responders) and nonimmune controls were identified using monoclonal antibodies by indirect immunofluorescence. In both responders and controls the infiltrate consisted mainly of T lymphocytes (T11+ and OKT3+) and monocytes (OKM1+, 63D3+, Mo2+) which initially accumulated in proximity to small blood vessels and later infiltrated the interstitial dermis and epidermis. More T lymphocytes reacted with OKT4 than with OKT8. 6 h after tuberculin the ratio of OKT4/OKT8 in tissue from responders exceeded that in blood, whereas in tissues studied at 15-48 h and in all control tissues those ratios in blood and tissue were similar. Evidence of T lymphocyte activation was sought using monoclonal antibodies anti-Tac, OKT9, and OKT10. In responders but not in controls the proportion of infiltrating cells reactive with these antibodies increased during the course of DTH. The presence of activated T lymphocytes in tissue was not associated with a comparable increase in peripheral blood cell populations identified by anti-Tac and OKT10. Studies using anti-B1, Leu-7, and anti-IgD/IgM revealed comparatively few reactive cells. Dual-labeling studies demonstrated that most Leu-7--reactive cells also bound T11 while fewer bound OKM1 or OKT8 and that cells reactive with OKIa1 and T11 constituted largely nonoverlapping populations. Specific patterns of reactivity were not observed when tissues were stained with anti-human C3, or poly C9-MA, a monoclonal antibody reactive with a neoantigen on polymerized C9 of the membrane attack complex of complement. The number of epidermal Langerhans cells identified by OKT6 was similar in responders and controls. Thus, the cutaneous response to tuberculin in sensitized individuals is characterized by early enrichment of

  14. How to manage asparaginase hypersensitivity in acute lymphoblastic leukemia.

    PubMed

    Burke, Michael J

    2014-12-01

    Outcomes for children with acute lymphoblastic leukemia (ALL) have improved significantly in recent decades, primarily due to dose-intensified, multi-agent chemotherapy regimens, of which asparaginase has played a prominent role. Despite this success, hypersensitivity remains a significant problem, often requiring the termination of asparaginase. Failure to complete the entire asparaginase therapy course due to clinical hypersensitivity, subclinical hypersensitivity (i.e., silent inactivation), or other treatment-related toxicity is associated with poor ALL outcomes. Thus, it is critical to rapidly identify patients who develop clinical/subclinical hypersensitivity and switch these patients to an alternate asparaginase formulation. This article provides an overview of asparaginase hypersensitivity, identification and management of hypersensitivity and subclinical hypersensitivity, and issues related to switching patients to asparaginase Erwinia chrysanthemi following hypersensitivity reaction.

  15. 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

  16. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

    PubMed Central

    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  17. Low-level laser therapy of dentin hypersensitivity: a short-term clinical trial.

    PubMed

    Orhan, Kaan; Aksoy, Umut; Can-Karabulut, Deniz C; Kalender, Atakan

    2011-09-01

    The aim of this study was to evaluate low-level laser therapy in cervical dentin hypersensitivity. A randomized controlled clinical trial was conducted with a total of 64 teeth. Dentin desensitizer and diode laser were applied on the cervical dentin surfaces. Distilled water and placebo laser was used as the placebo groups. The irradiance used was 4 J/cm(2) per treatment site. The baseline measurement of hypersensitivity was made by using visual analog scale (VAS). Twenty-four hours and 7 days after the application of desensitizer, diode laser and placebo groups, a new VAS analysis was conducted for the patients' sensitivity level. The mean pain scores of placebo groups were significantly higher than the desensitizer's and diode laser's mean scores (ANOVA, p < 0.05). The VAS analysis revealed a significant decrease in dentin hypersensitivity in 7 days with the use of the desensitizer and low-level laser therapy and no statistically significant difference was observed between these two treatments (p > 0.05). Although low-level laser and glutaraldehyde containing desensitizer present distinct modes of action, experimental agents caused a significant reduction of dentin hypersensitivity without showing secondary effects, not irritating the pulp or causing pain, not discoloring or staining the teeth, and not irritating the soft tissues at least for a period of 1 week with no drawbacks regarding handling and/or ease of application. Low-level laser therapy and desensitizer application had displayed similar effectiveness in reducing moderate dentin hypersensitivity.

  18. 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

  19. Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity.

    PubMed

    Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D; Cashikar, Anil G; King, Oliver D; Auluck, Pavan K; Geddie, Melissa L; Valastyan, Julie S; Karger, David R; Lindquist, Susan; Fraenkel, Ernest

    2009-03-01

    Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens. By comparing the results of these two assays across various stimuli, we found that genetic screens tend to identify response regulators, whereas mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We used this approach to reveal cellular pathways responding to the toxicity of alpha-synuclein, a protein implicated in several neurodegenerative disorders including Parkinson's disease. For this we screened an established yeast model to identify genes that when overexpressed alter alpha-synuclein toxicity. Bridging these data and data from mRNA profiling provided functional explanations for many of these genes and identified previously unknown relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470

  20. Effect of a fluoride solution on dentinal hypersensitivity.

    PubMed

    Thrash, W J; Jones, D L; Dodds, W J

    1992-12-01

    This two-phase experiment assessed the effects over time of a solution containing 1.09% sodium fluoride, .40% stannous fluoride, and .14% hydrogen fluoride (.717% fluoride solution, DentinBloc) on pain associated with dentinal hypersensitivity. During phase I, 30 subjects demonstrating dentinal hypersensitivity to a blast of cool air were divided into three double blind experimental groups. After baseline data were collected for all subjects, one group was instructed to apply the .717% fluoride solution twice a day. A second group was instructed to apply a gel containing .04% stannous fluoride (Gel-Kam) twice a day. A third group was instructed to apply distilled water. Each subject was assessed at 2, 4, 8, and 16 weeks utilizing the "method of limits" with a standardized, repeatable cold thermal stimulus. The results of a two factor repeated ANOVA indicated that those subjects who applied the .717% fluoride solution reported significantly less sensitivity at the 2-week period than the other groups (P < .05). In addition, those subjects whose solution contained the 0.4% stannous fluoride reported significantly less sensitivity at the 4- to 8-week periods (P < .05). Phase II of the study assessed the .717% fluoride solution on a more precise time course. These included: immediately, 15 minute, 1 day, 1 week and 2 weeks. A one factor repeated ANOVA revealed that this effect presented 15-minute post application (P < .05) and continued throughout the testing periods. It was concluded that the fully active 0.717% fluoride solution was an effective agent in the control of dentinal hypersensitivity after two 1-minute applications.

  1. Distinct subclonal tumour responses to therapy revealed by circulating cell-free DNA

    PubMed Central

    Gremel, G.; Lee, R. J.; Girotti, M. R.; Mandal, A. K.; Valpione, S.; Garner, G.; Ayub, M.; Wood, S.; Rothwell, D. G.; Fusi, A.; Wallace, A.; Brady, G.; Dive, C.; Dhomen, N.; Lorigan, P.; Marais, R.

    2016-01-01

    Background The application of precision medicine in oncology requires in-depth characterisation of a patient's tumours and the dynamics of their responses to treatment. Patients and methods We used next-generation sequencing of circulating cell-free DNA (cfDNA) to monitor the response of a KIT p.L576P-mutant metastatic vaginal mucosal melanoma to sequential targeted, immuno- and chemotherapy. Results Despite a KIT mutation, the response to imatinib was mixed. Unfortunately, tumours were not accessible for molecular analysis. To study the mechanism underlying the mixed clinical response, we carried out whole-exome sequencing and targeted longitudinal analysis of cfDNA. This revealed two tumour subclones; one with a KIT mutation that responded to imatinib and a second KIT-wild-type subclone that did not respond to imatinib. Notably, the subclones also responded differently to immunotherapy. However, both subclones responded to carboplatin/paclitaxel, and although the KIT-wild-type subclone progressed after chemotherapy, it responded to subsequent re-administration of paclitaxel. Conclusion We show that cfDNA can reveal tumour evolution and subclonal responses to therapy even when biopsies are not available. PMID:27502704

  2. 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

  3. Hydrocodone snorting leading to hypersensitivity pneumonitis.

    PubMed

    Pathak, Lakshmi Kant; Vijayaraghavan, Vimala

    2016-07-01

    We present a case of hypersensitivity pneumonitis caused by intranasal abuse of the prescription narcotic hydrocodone. The patient's clinical course was complicated by acute respiratory failure. A chest radiograph showed diffuse bilateral opacities. The patient was treated with noninvasive ventilation, a high dose of intravenous steroids, and bronchodilators, resulting in improvement of symptoms and radiographic appearance. PMID:27365873

  4. Hydrocodone snorting leading to hypersensitivity pneumonitis

    PubMed Central

    Vijayaraghavan, Vimala

    2016-01-01

    We present a case of hypersensitivity pneumonitis caused by intranasal abuse of the prescription narcotic hydrocodone. The patient's clinical course was complicated by acute respiratory failure. A chest radiograph showed diffuse bilateral opacities. The patient was treated with noninvasive ventilation, a high dose of intravenous steroids, and bronchodilators, resulting in improvement of symptoms and radiographic appearance. PMID:27365873

  5. 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.

  6. Effect of Two Desensitizing Agents in Reducing Dentin Hypersensitivity: An in-vivo Comparative Clinical Trial

    PubMed Central

    Torwane, Nilesh Arjun; Hongal, Sudhir; Goel, Pankaj; B.R, Chandrashekhar; Jain, Manish; Saxena, Eshani; Gouraha, Abhishek; Yadav, Sourabh

    2013-01-01

    Objective: A randomized, double blind, split mouth, controlled clinical trial was conducted to evaluate the effect of two desensitizing agents on reduction of Dentin Hypersensitivity (DH). Material and Methodology: A sample of 73 teeth from 13 patients, among which at least 3 teeth had dentin hypersensitivity, was randomly allocated into 3 treatment groups: Group A: treated with 30% ethenolic extract of Indian Propolis, Group B: treated with GC tooth mousse, and Group C: treated with sterile water. A Verbal Rating Scale (VRS) was used to record the degree of hypersensitivity, based on patient’s response to tactile and air blast stimuli. The baseline scores were obtained. Each intervention group received applications of their respective agents consecutively on 1st, 7th, 14th and 21st days. After each application, the scores were recorded. Results: Both the 30% Indian Propolis and GC tooth mousse showed significant reductions in dentin hypersensitivity. Conclusion: GC tooth mousse was found to be significantly better in reducing the dentinal hypersensitivity as compared to Propolis and sterile water (p< 0.01). PMID:24179939

  7. Analysis of morphine responses in mice reveals a QTL on Chromosome 7

    PubMed Central

    Crusio, Wim E.; Dhawan, Esha; Chesler, Elissa J.; Delprato, Anna

    2016-01-01

    In this study we identified a quantitative trait locus (QTL) on mouse Chromosome 7 associated with locomotor activity and rearing post morphine treatment. This QTL was revealed after correcting for the effects of another QTL peak on Chromosome 10 using composite interval mapping. The positional candidate genes are Syt9 and Ppfibp2. Several other genes within the interval are linked to neural processes, locomotor activity, and the defensive response to harmful stimuli. PMID:27746909

  8. TH1/TH2 balance in concomitant immediate and delayed-type hypersensitivity diseases.

    PubMed

    de Mello, Luane Marques; Bechara, Monique Isabel Silveira; Solé, Dirceu; Rodrigues, Virmondes

    2009-06-01

    In spite of the observation of mutual inhibitory properties of TH1 and TH2 CD4+ cells, a group of patients developed simultaneously immediate and delayed-type hypersensitivity reactions that are theoretically antagonistic. Patients presenting concomitant hypersensitivity reactions were evaluated for cytokine production. PBMC from 45 patients and 13 non-atopic individuals were cultured with mite allergen and mitogen and the supernatants obtained were evaluated for cytokine production by ELISA. The analysis of the cytokines levels revealed increased production of pro-inflammatory cytokine TNF-alpha in the non-atopic individuals after specific and mitogen stimulus. The IL-4 was largely observed on serum samples and IL-5 levels were higher in the double sensitized group (group DerpNi) after PHA stimulus. The IL-13 levels were increased in sensitized groups (Derp and DerpNi groups) after PHA stimuli. Atopic patients (Derp and DerpNi groups) presented lowest levels IFN-gamma and the analysis of TGF-beta production after rDER P I stimulation have shown increased levels among sensitized patients to Dermatophagoides pteronyssinus mite. IL-10 levels did not differ after antigen stimulation but basal production was higher on Derp and DerpNi groups. Furthermore, negative correlations were observed between IFN-gamma levels and IL-4, IL-13 and IL-10. This study has shown patients able to react, concomitantly, to the two types of antigens - rDER P I and NiSO4, present distinct pattern of cytokine production. The increased levels of IL-13 in the sensitive individuals to mite antigen (rDER P I) and IFN-gamma in NiSO4 sensitized individuals confirm the role of the type TH2 response in the atopies and TH1 type in DCA. PMID:19433108

  9. Genome-wide analysis reveals a highly diverse CD8 T cell response to murine cytomegalovirus.

    PubMed

    Munks, Michael W; Gold, Marielle C; Zajac, Allison L; Doom, Carmen M; Morello, Christopher S; Spector, Deborah H; Hill, Ann B

    2006-03-15

    Human CMV establishes a lifelong latent infection in the majority of people worldwide. Although most infections are asymptomatic, immunocompetent hosts devote an extraordinary amount of immune resources to virus control. To increase our understanding of CMV immunobiology in an animal model, we used a genomic approach to comprehensively map the C57BL/6 CD8 T cell response to murine CMV (MCMV). Responses to 27 viral proteins were detectable directly ex vivo, the most diverse CD8 T cell response yet described within an individual animal. Twenty-four peptide epitopes were mapped from 18 Ags, which together account for most of the MCMV-specific response. Most Ags were from genes expressed at early times, after viral genes that interfere with Ag presentation are expressed, consistent with the hypothesis that the CD8 T cell response to MCMV is largely driven by cross-presented Ag. Titration of peptide epitopes in a direct ex vivo intracellular cytokine staining assay revealed a wide range of functional avidities, with no obvious correlation between functional avidity and the strength of the response. The immunodominance hierarchy varied only slightly between mice and between experiments. However, H-2(b)-expressing mice with different genetic backgrounds responded preferentially to different epitopes, indicating that non-MHC-encoded factors contribute to immunodominance in the CD8 T cell response to MCMV.

  10. 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

  11. 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

  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 μg) produced no effect on behavioral measures of thermal or mechanical hypersensitivity whereas intrathecal morphine (1μg) and gabapentin (200 μg) 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

  13. 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

  14. 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.

  15. 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

  16. NADPH Oxidase-Derived ROS Induced by Chronic Intermittent Hypoxia Mediates Hypersensitivity of Lung Vagal C Fibers in Rats.

