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1

Early events in plant hypersensitive response leaves revealed by IR thermography  

NASA Astrophysics Data System (ADS)

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.

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

2001-10-01

2

Hypersensitive response-related death  

Microsoft Academic Search

The hypersensitive response (HR) of plants resistant to microbial pathogens involves a complex form of programmed cell death (PCD) that differs from developmental PCD in its consistent association with the induction of local and systemic defence responses. Hypersensitive cell death is commonly controlled by direct or indirect interactions between pathogen avirulence gene products and those of plant resistance genes and

Michèle C. Heath

2000-01-01

3

Basophil hypersensitivity response in rabbits.  

PubMed Central

A cutaneous basophil hypersensitivity response has been observed in rabbits immunized with bovine serum albumin and challenged intradermally with this antigen 7 days later. The cellular response appears to be similar to cutaneous basophil hypersensitivity reported in guinea pigs and humans. A basophil response was also observed in rabbits immunized with Staphylococcus aureus and challenged with viable staphylococcal cells 7 days later. A method of observing basophil infiltration in rabbits by means of connective tissue spreads obtained from the subcutaneous connective tissue is described. The rabbit should serve as an excellent model for the study of basophil responses as these animals have a significant basophil component with few if any tissue mast cells which may be confused both morphologically and functionally with the basophil. Images

Clark, J M; Altman, G; Fromowitz, F B

1977-01-01

4

Lipid profiling of the Arabidopsis hypersensitive response reveals specific lipid peroxidation and fragmentation processes: biogenesis of pimelic and azelaic acid.  

PubMed

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

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

2012-09-01

5

Hypersensitive response - A biophysical phenomenon of producers  

PubMed Central

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

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

2013-01-01

6

Hypersensitive response - A biophysical phenomenon of producers.  

PubMed

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

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

2013-06-01

7

A survey of resistance to Tomato bushy stunt virus in the genus Nicotiana reveals that the hypersensitive response is triggered by one of three different viral proteins.  

PubMed

In this study, we screened 22 Nicotiana spp. for resistance to the tombusviruses Tomato bushy stunt virus (TBSV), Cucumber necrosis virus, and Cymbidium ringspot virus. Eighteen species were resistant, and resistance was manifested in at least two different categories. In all, 13 species responded with a hypersensitive response (HR)-type resistance, whereas another five were resistant but either had no visible response or responded with chlorotic lesions rather than necrotic lesions. Three different TBSV proteins were found to trigger HR in Nicotiana spp. in an agroinfiltration assay. The most common avirulence (avr) determinant was the TBSV coat protein P41, a protein that had not been previously recognized as an avr determinant. A mutational analysis confirmed that the coat protein rather than the viral RNA sequence was responsible for triggering HR, and it triggered HR in six species in the Alatae section. The TBSV P22 movement protein triggered HR in two species in section Undulatae (Nicotiana glutinosa and N. edwardsonii) and one species in section Alatae (N. forgetiana). The TBSV P19 RNA silencing suppressor protein triggered HR in sections Sylvestres (N. sylvestris), Nicotiana (N. tabacum), and Alatae (N. bonariensis). In general, Nicotiana spp. were capable of recognizing only one tombusvirus avirulence determinant, with the exceptions of N. bonariensis and N. forgetiana, which were each able to recognize P41, as well as P19 and P22, respectively. Agroinfiltration failed to detect the TBSV avr determinants responsible for triggering HR in N. arentsii, N. undulata, and N. rustica. This study illustrates the breadth and variety of resistance responses to tombusviruses that exists in the Nicotiana genus. PMID:23075040

Angel, Carlos A; Schoelz, James E

2013-02-01

8

Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers.  

PubMed

Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ?100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes. PMID:23700312

Malin, Justin; Aniba, Mohamed Radhouane; Hannenhalli, Sridhar

2013-08-01

9

Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers  

PubMed Central

Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ?100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes.

Malin, Justin; Aniba, Mohamed Radhouane; Hannenhalli, Sridhar

2013-01-01

10

Cloning of tobacco genes that elicit the hypersensitive response  

Microsoft Academic Search

We used a functional screening method to isolate genes whose products elicit the hypersensitive response (HR) pathway of defense against plant pathogens. A cDNA library derived from tobacco leaves undergoing the HR was cloned into a tobacco mosaic virus (TMV)-based expression vector. Infectious transcripts were generated and used to inoculate tobacco plants lacking the N resistance gene (genotype Xanthi nn).

Erik E. Karrer; Roger N. Beachy; Curtis A. Holt

1998-01-01

11

Experimental hypersensitivity pneumonitis in guinea pigs. Kinetics and dose response.  

PubMed

Experimental hypersensitivity pneumonitis (HP) can be transferred by cells cultured in vitro with antigen, but not by noncultured cells. We determined the relationship between antigen concentration, time of culture, and development of competence to transfer HP and if separation of lymphoblasts from a noncultured cell population would allow transfer. We cultured lymph node cells from sensitized Strain II guinea pigs with a soluble extract of Micropolyspora faeni (10 micrograms/ml) for 48, 72, and 96 h, and isolated and transferred lymphoblasts intravenously to syngeneic recipients. Other animals received lymphoblasts from 72-h cultures exposed to 0, 0.1, 1, 10, or 30 micrograms/ml M. faeni. We also separated and transferred lymphoblasts from noncultured lymph node cell populations. Control animals received equal volumes of media. The animals were challenged intratracheally with M. faeni 48 h after the cell transfer, and they were killed 4 days after intratracheal challenge. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. All guinea pigs were maintained in HEPA-filtered air. There was a low level of pulmonary response to an intratracheal challenge of M. faeni in animals that received media and a substantial increase (p less than 0.01) in the extent of pulmonary abnormalities in the animals receiving lymphoblasts cultured for 72 and 96 but not for 48 h. Recipients of lymphoblasts cultured for 72 h with 1, 10, and 30 but not zero and 0.1 micrograms/ml M. faeni exhibited increased extent of pulmonary abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2930078

Schuyler, M; Crooks, L

1989-04-01

12

Host defenses in experimental scrub typhus: delayed-type hypersensitivity responses of inbred mice.  

PubMed

Delayed-type hypersensitivity responses of inbred mice during the course of lethal and chronic infections with strains of Rickettsia tsutsugamushi were evaluated by using the influx of radiolabeled cells into antigen-injected ears. Congenic strains of C3H mice, which previously have been shown to be resistant (C3H/RV) or sensitive (C3H/HeDub) to lethal intraperitoneal infection with the Gilliam strain of rickettsiae, both expressed delayed-type hypersensitivity early in the course of infection (5 to 7 days). The sensitive C3H/HeDub mice, however, exhibited a marked decline in reactivity just before death. In contrast, reactivity of C3H/RV mice remained high through day 9 and declined slowly through day 15 after infection. Similar results were obtained when BALB/c mice were infected with either the Karp or the Gilliam strain of rickettsiae, which produce a lethal or nonlethal infection, respectively, in this strain of mice. Rechallenge of C3H/RV mice elicited a rapid increase in reactivity, suggesting a secondary memory response. To analyze delayed-type hypersensitivity during chronic infection, C3H/HeDub mice were immunized by subcutaneous infection with the Gilliam strain of R. tsutsugamushi, and both delayed-type hypersensitivity reactivity and resistance to intraperitoneal challenge were examined. Delayed-type hypersensitivity reactivity developed slowly and peaked at 21 days postimmunization, which correlated with resistance to intraperitoneal challenge. Delayed-type hypersensitivity reactivity declined thereafter, but resistance to intraperitoneal challenge remained through 28 days postimmunization. Delayed-type hypersensitivity reactivity increased after secondary challenge at 28 days, again suggesting antigen memory generated by primary immunization. Transfer of delayed-type hypersensitivity reactivity was accomplished by using immune thymus-derived splenic lymphocytes isolated with nylon-wool columns. Abrogation of the ability of immune spleen cells to transfer delayed-type hypersensitivity reactivity after treatment with anti-Thy 1.2 alloantiserum and complement further supported the view that delayed-type hypersensitivity responses to scrub typhus rickettsiae were mediated by thymus-derived lymphocytes. PMID:6797944

Jerrells, T R; Osterman, J V

1982-01-01

13

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

PubMed Central

Delayed-type hypersensitivity responses of inbred mice during the course of lethal and chronic infections with strains of Rickettsia tsutsugamushi were evaluated by using the influx of radiolabeled cells into antigen-injected ears. Congenic strains of C3H mice, which previously have been shown to be resistant (C3H/RV) or sensitive (C3H/HeDub) to lethal intraperitoneal infection with the Gilliam strain of rickettsiae, both expressed delayed-type hypersensitivity early in the course of infection (5 to 7 days). The sensitive C3H/HeDub mice, however, exhibited a marked decline in reactivity just before death. In contrast, reactivity of C3H/RV mice remained high through day 9 and declined slowly through day 15 after infection. Similar results were obtained when BALB/c mice were infected with either the Karp or the Gilliam strain of rickettsiae, which produce a lethal or nonlethal infection, respectively, in this strain of mice. Rechallenge of C3H/RV mice elicited a rapid increase in reactivity, suggesting a secondary memory response. To analyze delayed-type hypersensitivity during chronic infection, C3H/HeDub mice were immunized by subcutaneous infection with the Gilliam strain of R. tsutsugamushi, and both delayed-type hypersensitivity reactivity and resistance to intraperitoneal challenge were examined. Delayed-type hypersensitivity reactivity developed slowly and peaked at 21 days postimmunization, which correlated with resistance to intraperitoneal challenge. Delayed-type hypersensitivity reactivity declined thereafter, but resistance to intraperitoneal challenge remained through 28 days postimmunization. Delayed-type hypersensitivity reactivity increased after secondary challenge at 28 days, again suggesting antigen memory generated by primary immunization. Transfer of delayed-type hypersensitivity reactivity was accomplished by using immune thymus-derived splenic lymphocytes isolated with nylon-wool columns. Abrogation of the ability of immune spleen cells to transfer delayed-type hypersensitivity reactivity after treatment with anti-Thy 1.2 alloantiserum and complement further supported the view that delayed-type hypersensitivity responses to scrub typhus rickettsiae were mediated by thymus-derived lymphocytes.

Jerrells, Thomas R.; Osterman, Joseph V.

1982-01-01

14

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

PubMed Central

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

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

2014-01-01

15

Characterization of the T-cell response in a patient with phenindione hypersensitivity.  

PubMed

The oral anticoagulant phenindione [2-phenyl-1H-indene-1,3(2H)-dione] is associated with hypersensitivity reactions in 1.5 to 3% of patients, the pathogenesis of which is unclear. We describe a patient who developed a severe hypersensitivity reaction that involved both the skin and lungs. A lymphocyte transformation test showed proliferation of T-cells from the hypersensitive patient, but not from four controls on exposure to phenindione in vitro. Drug-specific T-cell clones were generated and characterized in terms of their phenotype, functionality, and mechanism of antigen presentation. Forty-three human leukocyte antigen class II restricted CD4(+) alphabeta T-cell clones were identified. T-cell activation resulted in the secretion of interferon-gamma and interleukin-5. Five of seven clones proliferated with phenindione alone, whereas two clones also proliferated with 2-phenylindene. Certain T-cell clones were also stimulated by R- and S-warfarin; computer modeling revealed that warfarin can adopt a phenindione-like structure. Phenindione was presented to T-cells via two pathways: first, bound directly to major histocompatibility complex and second, bound to a processed peptide. Our data show that CD4(+) T-cells are involved in the pathophysiology of phenindione hypersensitivity. There may be cross-sensitivity with warfarin in some phenindione hypersensitive patients. PMID:15743920

Naisbitt, Dean J; Farrell, John; Chamberlain, Peter J; Hopkins, Josephine E; Berry, Neil G; Pirmohamed, Munir; Park, B Kevin

2005-06-01

16

Markers for hypersensitive response and senescence show distinct patterns of expression  

Microsoft Academic Search

Controlled cellular suicide is an important process that can be observed in various organs during plant development. From the generation of proper sexual organs in monoecious plants to the hypersensitive response (HR) that occurs during incompatible pathogen interactions, programmed cell death (PCD) can be readily observed. Although several biochemical and morphological parameters have been described for various types of cell

Dominique Pontier; Susheng Gan; Richard M. Amasino; Dominique Roby; Eric Lam

1999-01-01

17

The role of hypersensitivity and the immune response in influencing susceptibility to metal toxicity  

Microsoft Academic Search

An individual's immune status influences the metabolism and toxicity of metals. Common phenomena from increased cellular reactivity to platinum, mercury, gold, nickel, chromium, and beryllium are described. Effects are classified into four types of immune response. Cutaneous hypersensitivity is the most common, affecting industrial and general population groups. (62 references)

Kazantzis

1978-01-01

18

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

PubMed

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. PMID:7613142

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

1995-01-01

19

High cytokinin levels induce a hypersensitive-like response in tobacco  

PubMed Central

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

Novak, Jan; Pavlu, Jaroslav; Novak, Ondrej; Nozkova-Hlavackova, Vladimira; Spundova, Martina; Hlavinka, Jan; Koukalova, Sarka; Skalak, Jan; Cerny, Martin; Brzobohaty, Bretislav

2013-01-01

20

Identification of Arabidopsis mutants exhibiting an altered hypersensitive response in gene-for-gene disease resistance.  

PubMed

A mutational study was carried out to isolate Arabidopsis thaliana plants that exhibit full or partial disruption of the RPS2-mediated hypersensitive response (HR) to Pseudomonas syringae that express avrRpt2. Five classes of mutants were identified including mutations at RPS2, dnd mutations causing a "defense, no death" loss-of-HR phenotype, a lesion-mimic mutant that also exhibited an HR- phenotype, and a number of intermediate or partial-loss-of-HR mutants. Surprisingly, many of these mutants displayed elevated resistance to virulent P. syringae and, in some cases, to Peronospora parasitica. Constitutively elevated levels of pathogenesis-related (PR) gene expression and salicylic acid were also observed. In the lesion-mimic mutant, appearance of elevated resistance was temporally correlated with appearance of lesions. For one of the intermediate lines, resistance was shown to be dependent on elevated levels of salicylic acid. A new locus was identified and named IHR1, after the mutant phenotype of "intermediate HR." Genetic analysis of the intermediate-HR plant lines was difficult due to uncertainties in distinguishing the partial/intermediate mutant phenotypes from wild type. Despite this difficulty, the intermediate-HR mutants remain of interest because they reveal potential new defense-related loci and because many of these lines exhibit partially elevated disease resistance without dwarfing or other apparent growth defects. PMID:10707353

Yu, I; Fengler, K A; Clough, S J; Bent, A F

2000-03-01

21

Plant amphipathic proteins delay the hypersensitive response caused by harpin Pssand Pseudomonas syringae pv. syringae  

Microsoft Academic Search

HarpinPssfrom the plant pathogenPseudomonas syringaepv.syringaeis a proteinaceous elicitor that induces a hypersensitive response (HR) in non-host plants. The plant products which recognize harpinPssin the triggering of the HR are not yet known. According to the elicitor-receptor model, we hypothesize that an exogenous cell membrane receptor infiltrated into the intercellular space will interfere with the interaction between harpinPssand the putative receptor.

H.-J. Lin; H.-Y. Cheng; C.-H. Chen; H.-C. Huang; T.-Y. Feng

1997-01-01

22

Daily micronutrient supplements enhance delayed- hypersensitivity skin test responses in older people14  

Microsoft Academic Search

A placebo-controlled double-blind trial of the effects of daily micronutrien supplements on circulating vitamin and trace metal concentrations and delayed-hypersensitivity skim test (DHST) responses was conducted. Subjects, aged 59-85 y, were randomly assigned o placebo (n = 27) or micronutrient (n = 29) treatment groups. DHST and circulating concentrations of nine micronutrients were measured before and after 6 and 12

John D Bogden; Adrianne Bendich; Francis W Kemp; Kay S Bruening; Joan H Skurnk; Thomas Denny; Herman Baker; Donald B Louria

23

Hypersensitivity Vasculitis  

MedlinePLUS

Hypersensitivity Vasculitis joseph July 18, 2012 No Comments What is Hypersensitivity vasculitis? Hypersensitivity vasculitis (HV) is often used to ... blood vessels, called a leukocytoclastic vasculitis. What causes Hypersensitivity vasculitis? HV may be caused by a specific ...

24

Colostrinin Decreases Hypersensitivity and Allergic Responses to Common Allergens  

Microsoft Academic Search

Background: Colostrinin™ (CLN), isolated from mothers’ pre-milk fluid (colostrum), is a uniform mixture of low-molecular-weight, proline-rich polypeptides. CLN induces neurite outgrowth of pheochromocytoma cells, extends the lifespan of diploid fibroblast cells, inhibits ?-amyloid-induced apoptosis and improves cognitive functions when administered to Alzheimer’s disease patients. Objective: The aim of this study was to investigate potential allergic responses to CLN and its

Istvan Boldogh; Leopoldo Aguilera-Aguirre; Attila Bacsi; Barun K. Choudhury; Alfredo Saavedra-Molina; Marian Kruzel

2008-01-01

25

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

SciTech Connect

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

La Rosa, M.; Mancuso, G.R.; Greco, D.; Di Paola, M.; Schiliro, G.; Bagnato, G.F.; Bellanti, J.A. (Department of Pediatrics, University of Catania (Italy))

1991-06-01

26

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

PubMed

Ralstonia solanacearum is a Gram-negative soil-borne bacterium that causes bacterial wilt disease in more than 200 plant species, including economically important Solanaceae species. In R.?solanacearum, the hypersensitive response and pathogenicity (Hrp) type III secretion system is required for both the ability to induce the hypersensitive response (HR) in nonhost plants and pathogenicity in host plants. Recently, 72 effector genes, called rip (Ralstonia protein injected into plant cells), have been identified in R.?solanacearum?RS1000. RS1002, a spontaneous nalixidic acid-resistant derivative of RS1000, induced strong HR in the nonhost wild eggplant Solanum torvum in an Hrp-dependent manner. An Agrobacterium-mediated transient expression system revealed that Rip36, a putative Zn-dependent protease effector of R.?solanacearum, induced HR in S.?torvum. A mutation in the putative Zn-binding motif (E149A) completely abolished the ability to induce HR. In agreement with this result, the RS1002-derived ?rip36 and rip36E149A mutants lost the ability to induce HR in S.?torvum. An E149A mutation had no effect on the translocation of Rip36 into plant cells. These results indicate that Rip36 is an avirulent factor that induces HR in S.?torvum and that a putative Zn-dependent protease motif is essential for this activity. PMID:24745046

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

2014-04-01

27

Conjunctival immediate hypersensitivity: re-evaluation of histamine involvement in the vasopermeability response.  

PubMed

The recent development of a technique for quantitative measurement of conjunctival microvascular permeability has permitted detailed pharmacological evaluation of H1- and H2-receptor involvement in histamine-induced increases in conjunctival microvascular permeability and the role of histamine in microvascular permeability changes associated with immediate hypersensitivity responses in the conjunctiva. The conjunctival microvascular permeability response to histamine appears to be entirely mediated by H1-receptors. Pyrilamine (H1-receptor antagonist) virtually abolished the increase in conjunctival extravascular albumin content produced by graded doses of histamine, whereas cimetidine (H2-receptor antagonist) was ineffective. Moreover, selective histamine H2-receptor agonists did not elicit a dose-dependent vasopermeability response in the conjunctiva. Although H1-receptor blockade essentially abolished the microvascular permeability response to histamine, it only partially attenuated the conjunctival microvascular permeability response associated with immediate hypersensitivity and compound 48-80. It appears that conjunctival inflammation caused by mast cell degranulation comprises both a histaminergic and a nonhistaminergic component. PMID:2934347

Woodward, D F; Ledgard, S E; Nieves, A L

1986-01-01

28

ASK1 promotes the contact hypersensitivity response through IL-17 production  

PubMed Central

Contact hypersensitivity (CHS) is a form of delayed-type hypersensitivity triggered by the response to reactive haptens (sensitization) and subsequent challenge (elicitation). Here, we show that ASK1 promotes CHS and that suppression of ASK1 during the elicitation phase is sufficient to attenuate CHS. ASK1 knockout (KO) mice exhibited impaired 2,4-dinitrofluorobenzene (DNFB)-induced CHS. The suppression of ASK1 activity during the elicitation phase through a chemical genetic approach or a specific inhibitory compound significantly reduced the CHS response to a level similar to that observed in ASK1 KO mice. The reduced response was concomitant with the strong inhibition of production of IL-17, a cytokine that plays an important role in CHS and other inflammatory diseases, from sensitized lymph node cells. These results suggest that ASK1 is relevant to the overall CHS response during the elicitation phase and that ASK1 may be a promising therapeutic target for allergic contact dermatitis and other IL-17-related inflammatory diseases.

Mizukami, Junya; Sato, Takehiro; Camps, Montserrat; Ji, Hong; Rueckle, Thomas; Swinnen, Dominique; Tsuboi, Ryoji; Takeda, Kohsuke; Ichijo, Hidenori

2014-01-01

29

ASK1 promotes the contact hypersensitivity response through IL-17 production.  

PubMed

Contact hypersensitivity (CHS) is a form of delayed-type hypersensitivity triggered by the response to reactive haptens (sensitization) and subsequent challenge (elicitation). Here, we show that ASK1 promotes CHS and that suppression of ASK1 during the elicitation phase is sufficient to attenuate CHS. ASK1 knockout (KO) mice exhibited impaired 2,4-dinitrofluorobenzene (DNFB)-induced CHS. The suppression of ASK1 activity during the elicitation phase through a chemical genetic approach or a specific inhibitory compound significantly reduced the CHS response to a level similar to that observed in ASK1 KO mice. The reduced response was concomitant with the strong inhibition of production of IL-17, a cytokine that plays an important role in CHS and other inflammatory diseases, from sensitized lymph node cells. These results suggest that ASK1 is relevant to the overall CHS response during the elicitation phase and that ASK1 may be a promising therapeutic target for allergic contact dermatitis and other IL-17-related inflammatory diseases. PMID:24736726

Mizukami, Junya; Sato, Takehiro; Camps, Montserrat; Ji, Hong; Rueckle, Thomas; Swinnen, Dominique; Tsuboi, Ryoji; Takeda, Kohsuke; Ichijo, Hidenori

2014-01-01

30

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

PubMed Central

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.

Rodamilans, Bernardo; San Leon, David; Muhlberger, Louisa; Candresse, Thierry; Neumuller, Michael; Oliveros, Juan Carlos; Garcia, Juan Antonio

2014-01-01

31

Suppressed fever and hypersensitivity responses in chicks prenatally exposed to opiates.  

PubMed

We have established procedures to reliably induce opiate dependence in the chick embryo via in ovo injection, early in embryonic development, of the long-acting and potent opiate N-desmethyl-l-alpha-noracetylmethadol (NLAAM). Prior studies found that there is continual exposure to NLAAM throughout embryogenesis and shortly after hatching there are signs of spontaneous withdrawal. In the present study, we used three doses of NLAAM (2.5, 5, and 10 mg/kg egg weight) to determine if prenatal opiate exposure followed by postnatal withdrawal interfered with appropriate neural-endocrine-immune interactions in the young chick. To ensure that effects were not a consequence of inappropriately large doses, we first examined acute and chronic toxicity and additional characteristics of postnatal opiate withdrawal. We then measured the corticosterone and fever responses to LPS stimulation during the withdrawal period. After the conclusion of opiate withdrawal, we assessed the hypersensitivity response to phytohemagglutinin (PHA). The fever response to LPS and the hypersensitivity response to PHA were suppressed by prenatal opiate exposure and postnatal withdrawal. The corticosterone response to LPS was not affected, but there were exaggerated corticosterone responses to saline injection in chicks exposed in ovo to NLAAM. It was unlikely that the effects of prenatal NLAAM were the result of toxicity, as little chronic toxicity was seen with the lower two doses of NLAAM, doses that yielded significant suppressions of neural-endocrine-immune responses. However, effects found in the chicks treated with 10 mg NLAAM/kg may have been partly related to the greater toxicity and/or protracted postnatal withdrawal in this group. PMID:15331122

Schrott, Lisa M; Sparber, Sheldon B

2004-11-01

32

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

PubMed

Intradermal tests were carried out on 18 horses with clinical signs of Culicoides hypersensitivity (CHS) and 23 horses without clinical signs of CHS, and sera from these horses were analysed by SDS-PAGE and Western blotting (W-B). Intradermal injections of 0.1 ml of 25 microg/microl sterile Culicoides extract, 0.1 ml of 1:10,000 histamine (positive control) and 0.1 ml of physiological saline (negative control) were made in the dermis of the middle region of the neck. Analysis of reactions indicated that a 1 cm wheal and a skinfold thickness >10% at 24 h represented a valid cut-off between horses with and without CHS. In these conditions the test, even in winter when clinical signs were absent, had 100% sensitivity and specificity. The W-B was performed after running Culicoides extract on a 12% polyacrylamide gel. The test revealed the presence of several bands with molecular weight ranging from 6 to 200 kDa. In particular, a band of 65 kDa was predominantly found in hypersensitive horses by using an anti-IgE antibody while in normal horses the same band was mainly detected by using an anti-IgG antibody. Our results demonstrated that the skin test is a valid diagnostic test, with high sensitivity and specificity and that the band of about 65 kDa probably corresponds to the allergen involved in the pathogenesis of CHS. PMID:16411906

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

2006-02-01

33

Harpin, a hypersensitive response elicitor from Erwinia amylovora, regulates ion channel activities in Arabidopsis thaliana suspension cells  

Microsoft Academic Search

HrpN, the hypersensitive response elicitor from Erwinia amylovora, stimulated K+ outward rectifying currents in Arabidopsis thaliana suspension cells. It also decreased anion currents. These data demonstrate the ability of harpin to regulate different plasma membrane ion channels, putative components of signal transduction chains leading to defense responses and programmed cell death.

Hayat El-Maarouf; Marie Anne Barny; Jean Pierre Rona; François Bouteau

2001-01-01

34

Delayed hypersensitivity to Staphylococcus aureus in mice: in vivo responses to isolated Staphylococcal antigens.  

PubMed Central

The development of delayed hypersensitivity (DH) to Staphylococcus aureus in Swiss mice was evaluated by the footpad (FP) assay. In order to determine which component of the bacteria was responsible for the in vivo immune reactivity, purified Staphylococcal cell wall, cell membrane, protein A, lipoteichoic acid, teichoic acid, as well as lipid-free membrane proteins were isolated. The immune responses of mice receiving one to eight S. aureus injections indicated that the first DH peak, following three injections, was primarily dependent upon protein antigens associated with the bacterial membrane. Increased bacterial injections gave rise to a second DH peak following seven injections which was dependent upon multiple bacterial components including cell wall, protein A, and membrane proteins. Images Figure 1

Bolen, J B; Tribble, J L

1979-01-01

35

Retrospective study of clinical observations on insect hypersensitivity and response to immunotherapy in allergic dogs.  

PubMed Central

A retrospective study was conducted to evaluate the importance of insect hypersensitivity in atopic dogs in the northeastern United States. Fifty (63%) of 79 dogs tested with 7 insect allergens, other than flea, had positive reactions to one or more insects. No dog had positive reactions to insects only. Forty-four dogs underwent immunotherapy. Thirty-one had insect antigens in their prescription mixture and 13 had only conventional environmental allergens. There was no statistical difference in the response rate between the 2 groups. Thus, testing with insect allergens did not decrease the number of dogs with negative skin tests, and including insect allergens in immunotherapy mixtures did not improve the response rate.

Rothstein, E; Miller, W H; Scott, D W; Mohammed, H O

2001-01-01

36

Essential Role of Lymph Nodes in Contact Hypersensitivity Revealed in Lymphotoxin ? -deficient Mice  

Microsoft Academic Search

Lymph nodes (LNs) are important sentinal organs, populated by circulating lymphocytes and antigen-bearing cells exiting the tissue beds. Although cellular and humoral immune responses are induced in LNs by antigenic challenge, it is not known if LNs are essential for acquired im- munity. We examined immune responses in mice that lack LNs due to genetic deletion of lymphotoxin ligands or

Paul D. Rennert; Paula S. Hochman; Richard A. Flavell; David D. Chaplin; Sundararajan Jayaraman; Jeffrey L. Browning

37

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

SciTech Connect

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.

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

38

RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents.  

PubMed

Genetic mutation and pharmacological inhibition of Bruton's tyrosine kinase (Btk) both have been shown to prevent the development of collagen-induced arthritis (CIA) in mice, providing a rationale for the development of Btk inhibitors for treating rheumatoid arthritis (RA). In the present study, we characterized a novel Btk inhibitor, 6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one (RN486), in vitro and in rodent models of immune hypersensitivity and arthritis. We demonstrated that RN486 not only potently and selectively inhibited the Btk enzyme, but also displayed functional activities in human cell-based assays in multiple cell types, blocking Fc? receptor cross-linking-induced degranulation in mast cells (IC(50) = 2.9 nM), Fc? receptor engagement-mediated tumor necrosis factor ? production in monocytes (IC(50) = 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC(50) = 21.0 nM). RN486 displayed similar functional activities in rodent models, effectively preventing type I and type III hypersensitivity responses. More importantly, RN486 produced robust anti-inflammatory and bone-protective effects in mouse CIA and rat adjuvant-induced arthritis (AIA) models. In the AIA model, RN486 inhibited both joint and systemic inflammation either alone or in combination with methotrexate, reducing both paw swelling and inflammatory markers in the blood. Together, our findings not only demonstrate that Btk plays an essential and conserved role in regulating immunoreceptor-mediated immune responses in both humans and rodents, but also provide evidence and mechanistic insights to support the development of selective Btk inhibitors as small-molecule disease-modifying drugs for RA and potentially other autoimmune diseases. PMID:22228807

Xu, Daigen; Kim, Yong; Postelnek, Jennifer; Vu, Minh Diem; Hu, Dong-Qing; Liao, Cheng; Bradshaw, Mike; Hsu, Jonathan; Zhang, Jun; Pashine, Achal; Srinivasan, Dinesh; Woods, John; Levin, Anita; O'Mahony, Alison; Owens, Timothy D; Lou, Yan; Hill, Ronald J; Narula, Satwant; DeMartino, Julie; Fine, Jay S

2012-04-01

39

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

PubMed

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. PMID:24594386

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

2014-08-01

40

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

PubMed Central

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

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

2001-01-01

41

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

PubMed Central

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.

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

42

Effects of gliotoxin on Langerhans' cell function: contact hypersensitivity responses and skin graft survival.  

PubMed Central

Dendritic Langerhans' cells (LC), which are essential for the induction of cutaneous immunity, express high concentrations of class II major histocompatibility (MHC) glycoproteins (Ia in the mouse) on their plasma membrane. Application of gliotoxin, a member of the epipolythiodoxopiperazine (ETP) group of fungal metabolites, reduces epidermal LC density and alters their morphology from highly dendritic to a more rounded form. Here we demonstrate that gliotoxin also alters LC function, reducing contact hypersensitivity (CHS) responses due to the development of suppressor cells, and enhancing C57BL tail skin graft survival on BALB/c recipients. The reduction in LC density following gliotoxin application was shown to enhance skin graft survival, by reducing the concentration of Ia antigens within the graft, by using congenic mouse strains: B10.A(2R) x B10.A, differing only at H-2D, and B10.A(2R) x B10.A(4R), differing only at H-2 I-E. Treatment of B10.A(2R) tail skin with gliotoxin for 1 week did not affect its survival when grafted onto H-2D-disparate B10.A mice, whereas, when grafted onto H-2 I-E-disparate B10.A(4R) hosts, the grafts were not only accepted permanently, but induced specific unresponsiveness. It is concluded that gliotoxin has a marked effect on LC function, inhibiting CHS responses by the induction of suppressor cells and prolonging graft survival between H-2-disparate and congenic mouse strains.

McMinn, P C; Halliday, G M; Muller, H K

1990-01-01

43

Delayed hypersensitivity to Staphylococcus aureus in mice: in vitro responses to isolated Staphylococcal antigens  

PubMed Central

Isolated Staphylococcal cellular components were used to evaluate the in vitro reactivity of lymphocytes from mice with delayed hypersensitivity to Staphylococcus aureus. Macrophage migration inhibition studies showed that splenic lymphocytes from mice sensitized with three injections of S. aureus inhibited macrophage migration when stimulated with S. aureus sonicate antigen (SASA), cell membrane (CM), and purified membrane protein (PMP). Continued injections (seven) resulted in migration inhibition when the sensitized cells were reacted with SASA, CM, PMP, cell wall (CW), and protein A (PA). Lymphocyte stimulation studies following three injections further illustrated the role of membrane proteins in the early phase of mouse reactivity. Splenic lymphocytes were maximally stimulated by SASA, CM, and PMP. Lipoteichoic acid (LTA), teichoic acid (TA), and CW also were stimulatory but to a much lesser degree. Mice receiving seven S. aureus injections had a high basal stimulatory response which overshadowed the responses to the isolated staphylococcal components. All of the staphylococcal components except LTA were mitogenic for splenic B lymphocytes. The mitogenicity was dependent upon the presence of macrophages. Only SASA, CM, and PMP were mitogenic for non-enriched splenic lymphocytes.

Tribble, J. L.; Bolen, J. B.

1979-01-01

44

Hypersensitive response to Aphis gossypii Glover in melon genotypes carrying the Vat gene.  

PubMed

Aphis gossypii Glover causes direct and indirect damage to Cucumis melo L. crops. To decrease the harmful effects of this pest, one of the most economically and environmentally acceptable options is to use genetically resistant melon varieties. To date, several sources of resistance carrying the Vat gene are used in melon breeding programmes that aim to prevent A. gossypii colonization and the subsequent aphid virus transmission. The results suggest that the resistance conferred by this gene is associated with a microscopic hypersensitive response specific against A. gossypii. Soon after aphid infestation, phenol synthesis, deposits of callose and lignin in the cell walls, damage to the plasmalemma, and a micro-oxidative burst were detected in genotypes carrying the Vat gene. According to electrical penetration graph experiments, this response seems to occur after aphid stylets puncture the plant cells and not during intercellular stylet penetration. This type of plant tissue reaction was not detected in melon plants infested with Bemisia tabaci Gennadius nor Myzus persicae Sulzer. PMID:19474089

Villada, Emilio Sarria; González, Elisa Garzo; López-Sesé, Ana Isabel; Castiel, Alberto Fereres; Gómez-Guillamón, María Luisa

2009-01-01

45

Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs  

Microsoft Academic Search

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti-inflammatory and anti-hyperalgesic properties. The main objective of the present study was to evaluate the effects of PEA on the cutaneous allergic inflammatory reaction induced by different immunological and non-immunological stimuli in hypersensitive dogs. Six spontaneously Ascaris hypersensitive Beagle dogs were challenged with intradermal injections of Ascaris suum extract, substance P and

Santiago Cerrato; Pilar Brazis; Maria Federica della Valle; Alda Miolo; Stefania Petrosino; Vincenzo Di Marzo; Anna Puigdemont

46

Nitrate Efflux Is an Essential Component of the Cryptogein Signaling Pathway Leading to Defense Responses and Hypersensitive Cell Death in Tobacco  

PubMed Central

There is much interest in the transduction pathways by which avirulent pathogens or derived elicitors activate plant defense responses. However, little is known about anion channel functions in this process. The aim of this study was to reveal the contribution of anion channels in the defense response triggered in tobacco by the elicitor cryptogein. Cryptogein induced a fast nitrate (NO3?) efflux that was sensitive to anion channel blockers and regulated by phosphorylation events and Ca2+ influx. Using a pharmacological approach, we provide evidence that NO3? efflux acts upstream of the cryptogein-induced oxidative burst and a 40-kD protein kinase whose activation seems to be controlled by the duration and intensity of anion efflux. Moreover, NO3? efflux inhibitors reduced and delayed the hypersensitive cell death triggered by cryptogein in tobacco plants. This was accompanied by a delay or a complete suppression of the induction of several defense-related genes, including hsr203J, a gene whose expression is correlated strongly with programmed cell death in plants. Our results indicate that anion channels are involved intimately in mediating defense responses and hypersensitive cell death.

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

2002-01-01

47

Nerve Growth Factor, Neuropeptides, and Mast Cells in Ultraviolet-B-Induced Systemic Suppression of Contact Hypersensitivity Responses in Mice  

Microsoft Academic Search

The induction of systemic immunosuppression following ultraviolet B radiation exposure has been linked with the release of inflammatory and immunomodulatory mediators by cells of the epidermis and dermis. Nerve growth factor has not previously been linked with ultraviolet-B-induced immunosuppressive effects. Nerve growth factor antibodies abrogated ultraviolet-B-induced systemic suppression of contact hypersensitivity responses in BALB\\/C mice. Subcutaneous injection of nerve growth

Scott L. Townley; Michele A. Grimbaldeston; Ian Ferguson; Robert A. Rush; Shu-Hua Zhang; Xin-Fu Zhou; James M. Conner; John J. Finlay-Jones; Prue H. Hart

2002-01-01

48

Structural basis of metal hypersensitivity  

PubMed Central

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

Wang, Yang

2014-01-01

49

Diclofenac Hypersensitivity: Antibody Responses to the Parent Drug and Relevant Metabolites  

PubMed Central

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

Harrer, Andrea; Lang, Roland; Grims, Robert; Braitsch, Michaela; Hawranek, Thomas; Aberer, Werner; Vogel, Lothar; Schmid, Walther; Ferreira, Fatima; Himly, Martin

2010-01-01

50

Delayed-type hypersensitivity responses regulate collagen deposition in the lung.  

PubMed Central

A previous report showed that hamsters immunized by epicutaneous application of 2,4,6-trinitrochloro-1-benzene (TNCB) were susceptible to the development of pulmonary interstitial fibrosis (PIF) if challenged in the lung with the water-soluble form of this hapten 2,4,6-trinitrobenzene sulphonic acid (TNBS). In this study, we investigated the immunological mechanisms that contributed to increased collagen content in the lungs of hapten-immune hamsters after receiving a pulmonary challenge of the sensitizing hapten trinitrophenol (TNP). In order to evaluate the concept that delayed-type hypersensitivity (DTH) reaction modulated their response to TNP in the lung such that it eventuated into PIF, we compared the cutaneous DTH response (48 hr after challenge) with lung collagen deposition (14 days after challenge) in several lines (strains) of hamsters. The inbred LSH strain, was a high responder in the DTH assay to TNP and developed non-resolving PIF in the hapten-immune animals. This is called hapten-immune pulmonary interstitial fibrosis or HIPIF. We also observed that female LSH hamsters were more susceptible to HIPIF induced by TNP than males. On the other hand, age factors influenced DTH and PIF in random-bred LVG hamsters since young hamsters (3 months old) were low responders to TNP and did not develop PIF in the HIPIF model but matured LVG hamsters (retired breeders) possessed DTH reactivity to TNP and subsequently developed PIF. These results suggest that lung collagen deposition in hapten-immune hamster is regulated by T-lymphocyte-mediated immune inflammation (DTH) in the lung and both are dependent on the ability to develop a cutaneous DTH reaction to the hapten. The elucidation of possible mechanisms of DTH-mediated non-granulomatous, non-resolving PIF is important for understanding of the role of environmental chemicals similar in action to haptens in the mediation of skin and lung diseases.

