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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

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

3

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. PMID:24265926

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

2013-01-01

4

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

PubMed Central

The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots and roots grafted with the susceptible Bintje cultivar as well as non-grafted different parts of Sarpo Mira plants were inoculated with P. infestans. The progress of the infection and the number of HR lesions were monitored, and the regulation of PR genes was compared in detached and attached leaves. Additionally, the antimicrobial activity of plant extracts was assessed. The presented data show that roots are needed to achieve full pathogen resistance, that the removal of meristems in detached leaves inhibits the formation of HR lesions, that PR genes are differentially regulated in detached leaves compared with leaves of whole plants, and that antimicrobial compounds accumulate in leaves and roots of Sarpo Mira plants challenged with P. infestans. While meristems are necessary for the formation of HR lesions, the roots of Sarpo Mira plants participate in the production of defence-associated compounds that increase systemic resistance. Based on the literature and on the presented results, a model is proposed for mechanisms involved in Sarpo Mira resistance that may apply to other resistant potato cultivars. PMID:22844094

Or?owska, El?bieta; Llorente, Briardo

2012-01-01

5

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

PubMed

The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots and roots grafted with the susceptible Bintje cultivar as well as non-grafted different parts of Sarpo Mira plants were inoculated with P. infestans. The progress of the infection and the number of HR lesions were monitored, and the regulation of PR genes was compared in detached and attached leaves. Additionally, the antimicrobial activity of plant extracts was assessed. The presented data show that roots are needed to achieve full pathogen resistance, that the removal of meristems in detached leaves inhibits the formation of HR lesions, that PR genes are differentially regulated in detached leaves compared with leaves of whole plants, and that antimicrobial compounds accumulate in leaves and roots of Sarpo Mira plants challenged with P. infestans. While meristems are necessary for the formation of HR lesions, the roots of Sarpo Mira plants participate in the production of defence-associated compounds that increase systemic resistance. Based on the literature and on the presented results, a model is proposed for mechanisms involved in Sarpo Mira resistance that may apply to other resistant potato cultivars. PMID:22844094

Or?owska, Elzbieta; Basile, Alessio; Kandzia, Izabela; Llorente, Briardo; Kirk, Hanne Grethe; Cvitanich, Cristina

2012-08-01

6

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

PubMed Central

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.

2012-01-01

7

Programmed cell death, mitochondria and the plant hypersensitive response  

Microsoft Academic Search

The plant response to attempted infection by microbial pathogens is often accompanied by rapid cell death in and around the initial infection site, a reaction known as the hypersensitive response. This response is associated with restricted pathogen growth and represents a form of programmed cell death (PCD). Recent pharmacological and molecular studies have provided functional evidence for the conservation of

Eric Lam; Naohiro Kato; Michael Lawton

2001-01-01

8

Contact hypersensitivity response to glutaraldehyde in guinea pigs and mice.  

PubMed

Glutaraldehyde has a wide spectrum of uses which can result in dermal contact with the agent. The low number of reports of hypersensitive reactions to glutaraldehyde indicates a low incidence of sensitization. This paper describes the contact hypersensitivity response to glutaraldehyde in the guinea pig and the mouse. Female albino Hartley strain guinea pigs and female B6C3F1 mice were sensitized with 0.3, 1.0 and 3.0% glutaraldehyde and challenged with 10% glutaraldehyde. Doses of glutaraldehyde were selected from assays for primary irritancy. Guinea pigs received 100 microliters by direct dermal application, for 14 consecutive days, and mice received 20 microliters by direct dermal application, for 5 or 14 consecutive days, to sites prepared by shaving and dermabrading. Rest periods were 7 or 14 days for guinea pigs and 4 or 7 days for mice. Measurement of the contact hypersensitivity response in guinea pigs was both visual evaluation (scoring) at 24 and 48 hours following challenge and radioisotopic assay at 48 hours, and in mice by radioisotopic assay 48 hours after challenge. Both guinea pigs and mice demonstrated dose-dependent contact hypersensitivity responses to glutaraldehyde. The radioisotopic assay appeared to be more sensitive than visual evaluation in detecting contact allergic hypersensitivity to glutaraldehyde. PMID:2497558

Stern, M L; Holsapple, M P; McCay, J A; Munson, A E

1989-01-01

9

Both hypersensitive and non-hypersensitive responses are associated with resistance in Salix viminalis against the gall midge Dasineura marginemtorquens  

Microsoft Academic Search

Hypersensitivity responses (HR) play a major role in plant resistance to pathogens. It is often claimed that HR is also important in plant resistance to insects, although there is little unambiguous documentation. Large genotypic variation in resistance against the gall midge Dasineura marginemtorquens is found in Salix viminalis. Variation in larval performance and induced responses within a full-sib S. viminalis

Solveig Hoglund; Stig Larsson; Gunnar Wingsle

2005-01-01

10

The hypersensitive response facilitates plant infection by the necrotrophic pathogen Botrytis cinerea  

Microsoft Academic Search

Background: Plants have evolved efficient mechanisms to combat pathogen attack. One of the earliest responses to attempted pathogen attack is the generation of oxidative burst that can trigger hypersensitive cell death. This is called the hypersensitive response (HR) and is considered to be a major element of plant disease resistance. The HR is thought to deprive the pathogens of a

Eri M Govrin; Alex Levine

2000-01-01

11

Activation of cysteine proteases in cowpea plants during the hypersensitive response--a form of programmed cell death.  

PubMed

There is increasing evidence that the hypersensitive response during plant-pathogen interactions is a form of programmed cell death. In an attempt to understand the biochemical nature of this form of programmed cell death in the cowpea-cowpea rust fungus system, proteolytic activity in extracts of fungus-infected and uninfected cowpea plants was investigated, using exogenously added poly(ADP-ribose) polymerase as a marker. Unlike the proteolytic cleavage pattern of endogenous poly(ADP-ribose) polymerase in apoptotic animal cells, exogenously added poly(ADP-ribose) polymerase in extracts of fungus-infected plants was proteolytically cleaved into fragments of molecular masses 77, 52, 47, and 45 kDa. In vitro and in vivo protease inhibitor experiments revealed the activation of cysteine proteases, and possibly a regulatory role, during the hypersensitive response. PMID:9851880

D'Silva, I; Poirier, G G; Heath, M C

1998-12-15

12

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

PubMed

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

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

2013-06-01

13

The Hypersensitive Response and its Role in Local and Systemic Disease Resistance  

Microsoft Academic Search

A ubiquitous feature of plant\\/pathogen interactions is host cell death that is manifested as rapid collapse of tissue and is termed the hypersensitive response (HR). This response accompanies many but not all incompatible interactions and is considered one of the important mechanisms leading to resistance. The sites of HR the infection sites proper are invariably the focal points for transcriptional

Erich Kombrink; Elmon Schmelzer

2001-01-01

14

Elucidation of the hrp Clusters of Xanthomonas oryzae pv. oryzicola That Control the Hypersensitive Response in Nonhost Tobacco and Pathogenicity in Susceptible Host Rice  

Microsoft Academic Search

Xanthomonas oryzae pv. oryzicola, the cause of bacterial leaf streak in rice, possesses clusters of hrp genes that determine its ability to elicit a hypersensitive response (HR) in nonhost tobacco and pathogenicity in host rice. A 27-kb region of the genome of X. oryzae pv. oryzicola (RS105) was identified and sequenced, revealing 10 hrp ,9 hrc (hrp conserved), and 8

Li-fang Zou; Xing-ping Wang; Yong Xiang; Bing Zhang; Yu-Rong Li; You-lun Xiao; Jin-sheng Wang; Adrian R. Walmsley; Gong-you Chen

2006-01-01

15

Contact hypersensitivity response to o-benzyl-p-chlorophenol in mice.  

PubMed

o-Benzyl-p-chlorophenol was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 1.0, 3.0, and 10.0% o-benzyl-p-chlorophenol and challenged with 20.0% o-benzyl-p-chlorophenol. Doses of o-benzyl-p-chlorophenol were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of Freund's complete adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling test one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity response to o-benzyl-p-chlorophenol with or without adjuvant pretreatment. PMID:1935704

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

1991-01-01

16

Both hypersensitive and non-hypersensitive responses are associated with resistance in Salix viminalis against the gall midge Dasineura marginemtorquens.  

PubMed

Hypersensitivity responses (HR) play a major role in plant resistance to pathogens. It is often claimed that HR is also important in plant resistance to insects, although there is little unambiguous documentation. Large genotypic variation in resistance against the gall midge Dasineura marginemtorquens is found in Salix viminalis. Variation in larval performance and induced responses within a full-sib S. viminalis family is reported here; 36 sibling plants were completely resistant (larvae died within 48 h after egg hatch, no gall induction), 11 plants were totally susceptible, 25 plants were variable (living and dead larvae present on the same plant). Resistance was associated with HR, but to different degrees; 21 totally resistant genotypes showed typical HR symptoms (many distinct necrotic spots) whereas the remaining 15 genotypes showed no, or very few, such symptoms. Hydrogen peroxide, used as a marker for HR, was induced in genotypes expressing HR symptoms but not in resistant genotypes without symptoms, or in susceptible genotypes. These data suggest that production of hydrogen peroxide, and accompanying cell death, cannot explain larval mortality in the symptomless reaction. Another, as yet unknown, mechanism of resistance may be present. If so, then it is possible that this unknown mechanism also contributes to resistance in plants displaying HR. The apparent complexity observed in this interaction, with both visible and invisible plant responses associated with resistance against an adapted insect species, may have implications for the study of resistance factors in other plant-insect interactions. PMID:16263902

Höglund, Solveig; Larsson, Stig; Wingsle, Gunnar

2005-12-01

17

Preconception maternal immunization to dust mite inhibits the type I hypersensitivity response of offspring  

Microsoft Academic Search

Background: The maternal immunologic experience associated with early life exposure to allergens might contribute to the development of allergy during infancy. Objectives: We sought to analyze the effect of the mother's immunization before conception with the dust mite Dermatophagoides pteronyssinus on the allergen priming and hypersensitivity response in early immunized offspring. The kinetics of D pteronyssinus immunization were observed from

Jefferson Russo Victor Jr; Ana Elisa Fusaro; Alberto José da Silva Duarte; Maria Notomi Sato

2003-01-01

18

Nonthermal Microwave Radiations Affect the Hypersensitive Response of Tobacco to Tobacco Mosaic Virus  

Microsoft Academic Search

Objectives: The aim of the present study was to evaluate the effects of nonthermal extremely high-frequency microwave radiations in a plant-based bioassay, represented by tobacco plants reacting to tobacco mosaic virus with a hypersensitive response leading to the appearance of necrotic lesions at the infection sites. Design: This study was performed blind and different experimental protocols on tobacco plants inoculated

Lucietta Betti; Grazia Trebbi; Lisa Lazzarato; Maurizio Brizzi; Gian Lorenzo Calzoni; Fiorenzo Marinelli; Daniele Nani; Francesco Borghini

2004-01-01

19

Light-dependent hypersensitive response and resistance signaling against Turnip Crinkle Virus in Arabidopsis  

E-print Network

Light-dependent hypersensitive response and resistance signaling against Turnip Crinkle Virus.edu). Summary Resistance to Turnip Crinkle Virus (TCV) in Arabidopsis ecotype Dijon (Di)-17 is conferred: Turnip Crinkle Virus, salicylic acid, defense, Arabidopsis, signaling, ssi2, light. Introduction Plants

Kachroo, Pradeep

20

LIGHT DEPENDENT HYPERSENSITIVE RESPONSE AND RESISTANCE SIGNALING AGAINST TURNIP CRINKLE VIRUS IN ARABIDOPSIS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Resistance to turnip crinkle virus (TCV) in Arabidopsis ecotype Dijon (Di)-17 is conferred by the resistance gene HRT and a recessive locus rrt. Inoculation of TCV on Di-17 elicits a hypersensitive response (HR), which is accompanied by increased expression of the pathogenesis-related (PR) genes and...

21

Th2Biased Immune Responses Are Important in a Murine Model of Chronic Hypersensitivity Pneumonitis  

Microsoft Academic Search

Background: Chronic hypersensitivity pneumonitis (HP) can lead to irreversible pulmonary fibrosis. A good animal model is essential to elucidate the mechanisms of this disease. We previously reported that a Th2 predominance may play an important role in the fibrogenesis in chronic HP patients. A study was undertaken to evaluate whether Th2-biased immune responses were crucial during the processes of lung

Keiko Mitaka; Yasunari Miyazaki; Makito Yasui; Masashi Furuie; Shuji Miyake; Naohiko Inase; Yasuyuki Yoshizawa

2011-01-01

22

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

EPA Science Inventory

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

23

Alerted Defense System Attenuates Hypersensitive Response-Associated Cell Death in Arabidopsis siz1 Mutant  

Microsoft Academic Search

Plants defend themselves by inducing sophisticated multilevel defense responses against pathogenic attack. The first line\\u000a of defense against microbial pathogens is the process of nonself-recognition, which mediates the activation of the necessary\\u000a defense repertoire. The hypersensitive response (HR), a macroscopic collapse of plant leaves in primary infection site, is\\u000a one of such plant resistance responses. Subsequently, the HR triggers a

Min Gab Kim

2010-01-01

24

The Hypersensitive Glucocorticoid Response Specifically Regulates Period 1 and Expression of Circadian Genes  

PubMed Central

Glucocorticoids regulate gene expression by binding and activating the glucocorticoid receptor (GR). While ligand affinity determines the global sensitivity of the response, additional proteins act on the genome to tune sensitivity of some genes. However, the genomic extent and specificity of dose-specific glucocorticoid responses are unknown. We show that dose-specific glucocorticoid responses are extraordinarily specific at the genomic scale, able to distinctly express a single gene, the circadian rhythm gene for Period 1 (PER1), at concentrations consistent with the nighttime nadir of human cortisol. We mapped the PER1 response to a single GR binding site. The specific GR binding sequence did not impact sensitivity, and we instead attributed the response to a combination of additional transcription factors and chromatin accessibility acting in the same locus. The PER1 hypersensitive response element is conserved in the mouse, where we found similar upregulation of Per1 in pituitary cells. Targeted and transient overexpression of PER1 led to regulation of additional circadian rhythm genes hours later, suggesting that hypersensitive expression of PER1 impacts circadian gene expression. These findings show that hypersensitive GR binding occurs throughout the genome, drives targeted gene expression, and may be important to endocrine mediation of peripheral circadian rhythms. PMID:22801371

Reddy, Timothy E.; Gertz, Jason; Crawford, Gregory E.; Garabedian, Michael J.