    PubMed

    Yang, Chang-Huan; Zhuang, Wei-Ling; Shen, Yan-Jhih; Lai, Ching Jung; Kou, Yu Ru

    2016-01-01

    Obstructive sleep apnea (OSA), manifested by exposure to chronic intermittent hypoxia (CIH) and excess production of reactive oxygen species (ROS) in the airways, is associated with hyperreactive airway diseases. ROS, particularly when created by NADPH oxidase, are known to sensitize lung vagal C fibers (LVCFs), which may contribute to airway hypersensitivity pathogenesis. We investigated whether CIH augments the reflex and afferent responses of LVCFs to chemical stimulants and the roles of ROS and NADPH oxidase in such airway hypersensitivity. Rats were exposed to room air (RA) or CIH with/without daily treatment with MnTMPyP (a superoxide anion scavenger), apocynin (an NADPH oxidase inhibitor), or vehicle. At 16 h after their last exposure, intravenous capsaicin, adenosine, or α,β-methylene-ATP evoked an augmented apneic response in anesthetized rats with 14-days CIH exposure, compared to anesthetized rats with 14-days RA exposure. The augmented apneic responses to these LVCF stimulants were abolished by bilateral vagotomy or perivagal capsaicin treatment, which block LVCFs neural conduction and were significantly suppressed by treatment with MnTMPyP or apocynin, but not vehicle. Electrophysiological studies revealed that 14-days CIH exposure potentiated the responses of LVCFs to these stimulants. This effect was inhibited by treatment with MnTMPyP or apocynin treatment and was not seen in rats who received 7-days of CIH exposure. Biochemical analysis indicated that 14-days CIH exposure increased both lung lipid peroxidation, which is indicative of oxidative stress, and expression of the p47(phox) subunit in the membrane fraction of lung tissue, which is an index of NADPH oxidase activation. The former was prevented by treatment with either MnTMPyP or apocynin, while the later was prevented by treatment with apocynin only. These results suggest that 14-days CIH exposure sensitizes LVCFs in rats, leading to an exaggerated reflex and afferent responses to

  17. NADPH Oxidase-Derived ROS Induced by Chronic Intermittent Hypoxia Mediates Hypersensitivity of Lung Vagal C Fibers in Rats

    PubMed Central

    Yang, Chang-Huan; Zhuang, Wei-Ling; Shen, Yan-Jhih; Lai, Ching Jung; Kou, Yu Ru

    2016-01-01

    Obstructive sleep apnea (OSA), manifested by exposure to chronic intermittent hypoxia (CIH) and excess production of reactive oxygen species (ROS) in the airways, is associated with hyperreactive airway diseases. ROS, particularly when created by NADPH oxidase, are known to sensitize lung vagal C fibers (LVCFs), which may contribute to airway hypersensitivity pathogenesis. We investigated whether CIH augments the reflex and afferent responses of LVCFs to chemical stimulants and the roles of ROS and NADPH oxidase in such airway hypersensitivity. Rats were exposed to room air (RA) or CIH with/without daily treatment with MnTMPyP (a superoxide anion scavenger), apocynin (an NADPH oxidase inhibitor), or vehicle. At 16 h after their last exposure, intravenous capsaicin, adenosine, or α,β-methylene-ATP evoked an augmented apneic response in anesthetized rats with 14-days CIH exposure, compared to anesthetized rats with 14-days RA exposure. The augmented apneic responses to these LVCF stimulants were abolished by bilateral vagotomy or perivagal capsaicin treatment, which block LVCFs neural conduction and were significantly suppressed by treatment with MnTMPyP or apocynin, but not vehicle. Electrophysiological studies revealed that 14-days CIH exposure potentiated the responses of LVCFs to these stimulants. This effect was inhibited by treatment with MnTMPyP or apocynin treatment and was not seen in rats who received 7-days of CIH exposure. Biochemical analysis indicated that 14-days CIH exposure increased both lung lipid peroxidation, which is indicative of oxidative stress, and expression of the p47phox subunit in the membrane fraction of lung tissue, which is an index of NADPH oxidase activation. The former was prevented by treatment with either MnTMPyP or apocynin, while the later was prevented by treatment with apocynin only. These results suggest that 14-days CIH exposure sensitizes LVCFs in rats, leading to an exaggerated reflex and afferent responses to

  18. Quantitative Proteomics Reveals the Defense Response of Wheat against Puccinia striiformis f. sp. tritici

    PubMed Central

    Yang, Yuheng; Yu, Yang; Bi, Chaowei; Kang, Zhensheng

    2016-01-01

    Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is considered one of the most aggressive diseases to wheat production. In this study, we used an iTRAQ-based approach for the quantitative proteomic comparison of the incompatible Pst race CYR23 in infected and non-infected leaves of the wheat cultivar Suwon11. A total of 3,475 unique proteins were identified from three key stages of interaction (12, 24, and 48 h post-inoculation) and control groups. Quantitative analysis showed that 530 proteins were differentially accumulated by Pst infection (fold changes >1.5, p < 0.05). Among these proteins, 10.54% was classified as involved in the immune system process and stimulus response. Intriguingly, bioinformatics analysis revealed that a set of reactive oxygen species metabolism-related proteins, peptidyl–prolyl cis–trans isomerases (PPIases), RNA-binding proteins (RBPs), and chaperonins was involved in the response to Pst infection. Our results were the first to show that PPIases, RBPs, and chaperonins participated in the regulation of the immune response in wheat and even in plants. This study aimed to provide novel routes to reveal wheat gene functionality and better understand the early events in wheat–Pst incompatible interactions. PMID:27678307

  19. Molecular force modulation spectroscopy revealing the dynamic response of single bacteriorhodopsins.

    PubMed

    Janovjak, Harald; Müller, Daniel J; Humphris, Andrew D L

    2005-02-01

    Recent advances in atomic force microscopy allowed globular and membrane proteins to be mechanically unfolded on a single-molecule level. Presented is an extension to the existing force spectroscopy experiments. While unfolding single bacteriorhodopsins from native purple membranes, small oscillation amplitudes (6-9 nm) were supplied to the vertical displacement of the cantilever at a frequency of 3 kHz. The phase and amplitude response of the cantilever-protein system was converted to reveal the elastic (conservative) and viscous (dissipative) contributions to the unfolding process. The elastic response (stiffness) of the extended parts of the protein were in the range of a few tens pN/nm and could be well described by the derivative of the wormlike chain model. Discrete events in the viscous response coincided with the unfolding of single secondary structure elements and were in the range of 1 microNs/m. In addition, these force modulation spectroscopy experiments revealed novel mechanical unfolding intermediates of bacteriorhodopsin. We found that kinks result in a loss of unfolding cooperativity in transmembrane helices. Reconstructing force-distance spectra by the integration of amplitude-distance spectra verified their position, offering a novel approach to detect intermediates during the forced unfolding of single proteins. PMID:15574708

  20. 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

  1. 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.

  2. Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria

    PubMed Central

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

    2005-01-01

    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

  3. Effect of oil composition on both adjuvant-induced arthritis and delayed hypersensitivity to purified protein derivative and peptidoglycans in various rat strains.

    PubMed Central

    Kohashi, O; Pearson, M; Beck, F J; Alexander, M

    1977-01-01

    We confirmed that, when immunized with a conventional complete Freund adjuvant (water in oil), Lewis rats were highly susceptible to adjuvant arthritis, Fisher rats were less susceptible, and Buffalo rats were much less susceptible. However, mycobacterial delipidated cells in squalane (squalane-type adjuvant) produced severe arthritis with almost 100% incidence even in the less susceptible rat strains except for Buffalo rats. With regard to an immune response, Freund complete adjuvant induced strong delayed hypersensitivity to purified protein derivative (PPD) and peptidoglycan (PG) in all rat strains used, Whereas the squalane-type adjuvant induced these hypersensitivities only in Lewis and Buffalo rats, but not in Fisher and Brown Norway rats. No correlation was found between development of arthritis and delayed hypersensitivity to either PPD or PG, or both. It seems that PPD hypersensitivity may be inherited differently from PG hypersensitivity. PMID:892904

  4. Effect of oil composition on both adjuvant-induced arthritis and delayed hypersensitivity to purified protein derivative and peptidoglycans in various rat strains.

    PubMed

    Kohashi, O; Pearson, M; Beck, F J; Alexander, M

    1977-08-01

    We confirmed that, when immunized with a conventional complete Freund adjuvant (water in oil), Lewis rats were highly susceptible to adjuvant arthritis, Fisher rats were less susceptible, and Buffalo rats were much less susceptible. However, mycobacterial delipidated cells in squalane (squalane-type adjuvant) produced severe arthritis with almost 100% incidence even in the less susceptible rat strains except for Buffalo rats. With regard to an immune response, Freund complete adjuvant induced strong delayed hypersensitivity to purified protein derivative (PPD) and peptidoglycan (PG) in all rat strains used, Whereas the squalane-type adjuvant induced these hypersensitivities only in Lewis and Buffalo rats, but not in Fisher and Brown Norway rats. No correlation was found between development of arthritis and delayed hypersensitivity to either PPD or PG, or both. It seems that PPD hypersensitivity may be inherited differently from PG hypersensitivity.

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

    PubMed

    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. PMID:26595448

  6. [A misleading form of hypersensitivity pneumonitis].

    PubMed

    Gainet, M; Chaudemanche, H; Westeel, V; Lounici, A; Dubiez, A; Depierre, A; Dalphin, J C

    2000-11-01

    A 47-year-old woman, without significant past medical history, presented an acute dyspnea with hypoxia, marked pulmonary arterial hypertension (PAH) and signs of right heart failure. Chest x-ray showed a moderate dilatation of the right heart cavities. Pulmonary embolism was suggested. After detailed questioning and complete explorations, a bird hypersensitivity pneumonitis (HP) was demonstrated. This case illustrates a misleading presentation of an acute form of HP consisting of apparently isolated PAH.

  7. Hypersensitivity reactions to carboplatin in children.

    PubMed

    Lazzareschi, Ilaria; Ruggiero, Antonio; Riccardi, Riccardo; Attinà, Giorgio; Colosimo, Cesare; Lasorella, Anna

    2002-05-01

    Hypersensitivity reactions to carboplatin are rare but sometimes life-threatening events may occur requiring discontinuation of treatment. In our study, we describe clinical features and diagnostic procedures of carboplatin-associated reactions in children affected by low-grade astrocytoma and treated with multiple courses of carboplatin. In 6 out of 29 children, we reported allergic events. We also report a desensitization protocol for carboplatin administration, which allowed the patients to receive effective treatment without adverse reactions.

  8. Role of spinal 5-HT receptors in cutaneous hypersensitivity induced by REM sleep deprivation.

    PubMed

    Wei, Hong; Ma, Ainiu; Wang, Yong-Xiang; Pertovaara, Antti

    2008-06-01

    Previous studies indicate that rapid eye movement (REM) sleep deprivation facilitates pain sensitivity. Since serotoninergic raphe neurons are involved both in regulation of sleep and descending pain modulation, we studied whether spinal 5-HT receptors have a role in sleep deprivation-induced facilitation of pain-related behavior. REM sleep deprivation of 48h was induced by the flower pot method in the rat. The pain modulatory influence of various serotoninergic compounds administered intrathecally was assessed by determining limb withdrawal response to monofilaments. REM sleep deprivation produced a marked hypersensitivity. Sleep deprivation-induced hypersensitivity and normal sensitivity in controls were reduced both by a 5-HT(1A) receptor antagonist (WAY-100635) and a 5-HT(2C) receptor antagonist (RS-102221). An antagonist of the 5-HT(3) receptor (LY-278584) failed to modulate hypersensitivity in sleep-deprived or control animals. Paradoxically, sensitivity in sleep-deprived and control animals was reduced not only by a 5-HT(1A) receptor antagonist but also by a 5-HT(1A) receptor agonist (8-OHDPAT). The results indicate that serotoninergic receptors in the spinal cord have a complex role in the control of sleep-deprivation induced cutaneous hypersensitivity as well as baseline sensitivity in control conditions. While endogenous serotonin acting on 5-HT(1A) and 5-HT(2C) receptors may facilitate mechanical sensitivity in animals with a sleep deprivation-induced hypersensitivity as well as in controls, increased activation of spinal 5-HT(1A) receptors by an exogenous agonist leads to suppression of mechanical sensitivity in both conditions. Spinal 5-HT(3) receptors do not contribute to cutaneous hypersensitivity induced by sleep deprivation.

  9. Self responses along cingulate cortex reveal quantitative neural phenotype for high functioning autism

    PubMed Central

    Chiu, Pearl H.; Kayali, M. Amin; Kishida, Kenneth T.; Tomlin, Damon; Klinger, Laura G.; Klinger, Mark R.; Montague, P. Read

    2014-01-01

    Summary Attributing behavioral outcomes correctly to oneself or to other agents is essential for all productive social exchange. We approach this issue in high-functioning males with autism spectrum disorder (ASD) using two separate fMRI paradigms. First, using a visual imagery task, we extract a basis set for responses along the cingulate cortex of control subjects that reveals an agent-specific eigenvector (self eigenmode) associated with imagining oneself executing a specific motor act. Second, we show that the same self eigenmode arises during one's own decision (the self phase) in an interpersonal exchange game (iterated trust game). Third, using this exchange game, we show that ASD males exhibit a severely diminished self eigenmode when playing the game with a human partner. This diminished response covaries parametrically with their behaviorally assessed symptom severity suggesting its value as an objective endophenotype. These findings may provide a quantitative assessment tool for high functioning ASD. PMID:18255038

  10. Shellfish hypersensitivity: clinical and immunological characteristics.

    PubMed

    Castillo, R; Carrilo, T; Blanco, C; Quiralte, J; Cuevas, M

    1994-01-01

    Shellfish is one of the most frequent causes of food allergy. We studied 48 patients (25 male and 23 female) with a mean age of 24.2 +/- 1.8 with shellfish hypersensitivity. A clinical questionnaire was carried out and prick tests were performed using a series of aeroallergens and a battery of extracts of squid, shrimp, lobster, crab, mussel and clam. Prick tests were also performed using raw and boiled extracts from fresh squid, octopus and limpet. Total and specific IgE to these allergens were determined. The most frequent causes of symptoms were shrimp (33 cases) and squid (24 cases). The most frequently found symptoms were Urticaria/angioedema (39 patients), asthma (18 patients) and rhinitis (14 patients). Clinical association was found between Cephalopoedae and Lamelibranquiae (p < 0.05 for clam and p < 0.01 for mussel), but not among both groups and Crustaceans. Association between history and Prick was statistically significant for Crustaceae and Cephalopoedae (p < 0.01) but not for Lamalibranquiae. Association between history and CAP was not found for shellfish. Significant differences among prick-tests with raw and boiled extracts were not found. These results suggest that prick test yields better results than CAP does it, in shellfish hypersensitivity, that clinical association among shellfish hypersensitivity can occurs within the same and different Phylum reflecting common epitopes and that squid, octopus and limpet extracts contain a large amount of heat-stable allergens. PMID:8059680