Kimura, R; Hu, H; Stein-Streilein, J

1992-01-01

51

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

PubMed Central

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

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

2013-01-01

52

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

PubMed Central

Background Hybrid speciation is classified into homoploid and polyploid based on ploidy level. Common wheat is an allohexaploid species that originated from a naturally occurring interploidy cross between tetraploid wheat and diploid wild wheat Aegilops tauschii Coss. Aegilops tauschii provides wide naturally occurring genetic variation. Sometimes its triploid hybrids with tetraploid wheat show the following four types of hybrid growth abnormalities: types II and III hybrid necrosis, hybrid chlorosis, and severe growth abortion. The growth abnormalities in the triploid hybrids could act as postzygotic hybridization barriers to prevent formation of hexaploid wheat. Methodology/Principal Findings Here, we report on the geographical and phylogenetic distribution of Ae. tauschii accessions inducing the hybrid growth abnormalities and showed that they are widely distributed across growth habitats in Ae. tauschii. Molecular and cytological characterization of the type III necrosis phenotype was performed. The hybrid abnormality causing accessions were widely distributed across growth habitats in Ae. tauschii. Transcriptome analysis showed that a number of defense-related genes such as pathogenesis-related genes were highly up-regulated in the type III necrosis lines. Transmission electron microscope observation revealed that cell death occurred accompanied by generation of reactive oxygen species in leaves undergoing type III necrosis. The reduction of photosynthetic activity occurred prior to the appearance of necrotic symptoms on the leaves exhibiting hybrid necrosis. Conclusions/Significance Taking these results together strongly suggests that an autoimmune response might be triggered by intergenomic incompatibility between the tetraploid wheat and Ae. tauschii genomes in type III necrosis, and that genetically programmed cell death could be regarded as a hypersensitive response-like cell death similar to that observed in Arabidopsis intraspecific and Nicotiana interspecific hybrids. Only Ae. tauschii accessions without such inhibiting factors could be candidates for the D-genome donor for the present hexaploid wheat.

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

2010-01-01

53

BcSpl1, a cerato-platanin family protein, contributes to Botrytis cinerea virulence and elicits the hypersensitive response in the host.  

PubMed

Proteins belonging to the cerato-platanin family are small proteins with phytotoxic activity. A member of this family, BcSpl1, is one of the most abundant proteins in the Botrytis cinerea secretome. Expression analysis of the bcspl1 gene revealed that the transcript is present in every condition studied, showing the highest level in planta at the late stages of infection. Expression of a second cerato-platanin gene found in the B. cinerea genome, bcspl2, was not detected in any condition. Two bcspl1 knock-out mutants were generated and both showed reduced virulence in a variety of hosts. • bcspl1 was expressed in Pichia pastoris and the recombinant protein was able to cause a fast and strong necrosis when infiltrated in tomato, tobacco and Arabidopsis leaves, in a dose-dependent manner. The BcSpl1-treated plant tissues showed symptoms of the hypersensitive response such as induction of reactive oxygen species, electrolyte leakage, cytoplasm shrinkage, and cell autofluorescence, as well as the induction of defense genes considered to be markers of the hypersensitive response. The Arabidopsis bak1 mutation partially prevented the induction of necrosis in this plant by BcSpl1. Two different BcSpl1-derived 40-amino acids peptides were also active in inducing necrosis. PMID:21707620

Frías, Marcos; González, Celedonio; Brito, Nélida

2011-10-01

54

Nitric oxide interacts with salicylate to regulate biphasic ethylene production during the hypersensitive response.  

PubMed

C(2)H(4) is associated with plant defense, but its role during the hypersensitive response (HR) remains largely uncharacterized. C(2)H(4) production in tobacco (Nicotiana tabacum) following inoculation with HR-eliciting Pseudomonas syringae pathovars measured by laser photoacoustic detection was biphasic. A first transient rise (C(2)H(4)-I) occurred 1 to 4 h following inoculation with HR-eliciting, disease-forming, and nonpathogenic strains and also with flagellin (flg22). A second (avirulence-dependent) rise, at approximately 6 h (C(2)H(4)-II), was only seen with HR-eliciting strains. Tobacco leaves treated with the C(2)H(4) biosynthesis inhibitor, aminoethoxyvinylglycine, suggested that C(2)H(4) influenced the kinetics of a HR. Challenging salicylate hydroxylase-expressing tobacco lines and tissues exhibiting systemic acquired resistance suggested that C(2)H(4) production was influenced by salicylic acid (SA). Disrupted expression of a C(2)H(4) biosynthesis gene in salicylate hydroxylase tobacco plants implicated transcriptional control as a mechanism through which SA regulates C(2)H(4) production. Treating leaves to increase oxidative stress or injecting with SA initiated monophasic C(2)H(4) generation, but the nitric oxide (NO) donor sodium nitroprusside initiated biphasic rises. To test whether NO influenced biphasic C(2)H(4) production during the HR, the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester was coinoculated with the avirulent strain of P. syringae pv phaseolicola into tobacco leaves. The first transient C(2)H(4) rise appeared to be unaffected by N(G)-nitro-L-arginine methyl ester, but the second rise was reduced. These data suggest that NO and SA are required to generate the biphasic pattern of C(2)H(4) production during the HR and may influence the kinetics of HR formation. PMID:18799663

Mur, Luis A J; Laarhoven, Lucas J J; Harren, Frans J M; Hall, Michael A; Smith, Aileen R

2008-11-01

55

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

SciTech Connect

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.

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

1988-03-01

56

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

SciTech Connect

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

Niederkorn, J.Y.; Callanan, D.; Ross, J.R. (Univ. of Texas Southwestern Medical Center, Dallas (USA))

1990-08-01

57

Metal Hypersensitivity  

Microsoft Academic Search

Metal hypersensitivity leading onto hardware rejection is reported as a rare phenomenon. If not suspected, it can be a harrowing experience for the patient because it can lead to a seemingly never-ending cycle of tests and procedures. This case highlights the fact that although metal hypersensitivity is rare, it should be included in the differential once infection has been excluded.

Ashish Anand; Fred McGlynn; William Jiranek

2009-01-01

58

Increased contact hypersensitivity response in mice by topical application of 1?,25-dihydroxyvitamin D 3 to elicitation site  

Microsoft Academic Search

Recent evidence indicates that the biologically active metabolite of vitamin D3, 1a,25-dihydroxy-vitamin D3 [1a,25(OH)2D3], has an effect on the regulation of the immune response. We investigated whether topical treatment of mice with 1a,25(OH)2D3 influences the contact hypersensitivity (CHS) response to trinitrochlorobenzene (TNCB). 1a,25(OH)2D3 was applied to the dorsal trunk of A\\/J mice on days 0–3, and on day 4 topical

M. Tani; Y. Murata; S. Harada; T. Takashima; T. Horikawa

1989-01-01

59

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

PubMed Central

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

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

60

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

PubMed Central

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

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

2012-01-01

61

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

PubMed Central

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

2012-01-01

62

IL-17 and IFN-? mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses1  

PubMed Central

Hapten induced contact hypersensitivity (CHS) in the skin is a delayed type cellular immune response which can be mediated by CD8+ T cells that produce IFN-? or IL-17. However, mechanisms for these cytokines in the elicitation of CHS remain to be fully elucidated. Here we show that adoptive transfer of CHS with hapten primed wild type CD8+ T cells is reduced in IFN-?R?/? or IL-17R?/? mice compared to wild type controls. The infiltration of granulocytes and macrophages in the hapten challenged skin of IL-17R?/? recipients is significantly reduced whereas it is less affected in IFN-?R?/? recipients although CD8+ T cell infiltration is inhibited in both recipients. In contrast, the activity of reactive oxidative species is significantly inhibited in IFN-?R?/? but is less affected in IL-17R?/? recipients. Further analysis reveals that the expression of chemokines and cytokines is differentially regulated in the hapten challenged skin of IFN-?R?/? or IL-17R?/? recipients compared to wild type controls. Interestingly, injection of recombinant IL-17 in the skin induces inflammation with a high level of leukocyte infiltration whereas injection of IFN-? induces inflammation with a high level of reactive oxidative species. Moreover, neutralization of IL-17 in IFN-?R?/? or IFN-? in IL-17R?/? mice further suppresses the adoptive transfer of CHS by hapten primed wild type CD8+ T cells. The study demonstrates that IFN-? and IL-17 mediate the elicitation of CHS by different mechanisms and that both cytokines are required for optimal responses. This outcome improves understanding of pathogenesis and provides new insights into therapeutic strategies for CHS.

He, Donggou; Wu, Lizhi; Kim, Hee Kyung; Li, Hui; Elmets, Craig A.; Xu, Hui

2011-01-01

63

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

PubMed

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

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

2000-09-01

64

Trends in hypersensitivity drug reactions: more drugs, more response patterns, more heterogeneity.  

PubMed

Hypersensitivity drug reactions (HDRs) vary over time in frequency, drugs involved, and clinical entities. Specific reactions are mediated by IgE, other antibody isotypes (IgG or IgM), and T cells. Nonspecific HDRs include those caused by nonsteroidal anti-inflammatory drugs (NSAIDs). beta-Lactams--the most important of which are amoxicillin and clavulanic acid--are involved in specific immunological mechanisms. Fluoroquinolones (mainly moxifloxacin, followed by ciprofloxacin and levofloxacin) can also induce HDRs mediated by IgE and T cells. In the case of radio contrast media, immediate reactions have decreased, while nonimmediate reactions, mediated by T cells, have increased. There has been a substantial rise in hypersensitivity reactions to antibiotics and latex in perioperative allergic reactions to anesthetics. NSAIDs are the most frequent drugs involved in HDRs. Five well-defined clinical entities, the most common of which is NSAID-induced urticaria/angioedema, have been proposed in a new consensus classification. Biological agents are proteins including antibodies that have been humanized in order to avoid adverse reactions. Reactions can be mediated by IgE or T cells or they may be due to an immunological imbalance. Chimeric antibodies are still in use and may have epitopes that are recognized by the immune system, resulting in allergic reactions. PMID:25011351

Doña, I; Barrionuevo, E; Blanca-Lopez, N; Torres, M J; Fernandez, T D; Mayorga, C; Canto, G; Blanca, M

2014-01-01

65

The immune response to Haemophilus ducreyi resembles a delayed-type hypersensitivity reaction throughout experimental infection of human subjects.  

PubMed

Previous work in 3 subjects infected for 2 weeks indicated that experimental infection with Haemophilus ducreyi recruits CD4 cells to the skin at the pustular stage of disease. In order to describe the kinetics of the host response, 23 subjects were infected at 2 sites with a standardized dose of H. ducreyi. Subjects were biopsied 1 or 4 days after inoculation or when they developed a painful pustular lesion (days 7-14). Papules and pustules contained a predominant T cell infiltrate that consisted of CD45RO and CD4 cells of the alpha beta lineage. Both papules and pustules contained mixed or T helper 1 type cytokine mRNA and interleukin-8 and tumor necrosis factor-alpha mRNA. Although the subjects had no history of chancroid, their immune responses resembled delayed-type hypersensitivity reactions that occurred within 24 h of inoculation and persisted throughout the course of experimental infection. PMID:9815221

Palmer, K L; Schnizlein-Bick, C T; Orazi, A; John, K; Chen, C Y; Hood, A F; Spinola, S M

1998-12-01

66

Hypersensitivity pneumonitis  

PubMed Central

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

Lacasse, Yves; Cormier, Yvon

2006-01-01

67

Oral exposure to drugs with immune-adjuvant potential induces hypersensitivity responses to the reporter antigen TNP-OVA.  

PubMed

Immune-mediated drug hypersensitivity reactions are important causes of black box warnings and drug withdrawals. Despite the high demand for preclinical screening tools, no validated in vitro or in vivo models are available. In the current study, we used a previously described oral administration model using trinitrophenyl-ovalbumin (TNP-OVA) as an antigen to report immuno-adjuvating effects of the analgesic drug acetaminophen (APAP) and its nonhepatotoxic regioisomer 3'-hydroxyacetanilide (AMAP), the antibiotic ofloxacin (OFLX), the antiepileptic drug carbamazepine (CMZ), and the antidiabetic drug metformin (MET). Furthermore, APAP and AMAP were tested in a popliteal lymph node assay (PLNA) combined with TNP-OVA as reporter antigen (RA). C3H/HeOuJ mice were dosed by oral gavage with diclofenac (DF), APAP, AMAP, OFLX, MET, or CMZ. On the first exposure day, the mice received an ip injection with TNP-OVA. Fifteen days later, they were ear challenged with TNP-OVA and delayed-type hypersensitivity (DTH) responses were assessed 24 h later. One week after challenge, the ear-draining lymph node was removed and TNP-specific antibody-secreting cells were determined. DF, APAP, CMZ, and OFLX showed a significant increase in DTH responses to ear injection with TNP-OVA, whereas AMAP and MET did not. C57BL/6 mice were slightly less responsive to APAP and DF after oral gavage, and importantly both AMAP and APAP were negative in the RA-PLNA. The present work shows that the oral exposure model using RA and the RA-PLNA may serve to screen the immune-adjuvant potential of new chemical entities during preclinical drug development. PMID:21402728

Kwast, Lydia M; Fiechter, Daniëlle; Hassing, Ine; Bleumink, Rob; Boon, Louis; Ludwig, Irene S; Pieters, Raymond H H

2011-06-01

68

Silencing of the N family of resistance genes in Nicotiana edwardsonii compromises the hypersensitive response to tombusviruses.  

PubMed

The nontarget effects associated with silencing of the N gene in Nicotiana edwardsonii, an amphidiploid species derived from N. glutinosa and N. clevelandii, have been characterized in this study. The N protein confers resistance to Tobacco mosaic virus (TMV), and is representative of a family of nucleotide-binding site leucine-rich repeat proteins present in N. glutinosa. Previous studies have shown that silencing of the N gene or of other plant genes associated with N-mediated defenses abolishes host resistance to TMV, and this effect can be measured through enhancements in movement or replication of TMV in the N-silenced plants. However, the nontarget effects of gene silencing have not been investigated thoroughly. Notably, are the functions of other resistance (R) genes also affected in experiments designed to silence the N gene? To investigate whether heterologous sequences could silence the N gene, we selected an R gene homolog from N. glutinosa that differed from the N gene by approximately 17%, created a hairpin transgene, and developed transgenic N. edwardsonii plants. Expression of this hairpin in the transgenic N. edwardsonii plants compromised the hypersensitive response to TMV, demonstrating that a single hairpin transgene could silence a block of R genes related by sequence similarity. We then investigated whether the response of N-silenced plants to other viruses would be altered, and found that the hypersensitive response triggered against the tombusviruses Tomato bushy stunt virus and Cymbidium ringspot virus also was compromised. This study indicates that a Tombusvirus R gene shares some homology with the N gene, which could facilitate the cloning of this gene. PMID:17918628

Balaji, Boovaraghan; Cawly, John; Angel, Carlos; Zhang, Zhanyuan; Palanichelvam, Karuppaiah; Cole, Anthony; Schoelz, James

2007-10-01

69

CD8+ IL-17 producing T cells are important in effector functions for the elicitation of contact hypersensitivity responses1  

PubMed Central

Allergen induced contact hypersensitivity (CHS) is a T cell mediated delayed type immune response which has been considered to be primarily mediated by CD8+ Tc1 cells. IFN-?, the prototype Tc1 (Th1) cytokine, has been implicated as the primary inflammatory cytokine for CHS. In this report, we demonstrate that neutralization of IL-17 rather than IFN-? suppresses the elicitation of CHS. The suppression does not result from inhibition of the proliferation of allergen-activated T cells. Allergen sensitization induces the development of distinct CD8+ T cell subpopulations that produce IFN-? or IL-17. While CD8+ IL-17 producing cells are stimulated by IL-23, they are inhibited by IL-12, a prototypical stimulator of IFN-? producing Tc1 cells. This indicates that CD8+ IL-17 producing cells are distinct from Tc1 cells and are important in effector functions at the elicitation of CHS. The studies provide insights into a novel mechanism for CHS.

He, Donggou; Wu, Lizhi; Kim, Hee Kyung; Li, Hui; Elmets, Craig A.; Xu, Hui

2011-01-01

70

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

PubMed Central

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

Raffaele, Sylvain; Vailleau, Fabienne; Leger, Amandine; Joubes, Jerome; Miersch, Otto; Huard, Carine; Blee, Elisabeth; Mongrand, Sebastien; Domergue, Frederic; Roby, Dominique

2008-01-01

71

Role of Network Branching in Eliciting Differential Short-Term Signaling Responses in the Hypersensitive Epidermal Growth Factor Receptor Mutants Implicated in Lung Cancer  

Microsoft Academic Search

We study the effects of EGFR inhibition in wild-type and mutant cell lines upon tyrosine kinase inhibitor TKI treatment through a systems level deterministic and spatially homogeneous model to help characterize the hypersensitive response of the cancer cell lines harboring constitutively active mutant kinases to inhibitor treatment. By introducing a molecularly resolved branched network systems model (the molecular resolution is

Jeremy Purvis; Vibitha Ilango; Ravi Radhakrishnan

2008-01-01

72

Delayed-type hypersensitivity to Phlebotomus papatasi sand fly bite: An adaptive response induced by the fly?  

PubMed Central

The saliva of bloodsucking arthropods contains a large array of pharmacologically active compounds that assist hematophagy. Arthropod saliva is also responsible for causing uncomfortable allergic responses in its vertebrate hosts. In this article, we investigate whether the sand fly Phlebotomus papatasi, known to produce a strong delayed-type hypersensitivity (DTH) in humans, could benefit from, and possibly adaptively induce, this response in their vertebrate hosts. In this study, we show that flies fed on humans to completion nearly twice as fast in DTH sites as compared with normal skin sites. DTH sites had significantly larger blood flow as measured by the laser Doppler method. Sand flies feeding at sites in mouse ears that had a DTH response also fed faster than at normal sites. We conclude that in the case of P. papatasi, and possibly other arthropods such as fleas and bed bugs, the strong saliva-induced DTH response may reflect an adaptation of the fly to manipulate host immunity for the insect's own advantage.

Belkaid, Yasmine; Valenzuela, Jesus G.; Kamhawi, Shaden; Rowton, Edgar; Sacks, David L.; Ribeiro, Jose M. C.

2000-01-01

73

Identification and Characterization of an Arabidopsis Ecotype Which Fails to Mount a Hypersensitive Response When Infiltrated with Pseudomonas Syringae Strains Carrying a Vrrpt2  

Microsoft Academic Search

\\u000a Effective plant defense responses against particular pathogens often involve a one-for-one correspondence between an avirulence\\u000a (avr) gene in the pathogen and a resistance gene in the host [1]. Resistance genes are thought to encode receptors that perceive signals generated by avr genes and these specific recognition events are hypothesized to trigger the host defense response, including the so-called\\u000a hypersensitive response

Michael Mindrinos; Fumiaki Katagiri; Jane Glazebrook; Frederick M. Ausubel

74

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

PubMed

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. PMID:23079112

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

2012-12-01

75

Electromagnetic Hypersensitivity  

Microsoft Academic Search

\\u000a Electromagnetic hypersensitive persons (EHS) attribute their nonspecific health symptoms to environmental electromagnetic\\u000a fields (EMF) of different sources in or outside their homes. In general, causal attribution is not restricted to specific\\u000a EMF frequencies but involves a wide range from extremely low frequencies (ELF) up to radio frequencies (RF) including mobile\\u000a telecommunication microwaves and radar. EHS argue that existing exposure limits

Norbert Leitgeb

76

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

PubMed Central

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.

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

2013-01-01

77

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

PubMed

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

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

2013-01-01

78

Changes in the cytoskeleton accompanying infection-induced nuclear movements and the hypersensitive response in plant cells invaded by rust fungi.  

PubMed

During the infection of cowpea (Vigna unguiculata) by the cowpea rust fungus (Uromyces vignae, race 1 ) the plant nucleus moves towards and away from the invading hypha and eventually moves close to the fungus in the susceptible cultivar while it remains away in two cultivars which subsequently respond by resistance gene-dependent plant cell death (the hypersensitive response, HR). The role of plant cytoskeleton in these responses was investigated by fluorescent microscopy and treatments with anticytoskeletal drugs. Observations of microtubule organization prior to cell death revealed that the sequence of events leading to protoplast collapse differed between the two resistant cultivars, suggesting a possibility of multiple pathways for cellular degradation during the HR. Different fixations produced two different microfilament patterns: a filament network and cables. Microfilament network remained visible even at later stages of cell death. Oryzalin and taxol reduced the incidence of autofluorescence that develops late in the death process, indicating a role of microtubules in the deposition of phenolics by adjacent living cells. Cell death and nuclear movements were not affected by oryzalin and taxol but were inhibited by cytochalasin E, suggesting that the microfilaments are required for the HR. PMID:22507136

Skalamera, D; Heath, M C

1998-10-01

79

Delayed hypersensitivity to Staphylococcus aureus in mice: characterization of a membrane immunogen involved in delayed hypersensitivity.  

PubMed Central

Staphylococcal membrance proteins are potent initiators of delayed hypersensitivity following multiple subcutaneous injections of viable organisms. When the membranes are separated by exclusion chromatography they separate into three distinct fractions, one of which was responsible for the elicitation of footpad (FP) reactivity in sensitized mice. The active immunogen was characterized as a glycoprotein having a molecular weight of approximately 15,600 Daltons, with the peptide and carbohydrate moieties linked by covalent bonding. In vitro spleen cell stimulation and macrophage migration inhibition studies revealed that the active FP fraction was also the immunogen involved in these responses. The immunogenic fraction also had mitogenic properties as evidenced by the stimulation of non-sensitized spleen cells. These data characterize a glycoprotein present in Staphylococcus aureus cell membrane which is both immunogenic and mitogenic and is the principal immunogen responsible for the early delayed hypersensitivity response. Images Figure 2

Bolen, J B; Tribble, J L

1981-01-01

80

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

PubMed Central

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.

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

2006-01-01

81

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

PubMed

Law students show significant deficits in emotional and physical well-being compared with groups of students in other areas of higher education. Furthermore, evidence suggests that these effects may be worse for women than for men. The use of active coping can positively affect immunity under stress, but this may be most true for men in the context of law school. The current study examined the delayed-type hypersensitivity (DTH) skin responses of first-year law students (n=121) and a comparison group (n=30). Students' health behaviors, self-evaluative emotions, and coping strategies were also reported. Male law students had larger DTH responses than females, but this gender effect was not present in the comparison group. Endorsement of perseverance under stress (n=19), an active coping strategy, moderated the gender effect on immunity. Perseverance associated with larger DTH responses and more positive self-evaluative emotion, but only among men. These results indicate that active coping may be less efficacious for women than for men in law school, which in turn may limit women's opportunities to attenuate negative effects of law school. PMID:19162169

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

2009-07-01

82

Suppression of Urushiol-Induced Delayed-Type Hypersensitivity Responses in Mice with Serum IgG Immunoglobulin form Human Hyposensitized Donors  

Microsoft Academic Search

Serum IgG immunoglobulin fractions from human subjects hyposensitized to poison ivy\\/oak by oral administration of urushiol suppressed the induction of delayed-type hypersensitivity (DTH) responses in mice to this hapten. This suppressive activity was hapten specific because it did not modify DTH responses to dinitrofluorobenzene (DNFB). Absorption of human serum with lymph node cells from urushiol- sensitized but not DNFB-sensitized mice

Jean-Luc Stampf; Neal Castagnoli; William Epstein; Robert W. Baldwin; Vera Byers

1990-01-01

83

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

PubMed

The use of drug eluting stents constitutes a major breakthrough in current interventional cardiology because it is more than halves the need of repeat interventions. It is incontrovertible that coronary stents, in general, have been beneficial for the vast majority of patients. A small increase in thrombosis, following DES implantation, is offset by a diminished risk of complications associated with repeat vascularization. However, late and, especially, very late stent thrombosis is a much feared complication because it is associated with myocardial infarction with increased mortality. Despite that stent thrombosis is thought to be multifactorial, so far clinical reports and reported pathology findings in patients died from coronary stent thrombosis as well as animal studies and experiments, point toward a hypersensitivity inflammation. The stented and thrombotic areas are infiltrated by interacting, via bidirectional stimuli inflammatory cells including eosinophils, macrophages, T-cells and mast cells. Stented regions constitute an ideal surrounding for endothelial damage and dysfunction, together with hemorheologic changes and turbulence as well as platelet dysfunction, coagulation and fibrinolytic disturbances. Drug eluting stent components include the metal strut which contains nickel, chromium, manganese, titanium, molybdenum, the polymer coating and the impregnated drugs which for the first generation stents are: the antimicrotubule antineoplastic agent paclitaxel and the anti-inflammatory, immunosuppressive and antiproliferative agent sirolimus. The newer stents which are called cobalt-chromiun stents and elute the sirolimus analogs everolimus and zotarolimus both contain nickel and other metals. All these components constitute an antigenic complex inside the coronary arteries which apply chronic, continuous, repetitive and persistent inflammatory action capable to induced Kounis syndrome and stent thrombosis. Allergic inflammation goes through three phases, the early phase, the late phase and the chronic phase and these three phases correspond temporally with early (acute and sub acute), late and very late stent thrombosis. Bioabsorbable allergy free poly lactic acid self expanding stents, nickel free stainless steel materials, stent coverage with nitric oxide donors and antibodies with endothelial progenitor cell capturing abilities as well as stents eluting anti-inflammatory and anti-allergic agents might be the solution of this so feared and devastating stent complication. PMID:21700348

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

2012-04-19

84

Suppression of the delayed-type hypersensitivity and cell-mediated immune responses to Listeria monocytogenes induced by Pseudomonas aeruginosa.  

PubMed Central

Pseudomonas aeruginosa-mediated suppression of the immune response to Listeria monocytogenes was investigated in mice. Because delayed-type hypersensitivity (DTH) footpad swelling to L. monocytogenes was suppressed equally in lipopolysaccharide-responsive and -hyporesponsive mouse strains, the lipopolysaccharide component of P. aeruginosa could not have been the suppressive agent. Mucoid P. aeruginosa cells were no more suppressive than their nonmucoid revertants; therefore, mucoid coating was not an additional immunosuppressive element. Interleukin-1 and macrophage inhibitory factor production to L. monocytogenes and clearance of L. monocytogenes from mouse spleens were all decreased by prior Pseudomonas infection, indicating that cell-mediated immunity, as well as DTH, was decreased to a sublethal Listeria dose. The timing of Pseudomonas exposure relative to Listeria sensitization was varied. P. aeruginosa injected 24 or 6 h before or at the same time as L. monocytogenes depressed DTH to Listeria challenge 7 days later. Animals treated in this way could not respond to reinfection with L. monocytogenes at 13 days. P. aeruginosa administered to L. monocytogenes-sensitized mice at the time of footpad challenge was suppressive, but these mice responded normally upon reinfection. It appears that P. aeruginosa induced two types of suppression to L. monocytogenes: a transient suppression, affecting DTH challenge but not resensitization, and a longer lasting suppression that did not permit mice exposed to P. aeruginosa at the time of Listeria sensitization to respond to subsequent Listeria exposure.

Blackwood, L L; Lin, T; Rowe, J I

1987-01-01

85

Induction of delayed-type hypersensitivity responses to PPD: dendritic cells in synergy with 5-hydroxytryptamine can substitute for macrophages.  

PubMed Central

We describe the use of 5-hydroxytryptamine (5HT) as an adjuvant in the induction of the delayed-type hypersensitivity (DTH) response to purified protein derivative (PPD). Based upon our previous studies with antigen-pulsed macrophages (M phi), we have shown that both the Day 2 early (2 hr) reaction and the Day 3 (24 hr) reaction are augmented if 5HT is incorporated into the priming injection. Furthermore, we have confirmed that in contrast to M phi, antigen-pulsed dendritic cells (DC) fail to prime the early (2 hr) component of DTH. However, DC do prime the early response if injected along with 5HT. A peripheral 5HT antagonist, ICS 205-930, inhibits both the M phi-mediated and the 5HT/DC-primed reactions. These findings support the hypothesis that DTH reactions require a cascade of both inflammatory and immunological signals, and that in mice vascular permeability mediated via 5HT is important in the early phase of the reaction.

Roberts, D; Katz, D R; Mukherjee, S; Rook, G A

1988-01-01

86

Inhibition of UV-induced uric acid production using allopurinol prevents suppression of the contact hypersensitivity response.  

PubMed

Exposure to solar ultraviolet (UV) radiation suppresses adaptive immune responses. This contributes to skin carcinogenesis but may protect from some autoimmune diseases. However, the molecular changes occurring within UV-exposed skin that precipitate the downstream events leading to immune suppression are not fully understood. Using a combination of in vitro and in vivo mouse models, we have discovered that UV induces significant cutaneous production of immune suppressive uric acid. The ability of UV-induced uric acid to inhibit a contact hypersensitivity response was successfully blocked by the gout-treating drug Allopurinol. Up-regulation of NLRP3 mRNA by UV was also found to be dependent on UV-induced uric acid. This suggested that the target of UV-induced uric acid included proteins involved in the formation and activation of the NLRP3-inflammasome. However, in contrast to NLRP3, the adaptor protein ASC, which is required for formation of the NLRP3-inflammasome, was significantly down-regulated. Furthermore, this down-regulation was not dependent on UV-induced uric acid production because Allopurinol treatment failed to prevent the reduction in ASC. Hence, our results identify uric acid as an important molecule involved in sterile UV-induced inflammation and immune suppression. UV-induced uric acid may therefore offer a unique therapeutic target for preventing and treating skin cancer. PMID:23387472

Leighton, Sarah; Kok, Lai-Fong; Halliday, Gary M; Byrne, Scott N

2013-03-01

87

IL-1 Receptor Signaling Is Required at Multiple Stages of Sensitization and Elicitation of the Contact Hypersensitivity Response  

PubMed Central

Contact hypersensitivity (CHS) is a CD8 T cell-mediated response to hapten skin sensitization and challenge. The points at which IL-1 receptor (IL-1R) signaling is required during this complex, multistep immune response have not been clearly delineated. The role of IL-1R signaling during 2, 4 dinitrofluorobenezene (DNFB) sensitization to induce hapten-specific CD8 effector T cells and in the trafficking of the effector T cells to the DNFB challenge site to elicit the response were investigated using IL-1R deficient mice. DNFB-sensitized IL-1R?/? mice had low CHS responses to hapten challenge that were caused in part by marked decreases in hapten-specific CD8 T cell development to IL-17 and IFN-? producing cells during sensitization. Hapten-primed wild-type CD8 T cell transfer to naïve IL-1R?/? mice did not result in T cell activation in response to hapten challenge indicating a need for IL-1R signaling for the localization and/or activation of the CD8 T cells at the challenge site. Decreased CD8 T cell priming in sensitized IL-1R?/? mice was associated with marked decreases in hapten-presenting dendritic cell migration from the sensitized skin to draining lymph nodes. Transfer of hapten-presenting dendritic cells from wild-type donors to naïve IL-1R?/? mice resulted in decreased numbers of the dendritic cells in the draining lymph nodes and decreased priming of hapten-specific CD8 T cells when compared to dendritic cell transfer to naïve wild-type recipients. These results indicate that IL-1R signaling is required at multiple steps during the course of sensitization and challenge to elicit CHS.

Kish, Danielle D.; Gorbachev, Anton. V.; Fairchild, Robert L.

2011-01-01

88

Endogenous and exogenous elicitors of a hypersensitive response in Gracilaria conferta (Rhodophyta)  

Microsoft Academic Search

Certain forms of oligocellulose and certainbacterially excreted peptides were identified asendogenous and exogenous elicitors, respectively, ofa tip bleaching response in Gracilaria conferta(Schousboe ex Montagne) J. et G. Feldmann. Thehalf-maximal tip bleaching response was observed when31.1 µM cellobiose or 11.6 µM cellotetraosewere present in the growth medium. In contrast, noresponse was detected after exposure to glucose,cellotriose, cellopentaose or maltooligosaccharides.The response was

Florian Weinberger; Michael Friedlander

2000-01-01

89

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

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.

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

2011-01-01

90

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

PubMed Central

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

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

2013-01-01

91

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

PubMed

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

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

1999-06-15

92

Two coiled-coil regions of Xanthomonas oryzae pv. oryzae harpin differ in oligomerization and hypersensitive response induction.  

PubMed

Hpa1(Xoo) (harpin) is a type III secreted protein of the rice blight bacterial pathogen Xanthomonas oryzae pv. oryzae that elicits a hypersensitive response (HR) in nonhost tobacco. Hpa1(Xoo) is predicted to contain two potential coiled-coil (CC) regions, one at the N-terminus with a high probability of formation, and one at the C-terminus with a lower probability of formation. We constructed several CC-equivalent peptides by a chemosynthetic method, and investigated the structure-function of the predicted Hpa1(Xoo) CC regions, using biophysical and biochemical approaches. Both peptides elicited an HR in tobacco. Mutant versions of the N- and C-terminal peptides that were predicted to disrupt or favor CC formation were generated. The resulting altered HR activity and oligomerization indicated that the N-terminal CC region is essential for eliciting HR, but the C-terminus is not. The results also indicate that a 14-residue fragment (LDQLLCQLISALLQ) within the N-terminal CC region is a minimal and independent functional element for HR-induction in tobacco leaves. We propose that HR-induction requires a specific oligomerization of the CC regions of Hpa1(Xoo). PMID:20532949

Ji, Zhaolin; Song, Congfeng; Lu, Xuzhong; Wang, Jinsheng

2011-02-01

93

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

PubMed

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

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

2008-09-01

94

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

PubMed

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

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

2013-03-01

95

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

PubMed Central

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

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

2013-01-01

96

Purification and characterization of two novel hypersensitive response-inducing specific elicitors produced by the cowpea rust fungus.  

PubMed

Two novel elicitor peptides that are produced by the race 1 of the cowpea rust fungus Uromyces vignae and that specifically induce a hypersensitive response (a putative form of programmed cell death) in a resistant cultivar of cowpea (Vigna unguiculata L. Walp) have been purified to homogeneity. Purification steps included gel filtration, anion-exchange chromatography, continuous elution electrophoresis, and reversed-phase C18 high performance liquid chromatography. The relative molecular masses of the peptide elicitors as deduced from Tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 5600 Da (major) and 5800 Da (minor), respectively. Peptide 1 (major) and the minor copurifying peptide (peptide 2) resolved at the final C18 high performance liquid chromatography step. The NH2 terminus of peptide 1 was deblocked with anhydrous trifluoroacetic acid prior to sequencing. However, the NH2 terminus of peptide 2 was free. The acidic and hydrophobic peptides show some homology between themselves but do not show any significant similarity with known proteins. The two specific elicitors may be products of two avirulence genes corresponding to the two genes for resistance in the resistant cultivar. PMID:9020095

D'Silva, I; Heath, M C

1997-02-14

97

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

PubMed Central

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

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

2008-01-01

98

The role of vacuolar processing enzyme (VPE) from Nicotiana benthamiana in the elicitor-triggered hypersensitive response and stomatal closure.  

PubMed

Elicitors/pathogen-associated molecular patterns (PAMPs) trigger the plant immune system, leading to rapid programmed cell death (hypersensitive response, HR) and stomatal closure. Previous reports have shown that the vacuolar processing enzyme (VPE), a cysteine proteinase responsible for the maturation of vacuolar proteins, has caspase-1-like activity and mediates TMV- and mycotoxin-induced cell death. The role of VPE from Nicotiana benthamiana in the response to three elicitors: bacterial harpin, fungal Nep1, and oomycete boehmerin, is described here. Single-silenced (NbVPE1a or NbVPE1b) and dual-silenced (NbVPE1a/1b) N. benthamiana plants were produced by virus-induced gene silencing. Although NbVPE silencing does not affect H(2)O(2) accumulation triggered by boehmerin, harpin, or Nep1, the HR is absent in NbVPE1a- and NbVPE1a/1b-silenced plants treated with harpin alone. However, NbVPE-silenced plants develop a normal HR after boehmerin and Nep1 treatment. These results suggest that harpin-triggered HR is VPE-dependent. Surprisingly, all gene-silenced plants show significantly impaired elicitor-induced stomatal closure and elicitor-promoted nitric oxide (NO) production in guard cells. Dual-silenced plants show increased elicitor-triggered AOS production in guard cells. The accumulation of transcripts associated with defence and cell redox is modified by VPE silencing in elicitor signalling. Overall, these results indicate that VPE from N. benthamiana functions not only in elicitor-induced HR, but also in elicitor-induced stomatal closure, suggesting that VPE may be involved in elicitor-triggered immunity. PMID:20603283

Zhang, Huajian; Dong, Suomeng; Wang, Meifang; Wang, Wei; Song, Wenwen; Dou, Xianying; Zheng, Xiaobo; Zhang, Zhengguang

2010-08-01

99

Langerhans Cells require MyD88-dependent signals for C. albicans response but not for contact hypersensitivity or migration  

PubMed Central

Langerhans cells (LC) are a subset of skin-resident DC that reside in the epidermis as immature DC where they acquire antigen. A key step in the life cycle of LC is their activation into mature DC in response to various stimuli including epicutaneous sensitization with hapten and skin infection with C. albicans. Mature LC migrate to the skin-draining LN where they present antigen to CD4 T cells and modulate the adaptive immune response. LC migration is thought to require the direct action of IL-1? and IL- 18 on LC. In addition, TLR-ligands are present in C. albicans and hapten sensitization produces endogenous TLR-ligands. Both could contribute to LC activation. We generated Langerin-Cre MyD88fl mice in which LC are insensitive to IL-1 family members and most TLR-ligands. LC migration in the steady-state, after hapten sensitization and after infection with C. albicans was unaffected. Contact hypersensitivity in Langerin-Cre MyD88fl mice was similarly unaffected. Interestingly, in response to C. albicans infection these mice displayed reduced proliferation of antigen-specific CD4 T cells and defective Th17 subset differentiation. Surface expression of co-stimulatory molecules was intact on LC but expression of IL-1?, IL-6, and IL-23 was reduced. Thus, sensitivity to MyD88-dependent signals is not required for LC migration but is required for the full activation and function of LC in the setting of fungal infection.

Haley, Krystal; Igyarto, Botond Z.; Ortner, Daniela; Bobr, Aleh; Kashem, Sakeen; Schenten, Dominik; Kaplan, Daniel H.

2012-01-01

100

A single exposure of solar simulated radiation suppresses contact hypersensitivity responses both locally and systemically in humans: quantitative studies with high-frequency ultrasound  

Microsoft Academic Search

Ultraviolet radiation (UVR)-induced suppression of cutaneous cell-mediated immunity plays an important role in the development of photocarcinogenesis in the mouse and a similar role is suspected in humans. Cell-mediated immunity is readily tested in vivo by measuring the contact hypersensitivity (CHS) response to topically applied haptens. CHS in humans is usually determined clinically, with a subjective scoring system. However, these

Deirdre A. Kelly; Susan L. Walker; Jane M. McGregor; Antony R. Young

1998-01-01

101

Nitric oxide and reactive oxygen species do not elicit hypersensitive cell death but induce apoptosis in the adjacent cells during the defense response of oat.  