2012-01-01

25

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. PMID:23644362

Novák, Jan; Pavl?, Jaroslav; Novák, Ond?ej; Nožková-Hlavá?ková, Vladimíra; Špundová, Martina; Hlavinka, Jan; Koukalová, Šárka; Skalák, Jan; ?erný, Martin; Brzobohatý, B?etislav

2013-01-01

26

Primary Generalized Glucocorticoid Resistance and Hypersensitivity: The End-Organ Involvement in the Stress Response  

NSDL National Science Digital Library

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

Evangelia Charmandari (University of Athens Medical School; REV)

2012-10-02

27

Harpin, Elicitor of the Hypersensitive Response Produced by the Plant Pathogen Erwinia amylovora  

Microsoft Academic Search

A proteinaceous elicitor of the plant defense reaction known as the hypersensitive response was isolated from Erwinia amylovora, the bacterium that causes fire blight of pear, apple, and other rosaceous plants. The elicitor, named harpin, is an acidic, heat-stable, cell-envelope-associated protein with an apparent molecular weight of 44 kilodaltons. Harpin caused tobacco leaf lamina to collapse and caused an increase

Zhong-Min Wei; Ron J. Laby; Cathy H. Zumoff; David W. Bauer; Sheng Yang He; Alan Collmer; Steven V. Beer

1992-01-01

28

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

29

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

PubMed

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

Wilson, A D

2014-11-01

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. PMID:24959894

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

2014-01-01

31

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

32

Indole-3-acetic acid reverses the harpin-induced hypersensitive response and alters the expression of hypersensitive-response-related genes in tobacco.  

PubMed

Harpin proteins stimulate hypersensitive response (HR) in plants. However, the mechanism by which HR is regulated is not clear. The role of the auxin, indole-3-acetic acid (IAA), in the control of harpin-stimulated HR was investigated. IAA was used to inhibit HR that was stimulated by purified fusion harpin(Xoo) protein in tobacco. Semi-quantitative PCR and qRT-PCR were employed to detect the expression of HR related genes. IAA at 100 ?M reversed harpin-induced HR which was inhibited by 500 ?M 2,3,5-triiodobenzoic acid (TIBA). Semi-quantitative PCR and qRT-PCR showed the combined application of 100 ?M IAA and harpin protein from Xanthomonas oryzae enhanced the expression of HR marker gene, hsr203J, but weakened the expression of the disease-defense gene, chia5. TIBA also decreased the expression of hsr203J but increased the expression of chia5. Thus, the auxin can reverse harpin(Xoo)-induced HR. PMID:24557069

Song, Jie; Gong, Xiao-chong; Miao, Wei-guo; Zheng, Fu-cong; Song, Cong-feng; Wang, Ming-hua

2014-05-01

33

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

34

Hypersensitivity pneumonitis  

MedlinePLUS

... Mushroom picker's disease; Humidifier or air-conditioner lung; Bird breeder's or bird fancier's lung ... to hypersensitivity pneumonitis. Examples of hypersensitivity pneumonitis include: Bird fancier's lung: This is the most common type ...

35

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. PMID:11161014

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

2001-01-01

36

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. PMID:23719893

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

37

Diminished contact hypersensitivity response in IL-4 deficient mice at a late phase of the elicitation reaction.  

PubMed

Contact hypersensitivity (CHS) is thought to depend on the activation of T cells of Th1 and/or Tc1 type. The role of Th2/Tc2 cells in the contact allergic reaction is not clear. The aim of this study was to analyse the functional contribution of Th2/Tc2 cells in CHS using the interleukin-4 (IL-4) deficient mouse model. Interleukin-4 deficient (IL4T) and control (wt) mice were sensitized by epicutaneous application of 2,4-dinitrofluorobenzene. The ear swelling response measured 24 h after challenge was similar in IL4T and control mice. However, from 48 h onwards, ear swelling values were significantly reduced in IL4T mice. The stimulatory capacity of freshly isolated as well as 3-day cultured epidermal cells, prepared from IL4T and wt mice, for allogeneic T cells in a primary and secondary response, was comparable. The reduced number of T cell receptor (TCR) gamma delta+ cells observed in epidermal sheets prepared from IL4T mice was not responsible for the decreased ear swelling response in IL4T mice, because the use of TCR delta deficient mice lacking TCR gamma delta+ cells revealed a down-regulatory role of this cell population in the CHS response. The data indicate that the effector stage of the CHS response can be subdivided into two phases. The first phase proceeds efficiently in IL-4 deficient mice indicating the dependence on Th1/Tc1 cells, while the second phase does not develop in mice lacking IL-4, suggesting the possibility that Th2/Tc2 cells intensify the reaction. PMID:9122622

Weigmann, B; Schwing, J; Huber, H; Ross, R; Mossmann, H; Knop, J; Reske-Kunz, A B

1997-03-01

38

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

39

Two distinct types of cellular mechanisms in the development of delayed hypersensitivity in mice: requirement of either mast cells or macrophages for elicitation of the response.  

PubMed

Using mast cell-deficient mutant W/Wv mice and their normal counterpart we re-evaluated the significance of participation of mast cells in allergic inflammatory response. W/Wv mice developed immediate hypersensitivity (IH) footpad reaction (FPR) to a somewhat lesser degree than the normal mice, suggesting that the mast cell might amplify the response. To exert classical tuberculin (tbc) delayed-type hypersensitivity (DTH) mast cells were not an essential cellular component. Vasoactive amines were essential to develop the response, but it did not necessarily originate from mast cells. When mice were immunized with methylated human serum albumin (MHSA) emulsified in incomplete Freund's adjuvant (IFA), mast cells were required to elicit DTH FPR. This was confirmed by the lack of the response in W/Wv mice, and the restoration of FPR by local transplantation of mature mast cells into mutant mice. This mast cell-dependent (MD) DTH was different from tbc DTH as follows: mast cell dependency, macrophage dependency as revealed by ferritin sensitivity, kinetics of sensitization, effect of host's age and histopathology. Thus we concluded that there are two types of DTH in mice; one is macrophage-dependent tbc and the other is mast cell-dependent DTH. The correspondence of the DTH to the Jones-Mote (JM) DTH is discussed, although the dominance of mast cells in MD DTH lesion was not observed. PMID:8478030

Torii, I; Morikawa, S; Harada, T; Kitamura, Y

1993-03-01

40

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

PubMed

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

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

2007-01-01

41

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

42

Variation in Plant Defense against Invasive Herbivores: Evidence for a Hypersensitive Response in Eastern Hemlocks ( Tsuga canadensis )  

Microsoft Academic Search

Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces\\u000a a defensive hypersensitive response, a defense mechanism consisting of elevated H2O2 levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae (‘HWA’) and elongate hemlock scale Fiorinia externa (‘EHS’) feed on eastern hemlocks;

Laura Radville; Arielle Chaves; Evan L. Preisser

2011-01-01

43

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

PubMed Central

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

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

2012-01-01

44

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

45

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

PubMed Central

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

2014-01-01

46

?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. PMID:24133248

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

47

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. PMID:22624059

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

2012-01-01

48

Ir gene controlled carrier effects in the induction and elicitation of hapten-specific delayed-type hypersensitivity responses.  

PubMed

The genetic requirements of carrier recognition were examined in the priming and elicitation of hapten specific, T-cell mediated, delayed-type hypersensitivity (DTH) responses. It was shown that nitrophenyl acetyl-poly-(L-glu56-L-lys35-L-phe9) (NP-GLO) could prime for NP responses only in strains of mice which are Ir gene responders to GLO. In contrast to this requirement, NO-GLO could elicit an NP-specific response in NP-bovine gamma globulin primed mice, even in GLO nonresponder strains. Furthermore, the nonimmunogenic molecule, NP-GL, could elicit an NP-specific DTH response in animals primed with NP on an immunogenic carrier. PMID:115960

Weinberger, J Z; Benacerraf, B; Dorf, M E

1979-11-01

49

DELAYED HYPERSENSITIVITY  

PubMed Central

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed. PMID:13385403

Uhr, Jonathan W.; Salvin, S. B.; Pappenheimer, A. M.

1957-01-01

50

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

51

Carmine hypersensitivity masquerading as azithromycin hypersensitivity.  

PubMed

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

Greenhawt, Matthew; McMorris, Marc; Baldwin, James

2009-01-01

52

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

PubMed Central

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

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

2013-01-01

53

A connected set of genes associated with programmed cell death implicated in controlling the hypersensitive response in maize caused by a maize auto-active resistance gene  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

54

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

55

Gender Differences in Delayed-Type Hypersensitivity Response: Effects of Stress and Coping in First Year Law Students  

PubMed Central

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.

2009-01-01

56

Immune response to enzyme replacement therapy: clinical signs of hypersensitivity reactions and altered enzyme distribution in a high titre rat model  

Microsoft Academic Search

Immune responses to enzyme replacement therapy (ERT) have been reported and can result in a hypersensitivity\\/anaphylactic reaction during or immediately after enzyme infusion. We have investigated the infusion of the lysosomal enzyme N-acetylgalactosamine 4-sulphatase (4-sulphatase) into immunized, high titre rats as a model of immune response to ERT. To simulate ERT, high and low titre rats were infused with different

Doug A. Brooks; John J. Hopwood; Barbara M. King

1998-01-01

57

Copper hypersensitivity.  

PubMed

The world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions. PMID:25098945

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

2014-10-01

58

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. PMID:23720369

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

2013-01-01

59

In vitro elicitation of intestinal immune responses in teleost fish: evidence for a type IV hypersensitivity reaction in rainbow trout.  

PubMed

In fish the gut immune system has been the subject of few investigations until now. Here, we provide novel morphological and immunological data on the gut isolated from rainbow trout Salmo gairdneri. The pyloric (P) and terminal (T) segments of trout gut, when morphologically examined, evidenced lymphocytes and macrophages (MØ) loosely dispersed in the intestinal mucosa and in the lamina propria in the absence of typical Peyer's patches-like structures. Furthermore, incubation of P and T sections with Candida albicans (Ca) and functional analysis of supernatants generated some interesting results. In fact, active supernatants, when compared with controls, exhibited cytokine-like activities attributable to the presence of interferon (IFN)-gamma and migration inhibiting factor (MIF), respectively. In particular, IFN-gamma-like activity gave rise to an enhancement of Ca phagocytosis by MØ, whereas MIF inhibited MØ migration in agarose. Taken together, these in vitro data suggest that the gut-associated lymphoreticular tissue in fish possesses the appropriate armamentarium to mount a type IV hypersensitivity response when challenged by microbial antigens. PMID:17464768

Jirillo, F; Passantino, G; Massaro, M A; Cianciotta, A; Crasto, A; Perillo, A; Passantino, L; Jirillo, E

2007-01-01

60

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. PMID:23222653

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

61

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

62

Bean dwarf mosaic virus BV1 protein is a determinant of the hypersensitive response and avirulence in Phaseolus vulgaris.  