  11. Stent hypersensitivity and infection in sinus cavities

    PubMed Central

    Soufras, George D.; Hahalis, George

    2013-01-01

    Persistent mucosal inflammation, granulation tissue formation, hypersensitivity, and multifactorial infection are newly described complications of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. In an important report published in Allergy and Rhinology, a 45-year-old male patient suffering from recalcitrant chronic rhinosinusitis underwent functional endoscopic sinus surgery and was found, for the first time, to have steroid-eluting catheters that were inadvertently left in the ethmoid and frontal sinuses. The retained catheters had caused persistent mucosal inflammation and formation of granulation tissue denoting hypersensitivity reaction. These consequences had induced perpetuation of symptoms of chronic rhinosinusitis. Meticulous removal of the retained stents with the nitinol wings from inflamed tissues of the frontal, ethmoidal, and sphenoethmoidal recesses in which they were completely imbedded was successfully performed without polypoid regrowth. Cultures of specimens taken from both left and right stents showed heavy growth of Stenotrophomonas maltophilia and moderate growth of Klebsiella oxytoca, coagulase negative Staphylococcus, and beta-hemolytic Streptococcus anginosus. Fungal infection was not detected. The current knowledge and experience regarding stent hypersensitivity and infection in relation with the use of stents in sinus cavities is reviewed. PMID:24498522

  12. 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

  13. Diagnosis and treatment of dentinal hypersensitivity.

    PubMed

    Porto, Isabel C C M; Andrade, Ana K M; Montes, Marcos A J R

    2009-09-01

    This bibliographic review provides a general view of the etiology, characteristics and treatment of dentinal hypersensitivity, so that professionals can use this information in the therapeutic management of this clinical condition. For this purpose, the authors have analyzed whole texts of relevant articles on the subject. This study showed that the predisposing factors associated with the causes of dentinal hypersensitivity must be controlled or eliminated, by educating the patient regarding the excessive intake of acidic food, as well as providing guidance on the proper tooth brushing technique and analysis of occlusion. Effective treatment must be preceded by a proper diagnosis, established after the exclusion of any other possible causes of the pain. These cases must be managed efficiently, quickly and permanently. The availability of a wide variety of treatment could be an indicator that there is still no effective desensitizing agent to completely resolve the patient's discomfort, or that it is difficult to treat, irrespective of the available treatment options. Even with the large number of published studies, it has not been possible to reach a consensus about the product that represents the gold standard in the treatment of dentinal hypersensitivity. PMID:19776498

  14. Shellfish hypersensitivity: clinical and immunological characteristics.

    PubMed

    Castillo, R; Carrilo, T; Blanco, C; Quiralte, J; Cuevas, M

    1994-01-01

    Shellfish is one of the most frequent causes of food allergy. We studied 48 patients (25 male and 23 female) with a mean age of 24.2 +/- 1.8 with shellfish hypersensitivity. A clinical questionnaire was carried out and prick tests were performed using a series of aeroallergens and a battery of extracts of squid, shrimp, lobster, crab, mussel and clam. Prick tests were also performed using raw and boiled extracts from fresh squid, octopus and limpet. Total and specific IgE to these allergens were determined. The most frequent causes of symptoms were shrimp (33 cases) and squid (24 cases). The most frequently found symptoms were Urticaria/angioedema (39 patients), asthma (18 patients) and rhinitis (14 patients). Clinical association was found between Cephalopoedae and Lamelibranquiae (p < 0.05 for clam and p < 0.01 for mussel), but not among both groups and Crustaceans. Association between history and Prick was statistically significant for Crustaceae and Cephalopoedae (p < 0.01) but not for Lamalibranquiae. Association between history and CAP was not found for shellfish. Significant differences among prick-tests with raw and boiled extracts were not found. These results suggest that prick test yields better results than CAP does it, in shellfish hypersensitivity, that clinical association among shellfish hypersensitivity can occurs within the same and different Phylum reflecting common epitopes and that squid, octopus and limpet extracts contain a large amount of heat-stable allergens.

  15. Possible role for TRPV1 in neomycin-induced inhibition of visceral hypersensitivity in rat.

    PubMed

    van den Wijngaard, R M; Welting, O; Bulmer, D C; Wouters, M M; Lee, K; de Jonge, W J; Boeckxstaens, G E

    2009-08-01

    Transient receptor ion channel 1 (TRPV1) is a nociceptor involved in visceral hypersensitivity. Aminoglycosides like neomycin are not only potent antibiotics but in vitro data suggest that neomycin also acts as a TRPV1-antagonist and alleviates somatic pain responses. To what extent neomycin reduces visceral hypersensitivity remains unknown. Therefore, we aimed to investigate whether neomycin can inhibit in vivo TRPV1-dependent hypersensitivity responses in two rat models of visceral pain. In the first model rats were pretreated with intraperitoneal (i.p.) capsazepine, the selective TRPV1 antagonist SB-705498, neomycin or vehicle alone and 30 min later instilled with intracolonic TRPV1-activating capsaicin. Likewise, rats were pretreated with 10 days oral neomycin and then subjected to intracolonic capsaicin. The visceromotor response (VMR) to distension was measured before and after capsaicin application. In addition, the VMR to distension was measured in adult maternal separated rats before and after acute stress. Before the 2nd distension protocol these rats were treated with i.p. neomycin, amoxycillin or vehicle alone. Our results showed that capsaicin administration induced an enhanced VMR to distension that was prevented by i.p. capsazepine, SB-705498 and neomycin. Oral neomycin treatment changed bacterial faecal content but could not inhibit capsaicin induced visceral hypersensitivity. In maternal separated rats acute stress induced an enhanced response to distension that was reversed by i.p. neomycin, but not amoxycillin. These data indicate that (i.p.) neomycin can inhibit visceral hypersensitivity to distension in a nonbactericidal manner and suggest that TRPV1-modulation may be involved.

  16. 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

  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.

  18. 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.

  19. Rangeland monitoring reveals long-term plant responses to precipitation and grazing at the landscape scale

    USGS Publications Warehouse

    Munson, Seth M.; Duniway, Michael C.; Johanson, Jamin K.

    2015-01-01

    Managers of rangeland ecosystems require methods to track the condition of natural resources over large areas and long periods of time as they confront climate change and land use intensification. We demonstrate how rangeland monitoring results can be synthesized using ecological site concepts to understand how climate, site factors, and management actions affect long-term vegetation dynamics at the landscape-scale. Forty-six years of rangeland monitoring conducted by the Bureau of Land Management (BLM) on the Colorado Plateau reveals variable responses of plant species cover to cool-season precipitation, land type (ecological site groups), and grazing intensity. Dominant C3 perennial grasses (Achnatherum hymenoides, Hesperostipa comata), which are essential to support wildlife and livestock on the Colorado Plateau, had responses to cool-season precipitation that were at least twice as large as the dominant C4 perennial grass (Pleuraphis jamesii) and woody vegetation. However, these C3 perennial grass responses to precipitation were reduced by nearly one-third on grassland ecological sites with fine- rather than coarse-textured soils, and there were no detectable C3 perennial grass responses to precipitation on ecological sites dominated by a dense-growing shrub, Coleogyne ramosissima. Heavy grazing intensity further reduced the responses of C3 perennial grasses to cool-season precipitation on ecological sites with coarse-textured soils and surprisingly reduced the responses of shrubs as well. By using ecological site groups to assess rangeland condition, we were able to improve our understanding of the long-term relationships between vegetation change and climate, land use, and site characteristics, which has important implications for developing landscape-scale monitoring strategies.

  20. 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

  1. 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

  2. Alleviating pain hypersensitivity through activation of type 4 metabotropic glutamate receptor.

    PubMed

    Vilar, Bruno; Busserolles, Jérôme; Ling, Bing; Laffray, Sophie; Ulmann, Lauriane; Malhaire, Fanny; Chapuy, Eric; Aissouni, Youssef; Etienne, Monique; Bourinet, Emmanuel; Acher, Francine; Pin, Jean-Philippe; Eschalier, Alain; Goudet, Cyril

    2013-11-27

    Hyperactivity of the glutamatergic system is involved in the development of central sensitization in the pain neuraxis, associated with allodynia and hyperalgesia observed in patients with chronic pain. Herein we study the ability of type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal glutamate signaling and alleviate chronic pain. We show that mGlu4 are located both on unmyelinated C-fibers and spinal neurons terminals in the inner lamina II of the spinal cord where they inhibit glutamatergic transmission through coupling to Cav2.2 channels. Genetic deletion of mGlu4 in mice alters sensitivity to strong noxious mechanical compression and accelerates the onset of the nociceptive behavior in the inflammatory phase of the formalin test. However, responses to punctate mechanical stimulation and nocifensive responses to thermal noxious stimuli are not modified. Accordingly, pharmacological activation of mGlu4 inhibits mechanical hypersensitivity in animal models of inflammatory or neuropathic pain while leaving acute mechanical perception unchanged in naive animals. Together, these results reveal that mGlu4 is a promising new target for the treatment of chronic pain. PMID:24285900

  3. [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.

  4. 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.

  5. Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents

    PubMed Central

    Shinoda, M.; Feng, B.; Albers, K. M.; Gebhart, G. F.

    2011-01-01

    Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor α-3 (GFRα3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFRα3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFRα3 KO mice. The proportion of GFRα3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFRα3 KO mice. These findings suggest that enhanced GFRα3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity. PMID:21193524

  6. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    PubMed

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits.

  7. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    PubMed

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. PMID:27091876

  8. T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance.

    PubMed

    Yun, James; Cai, Fenfen; Lee, Frederick J; Pichler, Werner J

    2016-04-01

    T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B(*)57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B(*)57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised. PMID:27141480

  9. T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance

    PubMed Central

    Cai, Fenfen; Lee, Frederick J; Pichler, Werner J

    2016-01-01

    T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B*57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B*57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised. PMID:27141480

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

    SciTech Connect

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

    2004-04-08

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

  11. 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.

  12. A physiologic differentiation between delayed and immediate hypersensitivity

    PubMed Central

    Apicella, Michael A.; Allen, James C.

    1969-01-01

    Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to purified protein derivative (PPD), and a passively transferred immediate hypersensitivity reaction to ovalbumin. While the immediate hypersensitivity reaction transiently alters vascular permeability as shown by increased movement of macromolecules into the chest, the delayed hypersensitivity reaction is marked by a decreased capacity to resorb macromolecules from the pleural space. The data suggest that the two hypersensitivity reactions may be distinguished by these physiologic differences. Additional data from studies of a chemically induced pleural effusion in these animals suggest that some type of outflow obstruction is necessary for the development of effusion, but that the outflow defect caused by the irritating chemical is based on a different mechanism than that seen during the delayed hypersensitivity reaction. PMID:4179171

  13. Learning theories reveal loss of pancreatic electrical connectivity in diabetes as an adaptive response.

    PubMed

    Goel, Pranay; Mehta, Anita

    2013-01-01

    Cells of almost all solid tissues are connected with gap junctions which permit the direct transfer of ions and small molecules, integral to regulating coordinated function in the tissue. The pancreatic islets of Langerhans are responsible for secreting the hormone insulin in response to glucose stimulation. Gap junctions are the only electrical contacts between the beta-cells in the tissue of these excitable islets. It is generally believed that they are responsible for synchrony of the membrane voltage oscillations among beta-cells, and thereby pulsatility of insulin secretion. Most attempts to understand connectivity in islets are often interpreted, bottom-up, in terms of measurements of gap junctional conductance. This does not, however, explain systematic changes, such as a diminished junctional conductance in type 2 diabetes. We attempt to address this deficit via the model presented here, which is a learning theory of gap junctional adaptation derived with analogy to neural systems. Here, gap junctions are modelled as bonds in a beta-cell network, that are altered according to homeostatic rules of plasticity. Our analysis reveals that it is nearly impossible to view gap junctions as homogeneous across a tissue. A modified view that accommodates heterogeneity of junction strengths in the islet can explain why, for example, a loss of gap junction conductance in diabetes is necessary for an increase in plasma insulin levels following hyperglycemia.

  14. 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

  15. Expression of secreted Wnt pathway components reveals unexpected complexity of the planarian amputation response

    PubMed Central

    Gurley, Kyle A.; Elliott, Sarah A.; Simakov, Oleg; Schmidt, Heiko A.; Holstein, Thomas W.; Sánchez Alvarado, Alejandro

    2010-01-01

    Regeneration is widespread throughout the animal kingdom, but our molecular understanding of this process in adult animals remains poorly understood. Wnt/β-catenin signaling plays crucial roles throughout animal life from early development to adulthood. In intact and regenerating planarians, the regulation of Wnt/β-catenin signaling functions to maintain and specify anterior/posterior (A/P) identity. Here, we explore the expression kinetics and RNAi phenotypes for secreted members of the Wnt signaling pathway in the planarian Schmidtea mediterranea. Smed-wnt and sFRP expression during regeneration is surprisingly dynamic and reveals fundamental aspects of planarian biology that have been previously unappreciated. We show that after amputation, a wounding response precedes rapid reorganization of the A/P axis. Furthermore, cells throughout the body plan can mount this response and reassess their new A/P location in the complete absence of stem cells. While initial stages of the amputation response are stem cell independent, tissue remodeling and the integration of new A/P address with anatomy are stem cell dependent. We also show that WNT5 functions in a reciprocal manner with SLIT to pattern the planarian mediolateral axis, while WNT11-2 patterns the posterior midline. Moreover, we perform an extensive phylogenetic analysis on the Smed-wnt genes using a method that combines and integrates both sequence and structural alignments, enabling us to place all nine genes into Wnt subfamilies for the first time. PMID:20707997

  16. Altered ARA2 (RABA1a) expression in Arabidopsis reveals the involvement of a Rab/YPT family member in auxin-mediated responses.

    PubMed

    Koh, Eun-Ji; Kwon, Ye-Rim; Kim, Kang-Il; Hong, Suk-Whan; Lee, Hojoung

    2009-05-01

    Ras super family proteins serve as molecular switches regulating many different cellular processes. However, given the large number of family members, sequence information has provided little insight into the function of individual proteins. This study examined phenotypic alterations in an Arabidopsis ara2 mutant, in which a Ras super family member-encoding gene is disrupted by a T-DNA insertion. Although one mutant line (Salk_013811) was hypersensitive to auxin, its T-DNA insertion was in the 5'-UTR of ARA2. Thus, we examined a true ARA2 knock-out mutant (Salk_077747) which contains an insertion in the first exon of ARA2. We found that ARA2 expression is responsive to auxin and at low concentrations, ara2 mutant plants exhibit increased numbers of lateral roots. ARA2 overexpression causes plants to exhibit hypersensitivity to auxin, due to altered expression of auxin-responsive genes, and these plants exhibited reduced numbers of lateral roots. A GFP-ARA2 fusion protein localized to the endosomes, suggesting that ARA2 may play a role in vesicle trafficking of components involved in polar auxin transport. Taken together, these results show that ARA2 is an essential component of a pathway that couples auxin signaling to plant growth and development.

  17. New insights into visceral hypersensitivity--clinical implications in IBS.

    PubMed

    Zhou, QiQi; Verne, G Nicholas

    2011-06-01

    A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders.