PubMed

Nitric oxide (NO) acts as a signaling molecule in many cellular responses in plants and animals. Oat plants (Avena sativa L.) evoke the hypersensitive response (HR), which shares morphological and biochemical features with mammalian apoptosis, such as DNA laddering and heterochromatin condensation, in response to the avirulent crown rust fungus (Puccinia coronata f. sp. avenae). We examined the role of NO and reactive oxygen species (ROS) in the initiation of hypersensitive cell death, which is induced by direct contact with the pathogen, and apoptotic cell death in the adjacent cells. Cytofluorimetric analysis using the fluorescent NO probe DAF and the H2O2 probe DCF demonstrated that NO and H2O2 were generated simultaneously in primary leaves at an early stage of the defense response. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) markedly enhanced H2O2 accumulation detected by 3,3-diaminobenzidine staining and DCF, whereas treatment with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) strongly suppressed it. Superoxide dismutase (SOD) increased NO accumulation, suggesting that endogenous NO may modulate the level of H2O2 by interacting with O2- in the HR lesion. Cytological observation showed that administration of cPTIO, SNAP, or SOD had no effect on elicitation of hypersensitive cell death, but clearly reduced heterochromatin condensation in the nearby cells and DNA laddering. These findings indicate that NO and ROS are not essential mediators for the initiation of hypersensitive cell death. However, NO and O2- but not H2O2 are required for the onset of apoptotic cell death in the adjacent cells, where excess NO may exert its anti-apoptotic function by regulating cellular redox state. PMID:15000391

Tada, Yasuomi; Mori, Tomoyo; Shinogi, Takeshi; Yao, Nan; Takahashi, Satsuki; Betsuyaku, Shigeyuki; Sakamoto, Masaru; Park, Pyoyun; Nakayashiki, Hitoshi; Tosa, Yukio; Mayama, Shigeyuki

2004-03-01

102

Ferredoxin from sweet pepper ( Capsicum annuum L.) intensifying harpin pss -mediated hypersensitive response shows an enhanced production of active oxygen species (AOS)  

Microsoft Academic Search

The hypersensitive response (HR) is a form of cell death associated with plant resistance to pathogen infection. Harpinpss, an elicitor from the bacterium Pseudomonas syringae pv. syringae, induces a HR in non-host plants. Previously, we reported an amphipathic protein from sweet pepper interfering with harpinpss-mediated HR. In this report, we isolated and characterized a cDNA clone encoded that amphipathic protein

Badri Venkata Dayakar; Hao-Jan Lin; Cheng-Hsien Chen; Mang-Jye Ger; Bor-Heng Lee; Chia-Hwei Pai; David Chow; Hsiang-En Huang; Shaw-Yhi Hwang; Mei-Chu Chung; Teng-Yung Feng

2003-01-01

103

The Pseudomonas syringae pv. tomato HrpW Protein Has Domains Similar to Harpins and Pectate Lyases and Can Elicit the Plant Hypersensitive Response and Bind to Pectate  

Microsoft Academic Search

The host-specific plant pathogen Pseudomonas syringae elicits the hypersensitive response (HR) in nonhost plants and secretes the HrpZ harpin in culture via the Hrp (type III) secretion system. Previous genetic evidence suggested the existence of another harpin gene in the P. syringae genome. hrpW was found in a region adjacent to the hrp cluster in P. syringae pv. tomato DC3000.

AMY O. CHARKOWSKI; JAMES R. ALFANO; GAIL PRESTON; JING YUAN; SHENG YANG HE; ALAN COLLMER

104

Mutational Analysis of Xanthomonas Harpin HpaG Identifies a Key Functional Region That Elicits the Hypersensitive Response in Nonhost Plants  

Microsoft Academic Search

HpaG is a type III-secreted elicitor protein of Xanthomonas axonopodis pv. glycines. We have determined the critical amino acid residues important for hypersensitive response (HR) elicitation by random and site- directed mutagenesis of HpaG and its homolog XopA. A plasmid clone carrying hpaG was mutagenized by site-directed mutagenesis, hydroxylamine mutagenesis, and error-prone PCR. A total of 52 mutants were obtained,

Jung-Gun Kim; Eunkyung Jeon; Jonghee Oh; Jae Sun Moon; Ingyu Hwang

2004-01-01

105

Domain Swapping and Gene Shuffling Identify Sequences Required for Induction of an Avr-Dependent Hypersensitive Response by the Tomato Cf4 and Cf9 Proteins  

Microsoft Academic Search

The tomato Cf-4 and Cf-9 genes confer resistance to infection by the biotrophic leaf mold pathogen Cladosporium. Their protein products induce a hypersensitive response (HR) upon recognition of the fungus-encoded Avr4 and Avr9 peptides. Cf-4 and Cf-9 share . 91% sequence identity and are distinguished by sequences in their N-terminal domains A and B, their N-terminal leucine-rich repeats (LRRs) in

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

2001-01-01

106

Transforming growth factor-?/Smad3 signalling regulates inflammatory responses in a murine model of contact hypersensitivity  

PubMed Central

Background Transforming growth factor (TGF)-? is an important modulator of immune functions and cellular responses, such as differentiation, proliferation, migration and apoptosis. The Smad proteins, which are intracellular TGF-? signal transducers, mediate most actions of TGF-?. Objectives This study examines the role of Smad3 in a murine model of contact hypersensitivity (CHS). Methods The CHS response to oxazolone was studied in Smad3-deficient mice. The ear swelling response was measured and skin biopsies from oxazolone-sensitized skin areas were obtained for RNA isolation, immunohistochemical analyses and histology. Ear draining lymph nodes were collected for RNA isolation and proliferation tests. Quantitative real-time polymerase chain reaction was used to quantify mRNA expression of cytokines, chemokines and transcription factors. Results The expression of proinflammatory [interleukin (IL)-1?, tumour necrosis factor-?, IL-6], Th2 (IL-4) and Th17 type cytokines (IL-17), as well as regulatory components (TGF-?, Foxp3) increased significantly at the mRNA level in the skin of oxazolone-treated Smad3?/? mice when compared with wild-type controls. The expression of the Th1 type cytokine IFN-? and the chemokines CXCL9 and CXCL10 was, however, unaffected by the lack of Smad3. The number of neutrophils and expression of the chemokines CCL3 and CXCL5, which are both involved in neutrophil recruitment, were increased in mice lacking Smad3. Also Th2 type chemokines CCL24, CCL3 and CXCL5 were increased in the skin of Smad3?/? mice compared with wild-type mice. In the lymph nodes, mRNA of IL-1? and IL-17, but not IL-4, TGF-? or Foxp3, was increased in Smad3?/? mice during the CHS response. Conclusions The lack of intact TGF-? signalling via Smad3 results in an increased proinflammatory, Th2 and Th17 type response in the skin, as well as increased expression of regulatory elements such as TGF-? and Foxp3. Understanding the role of Smad3 in the CHS response may offer treatment and prevention strategies in this often disabling disease.

Anthoni, M; Fyhrquist-Vanni, N; Wolff, H; Alenius, H; Lauerma, A

2008-01-01

107

Glycerol monomycolate, a latent tuberculosis-associated mycobacterial lipid, induces eosinophilic hypersensitivity responses in guinea pigs.  

PubMed

Dynamic changes in the lipid composition of the cell wall occur in pathogenic mycobacteria that are often intended for adaptation to the host environment. Dormant mycobacteria should have evolved efficient maneuvers for cohabitation, allowing the microbes to persist for years within the host. Glycerol monomycolate (GroMM) has been implicated as a specific immune target in human individuals with latent, but not active, tuberculosis, but the in vivo response to GroMM and the relevance of it to latent infection remain poorly understood. Here, we immunized guinea pigs with bacillus Calmette-Guerin (BCG) expressing high levels of GroMM and then, monitored skin reactions at the site of challenge with GroMM-containing liposome. We found that BCG-immunized guinea pigs mounted enhanced skin reactions to GroMM with prominent local infiltration by eosinophils. Consistent with this, GroMM-stimulated lymph node cells upregulated the expression of T helper (Th)2-type cytokines, such as interleukin (IL)-5 and IL-10, that could potentially counteract the microbe-eliminating Th1-type cytokine response. On the basis of these observations, we predict that the host response to GroMM produced by dormant mycobacteria would contribute to their long-term survival in the host. PMID:21575604

Hattori, Yuki; Matsunaga, Isamu; Komori, Takaya; Urakawa, Tetsuo; Nakamura, Takashi; Fujiwara, Nagatoshi; Hiromatsu, Kenji; Harashima, Hideyoshi; Sugita, Masahiko

2011-06-01

108

Avocado hypersensitivity.  

PubMed

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. PMID:8074265

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

1994-07-01

109

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

PubMed

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

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

1990-09-01

110

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

PubMed Central

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

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

2011-01-01

111

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

PubMed Central

Background Programmed cell death (PCD) is a necessary part of the life of multi-cellular organisms. A type of plant PCD is the defensive hypersensitive response (HR) elicited via recognition of a pathogen by host resistance (R) proteins. The lethal, recessive accelerated cell death 11 (acd11) mutant exhibits HR-like accelerated cell death, and cell death execution in acd11 shares genetic requirements for HR execution triggered by one subclass of R proteins. Methodology/Principal Findings To identify genes required for this PCD pathway, we conducted a genetic screen for suppressors of acd11, here called lazarus (laz) mutants. In addition to known suppressors of R protein-mediated HR, we isolated 13 novel complementation groups of dominant and recessive laz mutants. Here we describe laz1, which encodes a protein with a domain of unknown function (DUF300), and demonstrate that LAZ1 contributes to HR PCD conditioned by the Toll/interleukin-1 (TIR)-type R protein RPS4 and by the coiled-coil (CC)-type R protein RPM1. Using a yeast-based topology assay, we also provide evidence that LAZ1 is a six transmembrane protein with structural similarities to the human tumor suppressor TMEM34. Finally, we demonstrate by transient expression of reporter fusions in protoplasts that localization of LAZ1 is distributed between the cytosol, the plasma membrane and FM4–64 stained vesicles. Conclusions/Significance Our findings indicate that LAZ1 functions as a regulator or effector of plant PCD associated with the HR, in addition to its role in acd11-related death. Furthermore, the similar topology of a plant and human DUF300 proteins suggests similar functions in PCD across the eukaryotic kingdoms, although a direct role for TMEM34 in cell death control remains to be established. Finally, the subcellular localization pattern of LAZ1 suggests that it may have transport functions for yet unknown, death-related signaling molecules at the plasma membrane and/or endosomal compartments. In summary, our results validate the utility of the large-scale suppressor screen to identify novel components with functions in plant PCD, which may also have implications for deciphering cell death mechanisms in other organisms.

Malinovsky, Frederikke G.; Brodersen, Peter; Fiil, Berthe Katrine; McKinney, Lea Vig; Thorgrimsen, Stephan; Beck, Martina; Nielsen, H. Bj?rn; Pietra, Stefano; Zipfel, Cyril; Robatzek, Silke; Petersen, Morten; Hofius, Daniel; Mundy, John

2010-01-01

112

De Novo Foliar Transcriptome of Chenopodium amaranticolor and Analysis of Its Gene Expression During Virus-Induced Hypersensitive Response  

PubMed Central

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

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

2012-01-01

113

Early H2O2 Accumulation in Mesophyll Cells Leads to Induction of Glutathione during the Hyper-Sensitive Response in the Barley-Powdery Mildew Interaction1  

PubMed Central

H2O2 production and changes in glutathione, catalase, and peroxidase were followed in whole-leaf extracts from the susceptible (AlgS [Algerian/4* (F14) Man.(S)]; ml-a1 allele) and resistant (AlgR [Algerian/4* (F14) Man.(R)]; Ml-a1 allele) barley (Hordeum vulgare) isolines between 12 and 24 h after inoculation with powdery mildew (Blumeria graminis [DC]. Speer [syn. Erysiphe graminis DC] f.sp hordei Marchal). Localized papilla responses and cell death hypersensitive responses were not observed within the same cell. In hypersensitive response sites, H2O2 accumulation first occurred in the mesophyll underlying the attacked epidermal cell. Subsequently, H2O2 disappeared from the mesophyll and accumulated around attacked epidermal cells. In AlgR, transient glutathione oxidation coincided with H2O2 accumulation in the mesophyll. Subsequently, total foliar glutathione and catalase activities transiently increased in AlgR. These changes, absent from AlgS, preceded inoculation-dependent increases in peroxidase activity that were observed in both AlgR and AlgS at 18 h. An early intercellular signal precedes H2O2, and this elicits anti-oxidant responses in leaves prior to events leading to death of attacked cells.

Vanacker, Helene; Carver, Tim L.W.; Foyer, Christine H.

2000-01-01

114

An autophotographic determination of the active oxygen generation in potato tuber discs during hypersensitive response to fungal infection or elicitor  

Microsoft Academic Search

During the hypersensitive reaction of potato tuber discs following inoculation with an incompatible race of Phytophthora infestans or treatment with the fungal wall elicitor (HWC-elicitor), a chemiluminescence (CL) was autophotographically detected on the tissues-surface by exposing X-ray film for several minutes to the fungal-inoculated or HWC-elicitor treated surface of tuber discs together with luminol. A densitometric analysis of CL on

Yoshio Miura; Hirofumi Yoshioka; Noriyuki Doke

1995-01-01

115

A New Cell Wall Located N-rich Protein is Strongly Induced During the Hypersensitive Response in Glycine Max L  

Microsoft Academic Search

Soybean (Glycine max (L.) Merill, cv. Williams 82) plants and cell cultures respond to avirulent pathogens with a hypersensitive reaction. After inoculation of soybean with Pseudomonas syringae pv. glycinea, carrying the avirulence gene avrA, or zoospores from the fungus Phytophthora sojae Race 1, a resistance-gene-dependent cell death programme is activated. A new gene was identified by differential display of mRNAs

Andrea A. Ludwig; Raimund Tenhaken

2001-01-01

116

Patients with Chest Pain and Occult Gastroesophageal Reflux Demonstrate Visceral Pain Hypersensitivity which may be Partially Responsive to Acid Suppression  

Microsoft Academic Search

OBJECTIVES:Mechanisms of chest pain in gastroesophageal reflux disease (GERD) are poorly understood. The recent demonstration in healthy subjects that lower esophageal acid exposure induces pain hypersensitivity within the nonacid-exposed upper esophagus (secondary allodynia) raises the possibility that an increase in spinal neuronal excitability (i.e., central sensitization) contributes to chest pain in GERD. The aim of this study was to determine

Sanchoy Sarkar; David G. Thompson; Clifford J. Woolf; Anthony R. Hobson; Teri Millane; Qasim Aziz

2004-01-01

117

Immunologic evaluation of ofloxacin hypersensitivity.  

PubMed

Quinolone hypersensitivity, most of which is immediate type, is rare but has increased in recent years. The pathogenic mechanisms underlying immediate reactions are not defined clearly. This study was aimed to observe the clinical characteristics of immediate hypersensitivity to ofloxacin and to investigate the pathogenic mechanism with detection of serum specific IgE to ofloxacin using an enzyme-linked immunoasorbent assay (ELISA). We recruited 5 patients with immediate hypersensitivity reactions to ofloxacin (group I), and as control groups, 5 subjects with ciprofloxacin hypersensitivity (group II) and 20 healthy subjects with no history of drug allergy. Serum specific-IgE to ofloxacin-human serum albumin (HSA) conjugate was detectable in four group I subjects (80%) and three group II subjects (60%). The ELISA inhibition test showed significant inhibition with both ofloxacin-HSA conjugate and free ofloxacin in a dose-dependent manner. As to ciprofloxacin, significant inhibition was noted upon addition of free ciprofloxacin in one subject, while minimal inhibition was noted in the other. We confirmed that an IgE-mediated response is a major pathogenic mechanism of ofloxacin hypersensitivity. Cross reactivity between ofloxacin and ciprofloxacin was noted with individual difference. PMID:23115735

Nam, Young-Hee; Kim, Jeong Eun; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Shin, Yoo Seob; Ye, Young-Min; Park, Hae-Sim

2012-11-01

118

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

PubMed Central

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

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

1998-01-01

119

Plant Innate Immunity Induced by Flagellin Suppresses the Hypersensitive Response in Non-Host Plants Elicited by Pseudomonas syringae pv. averrhoi  

PubMed Central

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 Pta?fliC, PA5?fliC 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 PA5?fliC. PA5?fgt1 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 PA5?fliC 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.

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

2012-01-01

120

Specific and aspecific immune responsiveness in lung cancer patients: cutaneous delayed hypersensitivity reactions to a lung cancer-associated antigen.  

PubMed

The ability of a lung cancer-associated antigen (LCAA) to provoke specific cutaneous delayed-hypersensitivity reactions has been studied on a group of 59 lung cancer patients. Biological activity of LCAA, monitored by skin testing, was demonstrated in 32% (17 of 53) of lung cancer patients, in 48.0% with limited disease, and in 17.2% with extensive disease. All the responders were in the group of normal reactors to standard recall antigens, if three antigens were used (PPDSK-SD, candida). No correlation was found between biological activity of LCAA and level of immunocompetence evaluated by lymphocyte-blastic transformation with PHA and count of rosette E-forming cells. These studies on the capacity to evoke specific DTH reactions in lung-cancer patients will be extended to the use of assays in vitro in the perspective of a more significant evaluation of immunocompetence levels. PMID:6160358

Sega, E; Mottolese, M; Cordiali-Fei, P; Citro, G; Colizza, S; Alcione, A; Di Paola, M

1980-01-01

121

Role of network branching in eliciting differential short-term signaling responses in the hypersensitive epidermal growth factor receptor mutants implicated in lung cancer.  

PubMed

We study the effects of EGFR inhibition in wild-type and mutant cell lines upon tyrosine kinase inhibitor TKI treatment through a systems level deterministic and spatially homogeneous model to help characterize the hypersensitive response of the cancer cell lines harboring constitutively active mutant kinases to inhibitor treatment. By introducing a molecularly resolved branched network systems model (the molecular resolution is introduced for EGFR reactions and interactions in order to distinguish differences in activation between wild-type and mutants), we are able to quantify differences in (1) short-term signaling in downstream ERK and Akt activation, (2) the changes in the cellular inhibition EC50 associated with receptor phosphorylation (i.e., 50% inhibition of receptor phosphorylation in the cellular context), and (3) EC50 for the inhibition of activated downstream markers ERK-(p) and Akt-(p), where (p) denotes phosphorylated, upon treatment with the inhibitors in cell lines carrying both wild-type and mutant forms of the receptor. Using the branched signaling model, we illustrate a possible mechanism for preferential Akt activation in the cell lines harboring the oncogenic mutants of EGFR implicated in non-small-cell lung cancer and the enhanced efficacy of the inhibitor erlotinib especially in ablating the cellular Akt-(p) response. Using a simple phenomenological model to describe the effect of Akt activation on cellular decisions, we discuss how this preferential Akt activation is conducive to cellular oncogene addiction and how its disruption can lead to dramatic apoptotic response and hence remarkable inhibitor efficacies. We also identify key network nodes of our branched signaling model through sensitivity analysis as those rendering the network hypersensitive to enhanced ERK-(p) and Akt-(p); intriguingly, the identified nodes have a strong correlation with species implicated in oncogenic transformations in human cancers as well as in drug resistance mechanisms identified for the inhibitors in non-small-cell lung cancer therapy. PMID:18412405

Purvis, Jeremy; Ilango, Vibitha; Radhakrishnan, Ravi

2008-01-01

122

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

PubMed Central

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

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

2009-01-01

123

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

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

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

2014-05-01

124

Role of the penetration-resistance genes PEN1, PEN2 and PEN3 in the hypersensitive response and race-specific resistance in Arabidopsis thaliana.  

PubMed

Plants are highly capable of recognizing and defending themselves against invading microbes. Adapted plant pathogens secrete effector molecules to suppress the host's immune system. These molecules may be recognized by host-encoded resistance proteins, which then trigger defense in the form of the hypersensitive response (HR) leading to programmed cell death of the host tissue at the infection site. The three proteins PEN1, PEN2 and PEN3 have been found to act as central components in cell wall-based defense against the non-adapted powdery mildew Blumeria graminis fsp. hordei (Bgh). We found that loss of function mutations in any of the three PEN genes cause decreased hypersensitive cell death triggered by recognition of effectors from oomycete and bacterial pathogens in Arabidopsis. There were considerable additive effects of the mutations. The HR induced by recognition of AvrRpm1 was almost completely abolished in the pen2 pen3 and pen1 pen3 double mutants and the loss of cell death could be linked to indole glucosinolate breakdown products. However, the loss of the HR in pen double mutants did not affect the plants' ability to restrict bacterial growth, whereas resistance to avirulent isolates of the oomycete Hyaloperonospora arabidopsidis was strongly compromised. In contrast, the double and triple mutants demonstrated varying degrees of run-away cell death in response to Bgh. Taken together, our results indicate that the three genes PEN1, PEN2 and PEN3 extend in functionality beyond their previously recognized functions in cell wall-based defense against non-host pathogens. PMID:24889055

Johansson, Oskar N; Fantozzi, Elena; Fahlberg, Per; Nilsson, Anders K; Buhot, Nathalie; Tör, Mahmut; Andersson, Mats X

2014-08-01

125

Clinical features of immediate hypersensitivity to isopropylantipyrine.  

PubMed

Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs (NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediate hypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity; and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation tests with IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestations were cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patients showed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. The response time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and cross-intolerant NSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs. PMID:23277879

Hwang, Eui-Kyung; Nam, Young-Hee; Jin, Hyun Jung; Shin, Yoo Seob; Ye, Young-Min; Park, Hae-Sim

2013-01-01

126

Clinical Features of Immediate Hypersensitivity to Isopropylantipyrine  

PubMed Central

Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs (NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediate hypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity; and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation tests with IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestations were cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patients showed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. The response time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and cross-intolerant NSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs.

Hwang, Eui-Kyung; Nam, Young-Hee; Jin, Hyun Jung; Shin, Yoo Seob; Ye, Young-Min

2013-01-01

127

Abrogation of the capacity of delayed-type hypersensitivity responses to alloantigens by intravenous injection of neuraminidase-treated allogeneic cells  

SciTech Connect

BALB/c or C3H/He mice were inoculated i.v. with allogeneic spleen cells untreated or treated with neuraminidase. Appreciable or potent anti-allo-delayed-type hypersensitivity (DTH) responses were observed when mice were inoculated i.v. with untreated allogeneic cells or inoculated i.v. with those cells followed by s.c. immunization with untreated allogeneic cells. In contrast, i.v. inoculation of neuraminidase-treated allogeneic cells (presensitization) not only failed to induce any significant anti-allo-DTH responses but also abolished the capability of the animals to develop DTH responses after s.c. immunization, indicating the tolerance induction. This tolerance was alloantigen-specific, and rapidly inducible and long lasting. The induction of suppressor cell activity was demonstrated in tolerant mice. When spleen cells from such tolerant mice were transferred i.v. into 600 R x-irradiated syngeneic recipient mice alone or together with normal syngeneic spleen cells, these tolerant spleen cells themselves failed to induce DTH responses but did not exhibit suppressive effect on the generation of DTH responses induced by normal spleen cells cotransferred. These results indicate that i.v. administration of neuraminidase-treated allogeneic cells results in the induction of alloantigen-specific tolerance which is not always associated with the induction of suppressor cell activity but rather with the elimination or functional impairment of alloantigen-specific clones.

Sano, S.; Suda, T.; Qian, J.H.; Sato, S.; Ikegami, R.; Hamaoka, T.; Fujiwara, H.

1987-12-01

128

Treating dentin hypersensitivity  

PubMed Central

Background Methods used by dental practitioners to diagnose and treat dentin hypersensitivity are not well documented. The authors conducted a survey of dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) to ascertain the treatment methods they used. Methods Via an Internet survey, the authors collected data regarding methods used for diagnosis and treatment of dentin hypersensitivity from 209 Northwest PRECEDENT dentists. Results The PRECEDENT dentists indicated that they most often used fluoride varnishes and gels, advice regarding toothbrushing and diet, bonding agents, restorative materials and glutaraldehyde/2-hydroxyethyl methacrylate (HEMA) to treat dentin hypersensitivity. They reported that the most successful treatments were fluorides, glutaraldehyde/HEMA, bonding agents, potassium nitrates and restorative treatments; they considered observation, advice regarding toothbrushing and diet and laser therapy to be the least successful. Dentists listed fluorides, calcium phosphates, glutaraldehyde/HEMA and bonding agents as the treatments most desirable for inclusion in a future randomized clinical trial of dental hypersensitivity treatments. Conclusions Dentists rely on patients to assess the severity of dentin hypersensitivity. Modalities for the diagnosis and treatment of hypersensitivity are diverse. Methods used to diagnose and treat dentin hypersensitivity in practice are challenging to justify. Clinical Implications Practitioners should be aware of the diversity of methods available for diagnosing and treating dentin hypersensitivity as they manage the care of their patients with this condition.

Cunha-Cruz, Joana; Wataha, John C.; Zhou, Lingmei; Manning, Walter; Trantow, Michael; Bettendorf, Meishan M.; Heaton, Lisa J.; Berg, Joel

2011-01-01

129

Hypersensitivity to electricity  

Microsoft Academic Search

Those who believe that electric appliances trigger adverse symptoms have coined the label hypersensitivity to electricity. Scientific research has not been able to identify a direct link between electromagnetic fields and symptoms, and no diagnostic criteria exist. Groups with reported hypersensitivity are very heterogeneous. A need exists for an operational working definition and improved characterization of groups. We report an

Lena Hillert; Birgitta Kolmodin Hedman; Erik Söderman; Bengt B Arnetz

1999-01-01

130

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

PubMed

Chromoblastomycosis is a subcutaneous fungal disease caused by dematiaceous fungi, especially by Fonsecaea pedrosoi, regarded as its major causative agent in Brazil. In recent years there has been a decline in the use of skin testing for delayed-type hypersensitivity (DTH) in epidemiological surveys of fungal infections, mainly because of the unpredictability of positive reactions and lack of specificity of the antigens used. The aim of the present study was to assess delayed-type skin tests in guinea pigs experimentally infected with F. pedrosoi using exoantigens prepared from two culture filtrates. Sixteen adult male guinea pigs were inoculated intratesticularly with fungal cells and submitted to sensitivity assays 4 weeks after inoculation. They received an intradermal injection with crude and fractionated antigens from Alviano's and Smith's cultures, and were assessed 24 and 48 h thereafter. Except for one animal, all of them had positive indurations after 48 h. There were no statistical differences between the measurements at 24 and 48 h for each exoantigen used, neither among the induration measurements at 48 h when different preparations were compared. Our results suggest that a delayed-type skin test using antigens produced in synthetic media may be useful for the assessment of primary exposure to chromoblastomycosis. PMID:16830192

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

2006-07-01

131

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

PubMed Central

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-? production, as well as decreased ROR?t 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.

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

2014-01-01

132

Chronic cough hypersensitivity syndrome  

PubMed Central

Chronic cough has been suggested to be due to three conditions, asthma, post nasal drip, and reflux disease. A different paradigm has evolved in which cough is viewed as the primary condition characterised by afferent neuronal hypersensitivity and different aspects of this syndrome are manifest in the different phenotypes of cough. There are several advantages to viewing cough hypersensitivity as the unifying diagnosis; Communication with patients is aided, aetiology is not restricted and therapeutic avenues opened. Cough Hypersensitivity Syndrome is a more applicable label to embrace the clinical manifestations of this disabling disease.

2013-01-01

133

Experimental murine hypersensitivity pneumonitis.  

PubMed

To establish a model of experimental hypersensitivity pneumonitis (EHP) in mice and to examine the influence of genetic background on the pulmonary inflammatory response to Micropolyspora faeni, we determined the responses of C57BL/6, SJL/J, and C3H/HeJ mice to intratracheal (i.t.) injections of M. faeni. Recipient animals received lymph node cells (LNC), peritoneal exudate cells (PEC), and spleen cells (SC) from sensitized mice cultured in vitro with M. faeni. Controls included serum containing anti-M. faeni antibody; uncultured SC from M. faeni-sensitized donors, and M. faeni-cultured SC from ovalbumin (OA)-sensitized donors. Recipients were challenged i.t. with M. faeni or normal saline 48 hr after the cell or serum transfer. We developed a model of EHP in mice. Increasing amounts of i.t. M. faeni were associated with increasing extent of pulmonary inflammation with no difference between the mouse strains. There was substantial increase of the extent of pulmonary abnormalities in the animals receiving cultured SC. The number of transferred cells and the M. faeni concentration correlated with the extent of pulmonary histologic abnormalities. Cultured PEC and LNC could transfer EHP in C3H/HeJ mice only. Serum containing anti-M. faeni antibody, cultured SC from OA-sensitized donors, and noncultured SC from sensitized donors could not transfer EHP. We conclude that it is possible to adoptively transfer EHP. PMID:1873822

Schuyler, M; Gott, K; Haley, P

1991-09-01

134

Preservation of the Delayed-Type Hypersensitivity Response to Alloantigen by Xyloglucans or Oligogalacturonide does not Correlate with the Capacity to Reject Ultraviolet-Induced Skin Tumors in Mice  

Microsoft Academic Search

Chronic exposure to ultraviolet radiation suppresses T cell-mediated immune responses and induces the formation of suppressor T lymphocytes that prevent the rejection of highly antigenic ultraviolet-induced skin cancers in mice. Tamarind seed xyloglucans and pectinic oligogalacturonides prevent suppression of delayed-type hypersensitivity immune responses in mice to Candida albicans and alloantigen caused by a single exposure of ultraviolet radiation. We therefore

Faith M. Strickland; Yan Sun; Alan Darvill; Stefan Eberhard; Markus Pauly; Peter Albersheim

2001-01-01

135

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

Microsoft Academic Search

BACKGROUND: In plants, HIR (Hypersensitive Induced Reaction) proteins, members of the PID (Proliferation, Ion and Death) superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley.

Liang Zhou; Ming-Yan Cheung; Man-Wah Li; Yaping Fu; Zongxiu Sun; Sai-Ming Sun; Hon-Ming Lam

2010-01-01

136

Diabetic acido-ketosis revealing thiamine-responsive megaloblastic anemia.  

PubMed

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder characterized by megaloblastic anemia, diabetes mellitus and progressive sensorineural deafness. We report the cases of two infants, aged 4 and 5 months, hospitalized for diabetic ketoacidosis requiring insulin therapy. Laboratory tests revealed megaloblasic anemia, thrombocytopenia and normal thiamine level. Neurosensorial investigations showed bilateral deafness and ophthalmic involvement. Treatment with oral thiamine normalized hematological disorders and controlled diabetes; however, thiamine therapy had no impact on neurosensorial disorders. PMID:19922902

Bouyahia, O; Ouderni, M; Ben Mansour, F; Matoussi, N; Khaldi, F

2009-12-01

137

Epidemiology and Food Hypersensitivity  

Microsoft Academic Search

Food hypersensitivity (FHS) has attracted much awareness over the last three decades and the general public perceives FHS\\u000a as a major health problem. A revised nomenclature for allergy has recently been published as a position paper by the European\\u000a Academy of Allergology and Clinical Immunology (EAACI) [1]. Generally, hypersensitivity causes objectively reproducible symptoms\\u000a or signs, initiated by exposure to a

Morten Osterballe

138

The putative secreted serine protease Chp-7 is required for full virulence and induction of a nonhost hypersensitive response by Clavibacter michiganensis subsp. sepedonicus.  

PubMed

Molecular biological studies on Clavibacter michiganensis subsp. sepedonicus, the causal agent of bacterial ring rot of potato, have gained greater feasibility due to the recent availability of whole genomic sequences and genetic tools for related taxa. Here, we describe the first report of construction and characterization of a transposon (Tn) mutant library of C. michiganensis subsp. sepedonicus sp. strain R10. Since virulence of R10 in potato has been shown previously to be associated with elicitation of a nonhost hypersensitive response (HR), the mutant library was screened initially for loss of HR in tobacco. The screen identified two HR-negative mutants containing Tn insertions within the same gene, CMS2989 (chp-7), although at distinct locations. chp-7 is one of 11 pat-1 homologs in C. michiganensis subsp. sepedonicus. HR-negative mutants of R10 multiplied to the same extent as wild type in planta but were less virulent in potato. Complementation with chp-7 restored virulence as well as the HR phenotype. Together, these findings demonstrate a role for chp-7 in C. michiganensis subsp. sepedonicus-plant interactions. PMID:19522563

Nissinen, Riitta; Xia, Yunjian; Mattinen, Laura; Ishimaru, Carol A; Knudson, Dennis L; Knudson, Susan E; Metzler, Mary; Pirhonen, Minna

2009-07-01

139

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

PubMed

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. PMID:24882556

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

2014-09-01

140

Pseudomonas corrugata contains a conserved N-acyl homoserine lactone quorum sensing system; its role in tomato pathogenicity and tobacco hypersensitivity response.  

PubMed

Pseudomonas corrugata is a phytopathogenic bacterium, causal agent of tomato pith necrosis, yet it is an ubiquitous bacterium that is part of the microbial community in the soil and in the rhizosphere of different plant species. Although it is a very heterogeneous species, all the strains tested were able to produce short chain acyl homoserine lactone (AHL) quorum sensing signal molecules. The main AHL produced was N-hexanoyl-L-homoserine lactone (C(6)-AHL). An AHL quorum sensing system, designated PcoI/PcoR, was identified and characterized. The role of the quorum sensing system in the expression of a variety of traits was evaluated. Inactivation of pcoI abolished the production of AHLs. The pcoR mutant, but not the pcoI mutant, was impaired in swarming, unable to cause a hypersensitivity response on tobacco and resulted in a reduced tomato pith necrosis phenotype. The pcoI mutant showed a reduced antimicrobial activity against various fungi and bacteria when assayed on King's B medium. These results demonstrate that the AHL quorum sensing in Ps. corrugata regulates traits that contribute to virulence, antimicrobial activity and fitness. This is the first report of genes of Ps. corrugata involved in the disease development and biological control activity. PMID:17537174

Licciardello, Grazia; Bertani, Iris; Steindler, Laura; Bella, Patrizia; Venturi, Vittorio; Catara, Vittoria

2007-08-01

141

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

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

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

1995-01-01

142

Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.  

PubMed

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

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

2004-03-30

143

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

SciTech Connect

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

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

1987-09-01

144

Glucocorticoid hypersensitivity syndrome--a case report.  

PubMed

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. PMID:23757909

Krysiak, R; Okopien, B

2012-11-01

145

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

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. PMID:23581823

Zheng, Desen; Burr, Thomas J

2013-07-01

146

[Cloning and characterization of an harpin-encoding gene from Xanthomonas axonopodis pv. glycines required for hypersensitive response on nonhost plant tobacco].  

PubMed

An hpa1 gene was cloned into an expression vector, pET30a(+), from the genomic DNA of Xanthomonas axonopodis pv. glycines (Xag), the causal agent of soybean bacterial pustule, with degenerated primers by polymerase amplification reaction (PCR). The gene product was extracted from the conjugate (BHR-3) of BL21 (DES) with the recombined vector pHR3 after the engineering strain was induced by IPTG in LB medium. The SDS-PAGE gel showed that the gene product was 15.1kD. The product was heat-stable (10 min at 100 degrees C), protease K sensitive, and able to trigger hypersensitive response (HR) in common tobacco, but was unable to elicit HR in NahG transgenic tobacco in which salicylic acid accumulation was abolished. Moreover, the HR elicitation of the protein in tobacco was dispelled by eukayotic metabolic inhibitors, actinomycin D, cycloheximide and LaCl3. The 402 bp hpa1 gene in this study putatively encoded a 133 ammonia acid protein of which glycine (G) was rich with 21.1%. Sequence comparison indicated that the hpa1 gene and its protein was 51.4% - 93.8% identity with those of Xanthomonas oryzae pv. oryzae and other Xanthomonas species and pathovars. Alignments of harpin proteins of Xanthomonas genus displayed that the glycine-rich region with GGG-GG motif was variable. The comparison also showed that the harpin-encoding gene of Xag (nominated here as hpa1(Xag)) did not possess any similarity with that of Erwinia amylovora, Pseudomonas syringae and Ralstonia solanacearum at nucleotide and protein levels. It is concluded that hpa1(Xag) gene encodes an harpin protein which elicits a typical HR in nonhost tobacco. PMID:16245857

Chen, Gong-You; Zhang, Bing; Wu, Xiao-Min; Zhao, Mei-Qin

2005-08-01

147

A combination of cross correlation and trend analyses reveals that Kawasaki disease is a pollen-induced delayed-type hyper-sensitivity disease.  

PubMed

Based on ecological analyses we proposed in 2003 the relation of Kawasaki Disease (KD) onset causing acute febrile systemic vasculitis, and pollen exposure. This study was aimed at investigating the correlation between pollen release and the change in the numbers of KD patients from 1991 to 2002 in Kanagawa, Japan. Short-term changes in the number of KD patients and medium- to long-term trends were analyzed separately. Short-term changes in the number of KD patients showed a significant positive cross correlation (CC) with 9- to 10-month delay following pollen releases, and a smaller but significant CC with 3- to 4-month delay. Further, a temporal relationship revealed by positive CC distribution showed that pollen release preceded KD development, suggesting that pollen release leads to KD development. A trend in patient numbers was fitted by an exponential curve with the time constant of 0.005494. We hypothesized that the trend was caused by the cumulative effects of pollen exposure for elapsed months on patients who may develop KD. By comparing the time constants of fitted exponential curve for each pollen accumulation period with 0.005494, the exposure period was estimated to be 21.4 months, which explains why approximately 50% of patients developed KD within 24 months from birth. PMID:24599039

Awaya, Akira; Nishimura, Chiaki

2014-03-01

148

A Combination of Cross Correlation and Trend Analyses Reveals that Kawasaki Disease is a Pollen-Induced Delayed-Type Hyper-Sensitivity Disease  

PubMed Central

Based on ecological analyses we proposed in 2003 the relation of Kawasaki Disease (KD) onset causing acute febrile systemic vasculitis, and pollen exposure. This study was aimed at investigating the correlation between pollen release and the change in the numbers of KD patients from 1991 to 2002 in Kanagawa, Japan. Short-term changes in the number of KD patients and medium- to long-term trends were analyzed separately. Short-term changes in the number of KD patients showed a significant positive cross correlation (CC) with 9- to 10-month delay following pollen releases, and a smaller but significant CC with 3- to 4-month delay. Further, a temporal relationship revealed by positive CC distribution showed that pollen release preceded KD development, suggesting that pollen release leads to KD development. A trend in patient numbers was fitted by an exponential curve with the time constant of 0.005494. We hypothesized that the trend was caused by the cumulative effects of pollen exposure for elapsed months on patients who may develop KD. By comparing the time constants of fitted exponential curve for each pollen accumulation period with 0.005494, the exposure period was estimated to be 21.4 months, which explains why approximately 50% of patients developed KD within 24 months from birth.

Awaya, Akira; Nishimura, Chiaki

2014-01-01

149

Food hypersensitivity by inhalation  

Microsoft Academic Search

Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food.

Daniel A Ramirez Jr; Sami L Bahna

2009-01-01

150

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

PubMed Central

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.

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

2012-01-01

151

Systemic tocainide relieves mechanical hypersensitivity and normalizes the responses of hyperexcitable dorsal horn wide-dynamic-range neurons after transient spinal cord ischemia in rats  

Microsoft Academic Search

In the present study we examined the effect of systemic tocainide on sensory hypersensitivity in rats after spinal cord ischemia induced by a photochemical technique. After induction of spinal cord ischemia the rats exhibited a sensory disturbance which was mainly expressed as vocalization to innocuous cutaneous mechanical stimuli (allodynia) in the flank area during the following several days. Tocainide at

J. X. Hao; Y. X. Yu; Å. Seiger; Z. Wiesenfeld-Hallin

1992-01-01

152

Hypersensitivity to Suture Anchors  

PubMed Central

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

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

2013-01-01

153

Hypersensitivity reactions to fluoroquinolones  

Microsoft Academic Search

Fluoroquinolone antibiotics cause immediate and delayed hypersensitivity reactions, and may also affect internal organs and\\u000a circulating blood cells. The underlying pathomechanisms are only partly understood. The extent of cross-reactivity among different\\u000a quinolones depends on the type of clinical manifestation and its underlying mechanism. Despite recent advances, reliable diagnostic\\u000a tests are still lacking. Recent studies have shown quinolone-specific IgE in vitro

Kathrin Scherer; Andreas J. Bircher

2005-01-01

154

Induction of Shrimp Tropomyosin-Specific Hypersensitivity in Mice  

Microsoft Academic Search

Background: Shellfish hypersensitivity is amongst the most common food allergies. The major shellfish allergen was identified as tropomyosin. Here, we investigated the immediate hypersensitivity responses, IgE and cell-mediated immune response in mice sensitized with recombinant shrimp tropomyosin. Methods: Shrimp tropomyosin was cloned and expressed as a His-tagged fusion recombinant protein in Escherichia coli. Three- to 4-week-old BALB\\/c mice were sensitized

Patrick S. C. Leung; Yuen Shan Lee; Chi Yan Tang; Wing Yee Kung; Ya-Hui Chuang; Bor-Luen Chiang; Ming Chiu Fung; Ka Hou Chu

2008-01-01

155

Dentin Hypersensitivity and Oxalates  

PubMed Central

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.