PubMed

The capacities of the begomoviruses Bean dwarf mosaic virus (BDMV) and Bean golden yellow mosaic virus (BGYMV) to differeBean dwarf mosaic viru certain common bean (Phaseolus vulgaris) cultivars were used to identify viral determinants of the hypersensitive response (HR) and avirulence (avr) in BDMV. A series of hybrid DNA-B components, containing BDMV and BGYMV sequences, was constructed and coinoculated with BDMV DNA-A (BDMV-A) or BDMVA-green florescent protein into seedlings of cv. Topcrop (susceptible to BDMV and BGYMV) and the BDMV-resistant cvs. Othello and Black Turtle Soup T-39 (BTS). The BDMV avr determinant, in bean hypocotyl tissue, was mapped to the BDMV BV1 open reading frame and, most likely, to the BV1 protein. The BV1 also was identified as the determinant of the HR in Othello. However, the HR was not required for resistance in Othello nor was it associated with BDMV resistance in BTS. BDMV BV1, a nuclear shuttle protein that mediates viral DNA export from the nucleus, represents a new class of viral avr determinant. These results are discussed in terms of the relationship between the HR and resistance. PMID:11059485

Garrido-Ramirez, E R; Sudarshana, M R; Lucas, W J; Gilbertson, R L

2000-11-01

63

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

PubMed

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

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

2004-03-01

64

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

65

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

PubMed Central

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 H2O2 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

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

2010-01-01

66

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

PubMed Central

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

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

2014-01-01

67

Environmental chemicals, respiratory hypersensitization and international chemical safety  

Microsoft Academic Search

Allergic hypersensitization to a variety of chemicals, natural and synthetic, is a worldwide health problem. Respiratory tract hypersensitization is responsible for significant morbidity and, in some cases, mortality. An important step in managing and controlling health risks, such as allergic hypersensitization, is to identify the chemical hazard, define dose-effect and dose-response relationships, evaluate exposure, and characterize risk. In practical terms,

Edward Smith

1996-01-01

68

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

PubMed

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

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

2009-05-01

69

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

PubMed

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

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

2014-01-01

70

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

PubMed

The hypersensitive response (HR) is a form of cell death associated with plant resistance to pathogen infection. Harpin(pss), 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 harpin(pss)-mediated HR. In this report, we isolated and characterized a cDNA clone encoded that amphipathic protein from sweet pepper. This protein is designated as PFLP (plant ferredoxin-like protein) by virtue of its high homology with plant ferredoxin protein containing an N-terminal signal peptide responsible for chloroplast targeting and a putative 2Fe-2S domain responsible for redox activity. Recombinant PFLP obtained from Escherichia coli was able to significantly increase active oxygen species (AOS) generation when mixed with harpin(pss) in tobacco suspension cells. It also showed enhanced HR when co-infiltrated with harpin(pss) in tobacco leaves. We used a transgenic tobacco suspension cells system that constitutively expresses the Pflp gene driven by the CaMV 35S promoter to study the function of PFLP in enhancing harpin(pss)-mediated hypersensitive cell death in vivo. In response to harpin(pss), suspension cells derived from Pflp transgenic tobacco showed a significant increase both in the generation of AOS and in cell death as compared to the wild type. AOS inhibitors diphenylene iodonium chloride (DPI) and lanthanum chlorate (LaCl3) were used to study the involvement of AOS in harpin(pss)-induced cell death. Our results demonstrate enhanced generation of AOS is necessary to cause enhanced hypersensitive cell death in Pflp transgenic tobacco cells and it is plasma membrane-bound NADPH-oxidase-dependent. Sub-cellular localization studies showed that PFLP is present in the cytoplasm and chloroplast of Pflp transgenic tobacco cells, but only in the chloroplast, not in the cytoplasm, of wild-type tobacco cells. It is possible that PFLP can change the redox state of the cell upon harpin(pss) inoculation to increase AOS generation and hypersensitive cell death. Overall, this study will provide a new insight in the functional properties of ferredoxin in hypersensitive cell death. PMID:12777051

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

2003-04-01

71

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

PubMed

Plant disease resistance (R) proteins that confer resistance to viruses recognize viral gene products with diverse functions, including viral suppressors of RNA silencing (VSRs). The P0 protein from poleroviruses is a VSR that targets the ARGONAUTE1 (AGO1) protein for degradation, thereby disrupting RNA silencing and antiviral defences. Here, we report resistance against poleroviruses in Nicotiana glutinosa directed against Turnip yellows virus (TuYV) and Potato leafroll virus (PLRV). The P0 proteins from TuYV (P0(T) (u) ), PLRV (P0(PL) ) and Cucurbit aphid-borne yellows virus (P0(CA) ) were found to elicit a hypersensitive response (HR) in N.?glutinosa accession TW59, whereas other accessions recognized P0(PL) only. Genetic analysis showed that recognition of P0(T) (u) by a resistance gene designated RPO1 (Resistance to POleroviruses 1) is inherited as a dominant allele. Expression of P0 from a Potato virus X (PVX) expression vector transferred recognition to the recombinant virus on plants expressing RPO1, supporting P0 as the unique Polerovirus factor eliciting resistance. The induction of HR required a functional P0 protein, as P0(T) (u) mutants with substitutions in the F-box motif that abolished VSR activity were unable to elicit HR. We surmised that the broad P0 recognition seen in TW59 and the requirement for the F-box protein motif could indicate detection of P0-induced AGO1 degradation and disruption of RNA silencing; however, other viral silencing suppressors, including the PVX P25 that also causes AGO1 degradation, failed to elicit HR in N.?glutinosa. Investigation of P0 elicitation of RPO1 could provide insight into P0 activities within the cell that trigger resistance. PMID:25187258

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

2014-09-01

72

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. PMID:21558543

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

2011-01-01

73

Delayed drug hypersensitivity reactions - new concepts.  

PubMed

Immune reactions to small molecular compounds such as drugs can cause a variety of diseases mainly involving skin, but also liver, kidney, lungs and other organs. In addition to the well-known immediate, IgE-mediated reactions to drugs, many drug-induced hypersensitivity reactions appear delayed. Recent data have shown that in these delayed reactions drug-specific CD4(+) and CD8(+) T cells recognize drugs through their T cell receptors (TCR) in an MHC-dependent way. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthems revealed that distinct T cell functions lead to different clinical phenotypes. Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T cell reactions, which by releasing certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4(+) or CD8(+) T cells (type IVc) seem to participate in all type IV reactions. Drugs are not only immunogenic because of their chemical reactivity, but also because they may bind in a labile way to available TCRs and possibly MHC-molecules. This seems to be sufficient to stimulate certain, probably preactivated T cells. The drug seems to bind first to the fitting TCR, which already exerts some activation. For full activation, an additional interaction of the TCR with the MHC molecules is needed. The drug binding to the receptor structures is reminiscent of a pharmacological interaction between a drug and its (immune) receptor and was thus termed the p-i concept. In some patients with drug hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. The T cell reaction to the drug might thus not be due to a classical, primary response, but is due to peptide-specific T cells which happen to be stimulated by a drug. This new concept has major implications for understanding clinical and immunological features of drug hypersensitivity and a model to explain the frequent skin symptoms in drug hypersensitivity is proposed. PMID:17581192

Posadas, S J; Pichler, W J

2007-07-01

74

Immune pathomechanism of drug hypersensitivity reactions.  

PubMed

Drug hypersensitivity research has progressed enormously in recent years, and a greater understanding of mechanisms has contributed to improved drug safety. Progress has been made in genetics, enabling personalized medicine for certain drugs, and in understanding drug interactions with the immune system. In a recent meeting in Rome, the clinical, chemical, pharmacologic, immunologic, and genetic aspects of drug hypersensitivity were discussed, and certain aspects are briefly summarized here. Small chemicals, including drugs, can induce immune reactions by binding as a hapten to a carrier protein. Park (Liverpool, England) demonstrated (1) that drug haptens bind to protein in patients in a highly restricted manner and (2) that irreversibly modified carrier proteins are able to stimulate CD4(+) and CD8(+) T cells from hypersensitive patients. Drug haptens might also stimulate cells of the innate immune system, in particular dendritic cells, and thus give rise to a complex and complete immune reaction. Many drugs do not have hapten-like characteristics but might gain them on metabolism (so-called prohaptens). The group of Naisbitt found that the stimulation of dendritic cells and T cells can occur as a consequence of the transformation of a prohapten to a hapten in antigen-presenting cells and as such explain the immune-stimulatory capacity of prohaptens. The striking association between HLA-B alleles and the development of certain drug reactions was discussed in detail. Mallal (Perth, Australia) elegantly described a highly restricted HLA-B?5701-specific T-cell response in abacavir-hypersensitive patients and healthy volunteers expressing HLA-B?5701 but not closely related alleles. Expression of HLA-B?1502 is a marker known to be necessary but not sufficient to predict carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Han Chinese. The group of Chen and Hong (Taiwan) described the possible "missing link" because they showed that the presence of certain T-cell receptor (TCR) clonotypes was necessary to elicit T-cell responses to carbamazepine. The role of TCRs in drug binding was also emphasized by Pichler (Bern, Switzerland). Following up on their "pharmacological interactions of drugs with immune receptors" concept (p-i concept), namely that drugs can bind directly to TCRs, MHC molecules, or both and thereby stimulate T cells, they looked for drug-binding sites for the drug sulfamethoxazole in drug-specific TCRs: modeling revealed up to 7 binding sites on the CDR3 and CDR2 regions of TCR V? and V?. Among many other presentations, the important role of regulatory T cells in drug hypersensitivity was addressed. PMID:21354503

Pichler, Werner J; Naisbitt, Dean J; Park, B Kevin

2011-03-01

75

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

PubMed

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

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

2012-01-01

76

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. PMID:23029338

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

2012-01-01

77

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

PubMed

Plant NBS-LRR genes are abundant and have been increasingly cloned from plant genomes. In this study, a method based on agroinfiltration and virus inoculation was developed for the simple and inexpensive screening of candidate R genes that confer a hypersensitive response to plant viruses. The well-characterized resistance genes Rx and N, which confer resistance to Potato virus X (PVX) and tobamovirus, respectively, were used to optimize a transient expression assay for detection of hypersensitive response in Nicotiana benthamiana. Infectious sap of PVX and Tobacco mosaic virus were used to induce hypersensitive response in Rx- and N-infiltrated leaves, respectively. The transient expression of the N gene induced local hypersensitive response upon infection of another tobamovirus, Pepper mild mottle virus, through both sap and transcript inoculation. When this method was used to screen 99 candidate R genes from pepper, an R gene that confers hypersensitive response to the potyvirus Pepper mottle virus was identified. The method will be useful for the identification of plant R genes that confer resistance to viruses. PMID:24552951

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

2014-06-01

78

Constitutive expression of hrap gene in transgenic tobacco plant enhances resistance against virulent bacterial pathogens by induction of a hypersensitive response.  

PubMed

Hypersensitive response-assisting protein (HRAP) has been previously reported as an amphipathic plant protein isolated from sweet pepper that intensifies the harpin(Pss)-mediated hypersensitive response (HR). The hrap gene has no appreciable similarity to any other known sequences, and its activity can be rapidly induced by incompatible pathogen infection. To assess the function of the hrap gene in plant disease resistance, the CaMV 35S promoter was used to express sweet pepper hrap in transgenic tobacco. Compared with wild-type tobacco, transgenic tobacco plants exhibit more sensitivity to harpin(Pss) and show resistance to virulent pathogens (Pseudomonas syringae pv. tabaci and Erwinia carotovora subsp. carotovora). This disease resistance of transgenic tobacco does not originate from a constitutive HR, because endogenous level of salicylic acid and hsr203J mRNA showed similarities in transgenic and wildtype tobacco under noninfected conditions. However, following a virulent pathogen infection in hrap transgenic tobacco, hsr203J was rapidly induced and a micro-HR necrosis was visualized by trypan blue staining in the infiltration area. Consequently, we suggest that the disease resistance of transgenic plants may result from the induction of a HR by a virulent pathogen infection. PMID:12182333

Ger, Mang-jye; Chen, Cheng-Hsien; Hwang, Shaw-Yhi; Huang, Hsiang-En; Podile, Appa Rao; Dayakar, Badri Venkata; Feng, Teng-yung

2002-08-01

79

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. PMID:22911741

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

2012-01-01

80

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

PubMed Central

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

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

1979-01-01

81

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

PubMed

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

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

1979-07-01

82

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. PMID:23277879

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

2013-01-01

83

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. PMID:19690018

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

2009-01-01

84

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

EPA Science Inventory

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

85

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

EPA Science Inventory

ABSTRACT for 2001 DMS213 TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHEAL (IT) EXPOSURES. E Boykin, M Ward, MJ Selgrade, and D Sailstad. NHEERL, ORD, US EPA, RTP, NC, USA. TMA causes respiratory hypersensitivity (RH) responses. W...

86

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. PMID:24699635

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

2014-01-01

87

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

PubMed

In the present work we have studied the accumulation of gentisic acid (2,5-dihydroxybenzoic acid, a metabolic derivative of salicylic acid, SA) in the plant-pathogen systems, Cucumis sativus and Gynura aurantiaca, infected with either prunus necrotic ringspot virus (PNRSV) or the exocortis viroid (CEVd), respectively. Both pathogens produced systemic infections and accumulated large amounts of the intermediary signal molecule gentisic acid as ascertained by electrospray ionization mass spectrometry (ESI-MS) coupled on line with high performance liquid chromatography (HPLC). The compound was found mostly in a conjugated (beta-glucoside) form. Gentisic acid has also been found to accumulate (although at lower levels) in cucumber inoculated with low doses of Pseudomonas syringae pv. tomato, producing a nonnecrotic reaction. In contrast, when cucumber was inoculated with high doses of this pathogen, a hypersensitive reaction occurred, but no gentisic-acid signal was induced. This is consistent with our results supporting the idea that gentisic-acid signaling may be restricted to nonnecrotizing reactions of the host plant (Bellés et al. in Mol Plant-Microbe Interact 12:227-235, 1999). In cucumber and Gynura plants, the activity of gentisic acid as inducing signal was different to that of SA, thus confirming the data found for tomato. Exogenously supplied gentisic acid was able to induce peroxidase activity in both Gynura and cucumber plants in a similar way as SA or pathogens. However, gentisic-acid treatments strongly induced polyphenol oxidase activity in cucumber, whereas pathogen infection or SA treatment resulted in a lower induction of this enzyme. Nevertheless, gentisic acid did not induce other defensive proteins which are induced by SA in these plants. This indicates that gentisic acid could act as an additional signal to SA for the activation of plant defenses in cucumber and Gynura plants. PMID:16331468

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

2006-02-01

88

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

PubMed

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

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

2015-04-01

89

[HLA-B*5701 and abacavir hypersensitivity reaction].  