  18. Titanium hypersensitivity. A hidden threat for dental implant patients?

    PubMed

    Bilhan, Hakan; Bural, Canan; Geckili, Onur

    2013-01-01

    Titanium and its alloys have been widely used for dental prosthetic devices because of their superior mechanical properties and biocompatibility. However, the incidence of titanium hypersensitivity or allergy is still unknown and the discussion about its existence is ongoing. Unexplained implant failures have also forced dental clinicians to investigate the possibility of titanium hypersensitivity or allergy. This review focuses on the potential of dental implant-related titanium hypersensitivity or allergic reactions. It includes an examination of the existing scientific literature and current knowledge. Evidence-based data and studies related to titanium hypersensitivity in dental implant patients are also discussed.

  19. Intracranial recordings reveal transient response dynamics during information maintenance in human cerebral cortex.

    PubMed

    Noy, Niv; Bickel, Stephan; Zion-Golumbic, Elana; Harel, Michal; Golan, Tal; Davidesco, Ido; Schevon, Catherine A; McKhann, Guy M; Goodman, Robert R; Schroeder, Charles E; Mehta, Ashesh D; Malach, Rafael

    2015-10-01

    Despite an extensive body of work, it is still not clear how short term maintenance of information is implemented in the human brain. Most prior research has focused on "working memory"-typically involving the storage of a number of items, requiring the use of a phonological loop and focused attention during the delay period between encoding and retrieval. These studies largely support a model of enhanced activity in the delay interval as the central mechanism underlying working memory. However, multi-item working memory constitutes only a subset of storage phenomena that may occur during daily life. A common task in naturalistic situations is short term memory of a single item-for example, blindly reaching to a previously placed cup of coffee. Little is known about such single-item, effortless, storage in the human brain. Here, we examined the dynamics of brain responses during a single-item maintenance task, using intracranial recordings implanted for clinical purpose in patients (ECoG). Our results reveal that active electrodes were dominated by transient short latency visual and motor responses, reflected in broadband high frequency power increases in occipito-temporal, frontal, and parietal cortex. Only a very small set of electrodes showed activity during the early part of the delay period. Interestingly, no cortical site displayed a significant activation lasting to the response time. These results suggest that single item encoding is characterized by transient high frequency ECoG responses, while the maintenance of information during the delay period may be mediated by mechanisms necessitating only low-levels of neuronal activations.

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

    PubMed Central

    Barbosa, Catarina; García-Martínez, José; Pérez-Ortín, José 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

  1. 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.

  2. Intracranial recordings reveal transient response dynamics during information maintenance in human cerebral cortex.

    PubMed

    Noy, Niv; Bickel, Stephan; Zion-Golumbic, Elana; Harel, Michal; Golan, Tal; Davidesco, Ido; Schevon, Catherine A; McKhann, Guy M; Goodman, Robert R; Schroeder, Charles E; Mehta, Ashesh D; Malach, Rafael

    2015-10-01

    Despite an extensive body of work, it is still not clear how short term maintenance of information is implemented in the human brain. Most prior research has focused on "working memory"-typically involving the storage of a number of items, requiring the use of a phonological loop and focused attention during the delay period between encoding and retrieval. These studies largely support a model of enhanced activity in the delay interval as the central mechanism underlying working memory. However, multi-item working memory constitutes only a subset of storage phenomena that may occur during daily life. A common task in naturalistic situations is short term memory of a single item-for example, blindly reaching to a previously placed cup of coffee. Little is known about such single-item, effortless, storage in the human brain. Here, we examined the dynamics of brain responses during a single-item maintenance task, using intracranial recordings implanted for clinical purpose in patients (ECoG). Our results reveal that active electrodes were dominated by transient short latency visual and motor responses, reflected in broadband high frequency power increases in occipito-temporal, frontal, and parietal cortex. Only a very small set of electrodes showed activity during the early part of the delay period. Interestingly, no cortical site displayed a significant activation lasting to the response time. These results suggest that single item encoding is characterized by transient high frequency ECoG responses, while the maintenance of information during the delay period may be mediated by mechanisms necessitating only low-levels of neuronal activations. PMID:26147431

  3. A microfluidic platform reveals differential response of regulatory T cells to micropatterned costimulation arrays.

    PubMed

    Lee, Joung-Hyun; Dustin, Michael L; Kam, Lance C

    2015-11-01

    T cells are key mediators of adaptive immunity. However, the overall immune response is often directed by minor subpopulations of this heterogeneous family of cells, owing to specificity of activation and amplification of functional response. Knowledge of differences in signaling and function between T cell subtypes is far from complete, but is clearly needed for understanding and ultimately leveraging this branch of the adaptive immune response. This report investigates differences in cell response to micropatterned surfaces by conventional and regulatory T cells. Specifically, the ability of cells to respond to the microscale geometry of TCR/CD3 and CD28 engagement is made possible using a magnetic-microfluidic device that overcomes limitations in imaging efficiency associated with conventional microscopy equipment. This device can be readily assembled onto micropatterned surfaces while maintaining the activity of proteins and other biomolecules necessary for such studies. In operation, a target population of cells is tagged using paramagnetic beads, and then trapped in a divergent magnetic field within the chamber. Following washing, the target cells are released to interact with a designated surface. Characterization of this system with mouse CD4(+) T cells demonstrated a 50-fold increase in target-to-background cell purity, with an 80% collection efficiency. Applying this approach to CD4(+)CD25(+) regulatory T cells, it is then demonstrated that these rare cells respond less selectively to micro-scale features of anti-CD3 antibodies than CD4(+)CD25(-) conventional T cells, revealing a difference in balance between TCR/CD3 and LFA-1-based adhesion. PKC-θ localized to the distal pole of regulatory T cells, away from the cell-substrate interface, suggests a mechanism for differential regulation of TCR/LFA-1-based adhesion. Moreover, specificity of cell adhesion to anti-CD3 features was dependent on the relative position of anti-CD28 signaling within the cell

  4. A microfluidic platform reveals differential response of regulatory T cells to micropatterned costimulation arrays.

    PubMed

    Lee, Joung-Hyun; Dustin, Michael L; Kam, Lance C

    2015-11-01

    T cells are key mediators of adaptive immunity. However, the overall immune response is often directed by minor subpopulations of this heterogeneous family of cells, owing to specificity of activation and amplification of functional response. Knowledge of differences in signaling and function between T cell subtypes is far from complete, but is clearly needed for understanding and ultimately leveraging this branch of the adaptive immune response. This report investigates differences in cell response to micropatterned surfaces by conventional and regulatory T cells. Specifically, the ability of cells to respond to the microscale geometry of TCR/CD3 and CD28 engagement is made possible using a magnetic-microfluidic device that overcomes limitations in imaging efficiency associated with conventional microscopy equipment. This device can be readily assembled onto micropatterned surfaces while maintaining the activity of proteins and other biomolecules necessary for such studies. In operation, a target population of cells is tagged using paramagnetic beads, and then trapped in a divergent magnetic field within the chamber. Following washing, the target cells are released to interact with a designated surface. Characterization of this system with mouse CD4(+) T cells demonstrated a 50-fold increase in target-to-background cell purity, with an 80% collection efficiency. Applying this approach to CD4(+)CD25(+) regulatory T cells, it is then demonstrated that these rare cells respond less selectively to micro-scale features of anti-CD3 antibodies than CD4(+)CD25(-) conventional T cells, revealing a difference in balance between TCR/CD3 and LFA-1-based adhesion. PKC-θ localized to the distal pole of regulatory T cells, away from the cell-substrate interface, suggests a mechanism for differential regulation of TCR/LFA-1-based adhesion. Moreover, specificity of cell adhesion to anti-CD3 features was dependent on the relative position of anti-CD28 signaling within the cell

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

    PubMed

    Fyhrquist, Nanna; Wolff, Henrik; Lauerma, Antti; Alenius, Harri

    2012-01-01

    The relative roles of CD4+ and CD8+ T cells in contact hypersensitivity responses have not been fully solved, and remain an important question. Using an adoptive transfer model, we investigated the role of the respective T cell subset. Magnetic bead separated CD4+ and CD8+ T cells from oxazolone sensitized C57BL/6 mice were transferred into RAG-/- mice, followed by hapten challenge and analysis of inflammatory parameters at 24 hours post exposure. The CD4+ T cell recipient mice developed partial contact hypersensitivity responses to oxazolone. CD8+ T cells caused significant amplification of the response in recipients of both CD4+ and CD8+ T cells including ear swelling, type 1 inflammatory mediators, and cell killing. Unexpectedly, CD8+ T cells were not sufficient to mediate contact hypersensitivity, although abundantly present in the lymph nodes in the CD8+ T cell reconstituted mice. There were no signs of inflammation at the site of hapten exposure, indicating impaired recruitment of CD8+ T cells in the absence of CD4+ T cells. These data show that CD4+ T cells mediate contact hypersensitivity to oxazolone, but CD8+ T cells contribute with the most potent effector mechanisms. Moreover, our results suggest that CD4+ T cell function is required for the mobilization of CD8+ effector T cells to the site of hapten exposure. The results shed new light on the relative importance of CD4+ and CD8+ T cells during the effector phase of contact hypersensitivity. PMID:22916101

  6. 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

  7. Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

    PubMed

    Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

    2016-09-01

    There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events.

  8. Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

    PubMed

    Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

    2016-09-01

    There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events. PMID:27480881

  9. 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.

  10. Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade

    PubMed Central

    Nakamura, Takao; Ohbayashi, Masaharu; Kuo, Chuan Hui; Komatsu, Naoki; Yakura, Keiko; Tominaga, Takeshi; Inoue, Yoshitsugu; Higashi, Hidemitsu; Murata, Meguru; Takeda, Shuzo; Fukushima, Atsuki; Liu, Fu-Tong; Rothenberg, Marc E.; Ono, Santa Jeremy

    2009-01-01

    The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co-stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva are ablated in mice deficient in eotaxin-1, despite normal numbers of tissue mast cells and levels of IgE. To further define the co-stimulatory signals mediated by chemokine receptor 3 (CCR3), an eotaxin-1 receptor, effects of CCR3 blockade were tested with an allergic conjunctivitis model and in ex vivo isolated connective tissue-type mast cells. Our results show that CCR3 blockade significantly suppresses allergen-mediated hypersensitivity reactions as well as IgE-mediated mast cell degranulation. We propose that a co-stimulatory axis by CCR3, mainly stimulated by eotaxin-1, is pivotal in mast cell-mediated hypersensitivity reactions. PMID:19147836

  11. Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome

    PubMed Central

    Feng, Bin; La, Jun Ho; Schwartz, Erica S.

    2012-01-01

    Irritable bowel syndrome (IBS) is characterized as functional because a pathobiological cause is not readily apparent. Considerable evidence, however, documents that sensitizing proinflammatory and lipotoxic lipids, mast cells and their products, tryptases, enteroendocrine cells, and mononuclear phagocytes and their receptors are increased in tissues of IBS patients with colorectal hypersensitivity. It is also clear from recordings in animals of the colorectal afferent innervation that afferents exhibit long-term changes in models of persistent colorectal hypersensitivity. Such changes in afferent excitability and responses to mechanical stimuli are consistent with relief of discomfort and pain in IBS patients, including relief of referred abdominal hypersensitivity, upon intra-rectal instillation of local anesthetic. In the aggregate, these experimental outcomes establish the importance of afferent drive in IBS, consistent with a larger literature with respect to other chronic conditions in which pain is a principal complaint (e.g., neuropathic pain, painful bladder syndrome, fibromyalgia). Accordingly, colorectal afferents and the environment in which these receptive endings reside constitute the focus of this review. That environment includes understudied and incompletely understood contributions from immune-competent cells resident in and recruited into the colorectum. We close this review by highlighting deficiencies in existing knowledge and identifying several areas for further investigation, resolution of which we anticipate would significantly advance our understanding of neural and neuro-immune contributions to IBS pain and hypersensitivity. PMID:22403791

  12. 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

  13. 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

  14. Hypersensitivity and nanoparticles: update and research trends

    PubMed Central

    MOCAN, TEODORA; MATEA, CRISTIAN T.; IANCU, CORNEL; AGOSTON-COLDEA, LUCIA; MOCAN, LUCIAN; ORASAN, REMUS

    2016-01-01

    Nanotechnology holds a great promise for a wide range of medical-intent applications (diagnostic, treatment and prophylaxis of various diseases). Their advantages are due to their size, versatility and potential for multiple simultaneous applications. However, concerns have been formulated by scientific world due to insufficient data on toxicity of nanomaterials. One area of interest is represented by the interactions between nanoparticles and the components of the immune system. We review herein reported data on hypersensitivity reactions. The role exerted by nanoparticles in both immunostimulation and immunosuppression in allergen-driven mechanisms was studied, as well as future trends in worldwide research. PMID:27152071

  15. Dentin hypersensitivity: differential diagnosis, tests, and etiology.

    PubMed

    Trushkowsky, Richard D; Garcia-Godoy, Franklin

    2014-02-01

    Dentin hypersensitivity (DHS) is a painful condition that affects up to 57 percent of the adult population. It occurs as a result of exposure of dentin to the oral environment. Ensuring the correct diagnosis of this condition is based on history and examination. An oral screening for DHS should encompass such elements as patient history, clinical examination that includes radiographs, a variety of tests, identification of risk factors, and a differential diagnosis. An understanding of dentinal fluid and odontoblasts is also beneficial for diagnosis. PMID:24571559

  16. Language-specific phoneme representations revealed by electric and magnetic brain responses.

    PubMed

    Näätänen, R; Lehtokoski, A; Lennes, M; Cheour, M; Huotilainen, M; Iivonen, A; Vainio, M; Alku, P; Ilmoniemi, R J; Luuk, A; Allik, J; Sinkkonen, J; Alho, K

    1997-01-30

    There is considerable debate about whether the early processing of sounds depends on whether they form part of speech. Proponents of such speech specificity postulate the existence of language-dependent memory traces, which are activated in the processing of speech but not when equally complex, acoustic non-speech stimuli are processed. Here we report the existence of these traces in the human brain. We presented to Finnish subjects the Finnish phoneme prototype /e/ as the frequent stimulus, and other Finnish phoneme prototypes or a non-prototype (the Estonian prototype /õ/) as the infrequent stimulus. We found that the brain's automatic change-detection response, reflected electrically as the mismatch negativity (MMN), was enhanced when the infrequent, deviant stimulus was a prototype (the Finnish /ö/) relative to when it was a non-prototype (the Estonian /õ/). These phonemic traces, revealed by MMN, are language-specific, as /õ/ caused enhancement of MMN in Estonians. Whole-head magnetic recordings located the source of this native-language, phoneme-related response enhancement, and thus the language-specific memory traces, in the auditory cortex of the left hemisphere. PMID:9009189

  17. Ribosome•RelA structures reveal the mechanism of stringent response activation

    PubMed Central

    Loveland, Anna B; Bah, Eugene; Madireddy, Rohini; Zhang, Ying; Brilot, Axel F; Grigorieff, Nikolaus; Korostelev, Andrei A