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

2011-01-01

156

The canine model of dietary hypersensitivity.  

PubMed

IgE-mediated dietary hypersensitivity affects approximately 1% of the canine population. There are no breed associations and < or =50% of the patients are aged <1 year at presentation. The most common causative allergens are beef, chicken, milk, eggs, maize, wheat and soyabean. Affected dogs generally display cutaneous disease and 10-15% of the patients may have concurrent alimentary involvement. Diagnosis is currently based on dietary restriction followed by provocation. Procedures for the detection of serum allergen-specific IgE and IgG antibodies are widely available, but these tests correlate poorly with clinical presentation and dietary testing. Recent studies have demonstrated the allergen specificity of IgE antibodies by immunoblotting and have described blood lymphocyte proliferative responses to food allergens. In addition to investigations of spontaneously-arising dietary hypersensitivity, it has also proved possible to study this disorder experimentally. Small colonies of dogs sensitive to particular dietary proteins have been used to study clinical and serological responses to allergen challenge. Hypersensitivity has been experimentally induced in dogs of an atopic phenotype by repeated subcutaneous injection of alum-adjuvanted dietary allergen during neonatal life. These models have been used to trial a range of modified protein or hydrolysate diets. The dog provides a unique large-animal model for investigation of the immunopathogenesis of human dietary hypersensitivity. The dog is closely related genetically to man and shares environmental disease triggers with man. Spontaneously arising canine dietary hypersensitivity is a good clinical mimic of the human disease, and ability to therapeutically manipulate this adverse response in the dog might lead to benefits for human patients. PMID:16313687

Day, Michael J

2005-11-01

157

A R2R3-MYB gene, AtMYB30, acts as a positive regulator of the hypersensitive cell death program in plants in response to pathogen attack  

PubMed Central

Hypersensitive response (HR) is a programmed cell death that is commonly associated with disease resistance in plants. Among the different HR-related early induced genes, the AtMYB30 gene is specifically, rapidly, and transiently expressed during incompatible interactions between Arabidopsis and bacterial pathogens. Its expression was also shown to be deregulated in Arabidopsis mutants affected in the control of cell death initiation. Here, we demonstrate that overexpression in Arabidopsis and tobacco of AtMYB30 (i) accelerates and intensifies the appearance of the HR in response to different avirulent bacterial pathogens, (ii) causes HR-like responses to virulent strains, and (iii) increases resistance against different bacterial pathogens, and a virulent biotrophic fungal pathogen, Cercospora nicotianae. In antisense AtMYB30 Arabidopsis lines, HR cell death is strongly decreased or suppressed in response to avirulent bacterial strains, resistance against different bacterial pathogens decreased, and the expression of HR- and defense-related genes was altered. Taken together, these results strongly suggest that AtMYB30 is a positive regulator of hypersensitive cell death.

Vailleau, Fabienne; Daniel, Xavier; Tronchet, Maurice; Montillet, Jean-Luc; Triantaphylides, Christian; Roby, Dominique

2002-01-01

158

Diagnostic testing of dogs for food hypersensitivity.  

PubMed

Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs. PMID:2004984

Jeffers, J G; Shanley, K J; Meyer, E K

1991-01-15

159

Immediate-type hypersensitivity drug reactions.  

PubMed

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

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

2014-07-01

160

Egg hypersensitivity in review.  

PubMed

Egg hypersensitivity is the second most common food allergy with a prevalence of up to 1.7% and the discovery of information about egg allergy is ongoing. This review aims to summarize the current understanding of the allergens involved, natural history, clinical presentation, diagnostic strategies, treatment options, egg-containing vaccine guidelines, and future therapies for health care providers in managing egg hypersensitivity. Recent clinically applicable articles are reviewed for the allergist as an update for the state of the art management of egg allergy. Approximately 70% of children will outgrow egg allergy by 16 years of age and children are able to tolerate well-cooked eggs sooner than uncooked eggs. Egg-specific IgE of >50 kIU(A)/L can be used as a predictor for persistent egg allergy. Double-blind placebo-controlled food challenges are still the gold standard for diagnosis. Oral immunotherapy trials still are not generalizable for routine clinical practice, but the influenza vaccine can be given to most egg-allergic patients. Allergists can now educate, diagnose, and manage egg-allergic patients with state-of-the-art information to improve patient's quality of life as never before. PMID:23406934

Hasan, Sana A; Wells, Regina D; Davis, Carla M

2013-01-01

161

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

PubMed Central

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

Suckow, Shelby K; Caudle, Robert M

2009-01-01

162

An unexpected positive hypersensitive reaction to eugenol.  

PubMed

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

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

2013-01-01

163

Bmp indicator mice reveal dynamic regulation of transcriptional response.  

PubMed

Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE), originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool. PMID:22984405

Javier, Anna L; Doan, Linda T; Luong, Mui; Reyes de Mochel, N Soledad; Sun, Aixu; Monuki, Edwin S; Cho, Ken W Y

2012-01-01

164

Bmp Indicator Mice Reveal Dynamic Regulation of Transcriptional Response  

PubMed Central

Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE), originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool.

Javier, Anna L.; Doan, Linda T.; Luong, Mui; Reyes de Mochel, N. Soledad; Sun, Aixu; Monuki, Edwin S.; Cho, Ken W. Y.

2012-01-01

165

Chapter 28: Classification of hypersensitivity reactions.  

PubMed

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. PMID:22794701

Uzzaman, Ashraf; Cho, Seong H

2012-01-01

166

Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome  

PubMed Central

Background Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS), a Chinese Spring terminal deletion line (CS_5AL-10) and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions. Results The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed) in Creso (which lacks the D genome) or in the CS_5AL-10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region). Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10. Conclusion Bread and durum wheat genotypes were characterized by a different physiological reaction to water stress and by a substantially different molecular response. The genome organization accounted for differences in the expression level of hundreds of genes located on the D genome or controlled by regulators located on the D genome. When a genomic stress (deletion of a chromosomal region) was combined with low water availability, a molecular response based on the activation of transposons and retrotransposons was observed.

Aprile, Alessio; Mastrangelo, Anna M; De Leonardis, Anna M; Galiba, Gabor; Roncaglia, Enrica; Ferrari, Francesco; De Bellis, Luigi; Turchi, Luana; Giuliano, Giovanni; Cattivelli, Luigi

2009-01-01

167

Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity.  

PubMed

Motor and visual cortices of normal volunteers were activated by transcranial magnetic stimulation. The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (HR-EEG) and located using inversion algorithms. The stimulation of the left sensorimotor hand area elicited an immediate response at the stimulated site. The activation had spread to adjacent ipsilateral motor areas within 5-10 ms and to homologous regions in the opposite hemisphere within 20 ms. Similar activation patterns were generated by magnetic stimulation of the visual cortex. This new non-invasive method provides direct information about cortical reactivity and area-to-area neuronal connections. PMID:9427322

Ilmoniemi, R J; Virtanen, J; Ruohonen, J; Karhu, J; Aronen, H J; Näätänen, R; Katila, T

1997-11-10

168

A chemical screen for suppressors of the avrRpm1-RPM1-dependent hypersensitive cell death response in Arabidopsis thaliana.  

PubMed

Arabidopsis thaliana RPM1 encodes an intracellular immune sensor that conditions disease resistance to Pseudomonas syringae expressing the type III effector protein AvrRpm1. Conditional expression of this type III effector in a transgenic line carrying avrRpm1 under the control of a steroid-inducible promoter results in RPM1-dependent cell death that resembles the cell death response of the incompatible RPM1-avrRpm1 plant-bacterium interaction. This line was previously used in a genetic screen, which revealed two genes that likely function in the folding of pre-activation RPM1. We established a chemical screen for small molecules that suppress steroid-inducible and RPM1-avrRpm1-dependent cell death in Arabidopsis seedlings. Screening of a library comprising 6,800 compounds of natural origin identified two trichothecene-type mycotoxins, 4,15-diacetoxyscirpenol (DAS) and neosolaniol (NEO), which are synthesized by Fusarium and other fungal species. However, protein blot analysis revealed that DAS and NEO inhibit AvrRpm1 synthesis rather than suppress RPM1-mediated responses. This inhibition of translational activity likely explains the survival of the seedlings under screening conditions. Likewise, flg22-induced defense responses are also impaired at the translational, but not the transcriptional, level by DAS or NEO. Unexpectedly, both compounds not only prevented AvrRpm1 synthesis, but rather caused an apparent hyper-accumulation of RPM1 and HSP70. The hyper-accumulation phenotype is likely unrelated to the ribotoxic function of DAS and NEO and could be due to an inhibitory activity on the proteolytic machinery of Arabidopsis or elicitor-like activities of type A trichothecenes. PMID:20140739

Serrano, Mario; Hubert, David A; Dangl, Jeffery L; Schulze-Lefert, Paul; Kombrink, Erich

2010-04-01

169

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

PubMed Central

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

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

2013-01-01

170

Transcriptomic analysis reveals pH-responsive antioxidant gene networks.  

PubMed

Reactive oxygen species (ROS) are produced in different physiological conditions. In response to ROS imbalance cells activate oxidative stress defenses, which include more than 60 antioxidant genes. It has been suggested that gene products associated with ROS detoxification can work coordinately, acting as an antioxidant-defense network. However, the functional overlap among oxidative stress defenses and other related cell functions makes difficult the characterization of this network. We previously described a network-based model to characterize the interactions existing among different antioxidant gene products and their substrates. Here, we test whether this network-based model of human antioxidant genes can respond to different physiological conditions. We used a systems biology approach applied to the analysis of two independent gene expression datasets: transcriptomes from HeLa cells and primary astrocytes maintained under hypoxic conditions and transcriptomes from SKGT4 cells exposed to low pH environment. We found that the proposed gene network model responds selectively to both hypoxia and acidosis. We anticipate that this antioxidant gene network model can be helpful to describe stress-responsive expression profiles in different cell types. PMID:22652892

Dalmolin, Rodrigo Juliani Siqueira; Gelain, Daniel Pens; Klamt, Fabio; Castro, Mauro Antonio Alves; Moreira, Jose Claudio Fonseca

2012-01-01

171

Proteomic analysis of rice plasma membrane reveals proteins involved in early defense response to bacterial blight.  

PubMed

Plant plasma membrane (PM) proteins play important roles in signal transduction during defense response to an attacking pathogen. By using an improved method of PM protein preparation and PM-bound green fluorescent protein fusion protein as a visible marker, we conducted PM proteomic analysis of the rice suspension cells expressing the disease resistance gene Xa21, to identify PM components involved in the early defense response to bacterial blight (Xanthomonas oryzae pv. oryzae). A total of 20 regulated protein spots were observed on 2-D gels of PM fractions at 12 and 24 h after pathogen inoculation, of which some were differentially regulated between the incompatible and compatible interactions mediated by Xa21, with good correlation between biological repeats. Eleven protein spots with predicted functions in plant defense were identified by MS/MS, including nine putative PM-associated proteins H+-ATPase, protein phosphatase, hypersensitive-induced response protein (OsHIR1), prohibitin (OsPHB2), zinc finger and C2 domain protein, universal stress protein (USP), and heat shock protein. OsHIR1 was modified by the microbial challenge, leading to two differentially accumulated protein spots. Transcript analysis showed that most of the genes were also regulated at transcriptional levels. Our study would provide a starting point for functionality of PM proteins in the rice defense. PMID:17407182

Chen, Fang; Yuan, Yuexing; Li, Qun; He, Zuhua

2007-05-01

172

Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment  

PubMed Central

Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.

Wikoff, William R.; Frye, Reginald F.; Zhu, Hongjie; Gong, Yan; Boyle, Stephen; Churchill, Erik; Cooper-Dehoff, Rhonda M.; Beitelshees, Amber L.; Chapman, Arlene B.; Fiehn, Oliver; Johnson, Julie A.; Kaddurah-Daouk, Rima

2013-01-01

173

Bacterial evolution of antibiotic hypersensitivity  

PubMed Central

The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large-scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole-genome sequencing of laboratory-evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton-motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF-dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade-offs under antibiotic selection.

Lazar, Viktoria; Pal Singh, Gajinder; Spohn, Reka; Nagy, Istvan; Horvath, Balazs; Hrtyan, Monika; Busa-Fekete, Robert; Bogos, Balazs; Mehi, Orsolya; Csorgo, Balint; Posfai, Gyorgy; Fekete, Gergely; Szappanos, Balazs; Kegl, Balazs; Papp, Balazs; Pal, Csaba

2013-01-01

174

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

PubMed Central

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.

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

2014-01-01

175

Mycobacterium immunogenum causes hypersensitivity pneumonitis-like pathology in mice.  

PubMed

A surprising number of cases of hypersensitivity pneumonitis have been observed at work sites employing automotive machinists. Because hypersensitivity pneumonitis is not typically associated with exposure to metalworking fluid aerosols, this study examined whether Mycobacterium immunogenum (M. immunogenum), a rapidly growing mycobacterium isolated from several affected work sites, could induce hypersensitivity pneumonitis in mice. Hypersensitivity pneumonitis-like histologic changes occurred in mice treated with heat-killed and lysed M. immunogenum. These lung lesions were characterized by peribronchial and perivascular lymphohistiocytic inflammation and noncaseating granulomas in the parenchyma. The pathologic changes observed in mice instilled with M. immunogenum-contaminated used metalworking fluid were indistinguishable from those observed with M. immunogenum alone. The role of genetic factors in M. immunogenum-induced lung lesions was examined by comparison of the response of eight inbred strains of mice. The observed immunologic changes in the lung were significantly greater in C57Bl/6, 129, and BALB/c mice than in the other strains, suggesting that genetic factor(s) contribute to the susceptibility of workers exposed to M. immunogenum-contaminated metalworking fluid aerosols. Thus, these studies provide indirect evidence that M. immunogenum is an unrecognized class of microorganisms capable of causing hypersensitivity pneumonitis and plays a role in the outbreaks of hypersensitivity pneumonitis in automotive plants. PMID:16556584

Gordon, Terry; Nadziejko, Christine; Galdanes, Karen; Lewis, Dan; Donnelly, Kevin

2006-05-01

176

Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response  

PubMed Central

Summary The regulatory networks of the DNA damage response (DDR) encompass many proteins and posttranslational modifications. Here, we use mass spectrometry-based proteomics to analyze the systems-wide response to DNA damage by parallel quantification of the DDR-regulated phosphoproteome, acetylome and proteome. We show that phosphorylation-dependent signaling networks are regulated more strongly compared to acetylation. Among the phosphorylated proteins identified are many putative substrates of DNA-PK, ATM and ATR kinases, but a majority of phosphorylated proteins do not share the ATM/ATR/DNA-PK target consensus, suggesting an important role of downstream kinases in amplifying DDR signals. We show that the splicing-regulator phosphatase PPM1G is recruited to sites of DNA damage, while the splicing-associated protein THRAP3 is excluded from these regions. Moreover, THRAP3 depletion causes cellular hypersensitivity to DNA damaging agents, thus suggesting an important link between RNA metabolism and DNA repair. Our results broaden the knowledge of DNA damage signaling networks and identify novel components of the DDR.

Beli, Petra; Lukashchuk, Natalia; Wagner, Sebastian A.; Weinert, Brian T.; Olsen, Jesper V.; Baskcomb, Linda; Mann, Matthias; Jackson, Stephen P.; Choudhary, Chunaram

2013-01-01

177

Experimental hypersensitivity pneumonitis: cellular requirements  

PubMed Central

We previously demonstrated that Thy1.2+, CD4+, Ia? T cells are responsible for transfer of murine adoptive experimental hypersensitivity pneumonitis (adoptive EHP). To characterize the culture conditions necessary for development of these cells, we depleted cell cultures of Thy1.2+, CD4+, CD8+, or Ia+ cells using MoAbs and complement or magnetic beads, prior to culture of sensitized C3H/HeJ murine spleen cells (SC) with Micropolyspora faeni. After culture, cells were transferred to recipients which were later challenged intratracheally with M. faeni. The extent of pulmonary inflammatory changes in these animals was determined 4 days after intratracheal (i.t.) challenge with M. faeni. Cultured M. faeni-sensitized SC which had been treated before culture with media, complement only, anti-CD8 plus complement or magnetic beads alone could transfer EHP to naive animals. SC treated with anti-Thy1.2 or anti-CD4 plus complement could not transfer EHP. Treatment of SC with anti-Iak plus magnetic beads diminished the ability of cultured cells to transfer EHP. We conclude that the ability to produce cells able to adoptively transfer EHP is dependent on the presence of Thy1.2+, CD4+ and Ia+ cells, but not CD8+ cells, at the onset of culture.

SCHUYLER, M; GOTT, K; EDWARDS, B

1996-01-01

178

Experimental hypersensitivity pneumonitis: cellular requirements.  

PubMed

We previously demonstrated that Thy1.2+, CD4+, Ia-T cells are responsible for transfer of murine adoptive experimental hypersensitivity pneumonitis (adoptive EHP). To characterize the culture conditions necessary for development of these cells, we depleted cell cultures of Thy1.2+, CD4+, CD8+, or Ia+ cells using MoAbs and complement or magnetic beads, prior to culture of sensitized C3H/HeJ murine spleen cells (SC) with Micropolyspora faeni. After culture, cells were transferred to recipients which were later challenged intratracheally with M. faeni. The extent of pulmonary inflammatory changes in these animals was determined 4 days after intratracheal (i.t.) challenge with M. faeni. Cultured M. faeni-sensitized SC which had been treated before culture with media, complement only, anti-CD8 plus complement or magnetic beads alone could transfer EHP to naive animals. SC treated with anti-Thy1.2 or anti-CD4 plus complement could not transfer EHP. Treatment of SC with anti-Iak plus magnetic beads diminished the ability of cultured cells to transfer EHP. We conclude that the ability to produce cells able to adoptively transfer EPH is dependent on the presence of Thy1.2+, CD4+, and Ia+ cells, but not CD8+ cells, at the onset of culture. PMID:8697626

Schuyler, M; Gott, K; Edwards, B

1996-07-01

179

Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: analysis of dose-response following topical induction and time course following repeated inhalation challenge.  

PubMed

Trimellitic anhydride (TMA) is a low-molecular-weight chemical known to cause occupational asthma. The dose-response study was designed to determine whether respiratory responses during a single inhalation challenge with TMA (25-30 mg/m3 for 30 min, 3 weeks after the initial induction), the ensuing non-specific airway hyperresponsiveness (AH) to methacholine (MCh) aerosol, and infiltration of eosinophilic granulocytes into the lungs of sensitized Brown Norway (BN) rats are associated and dependent on the concentration of TMA used for topical induction. The initial topical exposure concentrations were 1, 5, and 25% TMA in acetone:olive oil (AOO) followed by a booster induction 1 week later. In the time course study BN rats received AOO alone or were sensitized to the minimal sensitizing topical concentration of TMA (5%) and were the subsequently challenged with TMA on Days 17, 24, 41, 47, 55, and 66, followed by a MCh challenge 1 day later. One additional group of rats was sensitized to 5% TMA but were repeatedly challenged with MCh without prior TMA challenge. In the dose-response study the rats sensitized topically to TMA (5 and 25% in AOO) displayed unequivocal changes in breathing patterns upon challenge with TMA, including an increased responsiveness to MCh aerosol. These findings were associated with a sustained pulmonary eosinophilic inflammation. All endpoints demonstrated consistently that 5% TMA in AOO constitutes the minimal sensitizing concentration. When rats were topically sensitized with this concentration and repeatedly challenged with TMA over a time period of 7 weeks, it became apparent that challenge exposures in BN rats may be false negative when performed at time periods less than 3 weeks after the initial induction. Despite the time-related increased responsiveness elicited by the repeated TMA challenge exposures, the MCh challenge revealed increased non-specific airway hyperreactivity exclusively on Day 17. After the sixth TMA-challenge, the respiratory response and lung weights of rats sensitized topically were essentially similar to those observed in the repetitively re-challenged control group (induction: vehicle only; repeated booster challenge exposures with TMA). Thus, it appears, that in this animal model the effective concentration for successful topical sensitization must be at least approximately 5%. The repeated low-dose re-challenge with TMA in topically sensitized rats resulted in similar or slightly aggravated time-related responses over a period of 7 weeks. An over-proportionally increased susceptibility of rats receiving a topical priming dose prior to repeated inhalation challenge exposures was not observed. In summary, this study shows that the analysis of functional changes in breathing patterns is suitable to identify respiratory allergy. Repeated short-term inhalation exposures to mildly irritant concentrations (but low doses) of chemical asthmagens may be of higher concern than topical exposures. PMID:14636692

Pauluhn, Jürgen

2003-12-15

180

Hypersensitivity to aeroallergens in children with atopic dermatitis.  

PubMed

Atopic dermatitis (AD) is a chronically relapsing, inflammatory skin disease characterized by severe itch, rash and dry skin. Hypersensitivity to aeroallergens is found in 40%-50% of children with AD and it is the cause of intensive skin lesions. The aim of the study was to assess the presence of hypersensitivity to aeroallergens in AD children. The study included 114 children (56 boys and 58 girls), median age 27.5 months, who had been diagnosed with AD according to Hanifin and Rajka criteria. The severity of the disease was assessed by the SCORAD index. To recognize hypersensitivity to aeroallergens, the following parameters were analyzed: medical history, values of absolute eosinophil count, total IgE antibodies, specific IgE antibodies to aeroallergens, and results of the skin prick test for aeroallergens. A moderate form of the disease was present in 61.4% of study children, with a median SCORAD index score of 28.5 points; 12.3% of study children showed hypersensitivity to aeroallergens (history of hypersensitivity to aeroallergens in 27.2%, increased absolute eosinophil count in 53.5%, increased total IgE antibodies in 56.1%, positive skin prick test in 20.2%, and positive specific IgE antibodies to aeroallergens in 12.3% of children). The most common aeroallergens responsible were house dust in 6.1% and Dermatophagoides pteronyssinus in 3.5% of children with AD. Hypersensitivity to aeroallergens was recorded in the same number of children with mild and severe forms of the disease and in 5.7% of children with a moderate form. In conclusion, the presence of hypersensitivity to aeroallergens in children with AD is significant. By discovering and removing the aeroallergens responsible, it is possible to achieve reduction in the intensity of skin lesions and frequency of exacerbations. PMID:23540167

Cosi?ki?, Almira; Skoki?, Fahrija; Coli?-Hadzi?, Belkisa; Suljendi?, Sanimir; Hasanovi?, Evlijana

2012-12-01

181

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

PubMed Central

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

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

2012-01-01

182

Function of the oxidative burst in hypersensitive disease resistance.  

PubMed Central

Microbial elicitors or attempted infection with an avirulent pathogen strain causes the rapid production of reactive oxygen intermediates. Recent findings indicate that H2O2 from this oxidative burst plays a central role in the orchestration of the hypersensitive response: (i) as the substrate driving the cross-linking of cell wall structural proteins to slow microbial ingress prior to the deployment of transcription-dependent defenses and to trap pathogens in cells destined to undergo hypersensitive cell death, (ii) as a local threshold trigger of this programmed death in challenged cells, and (iii) as a diffusible signal for the induction in adjacent cells of genes encoding cellular protectants such as glutathione S-transferase and glutathione peroxidase. These findings provide the basis for an integrated model for the orchestration of the localized hypersensitive resistance response to attack by an avirulent pathogen. Images Fig. 1 Fig. 2 Fig. 3

Tenhaken, R; Levine, A; Brisson, L F; Dixon, R A; Lamb, C

1995-01-01

183

Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation  

PubMed Central

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

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

2012-01-01

184

The LCB2 subunit of the sphingolip biosynthesis enzyme serine palmitoyltransferase can function as an attenuator of the hypersensitive response and Bax-induced cell death.  

PubMed

Previous results showed that expression of the gene encoding the LONG-CHAIN BASE2 (LCB(2)) subunit of serine palmitoyltransferase (SPT), designated BcLCB(2), from nonheading Chinese cabbage (Brassica campestris ssp. chinensis) was up-regulated during hypersensitive cell death (HCD) induced by the Phytophthora boehmeriae elicitor PB90. Overexpression of BcLCB(2) in Nicotiana tabacum leaves suppressed the HCD normally initiated by elicitors and PB90-triggered H(2)O(2) accumulation. BcLCB(2) also functioned as a suppressor of mouse Bcl-2 associated X (Bax) protein-mediated HCD and cell death caused by Ralstonia solanacearum. BcLCB(2) overexpression suppressed Bax- and oxidant stress-triggered yeast cell death. Reactive oxygen species (ROS) accumulation induced by Bax was compromised in BcLCB(2)-overexpressing yeast cells. The findings that NbLCB(2) silencing in Nicotiana benthamiana enhanced elicitor-triggered HCD, combined with the fact that myriocin, a potent inhibitor of SPT, had no effect on Bax-induced programmed cell death, suggested that suppression of cell death was not involved in the dominant-negative effect that resulted from BcLCB(2) overexpression. A BcLCB(2) mutant assay showed that the suppression was not involved in SPT activity. The results suggest that plant HCD and stress-induced yeast cell death might share a common signal transduction pathway involving LCB(2), and that LCB(2) protects against cell death by inhibiting ROS accumulation, this inhibition being independent of SPT activity. PMID:19076721

Gan, Yunzhe; Zhang, Lisha; Zhang, Zhengguang; Dong, Suomeng; Li, Jun; Wang, Yuanchao; Zheng, Xiaobo

2009-01-01

185

Recent progress of elucidating the mechanisms of drug hypersensitivity  

PubMed Central

Recent technical approaches to investigating drug hypersensitivity have provided a great deal of information to solve the mechanisms that remain poorly understood. First, immunological investigations and in silico analysis have revealed that a novel interaction between T cells and antigen-presenting cells, namely the pharmacological interaction concept, is involved in drug recognition and the hapten theory. Second, progress in immunology has provided a new concept of CD4+ T cell subsets. Th17 cells have proven to be a critical player in acute generalized exanthematous pustulosis. Our recent findings suggest that this subset might contribute to the pathogenesis of Stevens-Johnson syndrome/toxic epidermal necrolysis. Third, alarmins, molecules associated with innate immunity, are also associated with exaggeration and the persistence of severe drug hypersensitivity. The latest innovative techniques are providing a new landscape to examine drug hypersensitivity.

2012-01-01

186

Use of contact hypersensitivity in immunotoxicity testing.  

PubMed

The histopathological examination of lymphoid organs together with a T-dependent antibody (TDAR) assay are the primary components of preclinical immunotoxicity assessment. Additional testing including measurement of cellular immunity may be considered. Besides ex vivo lymphocyte proliferation assays, either delayed or contact hypersensitivity models can be used. Contact hypersensitivity testing is typically performed either in mice or in guinea pigs and is directly derived from classical models used for the detection of contact sensitizing chemicals. Whatever the selected model, it is comprised of a sensitizing phase where the animals are applied a strong contact sensitizer topically, then a rest phase, and finally an eliciting phase where sensitized animals are challenged topically with the same contact sensitizer.In mice, the ear-swelling test is the reference procedure in which mice are sensitized to the ear or shaved abdominal skin and then challenged on the ear. Ear swelling usually measured from ear thickness reflects a cell-mediated immune response. In guinea pigs, a strong sensitizer is applied on the shaved skin of the abdomen or the interscapular area. The sensitized animals are challenged on another area of the shaved abdomen, and the cell-mediated response is assessed semiquantitatively from the magnitude of induced erythema inconsistently associated with edema. Treatment or exposure with immunosuppressive chemicals can result in a significantly decreased ear swelling or skin reaction. Contact hypersensitivity models are seldom used nowadays in preclinical immunotoxicity testing, most likely because of the lack of standardization and extensive validation as well as their use being restricted to mice or guinea pigs. PMID:19967518

Descotes, Jacques

2010-01-01

187

[Bronchial involvement in hypersensitivity pneumonitis].  

PubMed

Hypersensitivity pneumonitis is a respiratory disease resulting from the inhalation of antigens to which the exposed subject has been previously sensitized. Hypersensitivity pneumonitis is characterized by a diffuse and predominantly mononuclear cell inflammation of the alveolar regions that involves the small airways in most cases. It explains the presence of mosaic attenuation and expiratory air trapping at HRCT Scan. Chronic bronchitis, an obstructive defect at lung function tests and emphysema as long-term outcome are frequent consequences of this bronchial involvement. PMID:19394191

Dalphin, Jean-Charles; Manzoni, Philippe; Ranfaing, Elisabeth; Reboux, Gabriel

2009-11-01

188

Rituximab-Induced Hypersensitivity Pneumonitis  

PubMed Central

Rituximab is a chimeric anti-CD20 monoclonal antibody used to treat CD20+ non-Hodgkin's lymphoma. Although pulmonary adverse reactions such as cough, rhinitis, bronchospasm, dyspnea and sinusitis are relatively common, other respiratory conditions like cryptogenic organizing pneumonia, interstitial pneumonitis and diffuse alveolar hemorrhage have rarely been reported. Only 2 possible cases of rituximab-associated hypersensitivity pneumonitis have been described to date. We present a case of hypersensitivity pneumonitis with classic radiographic and histopathologic findings in a patient treated with rituximab who responded to prednisone.

Tonelli, Adriano R.; Lottenberg, Richard; Allan, Robert W.; Sriram, P.S.

2009-01-01

189

Development of a flow cytometry assay for the identification and differentiation of chemicals with the potential to elicit irritation, IgE-mediated, or T cell-mediated hypersensitivity responses.  

PubMed

These studies were conducted to investigate the potential use of a flow cytometric analysis method for the identification and differentiation of chemicals with the capacity to induce irritation, IgE- or T cell-mediated hypersensitivity responses. An initial study investigated the ability of equally sensitizing concentrations (determined by local lymph node assay) of IgE-mediated (Toluene Diisocyanate-TDI) and T cell-mediated (Dinitrofluorobenzene-DNFB) allergens to differentially modulate the IgE+B220+ population in the lymph nodes draining the dermal exposure site. Sodium lauryl sulfate (SLS) was also tested as a nonsensitizing irritant control. Female B6C3F1 mice were dermally exposed once daily for 4 consecutive days, with the optimum time point for analysis determined by examining the IgE+B220+ population 8, 10, and 12 days post-initial chemical exposure. At the peak time point, day 10, the IgE+B220+ population was significantly elevated in TDI (41%), while moderately elevated in DNFB (18%) exposed animals when compared to the vehicle (0.8%), and remained unchanged in SLS (2.2%) exposed animals when compared to the ethanol control (2.5%). Experiments in our laboratory and others have demonstrated that the draining lymph node B220+ population becomes significantly elevated following exposure to allergens (IgE- and T cell-mediated), not irritants, allowing for their differentiation. An existing mouse ear swelling assay was used to identify chemical irritants. Therefore, using the endpoints of percent ear swelling, percent B220+ cells, and percent IgE+B220+ cells, a combined irritancy/phenotypic analysis assay was developed and tested with tetradecane (irritant), toluene diisocyanate, trimellitic anhydride (IgE-mediated allergens), benzalkonium chloride, dinitrofluorobenzene, oxazolone, and dinitrochlorobenzene (T cell-mediated allergens) over a range of concentrations. Based upon the pattern of response observed, a paradigm was developed for continued evaluation: Irritant exposure will result in significant ear swelling without altering the B220+ or IgE+B220+ populations. Exposure to sensitizers (IgE-mediated or T cell-mediated) will increase the B220+ population and the percent ear swelling will remain unchanged or will significantly increase, depending on the irritancy capacity of the chemical. Both the IgE+B220+ and B220+ populations will become elevated at the same test concentration following exposure to IgE-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will be equal to the percent of B220+ cells. The B220+ population will increase at a lower test concentration than the IgE+B220+ population, following exposure to T cell-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will reach less than half that of the percent of B220+ cells. The irritancy/phenotypic analysis method may represent a single murine assay able to identify and differentiate chemicals with the capacity to induce irritation, or IgE-mediated or T cell-mediated responses. PMID:10353312

Manetz, T S; Meade, B J

1999-04-01

190

Ear piercing for individuals with metal hypersensitivity  

Microsoft Academic Search

Objective: To describe and evaluate an ear piercing and earring retention method for individuals with metal hypersensitivity. Setting: Private facial plastic surgery practice associated with a tertiary care medical center. Methods: Thirty-one patients with a history of hypersensitivity to metallic jewelry (62 ears) underwent earlobe piercing with an intravenous catheter. Results: None of the patients experienced an infection or hypersensitivity

Anthony J. Cornetta; David Reiter

2001-01-01

191

Dentinal hypersensitivity: review of aetiology, differential diagnosis, prevalence, and mechanism.  

PubMed

Dentinal hypersensitivity is a painful response to a non-noxious stimulus applied to exposed dentine in the oral environment. Dentine exposure results from a combination of two or more aetiological factors that lead to loss of enamel and/or loss of cementum. The hydrodynamic theory is the most accepted theory that explains the excitement of pulpal nerve fibres by a stimulus applied to the exposed dentine. Dentinal hypersensitivity had been reported to affect middle age people most often with no gender differences and has been shown to be influenced by tooth location. PMID:14964489

Al-Sabbagh, M; Andreana, S; Ciancio, S G

2004-01-01

192

Experimental hypersensitivity pneumonitis: lack of tolerance.  

PubMed

Most subjects repetitively exposed to agents responsible for hypersensitivity pneumonitis (HP) do not develop persistent or progressive pulmonary inflammation. To determine if immunologic tolerance is associated with resolution of pulmonary abnormalities despite continuing exposure, we examined markers of local immunologic reactivity in a model of HP in rabbits. Rabbits were exposed to Micropolyspora faeni (M. faeni), the agent responsible for farmer's lung disease, with 3 sensitizing and 2, 4, or 8 challenge intratracheal injections. We determined bronchoalveolar macrophage migration inhibition (MMI) induced by M. faeni antigen, mitogen, and antigen-induced lymphocyte proliferation of lymphocytes derived from the lungs and hilar lymph nodes, and the amount of IgG antibody to M. faeni in serum and bronchoalveolar lavage fluid. We found MMI of lavage cells from rabbits exposed to M. faeni. Migration inhibition was dependent on ongoing protein synthesis. Hilar node and pulmonary lymphocytes proliferated upon exposure to M. faeni antigen, and anti-M. faeni antibody was found in serum and lavage fluid from M. faeni-treated rabbits. There were no differences between rabbits challenged 2, 4, and 8 times. We conclude that resolution of pulmonary histologic abnormalities in this model of hypersensitivity pneumonitis is not associated with evidence of immunologic tolerance. PMID:6497159

Schuyler, M R; Schmitt, D

1984-11-01

193

Hypersensitivity to metals in orthodontics  

Microsoft Academic Search

To study the incidence of hypersensitivity to orthodontic metals, patch tests were carried out before and 2 months after the placement of orthodontic appliances in 38 patients (17 male, 21 female). The tested substances were cobalt chloride, copper sulfate, potassium dichromate, iron sulfate, manganese chloride, molybdenum salt, nickel sulfate, and titanium oxide. Eight strips containing the test substances were positioned

Luciane M Menezes; Luis C Campos; Catia C Quintão; Ana M Bolognese

2004-01-01

194

Electromagnetic hypersensitivity: Fact or Fiction?  

Microsoft Academic Search

As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home

Stephen J. Genuis; Chris Lipp

195

Oral Hypersensitivity Reactions  

MedlinePLUS

... although it is rare. Only 1% of the adverse reactions due to local anesthetics are considered truly allergic, ... an allergic response to the vast majority of adverse reactions attributed to local anesthetics are in reality caused ...

196

Immune Responses Induced in Cattle by Virulent and Attenuated Mycobacterium bovis Strains: Correlation of Delayed-Type Hypersensitivity with Ability of Strains To Grow in Macrophages  

Microsoft Academic Search

Comparison of immune responses induced in cattle by virulent and attenuated strains of Mycobacterium bovis will assist in identifying responses associated with resistance or susceptibility to disease. Four strains of M. bovis, one which is virulent in guinea pigs (WAg201) and three which are attenuated in guinea pigs (an isoniazid-resistant strain (WAg405), ATCC 35721, and BCG) were compared for their

D. NEIL WEDLOCK; FRANK E. ALDWELL; DESMOND M. COLLINS; GEOFFREY W. DE LISLE; THERESA WILSON; BRYCE M. BUDDLE

1999-01-01

197

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

PubMed

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

Yu, Chuan-Hang; Chang, Yu-Chao

2014-06-01

198

The tomato gene Pti1 encodes a serine\\/threonine kinase that is phosphorylated by Pto and is involved in the hypersensitive response  

Microsoft Academic Search

The Pto gene encodes a serine\\/threonine kinase that confers resistance to bacterial speck disease in tomato. Using the yeast two-hybrid system, we identified a second serine\\/threonine kinase, Pto-interacting 1 (Pti1), that physically interacts with Pto. Crossphosphorylation assays revealed that Pto specifically phosphorylates Ptil and that Ptil does not phosphorylate Pto. Fen, another serine\\/threonine kinase from tomato that is closely related

Jianmin Zhou; Ying-Tsu Loh; Ray A. Bressan; Gregory B. Martin

1995-01-01

199

Skin tests in NSAIDS hypersensitivity.  

PubMed

Prick tests are more specific but less sensitive than ID which can give false positive results. 3 NSAIDS groups can be considered: Aspirin, diclofenac and metamizol with a higher percentage of positivity. For others NSAIDS including the newer coxibs positivity around 50%. Nimesulid and acetaminophen with a lower of positivity. Skin tests can be used in NSAIDS hypersensitivity to confirm clinical history but also to choose, case by case, a drug less prone to give hypersentivity reactions. PMID:16929744

Palma-Carlos, A G; Medina, M; Palma-Carlos, M L

2006-06-01

200

Drug Hypersensitivity Reactions Involving Skin  

Microsoft Academic Search

Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside\\u000a immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions\\u000a appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely\\u000a skin involvement to fulminant systemic diseases which may

Oliver Hausmann; Benno Schnyder; Werner J. Pichler

201

Mast cell hyperplasia in experimental hypersensitivity pneumonitis.  

PubMed

We investigated the presence of mast cells in a model of experimental hypersensitivity pneumonitis (EPH). Guinea pigs exposed to 8 weekly intratracheal challenges with Micropolyspora faeni exhibited significant increases in the number of mast cells within the lung as compared to controls and animals challenged only 2 or 4 times. The number of cells in M. faeni-challenged animals were increased around bronchi, bronchioles, blood vessels and in alveolar septa. There appeared to be contraction of peribronchial, peribronchiolar and vascular smooth muscle. Ultrastructural examination of lung tissue revealed the presence of degranulating mast cells. Bronchoalveolar lavage histamine levels were increased after 8 but not after 2 or 4 weekly challenges. Serum anti-M. faeni antibody was present in all M. faeni-exposed animals but not in control animals. We conclude that mast cells and histamine levels in bronchoalveolar lavage fluid are increased in a model of EHP caused by repetitive, intratracheal injection of M. faeni particulate antigen. PMID:1769746

Haley, P J; Schuyler, M; Gott, K; Casale, T B

1991-01-01

202

Demonstration of species non-specificity of the effect of hypersensitivity pyrogen  

Microsoft Academic Search

Summary  \\u000a \\u000a \\u000a \\u000a (1) \\u000a \\u000a The author studied species specificity of the effect of pyrogenic substances arising in the reaction of delayed hypersensitive\\u000a cell extracts with specific antigenin vitro (the so-called hypersensitivity pyrogen).\\u000a \\u000a \\u000a \\u000a \\u000a (2) \\u000a \\u000a Rabbit, guinea pig, rat, and hen experiments revealed that the effect of this substance was not species-specific; hypersensitivity\\u000a pyrogen prepared in any donor reacts in all animal species tested.