PubMed

A potentially life-threatening hypersensitive reaction occurs in association with initiation of HIV nucleoside analogue abacavir therapy in 4 to 8% of patients. Preliminary studies appear to confirm the role of the immune system in abacavir hypersensitivity. The reaction is possibly the result of presentation of drug peptides onto HLA, that may induce a pathogenic T-cell response. Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele and prospective HLA-B*5701 genetic screening has now been instituted in clinical practice to reduce the risk of hypersensitivity reaction. PMID:19243901

Servonnet, A; Leclercq, E; Delacour, H; Ceppa, F

2010-12-01

90

Hypersensitivity Pneumonitis Caused by Trichoderma viride  

Microsoft Academic Search

Hypersensitivity pneumonitis (HP) can be induced by exposure to indoor molds contaminating humidifiers and heating or ventilation systems. A 54-year-old woman with dyspnea, cough, chest pain, and fever was seen in the emergency room. A chest radiograph revealed interstitial infiltrates and blood tests showed leukocytosis with neutrophilia and severe hypoxemia. A diagnosis of HP was made by a combination of

Alicia Enríquez-Matas; Santiago Quirce; Noelia Cubero; Joaquín Sastre; Rosario Melchor

2009-01-01

91

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

PubMed

Hypersensitive response (HR) cell death upon plant virus infection is an excellent plant strategy for inhibiting viral movement and obtaining systemic acquired resistance (SAR) against further infection. Various host factors are involved in these HR processes, either directly as viral resistance proteins or indirectly. We characterized a gene encoding the CaBtf3 [?-nascent polypeptide-associated complex (NAC) subunit] of NAC from the hot pepper plant. NAC contacts nascent polypeptides to prevent aggregation and degradation of newly synthesized proteins by controlling cotranslational protein folding. CaBtf3 protein fused to green fluorescent protein predominantly localized to the nucleus. Silencing phenotype of CaBtf3 upon the Tobacco mosaic virus (TMV)-P(0) inoculation exhibited reduced HR cell death and decreased expression of some HR-associated genes, but increased TMV coat protein levels compared with TRV2 control plants. Furthermore, silencing of NbBtf3, a highly homologous gene of CaBtf3, also led to the reduced Bax- and Pto-mediated cell death. The results indicate that CaBtf3 might be involved in HR cell death and could function as a transcription factor in the nucleus by transcriptional regulation of HR-related gene expression. PMID:22209846

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

2012-01-13

92

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

PubMed

The hypersensitive response (HR) of disease-resistant plant cells to fungal invasion is a rapid cell death that has some features in common with programmed cell death (apoptosis) in animals. We investigated the role of cytosolic free calcium ([Ca2+]i) in the HR of cowpea to the cowpea rust fungus. By using confocal laser scanning microscopy in conjunction with a calcium reporter dye, we found a slow, prolonged elevation of [Ca2+]i in epidermal cells of resistant but not susceptible plants as the fungus grew through the cell wall. [Ca2+]i levels declined to normal levels as the fungus entered and grew within the cell lumen. This elevation was related to the stage of fungal growth and not to the speed of initiation of subsequent cell death. Elevated [Ca2+]i levels also represent the first sign of the HR detectable in this cowpea-cowpea rust fungus system. The increase in [Ca2+]i was prevented by calcium channnel inhibitors. This effect was consistent with pharmacological tests in which these inhibitors delayed the HR. The data suggest that elevation of [Ca2+]i is involved in signal transduction leading to the HR during rust fungal infection. PMID:9548984

Xu; Heath

1998-04-01

93

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

PubMed Central

The hypersensitive response (HR) of disease-resistant plant cells to fungal invasion is a rapid cell death that has some features in common with programmed cell death (apoptosis) in animals. We investigated the role of cytosolic free calcium ([Ca2+]i) in the HR of cowpea to the cowpea rust fungus. By using confocal laser scanning microscopy in conjunction with a calcium reporter dye, we found a slow, prolonged elevation of [Ca2+]i in epidermal cells of resistant but not susceptible plants as the fungus grew through the cell wall. [Ca2+]i levels declined to normal levels as the fungus entered and grew within the cell lumen. This elevation was related to the stage of fungal growth and not to the speed of initiation of subsequent cell death. Elevated [Ca2+]i levels also represent the first sign of the HR detectable in this cowpea-cowpea rust fungus system. The increase in [Ca2+]i was prevented by calcium channnel inhibitors. This effect was consistent with pharmacological tests in which these inhibitors delayed the HR. The data suggest that elevation of [Ca2+]i is involved in signal transduction leading to the HR during rust fungal infection. PMID:9548984

Xu, H; Heath, MC

1998-01-01

94

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

95

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

PubMed Central

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

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

2014-01-01

96

Hypersensitivity pneumonitis from ordinary residential exposures.  

PubMed Central

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

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

2001-01-01

97

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

PubMed Central

Introduction Delayed-type hypersensitivity (DTH) testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)-suppressive HAART in the U.S. Military HIV Natural History Study. Methods Treatment-naïve subjects with VL <400 copies/mL after ?24 months on HAART were included (n=302). DTH testing consisted of ?3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0–1) or non-anergic (?2). Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation. Results Non-anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/?L, interquartile range (IQR) 315–517 vs. 373 cells/?L, IQR 228–487; p=0.104) and VL (4.3 log10 copies/mL, IQR 3.4–4.9 vs. 4.4 log10 copies/mL, IQR 3.6–5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/?L, IQR 115–358) and anergic groups (246 cells/?L, IQR 136–358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283). Conclusions DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre-HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL-suppressive HAART. PMID:24499779

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

2014-01-01

98

Pharmacologic manipulation of a four day murine delayed type hypersensitivity model  

Microsoft Academic Search

A murine delayed-type hypersensitivity (DTH) model was developed as a tool for drug discovery. Time course studies indicated that hind paw swelling was maximal at four days post-sensitization with picryl chloride. A pharmacological survey involving daily administration of drugs revealed that as a class, the glucocorticoids (e.g. dexamethasone and corticosterone) were the most potent inhibitors of the DTH response. The

Roger E. Roudebush; Henry U. Bryant

1993-01-01

99

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

100

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

101

Pharmacogenetics of drug hypersensitivity.  

PubMed

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

Phillips, Elizabeth J; Mallal, Simon A

2010-07-01

102

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

PubMed Central

Background Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. Methods Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (?), a truncated fragment containing the C-terminal domain (?-T) and peptides of ?-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Results Both ? and ?-T reacted with the different CMP-specific antibodies. ?-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the ?-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Conclusions Gly m 5 is a cross-reactive soy allergen and the ?-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide. PMID:24416141

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

2014-01-01

103

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

PubMed Central

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

Mihalko, William M.; Grupp, Thomas M.; Manning, Blaine T.; Dennis, Douglas A.; Goodman, Stuart B.; Saleh, Khaled J.

2015-01-01

104

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. PMID:24599039

Awaya, Akira; Nishimura, Chiaki

2014-01-01

105

Hypersensitivity to mercuric fluorescein compounds.  

PubMed

The mercurial compounds are known to be a common cause of allergic contact dermatitis. Immediate hypersensitivity is rarely induced by mercurial organic derivatives. However, none of the published cases showed both immediate and delayed hypersensitivity as was the case of one of our two patients. A boy and a woman experienced urticaria and anaphylaxis, respectively after topical application of Merchromine (Merbromine). We were able to demonstrate immediate hypersensitivity in both patients to mercuric fluorescein compounds by skin test and histamine liberation. In addition, the child but not the woman, showed delayed hypersensitivity to mercurial compounds. PMID:2479247

Barranco Sanz, P; Martín Muñoz, F; López Serrano, C; Martín Esteban, M; Ojeda Casas, J A

1989-01-01

106

Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.  

PubMed

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

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

1995-03-01

107

Interleukin-1 receptor antagonist suppresses contact hypersensitivity.  

PubMed

Interleukin-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of interleukin-1 (IL-1), blocks IL-1 binding to its receptors but has no agonistic activity. IL-1 is thought to play an important role in contact hypersensitivity (CHS), although the effects of exogenously administered IL-1 in CHS have been somewhat controversial. To clarify the role of IL-1 in CHS, we studied the effect of IL-1 receptor blockade using exogenous IL-1ra and evaluated these effects on CHS. We examined the in vivo effects of local administration of recombinant human IL-1ra in the murine CHS model. Local injection of IL-1ra to sensitized BALB/c mice just before challenge with dinitrofluorobenzene resulted in a significant reduction in the intensity of CHS responses, assessed by ear swelling. A dose-response study revealed that maximal inhibition of ear swelling (36% to 43%) was observed after intradermal injection of IL-1ra at doses of 10 to 100 micrograms/ear. This reduction in ear swelling in IL-1ra-injected ears consisted of less inflammatory cell infiltration and decreased edema in the dermis compared with controls. Suppression of CHS was observed when IL-1ra was applied in the 24-h interval preceding challenge with dinitrofluorobenzene, whereas no suppressive effect was observed when IL-1ra was applied 48 h before or after the challenge. Local administration of IL-1ra to naive mice 5 h before sensitization also suppressed CHS responses. However, IL-1ra injection did not suppress phenol-induced inflammation. These results suggest that IL-1ra is an effective inhibitor of both the sensitization and elicitation phases of CHS expression in mice, thus emphasizing the role of IL-1 as an immunologic potentiator of responses associated with CHS. PMID:7665908

Kondo, S; Pastore, S; Fujisawa, H; Shivji, G M; McKenzie, R C; Dinarello, C A; Sauder, D N

1995-09-01

108

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

PubMed

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. PMID:12119395

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

2002-07-23

109

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.  

PubMed

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. hrpW encodes a 42. 9-kDa protein with domains resembling harpins and pectate lyases (Pels), respectively. HrpW has key properties of harpins. It is heat stable and glycine rich, lacks cysteine, is secreted by the Hrp system, and is able to elicit the HR when infiltrated into tobacco leaf tissue. The harpin domain (amino acids 1 to 186) has six glycine-rich repeats of a repeated sequence found in HrpZ, and a purified HrpW harpin domain fragment possessed HR elicitor activity. In contrast, the HrpW Pel domain (amino acids 187 to 425) is similar to Pels from Nectria haematococca, Erwinia carotovora, Erwinia chrysanthemi, and Bacillus subtilis, and a purified Pel domain fragment did not elicit the HR. Neither this fragment nor the full-length HrpW showed Pel activity in A230 assays under a variety of reaction conditions, but the Pel fragment bound to calcium pectate, a major constituent of the plant cell wall. The DNA sequence of the P. syringae pv. syringae B728a hrpW was also determined. The Pel domains of the two predicted HrpW proteins were 85% identical, whereas the harpin domains were only 53% identical. Sequences hybridizing at high stringency with the P. syringae pv. tomato hrpW were found in other P. syringae pathovars, Pseudomonas viridiflava, Ralstonia (Pseudomonas) solanacearum, and Xanthomonas campestris. DeltahrpZ::nptII or hrpW::OmegaSpr P. syringae pv. tomato mutants were little reduced in HR elicitation activity in tobacco, whereas this activity was significantly reduced in a hrpZ hrpW double mutant. These features of hrpW and its product suggest that P. syringae produces multiple harpins and that the target of these proteins is in the plant cell wall. PMID:9748456

Charkowski, A O; Alfano, J R; Preston, G; Yuan, J; He, S Y; Collmer, A

1998-10-01

110

Sequential Analysis of the Numerical Stroop Effect Reveals Response Suppression  

PubMed Central

Automatic processing of irrelevant stimulus dimensions has been demonstrated in a variety of tasks. Previous studies have shown that conflict between relevant and irrelevant dimensions can be reduced when a feature of the irrelevant dimension is repeated. The specific level at which the automatic process is suppressed (e.g., perceptual repetition, response repetition), however, is less understood. In the current experiment we used the numerical Stroop paradigm, in which the processing of irrelevant numerical values of 2 digits interferes with the processing of their physical size, to pinpoint the precise level of the suppression. Using a sequential analysis, we dissociated perceptual repetition from response repetition of the relevant and irrelevant dimension. Our analyses of reaction times, error rates, and diffusion modeling revealed that the congruity effect is significantly reduced or even absent when the response sequence of the irrelevant dimension, rather than the numerical value or the physical size, is repeated. These results suggest that automatic activation of the irrelevant dimension is suppressed at the response level. The current results shed light on the level of interaction between numerical magnitude and physical size as well as the effect of variability of responses and stimuli on automatic processing. PMID:21500951

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

2011-01-01

111

Hypersensitivity pneumonitis due to an ultrasonic humidifier.  

PubMed

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

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

1998-02-01

112

Expectancies and hypnotic responsiveness: an experimental-design flaw revealed.  

PubMed

Recent research suggests that expectancies about being hypnotized have a determinant role in the hypnotic experience. The authors analyzed the relationship between expectancies and the phenomenology of hypnosis using the Phenomenology of Consciousness Inventory and Hypnotic Assessment Procedure. Participants (115) were assigned either to the imagination (hypnosis labeled as imagination) or the hypnosis conditions. Results revealed only a minor influence of expectancies and none on the label "hypnosis" across all variables. These findings indicate that the methodology commonly used to study the influence of expectancies on hypnotic responsiveness and phenomenology might represent a flaw in favor of a causal relationship between expectancies and hypnotic experience. PMID:25719518

Tomé Pires, Catarina; Ludeña, Maria Angeles; Lopes Pires, Carlos

2015-01-01

113

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. PMID:19772634

Suckow, Shelby K; Caudle, Robert M

2009-01-01

114

Food hypersensitivity by inhalation  

PubMed Central

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. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

Ramirez, Daniel A; Bahna, Sami L

2009-01-01

115

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

116

Effect of metabolic inhibitors on the formation of antibody to sheep erythrocytes, on development of delayed hypersensitivity, and on the immune response to infection with Mycobacterium tuberculosis in mice.  