    2016-01-01

    Stringent response is a conserved bacterial stress response underlying virulence and antibiotic resistance. RelA/SpoT-homolog proteins synthesize transcriptional modulators (p)ppGpp, allowing bacteria to adapt to stress. RelA is activated during amino-acid starvation, when cognate deacyl-tRNA binds to the ribosomal A (aminoacyl-tRNA) site. We report four cryo-EM structures of E. coli RelA bound to the 70S ribosome, in the absence and presence of deacyl-tRNA accommodating in the 30S A site. The boomerang-shaped RelA with a wingspan of more than 100 Å wraps around the A/R (30S A-site/RelA-bound) tRNA. The CCA end of the A/R tRNA pins the central TGS domain against the 30S subunit, presenting the (p)ppGpp-synthetase domain near the 30S spur. The ribosome and A/R tRNA are captured in three conformations, revealing hitherto elusive states of tRNA engagement with the ribosomal decoding center. Decoding-center rearrangements are coupled with the step-wise 30S-subunit 'closure', providing insights into the dynamics of high-fidelity tRNA decoding. DOI: http://dx.doi.org/10.7554/eLife.17029.001 PMID:27434674

  18. 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

  19. Transcriptome analysis reveals novel genes involved in nonhost response to bacterial infection in tobacco.

    PubMed

    Daurelio, Lucas Damián; Petrocelli, Silvana; Blanco, Francisca; Holuigue, Loreto; Ottado, Jorgelina; Orellano, Elena Graciela

    2011-03-01

    Plants are continuously exposed to pathogen challenge. The most common defense response to pathogenic microorganisms is the nonhost response, which is usually accompanied by transcriptional changes. In order to identify genes involved in nonhost resistance, we evaluated the tobacco transcriptome profile after infection with Xanthomonas axonopodis pv. citri (Xac), a nonhost phytopathogenic bacterium. cDNA-amplified fragment length polymorphism was used to identify differentially expressed transcripts in tobacco leaves infected with Xac at 2, 8 and 24h post-inoculation. From a total of 2087 transcript-derived fragments (TDFs) screened (approximately 20% of the tobacco transcriptome), 316 TDFs showed differential expression. Based on sequence similarities, 82 differential TDFs were identified and assigned to different functional categories: 56 displayed homology to genes with known functions, 12 to proteins with unknown functions and 14 did not have a match. Real-time PCR was carried out with selected transcripts to confirm the expression pattern obtained. The results reveal novel genes associated with nonhost resistance in plant-pathogen interaction in tobacco. These novel genes could be included in future strategies of molecular breeding for nonhost disease resistance. PMID:20828873

  20. Phosphoproteomic dynamics of chickpea (Cicer arietinum L.) reveals shared and distinct components of dehydration response.

    PubMed

    Subba, Pratigya; Barua, Pragya; Kumar, Rajiv; Datta, Asis; Soni, Kamlesh Kumar; Chakraborty, Subhra; Chakraborty, Niranjan

    2013-11-01

    Reversible protein phosphorylation is a ubiquitous regulatory mechanism that plays critical roles in transducing stress signals to bring about coordinated intracellular responses. To gain better understanding of dehydration response in plants, we have developed a differential phosphoproteome in a food legume, chickpea (Cicer arietinum L.). Three-week-old chickpea seedlings were subjected to progressive dehydration by withdrawing water, and the changes in the phosphorylation status of a large repertoire of proteins were monitored. The proteins were resolved by 2-DE and stained with phosphospecific fluorescent Pro-Q Diamond dye. Mass spectrometric analysis led to the identification of 91 putative phosphoproteins, presumably involved in a variety of functions including cell defense and rescue, photosynthesis and photorespiration, molecular chaperones, and ion transport, among others. Multiple sites of phosphorylation were predicted on several key elements, which include both the regulatory as well as the functional proteins. A critical survey of the phosphorylome revealed a DREPP (developmentally regulated plasma membrane protein) plasma membrane polypeptide family protein, henceforth designated CaDREPP1. The transcripts of CaDREPP1 were found to be differentially regulated under dehydration stress, further corroborating the proteomic results. This work provides new insights into the possible phosphorylation events triggered by the conditions of progressive water-deficit in plants.

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

    PubMed Central

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

    2015-01-01

    Summary 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 sub-networks 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 sub-networks that differentially represent behavioral choice and reaction time. Importantly, these sub-networks 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 datasets. Our results demonstrate a powerful new tool for identifying cortical sub-networks by objective classification of simultaneously recorded electrophysiological activity. PMID:25728571

  2. 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

  3. 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

  4. Revealing a latent variable: Individual differences in affective response to repeated injections

    PubMed Central

    Aydin, Cigdem; Frohmader, Karla; Akil, Huda

    2015-01-01

    Latent variables may exist in experimental designs and may interfere with reproducibility of findings. The present study reveals one 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-naïve outbred rats to the mild stress of a novel environment and classifying them as high responders (HR; upper 1/3rd) and low responders (LR; lower 1/3rd) 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 LRs, while the identical regimen significantly decreased the same measure in HRs, compared to 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

  5. 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

  6. Food hypersensitivity among Caucasian and non-Caucasian children.

    PubMed

    Dias, Renuka P; Summerfield, Alison; Khakoo, G A

    2008-02-01

    There are little data regarding the frequency of different foods that cause hypersensitivity in the UK. Furthermore, there are no data regarding food hypersensitivity related to ethnic variations. This prospective study involved 76 children with IgE-mediated food allergy presenting consecutively over 18 months to a Paediatric Allergy Clinic serving a well-defined population that is 21% non-Caucasian. A total of 52.6% of the paediatric allergy clinic population was non-Caucasian compared with 35.9% in General Paediatric Clinics giving a mean difference in percentage of 16.7 (5.6, 27.8), p < 0.01. The average number of food allergens per child in the non-Caucasian group was 2.05 vs. 1.22 in the Caucasian group, mean difference 0.83, which is significant (t = 4.15, d.f. = 74, p < 0.01). Analysis of other allergic conditions revealed no significant increase in the non-Caucasian group. The mean age of first reaction to any food was 2.6 yr (range 0.3-12 yr) in Caucasian, and 1.7 yr (range 0.3-8 yr) in non-Caucasian, children (p < 0.05). There were 125 reactions in the study population, with egg, peanut, tree nut, cow milk and cod being the commonest food allergens. Some novel foods, such as kiwi, lentil and sesame, were also represented in the top 10 food allergies, particularly in the non-Caucasian population. Ethnic minorities are over-represented in terms of the number of children with food allergy and number of food allergies per child, present at an earlier age with food allergy, and possibly have a greater variety of food allergies compared with Caucasians. This is important in terms of health education. Our findings need confirmation by a more detailed population based study, ideally using food challenges in addition to history and skin prick testing.

  7. 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

  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, Grégoire

    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. Are Some Neurons Hypersensitive to Metallic Nanoparticles?

    PubMed Central

    Scott, Bobby R.

    2010-01-01

    Engineered metallic nanomaterial particles (MENAP) represent a significant breakthrough in developing new products for use by consumers and industry. Skin application (e.g., via creams and sprays containing nanoparticles) may provide a key route of potential intake of MENAP and can lead to retrograde transport from nerve endings in the skin to the somatosensory neurons in dorsal root ganglia (DRG). This paper uses a novel theoretical model (stochastic threshold microdose [STM] model) to characterize survival of DRG neurons exposed in cell culture replicates to copper nanoparticles, based on published data. Cell death via autophagy is assumed here to occur as a result of the uptake (called hits) of the nanoparticles by mitochondria. Theoretical results are presented for the existence of a hypersensitive fraction (about 20%) of neurons that are killed in significant numbers when on average > 1 hit to the at-risk mitochondria occurs. Further, most hypersensitive neurons appear to be killed by a cumulative exposure of about 2,000 micromolar-hours and the remaining resistant cells may have dysfunctional mitochondria. Based on these theoretical findings, it is predicted that repeated exposure (e.g., over years) of the skin of humans to MENAP could lead to significant nervous system damage and related morbidity. PMID:22423227

  10. Phospholipase C/diacylglycerol kinase-mediated signalling is required for benzothiadiazole-induced oxidative burst and hypersensitive cell death in rice suspension-cultured cells.

    PubMed

    Chen, Jie; Zhang, Weidong; Song, Fengming; Zheng, Zhong

    2007-01-01

    The involvement of phospholipase C/diacylglycerol kinase (PLC/DGK)-mediated signalling in oxidative burst and hypersensitive cell death was studied in rice suspension-cultured cells treated with benzothiadiazole (BTH) and infected by Xanthomonas oryza pv. oryza (Xoo), the causal agent of rice leaf blight disease. Treatment of rice suspension cells with BTH resulted in a significant oxidative burst, as indicated by accumulation of superoxide anion and H(2)O(2), and hypersensitive cell death, as determined by Evans blue staining. A peak in oxidative burst was detected 3-4 h after BTH treatment and hypersensitive cell death was observed 8 h after treatment. In addition, significant oxidative burst and hypersensitive cell death were detected in BTH-treated suspension cells, but not in untreated control cells, after Xoo infection. Scavengers and antioxidants of active oxygen species, e.g., superoxide dismutase, catalase, N-acetylcysteine, and flavone, reduced significantly the BTH-induced oxidative burst and hypersensitive cell death, indicating that oxidative burst is required for BTH-induced hypersensitive cell death. Expression of the PLC/DGK pathway genes, a diacylglycerol kinase gene, OsDAGK1, and a phosphoinositide-specific phospholipase C gene, OsPI-PLC1, and a defence-related EREBP transcriptional factor gene, OsBIERF3, was activated in rice cells after BTH treatment and in the BTH-treated cells after Xoo infection. Treatment of rice cells with phosphatidic acid, a phospholipid signalling molecule, resulted in the production of oxidative burst and hypersensitive cell death. However, neomycin, a PLC inhibitor, inhibited partially but not completely the production of oxidative burst, hypersensitive cell death, and expression of OsBIERF3 and OsDAGK1 induced by BTH in rice cells. These results suggest that PLC/DGK-mediated signalling plays an important role in BTH-induced oxidative burst, hypersensitive response, and activation of defence response in rice.

  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. Soil Microbial Community Responses to a Decade of Warming as Revealed by Comparative Metagenomics

    PubMed Central

    Luo, Chengwei; Rodriguez-R, Luis M.; Johnston, Eric R.; Wu, Liyou; Cheng, Lei; Xue, Kai; Tu, Qichao; Deng, Ye; He, Zhili; Shi, Jason Zhou; Yuan, Mengting Maggie; Sherry, Rebecca A.; Li, Dejun; Luo, Yiqi; Schuur, Edward A. G.; Chain, Patrick; Tiedje, James M.

    2014-01-01

    Soil microbial communities are extremely complex, being composed of thousands of low-abundance species (<0.1% of total). How such complex communities respond to natural or human-induced fluctuations, including major perturbations such as global climate change, remains poorly understood, severely limiting our predictive ability for soil ecosystem functioning and resilience. In this study, we compared 12 whole-community shotgun metagenomic data sets from a grassland soil in the Midwestern United States, half representing soil that had undergone infrared warming by 2°C for 10 years, which simulated the effects of climate change, and the other half representing the adjacent soil that received no warming and thus, served as controls. Our analyses revealed that the heated communities showed significant shifts in composition and predicted metabolism, and these shifts were community wide as opposed to being attributable to a few taxa. Key metabolic pathways related to carbon turnover, such as cellulose degradation (∼13%) and CO2 production (∼10%), and to nitrogen cycling, including denitrification (∼12%), were enriched under warming, which was consistent with independent physicochemical measurements. These community shifts were interlinked, in part, with higher primary productivity of the aboveground plant communities stimulated by warming, revealing that most of the additional, plant-derived soil carbon was likely respired by microbial activity. Warming also enriched for a higher abundance of sporulation genes and genomes with higher G+C content. Collectively, our results indicate that microbial communities of temperate grassland soils play important roles in mediating feedback responses to climate change and advance the understanding of the molecular mechanisms of community adaptation to environmental perturbations. PMID:24375144

  13. 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.

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

    PubMed

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

    2014-10-01

    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.

  15. Hypersensitivity pneumonitis related to medium-density fiberboard.

    PubMed

    Toribio, Ramón; Cruz, María Jesús; Morell, Ferran; Muñoz, Xavier

    2012-01-01

    Pneumonitis due to hypersensitivity to wood fiber is mainly associated with the fungus that colonizes it. We present the case of a male affected with hypersensitivity pneumonitis in which the agent implicated was medium-density fiberboard, an engineered product whose main component is pine wood fiber. The causal agent was identified by means of a specific bronchial provocation test.

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

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

  2. 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 α,β-methylene adenosine triphosphate (αβmeATP), 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

  3. 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 naïve sensory neurons but was essential for appropriate transcriptional responses after injury, with Calca and Trpv1 expression consistently down-regulated in HDAC4 cKO compared to levels in the littermate controls (0.2–0.44-fold change, n = 4 in 2 separate experiments). This down-regulation corresponded to reduced sensitivity to 100 nM capsaicin in vitro (IC50 = 230 ± 20 nM, 76 ± 4.4% wild-type capsaicin responders vs. 56.9 ± 4.7% HDAC4 cKO responders) and to reduced thermal hypersensitivity in the complete Freund’s adjuvant (CFA) model of inflammatory pain (1.3–1.4-fold improvement over wild-type controls; n = 5–12, in 2 separate experiments). These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors.—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

  4. Irritable bowel syndrome in childhood: visceral hypersensitivity and psychosocial aspects.

    PubMed

    Iovino, P; Tremolaterra, F; Boccia, G; Miele, E; Ruju, F M; Staiano, A

    2009-09-01

    Visceral hypersensitivity is often considered to play a major etiologic role in the pathophysiology of irritable bowel syndrome in adults, and some authors argue that this increased sensitivity is mainly due to psychological factors. In contrast, there are no data in children with irritable bowel syndrome which confirm this relationship. The aim of the study was to evaluate the relationship between psychosocial aspects and sensorymotor function in children affected by irritable bowel syndrome. Ten children fulfilling the Rome II criteria for irritable bowel syndrome and seven healthy controls were enrolled. We studied the thresholds and the perception of visceral stimuli in the rectum by means of an electronic barostat (isobaric phasic distentions, 3 mmHg/1 min, interval 1 min) and a validated questionnaire. Personality features were evaluated by means of the Big Five Questionnaire for Children. Sleep, mood disturbance, anxiety and individual performance (missed school days, school results and social activities) were also evaluated. Children with irritable bowel syndrome showed significantly lower thresholds for discomfort (14.8 +/- 3.5 vs 22.3 +/- 6.9 mmHg, P = 0.010) and a higher cumulative perception score (28.2 +/- 11.1 vs 12.3 +/- 8.0, P = 0.005) compared with healthy controls. A higher emotional instability (57.8 +/- 7.0 vs 48.7 +/- 10.1, P = 0.047), sleep disturbance (7.2 +/- 1.0 vs 9.3 +/- 0.5, P = 0.004) and anxiety (6.3 +/- 2.0 vs 2.3 +/- 1.7, P = 0.009) were observed in irritable bowel syndrome patients. Moreover, in a multivariate analysis, the cumulative perception score was significantly related to emotional instability (P = 0.042). In conclusion children with irritable bowel syndrome exhibit visceral hypersensitivity and psychosocial impairment. Emotional instability, as a personality feature in these children, seems to modulate the perception response to visceral stimulations.