J. Johanovský

1961-01-01

203

Newer concepts of cancer of the colon and rectum: Delayed hypersensitivity responses of patients with carcinoma of the colon and other solid tumors  

Microsoft Academic Search

Summary  Eighty-nine patients were skin-tested with four delayed allergens: old tuberculin, mumps, streptokinase-streptodornase, andTrichophyton. Forty-eight of these patients, including 43 with carcinoma of the colon, had nonreticuloendothelial tumors. Patients with\\u000a tumors were otherwise in good health. There were significant differences between the delayed skin sensitivity of patients\\u000a with cancer and those without cancer, and between the responses to challenge with streptokinase-streptodornase

Barry S. Kronman; Howard M. Shapiro; S. Arthur Locallo

1972-01-01

204

Cordycepin-hypersensitive growth links elevated polyphosphate levels to inhibition of poly(A) polymerase in Saccharomyces cerevisiae  

PubMed Central

To identify genes involved in poly(A) metabolism, we screened the yeast gene deletion collection for growth defects in the presence of cordycepin (3?-deoxyadenosine), a precursor to the RNA chain terminating ATP analog cordycepin triphosphate. ?pho80 and ?pho85 strains, which have a constitutively active phosphate-response pathway, were identified as cordycepin hypersensitive. We show that inorganic polyphosphate (poly P) accumulated in these strains and that poly P is a potent inhibitor of poly(A) polymerase activity in vitro. Binding analyses of poly P and yeast Pap1p revealed an interaction with a kD in the low nanomolar range. Poly P also bound mammalian poly(A) polymerase, however, with a 10-fold higher kD compared to yeast Pap1p. Genetic tests with double mutants of ?pho80 and other genes involved in phosphate homeostasis and poly P accumulation suggest that poly P contributed to cordycepin hypersensitivity. Synergistic inhibition of mRNA synthesis through poly P-mediated inhibition of Pap1p and through cordycepin-mediated RNA chain termination may thus account for hypersensitive growth of ?pho80 and ?pho85 strains in the presence of the chain terminator. Consistent with this, a mutation in the 3?-end formation component rna14 was synthetic lethal in combination with ?pho80. Based on these observations, we suggest that binding of poly P to poly(A) polymerase negatively regulates its activity.

Holbein, Sandra; Freimoser, Florian M.; Werner, Thomas P.; Wengi, Agnieszka; Dichtl, Bernhard

2008-01-01

205

Glucocorticoid hypersensitivity as a rare but potentially fatal side effect of paediatric asthma treatment: a case report  

PubMed Central

Introduction Immediate-type hypersensitivity to glucocorticosteroids is rare but well known among allergists. Surprisingly, very few reports of glucocorticosteroid hypersensitivity in children exist although glucocorticosteroid treatment is particularly common in this age group. Case presentation We report the case of a 2-year-old boy who developed generalized urticaria, facial angio-oedema, nausea and severe dyspnoea after intravenous application of prednisolone-21-hydrogen succinate. Skin prick testing with prednisolone-21-hydrogen succinate elicited a positive result; no reactions were observed to prednisone, betamethasone or dexamethasone. While fluorescence enzyme immunoassay analysis revealed no specific IgE antibodies against prednisolone-21-hydrogen succinate, CD63-based basophil activation testing with the culprit drug prednisolone-21-hydrogen succinate was positive. In contrast, additional incubation of basophils with prednisone, betamethasone and dexamethasone did not elicit any significant response. Hence, we performed an oral provocation test with betamethasone and a titrated intravenous dexamethasone challenge. As both drugs were tolerated without any complications they were recommended for future treatment. Conclusion In a child with confirmed immediate-type hypersensitivity to glucocorticosteroids, it is still not possible to predict which glucocorticosteroid might be tolerated by solely relying on clinical history or results of skin and in vitro testing. Therefore, incremental glucocorticosteroid challenges under standardized clinical conditions remain necessary in order to facilitate a patient-tailored emergency treatment and to avoid severe reactions to glucocorticosteroids in these patients.

Lehmann, Sylvia; Ott, Hagen

2008-01-01

206

Differential effects of oral versus intrathymic administration of polymorphic major histocompatibility complex class II peptides on mononuclear and endothelial cell activation and cytokine expression during a delayed-type hypersensitivity response.  

PubMed Central

Oral and intrathymic exposure to antigen can each induce systemic antigen-specific immune tolerance, but the mechanisms have not been well defined. We studied the effects that the route of exposure to antigen has on the mechanisms of tolerance in vivo using synthetic polymorphic class II major histocompatibility complex (MHC) peptides in a skin delayed-type hypersensitivity (DTH) response model. Lewis rats were immunized by injection in the footpad with synthetic peptides (RT1.Bu and/or RT1.Du) derived from the hypervariable domain of MHC class II beta chain of the Wistar-Furth rat in complete Freund's adjuvant and challenged 2 weeks later by injection in the ear with the MHC peptides. An "oral" group received the peptide mixture by gavage (100 micrograms/day for 5 days) 3 days before immunization, and an "intrathymic" group received a single intrathymic injection of 100 micrograms of peptides 48 hours before immunization. Oral therapy reduced the DTH response to 23 +/- 7%, and intrathymic exposure reduced the DTH response to 26 +/- 6% (P < 0.001) as compared with control DTH responses of unmodified Lewis animals. Immunohistological evaluation of DTH skin lesions showed that oral and intrathymic therapy each decreased mononuclear cell infiltration, fibrin deposition, and endothelial activation when compared with that seen in control rats. In contrast, while both protocols markedly reduced interleukin (IL-2) and interferon-gamma expression, they had differing effects on local expression of IL-4, transforming growth factor-beta, IL-2R, and CD45RC (a possible discriminant between Th1 and Th2 cells in rats). Oral therapy was associated with increased expression of IL-4 and preservation of transforming growth factor-beta expression by residual IL-2R+, CD45RC- mononuclear and endothelial cells, whereas thymic exposure suppressed essentially all features of immune activation including IL-2R induction and cytokine expression. Our data a) document the detailed pattern of cytokine expression and mononuclear and endothelial cell activation markers during DTH responses and b) confirm that oral tolerance is associated with immune deviation to a predominance of Th2 cell function, whereas intrathymic tolerance may be mediated by T-cell anergy or clonal deletion. Images Figure 1 Figure 2

Hancock, W. W.; Khoury, S. J.; Carpenter, C. B.; Sayegh, M. H.

1994-01-01

207

Proteomic analysis reveals an aflatoxin-triggered immune response in cotyledons of Arachis hypogaea infected with Aspergillus flavus.  

PubMed

An immune response is triggered in host cells when host receptors recognize conserved molecular motifs, pathogen-associated molecular patterns (PAMPs), such as ?-glucans, and chitin at the cell surface of a pathogen. Effector-triggered immunity occurs when pathogens deliver effectors into the host cell to suppress the first immune signaling. Using a differential proteomic approach, we identified an array of proteins responding to aflatoxins in cotyledons of peanut (Arachis hypogaea) infected with aflatoxin-producing (toxigenic) but not nonaflatoxin-producing (atoxigenic) strains of Aspergillus flavus. These proteins are involved in immune signaling and PAMP perception, DNA and RNA stabilization, induction of defense, innate immunity, hypersensitive response, biosynthesis of phytoalexins, cell wall responses, peptidoglycan assembly, penetration resistance, condensed tannin synthesis, detoxification, and metabolic regulation. Gene expression analysis confirmed the differential abundance of proteins in peanut cotyledons supplemented with aflatoxins, with or without infection with the atoxigenic strain. Similarly, peanut germination and A. flavus growth were altered in response to aflatoxin B1. These findings show an additional immunity initiated by aflatoxins. With the PAMP- and effector-triggered immune responses, this immunity constitutes the third immune response of the immune system in peanut cotyledon cells. The system is also a three-grade coevolution of plant-pathogen interaction. PMID:22424419

Wang, Zizhang; Yan, Shijuan; Liu, Chunming; Chen, Fang; Wang, Tai

2012-05-01

208

Hypersensitivity to latex, chestnut, and banana.  

PubMed

The incidence of latex-allergic patients is probably higher than suspected. A spectrum of IgE-dependent allergic reactions to latex products including urticaria, rhinitis, asthma, angioedema, and life-threatening anaphylaxis has been increasingly reported in recent years. We describe three patients with rubber hypersensitivity and allergy to fruit (banana and chestnut). Immediate positive responses were obtained in prick tests with latex, banana, and chestnut extracts. Histamine release was positive and specific IgE antibodies to all three extracts were detected by fluorescence radioimmunoassay. In the RAST-inhibition studies, the extract of latex inhibited the binding of chestnut and banana, but chestnut and banana extracts did not inhibit the binding of latex. These results suggest a sensitivity to crossreacting antigens in latex allergy associated with allergy to certain fruits. PMID:7678723

Rodríguez, M; Vega, F; García, M T; Panizo, C; Laffond, E; Montalvo, A; Cuevas, M

1993-01-01

209

Angioneurotic edema: a rare case of hypersensitivity to metoclopramide  

PubMed Central

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.

Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

2013-01-01

210

Natural rubber latex hypersensitivity with skin prick test in operating room personnel.  

PubMed

Hypersensitivity reactions to natural rubber latex have increased recently, especially among people with high exposure to latex allergens. Hypersensitivity reactions to latex are related to many conditions like occupational asthma. Our study was performed to determine the prevalence of hypersensitivity to natural rubber latex and potential food cross reactions in operation room personnel in Shiraz hospitals. In this cross-sectional, descriptive study, 580 operation room personnel filled out our questionnaire which included data about their personal history, symptoms of latex hypersensitivity, and other related allergies such as food hypersensitivity. An informed consent was obtained and skin prick tests were performed for natural rubber latex and potential food cross reactions (kiwi, banana, and potato). The obtained data were analyzed by SPSS and Chi-square test.Results: 104 (17.9%) of the operating room personnel showed positive latex skin tests. We revealed a significant correlation between those with positive skin tests to latex with atopia, urthicaria, and food hypersensitivity. The prevalence did not vary by sex, age, education, surgical and non-surgical gloves users, or history of contact dermatitis. Latex hypersensitivity is common among operation room personnel. Evaluation of symptoms and prediction of future diseases necessitate screening tests in individuals at risk. PMID:20404394

Nabavizadeh, Seyed Hessamedin; Anushiravani, Amir; Amin, Reza

2009-12-01

211

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

PubMed

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. PMID:1831420

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

1991-08-16

212

Stress induces transient auditory hypersensitivity in rats.  

PubMed

Exposure to harsh environment induces stress reactions that increase probability of survival. Stress influences the endocrine, nervous and immune systems and affects the functioning of a variety of organs. Numerous researchers demonstrated that a 24-h exposure to an acoustic rodent repellent provokes stress reaction in exposed animals. In addition to the activated hypothalamic-pituitary-adrenal (HPA) axis, exposed animals had pathological reactions in the reproductive organs, bronchia and skin. Here, we examined the effect of above stress model on the auditory system of Wistar rats. We found that 24-h stress decreases the thresholds and increases the amplitudes of auditory brainstem responses and distortion product otoacoustic emissions. Resultant auditory hypersensitivity was transient and most pronounced between 3 and 6h post-stress, returning to control levels one week later. The concentration of corticosterone and tumor necrosis factor alpha was systemically elevated in stressed animals between 3 and 6h post-stress, confirming the activation of the HPA axis. In addition, expression of the HPA-axis-associated genes: glucocorticoid receptor (GR) and hypoxia-inducible factor 1 alpha (Hif1a) was modulated in the auditory tissues. In detail, in the inferior colliculus, we found an up-regulation of GR mRNA 3h post-stress and continuous up-regulation of Hif1a up to 24h post-stress. In the spiral ganglion, we found no differences in gene expression between stressed and control animals. In the organ of Corti, expression of GR mRNA remained stable, whereas that of Hif1a was significantly down-regulated one week after stress. In addition, the expression of an outer hair cell marker prestin was significantly up-regulated 6h post-stress. We conclude that 24-h stress induces transient hypersensitivity of the auditory system and modulates gene expression in a tissue-specific manner. Stress-induced auditory hypersensitivity could have evolutionary consequence by giving animals an advantage of hearing better under stress conditions. PMID:19840840

Mazurek, Birgit; Haupt, Heidemarie; Joachim, Ricarda; Klapp, Burghard F; Stöver, Timo; Szczepek, Agnieszka J

2010-01-01

213

Arabidopsis mutants reveal multiple singlet oxygen signaling pathways involved in stress response and development  

Microsoft Academic Search

Shortly after the release of singlet oxygen (1O2) in chloroplasts drastic changes in nuclear gene expression occur in the conditional flu mutant of Arabidopsis that reveal a rapid transfer of signals from the plastid to the nucleus. Factors involved in this retrograde\\u000a signaling were identified by mutagenizing a transgenic flu line expressing a 1O2-responsive reporter gene. The reporter gene consisted

Aiswarya Baruah; Klára Šimková; Klaus Apel; Christophe Laloi

2009-01-01

214

Heat Resistance and Salt Hypersensitivity in Lactococcus lactis Due to Spontaneous Mutation of llmg_1816 (gdpP) Induced by High-Temperature Growth  

PubMed Central

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 (?1816), 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 ?1816 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.

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

2012-01-01

215

Atopic dermatitis and food hypersensitivity reactions  

Microsoft Academic Search

Objective: To determine the role of food hypersensitivity in atopic dermatitis and to determine whether patients with atopic dermatitis who had food hypersensitivity could be identified by screening prick skin tests using a limited number of food allergens. Study design: Patients with atopic dermatitis attending the Arkansas Children's Hospital Pediatric Allergy Clinic underwent allergy prick skin testing to a battery

A. Wesley Burks; John M. James; Anne Hiegel; Gail Wilson; J. Gary Wheeler; Stacie M. Jones; Nancy Zuerlein

1998-01-01

216

Subjective symptoms and hypersensitivity to cellular telephones  

Microsoft Academic Search

Electromagnetic hypersensitivity has been reported to be caused by exposure to electromagnetic fields emitted from cellular telephones and cell-phone base stations. The prevalence varies considerably with geographic location. A particularly vexing challenge in studying this phenomenon is that the symptoms reported by electromagnetically hypersensitive individuals, such as headache and fatigue, are common and nonspecific: they may have many causes. A

James C. Lin

2004-01-01

217

Immediate hypersensitivity in the guinea pig conjunctiva. III. long-term persistence of the hypersensitive state and characterization of antibodies.  

PubMed

The ocular immediate hypersensitivity reaction in guinea pigs to topically applied normal rabbit serum can be evoked as long as 4 years after sensitization. The reaction was as severe and tended to persist for longer than that evoked 6 months after sensitization. Passive cutaneous anaphylaxis tests showed that very high titres of homocytotropic antibodies were present and that both IgE- and IgG1-like antibodies were involved. Sensitization with one set of injections instead of two was not consistently successful and the response on challenge was mild to moderate. Pretreatment of eyes with Isoptocarpine before antigenic challenge had no effect on the response. The addition of bacterial lipopolysaccharide to the first set of sensitizing injections produced hypersensitivity in animals which were otherwise refractory to sensitization. PMID:7012038

Dwyer, R S; Darougar, S; Jones, B R; Turk, J L

1981-01-01

218

Yeast translational response to high salinity: Global analysis reveals regulation at multiple levels  

PubMed Central

Genome-wide studies of steady-state mRNA levels revealed common principles underlying transcriptional changes in response to external stimuli. To uncover principles that govern other stages of the gene-expression response, we analyzed the translational response and its coordination with transcriptome changes following exposure to severe stress. Yeast cells were grown for 1 h in medium containing 1 M NaCl, which elicits a maximal but transient translation inhibition, and nonpolysomal or polysomal mRNA pools were subjected to DNA-microarray analyses. We observed a strong repression in polysomal association for most mRNAs, with no simple correlation with the changes in transcript levels. This led to an apparent accumulation of many mRNAs as a nontranslating pool, presumably waiting for recovery from the stress. However, some mRNAs demonstrated a correlated change in their polysomal association and their transcript levels (i.e., potentiation). This group was enriched with targets of the transcription factors Msn2/Msn4, and the translational induction of several tested mRNAs was diminished in an Msn2/Msn4 deletion strain. Genome-wide analysis of a strain lacking the high salinity response kinase Hog1p revealed that the group of translationally affected genes is significantly enriched with motifs that were shown to be associated with the ARE-binding protein Pub1. Since a relatively small number of genes was affected by Hog1p deletion, additional signaling pathways are likely to be involved in coordinating the translational response to severe salinity stress.

Melamed, Daniel; Pnueli, Lilach; Arava, Yoav

2008-01-01

219

Quantitative Proteomics Reveals That Hsp90 Inhibition Preferentially Targets Kinases and the DNA Damage Response*  

PubMed Central

Despite the increasing importance of heat shock protein 90 (Hsp90) inhibitors as chemotherapeutic agents in diseases such as cancer, their global effects on the proteome remain largely unknown. Here we use high resolution, quantitative mass spectrometry to map protein expression changes associated with the application of the Hsp90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG). In depth data obtained from five replicate SILAC experiments enabled accurate quantification of about 6,000 proteins in HeLa cells. As expected, we observed activation of a heat shock response with induced expression of molecular chaperones, which refold misfolded proteins, and proteases, which degrade irreparably damaged polypeptides. Despite the broad range of known Hsp90 substrates, bioinformatics analysis revealed that particular protein classes were preferentially affected. These prominently included proteins involved in the DNA damage response, as well as protein kinases and especially tyrosine kinases. We followed up on this observation with a quantitative phosphoproteomic analysis of about 4,000 sites, which revealed that Hsp90 inhibition leads to much more down- than up-regulation of the phosphoproteome (34% down versus 6% up). This study defines the cellular response to Hsp90 inhibition at the proteome level and sheds light on the mechanisms by which it can be used to target cancer cells.

Sharma, Kirti; Vabulas, R. Martin; Macek, Boris; Pinkert, Stefan; Cox, Jurgen; Mann, Matthias; Hartl, F. Ulrich

2012-01-01

220

Food hypersensitivity and allergic diseases.  

PubMed

Allergic disease is a common cause of morbidity, particularly in young children. The prevalence of allergic disease has increased in the last 20 y in most countries. The sequential order of occurrence of allergy is food hypersensitivity, gastrointestinal manifestations, atopic eczema, asthma and hay fever. A variety of factors increase the risk of allergic disease, for example hereditary predisposition, exposure to 'allergenic' foods and environmental triggers such as house dust mites and tobacco in early life. Prolonged breast feeding, the use of a partial whey hydrolysed formula, delayed introduction of certain 'allergenic foods', and avoidance of inhalant allergens reduces the incidence of eczema and asthma, especially in high-risk infants. These preventive measures are extremely cost-effective and should be adopted widely at the community level. PMID:12142964

Chandra, R K

2002-08-01

221

Oxazolone-Induced Contact Hypersensitivity Reduces Lymphatic Drainage but Enhances the Induction of Adaptive Immunity  

PubMed Central

Contact hypersensitivity (CHS) induced by topical application of haptens is a commonly used model to study dermal inflammatory responses in mice. Several recent studies have indicated that CHS-induced skin inflammation triggers lymphangiogenesis but may negatively impact the immune-function of lymphatic vessels, namely fluid drainage and dendritic cell (DC) migration to draining lymph nodes (dLNs). On the other hand, haptens have been shown to exert immune-stimulatory activity by inducing DC maturation. In this study we investigated how the presence of pre-established CHS-induced skin inflammation affects the induction of adaptive immunity in dLNs. Using a mouse model of oxazolone-induced skin inflammation we observed that lymphatic drainage was reduced and DC migration from skin to dLNs was partially compromised. At the same time, a significantly stronger adaptive immune response towards ovalbumin (OVA) was induced when immunization had occurred in CHS-inflamed skin as compared to uninflamed control skin. In fact, immunization with sterile OVA in CHS-inflamed skin evoked a delayed-type hypersensitivity (DTH) response comparable to the one induced by conventional immunization with OVA and adjuvant in uninflamed skin. Striking phenotypic and functional differences were observed when comparing DCs from LNs draining uninflamed or CHS-inflamed skin. DCs from LNs draining CHS-inflamed skin expressed higher levels of co-stimulatory molecules and MHC molecules, produced higher levels of the interleukin-12/23 p40 subunit (IL-12/23-p40) and more potently induced T cell activation in vitro. Immunization experiments revealed that blockade of IL-12/23-p40 during the priming phase partially reverted the CHS-induced enhancement of the adaptive immune response. Collectively, our findings indicate that CHS-induced skin inflammation generates an overall immune-stimulatory milieu, which outweighs the potentially suppressive effect of reduced lymphatic vessel function.

Aebischer, David; Willrodt, Ann-Helen; Halin, Cornelia

2014-01-01

222

Effect of enalapril on allergen-induced cutaneous hypersensitivity reaction.  

PubMed Central

1. To test the hypothesis that the in vivo inhibition of angiotensin converting enzyme in a patient who presents atopy, results in a significant increase in cutaneous bradykinin and prostaglandin production, the effect of enalapril on the cutaneous hypersensitivity reaction was examined in 10 atopic volunteers. 2. A crossover study design was used and volunteers were randomly allocated to treatment with either enalapril (10 mg) alone, or in combination with indomethacin (75 mg), with and without ketotifen (1 mg). Drugs were administered twice daily for 2 days. 3. Allergen (Southern Grass Mix) was administered intradermally 2 h after last drug dosage and the surface areas of the immediate wheal-and-flare-reactions were measured 15 min later. The late phase of the cutaneous response was evaluated 6 h later by determining skinfold thickness and surface area. 4. Enalapril alone had no effect on any of the parameters measured. 5. The cutaneous hypersensitivity reaction was significantly reduced with regard to both immediate and late cutaneous responses when the indomethacin and ketotifen combination was added to enalapril therapy. 6. When only indomethacin was added to enalapril pretreatment the flare reaction was significantly reduced, but whealing was unaffected. 7. This study presents further evidence that mast cell mediators other than prostaglandins are involved in the cutaneous hypersensitivity reaction. Furthermore, that endogenous bradykinin production after enalapril pretreatment either never reaches the supraphysiological concentrations used in previous experiments, or that bradykinin is rapidly and effectively broken down to inactive peptides by other carboxypeptidase enzymes.

Snyman, J R; Sommers, D K

1991-01-01

223

Diabetic Visceral Hypersensitivity Is Associated With Activation of Mitogen-Activated Kinase in Rat Dorsal Root Ganglia  

PubMed Central

OBJECTIVE Diabetic patients often experience visceral hypersensitivity and anorectal dysfunction. We hypothesize that the enhanced excitability of colon projecting dorsal root ganglia (DRG) neurons observed in diabetes is caused by a decrease in the amplitude of the transient A-type K+ (IA) currents resulting from increased phosphorylation of mitogen-activated protein kinases (MAPK) and reduced opening of Kv4.2 channels. RESEARCH DESIGN AND METHODS We performed patch-clamp recordings of colon projecting DRG neurons from control and streptozotocin-induced diabetic (STZ-D) rats. Western blot analyses and immunocytochemistry studies were used to elucidate the intracellular signaling pathways that modulate the IA current. In vivo studies were performed to demonstrate that abnormal MAPK signaling is responsible for the enhanced visceromotor response to colorectal distention in STZ-D rats. RESULTS Patch-clamp studies demonstrated that IA current was diminished in the colon projecting DRG neurons of STZ-D rats. Western blot analysis of STZ-D DRG neurons revealed increases in phosphorylated MAPK and KV4.2. In diabetic DRG neurons, increased intracellular Ca2+ ([Ca2+]i), protein kinase C (PKC), and MAPK were involved in the regulation of IA current through modulation of Kv4.2. Hypersensitive visceromotor responses to colorectal distention in STZ-D rats were normalized by administration of MAPK inhibitor U0126. CONCLUSIONS We demonstrated that reduction of the IA current in STZ-D DRG neurons is triggered by impaired [Ca2+]i ion homeostasis, and this in turn activates the PKC-MAPK pathways, resulting in decreased opening of the Kv4.2 channels. Hence, the PKC-MAPK–Kv4.2 pathways represent a potential therapeutic target for treating visceral hypersensitivity in diabetes.

Grabauskas, Gintautas; Heldsinger, Andrea; Wu, Xiaoyin; Xu, Dabo; Zhou, ShiYi; Owyang, Chung

2011-01-01

224

Post-receptor defect accounts for phosphorylase hypersensitivity in cultured diabetic cardiomyocytes  

Microsoft Academic Search

The basis for the hypersensitive response of glycogen phosphorylase to epinephrine stimulation was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. To assess potential G-protein involvement in the response, normal and diabetic derived myocytes were incubated with either cholera or pertussis toxin prior to hormonal stimulation. Pretreatment of cardiomyocytes with cholera toxin resulted in a potentiated response

Jo Ann Buczek-Thomas; Stephen R. Jaspers; Thomas B. Miller

1992-01-01

225

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

PubMed

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

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

2010-10-01

226

Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination  

PubMed Central

Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4–6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFN?, IL-2 and/or TNF? in vitro in response to influenza vaccine or peptide. Ki-67+ cell numbers then decline rapidly, and ten days after vaccination, both Ki-67+ and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be substantially reshaped by vaccination, even if the overall memory cell numbers do not change significantly.

Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J.; Wu, Hulin; Zand, Martin S.; Mosmann, Tim R.

2013-01-01

227

Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity  

PubMed Central

Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy.

Shaham, Oded; Wei, Ru; Wang, Thomas J; Ricciardi, Catherine; Lewis, Gregory D; Vasan, Ramachandran S; Carr, Steven A; Thadhani, Ravi; Gerszten, Robert E; Mootha, Vamsi K

2008-01-01

228

Topical cis-urocanic acid suppresses both induction and elicitation of contact hypersensitivity in BALB/C mice.  

PubMed

Cis-urocanic acid, converted from trans-urocanic acid in stratum corneum by ultraviolet B irradiation, has been shown to impair contact hypersensitivity induction. To study whether topical cis-urocanic acid also alters contact hypersensitivity elicitation, as well as immediate hypersensitivity and acute irritation, we treated mice with 1% topical cis-urocanic acid or vehicle prior to induction or elicitation of hypersensitivity to contact allergen oxazolone or respiratory allergen trimellitic anhydride or prior to acute irritation from croton oil. Topical cis-urocanic acid suppressed both induction and elicitation of contact hypersensitivity to oxazolone. However, no effect by cis-urocanic acid on induction or elicitation of trimellitic anhydride allergy or croton oil irritation was seen. The possible efficacy of topical cis-urocanic acid as a treatment of inflammatory skin diseases responsive to ultraviolet B irradiation may be worthwhile to investigate. PMID:8578946

Lauerma, A I; Aioi, A; Maibach, H I

1995-07-01

229

Stipatosis or hypersensitivity pneumonitis caused by esparto (Stipa tenacissima) fibers.  

PubMed

Hypersensitivity pneumonitis or extrinsic allergic alveolitis may be defined as an immunological pulmonary disease caused by a variety of antigens reaching the lungs through inhaled organic and inorganic dusts derived from different sources, although they are usually occupational. Farmer's lung and pigeon breeder's lung are probably the most well-known types of hypersensitivity pneumonitis worldwide. Esparto grass (Stipa tenacissima), which is a grammineous plant which is commonly found in the Mediterranean countries, has a wide variety of uses. Esparto fiber is used for the manufacturing of ropes, hemp sandals, rush mats and parkets; for decorative stucco plates, used on walls and ceilings. Esparto supports a large industry in Spain. The first reports referring to esparto dust as a cause of respiratory disease did not appear until the 1960s, and it was first described as a byssinosis-like disorder. The first cases reported, in which immunologic and challenge tests were used to confirm this association, were described 14 years ago and referred as hypersensitivity pneumonitis nominated as stipatosis. Later, a large number of cases of esparto dust-induced hypersensitivity pneumonitis were reported by different authors, so that esparto may be nowadays considered as the main substance causing extrinsic allergic alveolitis in Spain. Afumigatus has been revealed to be the main inducing cause of stipatosis but probably is not the only one since other microorganisms could be implicated. On the other hand esparto fibers may also cause occupational asthma. In this article the prominent clinical findings of this disease as well as the results of serologic, bronchoalveolar lavage (BAL) and specific inhalation tests are shown. A complete historical review of esparto-induced allergic respiratory disease is also described. PMID:11642575

Hinojosa, M

2001-01-01

230

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

PubMed Central

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.

1989-01-01

231

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

PubMed Central

Background: Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. Results: We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ER? was expressed in developing heart valves but not in the liver, whereas ER?2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves. Citation: Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. 2014. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples. Environ Health Perspect 122:356–362;?http://dx.doi.org/10.1289/ehp.1307329

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

2014-01-01

232

Metabolomics reveals comprehensive reprogramming involving two independent metabolic responses of Arabidopsis to UV-B light.  

PubMed

Because of ever-increasing environmental deterioration it is likely that the influx of UV-B radiation (280-320 nm) will increase as a result of the depletion of stratospheric ozone. Given this fact it is essential that we better understand both the rapid and the adaptive responses of plants to UV-B stress. Here, we compare the metabolic responses of wild-type Arabidopsis with that of mutants impaired in flavonoid (transparent testa 4, tt4; transparent testa 5, tt5) or sinapoyl-malate (sinapoylglucose accumulator 1, sng1) biosynthesis, exposed to a short 24-h or a longer 96-h exposure to this photo-oxidative stress. In control experiments we subjected the genotypes to long-day conditions as well as to 24- and 96-h treatments of continuous light. Following these treatments we evaluated the dynamic response of metabolites including flavonoids, sinapoyl-malate precursors and ascorbate, which are well known to play a role in cellular protection from UV-B stress, as well as a broader range of primary metabolites, in an attempt to more fully comprehend the metabolic shift following the cellular perception of this stress. Our data reveals that short-term responses occur only at the level of primary metabolites, suggesting that these effectively prime the cell to facilitate the later production of UV-B-absorbing secondary metabolites. The combined results of these studies together with transcript profiles using samples irradiated by 24-h UV-B light are discussed in the context of current models concerning the metabolic response of plants to the stress imposed by excessive UV-B irradiation. PMID:21466600

Kusano, Miyako; Tohge, Takayuki; Fukushima, Atsushi; Kobayashi, Makoto; Hayashi, Naomi; Otsuki, Hitomi; Kondou, Youichi; Goto, Hiroto; Kawashima, Mika; Matsuda, Fumio; Niida, Rie; Matsui, Minami; Saito, Kazuki; Fernie, Alisdair R

2011-07-01

233

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

PubMed Central

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

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

2013-01-01

234

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

PubMed

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

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

2013-01-01

235

Sympathoinhibition and hypotension in carotid sinus hypersensitivity  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

236

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

PubMed

Regeneration is widespread throughout the animal kingdom, but our molecular understanding of this process in adult animals remains poorly understood. Wnt/?-catenin signaling plays crucial roles throughout animal life from early development to adulthood. In intact and regenerating planarians, the regulation of Wnt/?-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 re-organization 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 a 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

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

2010-11-01

237

Transcriptome profile reveals heat response mechanism at molecular and metabolic levels in rice flag leaf.  

PubMed

Flag leaf is one of the key photosynthesis organs during rice reproductive stage. A time course microarray analysis of rice flag leaf was done after 40°C treatment for 0 min, 20 min, 60 min, 2h, 4h, and 8h. The identified significant heat responsive genes were mainly involved in transcriptional regulation, transport, protein binding, antioxidant, and stress response. KMC analysis discovered the time-dependent gene expression pattern under heat. MapMan analysis demonstrated that, under heat treatment, Hsp genes and genes involved in glycolysis and ubiquitin-proteasome were enhanced, and genes involved in TCA, carotenoid, dihydroflavonol and anthocyanin metabolisms and light-reaction in the photosynthesis were widely repressed. Meanwhile, some rate-limiting enzyme genes in shikimate, lignin, and mevalonic acid metabolisms were up-regulated, revealing the importance of maintaining specific secondary metabolites under heat stress. The present study increased our understanding of heat response in rice flag leaf and provided good candidate genes for crop improvement. PMID:23994682

Zhang, Xianwen; Rerksiri, Wirat; Liu, Ailing; Zhou, Xiaoyun; Xiong, Hairong; Xiang, Jianhua; Chen, Xinbo; Xiong, Xingyao

2013-11-10

238

Response of Arabidopsis to Iron Deficiency Stress as Revealed by Microarray Analysis1  

PubMed Central

Gene expression in response to Fe deficiency was analyzed in Arabidopsis roots and shoots through the use of a cDNA collection representing at least 6,000 individual gene sequences. Arabidopsis seedlings were grown 1, 3, and 7 d in the absence of Fe, and gene expression in roots and shoots was investigated. Following confirmation of data and normalization methods, expression of several sequences encoding enzymes known to be affected by Fe deficiency was investigated by microarray analysis. Confirmation of literature reports, particularly for changes in enzyme activity, was not always possible, but changes in gene expression could be confirmed. An expression analysis of genes in glycolysis, the tricarboxylic acid cycle, and oxidative pentose phosphate pathway revealed an induction of several enzymes within 3 d of Fe-deficient growth, indicating an increase in respiration in response to Fe deficiency. In roots, transcription of sequences corresponding to enzymes of anaerobic respiration was also induced, whereas in shoots, the induction of several genes in gluconeogenesis, starch degradation, and phloem loading was observed. Thus, it seemed likely that the energy demand in roots required for the Fe deficiency response exceeded the capacity of oxidative phosphorylation, and an increase in carbon import and anaerobic respiration were required to maintain metabolism.

Thimm, Oliver; Essigmann, Bernd; Kloska, Sebastian; Altmann, Thomas; Buckhout, Thomas J.

2001-01-01

239

Subacute hypersensitivity pneumonitis in an HIV infected patient receiving antiretroviral therapy  

PubMed Central

Abnormal pulmonary immune response to various antigens can lead to hypersensitivity pneumonitis. This disease has not previously been reported in HIV infected patients. This case report describes an HIV infected woman who developed subacute hypersensitivity pneumonitis in response to bird exposure. The disease manifested itself only after the patient experienced an improvement in her CD4 positive T lymphocyte count secondary to antiretroviral therapy. This case emphasises the need to consider non-HIV associated diseases in patients with HIV and suggests that diseases in which host immune response plays an essential role in pathogenesis may become more prevalent in HIV infected patients receiving effective antiretroviral therapy.??

Morris, A.; Nishimura, S.; Huang, L.

2000-01-01

240

A novel TRPV1 receptor antagonist JNJ-17203212 attenuates colonic hypersensitivity in rats.  

PubMed

This study examined the efficacy of a novel TRPV1 antagonist, JNJ-17203212, in two experimental rat models that exhibit a hypersensitive visceral motor response (VMR) to colorectal distension (CRD). In the first model, intraluminal administration of acetic acid (1% solution) into the distal colon produced an acute colonic hypersensitivity. In the second model, intraluminal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the distal colon produced a chronic, post-inflammatory colonic hypersensitivity 30 days post-TNBS administration. Throughout this study, colonic sensitivity was assessed via quantification of VMR to CRD in rats following a single, oral administration of JNJ-17203212 (3, 10 or 30 mg/kg) or vehicle. Intraluminal administration of acetic acid and TNBS resulted in increased VMR to CRD when compared to controls. In both groups, VMR to CRD was significantly reduced by administration of JNJ-17203212 at 30 mg/kg. The results of this study show that the selective TRPV1 antagonist, JNJ-17203212, reduces sensitivity to luminal distension in both an acute, noninflammatory and a chronic, post-inflammatory rodent model of colonic hypersensitivity. These data indicate that TRPV1 is involved in the pathogenesis of visceral hypersensitivity and that JNJ-17203212 may be a potential therapeutic agent for functional bowel disorders characterized by abdominal hypersensitivity, such as irritable bowel syndrome. PMID:21132125

Wiskur, B J; Tyler, K; Campbell-Dittmeyer, K; Chaplan, S R; Wickenden, A D; Greenwood-Van Meerveld, B

2010-10-01

241

A double blind controlled trial comparing three treatment modalities for dentin hypersensitivity  

PubMed Central

Aim: This randomized, double blind, split mouth study was aimed to compare three dentin desensitizing treatment modalities. Methods: Two hundred sixty teeth of 25 patients; each having at least 2 hypersensitive teeth in each quadrant, were included. Teeth were randomized to 4 groups: Group A treated with 2% NaF solution, Group B received GLUMA®; an aqueous solution of Hydroxy-Ethyl-Methacrylate and Glutarldehyde, (HEMA-G), Group C received iontophoresis with distilled water (placebo) and Group D was treated with NaF-iontophoresis. Pain response was evaluated on a visual analogue scale (VAS), by using tactile, air blast and cold-water stimuli at 0-day, 15-day, 1-month and 3-months interval. Results: All treatments were effective in reducing dentinal hypersensitivity significantly, Group D and Group B were more effective than Group A and Group C at all time intervals. Group D and Group B were equally effective in reducing dentinal hypersensitivity at 15-day and 1-month interval but Group D was more effective at 3-months. Conclusion: All treatment modalities were more effective in reducing hypersensitivity than placebo. 2% NaF-iontophoresis and HEMA-G were more effective than 2% NaF local application at all time intervals. But at 3-months, 2% NaF-iontophoresis was more effective than HEMA-G, while placebo produced no significant effect in reduction of hypersensitivity. Key words:Hypersensitivity, desensitisation, iontophoresis, dentin adhesive, sodium fluoride.

Bhavsar, Neeta; Sahayata, Vishal; Acharya, Aneesha; Kshatriya, Payal

2012-01-01

242

Drug Hypersensitivity: Clinical Manifestations and Diagnosis  

Microsoft Academic Search

Drug hypersensitivity, including the allergic type, is one of the side effects of drugs and is a daily worry for the clinician.\\u000a Even though urticarial and maculopapular eruptions are the most frequent manifestations, there are many clinical forms, mirroring\\u000a many distinct pathophysiological events. The diagnosis of drug hypersensitivity often relies on clinical histories, skin tests,\\u000a patch tests, and a few

Pascal Demoly; Antonino Romano

243

Electrical Hypersensitivity in Humans —Fact or Fiction?  

Microsoft Academic Search

The phenomenon of the so-called electrical hypersensitivity in the weak electromagnetic fields of everyday life, potentially causing different health symptoms, is reviewed under consideration of current results from in-vivo and in-vitro investigations as well as of statistical data.Electrical hypersensitivity cannot be explained by means of the known and validated influence mechanisms of electromagnetic fields in humans, as their thresholds are

Jiri Silny

1999-01-01

244

Hepatitis B surface antigen induces an early-type hypersensitivity.  

PubMed

In addition to the delayed-type hypersensitivity (DTH), a unique type of hypersensitivity could be induced at a late stage of the immune responses after hepatitis B surface antigen (HBsAg) immunization. This antigen-specific ear swelling that develops within 1 h after antigen challenge has been referred to as the early-type hypersensitivity (ETH) in contrast to the 24-h DTH. Although expression of ETH was earlier than DTH, the induction of the former needed 3 days longer than that of the latter. In ETH, the plasma protein leaked into the tissue and the vasopermeability increased within 15 min, causing the oedema of ETH. The observation that cyproheptadine, not dexamethasone, inhibited ETH suggests that it is mediated through the release of histamine and/or serotonin. Furthermore, ETH could be transferred by immune sera. Heat treatment (56 C for 4 h) did not destroy the transfer, suggesting that it was not mediated by IgE. The human anti-HBs sera from either hepatitis B virus infection or HBsAg vaccinee also contained the activity to transfer the ETH in mice. PMID:1993355

Lei, H Y; Wang, J Y; Chang, T T; Wang, C C

1991-02-01

245

Radiation hypersensitivity and radioresistant DNA synthesis in ataxia-telangiectasia  

SciTech Connect

Patients with the autosomal recessive genetic disease, ataxia-telangiectasia (A-T), are cancer-prone and hypersensitive to the killing effects of ionizing radiation. In an attempt to isolate the gene(s) responsible for the hypersensitivity of A-T cells, they were transfected with normal human DNA in cosmid vectors containing a rescuable marker (G-418 resistance), and revertants to normal sensitivity were isolated and characterized. The failure of radioresistant revertants to demonstrate a reversion of the phenotype, radioresistant DNA synthesis, shows that this feature is dependent on a gene separate from the one conferring resistance to cell killing. Cells from every A-T patient thus far examined demonstrate both hypersensitivity, in terms of radiation-induced cell killing, and radioresistant DNA synthesis. The results reported here, however, show that the former is not a result of the latter, as previously proposed. Moreover, the fact that these two characteristics can be uncoupled obscures the role(s) that either of them plays in the etiology of the disease, or in the development in its other features, including cancer-proneness.