PubMed Central

The effect of a number of metabolic inhibitors was determined on: (i) the production of cellular immunity to infection with Mycobacterium tuberculosis in mice by vaccination with mycobacterial ribonucleic acid (RNA), (Ii) the production of cellular immunity to infection with M. tuberculosis in mice with viable H37Ra cells, (iii) the induction of antibody formation to sheep erythrocytes, and (iv) the induction of delayed hypersensitivity in mice to purified protein derivative. The pattern of inhibition produced by metabolic inhibitors on cellular immunity to infection with M. tuberculosis produced by mycobacterial RNA was entirely different from the pattern of inhibition produced by the same metabolic inhibitors on antibody formation to sheep erythrocytes. The effect of the metabolic inhibitors on the induction of delayed hypersensitivity to purified protein derivative did not correlate with the pattern of inhibition produced by the same compounds on antibody formation or on the development of immunity produced by mycobacterial RNA. Cellular immunity to infection produced in mice by viable H37Ra cells was not reduced by any of the metabolic inhibitors except actinomycin D. The possible reasons for the lack of activity of the metabolic inhibitors on the immune response to viable H37Ra cells and the lack of correlation with the pattern of inhibition found in mice vaccinated with mycobacterial RNA is discussed. PMID:415003

Youmans, A S; Youmans, G P

1978-01-01

117

Metabolic phenotyping reveals a lipid mediator response to ionizing radiation.  

PubMed

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

Laiakis, Evagelia C; Strassburg, Katrin; Bogumil, Ralf; Lai, Steven; Vreeken, Rob J; Hankemeier, Thomas; Langridge, James; Plumb, Robert S; Fornace, Albert J; Astarita, Giuseppe

2014-09-01

118

Sulfite hypersensitivity. A critical review  

SciTech Connect

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

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

1987-01-01

119

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

PubMed

The Asian rice gall midge, Orseolia oryzae (Diptera: Cecidomyiidae), is the third most destructive insect pest of rice (Oryza sativa L.). Till date, 11 gall midge resistance gene loci have been characterized in different rice varieties. To elucidate molecular basis of incompatible (hypersensitive response plus [HR+] type) and compatible rice-gall midge interactions, two suppressive subtraction hybridization cDNA libraries were constructed. These were enriched for differentially expressed transcripts after gall midge infestation in two rice varieties (resistant Suraksha and susceptible TN1). In total, 2784 ESTs were generated and sequenced from the two libraries, of which 1536 were from the resistant Suraksha and 1248 were from the susceptible TN1. Majority (80%) of the ESTs was non-redundant sequences with known functions and was classified into three principal gene ontology (GO) categories and 12 groups. Upregulation of NBS-LRR, Cytochrome P450, heat shock proteins, phenylalanine ammonia lyase and OsPR10? genes from the Suraksha library, as revealed by real-time PCR, indicated that R gene mediated, salicylic acid related defense pathway is likely to be involved in gall midge resistance. Present study suggested that resistance in Suraksha against gall midge is similar in nature to the resistance observed in plants against pathogens. However, in TN1, genes related to primary metabolism and redox were induced abundantly. Results suggested that genes encoding translationally controlled tumor protein and NAC domain proteins are likely to be involved in the gall midge susceptibility. PMID:23257077

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

2013-02-01

120

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. PMID:24686111

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

2014-01-01

121

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

EPA Science Inventory

SOT 2001 DMS214 TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER MULTIPLE INTRATRACHEAL (IT) EXPOSURES. D Sailstad, E Boykin, M Ward, and MJ Selgrade. NHEERL, ORD, US EPA, RTP, NC, USA. TMA causes Th2 related respiratory hypersensitivity (RH) responses. W...

122

Measurements of Eosinophil Activation before and after Food Challenges in Adults with Food Hypersensitivity  

Microsoft Academic Search

Background: Objective assessment of inflammatory reactions in the gastrointestinal tract could be useful in the diagnosis of food hypersensitivity. The aim of the present study was to investigate the involvement of eosinophils and mast cells in the inflammatory response of patients with food hypersensitivity before and after food challenges. Methods: Eleven patients (4 with IgE-mediated allergy and 7 without) with

J. van Odijk; C. G. B. Peterson; S. Ahlstedt; U. Bengtsson; M. P. Borres; L. Hulthén; J. Magnusson; T. Hansson

2006-01-01

123

Hypersensitivity pneumonitis induced by Shiitake mushroom spores.  

PubMed

Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account. PMID:22329454

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

2012-08-01

124

Clinical and immunogenetic correlates of abacavir hypersensitivity.  

PubMed

A patch test (PT) may be useful in defining true abacavir hypersensitivity syndrome (AHS). Seven previously PT-positive patients remote from the original AHS were shown to have robust 24 h responses, supporting PT durability. HLA-B*5701 was present in all seven PT-positive versus one of 11 controls tolerating abacavir (P < 0.001). Five of seven PT (71%) versus one of 11 controls (9%) (P = 0.005) showed significant abacavir-specific CD8 proliferation, suggesting a direct role for HLA-B*5701-restricted CD8 cells in the pathophysiology of AHS. PMID:15905681

Phillips, Elizabeth J; Wong, Gavin A; Kaul, Rupert; Shahabi, Kamnoosh; Nolan, David A; Knowles, Sandra R; Martin, Annalise M; Mallal, Simon A; Shear, Neil H

2005-06-10

125

Delayed dermatologic hypersensitivity reaction secondary to ipilimumab.  

PubMed

The treatment of melanoma has long favored the use of immunologic agents. Ipilimumab is a monoclonal antibody used to enhance the immune response. This therapy is associated with a variety of adverse reactions including skin reactions. Although dermatologic toxicities associated with the use of ipilimumab are common, delayed hypersensitivity reactions related to the drug have yet to be identified. This report is believed to be the first case of a delayed, severe dermatologic drug-related reaction secondary to ipilimumab. This case highlights the potential for severe toxicity for long periods after administration of ipilimumab. PMID:25839442

Ludlow, Steven P; Kay, Noriko

2015-05-01

126

Recent progress of elucidating the mechanisms of drug hypersensitivity.  

PubMed

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. PMID:22872823

Hashizume, Hideo

2012-07-01

127

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. PMID:22872823

2012-01-01

128

Experimental model for dermal granulomatous hypersensitivity in Q fever.  

PubMed Central

Q fever has been associated with granulomatous changes in clinical biopsy material obtained from liver and bone marrow. Local reactions to skin testing have been described in previously sensitized humans, but histological studies of such reactions have not been reported. We note that delayed hypersensitivity reactions to whole-cell phase I Q fever vaccine in immunized guinea pigs have a time course of development of induration characteristic of granulomatous hypersensitivity. Histological examination of such skin reactions on day 9 after testing revealed epithelioid cell infiltration and the presence of large numbers of multinucleated giant cells. Prominent in the sections were fragments of disintegrating polymorphonuclear leukocytes having the appearance of leukocytoclasis. Electron microscopic studies confirmed the presence of epithelioid changes in cells of the mononuclear phagocyte series, as well as extensive collagen deposition. This animal system affords a readily reproducible model of dermal granulomatous hypersensitivity and an opportunity to analyze the immunological basis of this reaction. Images PMID:6822420

Ascher, M S; Berman, M A; Parker, D; Turk, J L

1983-01-01

129

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

PubMed Central

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

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

2013-01-01

130

House Dust Mite Hypersensitivity: Morning Dipping and Severity of Wheeze  

Microsoft Academic Search

Atopic subjects with asthma are frequently hypersensitive to house dust mite (Dermatophagiodes pyteronyssinus). Exaggerated nocturnal or early morning wheezing might occur in these patients, because of exposure to the allergen during the night, particularly in, view of the biphasic response that it produces in airway resistance. This might be of diagnostic value in determining the relevance of house dust mite

C. K. Connolly

1981-01-01

131

Anaphylactic hypersensitivity to mercurochrome (merbrominum).  

PubMed

By the use of intradermal tests, passive transfer (P.K.), and an in vitro histamine release test, we were able to demonstrate immediate hypersensitivity to Mercurochrome in a young man who had suffered anaphylactic shock after having contact with this antiseptic. Cross-reactions among different organic mercurial compounds were observed. PMID:2579604

Corrales Torres, J L; De Corres, F

1985-03-01

132

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

PubMed

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

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

2012-08-01

133

Perturbation-Response Scanning Reveals Ligand Entry-Exit Mechanisms of Ferric Binding Protein  

E-print Network

Perturbation-Response Scanning Reveals Ligand Entry-Exit Mechanisms of Ferric Binding Protein Canan in the presence of the ligand is proposed. We introduce a new tool that we term perturbation-response scanning of computational perturbation/response techniques based on linear response theory, by sequentially applying

Yanikoglu, Berrin

134

Pharmacometabolomics Reveals That Serotonin Is Implicated in Aspirin Response Variability  

PubMed Central

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

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

2014-01-01

135

What boxing-related stimuli reveal about response behaviour.  

PubMed

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

Ottoboni, Giovanni; Russo, Gabriele; Tessari, Alessia

2015-05-01

136

Milk hypersensitivity in young adults  

Microsoft Academic Search

Objective: To estimate the prevalence of milk hypersensitivity in Finnish adults.Design: Cross-sectional study.Subjects: Two hundred men and 206 women aged 27 y randomly recruited from the population register in southwestern Finland.Interventions: The subjects were interviewed about their dairy product consumption, abdominal discomfort after dairy product intake and lactose intolerance. From serum samples, serum reactivity to milk protein and milk-specific IgG1,

L Pelto; O Impivaara; S Salminen; T Poussa; S Seppänen; E-M Lilius

1999-01-01

137

Dapsone hypersensitivity syndrome causing disseminated intravascular coagulation  

PubMed Central

Dapsone hypersensitivity syndrome is an idiosyncratic reaction to this drug and can present with different clinical manifestations of varying severity. We describe a patient with disseminated intravascular coagulation (DIC) as an adverse reaction to dapsone. To the best of our knowledge, this is the first time it has been described in the literature. She presented with fever, rash and abdominal pain; she also had marked eosinophilia and features suggestive of oxidative haemolysis. Her course was complicated by DIC, splenic infarction and gastrointestinal bleeding. Extensive investigations did not reveal any alternative aetiology. She was initially treated with supportive measures and folic acid; steroids were administered later, following clinical deterioration. There was gradual improvement and the steroids were tapered. The patient recovered fully and remains well; her underlying chronic dermatologic condition is under satisfactory control with other medications. PMID:21829418

Figtree, Melanie Clare; Miyakis, Spiros; Tanaka, Kumiko; Martin, Linda; Konecny, Pam; Krilis, Steven

2009-01-01

138

[Hypersensitivity pneumonitis caused by Trichoderma viride].  

PubMed

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

Enríquez-Matas, Alicia; Quirce, Santiago; Cubero, Noelia; Sastre, Joaquín; Melchor, Rosario

2009-06-01

139

Genotyping for Severe Drug Hypersensitivity  

PubMed Central

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

Karlin, Eric; Phillips, Elizabeth

2014-01-01

140

Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast  

PubMed Central

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

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

2014-01-01

141

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. PMID:23536766

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

142

Alum-precipitated autoclaved Leishmania major plus bacille Calmette-Guérrin, a candidate vaccine for visceral leishmaniasis: safety, skin-delayed type hypersensitivity response and dose finding in healthy volunteers.  

PubMed

In a previous efficacy study, autoclaved Leishmania major (ALM) + bacille Calmette-Guérrin (BCG) vaccine was shown to be safe, but not superior to BCG alone, in protecting against visceral leishmaniasis. From June 1999 to June 2000, we studied the safety and immunogenicity of different doses of alum-precipitated ALM + BCG vaccine mixture administered intradermally to evaluate whether the addition of alum improved the immunogenicity of ALM. Twenty-four healthy adult volunteers were recruited and sequentially allocated to receive either 10 microg, 100 microg, 200 microg, or 400 microg of leishmanial protein in the alum-precipitated ALM + BCG vaccine mixture. Side effects were minimal for all doses and confined to the site of injection. All volunteers in the 10 microg, 100 microg, and 400 microg groups had a leishmanin skin test (LST) reaction of > or = 5 mm by day 42 and this response was maintained when tested after 90 d. Only 1 volunteer out of 5 in the 200 microg group had a LST reaction of > or = 5 mm by day 42 and the reasons for the different LST responses in this group are unclear. This is the first time that an alum adjuvant with ALM has been in used in humans and the vaccine mixture was safe and induced a strong delayed type hypersensitivity (DTH) reaction in the study volunteers. On the basis of this study we suggest that 100 1 microg of leishmanial protein in the vaccine mixture is a suitable dose for future efficacy studies, as it induced the strongest DTH reaction following vaccination. PMID:15228261

Kamil, A A; Khalil, E A G; Musa, A M; Modabber, F; Mukhtar, M M; Ibrahim, M E; Zijlstra, E E; Sacks, D; Smith, P G; Zicker, F; El-Hassan, A M

2003-01-01

143

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. PMID:22923415

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

2012-01-01

144

Development and validation of the Newcastle laryngeal hypersensitivity questionnaire  

PubMed Central

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

2014-01-01

145

Prasugrel-Induced Hypersensitivity Skin Reaction  

PubMed Central

We report a case of hypersensitivity skin reaction to prasugrel. The patient exhibited a generalized skin rash after treatment with prasugrel, which was resolved after discontinuation of prasugrel and substitution to clopidogrel. Clopidogrel was successfully administered as an alternative to prasugrel without any signs of further hypersensitivity. PMID:25278991

Park, Sang-Don; Baek, Yong-Soo; Lee, Seon-Young; Shin, Sung-Hee; Woo, Sung-Il; Kim, Dae-Hyeok; Kwan, Jun

2014-01-01

146

Hypersensitivity reactions to biological drugs.  