  5. 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

  6. Ablation of Pparg2 impairs lipolysis and reveals murine strain differences in lipolytic responses.

    PubMed

    Rodriguez-Cuenca, Sergio; Carobbio, Stefania; Vidal-Puig, Antonio

    2012-05-01

    We investigate the role of PPARg2 as a regulator of lipolysis and its interaction with specific genetic backgrounds as determinants of the severity of the metabolic phenotype. This question was prompted by our previous characterization of Pparg2-knockout (KO) mice that revealed striking genetic background differences in the severity of their adipose tissue development impairment and dysfunction. Analysis is done of pharmacological lipolytic responses combined with protein and mRNA expression analysis in isolated adipocytes from the gonadal pad of Pparg2-KO mice in 2 different backgrounds (129S6/SvEv and C57BL/6). We provide evidence of the prolipolytic role of PPARg2 and how these effects are modulated by genetic background, leading to differential severity of metabolic syndrome. Specifically, ablation of Pparg2 reduced both basal and stimulated lipolysis as a result of impaired β(3)-AR signaling, a general defect at downstream lipases, and increased insulin-mediated antilipolytic action. Of note, the C57BL/6 Pparg2-KO mice exhibited more active lipolytic response to catecholamines than 129S6/SvEv Pparg2-KO mice with respect to their wild-type controls. Pparg2-KO mice exhibit metabolic inflexibility resulting from the combined effects of impaired lipid deposition coupled with impaired lipolytic lipid mobilization. The genetic background-dependent differences in lipolysis may account for Pparg2-KO background-specific differences in the severity of their metabolic disturbances. Our findings identify the isoform Pparg2 as an integrator of the adipose lipid metabolism coordinating both anabolic and catabolic processes. PMID:22319009

  7. 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.

  8. 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.

  9. 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

  10. 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 δ15N 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.

  11. Comparative Metagenomic Analysis Reveals Mechanisms for Stress Response in Hypoliths from Extreme Hyperarid Deserts.

    PubMed

    Le, Phuong Thi; Makhalanyane, Thulani P; Guerrero, Leandro D; Vikram, Surendra; Van de Peer, Yves; Cowan, Don A

    2016-01-01

    Understanding microbial adaptation to environmental stressors is crucial for interpreting broader ecological patterns. In the most extreme hot and cold deserts, cryptic niche communities are thought to play key roles in ecosystem processes and represent excellent model systems for investigating microbial responses to environmental stressors. However, relatively little is known about the genetic diversity underlying such functional processes in climatically extreme desert systems. This study presents the first comparative metagenome analysis of cyanobacteria-dominated hypolithic communities in hot (Namib Desert, Namibia) and cold (Miers Valley, Antarctica) hyperarid deserts. The most abundant phyla in both hypolith metagenomes were Actinobacteria, Proteobacteria, Cyanobacteria and Bacteroidetes with Cyanobacteria dominating in Antarctic hypoliths. However, no significant differences between the two metagenomes were identified. The Antarctic hypolithic metagenome displayed a high number of sequences assigned to sigma factors, replication, recombination and repair, translation, ribosomal structure, and biogenesis. In contrast, the Namib Desert metagenome showed a high abundance of sequences assigned to carbohydrate transport and metabolism. Metagenome data analysis also revealed significant divergence in the genetic determinants of amino acid and nucleotide metabolism between these two metagenomes and those of soil from other polar deserts, hot deserts, and non-desert soils. Our results suggest extensive niche differentiation in hypolithic microbial communities from these two extreme environments and a high genetic capacity for survival under environmental extremes. PMID:27503299

  12. Brain responses in humans reveal ideal observer-like sensitivity to complex acoustic patterns

    PubMed Central

    Pearce, Marcus T.; Griffiths, Timothy D.; Chait, Maria

    2016-01-01

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

    PubMed Central

    Amrani, Amira; Bergon, Aurélie; Holota, Hélène; 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

  14. 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

  15. 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.

  16. 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 δ15N 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

  17. 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.

  18. Time-series analysis reveals genetic responses to intensive management of razorback sucker (Xyrauchen texanus).

    PubMed

    Dowling, Thomas E; Turner, Thomas F; Carson, Evan W; Saltzgiver, Melody J; Adams, Deborah; Kesner, Brian; Marsh, Paul C

    2014-03-01

    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 (N b /N a) increased significantly despite sevenfold reduction of N a. 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

  19. Soil metaproteomics reveals an inter-kingdom stress response to the presence of black truffles

    PubMed Central

    Zampieri, Elisa; Chiapello, Marco; Daghino, Stefania; Bonfante, Paola; Mello, Antonietta

    2016-01-01

    For some truffle species of the Tuber genus, the symbiotic phase is often associated with the presence of an area of scant vegetation, commonly known as the brûlé, around the host tree. Previous metagenomics studies have identified the microorganisms present inside and outside the brûlé of a Tuber melanosporum truffle-ground, but the molecular mechanisms that operate in this ecological niche remain to be clarified. To elucidate the metabolic pathways present in the brûlé, we conducted a metaproteomics analysis on the soil of a characterized truffle-ground and cross-referenced the resulting proteins with a database we constructed, incorporating the metagenomics data for the organisms previously identified in this soil. The soil inside the brûlé contained a larger number of proteins and, surprisingly, more proteins from plants, compared with the soil outside the brûlé. In addition, Fisher’s Exact Tests detected more biological processes inside the brûlé; these processes were related to responses to multiple types of stress. Thus, although the brûlé has a reduced diversity of plant and microbial species, the organisms in the brûlé show strong metabolic activity. Also, the combination of metagenomics and metaproteomics provides a powerful tool to reveal soil functioning. PMID:27161395

  20. 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

  1. 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

  2. Optical tweezers reveal a dynamic mechanical response of cationic peptide-DNA complexes

    NASA Astrophysics Data System (ADS)

    Lee, Amy; Zheng, Tai; Sucayan, Sarah; Chou, Szu-Ting; Tricoli, Lucas; Hustedt, Jason; Kahn, Jason; Mixson, A. James; Seog, Joonil

    2013-03-01

    Nonviral carriers have been developed to deliver nucleic acids by forming nanoscale complexes; however, there has been limited success in achieving high transfection efficiency. Our hypothesis is that a factor affecting gene delivery efficiency is the mechanical response of the condensed complex. To begin to test this hypothesis, we directly measured the mechanical properties of DNA-carrier complexes using optical tweezers. Histidine-lysine (HK) polymer, Asparagine-lysine (NK) polymer and poly-L-lysine were used to form complexes with a single DNA molecule. As carriers were introduced, a sudden decrease in DNA extension occurrs at a force level which is defined as critical force (Fc). Fc is carrier and concentration dependent. Pulling revealed reduction in DNA extension length for HK-DNA complexes. The characteristics of force profiles vary by agent and can be dynamically manipulated by changes in environmental conditions such as ionic strength of the buffer as well as pH. Heparin can remove cationic reagents which are otherwise irreversibly bound to DNA. The implications for optimizing molecular interactions to enhance transfection efficiency will be discussed.

  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 naïve 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

  4. A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity.

    PubMed

    Kozachik, Sharon L; Page, Gayle G

    2016-05-01

    Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic-pituitary-adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up-down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy. PMID:26512050

  5. A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity.

    PubMed

    Kozachik, Sharon L; Page, Gayle G

    2016-05-01

    Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic-pituitary-adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up-down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy.

  6. 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

  7. Transcriptome Analysis of Cotton (Gossypium hirsutum L.) Genotypes That Are Susceptible, Resistant, and Hypersensitive to Reniform Nematode (Rotylenchulus reniformis).

    PubMed

    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

  8. Transcriptome Analysis of Cotton (Gossypium hirsutum L.) Genotypes That Are Susceptible, Resistant, and Hypersensitive to Reniform Nematode (Rotylenchulus reniformis).

    PubMed

    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.

  9. Drug hypersensitivity syndrome with significant gastrointestinal involvement.

    PubMed

    Chung, Wan-Ling; Teo, Lynn; Wang, Yi-Shi; Liu, Tsun-Tsien

    2012-11-01

    Drug hypersensitivity syndrome (DHS) is an idiosyncratic systemic reaction to a drug. The clinical presentation of this syndrome comprises a diverse spectrum, ranging from mild to fulminating organ failure. Nonspecific gastrointestinal symptoms are common in DHS, but severe morbidities and mortalities attributed to gut disease in DHS are rarely described. We present a case of DHS with significant gastrointestinal symptoms of prolonged profuse watery diarrhoea and persistent hypokalaemia requiring judicious intravenous water and electrolyte replacement. The symptoms resolved only after the introduction of intravenous hydrocortisone. It is important to consider intravenous corticosteroids if the gastrointestinal system is involved, as accelerated gut motility and mucosal damage would affect absorption of oral medications. Supportive treatment with the monitoring of fluid and electrolytes status and judicious replacement remains fundamental in the management of DHS patients with gut involvement.

  10. Non-surgical management of tooth hypersensitivity.

    PubMed

    Clark, Danielle; Levin, Liran

    2016-10-01

    Tooth sensitivity is a common complaint of patients in dental practices. Studies have demonstrated dentinal hypersensitivity to affect 10-30% of the population. There are various potential causes of tooth sensitivity and a variety of available treatment options. This narrative review will discuss the possible aetiology of this condition, as well as the treatment modalities available. A tailor-made treatment plan that starts with the most non-invasive treatment options and escalates only when those options have proven insufficient in alleviating symptoms should be provided for each patient. Only after all non- and less-invasive methods have failed to reduce the symptoms should more invasive treatment options, such as root-coverage, be considered. PMID:27301300

  11. Plant physiology and proteomics reveals the leaf response to drought in alfalfa (Medicago sativa L.)

    PubMed Central

    Aranjuelo, Iker; Molero, Gemma; Erice, Gorka; Avice, Jean Christophe; Nogués, Salvador

    2011-01-01

    Despite its relevance, protein regulation, metabolic adjustment, and the physiological status of plants under drought is not well understood in relation to the role of nitrogen fixation in nodules. In this study, nodulated alfalfa plants were exposed to drought conditions. The study determined the physiological, metabolic, and proteomic processes involved in photosynthetic inhibition in relation to the decrease in nitrogenase (Nase) activity. The deleterious effect of drought on alfalfa performance was targeted towards photosynthesis and Nase activity. At the leaf level, photosynthetic inhibition was mainly caused by the inhibition of Rubisco. The proteomic profile and physiological measurements revealed that the reduced carboxylation capacity of droughted plants was related to limitations in Rubisco protein content, activation state, and RuBP regeneration. Drought also decreased amino acid content such as asparagine, and glutamic acid, and Rubisco protein content indicating that N availability limitations were caused by Nase activity inhibition. In this context, drought induced the decrease in Rubisco binding protein content at the leaf level and proteases were up-regulated so as to degrade Rubisco protein. This degradation enabled the reallocation of the Rubisco-derived N to the synthesis of amino acids with osmoregulant capacity. Rubisco degradation under drought conditions was induced so as to remobilize Rubisco-derived N to compensate for the decrease in N associated with Nase inhibition. Metabolic analyses showed that droughted plants increased amino acid (proline, a major compound involved in osmotic regulation) and soluble sugar (D-pinitol) levels to contribute towards the decrease in osmotic potential (Ψs). At the nodule level, drought had an inhibitory effect on Nase activity. This decrease in Nase activity was not induced by substrate shortage, as reflected by an increase in total soluble sugars (TSS) in the nodules. Proline accumulation in the nodule

  12. Plant physiology and proteomics reveals the leaf response to drought in alfalfa (Medicago sativa L.).

    PubMed

    Aranjuelo, Iker; Molero, Gemma; Erice, Gorka; Avice, Jean Christophe; Nogués, Salvador

    2011-01-01

    Despite its relevance, protein regulation, metabolic adjustment, and the physiological status of plants under drought is not well understood in relation to the role of nitrogen fixation in nodules. In this study, nodulated alfalfa plants were exposed to drought conditions. The study determined the physiological, metabolic, and proteomic processes involved in photosynthetic inhibition in relation to the decrease in nitrogenase (N(ase)) activity. The deleterious effect of drought on alfalfa performance was targeted towards photosynthesis and N(ase) activity. At the leaf level, photosynthetic inhibition was mainly caused by the inhibition of Rubisco. The proteomic profile and physiological measurements revealed that the reduced carboxylation capacity of droughted plants was related to limitations in Rubisco protein content, activation state, and RuBP regeneration. Drought also decreased amino acid content such as asparagine, and glutamic acid, and Rubisco protein content indicating that N availability limitations were caused by N(ase) activity inhibition. In this context, drought induced the decrease in Rubisco binding protein content at the leaf level and proteases were up-regulated so as to degrade Rubisco protein. This degradation enabled the reallocation of the Rubisco-derived N to the synthesis of amino acids with osmoregulant capacity. Rubisco degradation under drought conditions was induced so as to remobilize Rubisco-derived N to compensate for the decrease in N associated with N(ase) inhibition. Metabolic analyses showed that droughted plants increased amino acid (proline, a major compound involved in osmotic regulation) and soluble sugar (D-pinitol) levels to contribute towards the decrease in osmotic potential (Ψ(s)). At the nodule level, drought had an inhibitory effect on N(ase) activity. This decrease in N(ase) activity was not induced by substrate shortage, as reflected by an increase in total soluble sugars (TSS) in the nodules. Proline accumulation

  13. 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.

  14. Differential Molecular Responses of Rapeseed Cotyledons to Light and Dark Reveal Metabolic Adaptations toward Autotrophy Establishment

    PubMed Central

    He, Dongli; Damaris, Rebecca N.; Fu, Jinlei; Tu, Jinxing; Fu, Tingdong; Xi, Chen; Yi, Bin; Yang, Pingfang

    2016-01-01

    Photosynthesis competent autotrophy is established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark conditions, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high levels of the isocitrate lyase (ICL). By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase in proteases, fatty acid β-oxidation and glyoxylate-cycle related proteins was accompanied by rapid degradation of the stored proteins and lipids with an accumulation of the amino acids. While light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase in reducing-sugars. However, the levels of some chlorophyllide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to decrease oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to autotrophy. PMID:27471506

  15. Differential Molecular Responses of Rapeseed Cotyledons to Light and Dark Reveal Metabolic Adaptations toward Autotrophy Establishment.