Painter, R.B.

1985-11-01

246

Advanced phenotyping in hypersensitivity drug reactions to NSAIDs.  

PubMed

Non-steroidal anti-inflammatory drugs (NSAIDs) are the medications most frequently involved in hypersensitivity drug reactions. Because NSAIDs are prescribed for many conditions, this is a world-wide problem affecting patients of all ages. Various hypersensitivity reactions have been reported, mainly affecting the skin and/or the respiratory airways. The most frequent of these is acute urticaria, which can be induced by several different NSAIDs. Both specific and non-specific immunological pathways have been proposed as underlying mechanisms. This review presents the clinical phenotypes and the drugs involved in NSAID hypersensitivity. Five major clinical syndromes can be distinguished: aspirin-exacerbated respiratory disease (AERD), aspirin-exacerbated cutaneous disease (AECD), multiple NSAID-induced urticaria/angioedema (MNSAID-UA), single NSAID-IgE reactions and single NSAID T cell responses. However, further classification is possible within these five major entities, by detailed descriptions of the clinical characteristics enabling more phenotypes to be defined. This detailed differentiation now seems required in order to undertake appropriate pharmacogenetic studies. PMID:24074328

Ayuso, P; Blanca-López, N; Doña, I; Torres, M J; Guéant-Rodríguez, R M; Canto, G; Sanak, M; Mayorga, C; Guéant, J L; Blanca, M; Cornejo-García, J A

2013-10-01

247

Drug Induced Hypersensitivity and the HLA Complex  

PubMed Central

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

Alfirevic, Ana; Pirmohamed, Munir

2011-01-01

248

Global Phosphoproteome Profiling Reveals Unanticipated Networks Responsive to Cisplatin Treatment of Embryonic Stem Cells ? †  

PubMed Central

Cellular responses to DNA-damaging agents involve the activation of various DNA damage signaling and transduction pathways. Using quantitative and high-resolution tandem mass spectrometry, we determined global changes in protein level and phosphorylation site profiles following treatment of SILAC (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected. Although the ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) consensus sequence (S/T-Q motif) was significantly overrepresented among hyperphosphorylated peptides, about half of the >2-fold-upregulated phosphorylation sites based on the consensus sequence were not direct substrates of ATM and ATR. Eleven protein kinases mainly belonging to the mitogen-activated protein kinase (MAPK) family were identified as being regulated in their kinase domain activation loop. The biological importance of three of these kinases (cyclin-dependent kinase 7 [CDK7], Plk1, and KPCD1) in the protection against cisplatin-induced cytotoxicity was demonstrated by small interfering RNA (siRNA)-mediated knockdown. Our results indicate that the cellular response to cisplatin involves a variety of kinases and phosphatases not only acting in the nucleus but also regulating cytoplasmic targets, resulting in extensive cytoskeletal rearrangements. Integration of transcriptomic and proteomic data revealed a poor correlation between changes in the relative levels of transcripts and their corresponding proteins, but a large overlap in affected pathways at the levels of mRNA, protein, and phosphoprotein. This study provides an integrated view of pathways activated by genotoxic stress and deciphers kinases that play a pivotal role in regulating cellular processes other than the DNA damage response.

Pines, Alex; Kelstrup, Christian D.; Vrouwe, Mischa G.; Puigvert, Jordi C.; Typas, Dimitris; Misovic, Branislav; de Groot, Anton; von Stechow, Louise; van de Water, Bob; Danen, Erik H. J.; Vrieling, Harry; Mullenders, Leon H. F.; Olsen, Jesper V.

2011-01-01

249

Emerging role of astroglia in pain hypersensitivity  

PubMed Central

Summary Recent studies suggest that astroglia, a major non-neuronal cell type in the central nervous system, actively participate in synaptic activity and potentially contribute to neurological disorders including chronic pain. Astroglia exhibit a hyperactive phenotype, also referred to as reactive astrocytosis, in response to peripheral injury. This process is often referred to as astroglial activation. By immunostaining against glial fibrillary acidic proteins, an intermediate cytoskeleton filament protein selectively localized to matured astrocytes, hypertrophy of astrocytes are clearly visible in the spinal cord dorsal horn and spinal trigeminal nucleus following a variety of injuries. Injury-related astroglial activation correlates with behavioral hyperalgesia and conversely, astroglial inhibition attenuates pain hypersensitivity. Astrocytes have a close anatomical relationship with neurons. Interactions between astrocytes and neurons contribute to the mechanisms of chronic pain. Astroglial activation is accompanied by initiation of cellular signal transduction pathways that lead to transcriptional gene regulation and release of a variety of chemical mediators or gliotransmitters, down-regulation of glutamate transporter activity that directly affects synaptic transmission, changes in gap junction proteins by which calcium waves spread, and alterations of the blood brain barrier. These coordinated changes in astroglial functions in turn modulate neuronal activity and facilitate pain transmission.

Ren, Ke

2009-01-01

250

Experimental hypersensitivity pneumonitis: influence of donor sensitization.  

PubMed

Experimental hypersensitivity pneumonitis (EHP) can be transferred to strain 2 guinea pigs by lymphoblasts from lymph node cells from sensitized guinea pigs cultured in vitro with antigen. We sought to examine the relationship between characteristics of the donor animal and development of competence to transfer EHP. We also compared cell populations that were capable and incapable of transfer using flow cytometry and fluorescein conjugated anti-Ig to determine cell size and surface IgG + (SIg +: surface immunoglobulin-positive) cells. Lymph node cells from donor animals were cultured with a soluble extract of Micropolyspora faeni (10 micrograms/ml) for 72 hours; blasts were then isolated and transferred intravenously to syngeneic recipients. Control recipients received an equal volume of medium. Four groups of donors were used: animals systemically sensitized with Freund's adjuvant and M. faeni and challenged with two, four, or eight weekly intratracheal injections of M. faeni (2-, 4-, and 8-week group); and animals sensitized with Freund's adjuvant and normal saline and challenged with two weekly intratracheal injections of normal saline (NS group). Recipients were challenged intratracheally with M. faeni 48 hours after the cell transfer and killed 4 days thereafter. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. All animals were maintained in high efficiency particulate accumulator-filtered air. There was a low level of pulmonary response to an intratracheal challenge of M. faeni in animals that received media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2341765

Schuyler, M; Gott, K; Shopp, G; Crooks, L

1990-05-01

251

Cockatiel-induced hypersensitivity pneumonitis.  

PubMed Central

Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis.

McCluskey, James D; Haight, Robert R; Brooks, Stuart M

2002-01-01

252

Recent advances in hypersensitivity pneumonitis.  

PubMed

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

Lacasse, Yves; Girard, Mélissa; Cormier, Yvon

2012-07-01

253

Akt2 deficiency promotes cardiac induction of Rab4a and myocardial ?-adrenergic hypersensitivity.  

PubMed

Patients with diabetes mellitus can develop cardiac dysfunction in the absence of underlying coronary artery disease or hypertension; a condition defined as diabetic cardiomyopathy. Mice lacking the intracellular protein kinase Akt2 develop a syndrome that is similar to diabetes mellitus type 2. Expression profiling of akt2(-/-) myocardium revealed that Rab4a, a GTPase involved in glucose transporter 4 translocation and ?-adrenergic receptor (?AR) recycling to the plasma membrane, was significantly induced. We therefore hypothesized that Akt2 deficiency increases myocardial ?-adrenergic sensitivity. Confirmatory analysis revealed up-regulation of Rab4a mRNA and protein in akt2(-/-) myocardium. In cultured cardiomyocyte experiments, Rab4a was induced by pharmacological inhibition of Akt as well as by specific knockdown of Akt2 with siRNA. Isolated akt2(-/-) hearts were hypersensitive to isoproterenol (ISO) but exhibited normal sensitivity to forskolin. Prolonged ISO treatment led to increased cardiac hypertrophy in akt2(-/-) mice compared to wild type mice. In addition, spontaneous hypertrophy was noted in aged akt2(-/-) hearts that was inhibited by treatment with the ?AR blocker propranolol. In agreement with previous results demonstrating increased fatty acid oxidation rates in akt2(-/-) myocardium, we found increased peroxisome proliferator-activated receptor ? (PPAR?) activity in the hearts of these animals. Interestingly, increased myocardial Rab4a expression was present in mice with cardiac-specific overexpression of PPAR? and was also observed upon stimulation of PPAR? activity in cultured cardiomyocytes. Accordingly, propranolol attenuated the development of cardiac hypertrophy in the PPAR? transgenic mice as well. Our results indicate that reduced Akt2 leads to up-regulation of Rab4a expression in cardiomyocytes in a cell-autonomous fashion that may involve activation of PPAR?. This maladaptive response is associated with hypersensitivity of akt2(-/-) myocardium to ?-adrenergic stimulation. PMID:20728450

Etzion, Sharon; Etzion, Yoram; DeBosch, Brian; Crawford, Peter A; Muslin, Anthony J

2010-12-01

254

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

PubMed

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. PMID:24083463

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

2013-11-01

255

Microarray analysis of Pseudomonas aeruginosa reveals induction of pyocin genes in response to hydrogen peroxide  

PubMed Central

Background Pseudomonas aeruginosa, a pathogen infecting those with cystic fibrosis, encounters toxicity from phagocyte-derived reactive oxidants including hydrogen peroxide during active infection. P. aeruginosa responds with adaptive and protective strategies against these toxic species to effectively infect humans. Despite advances in our understanding of the responses to oxidative stress in many specific cases, the connectivity between targeted protective genes and the rest of cell metabolism remains obscure. Results Herein, we performed a genome-wide transcriptome analysis of the cellular responses to hydrogen peroxide in order to determine a more complete picture of how oxidative stress-induced genes are related and regulated. Our data reinforce the previous conclusion that DNA repair proteins and catalases may be among the most vital antioxidant defense systems of P. aeruginosa. Our results also suggest that sublethal oxidative damage reduces active and/or facilitated transport and that intracellular iron might be a key factor for a relationship between oxidative stress and iron regulation. Perhaps most intriguingly, we revealed that the transcription of all F-, R-, and S-type pyocins was upregulated by oxidative stress and at the same time, a cell immunity protein (pyocin S2 immunity protein) was downregulated, possibly leading to self-killing activity. Conclusion This finding proposes that pyocin production might be another novel defensive scheme against oxidative attack by host cells.

Chang, Wook; Small, David A; Toghrol, Freshteh; Bentley, William E

2005-01-01

256

Quantitative Proteomics Reveal ATM Kinase-dependent Exchange in DNA Damage Response Complexes  

PubMed Central

ATM is a protein kinase that initiates a well-characterized signaling cascade in cells exposed to ionizing radiation (IR). However, the role for ATM in coordinating critical protein interactions and subsequent exchanges within DNA damage response (DDR) complexes is unknown. We combined SILAC-based tandem mass spectrometry and a subcellular fractionation protocol to interrogate the proteome of irradiated cells treated with or without the ATM kinase inhibitor KU55933. We developed an integrative network analysis to identify and prioritize proteins that were responsive to KU55933, specifically in chromatin, and that were also enriched for physical interactions with known DNA repair proteins. This analysis identified 53BP1 and annexin A1 (ANXA1) as strong candidates. Using fluorescence recovery after photobleaching, we found that the exchange of GFP-53BP1 in DDR complexes decreased with KU55933. Further, we found that ANXA1 knockdown sensitized cells to IR via a mechanism that was not potentiated by KU55933. Our study reveals a role for ATM kinase activity in the dynamic exchange of proteins in DDR complexes and identifies a role for ANXA1 in cellular radioprotection.

Choi, Serah; Srivas, Rohith; Fu, Katherine Y.; Hood, Brian L.; Dost, Banu; Gibson, Gregory A.; Watkins, Simon C.; Van Houten, Bennett; Bandeira, Nuno; Conrads, Thomas P.; Ideker, Trey; Bakkenist, Christopher J.

2012-01-01

257

Opioid-induced latent sensitization in a model of non-inflammatory viscerosomatic hypersensitivity  

PubMed Central

Exposure to opioids can induce a state of “latent sensitization” characterized by long-lasting enhanced responses to subsequent cutaneous injury. Here, we explored the possibility that prior treatment with morphine could induce a state of latent sensitization to visceral pain conditions. Following butyrate enemas to induce non-inflammatory visceral pain, acute morphine administration produced dose-related inhibition of referred viscerosomatic hypersensitivity. Treatment with morphine for a period of six days resulted in a persistent hyperalgesia that resolved many days after termination of drug administration. In morphine pre-exposed rats, butyrate-induced referred hypersensitivity was enhanced and extended in duration. No differences were observed in the morphine dose-response curve in suppression of acute nociception (i.e., the hot-plate assay) when morphine pre-exposed rats were compared to naïve rats indicating that opioid antinociceptive tolerance was not present. However, the morphine dose-response curve to suppress evoked viscerosomaticl hypersensitivity was displaced to the right by approximately 4-fold in morphine pre-exposed rats. Induction of viscerosomativ hypersensitivity resulted in an increased labeling of CGRP-, but not substance P-positive cells in the lumbar dorsal root ganglia; increased labeling was not affected by prior exposure to morphine. The data indicate that a period of morphine exposure can induce a state of “latent-sensitization” to subsequent visceral pain characterized by extended duration of hypersensitivity. This condition likely reflects enhanced visceral “pain” intensity as a consequence of persistent pronociceptive adaptive changes.

Lian, Bo; Vera-Portocarrero, Louis; King, Tamara; Ossipov, Michael H.; Porreca, Frank

2014-01-01

258

Problem gamblers exhibit reward hypersensitivity in medial frontal cortex during gambling  

Microsoft Academic Search

Problem gambling (PG) is increasingly conceptualized as an addiction akin to substance abuse, rather than an impulse control disorder, however the mechanism of addiction remains unclear. Neuroimaging investigations have supported a “reward deficiency” hypothesis for PG by suggesting a blunted response to gambling, particularly in the striatum. Here we describe electrophysiological evidence of a hypersensitive response to gambling feedback in

Scott A. K. Oberg; Gregory J. Christie; Matthew S. Tata

2011-01-01

259

Hypersensitive teeth. Part II: Treatment.  

PubMed

If the hydrodynamic theory for pain transmission were accepted, occlusion of the patent dentinal tubules would appear to be essential for treatment efficacy. There are many compounds with seemingly varied chemical forms that have been shown to be effective. Their exact mode of action however, is not clearly defined because well-designed, nonbiased, and controlled comparison studies between agents are lacking. The various toothpastes may have ingredients that actually occlude patent tubules or they may cause secondary desensitization by irrational or abrasive action. In any pain study, the nature of the placebo effect and other psychogenic factors play a significant role. Fluoride preparation with and without iontophoresis has been shown to alter tubule structure and form microprecipitates. The natural desensitization process, although slow, is nature's protection, allowing dentinal sclerosis of secondary dentin formation. Although the resin-adhesive systems, especially the new light-cured dentin bonding agents, appear immediately to be effective, the effect on the pulp remains unknown. Perhaps a combination of iontophoresis with sodium fluoride and light-cured dentin bonding material may yield protection and desensitization at a high level of predictability. With the population trends toward a more geriatric society, further research, knowledge, and understanding of dentinal hypersensitivity is of paramount importance. The expected increase in longevity of the dentition suggests that dentin exposure and sensitivity will increase as a clinical problem. There is a clear time-age relationship involved in gingival recession, erosion and attrition of the teeth, and the need for periodontal surgical therapy. For total comprehensive care, patient comfort is important and should be provided along with sound periodontal health and ideal restorative function. PMID:3528461

Krauser, J T

1986-09-01

260

Probabilistic independent component analysis for laser speckle contrast images reveals in vivo multi - component vascular responses to forepaw stimulation  

Microsoft Academic Search

Brain's functional response can be studied by observing the spatiotemporal dynamics of functional and structural changes in cerebral vasculature. However, very few studies explore detailed changes at the level of individual microvessels while revealing the simultaneous wide field view of microcirculation responses to functional stimulation. Here we use a high spatiotemporal resolution laser speckle contrast imaging method, in combination with

Nan Li; Galit Pelled; Nitish V. Thakor

2010-01-01

261

Hypersensitivity manifestations to the fruit mango  

PubMed Central

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

Sareen, Richa

2011-01-01

262

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

USGS Publications Warehouse

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. ER? is expressed in developing heart valves but not in the liver, whereas ER?2 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.

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

2014-01-01

263

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

PubMed Central

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

Davis, Lauren M. G.; Martinez, Ines; Walter, Jens; Goin, Caitlin; Hutkins, Robert W.

2011-01-01

264

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

PubMed

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 prospect of strengthening dentin and rendering it less susceptible to predisposing factors, while concurrently reducing dentin hypersensitivity. Clinical studies have shown that a new toothpaste containing 8% arginine, calcium carbonate, and 1450 ppm fluoride as sodium monofluorophosphate offers significantly increased efficacy in reducing sensitivity, compared to a market-leading toothpaste containing 2% potassium ion. Mechanism of action studies have shown that this technology physically seals dentin tubules with a plug that contains arginine, calcium carbonate, and phosphate. This plug, which is resistant to normal pulpal pressures and to acid challenge, effectively reduces dentin fluid flow and, thereby, reduces sensitivity. PMID:19489186

Cummins, Diane

2009-01-01

265

The similarity structure of distributed neural responses reveals the multiple representations of letters.  

PubMed

Most cognitive theories of reading and spelling posit modality-specific representations of letter shapes, spoken letter names, and motor plans as well as abstract, amodal letter representations that serve to unify the various modality-specific formats. However, fundamental questions remain regarding the very existence of abstract letter representations, the neuro-topography of the different types of letter representations, and the degree of cortical selectivity for orthographic information. We directly test quantitative models of the similarity/dissimilarity structure of distributed neural representations of letters using Multivariate Pattern Analysis-Representational Similarity Analysis (MVPA-RSA) searchlight methods to analyze the BOLD response recorded from single letter viewing. These analyses reveal a left hemisphere ventral temporal region selectively tuned to abstract letter representations as well as substrates tuned to modality-specific (visual, phonological and motoric) representations of letters. The approaches applied in this research address various shortcomings of previous studies that have investigated these questions and, therefore, the findings we report serve to advance our understanding of the nature and format of the representations that occur within the various sub-regions of the large-scale networks used in reading and spelling. PMID:24321558

Rothlein, David; Rapp, Brenda

2014-04-01

266

Delay discounting task in pigs reveals response strategies related to dopamine metabolite.  

PubMed

We developed a novel delay discounting task to investigate outcome impulsivity in pigs. As impulsivity can affect aggression, and might also relate to proactive and reactive coping styles, eight proactive (HR) and eight reactive (LR) pigs identified in a manual restraint test ("Backtest", after Bolhuis et al., 2003) were weaned and mixed in four pens of four unfamiliar pigs, so that each pen had two HR and two LR pigs, and aggression was scored in the 9h after mixing. In the delay discounting task, each pig chose between two levers, one always delivering a small immediate reward, the other a large delayed reward with daily increasing delays, impulsive individuals being the ones discounting the value of the large reward quicker. Two novel strategies emerged: some pigs gradually switched their preference towards the small reward ('Switchers') as predicted, but others persistently preferred the large reward until they stopped making choices ('Omitters'). Outcome impulsivity itself was unrelated to these strategies, to urinary serotonin metabolite (5-HIAA) or dopamine metabolite (HVA) levels, aggression at weaning, or coping style. However, HVA was relatively higher in Omitters than Switchers, and positively correlated with behavioural measures of indecisiveness and frustration during choosing. The delay discounting task thus revealed two response strategies that seemed to be related to the activity of the dopamine system and might indicate a difference in execution, rather than outcome, impulsivity. PMID:23954408

Melotti, Luca; Thomsen, Liat Romme; Toscano, Michael J; Mendl, Michael; Held, Suzanne

2013-08-15

267

Plasminogen activator urokinase expression reveals TRAIL responsiveness and supports fractional survival of cancer cells  

PubMed Central

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10/Apo2L) holds promise for cancer therapy as it induces apoptosis in a large variety of cancer cells while exerting negligible toxicity in normal ones. However, TRAIL can also induce proliferative and migratory signaling in cancer cells resistant to apoptosis induced by this cytokine. In that regard, the molecular mechanisms underlying the tumor selectivity of TRAIL and those balancing apoptosis versus survival remain largely elusive. We show here that high mRNA levels of PLAU, which encodes urokinase plasminogen activator (uPA), are characteristic of cancer cells with functional TRAIL signaling. Notably, decreasing uPA levels sensitized cancer cells to TRAIL, leading to markedly increased apoptosis. Mechanistic analyses revealed three molecular events taking place in uPA-depleted cells: reduced basal ERK1/2 prosurvival signaling, decreased preligand decoy receptor 2 (DcR2)-death receptor 5 (DR5) interaction and attenuated recruitment of DcR2 to the death-inducing signaling complex upon TRAIL challenge. These phenomena were accompanied by increased FADD and procaspase-8 recruitment and processing, thus guiding cells toward a caspase-dependent cell death that is largely independent of the intrinsic apoptosis pathway. Collectively, our results unveil PLAU mRNA levels as marker for the identification of TRAIL-responsive tumor cells and highlight a key role of uPA signaling in ‘apoptosis versus survival' decision-making processes upon TRAIL challenge.

Pavet, V; Shlyakhtina, Y; He, T; Ceschin, D G; Kohonen, P; Perala, M; Kallioniemi, O; Gronemeyer, H

2014-01-01

268

Genetic structure along an elevational gradient in Hawaiian honeycreepers reveals contrasting evolutionary responses to avian malaria  

PubMed Central

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.

2008-01-01

269

Plasminogen activator urokinase expression reveals TRAIL responsiveness and supports fractional survival of cancer cells.  

PubMed

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10/Apo2L) holds promise for cancer therapy as it induces apoptosis in a large variety of cancer cells while exerting negligible toxicity in normal ones. However, TRAIL can also induce proliferative and migratory signaling in cancer cells resistant to apoptosis induced by this cytokine. In that regard, the molecular mechanisms underlying the tumor selectivity of TRAIL and those balancing apoptosis versus survival remain largely elusive. We show here that high mRNA levels of PLAU, which encodes urokinase plasminogen activator (uPA), are characteristic of cancer cells with functional TRAIL signaling. Notably, decreasing uPA levels sensitized cancer cells to TRAIL, leading to markedly increased apoptosis. Mechanistic analyses revealed three molecular events taking place in uPA-depleted cells: reduced basal ERK1/2 prosurvival signaling, decreased preligand decoy receptor 2 (DcR2)-death receptor 5 (DR5) interaction and attenuated recruitment of DcR2 to the death-inducing signaling complex upon TRAIL challenge. These phenomena were accompanied by increased FADD and procaspase-8 recruitment and processing, thus guiding cells toward a caspase-dependent cell death that is largely independent of the intrinsic apoptosis pathway. Collectively, our results unveil PLAU mRNA levels as marker for the identification of TRAIL-responsive tumor cells and highlight a key role of uPA signaling in 'apoptosis versus survival' decision-making processes upon TRAIL challenge. PMID:24481457

Pavet, V; Shlyakhtina, Y; He, T; Ceschin, D G; Kohonen, P; Perälä, M; Kallioniemi, O; Gronemeyer, H

2014-01-01

270

Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart.  

PubMed

Recent advances in genome analysis have enabled the identification of numerous distal enhancers that regulate gene expression in various conditions. However, the enhancers involved in pathological conditions are largely unknown because of the lack of in vivo quantitative assessment of enhancer activity in live animals. Here, we established a noninvasive and quantitative live imaging system for monitoring transcriptional activity and identified a novel stress-responsive enhancer of Nppa and Nppb, the most common markers of heart failure. The enhancer is a 650-bp fragment within 50 kb of the Nppa and Nppb loci. A chromosome conformation capture (3C) assay revealed that this distal enhancer directly interacts with the 5'-flanking regions of Nppa and Nppb. To monitor the enhancer activity in a live heart, we established an imaging system using the firefly luciferase reporter. Using this imaging system, we observed that the novel enhancer activated the reporter gene in pressure overload-induced failing hearts (failing hearts: 5.7±1.3-fold; sham-surgery hearts: 1.0±0.2-fold; P<0.001, repeated-measures ANOVA). This method will be particularly useful for identifying enhancers that function only during pathological conditions. PMID:24391132

Matsuoka, Ken; Asano, Yoshihiro; Higo, Shuichiro; Tsukamoto, Osamu; Yan, Yi; Yamazaki, Satoru; Matsuzaki, Takashi; Kioka, Hidetaka; Kato, Hisakazu; Uno, Yoshihiro; Asakura, Masanori; Asanuma, Hiroshi; Minamino, Tetsuo; Aburatani, Hiroyuki; Kitakaze, Masafumi; Komuro, Issei; Takashima, Seiji

2014-04-01

271

HLA alleles and drug hypersensitivity reactions.  

PubMed

The human leucocyte antigen (HLA) system is well known for its association with certain diseases such as ankylosing spondylitis, celiac disease and many others. More recently, severe and even fatal drug hypersensitivity reactions linked to particular HLA alleles have been discovered. The significance of these discoveries has led the European Medicines Agency (EMA) and its member state agencies to recommend HLA gene testing before initiation of drug treatment. To date, the following drugs have been identified as causing significant drug hypersensitivity reactions in patients who have the following HLA alleles: abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02/A*31:01 and finally allopurinol and HLA-B*58:01. This review will outline and discuss these three drugs and their associated HLA alleles as well as examine the pathogenesis of the drug hypersensitivity reactions. PMID:22136512

Profaizer, T; Eckels, D

2012-04-01

272

TRPA1 Contributes to Cold Hypersensitivity  

PubMed Central

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.

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

273

Prevention of Ultraviolet Radiation-Induced Suppression of Contact and Delayed Hypersensitivity by Aloe barbadensis Gel Extract  

Microsoft Academic Search

We investigated the ability of Aloe barbadensis gel extract to prevent suppression of contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH) responses in mice by ultraviolet (UV) irradiation. Local immune suppression was induced in C3H mice by exposure to four daily doses of 400 J\\/m2 UV-B (280 – 320 nm) radiation from FS40 sunlamps, followed by sensitization with 0.5% fluorescein isothiocyanate

Faith M. Strickland; Ronald P. Pelley; Margaret L. Kripke

1994-01-01

274

Lamotrigine Hypersensitivity Syndrome and Spiking Fever  

PubMed Central

We report a case of a 26 year old woman with rash, lymphadenopathy, liver enzyme abnormalities and spiking fever. She was diagnosed with drug-induced hypersensitivity syndrome (DHS) to lamotrigine. Spiking fever in relation to drug-induced hypersensitivity syndrome has not earlier been described in adults. Spiking fever is an important symptom of the wide spectrum of disease presentation. The syndrome is commonly referred to as either Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) or DHS. In accord with previous authors we see both syndromes as two ends of a spectrum, with a wide range of symptoms and presentations. Therefore we plea for unity in nomenclature.

Bakker, Christiaan V; Hegt, Vincent Noordhoek; Praag, Marinus C G Van

2012-01-01

275

[Subacute hypersensitivity pneumonitis after occupational mold exposure].  

PubMed

Mold-induced hypersensitivity pneumonitis is a rare and usually slowly progressing disorder. Therefore, the diagnosis and etiological investigations may be challenging and may often cause delay, despite the fact that early diagnosis and avoidance of the disease inducing agent are essential for the management of the disease. When appropriately treated, hypersensitivity pneumonitis is usually a relatively benign disorder. Irreversible pulmonary fibrosis may develop in cases of prolonged exposure. The disorder is considered as an occupational disease if the sufficient exposure occurs at workplace. PMID:23786111

Eerikäinen, Johanna; Nynäs, Pia; Uitti, Jukka

2013-01-01

276

Fatal hypersensitivity pneumonitis associated with docetaxel.  

PubMed

We present a patient with advanced breast cancer treated with three cycles of docetaxel who developed repeated episodes of hypersensitivity pneumonitis, progressed to respiratory failure and death despite treatment with corticosteroids and supportive care. Docetaxel-induced hypersensitivity pneumonitis was diagnosed by excluding infection and tumor spread with bronchoalveolar lavage and lung biopsy. Physicians should consider such a condition in all patients who present with interstitial pneumonitis and respiratory failure when they are receiving docetaxel and treat them aggressively with steroids and supportive care, as it can be fatal. PMID:24158075

Gurram, Murali Krishna; Pulivarthi, Swaroopa; McGary, Carl T

2013-01-01

277

Hepatitis C virus reveals a novel early control in acute immune response.  

PubMed

Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-?B-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2?-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response. PMID:22022264

Arnaud, Noëlla; Dabo, Stéphanie; Akazawa, Daisuke; Fukasawa, Masayoshi; Shinkai-Ouchi, Fumiko; Hugon, Jacques; Wakita, Takaji; Meurs, Eliane F

2011-10-01

278

Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response  

PubMed Central

Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-?B-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2?-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response.

Arnaud, Noella; Dabo, Stephanie; Akazawa, Daisuke; Fukasawa, Masayoshi; Shinkai-Ouchi, Fumiko; Hugon, Jacques; Wakita, Takaji; Meurs, Eliane F.

2011-01-01

279

Chemotherapy hypersensitivity reactions in ovarian cancer.  

PubMed

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

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

2014-03-01

280

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

PubMed Central

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 (?s). 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 could also be associated with an osmoregulatory response to drought and might function as a protective agent against ROS. In droughted nodules, the decrease in N2 fixation was caused by an increase in oxygen resistance that was induced in the nodule. This was a mechanism to avoid oxidative damage associated with reduced respiration activity and the consequent increase in oxygen content. This study highlighted that even though drought had a direct effect on leaves, the deleterious effects of drought on nodules also conditioned leaf responsiveness.

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

2011-01-01

281

Pharmacological stimulation of locus coeruleus reveals a new antipsychotic-responsive pathway for deficient sensorimotor gating.  

PubMed

Surprisingly little is known about the modulation of core endophenotypes of psychiatric disease by discrete noradrenergic (NE) circuits. Prepulse inhibition (PPI), the diminution of startle responses when weak prestimuli precede the startling event, is a widely validated translational paradigm for information-processing deficits observed in several mental disorders including schizophrenia, Tourette's syndrome, and post-traumatic stress disorder (PTSD). Despite putative NE disturbances in these illnesses, NE regulation of PPI remains poorly understood. In these studies, regulation of PPI by the locus coeruleus (LC), the primary source of NE to forebrain, was evaluated in rats using well-established protocols to pharmacologically activate/inactivate this nucleus. The ability of drugs that treat deficient PPI in these illnesses to reverse LC-mediated PPI deficits was also tested. Stimulation of LC receptors produced an anatomically and behaviorally specific deficit in PPI that was blocked by clonidine (Cataprese, an ?2 receptor agonist that reduces LC neuronal firing after peri-LC delivery), a postsynaptic ?1 NE receptor antagonist (prazosin), and second-generation antipsychotics (olanzapine, seroquel), but not by drugs that antagonized dopamine-1 (SCH23390), dopamine-2 (the first-generation antipsychotic Haloperidol), or serotonin-2 receptors (ritanserin). These results indicate a novel substrate in the regulation of PPI and reveal a novel functional role for the LC. Hence, a hyperactive LC-NE system might underlie a deficient sensorimotor gating endophenotype in a subset of patients suffering from psychiatric illnesses including schizophrenia, Tourette's syndrome, and PTSD, and the ability to normalize LC-NE transmission could contribute to the clinical efficacy of certain drugs (Cataprese, prazosin, and second-generation antipsychotics) in these conditions. PMID:21508929

Alsene, Karen M; Bakshi, Vaishali P

2011-07-01

282

Increase of neuronal response variability at higher processing levels as revealed by simultaneous recordings.  

PubMed

A key problem for neuronal information processing is the variability of spike trains, something that is likely to constrain the encoding of sensory signals. We measured interspike-interval variability (coefficient of variation) as well as spike-count variability (Fano factor) in the metathoracic auditory system of locusts. We performed simultaneous intracellular recordings at the first three processing levels to establish identical physiological conditions. This allows us to assess whether variability is generated anew or is reduced during synaptic transmission and processing. Both the interspike-interval variability as well as the spike-count variability revealed similar trends and showed an increase from the periphery to higher processing levels. This result was confirmed by single-cell recordings. A comparison of ascending interneurons coding for sound direction and those encoding sound patterns showed that the latter respond more reliably to repeated stimulus presentations. In general, the variability of spiking responses was much lower than expected from a Poisson process. Furthermore, we observed a strong dependence of variability on the spike rate, which differed at the three levels investigated. The differences in spike rates account for most of the differences in variability observed between processing levels. For auditory receptors, we found a good agreement between the Fano factor and the squared coefficient of variation, suggesting similarities to a renewal process of spike generation at the periphery. At the level of interneurons, the Fano factor was lower than the squared coefficient of variation; this indicates a higher reliability than expected from the interspike-interval distribution. PMID:15716366

Vogel, A; Hennig, R M; Ronacher, B

2005-06-01

283

Comparison of Transcriptional Changes to Chloroplast and Mitochondrial Perturbations Reveals Common and Specific Responses in Arabidopsis  

PubMed Central

Throughout the life of a plant, the biogenesis and fine-tuning of energy organelles is essential both under normal growth and stress conditions. Communication from organelle to nucleus is essential to adapt gene regulation and protein synthesis specifically to the current needs of the plant. This organelle-to-nuclear communication is termed retrograde signaling and has been studied extensively over the last decades. In this study we have used large-scale gene expression data sets relating to perturbations of chloroplast and mitochondrial function to gain further insights into plant retrograde signaling and how mitochondrial and chloroplast retrograde pathways interact and differ. Twenty seven studies were included that assess transcript profiles in response to chemical inhibition as well as genetic mutations of organellar proteins. The results show a highly significant overlap between gene expression changes triggered by chloroplast and mitochondrial perturbations. These overlapping gene expression changes appear to be common with general abiotic, biotic, and nutrient stresses. However, retrograde signaling pathways are capable of distinguishing the source of the perturbation as indicated by a statistical overrepresentation of changes in genes encoding proteins of the affected organelle. Organelle-specific overrepresented functional categories among others relate to energy metabolism and protein synthesis. Our analysis also suggests that WRKY transcription factors play a coordinating role on the interface of both organellar signaling pathways. Global comparison of the expression profiles for each experiment revealed that the recently identified chloroplast retrograde pathway using phospho-adenosine phosphate is possibly more related to mitochondrial than chloroplast perturbations. Furthermore, new marker genes have been identified that respond specifically to mitochondrial and/or chloroplast dysfunction.

Van Aken, Olivier; Whelan, James

2012-01-01

284

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

PubMed Central

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).

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

2013-01-01

285

Impedance Responses Reveal ?2-Adrenergic Receptor Signaling Pluridimensionality and Allow Classification of Ligands with Distinct Signaling Profiles  

PubMed Central

The discovery that drugs targeting a single G protein-coupled receptor (GPCR) can differentially modulate distinct subsets of the receptor signaling repertoire has created a challenge for drug discovery at these important therapeutic targets. Here, we demonstrate that a single label-free assay based on cellular impedance provides a real-time integration of multiple signaling events engaged upon GPCR activation. Stimulation of the ?2-adrenergic receptor (?2AR) in living cells with the prototypical agonist isoproterenol generated a complex, multi-featured impedance response over time. Selective pharmacological inhibition of specific arms of the ?2AR signaling network revealed the differential contribution of Gs-, Gi- and G??-dependent signaling events, including activation of the canonical cAMP and ERK1/2 pathways, to specific components of the impedance response. Further dissection revealed the essential role of intracellular Ca2+ in the impedance response and led to the discovery of a novel ?2AR-promoted Ca2+ mobilization event. Recognizing that impedance responses provide an integrative assessment of ligand activity, we screened a collection of ?-adrenergic ligands to determine if differences in the signaling repertoire engaged by compounds would lead to distinct impedance signatures. An unsupervised clustering analysis of the impedance responses revealed the existence of 5 distinct compound classes, revealing a richer signaling texture than previously recognized for this receptor. Taken together, these data indicate that the pluridimensionality of GPCR signaling can be captured using integrative approaches to provide a comprehensive readout of drug activity.

Stallaert, Wayne; Dorn, Jonas F.; van der Westhuizen, Emma; Audet, Martin; Bouvier, Michel

2012-01-01

286

Delayed hypersensitivity to herpes simplex virus: murine model.  

PubMed Central

Cell-mediated immunity has been shown to be clinically important in recovery from herpes simplex virus (HSV) infections. To investigate the role of delayed hypersensitivity (DH) in immunity and protection against HSV, we developed a murine model using the ear-swelling assay. Mice were infected subcutaneously with HSV-1 and ear-challenged, and the swelling was quantified. Significant ear swelling was detected by 3 to 4 days postinfection and peaked at 6 days. The kinetics of development of ear swelling were typical of DH: maximal swelling occurred 24 h post challenge and was diminished by 48 h, and the cellular infiltrate was predominantly mononuclear. Four-hour swelling, indicative of antibody-mediated, immediate-type hypersensitivity, was not detected until 15 days post immunization. The DH response was virus specific and could be transferred to normal recipients with lymph node T cells, but not with B cells or immune serum. This system will provide a useful model for evaluating the protective role of DH in HSV infection and for studying the specificity and interaction of T cells which mediate the response.

Schrier, R D; Pizer, L I; Moorhead, J W

1982-01-01

287

The ? agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome  

Microsoft Academic Search

Background & Aims: Visceral hypersensitivity plays a major role in the pathophysiology of inflammatory bowel syndrome (IBS). Opioid ? receptors on afferent nerves may modulate it and may be the target of new IBS treatments. The aim of this study was to evaluate the effects of fedotozine, a potent and selective ? agonist, on responses to colonic distention and colonic

Michel Delvaux; Dominique Louvel; Emmanuel Lagier; Bruno Scherrer; Jean-Louis Abitbol; Jacques Frexinos

1999-01-01

288

Salicylic acid in the machinery of hypersensitive cell death and disease resistance  

Microsoft Academic Search

Although extensive data has described the key role of salicylic acid (SA) in signaling pathogen-induced disease resistance, its function in physiological processes related to cell death is still poorly understood. Recent studies have explored the requirement of SA for mounting the hypersensitive response (HR) against an invading pathogen, where a particular cell death process is activated at the site of

María Elena Alvarez

2000-01-01

289

An Outbreak of Hypersensitivity Pneumonitis at a Metalworking Plant: A Longitudinal Assessment of Intervention Effectiveness  

Microsoft Academic Search

The authors describe a longitudinal assessment of intervention effectiveness in response to an outbreak of hypersensitivity pneumonitis (HP) at a metalworking facility. Thirty-five (29%) of the plant's 120 production workers were given a clinical diagnosis of HP during the two years of the investigation. Although quantitative exposure assessment tools were of limited utility, the investigators successfully used qualitative observations and

Anne Bracker; Eileen Storey; Chin Yang; Michael J. Hodgson

2003-01-01

290

Hypersensitivity Reactions to Drugs: Evaluation and Management  

Microsoft Academic Search

Most hypersensitivity reactions to drugs occur within several weeks of administration; signs and symptoms are often consistent with known immune-mediated reactions, including anaphylaxis, rashes, fever, cytopenias and vasculitis. The culprit immune mechanisms range from immunoglobulin E antibody to T cells inducing apoptosis of keratinocytes, in the case of bullous exfolia- tive rashes. Many drugs induce reactions via altered hepatic metabolism,

GILLIAN M. SHEPHERD

291

Clinical and Radiologic Manifestations of Hypersensitivity Pneumonitis  

Microsoft Academic Search

Summary: Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by recurring exposure to a variety of occupational and environmental antigens. It features widely variable clinical, radiologic, and histopathologic findings. Because the clinical findings of HP mimic multiple other diseases, a high degree of clinical suspicion and a thorough occupational and environmental history are essential for accurate diagnosis. There

Craig S. Glazer; Cecile S. Rose; David A. Lynch

292

Experimental hypersensitivity pneumonitis: location of transferring cells.  