PubMed

Strictly speaking, biological drugs are defined as drugs obtained using biotechnology that act on the immune system. They encompass monoclonal antibodies, fusion proteins, and cytokines. Although they are restricted to specific diseases, they have been increasingly used in recent years, with the consequent reporting of adverse reactions, many of which occur during the postmarketing phase. Because of the characteristics of adverse reactions, a new classification has been proposed. Hypersensitivity reactions are beta-type reactions and include infusion reactions and injection site reactions. In some cases, an immune mechanism mediated by IgE, IgG, or T cells is involved. Clinical symptoms vary widely, from skin reactions to anaphylaxis. Diagnostic studies are based on skin tests and in vitro tests (specific IgE, basophil activation test). Most are not standardized and are conducted in small groups of patients, thus making it impossible to obtain sensitivity and specificity values. With some biological drugs, desensitization protocols have proven successful. In this review, we discuss hypersensitivity reactions to biological drugs and the diagnostic tests used to assess these reactions. PMID:25219103

Corominas, M; Gastaminza, G; Lobera, T

2014-01-01

147

Enhanced Immunological Memory Responses to Listeria monocytogenes in Rodents, as Measured by Delayed-Type Hypersensitivity (DTH), Adoptive Transfer of DTH, and Protective Immunity, following Lactobacillus casei Shirota Ingestion  

Microsoft Academic Search

We have investigated the effect of orally administered Lactobacillus casei Shirota (L. casei) on immunological memory, as measured by delayed-type hypersensitivity (DTH) and acquired cellular resistance (ACR). The studies were performed in animal models in which the animals were rendered immune by a primary Listeria monocytogenes infection. It was shown that orally administered viable L. casei, and not heat-killed L.

R. de Waard; E. Claassen; G. C. A. M. Bokken; B. Buiting; J. Garssen; J. G. Vos

2003-01-01

148

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

PubMed Central

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

Lee, Kwangho

2012-01-01

149

Oxazolone-induced contact hypersensitivity reduces lymphatic drainage but enhances the induction of adaptive immunity.  

PubMed

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. PMID:24911791

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

2014-01-01

150

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. PMID:24911791

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

2014-01-01

151

Towards an ontological theory of substance intolerance and hypersensitivity.  

PubMed

A proper ontological treatment of intolerance--including hypersensitivity--to various substances is critical to patient care and research. However, existing methods and standards for documenting these conditions have flaws that inhibit these goals, especially translational research that bridges the two activities. In response, I outline a realist approach to the ontology of substance intolerance, including hypersensitivity conditions. I defend a view of these conditions as a subtype of disease. Specifically, a substance intolerance is a disease whose pathological process(es) are realized upon exposure to a quantity of substance of a particular type, and this quantity would normally not cause the realization of the pathological process(es). To develop this theory, it was necessary to build pieces of a theory of pathological processes. Overall, however, the framework of the Ontology for General Medical Science (which uses Basic Formal Ontology as its uppermost level) was a more-than-adequate foundation on which to build the theory. PMID:20152933

Hogan, William R

2011-02-01

152

Testing for drug hypersensitivity syndromes.  

PubMed

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

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

2013-02-01

153

Testing for Drug Hypersensitivity Syndromes  

PubMed Central

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

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

2013-01-01

154

Contribution of hyperpolarization-activated channels to heat hypersensitivity and ongoing activity in the neuritis model.  

PubMed

Neuritis can cause pain hypersensitivities in the absence of axonal degeneration. Such hypersensitivities are reputed to be maintained by ongoing activity into the spinal cord, which, in the neuritis model, is mainly generated from intact C-fiber neurons. The hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels has been implicated in nerve injury-induced pain hypersensitivities. The present study has examined the role of these channels in the development of heat and mechanical hypersensitivities in the neuritis model. The systemic administration of the HCN-specific blocker ZD7288 produced a reversal of heat but not mechanical hypersensitivity within one hour post-administration. Recordings from C-fiber neurons were performed to determine whether ZD7288 acts by inhibiting ongoing activity. ZD7288 (0.5mM) caused a 44.1% decrease in the ongoing activity rate following its application to the neuritis site. Immunohistochemical examination of the HCN2 channel subtype within the L5 dorsal root ganglia revealed an increase in expression in neuronal cell bodies of all sizes post-neuritis. In conclusion, HCN channels contribute to the development of neuritis-induced heat hypersensitivity and ongoing activity. Drugs that target HCN channels may be beneficial in the treatment of neuropathic pain in patients with nerve inflammation. PMID:25290015

Richards, N; Dilley, A

2015-01-22

155

Influence of lead acetate on hypersensitivity. Experimental study.  

PubMed

Recent studies showed that lead acetate has an important immunotoxicity for the phagocytic activity as well as humoral and cell-mediated immunity. We studied the influence of lead acetate on immediate and delayed hypersensitivity. The lead acetate exerts an important action on hypersensitivity reactions whether on rat mast cells degranulation (immediate hypersensitivity) or on contact hypersensitivity. PMID:6470497

Laschi-Loquerie, A; Descotes, J; Tachon, P; Evreux, J C

1984-01-01

156

Where Asthma and Hypersensitivity Pneumonitis Meet and Differ  

PubMed Central

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

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

2009-01-01

157

Involvement of NO in contact hypersensitivity.  

PubMed

The NO synthases (NOS) generate NO from L-arginine. High concentrations of NO have been shown to be responsible for tissue injury and cell death, while low concentrations of NO induce vasodilatation and other signaling effects. We have investigated the involvement of NO in contact hypersensitivity (CHS) reactions. CHS induced by treatment of BALB/c mice with the contact allergen 2,4-dinitrofluorobenzene (DNFB) was significantly reduced by the NOS inhibitor N-methyl-L-arginine (L-NMA), but not by the stereoisomer D-NMA, as shown by reduced ear swelling responses and evaluation of ear tissue sections. The CHS response was also reduced by aminoguanidine, which is known to preferentially inhibit the inducible isoform of the enzyme (iNOS), suggesting that iNOS contributed to the inflammatory response. We therefore investigated whether iNOS was expressed by epidermal cells. Epidermal Langerhans cells produced low but significant amounts of iNOS mRNA at the single-cell level as indicated by RT-PCR. Likewise, keratinocytes expressed basic iNOS mRNA levels. Elicitation of a CHS response by DNFB in vivo resulted in enhanced iNOS mRNA expression in Langerhans cells and keratinocytes, with higher levels of expression in Langerhans cells. The enhanced mRNA expression in Langerhans cells correlated with iNOS protein production as shown by immunofluorescence staining of epidermal sheets performing double staining with anti-iNOS and anti-MHC class II antibodies. Our data suggest that epidermal cell-derived NO contributes to the ear swelling reaction in CHS. PMID:9488156

Ross, R; Gillitzer, C; Kleinz, R; Schwing, J; Kleinert, H; Förstermann, U; Reske-Kunz, A B

1998-01-01

158

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. PMID:22143734

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

2012-01-01

159

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

PubMed Central

Background: Dentine hypersensitivity is a transient condition that often resolves with the natural sclerotic obturation of dentinal tubules. A potent topically applied in-office desensitizing treatment is indicated as the choice of treatment when dentine hypersensitivity is localized to one or two teeth. Aim: The present study aimed to evaluate and compare the clinical efficiency of CPP-ACP F, sodium fluoride, propolis, and distilled water that was used as placebo in treating dentinal hypersensitivity. Materials and Methods: 120 patients aged 20–40 years reporting with dentinal hypersensitivity in relation to canine, premolar and molars with erosion, abrasion, and gingival recession were randomly assigned to four groups of 30 patients each. Response to air jet and tactile stimuli were measured using visual analogue scale initially on 1st, 7th, 15th, 28th, 60th, and final assessment was done on the 90th day. Statistical Analysis: A statistical analysis was done using Anova test (Fischer's test) and Tukey HSD test for multicomparison. Results: The teeth treated with the test group showed decrease in the mean hypersensitivity values compared to control group, over a period of three months. The results showed propolis to be most efficient in treating dentinal hypersensitivity and CPP- ACPF showed to be the least efficient. Conclusion: All test groups were effective in reducing dentinal hypersensitivity, although they differed in rapidity of action over the period of 3 months. Further studies can be done using advanced materials and techniques. Multiple therapeutic modalities have been developed to treat dentinal hypersensitivity including products that impede nerve conduction of pain stimulus, products that mechanically occlude dentinal tubules, and calcium containing products designed to create plugs in the tubules utilizing a demineralization mechanism. PMID:23112475

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

2012-01-01

160

Spatial Organization of Embryonic Stem Cell Responsiveness to Autocrine Gp130 Ligands Reveals an Autoregulatory Stem  

E-print Network

Spatial Organization of Embryonic Stem Cell Responsiveness to Autocrine Gp130 Ligands Reveals an Autoregulatory Stem Cell Niche RYAN E. DAVEY,a PETER W. ZANDSTRA a,b a Institute of Biomaterials and Biomedical, Ontario, Canada Key Words. Autocrine signaling · Embryonic stem cell · Niche · Self-renewal · Stem cell

Zandstra, Peter W.

161

RESEARCH ARTICLE Open Access RNA-Seq reveals complex genetic response to  

E-print Network

RESEARCH ARTICLE Open Access RNA-Seq reveals complex genetic response to deepwater horizon oil the blowout of the Deepwater Horizon (DH) drilling platform was one of the largest in history discharging more In April of 2010, the explosion of the Deepwater Hori- zon oil drilling platform initiated the largest deep

Whitehead, Andrew

162

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

163

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

PubMed

We describe a nonsmoking ceramic tile worker 25 yr of age who developed a worsening dry cough and dyspnea after 3.5 yr as a sorter and glazer of tiles. Open lung biopsy revealed an intense granulomatous interstitial pneumonia with mild fibrosis, compatible with hypersensitivity pneumonitis, and numerous very small birefringent crystals around the terminal airways and occasionally in granulomas. Pulmonary particle analysis revealed an inhaled dust burden nearly 100-fold the normal background level, mainly consisting of clay minerals and zirconium silicate. The patient had no history or clinical or laboratory findings suggesting any organic etiologic agent. A sarcoid granulomatosis type of chronic pulmonary hypersensitivity reaction is known after long-term exposure to zirconium, but this case demonstrates that zirconium can also cause an acute and fulminant allergic alveolitislike hypersensitivity reaction. PMID:8214930

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

1993-10-01

164

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. PMID:20161683

Ren, Ke

2009-01-01

165

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. PMID:12117652

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

2002-01-01

166

Cockatiel-induced hypersensitivity pneumonitis.  

PubMed

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. PMID:12117652

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

2002-07-01

167

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

EPA Science Inventory

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

168

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

PubMed

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

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

2014-01-01

169

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

PubMed Central

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

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

2014-01-01

170

Profiles of cytokine mRNAs in the skin and lymph nodes of SENCAR mice treated epicutaneously with dibenzo[a,l]pyrene or dimethylbenz[a]anthracene reveal a direct correlation between carcinogen-induced contact hypersensitivity and epidermal hyperplasia.  

PubMed

The potent carcinogenicity of dibenzo[a,l]pyrene (DB[a,l]P) in mouse skin is associated with an inflammatory response and a striking epidermal hyperplasia. The mechanism of these tissue responses is not known. However, a recent study has shown DB[a,l]P to be a contact sensitizer. In view of the programmed expression of cytokines during induction of contact hypersensitivity (CHS) and elicitation of CHS reactions, we analyzed cytokine mRNAs in treated skin and draining lymph nodes of SENCAR mice, at selected times after a single, epicutaneous application of DB[a,l]P or dimethylbenz[a]anthracene (DMBA), a substantially weaker carcinogen and a weaker contact sensitizer than DB[a,l]P. Cytokine mRNAs were quantified by first-strand DNA synthesis with reverse transcriptase (RT) and DNA amplification by the polymerase chain reaction (PCR). Histopathology of treated skin was determined in the same experiments. Time-response profiles of interferon (IFN) gamma and interleukin (IL) 2 in the DLN and IL1beta, IL10, tumor necrosis factor (TNF) alpha, and IL4 mRNAs in the skin of mice treated with 200 nmol of DB[a,l]P were in remarkable agreement with established profiles in mice treated with conventional contact sensitizers, e.g., oxazolone or dinitrochlorobenzene. Strong upregulation of DLN IFNgamma mRNA coupled with little change in IL 2 mRNA suggested a CD8(+) T-cell response characteristic of CHS induction. Coordinate expression of epidermal IL1beta, TNFalpha, and IL10 mRNAs, 24 h after DB[a,l]P treatment, was also characteristic of CHS induction. IL1beta and IL10 are upregulated by allergens and not by chemical irritants. Time-response profiles of epidermal IL1beta, TNFalpha, IL10, and IL4 mRNAs, 3-14 d after DB[a,l]P treatment, corresponded with expression of these cytokines during elicitation of CHS reactions. Epidermal IL4 is specifically upregulated during CHS reactions. Cytokine mRNA responses were dose-dependent (50, 100, and 200 nmol of DB[a,l]P) and markedly weaker in animals treated with 400 nmol of DMBA. Significantly, the intensity of epidermal hyperplasia correlated with the strength of the cytokine mRNA signals in DLN and skin. In conclusion, our data support carcinogen-specific CHS as a mechanism by which the very potent carcinogen DB[a,l]P induces epidermal hyperplasia, a requirement for tumor promotion in mouse skin. PMID:10657905

Casale, G P; Cheng, Z; Liu, J n; Cavalieri, E L; Singhal, M

2000-02-01

171

Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA.  