    PubMed

    He, Dongli; Damaris, Rebecca N; Fu, Jinlei; Tu, Jinxing; Fu, Tingdong; Xi, Chen; Yi, Bin; Yang, Pingfang

    2016-01-01

    Photosynthesis competent autotrophy is established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark conditions, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high levels of the isocitrate lyase (ICL). By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase in proteases, fatty acid β-oxidation and glyoxylate-cycle related proteins was accompanied by rapid degradation of the stored proteins and lipids with an accumulation of the amino acids. While light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase in reducing-sugars. However, the levels of some chlorophyllide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to decrease oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to autotrophy. PMID:27471506

  16. Incidence and time course of dentinal hypersensitivity after periodontal surgery.

    PubMed

    Al-Sabbagh, Mohanad; Beneduce, Carla; Andreana, Sebastiano; Ciancio, Sebastian G

    2010-01-01

    This study sought to characterize the incidence and clinical progression of dentinal hypersensitivity after periodontal surgery. Fourteen patients scheduled for open-flap periodontal debridement participated in the study. Ten subjects completed the study and were evaluated for six consecutive weeks after periodontal surgery. Tactile hypersensitivity was assessed using the Yeaple probe; thermal hypersensitivity measurements were obtained using a blast of air from the air/water syringe; and subjective hypersensitivity measurements were obtained using a visual analog scale (VAS). Measurements were taken preoperatively, one week postoperatively, and once a week for the next five consecutive weeks, for a total of six measurements after periodontal surgery. Depending on the stimuli used, dentinal hypersensitivity at one week after periodontal surgery ranged from 67 to 76%. Preoperative tactile and thermal hypersensitivity incidence combined was 30% at baseline. One week after periodontal surgery, the combined incidence had increased to 79%; at six weeks postsurgery, it had decreased to 45%. This study shows that postoperative dentinal hypersensitivity increases at one and three weeks after open-flap periodontal debridement before spontaneously and gradually decreasing to levels similar to those presurgery, even in the absence of desensitizing therapy. PMID:20129876

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

    PubMed Central

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

    2009-01-01

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

  18. Late-onset Anticonvulsant Hypersensitivity Syndrome Mimicking Lymphoma.

    PubMed

    Geduk, Ayfer; Birtas Atesoglu, Elif; Mehtap, Ozgur; Terzi Demirsoy, Esra; Can, Burak; Tarkun, Pinar; Hacihanefioglu, Abdullah

    2015-01-01

    Anticonvulsant hypersensitivity syndrome is a fatal, idiosyncratic drug reaction that is caused by aromatic antiepileptic drugs. This cutaneous drug reaction is also called pseudolymphoma because of its clinical and histological similarities with malignant lymphoma. The primary clinical findings are fever, skin rashes, enlarged lymph nodes, single or multiple internal organ involvement and hematological abnormalities. Typically, anticonvulsant hypersensitivity syndrome occurs 1-8 weeks after drug administration. We herein present the case of a patient who had been on anticonvulsant therapy for five years and died from late-onset anticonvulsant hypersensitivity syndrome. PMID:26666613

  19. Dentin hypersensitivity: etiology, diagnosis and treatment; a literature review.

    PubMed

    Davari, Ar; Ataei, E; Assarzadeh, H

    2013-09-01

    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

  20. 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 IFNγ 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 IFNγ-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

  1. Rds and Rih mediate hypersensitive cell death independent of gene-for-gene resistance to the oat crown rust pathogen Puccinia coronata f. sp. avenae.

    PubMed

    Yu, G X; Braun, E; Wise, R P

    2001-12-01

    The Pca crown rust resistance cluster in the diploid Avena genus confers gene-for-gene specificity to numerous isolates of Puccinia coronata f. sp. avenae. Recombination breakpoint analysis indicates that specificities conferred by the Pca cluster are controlled by at least five distinct genes, designated Pc81, Pc82, Pc83, Pc84, and Pc85. Avena plants with the appropriate genotype frequently respond to P. coronata by undergoing hypersensitive cell death at the sites of fungal infection. Autofluorescence of host cells in response to P. coronata occurs in plants that develop visible necrotic lesions but not in plants that lack this phenotype. Two newly described, non-Pc loci were shown to control hypersensitive cell death. Rds (resistance-dependent suppressor of cell death) suppresses the hypersensitive response (HR), but not the resistance, mediated by the Pc82 resistance gene. In contrast, Rih (resistance-independent hypersensitive cell death) confers HR in both resistant and susceptible plants. Linkage analysis indicates that Rds is unlinked to the Pca cluster, whereas Rih is tightly linked to it. These results indicate that multiple synchronous pathways affect the development of hypersensitive cell death and that HR is not essential for resistance to crown rust. Further characterization of these genes will clarify the relationship between plant disease resistance and localized hypersensitive cell death.

  2. Pain and the defense response: structural equation modeling reveals a coordinated psychophysiological response to increasing painful stimulation.

    PubMed

    Donaldson, Gary W; Chapman, C Richard; Nakamura, Yoshi; Bradshaw, David H; Jacobson, Robert C; Chapman, Christopher N

    2003-03-01

    The defense response theory implies that individuals should respond to increasing levels of painful stimulation with correlated increases in affectively mediated psychophysiological responses. This paper employs structural equation modeling to infer the latent processes responsible for correlated growth in the pain report, evoked potential amplitudes, pupil dilation, and skin conductance of 92 normal volunteers who experienced 144 trials of three levels of increasingly painful electrical stimulation. The analysis assumed a two-level model of latent growth as a function of stimulus level. The first level of analysis formulated a nonlinear growth model for each response measure, and allowed intercorrelations among the parameters of these models across individuals. The second level of analysis posited latent process factors to account for these intercorrelations. The best-fitting parsimonious model suggests that two latent processes account for the correlations. One of these latent factors, the activation threshold, determines the initial threshold response, while the other, the response gradient, indicates the magnitude of the coherent increase in response with stimulus level. Collectively, these two second-order factors define the defense response, a broad construct comprising both subjective pain evaluation and physiological mechanisms.

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

    PubMed

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

    2012-06-30

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

  4. Altered Purinergic Signaling in Colorectal Dorsal Root Ganglion Neurons Contributes to Colorectal Hypersensitivity

    PubMed Central

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

    2010-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by pain and hypersensitivity in the relative absence of colon inflammation or structural changes. To assess the role of P2X receptors expressed in colorectal dorsal root ganglion (c-DRG) neurons and colon hypersensitivity, we studied excitability and purinergic signaling of retrogradely labeled mouse thoracolumbar (TL) and lumbosacral (LS) c-DRG neurons after intracolonic treatment with saline or zymosan (which reproduces 2 major features of IBS—persistent colorectal hypersensitivity without inflammation) using patch-clamp, immunohistochemical, and RT-PCR techniques. Although whole cell capacitances did not differ between LS and TL c-DRG neurons and were not changed after zymosan treatment, membrane excitability was increased in LS and TL c-DRG neurons from zymosan-treated mice. Purinergic agonist adenosine-5′-triphosphate (ATP) and α,β-methylene ATP [α,β-meATP] produced inward currents in TL c-DRG neurons were predominantly P2X3-like fast (∼70% of responsive neurons); P2X2/3-like slow currents were more common in LS c-DRG neurons (∼35% of responsive neurons). Transient currents were not produced by either agonist in c-DRG neurons from P2X3−/− mice. Neither total whole cell Kv current density nor the sustained or transient Kv components was changed in c-DRG neurons after zymosan treatment. The number of cells expressing P2X3 protein and its mRNA and the kinetic properties of ATP- and α,β-meATP-evoked currents in c-DRG neurons were not changed by zymosan treatment. However, the EC50 of α,β-meATP for the fast current decreased significantly in TL c-DRG neurons. These findings suggest that colorectal hypersensitivity produced by intracolonic zymosan increases excitability and enhances purinergic signaling in c-DRG neurons. PMID:20861433

  5. Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks.

    PubMed

    Willis, Nicholas A; Zhou, Chunshui; Elia, Andrew E H; Murray, Johanne M; Carr, Antony M; Elledge, Stephen J; Rhind, Nicholas

    2016-06-28

    The cellular response to DNA damage during S-phase regulates a complicated network of processes, including cell-cycle progression, gene expression, DNA replication kinetics, and DNA repair. In fission yeast, this S-phase DNA damage response (DDR) is coordinated by two protein kinases: Rad3, the ortholog of mammalian ATR, and Cds1, the ortholog of mammalian Chk2. Although several critical downstream targets of Rad3 and Cds1 have been identified, most of their presumed targets are unknown, including the targets responsible for regulating replication kinetics and coordinating replication and repair. To characterize targets of the S-phase DDR, we identified proteins phosphorylated in response to methyl methanesulfonate (MMS)-induced S-phase DNA damage in wild-type, rad3∆, and cds1∆ cells by proteome-wide mass spectrometry. We found a broad range of S-phase-specific DDR targets involved in gene expression, stress response, regulation of mitosis and cytokinesis, and DNA replication and repair. These targets are highly enriched for proteins required for viability in response to MMS, indicating their biological significance. Furthermore, the regulation of these proteins is similar in fission and budding yeast, across 300 My of evolution, demonstrating a deep conservation of S-phase DDR targets and suggesting that these targets may be critical for maintaining genome stability in response to S-phase DNA damage across eukaryotes.

  6. 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.

  7. [A patient with paclitaxel hypersensitivity treated with nab-paclitaxel].

    PubMed

    Ouchi, Akira; Ouchi, Akira; Asano, Masahiko; Aono, Keiya; Watanabe, Tetsuya; Kato, Takehiro

    2014-07-01

    A 63-year-old man with multiple liver metastases from gastric cancer was treated with S-1 plus cisplatin; however, the number of multiple liver metastases increased. The patient received paclitaxel(PTX)treatment, but a hypersensitivity reaction occurred after administering the second dose; therefore, he received docetaxel treatment. A hypersensitivity reaction occurred after administering the first dose of docetaxel; therefore, he received irinotecan treatment. However, irinotecan administration was stopped because of severe diarrhea and weight reduction. Subsequently, at the patient's request, nab-PTX treatment was initiated by administering a premedication regimen of dexamethasone(8mg)and chlorpheniramine(10mg); no hypersensitivity reactions were reported thereafter. Nab-PTX is a contraindication; however, it might be possible to use nab-PTX for treating patients with PTX hypersensitivity.

  8. 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

  9. Hypersensitivity pneumonitis: a historical, clinical, and radiologic review.

    PubMed

    Hirschmann, Jan V; Pipavath, Sudhakar N J; Godwin, J David

    2009-11-01

    Most cases of hypersensitivity pneumonitis develop only after many years of inhaling allergens, which include microbes, animal or plant proteins, and certain chemicals that form haptens. The initial clinical presentation is either episodes of acute illness with dyspnea and prominent constitutional symptoms, such as fever, or an insidious onset of dyspnea, coughing, and weight loss, sometimes with superimposed acute episodes. The histopathologic process consists of chronic inflammation of the bronchi and peribronchiolar tissue, often with poorly defined granulomas and giant cells in the interstitium or alveoli. Fibrosis and emphysema may develop. The radiologic findings include diffuse ground-glass opacification, centrilobular ground-glass opacities, air trapping, fibrosis, lung cysts, and emphysema. The histologic and radiologic features in some cases may resemble those of usual interstitial pneumonia or nonspecific interstitial pneumonia. The diagnosis usually rests on a variable combination of findings from history, serology, radiography, lung biopsy, and bronchoalveolar lavage, which characteristically reveals a lymphocyte content of more than 30%, often with an increased CD4-to-CD8 ratio of T cells. Treatment includes avoiding the allergen, if possible, and, in severe cases, systemic corticosteroids. The long-term prognosis is usually good, but some patients develop severe respiratory insufficiency, and a few die of the disease.

  10. 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

  11. Carboplatin-induced severe hypersensitivity reaction: role of IgE-dependent basophil activation and FcεRI.

    PubMed

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

    2014-11-01

    Basophil activation was observed in patients with a history of carboplatin-induced severe hypersensitivity reaction (HR). However, the precise mechanism by which carboplatin induces basophil activation and the associated surrogate markers remains to be elucidated. To investigate whether IgE-dependent mechanisms, including the overexpression of FcεRI, participate in carboplatin-induced basophil activation, 13 ovarian cancer patients were enrolled: 5 with a history of carboplatin-induced severe hypersensitivity reaction within the past 2 years, and 8 with no such history. The expression levels of FcεRI, IgE, and CD203c on basophils were measured using a flow cytometer. Immunoglobulin E-dependent basophil activation was evaluated by testing for IgE passive sensitization using lactic acid, and by testing for phosphatidylinositol 3-kinase inhibition, using wortmannin. In three patients positive for carboplatin hypersensitivity, pretreatment with wortmannin almost completely inhibited carboplatin-induced basophil activation (P < 0.05). In a healthy control subject, whose own IgE showed no response to carboplatin, acquired reactivity to carboplatin when exposed to plasma from patients positive for carboplatin hypersensitivity. This did not occur when the same experiment was carried out using plasma from the patients negative for carboplatin hypersensitivity. Moreover, pretreatment with omalizumab, a monoclonal anti-IgE antibody, almost completely blocked carboplatin-induced basophil activation in the plasma of patients positive for carboplatin hypersensitivity. On further investigation, the HR-positive group had significantly higher levels of FcεRI compared with the negative group (P < 0.05). In conclusion, an IgE-dependent mechanism incorporating FcεRI overexpression participates in carboplatin-induced severe HR. These results establish the relevance of monitoring the pharmacodynamic changes of basophils to prevent carboplatin-induced severe HR.

  12. Hypersensitivity associated with sugammadex administration: a systematic review.

    PubMed

    Tsur, A; Kalansky, A

    2014-11-01

    Sugammadex is a drug used to reverse neuromuscular blockade induced by rocuronium or vecuronium. It has not yet been approved by the Food and Drug Administration in the USA due to concerns regarding hypersensitivity. The objective of this review was to identify similarities in the presentation of hypersensitivity reactions to sugammadex. A comprehensive search was performed in PubMed, Scopus and Web of Science for cases reporting hypersensitivity reactions to sugammadex. In addition, we contacted regulatory agencies and the company marketing the drug for unpublished reports. Reports were included if they were in English, primary investigations, lacked an alternative probable explanation for the reaction and included a comprehensive description of the hypersensitivity. We identified 15 cases of hypersensitivity following sugammadex administration. All cases that reported exact timing (14/15) occurred in 4 min or less. Most of the patients (11/15; 73%) met World Anaphylaxis Organization criteria for anaphylaxis. Awareness must be raised for the possibility of drug-induced hypersensitivity during the critical 5-min period immediately following sugammadex administration.

  13. 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...

  14. 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…

  15. A replicated climate change field experiment reveals rapid evolutionary response in an ecologically important soil invertebrate.