PubMed

Cultured cells from Micropolyspora faeni-sensitized donors can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP). We sought to determine the location of transferred cells in recipient animals, the influence of the origin of the cultured cells, and the effect of specific intratracheal challenge. We labeled cultured sensitized spleen or lung-associated lymph node (LALN) cells with CFDA-SE, a cytoplasmic stain, before transfer to naive recipients, which were sacrificed 1 h, 1 day, or 4 days thereafter. We also transferred labeled cultured spleen cells to recipients that were challenged with intratracheal M. faeni and sacrificed 4 days later (MF). Controls were recipients of M. faeni-sensitized and cultured cells challenged with intratracheal normal saline (NS) and recipients of ovalbumin (OVA)-sensitized cells cultured with M. faeni and challenged with intratracheal M. faeni (OVA). The number and proportion of cells that were stained were determined in dispersed spleen, peripheral and lung-associated lymph nodes, and lung parenchyma. The extent of the pulmonary inflammatory response was measured by determining the proportion of microscopic fields that were abnormal and the total number of dispersed pulmonary cells. CFDA-SE stained cells uniformly, and stained cells could be detected in recipients for up to 7 days after transfer. CFDA-SE treatment (0.5 microM) did not affect the ability of cells to transfer EHP adoptively. Transferred cells could be detected easily in lung, lung-associated and peripheral lymph nodes, blood, and spleen. Transferred cells localized to the lung at 1 h but then rapidly decreased with no difference between labeled cells from spleen and LALN. After intratracheal M. faeni challenge, there was no difference in the proportion of labeled cells in the lung among any of the groups (MF, NS, or OVA). There was an increase in the number of lung cells in the MF group compared with the control (NS and OVA) groups. We conclude that cells capable of transfer are transiently (1 h) trapped in the lung but are much decreased in the lung by four days after transfer. After intratracheal antigen challenge of recipients, there is a substantial increase in the number of pulmonary cells in animals exhibiting adoptive EHP but not in the control groups. Transferred cells responsible for EHP are increased in the lungs of animals with adoptive EHP. PMID:9638641

Schuyler, M; Gott, K; Fei, R; Edwards, B

1998-01-01

293

A clinical study of patients with hypersensitive teeth.  

PubMed

Hypersensitive teeth have been a nemesis to patients in every dental practice. This clinical study was done to find a causal relationship of hypersensitive teeth and other organs of special senses, namely, sight, hearing, taste, smell, and touch. The analysis of the findings offers a basis for conclusion that dentition hypersensitivity and hypersensitivity of the special senses have a causal relationship. The dental clinician can provide the patient with an understanding and explanation of the cause(s) of hypersensitivity that will assist in a cooperative analysis of the symptoms and aid in the treatment to alleviate the pain. PMID:12572184

Bitter, Norman C

2002-01-01

294

Progressive hearing loss in an infant in a neonatal intensive care unit as revealed by auditory evoked brainstem responses  

Microsoft Academic Search

We herein report a case of a 14-month-old infant who revealed a progressive hearing loss by repeated auditory evoked brainstem responses (ABR) during his 1 year stay in the neonatal intensive care unit (NICU). He was born prematurely with asphyxia, hyperbilirubinemia and respiratory distress. During his 1 year stay in the NICU he was under constant mechanical ventilation. Repeated ABRs

Lihui Huang; Kimitaka Kaga; Kazuhiro Hashimoto

2002-01-01

295

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

PubMed

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

Funke, M; Fellrath, J-M

2008-08-01

296

Systems Scale Interactive Exploration Reveals Quantitative and Qualitative Differences in Response to Influenza and Pneumococcal Vaccines  

PubMed Central

SUMMARY Systems immunology approaches were employed to investigate innate and adaptive immune responses to influenza and pneumococcal vaccines. These two non-live vaccines show different magnitudes of transcriptional responses at different time points after vaccination. Software solutions were developed to explore correlates of vaccine efficacy measured as antibody titers at day 28. These enabled a further dissection of transcriptional responses. Thus, the innate response, measured within hours in the peripheral blood, was dominated by an interferon transcriptional signature after influenza vaccination and by an inflammation signature after pneumococcal vaccination. Day 7 plasmablast responses induced by both vaccines was more pronounced after pneumococcal vaccination. Together, these results suggest that comparing global immune responses elicited by different vaccines will be critical to our understanding of the immune mechanisms underpinning successful vaccination.

Obermoser, Gerlinde; Presnell, Scott; Domico, Kelly; Xu, Hui; Wang, Yuanyuan; Anguiano, Esperanza; Thompson-Snipes, LuAnn; Ranganathan, Rajaram; Zeitner, Brad; Bjork, Anna; Anderson, David; Speake, Cate; Ruchaud, Emily; Skinner, Jason; Alsina, Laia; Sharma, Mamta; Dutartre, Helene; Cepika, Alma; Israelsson, Elisabeth; Nguyen, Phuong; Nguyen, Quynh-Anh; Harrod, A. Carson; Zurawski, Sandra M.; Pascual, Virginia; Ueno, Hideki; Nepom, Gerald T.; Quinn, Charlie; Blankenship, Derek; Palucka, Karolina; Banchereau, Jacques; Chaussabel, Damien

2013-01-01

297

Stable DNA Unwinding, not "Breathing," Accounts for Single-Strand-Specific Nuclease Hypersensitivity of Specific A + T-Rich Sequences  

NASA Astrophysics Data System (ADS)

A long A+T-rich sequence in supercoiled pBR322 DNA is hypersensitive to single-strand-specific nucleases at 37 degrees C but not at reduced temperature. The basis for the nuclease hypersensitivity is stable DNA unwinding as revealed by (i) the same temperature dependence for hypersensitivity and for stable unwinding of plasmid topoisomers after two-dimensional gel electrophoresis, (ii) preferential nuclease digestion of stably unwound topoisomers, and (iii) quantitative nicking of stably unwound topoisomers in the A+T-rich region. Nuclease hypersensitivity of A+T-rich sequences is hierarchical, and either deletion of the primary site or a sufficient increase in the free energy of supercoiling leads to enhanced nicking at an alternative A+T-rich site. The hierarchy of nuclease hypersensitivity reflects a hierarchy in the free energy required for unwinding naturally occurring sequences in supercoiled DNA. This finding, along with the known hypersensitivity of replication origins and transcriptional regulatory regions, has important implications for using single-strand-specific nucleases in DNA structure-function studies.

Kowalski, David; Natale, Darren A.; Eddy, Martha J.

1988-12-01

298

Response to intervals as revealed by brainwave measurement and verbal means  

Microsoft Academic Search

The purpose of this study was to enhance understanding of the meaning of the interval as a musical parameter. This was done by examining both verbal reports and brainwave (Event?Related Potential, or ERP) responses to intervals. In an experiment with ERP (the oddball task), we examined the responses of listeners trained in Western music to isolated harmonic intervals. In the

Dalia Cohen; Joseph Mendel; Hillel Prat; Anat Bamea

1994-01-01

299

Hidden responses to environmental variation: maternal effects reveal species niche dimensions.  

PubMed

Species responses to fluctuating environments structure population and community dynamics in variable ecosystems. Although offspring number is commonly used to measure these responses, maternal effects on offspring quality may be an important but largely unrecognised determinant of long-term population growth. We selected 29 species across a Mediterranean annual plant phylogeny, and grew populations of each species in wet and dry conditions to determine responses in seed number and maternal effects (seed size, seed dormancy, and seedling growth). Maternal effects were evident in over 40% of species, but only 24% responded through seed number. Despite a strong trade-off between seed size and seed number among species, there was no consistent trade-off within species; we observed correlations that ranged from positive to negative. Overall, species in this plant guild show a complex range of responses to environmental variation that may be underestimated when only seed number responses are considered. PMID:24602193

Germain, Rachel M; Gilbert, Benjamin

2014-06-01

300

Hypersensitivity pneumonitis in a hardwood processing plant related to heavy mold exposure.  

PubMed

Two workers employed in a hardwood floor plant presented symptoms suggestive of hypersensitivity pneumonitis (HP). At that plant, kiln-dried wood often shows moldy growth and is subsequently brought inside for processing. This study evaluated the environment in attempt to identify the causative antigen and verify whether other workers of this and similar plants had or were at risk of developing HP. Dust from dust-removing systems and molds on the surface of wood planks were collected and air samples taken from a sister plant. Blood samples, spirometry, and symptoms' questionnaires were obtained from 11 co-workers. Dense Paecilomyces growth was observed on the surface of the dried processed wood in the index plant. This fungal genus was not detected in the sister plant. An additional worker had symptoms suggestive of HP, and his bronchoalveolar lavage revealed a lymphocytic alveolitis. The 3 confirmed cases of HP and the other 10 workers had positive specific IgG antibodies to Paecilomyces. We report 3 cases of HP out of 13 workers and a 100% sensitization to molds in workers of a hardwood processing plant. This rate is much higher than what is commonly seen in other environments associated with HP. The drying process is suspected of being responsible for the massive Paecilomyces contamination likely responsible for the HP. PMID:16621767

Veillette, Marc; Cormier, Yvon; Israël-Assayaq, Evelyne; Meriaux, Anne; Duchaine, Caroline

2006-06-01

301

Adrenergic ?2-Receptors Mediates Visceral Hypersensitivity Induced by Heterotypic Intermittent Stress in Rats  

PubMed Central

Chronic visceral pain in patients with irritable bowel syndrome (IBS) has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE) plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS). Abdominal withdrawal reflex scores (AWRs) used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs) were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of ?2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a ?-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a ?-adrenoceptor antagonist phentolamine. Using specific ?–adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by ?2 adrenoceptor antagonist but not by ?1- or ?3-adrenoceptor antagonist. Administration of a selective ?2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of ?-adrenoceptor antagonist suppressed sustained potassium current density (IK) without any alteration of fast-inactivating potassium current density (IA). Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by ?2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of ?2-adrenoceptor in DRGs and the muscularis externa of the colon. The present study might provide a potential molecular target for therapy of visceral hypersensitivity in patents with IBS.

Zhou, Yuan-Yuan; Ju, Zhong; Zhang, Hong-Hong; Hu, Chuang-Ying; Xiao, Ying; Xu, Guang-Yin

2014-01-01

302

Experimental hypersensitivity pneumonitis: suppressor cell influences.  

PubMed

Experimental hypersensitivity pneumonitis (EHP) can be transferred to strain 2 guinea pigs by lymph node cells (LNC) cultured in vitro with antigen. Using mixtures of cell populations, we sought to determine if functional suppressor cells were present in our system. We also characterized the composition of cell populations that were capable (blast 10 micrograms/mL Micropolyspora faeni from 2-week donor animals) and incapable (blast 0 micrograms/mL M. faeni from 2-week donor animals; blast 10 micrograms/mL from 8-week donor animals) using flow cytometry, anti-Ig and monoclonal antibody 8BE6 (T cell marker) of transferring EHP. Two groups of donors were used: animals sensitized with Freund's adjuvant and M. faeni and challenged with either two or eight weekly intratracheal (IT) injections of M. faeni (2- and 8-week groups). LNC from donor animals were cultured with a soluble extract of M. faeni (10 or 0 micrograms/mL) blasts isolated and transferred IV to syngeneic recipients. Control animals received media IV. Recipients were challenged IT with M. faeni 48 h after the cell transfer and sacrificed 4 days thereafter. All animals were maintained in HEPA filtered air. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. There was a low level of pulmonary response to an IT challenge of M. faeni in media recipients. There was a substantial increase (P less than .01) in pulmonary abnormalities in the animals receiving blasts from the 10-micrograms/mL M. faeni 2-week group. Addition of cells from incompetent cell populations (0 micrograms/mL M. faeni 2-week donors or 10 micrograms/mL M. faeni 8-week donors) did not alter the ability of competent populations to transfer EHP. Cells cultured with antigen had a decreased proportion of T cells and an increased proportion of SIg+ and large cells. Competent and incompetent cell populations did not differ in regard to proportion of large cells, surface Ig+, or T cells. We conclude that the inability of certain cell populations to transfer EHP is not associated with the appearance of functional suppressor cells. Differences of ability to transfer EHP do not correlate with differences of size distribution or T and B cell composition. PMID:1720385

Schuyler, M R; Gott, K; Shopp, G; Crooks, L

1991-01-01

303

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

PubMed

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

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

1995-03-15

304

Global analyses of human immune variation reveal baseline predictors of postvaccination responses.  

PubMed

A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the 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 were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination 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

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

2014-04-10

305

Which Response Format Reveals the Truth about Donations to a Public Good?  

Microsoft Academic Search

Several contingent valuation studies have found that the open-ended format yields lower estimates of willingness to pay (WTP) than does the closed-ended, or dichotomous choice, format. In this study, WTP for a public environmental good was estimated under four conditions: actual payment in response to open-ended and closed-ended requests, and hypothetical payment in response to open-ended and closed-ended requests. The

Thomas C. Brown; Patricia A. Champ; Richard C. Bishop; Daniel W. McCollum

1996-01-01

306

DNA Microarray Analysis of Anaerobic Methanosarcina Barkeri Reveals Responses to Heat Shock and Air Exposure  

SciTech Connect

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.

Zhang, Weiwen; Culley, David E.; Nie, Lei; Brockman, Fred J.

2006-04-08

307

Quantitative Proteomics and Dynamic Imaging of the Nucleolus Reveal Distinct Responses to UV and Ionizing Radiation*  

PubMed Central

The nucleolus is a nuclear organelle that coordinates rRNA transcription and ribosome subunit biogenesis. Recent proteomic analyses have shown that the nucleolus contains proteins involved in cell cycle control, DNA processing and DNA damage response and repair, in addition to the many proteins connected with ribosome subunit production. Here we study the dynamics of nucleolar protein responses in cells exposed to stress and DNA damage caused by ionizing and ultraviolet (UV) radiation in diploid human fibroblasts. We show using a combination of imaging and quantitative proteomics methods that nucleolar substructure and the nucleolar proteome undergo selective reorganization in response to UV damage. The proteomic responses to UV include alterations of functional protein complexes such as the SSU processome and exosome, and paraspeckle proteins, involving both decreases and increases in steady state protein ratios, respectively. Several nonhomologous end-joining proteins (NHEJ), such as Ku70/80, display similar fast responses to UV. In contrast, nucleolar proteomic responses to IR are both temporally and spatially distinct from those caused by UV, and more limited in terms of magnitude. With the exception of the NHEJ and paraspeckle proteins, where IR induces rapid and transient changes within 15 min of the damage, IR does not alter the ratios of most other functional nucleolar protein complexes. The rapid transient decrease of NHEJ proteins in the nucleolus indicates that it may reflect a response to DNA damage. Our results underline that the nucleolus is a specific stress response organelle that responds to different damage and stress agents in a unique, damage-specific manner.

Moore, Henna M.; Bai, Baoyan; Boisvert, Francois-Michel; Latonen, Leena; Rantanen, Ville; Simpson, Jeremy C.; Pepperkok, Rainer; Lamond, Angus I.; Laiho, Marikki

2011-01-01

308

Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria  

PubMed Central

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.

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

2005-01-01

309

Hypersensitivity pneumonitis associated with environmental mycobacteria.  

PubMed

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

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

2005-06-01

310

Transgenic AEQUORIN reveals organ-specific cytosolic Ca2+ responses to anoxia and Arabidopsis thaliana seedlings.  

PubMed Central

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.

Sedbrook, J C; Kronebusch, P J; Borisy, G G; Trewavas, A J; Masson, P H

1996-01-01

311

Transgenic AEQUORIN reveals organ-specific cytosolic Ca2+ responses to anoxia and Arabidopsis thaliana seedlings  

NASA Technical Reports Server (NTRS)

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.

Sedbrook, J. C.; Kronebusch, P. J.; Borisy, G. G.; Trewavas, A. J.; Masson, P. H.

1996-01-01

312

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

PubMed

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 ?-3 (GFR?3) 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 GFR?3 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 GFR?3 KO mice. The proportion of GFR?3 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 GFR?3 KO mice. These findings suggest that enhanced GFR?3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity. PMID:21193524

Tanaka, T; Shinoda, M; Feng, B; Albers, K M; Gebhart, G F

2011-03-01

313

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

PubMed Central

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 ?-3 (GFR?3) 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 GFR?3 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 GFR?3 KO mice. The proportion of GFR?3 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 GFR?3 KO mice. These findings suggest that enhanced GFR?3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity.

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

2011-01-01

314

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

PubMed Central

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.

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

2013-01-01

315

Stent hypersensitivity and infection in sinus cavities  

PubMed Central

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.

Soufras, George D.; Hahalis, George

2013-01-01

316

Stent hypersensitivity and infection in sinus cavities.  

PubMed

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

Kounis, Nicholas G; Soufras, George D; Hahalis, George

2013-01-01

317

A novel single-cell screening platform reveals proteome plasticity during yeast stress responses.  

PubMed

Uncovering the mechanisms underlying robust responses of cells to stress is crucial for our understanding of cellular physiology. Indeed, vast amounts of data have been collected on transcriptional responses in Saccharomyces cerevisiae. However, only a handful of pioneering studies describe the dynamics of proteins in response to external stimuli, despite the fact that regulation of protein levels and localization is an essential part of such responses. Here we characterized unprecedented proteome plasticity by systematically tracking the localization and abundance of 5,330 yeast proteins at single-cell resolution under three different stress conditions (DTT, H2O2, and nitrogen starvation) using the GFP-tagged yeast library. We uncovered a unique "fingerprint" of changes for each stress and elucidated a new response arsenal for adapting to radical environments. These include bet-hedging strategies, organelle rearrangement, and redistribution of protein localizations. All data are available for download through our online database, LOQATE (localization and quantitation atlas of yeast proteome). PMID:23509072

Breker, Michal; Gymrek, Melissa; Schuldiner, Maya

2013-03-18

318

Stem transcriptome reveals mechanisms to reduce the energetic cost of shade-avoidance responses in tomato.  

PubMed

While the most conspicuous response to low red/far-red ratios (R:FR) of shade light perceived by phytochrome is the promotion of stem growth, additional, less obvious effects may be discovered by studying changes in the stem transcriptome. Here, we report rapid and reversible stem transcriptome responses to R:FR in tomato (Solanum lycopersicum). As expected, low R:FR promoted the expression of growth-related genes, including those involved in the metabolism of cell wall carbohydrates and in auxin responses. In addition, genes involved in flavonoid synthesis, isoprenoid metabolism, and photosynthesis (dark reactions) were overrepresented in clusters showing reduced expression in the stem of low R:FR-treated plants. Consistent with these responses, low R:FR decreased the levels of flavonoids (anthocyanin, quercetin, kaempferol) and selected isoprenoid derivatives (chlorophyll, carotenoids) in the stem and severely reduced the photosynthetic capacity of this organ. However, lignin contents were unaffected. Low R:FR reduced the stem levels of jasmonate, which is a known inducer of flavonoid synthesis. The rate of stem respiration was also reduced in low R:FR-treated plants, indicating that by downsizing the stem photosynthetic apparatus and the levels of photoprotective pigments under low R:FR, tomato plants reduce the energetic cost of shade-avoidance responses. PMID:22872775

Cagnola, Juan Ignacio; Ploschuk, Edmundo; Benech-Arnold, Tomás; Finlayson, Scott A; Casal, Jorge José

2012-10-01

319

Water stress reveals differential antioxidant responses of tolerant and non-tolerant sugarcane genotypes.  

PubMed

The biochemical responses of the enzymatic antioxidant system of a drought-tolerant cultivar (IACSP 94-2094) and a commercial cultivar in Brazil (IACSP 95-5000) grown under two levels of soil water restriction (70% and 30% Soil Available Water Content) were investigated. IACSP 94-2094 exhibited one additional active superoxide dismutase (Cu/Zn-SOD VI) isoenzyme in comparison to IACSP 95-5000, possibly contributing to the heightened response of IACSP 94-2094 to the induced stress. The total glutathione reductase (GR) activity increased substantially in IACSP 94-2094 under conditions of severe water stress; however, the appearance of a new GR isoenzyme and the disappearance of another isoenzyme were found not to be related to the stress response because the cultivars from both treatment groups (control and water restrictions) exhibited identical changes. Catalase (CAT) activity seems to have a more direct role in H2O2 detoxification under water stress condition and the shift in isoenzymes in the tolerant cultivar might have contributed to this response, which may be dependent upon the location where the excessive H2O2 is being produced under stress. The improved performance of IACSP 94-2094 under drought stress was associated with a more efficient antioxidant system response, particularly under conditions of mild stress. PMID:24308986

Boaretto, Luis F; Carvalho, Giselle; Borgo, Lucélia; Creste, Silvana; Landell, Marcos G A; Mazzafera, Paulo; Azevedo, Ricardo A

2014-01-01

320

Metabolomics Reveals Amino Acids Contribute to Variation in Response to Simvastatin Treatment  

PubMed Central

Statins are widely prescribed for reducing LDL-cholesterol (C) and risk for cardiovascular disease (CVD), but there is considerable variation in therapeutic response. We used a gas chromatography-time-of-flight mass-spectrometry-based metabolomics platform to evaluate global effects of simvastatin on intermediary metabolism. Analyses were conducted in 148 participants in the Cholesterol and Pharmacogenetics study who were profiled pre and six weeks post treatment with 40 mg/day simvastatin: 100 randomly selected from the full range of the LDL-C response distribution and 24 each from the top and bottom 10% of this distribution (“good” and “poor” responders, respectively). The metabolic signature of drug exposure in the full range of responders included essential amino acids, lauric acid (p<0.0055, q<0.055), and alpha-tocopherol (p<0.0003, q<0.017). Using the HumanCyc database and pathway enrichment analysis, we observed that the metabolites of drug exposure were enriched for the pathway class amino acid degradation (p<0.0032). Metabolites whose change correlated with LDL-C lowering response to simvastatin in the full range responders included cystine, urea cycle intermediates, and the dibasic amino acids ornithine, citrulline and lysine. These dibasic amino acids share plasma membrane transporters with arginine, the rate-limiting substrate for nitric oxide synthase (NOS), a critical mediator of cardiovascular health. Baseline metabolic profiles of the good and poor responders were analyzed by orthogonal partial least square discriminant analysis so as to determine the metabolites that best separated the two response groups and could be predictive of LDL-C response. Among these were xanthine, 2-hydroxyvaleric acid, succinic acid, stearic acid, and fructose. Together, the findings from this study indicate that clusters of metabolites involved in multiple pathways not directly connected with cholesterol metabolism may play a role in modulating the response to simvastatin treatment. Trial Registration ClinicalTrials.gov NCT00451828

Wikoff, William R.; Baillie, Rebecca A.; Zeng, Zhao-Bang; Karp, Peter D.; Fiehn, Oliver; Krauss, Ronald M.; Kaddurah-Daouk, Rima

2012-01-01

321

Cefuroxime induced lymphomatoid hypersensitivity reaction  

PubMed Central

An 84 year old women developed erythematous blotchy erythema and purpuric rashes over the lower limbs three days after being started on intravenous cefuroxime for acute diverticulitis. A skin biopsy specimen showed a mixed infiltrate of lymphoid cells and eosinophils; many of the lymphocytes were large, pleomorphic, and showed a raised mitotic rate. Immunohistochemistry showed the infiltrate to be T cell rich, with all the large cells being CD30 positive. Typical mycosis fungoides cells, marked epidermotropism, and Pautrier's abscesses were not seen. The rash disappeared 10 days after cessation of cefuroxime and the patient remained asymptomatic 15 months later. This apparent cutaneous T cell lymphoma-like reaction is best described as lymphomatoid vascular reaction. The drug induced immune response with an atypical cutaneous lymphoid infiltrate mimics a cutaneous pseudolymphoma.???Keywords: cefuroxime; atypical cutaneous lymphomatoid infiltrate; cutaneous T cell lymphoma

Saeed, S; Bazza, M; Zaman, M; Ryatt, K

2000-01-01

322

Dominant negative Bmp5 mutation reveals key role of BMPs in skeletal response to mechanical stimulation  

Microsoft Academic Search

BACKGROUND: Over a hundred years ago, Wolff originally observed that bone growth and remodeling are exquisitely sensitive to mechanical forces acting on the skeleton. Clinical studies have noted that the size and the strength of bone increase with weight bearing and muscular activity and decrease with bed rest and disuse. Although the processes of mechanotransduction and functional response of bone

Andrew M Ho; Paul C Marker; Hairong Peng; Andres J Quintero; David M Kingsley; Johnny Huard

2008-01-01

323

The interaction between murine melanoma and the immune system reveals that prolonged responses predispose for autoimmunity  

PubMed Central

An assessment of antitumor immunity versus autoimmunity as provoked by the specific depletion of Foxp3+ Tregs is now possible with the development of Foxp3-diphtheria toxin receptor-like transgenic mouse models. We have used the poorly immunogenic B16F10 melanoma model to characterize a very heterogeneous antitumor effect of the immune response induced by Treg depletion. Depletion and neutralization studies demonstrated the importance of host T cells and interferon ? (IFN?) in mediating the antitumor response developing in Treg-depleted mice. Such a response correlated with increased proliferation of granzyme B- and IFN?-producing T cells in the tumor. Furthermore, enhanced antitumor immunity modulated the expression of MHC Class I molecules by B16F10 melanoma cells in Treg-depleted mice. Since Foxp3+ Treg depletion induced a significantly heterogeneous antitumor response, for the first time we were able to assess antitumor immunity and autoimmunity across different groups of responding mice. Strikingly, the duration of the tumor-immune system interaction provoked in individual Treg-depleted mice positively correlated with their propensity to develop vitiligo. A rapid complete tumor rejection was not associated with the development of autoimmunity, however, a proportion of mice that suppressed, but did not effectively clear, B16F10 melanoma did develop vitiligo. The significant implication is that approaches that combine with Treg depletion to rapidly reject tumors may also diminish autoimmune toxicities. 

Ngiow, Shin Foong; von Scheidt, Bianca; Moller, Andreas; Smyth, Mark J.; Teng, Michele W. L.

2013-01-01

324

Arabidopsis thaliana mutant lpsi reveals impairment in the root responses to local phosphate availability.  

PubMed

Phosphate (Pi) deficiency triggers local Pi sensing-mediated inhibition of primary root growth and development of root hairs in Arabidopsis (Arabidopsis thaliana). Generation of activation-tagged T-DNA insertion pools of Arabidopsis expressing the luciferase gene (LUC) under high-affinity Pi transporter (Pht1;4) promoter, is an efficient approach for inducing genetic variations that are amenable for visual screening of aberrations in Pi deficiency responses. Putative mutants showing altered LUC expression during Pi deficiency were identified and screened for impairment in local Pi deficiency-mediated inhibition of primary root growth. An isolated mutant was analyzed for growth response, effects of Pi deprivation on Pi content, primary root growth, root hair development, and relative expression levels of Pi starvation-responsive (PSR) genes, and those implicated in starch metabolism and Fe and Zn homeostasis. Pi deprived local phosphate sensing impaired (lpsi) mutant showed impaired primary root growth and attenuated root hair development. Although relative expression levels of PSR genes were comparable, there were significant increases in relative expression levels of IRT1, BAM3 and BAM5 in Pi deprived roots of lpsi compared to those of the wild-type. Better understanding of molecular responses of plants to Pi deficiency or excess will help to develop suitable remediation strategies for soils with excess Pi, which has become an environmental concern. Hence, lpsi mutant will serve as a valuable tool in identifying molecular mechanisms governing adaptation of plants to Pi deficiency. PMID:24561248

Karthikeyan, Athikkattuvalasu S; Jain, Ajay; Nagarajan, Vinay K; Sinilal, Bhaskaran; Sahi, Shivendra V; Raghothama, Kashchandra G

2014-04-01

325

Multimodal Stimulation of Colorado Potato Beetle Reveals Modulation of Pheromone Response by Yellow Light  

PubMed Central

Orientation of insects to host plants and conspecifics is the result of detection and integration of chemical and physical cues present in the environment. Sensory organs have evolved to be sensitive to important signals, providing neural input for higher order multimodal processing and behavioral output. Here we report experiments to determine decisions made by Colorado potato beetle (CPB), Leptinotarsa decemlineata, in response to isolated stimuli and multimodal combinations of signals on a locomotion compensator. Our results show that in complete darkness and in the absence of other stimuli, pheromonal stimulation increases attraction behavior of CPB as measured in oriented displacement and walking speed. However, orientation to the pheromone is abolished when presented with the alternative stimulation of a low intensity yellow light in a dark environment. The ability of the pheromone to stimulate these diurnal beetles in the dark in the absence of other stimuli is an unexpected but interesting observation. The predominance of the phototactic response over that to pheromone when low intensity lights were offered as choices seems to confirm the diurnal nature of the insect. The biological significance of the response to pheromone in the dark is unclear. The phototactic response will play a key role in elucidating multimodal stimulation in the host-finding process of CPB, and perhaps other insects. Such information might be exploited in the design of applications to attract and trap CPB for survey or control purposes and other insect pests using similar orientation mechanisms.

Otalora-Luna, Fernando; Dickens, Joseph C.

2011-01-01

326

Who do they think they are? Wnt-responsive cells reveal their family trees  

PubMed Central

The nature of stem and progenitor cells in the mammary epithelium, and the relevance of cleared fat pad transplantation as a functional assay for them, has been thrown into doubt by recent lineage-tracking studies. Now two new studies based on tracking the progeny of Wnt-responsive cells are starting to help make sense of this fascinating problem.

2012-01-01

327

Selectivity of audiovisual ECoG responses revealed under naturalistic stimuli in the human cortex.  

PubMed

A fundamental debate in the study of cortical sensory systems concerns the scale of functional selectivity in cortical networks. Brain imaging studies have repeatedly demonstrated functional selectivity in entire cortical areas and networks using predetermined stimuli. However, it is not clear to what extent these networks are heterogeneous, i.e., whether the selectivity profiles in subregions within each sensory network show significant dissimilarity. Here, we studied local functional selectivity in the human cortex using naturalistic movie clips shown to 12 patients implanted with intracranial electrocorticography electrodes (590 in total), providing extensive cortical coverage. We examined the similarity of response profiles (40- to 80-Hz gamma-power modulations) across electrodes using a novel data driven approach without assuming any predefined category. Our results show that the functional selectivity of each highly responsive electrode was different from that of all other electrodes across the sensory cortex. Thus most responsive electrodes showed an activation profile that was unique in each patient and was similar to that of only 0.3% (1-2) of all other electrodes across all patients. Functional similarity between electrodes was linked to anatomical proximity. While in most electrodes the source of selectivity was complex, a small subset showed the well-documented selectivity to faces and actions. Our results indicate that the human sensory cortex is organized as a mosaic of functionally unique subregions in which each site manifests its own special response profile. PMID:23407355

Meshulam, Meir; Ramot, Michal; Harel, Michal; Kipervasser, Svetlana; Andelman, Fani; Neufeld, Miri Y; Kramer, Uri; Fried, Itzhak; Malach, Rafael

2013-05-01

328

Meta-analysis reveals profound responses of plant traits to glacial CO2 levels  

PubMed Central

A general understanding of the links between atmospheric CO2 concentration and the functioning of the terrestrial biosphere requires not only an understanding of plant trait responses to the ongoing transition to higher CO2 but also the legacy effects of past low CO2. An interesting question is whether the transition from current to higher CO2 can be thought of as a continuation of the past trajectory of low to current CO2 levels. Determining this trajectory requires quantifying the effect sizes of plant response to low CO2. We performed a meta-analysis of low CO2 growth experiments on 34 studies with 54 species. We quantified how plant traits vary at reduced CO2 levels and whether C3 versus C4 and woody versus herbaceous plant species respond differently. At low CO2, plant functioning changed drastically: on average across all species, a 50% reduction in current atmospheric CO2 reduced net photosynthesis by 38%; increased stomatal conductance by 60% and decreased intrinsic water use efficiency by 48%. Total plant dry biomass decreased by 47%, while specific leaf area increased by 17%. Plant types responded similarly: the only significant differences being no increase in SLA for C4 species and a 16% smaller decrease in biomass for woody C3 species at glacial CO2. Quantitative comparison of low CO2 effect sizes to those from high CO2 studies showed that the magnitude of response of stomatal conductance, water use efficiency and SLA to increased CO2 can be thought of as continued shifts along the same line. However, net photosynthesis and dry weight responses to low CO2 were greater in magnitude than to high CO2. Understanding the causes for this discrepancy can lead to a general understanding of the links between atmospheric CO2 and plant responses with relevance for both the past and the future.

Temme, A A; Cornwell, W K; Cornelissen, J H C; Aerts, R

2013-01-01

329

RNA-Seq reveals complex genetic response to deepwater horizon oil release in Fundulus grandis  

PubMed Central

Background The release of oil resulting from the blowout of the Deepwater Horizon (DH) drilling platform was one of the largest in history discharging more than 189 million gallons of oil and subject to widespread application of oil dispersants. This event impacted a wide range of ecological habitats with a complex mix of pollutants whose biological impact is still not yet fully understood. To better understand the effects on a vertebrate genome, we studied gene expression in the salt marsh minnow Fundulus grandis, which is local to the northern coast of the Gulf of Mexico and is a sister species of the ecotoxicological model Fundulus heteroclitus. To assess genomic changes, we quantified mRNA expression using high throughput sequencing technologies (RNA-Seq) in F. grandis populations in the marshes and estuaries impacted by DH oil release. This application of RNA-Seq to a non-model, wild, and ecologically significant organism is an important evaluation of the technology to quickly assess similar events in the future. Results Our de novo assembly of RNA-Seq data produced a large set of sequences which included many duplicates and fragments. In many cases several of these could be associated with a common reference sequence using blast to query a reference database. This reduced the set of significant genes to 1,070 down-regulated and 1,251 up-regulated genes. These genes indicate a broad and complex genomic response to DH oil exposure including the expected AHR-mediated response and CYP genes. In addition a response to hypoxic conditions and an immune response are also indicated. Several genes in the choriogenin family were down-regulated in the exposed group; a response that is consistent with AH exposure. These analyses are in agreement with oligonucleotide-based microarray analyses, and describe only a subset of significant genes with aberrant regulation in the exposed set. Conclusion RNA-Seq may be successfully applied to feral and extremely polymorphic organisms that do not have an underlying genome sequence assembly to address timely environmental problems. Additionally, the observed changes in a large set of transcript expression levels are indicative of a complex response to the varied petroleum components to which the fish were exposed.

2012-01-01

330

Characterization of the Antigen Specificity of T-Cell Clones from Piperacillin-Hypersensitive Patients with Cystic Fibrosis  

PubMed Central

?-Lactam antibiotics provide the cornerstone of treatment and reduce the rate of decline in lung function in patients with cystic fibrosis, but their use is limited by a high frequency of delayed-type allergic reactions. The objective of this study was to use cloned T-cells expressing a single T-cell receptor from five piperacillin-hypersensitive patients to characterize both the cellular pathophysiology of the reaction and antigen specificity to define the mechanism of activation of T-cells by piperacillin. More than 400 piperacillin-responsive CD4+, CD4+CD8+, or CD8+ T-cell clones were generated from lymphocyte transformation test and ELIspot-positive patients. The T-cell response (proliferation, T helper 2 cytokine secretion, and cytotoxicity) to piperacillin was concentration-dependent and highly specific. Enzyme-linked immunosorbent assay, gel electrophoresis, and mass spectrometry revealed that piperacillin bound exclusively to albumin in T-cell culture. Irreversible piperacillin binding at Lys 190, 195, 199, 432, and 541 on albumin and the stimulation of T-cells depended on incubation time. A synthetic piperacillin albumin conjugate stimulated T-cell receptors via a major histocompatibility complex- and processing-dependent pathway. Flucloxacillin competes for the same Lys residues on albumin as piperacillin, but the resulting conjugate does not stimulate T-cells, indicating that binding of the ?-lactam hapten in peptide conjugates confers structural specificity on the activation of the T-cell receptors expressed on drug-specific clones. Collectively, these data describe the cellular processes that underlie the structural specificity of piperacillin antigen binding in hypersensitive patients with cystic fibrosis.

El-Ghaiesh, Sabah; Monshi, Manal M.; Whitaker, Paul; Jenkins, Rosalind; Meng, Xiaoli; Farrell, John; Elsheikh, Ayman; Peckham, Daniel; French, Neil; Pirmohamed, Munir; Park, B. Kevin

2012-01-01

331

Characterization of the antigen specificity of T-cell clones from piperacillin-hypersensitive patients with cystic fibrosis.  

PubMed

?-Lactam antibiotics provide the cornerstone of treatment and reduce the rate of decline in lung function in patients with cystic fibrosis, but their use is limited by a high frequency of delayed-type allergic reactions. The objective of this study was to use cloned T-cells expressing a single T-cell receptor from five piperacillin-hypersensitive patients to characterize both the cellular pathophysiology of the reaction and antigen specificity to define the mechanism of activation of T-cells by piperacillin. More than 400 piperacillin-responsive CD4+, CD4+CD8+, or CD8+ T-cell clones were generated from lymphocyte transformation test and ELIspot-positive patients. The T-cell response (proliferation, T helper 2 cytokine secretion, and cytotoxicity) to piperacillin was concentration-dependent and highly specific. Enzyme-linked immunosorbent assay, gel electrophoresis, and mass spectrometry revealed that piperacillin bound exclusively to albumin in T-cell culture. Irreversible piperacillin binding at Lys 190, 195, 199, 432, and 541 on albumin and the stimulation of T-cells depended on incubation time. A synthetic piperacillin albumin conjugate stimulated T-cell receptors via a major histocompatibility complex- and processing-dependent pathway. Flucloxacillin competes for the same Lys residues on albumin as piperacillin, but the resulting conjugate does not stimulate T-cells, indicating that binding of the ?-lactam hapten in peptide conjugates confers structural specificity on the activation of the T-cell receptors expressed on drug-specific clones. Collectively, these data describe the cellular processes that underlie the structural specificity of piperacillin antigen binding in hypersensitive patients with cystic fibrosis. PMID:22371438

El-Ghaiesh, Sabah; Monshi, Manal M; Whitaker, Paul; Jenkins, Rosalind; Meng, Xiaoli; Farrell, John; Elsheikh, Ayman; Peckham, Daniel; French, Neil; Pirmohamed, Munir; Park, B Kevin; Naisbitt, Dean J

2012-06-01

332

Temporal dynamics reveal atypical brain response to social exclusion in autism  

PubMed Central

Despite significant social difficulties, children with autism spectrum disorder (ASD) are vulnerable to the effects of social exclusion. We recorded EEG while children with ASD and typical peers played a computerized game involving peer rejection. Children with ASD reported ostracism-related distress comparable to typically developing children. Event-related potentials (ERPs) indicated a distinct pattern of temporal processing of rejection events in children with ASD. While typically developing children showed enhanced response to rejection at a late slow wave indexing emotional arousal and regulation, those with autism showed attenuation at an early component, suggesting reduced engagement of attentional resources in the aversive social context. Results emphasize the importance of studying the time course of social information processing in ASD; they suggest distinct mechanisms subserving similar overt behavior and yield insights relevant to development and implementation of targeted treatment approaches and objective measures of response to treatment.