PubMed

Recent publications have shown that certain human leukocyte antigen (HLA) alleles are strongly associated with hypersensitivity to particular drugs. As HLA molecules are a critical element in T-cell stimulation, it is no surprise that particular HLA alleles have a direct functional role in the pathogenesis of drug hypersensitivity. In this context, a direct interaction of the relevant drug with HLA molecules as described by the p-i concept appears to be more relevant than presentation of hapten-modified peptides. In some HLA-associated drug hypersensitivity reactions, the presence of a risk allele is a necessary but incomplete factor for disease development. In carbamazepine and HLA-B*15:02, certain T-cell receptor (TCR) repertoires are required for immune activation. This additional requirement may be one of the 'missing links' in explaining why most individuals carrying this allele can tolerate the drug. In contrast, abacavir generates polyclonal T-cell response by interacting specifically with HLA-B*57:01 molecules. T cell stimulation may be due to presentation of abacavir or of altered peptides. While the presence of HLA-B*58:01 allele substantially increases the risk of allopurinol hypersensitivity, it is not an absolute requirement, suggesting that other factors also play an important role. In summary, drug hypersensitivity is the end result of a drug interaction with certain HLA molecules and TCRs, the sum of which determines whether the ensuing immune response is going to be harmful or not. PMID:22943588

Yun, J; Adam, J; Yerly, D; Pichler, W J

2012-11-01

172

Biophoton distress flares signal the onset of the hypersensitive reaction.  

PubMed

Detection of biophoton emission, a natural bioluminescence, has emerged as a non-destructive method to mark the onset of the hypersensitive resistance reaction in Arabidopsis, bean and tomato. Rapid biophoton emission in Arabidopsis requires an intact R-gene signalling network and increased levels of cytosolic calcium and nitric oxide. The burst of biophotons precedes macroscopic symptoms by several hours and its timing is characteristic for specific gene-for-gene interactions. The ability to monitor biophoton emission from whole plants in real time should allow detailed dissection of plant defence responses. PMID:15951222

Mansfield, John W

2005-07-01

173

Hypersensitivity pneumonitis in a technician using Pauli's reagent.  

PubMed Central

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

Evans, W V; Seaton, A

1979-01-01

174

HLA and pharmacogenetics of drug hypersensitivity.  

PubMed

Immunologically mediated drug reactions have been traditionally classified as unpredictable based on the fact that they cannot be predicted strictly on the pharmacological action of the drug. Such adverse drug reactions are associated with considerable morbidity and include severe cutaneous adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis and the drug hypersensitivity syndromes (drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome). Over the last decade there have been many associations between these syndromes and Class I and II HLA alleles of the MHC, which have enriched and driven our knowledge of their immunopathogenesis. Significant translation has also occurred in the case of HLA-B*5701 screening being used to exclude at risk patients from abacavir and prevent abacavir hypersensitivity. The ultimate translation of the knowledge of how drugs interact with HLA would be applicable to preclinical drug screening programs to improve the safety and cost-effectiveness of drug design and development. PMID:22920398

Pavlos, Rebecca; Mallal, Simon; Phillips, Elizabeth

2012-08-01

175

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

PubMed Central

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

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

2013-01-01

176

Transient and steady-state responses to mechanical stimulation of different fingers reveal interactions based on lateral inhibition  

E-print Network

1 Title: Transient and steady-state responses to mechanical stimulation of different fingers reveal responsible for this effect. The present study disentangles these two effects using steady state somatosensory electrophysiological brain response is elicited in the EEG activity. This response, called the steady-state

Gielen, C.C.A.M.

177

Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site.  

PubMed Central

The genomic organization of a gamma-interferon-inducible gene, IP-10, reveals three introns that interrupt the transcribed sequence into four functional domains. Comparison of the intron-exon structure of this gene to the gene for an homologous chemotactic platelet protein, platelet factor 4, establishes that both genes are interrupted in precisely the same positions within homologous codons; this demonstrates that they belong to a gene family that evolved from a common ancestor. IP-10 and PF4 are two members of a newly described gene family that is likely to include the homologous chemotactic and mitogenic platelet basic proteins (connective tissue-activating protein III and beta-thromboglobulin), the transformation-related protein 9E3, and 310c, a mitogen-stimulated leukocyte protein. A DNase I-hypersensitive site has been found in responsive cells in a region upstream of the RNA initiation site. This hypersensitive site is induced by gamma interferon and thus provides a structural basis for the transcriptional activation seen for this gene by gamma interferon. Images PMID:2824996

Luster, A D; Ravetch, J V

1987-01-01

178

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

PubMed

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

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

2015-02-01

179

Topical guanethidine relieves dentinal hypersensitivity and pain.  

PubMed Central

The topical application of guanethidine solution to the affected teeth has been successful in relieving natural and clinically induced dentinal pain and hypersensitivity in 13 of 14 dental patients in a pilot study. The mechanism of this analgesia was unclear but probably involved anti-noradrenergic block as there was no evidence of local anaesthesia. Further studies may generate new ideas about the cause of the excruciating pain and hypersensitivity often associated with the acute exposure of tooth dentine and lead to new ways of managing the discomforts of dental conservation and restoration. PMID:8410886

Hannington-Kiff, J G; Dunne, S M

1993-01-01

180

Permanent scatterer InSAR reveals seasonal and long-term aquifer-system response to groundwater pumping and artificial  

E-print Network

SAR reveals seasonal and long-term aquifer-system response to groundwater pumping and artificial rechargePermanent scatterer InSAR reveals seasonal and long-term aquifer-system response to groundwater pumping and artificial recharge John W. Bell,1 Falk Amelung,2 Alessandro Ferretti,3 Marco Bianchi,3

Amelung, Falk

181

Progressive tactile hypersensitivity: an inflammation-induced incremental increase in the excitability of the spinal cord.  

PubMed

Two established phenomena contribute to the generation of post-injury pain hypersensitivity: peripheral sensitization, an increase in transduction sensitivity of high threshold A delta and C-fibre nociceptors, and central sensitization, an increase in excitability of neurones in the spinal cord triggered exclusively by C-fibre inputs. We now describe a novel phenomenon: progressive tactile hypersensitivity, which contributes to a cumulative allodynia during inflammation. Behavioural measurements in conscious intact animals showed that repeated light touch stimuli delivered at 5-min intervals to an inflamed paw, established 48 h earlier by an intra-plantar injection of complete Freund's adjuvant (CFA), resulted in a progressive reduction in the mechanical withdrawal threshold by more than 75%, from its already hypersensitive basal level. This hypersensitive state persisted for several hours after discontinuing the touch stimuli and did not occur in non-inflamed animals. To monitor nociceptive processing and the afferent fibres responsible, we also measured activity in posterior biceps femoris/semitendinosus flexor motor neurones. In non-inflamed decerebrate-spinal rats, the cutaneous mechanical threshold and pinch-evoked activity of these neurones are stable when tested repeatedly at 5-min intervals and are characterised by absent or small responses to low intensity mechanical stimuli or electrical activation of A beta-fibres. In inflamed animals, the spontaneous activity, touch-, pinch- and A beta-afferent-evoked responses of hamstring flexor motor neurones are significantly increased. The flexor reflex becomes, moreover, progressively more sensitized by repetition every 5 min, of standard mechanical stimuli (touch and pinch), that do not modify excitability in control non-inflamed animals. A cumulative increase in A beta-afferent-evoked responses also occurs when the test stimulus only comprises stimulation of the sural nerve at A beta strength (10 Hz, 10 sec), showing that A beta-afferents have the capacity to produce progressive hypersensitivity. Progressive hypersensitivity, measured here as a progressive tactile allodynia after inflammation in either intact or decerebrate-spinal rats, with its gradual build-up and contribution from A beta fibres, is very different from the central sensitization induced by C-fibre stimulation which is characterised by a peak increase in excitability soon after the conditioning input followed by a steady decrement to baseline levels. Progressive hypersensitivity is likely to be the consequence of an alteration in the function and phenotype of afferents innervating inflamed tissue and the pattern of excitation they produce in spinal neurones. The phenomenon may have an important role in the development of inflammatory pain and hypersensitivity. PMID:8895236

Ma, Q P; Woolf, C J

1996-09-01

182

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. PMID:18495938

Melamed, Daniel; Pnueli, Lilach; Arava, Yoav

2008-01-01

183

Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy.  

PubMed

In order to address the question whether hypersensitivity reactions to dapsone are becoming more frequent, the clinical data of 7300 leprosy patients treated between 1949 and September 1988 at the McKean Rehabilitation Centre in Thailand were reviewed. Information from the period 1949 to 1969 was too incomplete to allow conclusions. The incidence of hypersensitivity reactions to dapsone between 1970 and 1982 was 0.3%. From 1982 (with the introduction of multidrug therapy) to September 1988, the incidence was 3.6%; a tenfold increase compared with the previous period. Of the 19 cases seen since 1982, 12 were diagnosed as Dapsone syndrome. Of a total of 13 patients seen since 1980 with Dapsone syndrome, 3 ended fatally, indicating the severity of the complication. The question is raised whether an unexplained drug interaction with rifampicin is responsible for the increase of hypersensitivity reactions to dapsone in patients treated for leprosy. PMID:2491425

Richardus, J H; Smith, T C

1989-12-01

184

NK 1 receptor-mediated mechanisms regulate colonic hypersensitivity in the guinea pig  

Microsoft Academic Search

Neurokinin-1 (NK1) receptors activated by substance P (SP) are involved in the processing of nociceptive information and are a potential target for therapy of visceral pain. We have evaluated the role of NK1 receptors using a selective antagonist of NK1 receptors in two animal models of colorectal hypersensitivity. The behavioral response to colorectal distension was assessed in freely moving guinea

Beverley Greenwood-Van Meerveld; Matthew S Gibson; Anthony C Johnson; Kalina Venkova; Debra Sutkowski-Markmann

2003-01-01

185

Mechanism of a Reaction in Vitro Associated with Delayed-Type Hypersensitivity  

Microsoft Academic Search

The cell type responsible for inhibition by antigen of migration in vitro of peritoneal exudate cells obtained from tuberculin-hypersensitive guinea pigs was studied. Exudate populations were separated into component cell types, the lymphocyte and the macrophage. Peritoneal lymphocytes from sensitive donors were the immunologically active cells in this system, the macrophages being merely indicator cells which migrate. Sensitized peritoneal lymphocyte

Barry R. Bloom; Boyce Bennett

1966-01-01

186

Functional Redundancy of Langerhans Cells and Langerin+ Dermal Dendritic Cells in Contact Hypersensitivity  

Microsoft Academic Search

The relative roles of Langerhans cells (LC), dermal dendritic cells (DC), and, in particular, the recently discovered Langerin+ dermal DC subset in the induction and control of contact hypersensitivity (CHS) responses remain controversial. Using an inducible mouse model, in which LC and other Langerin+ DC can be depleted by injection of diphtheria toxin, we previously reported impaired transport of topically

Madelon Noordegraaf; Vincent Flacher; Patrizia Stoitzner; Björn E Clausen

2010-01-01

187

Pustular drug hypersensitivity syndrome due to allopurinol  

PubMed Central

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

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

2015-01-01

188

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

189

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

PubMed Central

Background Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and anti-histamine itch therapy (cetirizine) on type-I-hypersensitivity itch and skin reaction in AD using a patient and examiner blinded, randomized, placebo-controlled, crossover trial. Methods Allergen–induced itch was evaluated in 20 AD patients after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC), and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 minutes, using our validated model. Outcome parameters included itch intensity, wheal and flare size, and the D2 Attention test. Results Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared to all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7, p<0.05). There was no significant difference between VAp and VC (p>0.1), though both therapies were significantly superior to their respective placebo interventions (p<0.05). Flare size following VAp was significantly smaller (p=0.034) than PAp. D2 attention test score was significantly lower following VC compared to all other groups (p<0.001). Conclusions Both VA and cetirizine significantly reduced type-I-hypersensitivity itch in AD patients, compared to both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially due to counter-irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention. PMID:22313287

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

2012-01-01

190

Treatments for hypersensitive noncarious cervical lesions  

PubMed Central

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

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

2014-01-01

191

Global analysis of neutrophil responses to Neisseria gonorrhoeae reveals a self-propagating inflammatory program.  