    PubMed

    Bataillon, Thomas; Galtier, Nicolas; Bernard, Aurelien; Cryer, Nicolai; Faivre, Nicolas; Santoni, Sylvain; Severac, Dany; Mikkelsen, Teis N; Larsen, Klaus S; Beier, Claus; Sørensen, Jesper G; Holmstrup, Martin; Ehlers, Bodil K

    2016-07-01

    Whether species can respond evolutionarily to current climate change is crucial for the persistence of many species. Yet, very few studies have examined genetic responses to climate change in manipulated experiments carried out in natural field conditions. We examined the evolutionary response to climate change in a common annelid worm using a controlled replicated experiment where climatic conditions were manipulated in a natural setting. Analyzing the transcribed genome of 15 local populations, we found that about 12% of the genetic polymorphisms exhibit differences in allele frequencies associated to changes in soil temperature and soil moisture. This shows an evolutionary response to realistic climate change happening over short-time scale, and calls for incorporating evolution into models predicting future response of species to climate change. It also shows that designed climate change experiments coupled with genome sequencing offer great potential to test for the occurrence (or lack) of an evolutionary response. PMID:27109012

  16. 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.

  17. Dentin hypersensitivity: Recent trends in management.

    PubMed

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-10-01

    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.

  18. DELAYED HYPERSENSITIVITY TO HAPTEN-PROTEIN CONJUGATES

    PubMed Central

    Cell, P. G. H.; Silverstein, Arthur M.

    1962-01-01

    Further data have been presented showing that the specificity of the delayed hypersensitivity reaction in the guinea pig to hapten-protein conjugates involves to a considerable degree a contribution by the protein carrier. The carrier contribution is such that sensitization to guinea pig albumin-m-azobenzenesulfonate, for example, does not result in cross-reaction with conjugates of the same hapten with unrelated proteins such as ovalbumin or human gamma globulin, nor were cross-reactions observed between conjugates prepared with the same hapten, coupled to the same protein, but by two different chemical routes, such that the point of attachment of the hapten to the protein differed. It thus appears that in this system both hapten and carrier protein are necessary, but that neither alone is in general sufficient to stimulate the delayed sensitive cell. Desensitization experiments with cross-reacting hapten-protein conjugates have suggested the presence of a multiplicity of antigenic determinants participating in the elicitation of the delayed lesion, and of a concomitant development of a heterogeneity of specificities in the population of delayed sensitive cells in the sensitized animal. The data are discussed in terms of the apparent requirement of the delayed sensitivity mechanism for a larger functional antigenic determinant than that required for interaction with circulating antibodies. Some possible explanations for this difference, and some of its consequences, are discussed. PMID:13897619

  19. Dentin hypersensitivity: Recent trends in management.

    PubMed

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-10-01

    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

  20. 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.

  1. 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

  2. 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.

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

    PubMed

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

    2014-04-01

    This study aims to identify the inhibitory role of the spinal glucagon like peptide-1 receptor (GLP-1R) signaling in pain hypersensitivity and its mechanism of action in rats and mice. First, GLP-1Rs were identified to be specifically expressed on microglial cells in the spinal dorsal horn, and profoundly upregulated after peripheral nerve injury. In addition, intrathecal GLP-1R agonists GLP-1(7-36) and exenatide potently alleviated formalin-, peripheral nerve injury-, bone cancer-, and diabetes-induced hypersensitivity states by 60-90%, without affecting acute nociceptive responses. The antihypersensitive effects of exenatide and GLP-1 were completely prevented by GLP-1R antagonism and GLP-1R gene knockdown. Furthermore, exenatide evoked β-endorphin release from both the spinal cord and cultured microglia. Exenatide antiallodynia was completely prevented by the microglial inhibitor minocycline, β-endorphin antiserum, and opioid receptor antagonist naloxone. Our results illustrate a novel spinal dorsal horn microglial GLP-1R/β-endorphin inhibitory pathway in a variety of pain hypersensitivity states. PMID:24719110

  4. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    PubMed

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities.

  5. SMARCAL1 Deficiency Predisposes to Non-Hodgkin Lymphoma and Hypersensitivity to Genotoxic Agents In vivo

    PubMed Central

    Baradaran-Heravi, Alireza; Raams, Anja; Lubieniecka, Joanna; Cho, Kyoung Sang; DeHaai, Kristi A.; Basiratnia, Mitra; Mari, Pierre-Olivier; Xue, Yutong; Rauth, Michael; Olney, Ann Haskins; Shago, Mary; Choi, Kunho; Weksberg, Rosanna A.; Nowaczyk, Malgorzata J.M.; Wang, Weidong; Jaspers, Nicolaas G.J.; Boerkoel, Cornelius F.

    2012-01-01

    Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder with prominent skeletal, renal, immunological, and ectodermal abnormalities. It is caused by mutations of SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA stress response protein. To determine the relationship of this function to the SIOD phenotype, we profiled the cancer prevalence in SIOD and assessed if defects of nucleotide excision repair (NER) and of nonhomologous end joining (NHEJ), respectively, explained the ectodermal and immunological features of SIOD. Finally, we determined if Smarcal1del/del mice had hypersensitivity to irinotecan (CPT-11), etoposide and hydroxyurea (HU) and whether exposure to these agents induced features of SIOD. Among 71 SIOD patients, three had non-Hodgkin lymphoma (NHL) and one had osteosarcoma. We did not find evidence of defective NER or NHEJ; however, Smarcal1-deficient mice were hypersensitive to several genotoxic agents. Also, CPT-11, etoposide and HU caused decreased growth and loss of growth plate chondrocytes. These data, which identify an increased prevalence of NHL in SIOD and confirm hypersensitivity to DNA damaging agents in vivo, provide guidance for the management of SIOD patients. PMID:22888040

  6. DNAaseI-hypersensitive minichromosomes of SV40 possess an elastic torsional strain in DNA.

    PubMed Central

    Luchnik, A N; Bakayev, V V; Yugai, A A; Zbarsky, I B; Georgiev, G P

    1985-01-01

    Previously, we have shown that DNA in a small fraction (2-5%) of SV40 minichromosomes was torsionally strained and could be relaxed by treating minichromosomes with topoisomerase I. This fraction was enriched with endogeneous RNA polymerase II (Luchnik et al., 1982, EMBO J., 1, 1353). Here we show that one and the same fraction of SV40 minichromosomes is hypersensitive to DNAase I and is relaxable by topoisomerase I. Moreover, this fraction completely loses its hypersensitivity to DNAase I upon relaxation. The possibility that this fraction of minichromosomes can be represented by naked DNA is ruled out by the results of studying the kinetics of minichromosome digestion by DNAase I in comparison to digestion of pure SV40 DNA and by measuring the buoyant density of SV40 chromatin in equilibrium CsCl gradient. Our data obtained with SV40 minichromosomes may be relevant to the mechanism responsible for DNAase I hypersensitivity in the loops or domains of cellular chromatin. Images PMID:2987817

  7. 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 vitro–specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens–Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. 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

  8. 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.

  9. Transcriptional dynamics reveal critical roles for non-coding RNAs in the immediate-early response.

    PubMed

    Aitken, Stuart; Magi, Shigeyuki; Alhendi, Ahmad M N; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O; Arner, Erik; Carninci, Piero; Forrest, Alistair R R; Hayashizaki, Yoshihide; Khachigian, Levon M; Okada-Hatakeyama, Mariko; Semple, Colin A

    2015-04-01

    The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE) time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs) and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset. PMID:25885578

  10. Transcriptional dynamics reveal critical roles for non-coding RNAs in the immediate-early response.

    PubMed

    Aitken, Stuart; Magi, Shigeyuki; Alhendi, Ahmad M N; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O; Arner, Erik; Carninci, Piero; Forrest, Alistair R R; Hayashizaki, Yoshihide; Khachigian, Levon M; Okada-Hatakeyama, Mariko; Semple, Colin A

    2015-04-01

    The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE) time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs) and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset.

  11. Transcriptional Dynamics Reveal Critical Roles for Non-coding RNAs in the Immediate-Early Response

    PubMed Central

    Aitken, Stuart; Magi, Shigeyuki; Alhendi, Ahmad M. N.; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O.; Arner, Erik; Carninci, Piero; Forrest, Alistair R. R.; Hayashizaki, Yoshihide; Khachigian, Levon M.; Okada-Hatakeyama, Mariko; Semple, Colin A.

    2015-01-01

    The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE) time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs) and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset. PMID:25885578

  12. Multi-omics analysis reveals regulators of the response to nitrogen limitation in Yarrowia lipolytica

    DOE PAGES

    Pomraning, Kyle R.; Kim, Young -Mo; Nicora, Carrie D.; Chu, Rosalie K.; Bredeweg, Erin L.; Purvine, Samuel O.; Hu, Dehong; Metz, Thomas O.; Baker, Scott E.

    2016-02-25

    Yarrowia lipolytica is an oleaginous ascomycete yeast that stores lipids in response to limitation of nitrogen. Furthermore, while the enzymatic pathways responsible for neutral lipid accumulation in Y. lipolytica are well characterized, regulation of these pathways has received little attention. We therefore sought to characterize the response to nitrogen limitation at system-wide levels, including the proteome, phosphoproteome and metabolome, to better understand how this organism regulates and controls lipid metabolism and to identify targets that may be manipulated to improve lipid yield.

  13. Microarray analysis reveals that Type I interferon strongly increases the expression of immune-response related genes in Ubp43 (Usp18) deficient macrophages

    PubMed Central

    Zou, Weiguo; Kim, Jung-Hwan; Handidu, Adedayo; Li, Xiang; Kim, Keun Il; Yan, Ming; Li, Jun; Zhang, Dong-Er

    2007-01-01

    Type I interferon (IFN) contributes significantly to innate immune responses to pathogen infections in macrophages. Our previous studies demonstrate that Ubp43, an ISG15-specific isopeptidase, is highly expressed in macrophages and noncatalytically inhibits Type I IFN signaling. To understand the effect of Type I IFN and Ubp43 in macrophage activation, we analyzed the expression of IFN-β stimulated genes in wild-type and Ubp43−/− bone marrow derived macrophages (BMMs). Here, we show that Ubp43 regulates IFN-β stimulated genes at genome level. IFN hypersensitivity of Ubp43−/− BMMs resulted in the identification of 749 unique genes that are upregulated by IFN-β, including a large group of previously unidentified IFN-stimulated genes. Functional analyses of these genes showed that Type I IFN strongly induced the expression of a group of immune response related genes, including genes for antigen presentation, antiviral responses, and chemokine and cytokine production. These results provide excellent biochemical support for the high resistance of viral and bacterial infection of Ubp43 knockout mice, suggesting that Ubp43 is a potential therapeutic target for the enhancement of immune responses against infections. PMID:17349616

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

    PubMed Central

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

    2016-01-01

    AIM: To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. METHODS: Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. RESULTS: Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. CONCLUSION: The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research. PMID:27298564

  15. 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.; O’Toole, 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

  16. Re-visiting Hypersensitivity Reactions to Taxanes: A Comprehensive Review.

    PubMed

    Picard, Matthieu; Castells, Mariana C

    2015-10-01

    Taxanes (a class of chemotherapeutic agents) are an important cause of hypersensitivity reactions (HSRs) in cancer patients. During the last decade, the development of rapid drug desensitization has been key to allow patients with HSRs to taxanes to be safely re-treated although the mechanisms of these HSRs are not fully understood. Earlier studies suggested that solvents, such as Cremophor EL used to solubilize paclitaxel, were responsible for HSRs through complement activation, but recent findings have raised the possibility that some of these HSRs are IgE-mediated. Taxane skin testing, which identifies patients with an IgE-mediated sensitivity, appears as a promising diagnostic and risk stratification tool in the management of patients with HSRs to taxanes. The management of patients following a HSR involves risk stratification and re-exposure could be performed either through rapid drug desensitization or graded challenge based on the severity of the initial HSR and the skin test result. Rapid drug desensitization has been shown to be an effective and safe method to re-introduce taxanes in hundreds of patients, including those with life-threatening HSRs. Patients with non-severe delayed skin HSRs may benefit from rapid drug desensitization since they may be at increased risk for an immediate HSR upon re-exposure. This review focuses on the clinical presentation, diagnosis, and novel mechanisms of immediate HSRs to taxanes. A new management strategy for HSRs to taxanes based on skin testing and rapid drug desensitization is proposed.

  17. 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 25–50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. PMID:24007741

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

    PubMed

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

    2013-12-01

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

  19. Global analyses of human immune variation reveal baseline predictors of post-vaccination responses

    PubMed Central

    Tsang, John S.; Schwartzberg, Pamela L.; Kotliarov, Yuri; Biancotto, Angelique; Xie, Zhi; Germain, Ronald N.; Wang, Ena; Olnes, Matthew J.; Narayanan, Manikandan; Golding, Hana; Moir, Susan; Dickler, Howard B.; Perl, Shira; Cheung, Foo

    2014-01-01

    A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of post-vaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time-points. Most of the parameters contributing to prediction delineated temporally-stable baseline differences across individuals, raising the prospect of immune monitoring before intervention. PMID:24725414

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes.

    PubMed

    Palmer, Alan R; Shackleton, Trevor M; Sumner, Christian J; Zobay, Oliver; Rees, Adrian

    2013-08-15

    A differential response to sound frequency is a fundamental property of auditory neurons. Frequency analysis in the cochlea gives rise to V-shaped tuning functions in auditory nerve fibres, but by the level of the inferior colliculus (IC), the midbrain nucleus of the auditory pathway, neuronal receptive fields display diverse shapes that reflect the interplay of excitation and inhibition. The origin and nature of these frequency receptive field types is still open to question. One proposed hypothesis is that the frequency response class of any given neuron in the IC is predominantly inherited from one of three major afferent pathways projecting to the IC, giving rise to three distinct receptive field classes. Here, we applied subjective classification, principal component analysis, cluster analysis, and other objective statistical measures, to a large population (2826) of frequency response areas from single neurons recorded in the IC of the anaesthetised guinea pig. Subjectively, we recognised seven frequency response classes (V-shaped, non-monotonic Vs, narrow, closed, tilt down, tilt up and double-peaked), that were represented at all frequencies. We could identify similar classes using our objective classification tools. Importantly, however, many neurons exhibited properties intermediate between these classes, and none of the objective methods used here showed evidence of discrete response classes. Thus receptive field shapes in the IC form continua rather than discrete classes, a finding consistent with the integration of afferent inputs in the generation of frequency response areas. The frequency disposition of inhibition in the response areas of some neurons suggests that across-frequency inputs originating at or below the level of the IC are involved in their generation. PMID:23753527

  6. 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

  7. 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

  8. Stachybotrys chartarum-Induced Hypersensitivity Pneumonitis Is TLR9 Dependent

    PubMed Central

    Bhan, Urvashi; Newstead, Michael J.; Zeng, Xianying; Ballinger, Megan N.; Standiford, Louis R.; Standiford, Theodore J.

    2011-01-01

    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)-γ. 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 106 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-α, IL-12, and IFN-γ. SC-mediated granulomatous inflammation required IFN-γ 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-γ 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

  9. The role for decorin in delayed-type hypersensitivity

    PubMed Central

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

    2016-01-01

    Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007

  10. EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness.

    PubMed

    Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

    2015-07-14

    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 specifi