McPartland, James C.; Crowley, Michael J.; Perszyk, Danielle R.; Naples, Adam; Mukerji, Cora E.; Wu, Jia; Molfese, Peter; Bolling, Danielle Z.; Pelphrey, Kevin A.; Mayes, Linda C.

2011-01-01

333

A dynamic and complex monochloramine stress response in Escherichia coli revealed by transcriptome analysis.  

PubMed

Despite the widespread use of monochloramine in drinking water treatment, there is surprisingly little information about its mode of action. In this study, DNA microarrays were used to investigate the global gene expression of Escherichia coli cells exposed to sub-lethal concentrations of monochloramine, with a focus on temporal dynamics. Genes induced by monochloramine were associated with several stress response functions, including oxidative stress, DNA repair, multidrug efflux, biofilm formation, antibiotic resistance, and cell wall repair. The diversity of functional associations supports a model of monochloramine action involving multiple cellular targets including cell membranes, nucleic acids, and proteins. These data suggest that E. coli responds to monochloramine exposure by activating diverse defense responses rather than a single antioxidant system and the exposure may also induce biofilm formation. The induction of multidrug efflux pumps and specific antibiotic resistance genes further suggests that exposure to monochloramine may contribute to reduced susceptibility to some antibiotics. PMID:23866139

Holder, Diane; Berry, David; Dai, Dongjuan; Raskin, Lutgarde; Xi, Chuanwu

2013-09-15

334

Combined Systems Approaches Reveal Highly Plastic Responses to Antimicrobial Peptide Challenge in Escherichia coli  

PubMed Central

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies.

Kozlowska, Justyna; Vermeer, Louic S.; Rogers, Geraint B.; Rehnnuma, Nabila; Amos, Sarah-Beth T. A.; Koller, Garrit; McArthur, Michael; Bruce, Kenneth D.; Mason, A. James

2014-01-01

335

Auditory nerve disease of both ears revealed by auditory brainstem responses, electrocochleography and otoacoustic emissions.  

PubMed

We report on two patients who showed absence of auditory brainstem response (ABR) but broad compound action potentials on electrocochleograms and almost normal otoacoustic emissions, together with absence of caloric response and preservation of per rotatory nystagmus for both ears. Patient 1, a 53-year-old woman, had noted auditory and vestibular problems since the age of 15 years, and Patient 2, a 68-year-old woman, had noted problems of the same age of 30 years. They could hear words and understand sentences if spoken slowly, but they could not discriminate monosyllables very well. Their auditory examinations disclosed mild threshold elevation in pure-tone audiometry and markedly poor scores in speech audiometry and good scores in auditory comprehension test. They were diagnosed as having auditory nerve disease of unknown cause. PMID:8975994

Kaga, K; Nakamura, M; Shinogami, M; Tsuzuku, T; Yamada, K; Shindo, M

1996-01-01

336

Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli.  

PubMed

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies. PMID:24789011

Kozlowska, Justyna; Vermeer, Louic S; Rogers, Geraint B; Rehnnuma, Nabila; Amos, Sarah-Beth T A; Koller, Garrit; McArthur, Michael; Bruce, Kenneth D; Mason, A James

2014-05-01

337

An Unbiased Genetic Screen Reveals the Polygenic Nature of the Influenza Virus Anti-Interferon Response  

PubMed Central

ABSTRACT Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space. IMPORTANCE In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response.

Perez-Cidoncha, Maite; Killip, Marian J.; Oliveros, Juan C.; Asensio, Victor J.; Fernandez, Yolanda; Bengoechea, Jose A.; Randall, Richard E.

2014-01-01

338

Temporal dynamics reveal atypical brain response to social exclusion in autism.  

PubMed

Despite significant social difficulties, children with autism spectrum disorder (ASD) are vulnerable to the effects of social exclusion. We recorded EEG while children with ASD and typical peers played a computerized game involving peer rejection. Children with ASD reported ostracism-related distress comparable to typically developing children. Event-related potentials (ERPs) indicated a distinct pattern of temporal processing of rejection events in children with ASD. While typically developing children showed enhanced response to rejection at a late slow wave indexing emotional arousal and regulation, those with autism showed attenuation at an early component, suggesting reduced engagement of attentional resources in the aversive social context. Results emphasize the importance of studying the time course of social information processing in ASD; they suggest distinct mechanisms subserving similar overt behavior and yield insights relevant to development and implementation of targeted treatment approaches and objective measures of response to treatment. PMID:21731598

McPartland, James C; Crowley, Michael J; Perszyk, Danielle R; Naples, Adam; Mukerji, Cora E; Wu, Jia; Molfese, Peter; Bolling, Danielle Z; Pelphrey, Kevin A; Mayes, Linda C

2011-07-01

339

Willing the spirits to reveal themselves: rural Kenyan mothers' responsibility to restore their children's health.  

PubMed

Women's contributions to the improvement and maintenance of health are being acknowledged the world over. Recent studies show that most health care is domestic and that women provide nearly 95 percent of this care. Their role as healers, nurses, doctors, folk practitioners, and lay therapists has also been recognized. This research report analyses exorcism as a special function performed by Duruma mothers on behalf of their ailing children. The women represent their children and identify the spirit(s) responsible for illnesses. This role is based on Duruma recognition of the close relationship between mothers and their children, specifically through pregnancy, lactation, and daily contact. For local people who believe in the spirit world, mothers' spirits are held to be responsible for exorcising children's illnesses. Thus health production by Duruma women goes a step further than that of women in other communities. PMID:9884995

Amuyunzu, M

1998-12-01

340

Gene Expression Profiling Reveals Distinct Cocaine-Responsive Genes in Human Fetal CNS Cell Types  

PubMed Central

Objectives Prenatal exposure to cocaine causes cytoarchitectural alterations in the developing neocortex. Previously, we reported that cocaine inhibits neural progenitor cell proliferation through oxidative endoplasmic reticulum stress and consequent down-regulation of cyclin A, whereas cyclin A expression was increased in astrocytes. In the present study, cell type-specific responses to cocaine were further explored. Methods Gene expression profiles were examined in five types of cells obtained from the human fetal cerebral cortex at 20 weeks gestation. Cells were treated with 100 µM cocaine in vitro for 24 hr, followed by gene expression analysis using a human neural/stem cell/drug abuse-focused cDNA array, with verification by quantitative real-time RT-PCR. Results Cocaine influenced transcription of distinct categories of genes in a cell type-specific manner. Cocaine down-regulated cytoskeleton-related genes including ezrin, ?2 actin, ?3d tubulin and ?8 tubulin in neural and/or A2B5+ progenitor cells. In contrast, cocaine modulated immune and cell death-related genes in microglia and astrocytes. In microglia, cocaine up-regulated the immunoregulatory and pro-apoptotic genes IL-1? and BAX. In astrocytes, cocaine down-regulated the immune response gene glucocorticoid receptor and up-regulated the anti-apoptotic genes 14-3-3 ? and HVEM. Therefore, cell types comprising the developing neocortex show differential responses to cocaine. Conclusions These data suggest that cocaine causes cytoskeletal abnormalities leading to disturbances in neural differentiation and migration in progenitor cells, while altering immune and apoptotic responses in glia. Understanding the mechanisms of cocaine’s effects on human CNS cells may help in the development of therapeutic strategies to prevent or ameliorate cocaine-induced impairments in fetal brain development.

Lee, Chun-Ting; Lehrmann, Elin; Hayashi, Teruo; Amable, Rose; Tsai, Shang-Yi; Chen, Jia; Sanchez, Joseph F.; Shen, James; Becker, Kevin G.; Freed, William J.

2009-01-01

341

Two components in the adrenal nicotinic secretory response revealed by cobalt ramps.  

PubMed

Prolonged stimulation with nicotine (50 microM) enhanced the secretion of catecholamines from perfused cat adrenal glands. The profile of secretion consisted of a quick activation phase to a peak of 7.68 micrograms/min followed by a second inactivation phase which exhibited a t1/2 of 3.75 min. Sustained stimulation with a solution enriched in K+ (59 mM) also evoked a transient secretory response, with a peak release of 8.62 micrograms/2 min and a t1/2 for inactivation of 4.8 min. Co2+ (10 mM) blocked the nicotinic response by 58% and the K(+)-evoked secretory response by over 96%. In the presence of Co2+ (5 mM), continuous perfusion with nicotine produced a transient but large initial secretory response; the gradual decrease of the extracellular Co2+ concentration, [Co2+]0, as a continuous ramp allowed the development of a second component of secretion which inactivated later on. When the glands were continuously stimulated with 59 mM K+ in the presence of Co2+, the first component of secretion was missing; the second component appeared as [Co2+]0 decreases as a ramp. In similar experiments performed in low-Na+ solution (10 mM Na+), only the first secretion component evoked by nicotine was observed. This finding suggests that the second component of secretion depends on Na+ entry through the nicotinic receptor, on the ensuing cell depolarization and on Ca2+ entry through voltage-dependent Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8428605

Montiel, C; Artalejo, A R; Sánchez-García, P; García, A G

1993-01-01

342

Proteomics reveals a core molecular response of Pseudomonas putida F1 to acute chromate challenge  

PubMed Central

Background Pseudomonas putida is a model organism for bioremediation because of its remarkable metabolic versatility, extensive biodegradative functions, and ubiquity in contaminated soil environments. To further the understanding of molecular pathways responding to the heavy metal chromium(VI) [Cr(VI)], the proteome of aerobically grown, Cr(VI)-stressed P. putida strain F1 was characterized within the context of two disparate nutritional environments: rich (LB) media and minimal (M9L) media containing lactate as the sole carbon source. Results Growth studies demonstrated that F1 sensitivity to Cr(VI) was impacted substantially by nutrient conditions, with a carbon-source-dependent hierarchy (lactate > glucose >> acetate) observed in minimal media. Two-dimensional HPLC-MS/MS was employed to identify differential proteome profiles generated in response to 1 mM chromate under LB and M9L growth conditions. The immediate response to Cr(VI) in LB-grown cells was up-regulation of proteins involved in inorganic ion transport, secondary metabolite biosynthesis and catabolism, and amino acid metabolism. By contrast, the chromate-responsive proteome derived under defined minimal growth conditions was characterized predominantly by up-regulated proteins related to cell envelope biogenesis, inorganic ion transport, and motility. TonB-dependent siderophore receptors involved in ferric iron acquisition and amino acid adenylation domains characterized up-regulated systems under LB-Cr(VI) conditions, while DNA repair proteins and systems scavenging sulfur from alternative sources (e.g., aliphatic sulfonates) tended to predominate the up-regulated proteome profile obtained under M9L-Cr(VI) conditions. Conclusions Comparative analysis indicated that the core molecular response to chromate, irrespective of the nutritional conditions tested, comprised seven up-regulated proteins belonging to six different functional categories including transcription, inorganic ion transport/metabolism, and amino acid transport/metabolism. These proteins might potentially serve as indicators of chromate stress in natural microbial communities.

2010-01-01

343

Auditory steady-state responses reveal amplitude modulation gap detection thresholds  

Microsoft Academic Search

Auditory evoked magnetic fields were recorded from the left hemisphere of healthy subjects using a 37-channel magnetometer while stimulating the right ear with 40-Hz amplitude modulated (AM) tone-bursts with 500-Hz carrier frequency in order to study the time-courses of amplitude and phase of auditory steady-state responses (ASSRs). The stimulus duration of 300 ms and the duration of the silent periods

Bernhard Ross; Christo Pantev

2004-01-01

344

Phosphoproteomic Analyses Reveal Early Signaling Events in the Osmotic Stress Response1[W][OPEN  

PubMed Central

Elucidating how plants sense and respond to water loss is important for identifying genetic and chemical interventions that may help sustain crop yields in water-limiting environments. Currently, the molecular mechanisms involved in the initial perception and response to dehydration are not well understood. Modern mass spectrometric methods for quantifying changes in the phosphoproteome provide an opportunity to identify key phosphorylation events involved in this process. Here, we have used both untargeted and targeted isotope-assisted mass spectrometric methods of phosphopeptide quantitation to characterize proteins in Arabidopsis (Arabidopsis thaliana) whose degree of phosphorylation is rapidly altered by hyperosmotic treatment. Thus, protein phosphorylation events responsive to 5 min of 0.3 m mannitol treatment were first identified using 15N metabolic labeling and untargeted mass spectrometry with a high-resolution ion-trap instrument. The results from these discovery experiments were then validated using targeted Selected Reaction Monitoring mass spectrometry with a triple quadrupole. Targeted Selected Reaction Monitoring experiments were conducted with plants treated under nine different environmental perturbations to determine whether the phosphorylation changes were specific for osmosignaling or involved cross talk with other signaling pathways. The results indicate that regulatory proteins such as members of the mitogen-activated protein kinase family are specifically phosphorylated in response to osmotic stress. Proteins involved in 5? messenger RNA decapping and phosphatidylinositol 3,5-bisphosphate synthesis were also identified as targets of dehydration-induced phosphoregulation. The results of these experiments demonstrate the utility of targeted phosphoproteomic analysis in understanding protein regulation networks and provide new insight into cellular processes involved in the osmotic stress response.

E. Stecker, Kelly; Minkoff, Benjamin B.; Sussman, Michael R.

2014-01-01

345

The heterogeneity of human antibody responses to vaccinia virus revealed through use of focused protein arrays.  

PubMed

The renewed interest in strategies to combat infectious agents with epidemic potential has led to a re-examination of vaccination protocols against smallpox. To help define which antigens elicit a human antibody response, we have targeted proteins known or predicted to be presented on the surface of the intracellular mature virion (IMV) or the extracellular enveloped virion (EEV). The predicted ectodomains were expressed in a mammalian in vitro coupled transcription/translation reaction using tRNA(lys) precharged with lysine-epsilon-biotin followed by solid phase immobilization on 384-well neutravidin-coated plates. The generated array is highly specific and sensitive in a micro-ELISA format. By comparison of binding of vaccinia-immune sera to the reticulocyte lysate-produced proteins and to secreted post-translationally modified proteins, we demonstrate that for several proteins including the EEV proteins B5 and A33, proper recognition is dependent upon appropriate folding, with little dependence upon glycosylation per se. We further demonstrate that the humoral immune response to vaccinia among different individuals is not uniform in specificity or strength, as different IMV and EEV targets predominate within the group of immunogenic proteins. This heterogeneity likely results from the diversity of HLA Class II alleles and CD4 T helper cell epitopes stimulating B cell antibody production. Our findings have important implications both for design of new recombinant subunit vaccines as well as for methods of assaying the human antibody response utilizing recombinant proteins produced in vitro. PMID:19146908

Duke-Cohan, Jonathan S; Wollenick, Kristin; Witten, Elizabeth A; Seaman, Michael S; Baden, Lindsey R; Dolin, Raphael; Reinherz, Ellis L

2009-02-18

346

Spectrotemporal resolution tradeoff in auditory processing as revealed by human auditory brainstem responses and psychophysical indices.  

PubMed

Auditory filter theory dictates a physiological compromise between frequency and temporal resolution of cochlear signal processing. We examined neurophysiological correlates of these spectrotemporal tradeoffs in the human auditory system using auditory evoked brain potentials and psychophysical responses. Temporal resolution was assessed using scalp-recorded auditory brainstem responses (ABRs) elicited by paired clicks. The inter-click interval (ICI) between successive pulses was parameterized from 0.7 to 25ms to map ABR amplitude recovery as a function of stimulus spacing. Behavioral frequency difference limens (FDLs) and auditory filter selectivity (Q10 of psychophysical tuning curves) were obtained to assess relations between behavioral spectral acuity and electrophysiological estimates of temporal resolvability. Neural responses increased monotonically in amplitude with increasing ICI, ranging from total suppression (0.7ms) to full recovery (25ms) with a temporal resolution of ?3-4ms. ABR temporal thresholds were correlated with behavioral Q10 (frequency selectivity) but not FDLs (frequency discrimination); no correspondence was observed between Q10 and FDLs. Results suggest that finer frequency selectivity, but not discrimination, is associated with poorer temporal resolution. The inverse relation between ABR recovery and perceptual frequency tuning demonstrates a time-frequency tradeoff between the temporal and spectral resolving power of the human auditory system. PMID:24793771

Bidelman, Gavin M; Syed Khaja, Ameenuddin

2014-06-20

347

Individual plastic responses by males to rivals reveal mismatches between behaviour and fitness outcomes  

PubMed Central

Plasticity in behaviour is of fundamental significance when environments are variable. Such plasticity is particularly important in the context of rapid changes in the socio-sexual environment. Males can exhibit adaptive plastic responses to variation in the overall level of reproductive competition. However, the extent of behavioural flexibility within individuals, and the degree to which rapidly changing plastic responses map onto fitness are unknown. We addressed this by determining the behaviour and fitness profiles of individual Drosophila melanogaster males subjected to up to three episodes of exposure to rivals or no rivals, in all combinations. Behaviour (mating duration) was remarkably sensitive to the level of competition and fully reversible, suggesting that substantial costs arise from the incorrect expression of even highly flexible behaviour. However, changes in mating duration matched fitness outcomes (offspring number) only in scenarios in which males experienced zero then high competition. Following the removal of competition, mating duration, but not offspring production, decreased to below control levels. This indicates that the benefit of increasing reproductive investment when encountering rivals may exceed that of decreasing investment when rivals disappear. Such asymmetric fitness benefits and mismatches with behavioural responses are expected to exert strong selection on the evolution of plasticity.

Bretman, Amanda; Westmancoat, James D.; Gage, Matthew J. G.; Chapman, Tracey

2012-01-01

348

Continuous functional magnetic resonance imaging reveals dynamic nonlinearities of "dose-response" curves for finger opposition.  

PubMed

Linear experimental designs have dominated the field of functional neuroimaging, but although successful at mapping regions of relative brain activation, the technique assumes that both cognition and brain activation are linear processes. To test these assumptions, we performed a continuous functional magnetic resonance imaging (MRI) experiment of finger opposition. Subjects performed a visually paced bimanual finger-tapping task. The frequency of finger tapping was continuously varied between 1 and 5 Hz, without any rest blocks. After continuous acquisition of fMRI images, the task-related brain regions were identified with independent components analysis (ICA). When the time courses of the task-related components were plotted against tapping frequency, nonlinear "dose- response" curves were obtained for most subjects. Nonlinearities appeared in both the static and dynamic sense, with hysteresis being prominent in several subjects. The ICA decomposition also demonstrated the spatial dynamics with different components active at different times. These results suggest that the brain response to tapping frequency does not scale linearly, and that it is history-dependent even after accounting for the hemodynamic response function. This implies that finger tapping, as measured with fMRI, is a nonstationary process. When analyzed with a conventional general linear model, a strong correlation to tapping frequency was identified, but the spatiotemporal dynamics were not apparent. PMID:10407059

Berns, G S; Song, A W; Mao, H

1999-07-15

349

Mechanisms Underlying Visceral Hypersensitivity in Irritable Bowel Syndrome  

Microsoft Academic Search

Visceral hypersensitivity is currently considered a key pathophysiological mechanism involved in pain perception in large\\u000a subgroups of patients with functional gastrointestinal disorders, including irritable bowel syndrome (IBS). In IBS, visceral\\u000a hypersensitivity has been described in 20%–90% of patients. The contribution of the central nervous system and psychological\\u000a factors to visceral hypersensitivity in patients with IBS may be significant, although still

Giovanni Barbara; Cesare Cremon; Roberto De Giorgio; Giovanni Dothel; Lisa Zecchi; Lara Bellacosa; Giovanni Carini; Vincenzo Stanghellini; Roberto Corinaldesi

2011-01-01

350

Understanding drug hypersensitivity: what to look for when prescribing abacavir.  

PubMed

Abacavir sulfate is an inhibitor of HIV-1 reverse transcriptase. Approximately 5% of patients given abacavir develop a hypersensitivity reaction, a clinical syndrome thought to be immune-mediated and described previously with many different drugs, including other antiretroviral agents. Although rare, fatal reactions have occurred. Actions aimed at reducing morbidity and risk of fatality with hypersensitivity reactions include patient education, early identification and evaluation of symptoms suggestive of hypersensitivity, and prompt discontinuation of abacavir once the diagnosis has been established. PMID:11806176

Hetherington, S

2001-12-01

351

Contribution of CD4(+ )and CD8(+) T-cells in contact hypersensitivity and allergic contact dermatitis.  

PubMed

Allergic contact dermatitis, also referred to as contact hypersensitivity, is one the most frequent inflammatory skin diseases, and is characterized by redness, papule and vesicles, followed by scaling and dryness. Allergic contact dermatitis is elicited upon skin contact with nonprotein chemicals, haptens, and corresponds to a cutaneous delayed type hypersensitivity reaction, mediated by hapten-specific T-cells. During the sensitization phase, both CD4(+) and CD8(+) T-cell precursors are activated in the draining lymph nodes by presentation of haptenated peptides by skin dendritic cells. Subsequent hapten painting on a remote skin site induces the recruitment and activation of specific T-cells at the site of challenge. This leads to apoptosis of keratinocytes, recruitment of inflammatory cells and development of clinical symptoms. Experimental studies from the last 10 years have demonstrated that, in normal contact hypersensitivity responses to strong haptens, CD8(+) type 1 T-cells are effector cells of contact hypersensitivity through cytotoxicity and interferon-gamma production, while CD4(+) T-cells are endowed with downregulatory functions. The latter may correspond to the recently described CD4(+)CD25(+) regulatory T-cell population. However, in some instances, especially when there is a deficient CD8(+) T-cell pool, CD4(+) T-cells can be effector cells of contact hypersensitivity. Ongoing studies will have to confirm that the pathophysiology of human allergic contact dermatitis is similar to the mouse contact hypersensitivity and that the contact hypersensitivity response to common weak haptens, most frequently involved in human allergic contact dermatitis, is similar to that reported for strong haptens. PMID:20477656

Vocanson, Marc; Hennino, Ana; Chavagnac, Cyril; Saint-Mezard, Pierre; Dubois, Bertrand; Kaiserlian, Dominique; Nicolas, Jean-Francois

2005-05-01

352

Titanium hypersensitivity. A hidden threat for dental implant patients?  

PubMed

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. PMID:24027897

Bilhan, Hakan; Bural, Canan; Geckili, Onur

2013-01-01

353

X-ray induction of persistent hypersensitivity to mutation  

SciTech Connect

The progeny of x-irradiated V79 cells are hypersensitive to PUVA-(8-methoxypsoralen plus longwave ultraviolet light) induced mutation at the locus for hypoxanthine-guanine phosphoribosyl transferase. This hypersensitivity is most evident at low doses of pUVA that do not induce mutation in non-x-irradiated cells. The hypersensitivity is evoked by x-irradiation delivered as a single dose or as multiple fractions over a long period and persists for at least 108 days of exponential growth. This radiation-induced hypersensitivity to subsequent mutation is a new phenomenon that may be relevant to multistage carcinogenesis.

Frank, J.P.; Williams, J.R.

1982-04-16

354

[Effects of potassium oxalate with fluoride gel on dentin hypersensitivity  

PubMed

This study observed the potassium oxalate including fluoride gel on the reduction of dentin hypersensitivity both in clinic and in laboratory.The results of the clinical treatment showed that this gel was statistically significant in reducing dentin hypersensitivity when the teeth treating by the gel for 4 minutes.The results of the scanning electric microscope(SEM) research indicated that the gel could create micro-globed particles deposition on the dentine surface.These particles have the ability to block the dentinal tubules and to decrease dentin hypersensitivity.In conclusion,this gel is an effective and safe topical agent for dentin hypersensitivity treatment. PMID:15160104

Yang, Y Z

1995-03-01

355

Directional responses following recombinant cytokine stimulation of rainbow trout (Oncorhynchus mykiss) RTS-11 macrophage cells as revealed by transcriptome profiling  

PubMed Central

Background The early stages of the immune response are regulated by key cytokines including both interleukin 1? (IL-1?) and interferon-? (IFN-?) which stimulate panels of responsive genes via conserved signal transduction pathways. To further our understanding of the transcriptional response to these cytokines in lower vertebrates we have utilized microarray analysis to characterize the transcriptional response to recombinant rainbow trout IL-1? and IFN-? in the trout macrophage cell line RTS-11. Results RNA was extracted from stimulated or control cells following 6 h incubation and used to hybridize to a salmonid cDNA microarray containing 16,006 different genes. Analysis of the arrays revealed mRNA transcripts that were differentially expressed as a result of exposure to the recombinant proteins, with some responses common for both cytokines. In general the recombinant IL-1? elicited a response where genes involved in the acute phase response were up-regulated, whilst the recombinant IFN-? induced strong up-regulation of genes involved in the MHC class I antigen presentation pathway. Key genes were chosen that were differentially regulated and analysed by real time PCR at additional time points, up to 48 h following stimulation. This allowed a deeper insight into the kinetics of the response to the cytokines in this cell line. Conclusion We demonstrated that in fish both rIL-1? and rIFN-? stimulated discrete panels of mRNA transcripts which indicted the cells were being directed towards different cellular functions, with IL-? inducing genes involved in the inflammatory response, whereas IFN-? induced genes associated with antigen presentation.

Martin, Samuel AM; Zou, Jun; Houlihan, Dominic F; Secombes, Christopher J

2007-01-01

356

Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy  

PubMed Central

The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI) and the use of 13C labeled substrates and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP) activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle.

Bartnik-Olson, Brenda L.; Harris, Neil G.; Shijo, Katsunori; Sutton, Richard L.

2013-01-01

357

Metagenomics reveals sediment microbial community response to Deepwater Horizon oil spill  

PubMed Central

The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ?4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences. Here we investigated the impact of oil deposition on microbial communities in surface sediments collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun metagenomic sequencing of 14 of these samples and mineralization experiments using 14C-labeled model substrates. The 16S rRNA gene data indicated that the most heavily oil-impacted sediments were enriched in an uncultured Gammaproteobacterium and a Colwellia species, both of which were highly similar to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in structuring the microbial community were nitrogen and hydrocarbons. Annotation of unassembled metagenomic data revealed the most abundant hydrocarbon degradation pathway encoded genes involved in degrading aliphatic and simple aromatics via butane monooxygenase. The activity of key hydrocarbon degradation pathways by sediment microbes was confirmed by determining the mineralization of 14C-labeled model substrates in the following order: propylene glycol, dodecane, toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)'s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not. Importantly, these data demonstrate that the indigenous sediment microbiota contributed an important ecosystem service for remediation of oil in the Gulf. However, PAHs were more recalcitrant to degradation, and their persistence could have deleterious impacts on the sediment ecosystem.

Mason, Olivia U; Scott, Nicole M; Gonzalez, Antonio; Robbins-Pianka, Adam; Baelum, Jacob; Kimbrel, Jeffrey; Bouskill, Nicholas J; Prestat, Emmanuel; Borglin, Sharon; Joyner, Dominique C; Fortney, Julian L; Jurelevicius, Diogo; Stringfellow, William T; Alvarez-Cohen, Lisa; Hazen, Terry C; Knight, Rob; Gilbert, Jack A; Jansson, Janet K

2014-01-01

358

Metagenomics reveals sediment microbial community response to Deepwater Horizon oil spill.  

PubMed

The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ?4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences. Here we investigated the impact of oil deposition on microbial communities in surface sediments collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun metagenomic sequencing of 14 of these samples and mineralization experiments using (14)C-labeled model substrates. The 16S rRNA gene data indicated that the most heavily oil-impacted sediments were enriched in an uncultured Gammaproteobacterium and a Colwellia species, both of which were highly similar to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in structuring the microbial community were nitrogen and hydrocarbons. Annotation of unassembled metagenomic data revealed the most abundant hydrocarbon degradation pathway encoded genes involved in degrading aliphatic and simple aromatics via butane monooxygenase. The activity of key hydrocarbon degradation pathways by sediment microbes was confirmed by determining the mineralization of (14)C-labeled model substrates in the following order: propylene glycol, dodecane, toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)'s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not. Importantly, these data demonstrate that the indigenous sediment microbiota contributed an important ecosystem service for remediation of oil in the Gulf. However, PAHs were more recalcitrant to degradation, and their persistence could have deleterious impacts on the sediment ecosystem. PMID:24451203

Mason, Olivia U; Scott, Nicole M; Gonzalez, Antonio; Robbins-Pianka, Adam; Bælum, Jacob; Kimbrel, Jeffrey; Bouskill, Nicholas J; Prestat, Emmanuel; Borglin, Sharon; Joyner, Dominique C; Fortney, Julian L; Jurelevicius, Diogo; Stringfellow, William T; Alvarez-Cohen, Lisa; Hazen, Terry C; Knight, Rob; Gilbert, Jack A; Jansson, Janet K

2014-07-01

359

Suppressive responses by visual food cues in postprandial activities of insular cortex as revealed by magnetoencephalography.  

PubMed

'Hara-Hachibu' in Japanese means a subjective sense by which we stop eating just before the motivation to eat is completely lost, a similar concept to caloric restriction (CR). Insular cortex is a critical platform which integrates sensory information into decision-making processes in eating behavior. We compared the responses of insular cortex, as assessed by magnetoencephalography (MEG), immediately after presentation of food images in the Fasting condition with those in the 'Hara-Hachibu' condition. Eleven healthy, right-handed males [age, 27.2±9.6 years; body mass index, 22.6±2.1kg/m(2) (mean±SD)] were enrolled in a randomized, two-crossover experiment (Fasting and 'Hara-Hachibu' conditions). Before the MEG recordings in the 'Hara-Hachibu' condition, the participants consumed rice balls as much as they judged themselves to have consumed shortly before reaching satiety. During the MEG recordings, they viewed food pictures projected on a screen. The intensities of MEG responses to viewing food pictures were significantly lower in the 'Hara-Hachibu' condition than those in the Fasting condition (P<0.05). The intensities of the MEG responses to the visual food stimuli in the 'Hara-Hachibu' condition was positively associated with the factor-3 (food tasted) (r=0.693, P=0.018) and aggregated scores (r=0.659, P=0.027) of the Power of Food Scale, a self-report measure of hedonic hunger. These findings may help to elucidate the neural basis of variability of appetite phenotypes under the condition of CR among individuals, and to develop possible strategies for the maintenance of adequate CR in daily life. PMID:24768717

Yoshikawa, Takahiro; Tanaka, Masaaki; Ishii, Akira; Watanabe, Yasuyoshi

2014-06-01

360

Extended DNFB-induced contact hypersensitivity models display characteristics of chronic inflammatory dermatoses.  

PubMed

Despite recent developments, there is a high medical need for new treatment options for chronic inflammatory dermatoses like allergic contact dermatitis (ACD) and psoriasis. Particularly, more predictive skin inflammation models are required to facilitate the process of drug discovery. Murine contact hypersensitivity (CHS) models adequately reflect ACD and are also used to characterize therapeutic approaches for psoriasis. Using the hapten 2,4-dinitrofluorobenzene (DNFB), we established new subacute and subchronic DNFB-induced CHS models in C57BL/6 mice, which more closely reflect the characteristics of chronic T-cell-dependent inflammatory dermatoses as pronounced keratinocyte proliferation, strong hypervascularization, immune cell infiltration and overexpression of T cell and inflammatory cytokines. For the subacute DNFB model, we demonstrated anti-inflammatory activity of the glucocorticoid, prednisolone, as well as of neutralization of TNF?, IL-12/IL-23 or IL-18. In the subchronic DNFB-induced CHS model, deficiency for MyD88 and IL-12/IL-35 p35 chain but not IL-12/IL-23 p40 chain led to decreased skin inflammation. Furthermore, as exemplified by the dose-dependently effective therapeutic prednisolone treatment, the subchronic model allows the continuous therapy of a pre-established stable contact dermatitis. Altogether, prolonged DNFB-induced mouse CHS models closely reflect ACD sensitive to glucocorticoids as standard therapy, reveal a more chronic skin inflammation and are responsive to cytokine antagonization. PMID:22151387

Röse, Lars; Schneider, Claudia; Stock, Christine; Zollner, Thomas M; Döcke, Wolf-Dietrich

2012-01-01

361

Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo  

Microsoft Academic Search

Background  Early life stages are generally most sensitive to toxic effects. Our knowledge on the action of manmade chemicals on the developing\\u000a vertebrate embryo is, however, rather limited. We addressed the toxicogenomic response of the zebrafish embryo in a systematic\\u000a manner by asking whether distinct chemicals would induce specific transcriptional profiles.\\u000a \\u000a \\u000a \\u000a \\u000a Results  We exposed zebrafish embryos to a range of environmental toxicants

Lixin Yang; Jules R Kemadjou; Christian Zinsmeister; Matthias Bauer; Jessica Legradi; Ferenc Müller; Michael Pankratz; Jens Jäkel; Uwe Strähle

2007-01-01

362

Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells  

SciTech Connect

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.

Fang, Liang [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China); Zhao, Fang; Shen, Xuefeng [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China); Ouyang, Weiming [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States)] [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States); Liu, Xinqin; Xu, Yan; Yu, Tao [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China); Jin, Boquan [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)

2012-12-01

363

Arabidopsis mutants deregulated in RCI2A expression reveal new signaling pathways in abiotic stress responses.  

PubMed

To uncover new pathways involved in low-temperature signal transduction, we screened for mutants altered in cold-induced expression of RCI2A, an Arabidopsis gene that is not a member of the CBF/DREB1 regulon and is induced not only by low temperature but also by abscisic acid (ABA), dehydration (DH) and NaCl. This was accomplished by generating a line of Arabidopsis carrying a transgene consisting of the RCI2A promoter fused to the firefly luciferase coding sequence. A number of mutants showing low or high RCI2A expression in response to low temperature were identified. These mutants also displayed deregulated RCI2A expression in response to ABA, DH or NaCl. Interestingly, however, they were not altered in stress-induced expression of RD29A, a CBF/DREB1-target gene, suggesting that the mutations affect signaling intermediates of CBF/DREB1-independent regulatory pathways. Several mutants showed alterations in their tolerance to freezing, DH or salt stress, as well as in their ABA sensitivity, which indicates that the signaling intermediates defined by the corresponding mutations play an important role in Arabidopsis tolerance to abiotic stresses. Based on the mutants identified, we discuss the involvement of CBF/DREB1-independent pathways in modulating stress signaling. PMID:15860016

Medina, Joaquín; Rodríguez-Franco, Marta; Peñalosa, Andrés; Carrascosa, María J; Neuhaus, Gunther; Salinas, Julio

2005-05-01

364

Chemical genetics reveals negative regulation of abscisic acid signaling by a plant immune response pathway  

PubMed Central

Summary Coordinated regulation of protection mechanisms against environmental abiotic stress and pathogen attack is essential for plant adaptation and survival. Initial abiotic stress can interfere with disease resistance signaling [1–6]. Conversely, initial plant immune signaling may interrupt subsequent ABA signal transduction [7, 8]. However, the processes involved in cross talk between these signaling networks have not been determined. By screening a 9,600 compound chemical library, we identified a small molecule DFPM that rapidly down-regulates ABA-dependent gene expression and also inhibits ABA-induced stomatal closure. Transcriptome analyses show that DFPM also stimulates expression of plant defense-related genes. Major early regulators of pathogen resistance responses, including EDS1, PAD4, RAR1, and SGT1b, are required for DFPM- and notably also for Pseudomonas-interference with ABA signal transduction, whereas salicylic acid, EDS16 and NPR1 are not necessary. While DFPM does not interfere with early ABA perception by PYR/RCAR receptors or ABA-activation of SnRK2 kinases, it disrupts cytosolic Ca2+ signaling and downstream anion channel activation in a pad4-dependent manner. Our findings provide evidence that activation of EDS1/PAD4-dependent plant immune responses rapidly disrupts ABA signal transduction and this occurs at the level of Ca2+ signaling, illuminating how the initial biotic stress pathway interferes with ABA signaling.

Kim, Tae-Houn; Hauser, Felix; Ha, Tracy; Xue, Shaowu; Bohmer, Maik; Nishimura, Noriyuki; Munemasa, Shintaro; Hubbard, Katharine; Peine, Nora; Lee, Byeong-ha; Lee, Stephen; Robert, Nadia; Parker, Jane E.; Schroeder, Julian I.

2011-01-01

365

Direct measurement of transcription rates reveals multiple mechanisms for configuration of the Arabidopsis ambient temperature response  

PubMed Central

Background Sensing and responding to ambient temperature is important for controlling growth and development of many organisms, in part by regulating mRNA levels. mRNA abundance can change with temperature, but it is unclear whether this results from changes in transcription or decay rates, and whether passive or active temperature regulation is involved. Results Using a base analog labelling method, we directly measured the temperature coefficient, Q10, of mRNA synthesis and degradation rates of the Arabidopsis transcriptome. We show that for most genes, transcript levels are buffered against passive increases in transcription rates by balancing passive increases in the rate of decay. Strikingly, for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay and not vice versa, suggesting a global transcriptional process exists that controls mRNA abundance by temperature. This is partly accounted for by gene body H2A.Z which is associated with low transcription rate Q10, but is also influenced by other marks and transcription factor activities. Conclusions Our data show that less frequent chromatin states can produce temperature responses simply by virtue of their rarity and the difference between their thermal properties and those of the most common states, and underline the advantages of directly measuring transcription rate changes in dynamic systems, rather than inferring rates from changes in mRNA abundance.

2014-01-01

366

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

PubMed Central

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.

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

2012-01-01

367

Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: An exploratory study in chronic whiplash patients  

PubMed Central

Background The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD) and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity). Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB) procedure in the cervical spine. Methods Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST) consisting of pressure pain thresholds (PPT's) and cold pain thresholds (CPT's). In patients with chronic WAD (n = 18), the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18) was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. Results At baseline, PPT's were decreased at all three sites in the WAD group (p < 0.001). Cold pain thresholds were increased in the cervical spine in the WAD group (p < 0.001). Post-MBB, the WAD group showed significant increases in PPT's at all sites (p < 0.05), and significant decreases in CPT's at the cervical spine (p < 0.001). Conclusions The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical zygapophyseal joints.

2010-01-01

368

RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus  

PubMed Central

Background In a context of climate change, phenotypic plasticity provides long-lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. Results Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by-treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. Conclusions For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance of biomass growth during the dry season. Its strategy may involve a decrease of photosynthetic activity during the dry season associated with resources reallocation through major changes in the expression of primary metabolism associated genes. Further efforts will be needed to assess the adaptive nature of the genes highlighted in this study.

2011-01-01

369

Plasma Proteome Response to Severe Burn Injury Revealed by 18O-Labeled "Universal" Reference-based Quantitative Proteomics  

PubMed Central

A burn injury represents one of the most severe forms of human trauma and is responsible for significant mortality worldwide. Here, we present the first quantitative proteomics investigation of the blood plasma proteome response to severe burn injury by comparing the plasma protein concentrations of 10 healthy control subjects with those of 15 severe burn patients at two time-points following the injury. The overall analytical strategy for this work integrated immunoaffinity depletion of the 12 most abundant plasma proteins with cysteinyl-peptide enrichment-based fractionation prior to LC-MS analyses of individual patient samples. Incorporation of an 18O-labeled “universal” reference among the sample sets enabled precise relative quantification across samples. In total, 313 plasma proteins confidently identified with two or more unique peptides were quantified. Following statistical analysis, 110 proteins exhibited significant abundance changes in response to the burn injury. The observed changes in protein concentrations suggest significant inflammatory and hypermetabolic response to the injury, which is supported by the fact that many of the identified proteins are associated with acute phase response signaling, the complement system, and coagulation system pathways. The regulation of ~35 proteins observed in this study is in agreement with previous results reported for inflammatory or burn response, but approximately 50 potentially novel proteins previously not known to be associated with burn response or inflammation are also found. Elucidating proteins involved in the response to severe burn injury may reveal novel targets for therapeutic interventions, as well as potential predictive biomarkers for patient outcomes such as multiple organ failure.