PubMed

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

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

2014-09-01

192

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

PubMed Central

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

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

2014-01-01

193

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

PubMed Central

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

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

2015-01-01

194

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

PubMed

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

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

2014-09-29

195

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 PMID:24425189

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

2014-01-01

196

Metabolite profiling and network analysis reveal coordinated changes in grapevine water stress response  

PubMed Central

Background Grapevine metabolism in response to water deficit was studied in two cultivars, Shiraz and Cabernet Sauvignon, which were shown to have different hydraulic behaviors (Hochberg et al. Physiol. Plant. 147:443–453, 2012). Results Progressive water deficit was found to effect changes in leaf water potentials accompanied by metabolic changes. In both cultivars, but more intensively in Shiraz than Cabernet Sauvignon, water deficit caused a shift to higher osmolality and lower C/N ratios, the latter of which was also reflected in marked increases in amino acids, e.g., Pro, Val, Leu, Thr and Trp, reductions of most organic acids, and changes in the phenylpropanoid pathway. PCA analysis showed that changes in primary metabolism were mostly associated with water stress, while diversification of specialized metabolism was mostly linked to the cultivars. In the phloem sap, drought was characterized by higher ABA concentration and major changes in benzoate levels coinciding with lower stomatal conductance and suberinization of vascular bundles. Enhanced suberin biosynthesis in Shiraz was reflected by the higher abundance of sap hydroxybenzoate derivatives. Correlation-based network analysis revealed that compared to Cabernet Sauvignon, Shiraz had considerably larger and highly coordinated stress-related changes, reflected in its increased metabolic network connectivity under stress. Network analysis also highlighted the structural role of major stress related metabolites, e.g., Pro, quercetin and ascorbate, which drastically altered their connectedness in the Shiraz network under water deficit. Conclusions Taken together, the results showed that Vitis vinifera cultivars possess a common metabolic response to water deficit. Central metabolism, and specifically N metabolism, plays a significant role in stress response in vine. At the cultivar level, Cabernet Sauvignon was characterized by milder metabolic perturbations, likely due to a tighter regulation of stomata upon stress induction. Network analysis was successfully implemented to characterize plant stress molecular response and to identify metabolites with a significant structural and biological role in vine stress response. PMID:24256338

2013-01-01

197

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

198

Airway Inflammation and Hypersensitivity Induced by Chronic Smoking  

PubMed Central

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

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

2011-01-01

199

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

PubMed

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

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

2012-01-01

200

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

PubMed

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

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

2015-01-01

201

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

PubMed Central

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

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

2015-01-01

202

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

PubMed Central

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

Barbosa, Catarina; García-Martínez, José; Pérez-Ortín, José E.; Mendes-Ferreira, Ana

2015-01-01

203

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

PubMed

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

Straka, Ma?gorzata M; Schmitz, Samuel; Lim, Hubert H

2014-08-15

204

Immunologic Evaluation of Immediate Hypersensitivity to Cefaclor  

PubMed Central

Purpose Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. Materials and Methods We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). Results The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. Conclusion The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients. PMID:25323882

Yoo, Hye-Soo; Kim, Seung-Hyun; Kwon, Hyouk-Soo; Kim, Tae-Bum; Nam, Young-Hee; Ye, Young-Min

2014-01-01

205

Excess fertilizer responsive miRNAs revealed in Linum usitatissimum L.  

PubMed

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

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

2015-02-01

206

Drug Hypersensitivity: Pharmacogenetics and Clinical Syndromes  

PubMed Central

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

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

2011-01-01

207

Drug hypersensitivity: pharmacogenetics and clinical syndromes.  

PubMed

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

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

2011-03-01

208

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. PMID:24498522

Soufras, George D.; Hahalis, George

2013-01-01

209

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

PubMed

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

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

2015-03-18

210

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

PubMed Central

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

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

2015-01-01

211

Revealing shared and distinct gene network organization in Arabidopsis immune responses by integrative analysis.  

PubMed

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

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

2015-03-01

212

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

213

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

214

Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity  

PubMed Central

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

Campillo-Navarro, Marcia; Chávez-Blanco, Alma D; Wong-Baeza, Isabel; Serafín-López, Jeanet; Flores-Mejía, Raúl; Estrada-Parra, Sergio; Estrada-García, Iris; Chacón-Salinas, Rommel

2014-01-01

215

Modulation of picryl chloride-induced contact hypersensitivity reaction in mice by nitric oxide.  

PubMed

We have studied the possible involvement of nitric oxide (NO) in the contact hypersensitivity reaction. A biphasic response of ear swelling was observed at 2 h (early phase) and 24 h (late phase) after application of the antigen to picryl chloride (PC1)-sensitized CBA/J mice. Intravenous injection of NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), at the time of PC1 challenge, inhibited in a concentration-dependent fashion the antigen-induced contact hypersensitivity reaction. Low-dose (1 mg/kg) L-NAME inhibited the early-phase reaction but not the late-phase reaction. High-dose (250 mg/kg) L-NAME inhibited both early- and late-phase reactions. D-NAME (enantiomer of L-NAME) did not inhibit the antigen-induced ear swelling. High-dose (250 mg/kg) L-arginine increased both early and late phase reactions. D-Arginine (enantiomer of L-arginine) did no increase the antigen-induced ear swelling. L-NAME injection, however, did not suppress phenol-induce irritant inflammation. Treatment of mice undergoing PC1-induced contact hypersensitivity reaction with L-NAME reduced the production of interleukin-2 and interferon-gamma by draining lymph node cells. Treatment with L-arginine, on the other hand increased the production of interleukin-2 and interferon-gamma. These results suggest that NO plays a modulating role in contact hypersensitivity reaction. PMID:8823359

Morita, H; Hori, M; Kitano, Y

1996-10-01

216

The Potential Utility of Iodinated Contrast Media (ICM) Skin Testing in Patients with ICM Hypersensitivity.  

PubMed

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM. PMID:25729245

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

2015-03-01

217

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

PubMed Central

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

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

2009-01-01

218

Cutaneous hypersensitivity test to evaluate phage display anti-tick borne vaccine antigen candidates  

Microsoft Academic Search

Early experiments performed by our group with the phage display technique revealed the potential for using epitope-displaying phages (mimotopes) as a tool for tick antigen discovery. Thus, as a preliminary study, inflammatory reactions induced by phage display tick-borne candidates were investigated by using the cutaneous hypersensitivity test. The profile of selected Rhipicephalus microplus mimotopes was assessed on tick field-exposed cattle

Carlos Roberto Prudencio; Aline Aparecida Rezende Rodrigues; Rone Cardoso; Guilherme Rocha Lino de Souza; Matias Pablo Juan Szabó; Luiz Ricardo Goulart

2011-01-01

219

Soil microbial community responses to a decade of warming as revealed by comparative metagenomics.  

PubMed

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

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

2014-03-01

220

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

SciTech Connect

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

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

2012-06-12

221

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

PubMed Central

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

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

2014-01-01

222

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

PubMed Central

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

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

2014-01-01

223

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

224

Adrenergic Stimulation Mediates Visceral Hypersensitivity to Colorectal Distension following Heterotypic Chronic Stress  

PubMed Central

Background & Aims Chronic stress exacerbates or causes relapse of symptoms such as abdominal pain and cramping in patients with irritable bowel syndrome (IBS). We investigated whether chronic stress increases plasma norepinephrine and sensitizes colon-specific dorsal root ganglion (DRG) neurons by increasing the expression of nerve growth factor (NGF) in the colon wall. Methods Heterotypic chronic stress (HeCS) was induced in male Wistar rats and neurologic and molecular responses were analyzed. Tissues were analyzed for NGF expression. Results HeCS significantly increased the visceromoter response to colorectal distension; expression of NGF increased in colonic muscularis externa and mucosa/submucosa. Rheobase decreased, resting membrane potential was depolarized, and electrogenesis of action potentials increased in colon-specific thoracolumbar DRG neurons. Luminal administration of resiniferatoxin in distal colon, systemic administration of anti-NGF antibody, or inhibition of the NGF receptor TrkA by k252A or antisense oligonucleotides in thoracolumbar DRG blocked the chronic stress-induced visceral hypersensitivity to colorectal distension. Blockade of ?1/?2- and ?1/?2-adrenergic receptors prevented the stress-induced visceral hypersensitivity and increased expression of NGF in the colon wall. HeCS did not induce any inflammatory response in the colon wall. Conclusion The peripheral stress mediator norepinephrine induces visceral hypersensitivity to colorectal distension in response to HeCS by increasing the expression of NGF in the colon wall, which sensitizes primary afferents in the absence of an inflammatory response. PMID:19800336

Winston, John H.; Xu, Guang-Yin; Sarna, Sushil K.

2009-01-01

225

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

PubMed Central

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

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

2007-01-01

226

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

PubMed

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

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

2014-01-01

227

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

228

Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity  

PubMed Central

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

Ferrusquía, José; Pérez-Martínez, Isabel; Gómez de la Torre, Ricardo; Fernández-Almira, María Luisa; de Francisco, Ruth; Rodrigo, Luis; Riestra, Sabino

2015-01-01

229

Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity.  

PubMed

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

Ferrusquía, José; Pérez-Martínez, Isabel; Gómez de la Torre, Ricardo; Fernández-Almira, María Luisa; de Francisco, Ruth; Rodrigo, Luis; Riestra, Sabino

2015-04-01

230

Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw.  

PubMed

Permafrost contains an estimated 1672?Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5?°C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. PMID:22056985

Mackelprang, Rachel; Waldrop, Mark P; DeAngelis, Kristen M; David, Maude M; Chavarria, Krystle L; Blazewicz, Steven J; Rubin, Edward M; Jansson, Janet K

2011-12-15

231

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

USGS Publications Warehouse

Background. The Hawaiian honeycreepers (Drepanidinae) are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens), the apapane (Himatione sanguinea), and the iiwi (Vestiaria coccinea) were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results. Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion. Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent. ?? 2008 Eggert et al; licensee BioMed Central Ltd.

Eggert, L.S.; Terwilliger, L.A.; Woodworth, B.L.; Hart, P.J.; Palmer, D.; Fleischer, R.C.

2008-01-01

232

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

PubMed Central

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

Rothlein, David; Rapp, Brenda

2014-01-01

233

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

NASA Astrophysics Data System (ADS)

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

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

2013-03-01

234

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. PMID:24481457

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

2014-01-01

235

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

PubMed

Time-series analysis is used widely in ecology to study complex phenomena and may have considerable potential to clarify relationships of genetic and demographic processes in natural and exploited populations. We explored the utility of this approach to evaluate population responses to management in razorback sucker, a long-lived and fecund, but declining freshwater fish species. A core population in Lake Mohave (Arizona-Nevada, USA) has experienced no natural recruitment for decades and is maintained by harvesting naturally produced larvae from the lake, rearing them in protective custody, and repatriating them at sizes less vulnerable to predation. Analyses of mtDNA and 15 microsatellites characterized for sequential larval cohorts collected over a 15-year time series revealed no changes in geographic structuring but indicated significant increase in mtDNA diversity for the entire population over time. Likewise, ratios of annual effective breeders to annual census size (N b /N a) increased significantly despite sevenfold reduction of N a. These results indicated that conservation actions diminished near-term extinction risk due to genetic factors and should now focus on increasing numbers of fish in Lake Mohave to ameliorate longer-term risks. More generally, time-series analysis permitted robust testing of trends in genetic diversity, despite low precision of some metrics. PMID:24665337

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

2014-03-01

236

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

PubMed Central

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

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

2014-01-01

237

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

238

LLLT in treating dentinary hypersensitivity: new concepts  

NASA Astrophysics Data System (ADS)

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

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

2006-02-01

239

[Occupational asthma due to hard metals hypersensitivity].  

PubMed

The authors report the case of a worker in the hard metal industry presenting with asthma due to cobalt and nickel. The diagnosis was supported by the history, positive skin tests and lymphocyte activation as well as elevated levels of the metals in the urine and BAL. Challenge led to a delayed asthmatic reaction occurring 3.5 to 24 hours after exposure. The BAL contained high levels of tungsten and cobalt, the level of the latter doubling 48 hours after exposure. After the provocation test a nasal and broncho-alveolar eosinophilia was observed. The possibility of a delayed hypersensitivity reaction to metals is discussed by the authors. PMID:12161703

De Hauteclocque, C; Morisset, M; Kanny, G; Kohler, C; Mouget, B; Moneret-Vautrin, D A

2002-06-01

240

Drug hypersensitivity syndrome induced by meglumine antimoniate.  

PubMed

We report a case of drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) induced by parenteral meglumine antimoniate (Glucantime) in a 40-year-old man who traveled to Bolivia and was treated for mucocutaneous leishmaniasis. Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm(3)). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug. Pentavalent antimonials should be definitively withdrawn in patients with hypereosinophilia > 1,000 cells/mm(3) accompanied by systemic manifestations consistent with DRESS. PMID:19478253

Jeddi, Fakhri; Caumes, Eric; Thellier, Marc; Jauréguiberry, Stéphane; Mazier, Dominique; Buffet, Pierre A

2009-06-01

241

Platelet, not endothelial, P-selectin expression contributes to generation of immunity in cutaneous contact hypersensitivity.  

PubMed

Leukocyte extravasation is a prerequisite for host defense and autoimmunity alike. Detailed understanding of the tightly controlled and overlapping sequences of leukocyte extravasation might aid development of novel therapeutic strategies. Leukocyte extravasation is initiated by interaction of selectins with appropriate carbohydrate ligands. Lack of P-selectin expression leads to decreased contact hypersensitivity responses. Yet, it remains unclear if this is due to inhibition of leukocyte extravasation to the skin or due to interference with initial immune activation in lymph nodes. In line with previous data, we here report a decreased contact hypersensitivity response, induced by 2,4,-dinitrofluorobenzene (DNFB), in P-selectin-deficient mice. Eliciting an immune reaction towards DNFB in wild-type mice, followed by adoptive transfer to P-selectin-deficient mice, had no impact on inflammatory response in recipients. This was significantly reduced in wild-type recipient mice adoptively transferred with DNFB immunity generated in P-selectin-deficient mice. To investigate if platelet or endothelial P-selectin was involved, mice solely lacking platelet P-selectin expression generated by bone marrow transplantation were used. Adoptive transfer of immunity from wild-type mice reconstituted with P-selectin-deficient bone marrow led to a decrease of inflammatory response. Comparing this decrease to the one observed using P-selectin-deficient mice, no differences were observed. Our observations indicate that platelet, not endothelial, P-selectin contributes to generation of immunity in DNFB-induced contact hypersensitivity. PMID:20056837

Ludwig, Ralf J; Bergmann, Peri; Garbaraviciene, Jurate; von Stebut, Esther; Radeke, Heinfried H; Gille, Jens; Diehl, Sandra; Hardt, Katja; Henschler, Reinhard; Kaufmann, Roland; Pfeilschifter, Josef M; Boehncke, Wolf-Henning

2010-03-01

242

Platelet, Not Endothelial, P-Selectin Expression Contributes to Generation of Immunity in Cutaneous Contact Hypersensitivity  

PubMed Central

Leukocyte extravasation is a prerequisite for host defense and autoimmunity alike. Detailed understanding of the tightly controlled and overlapping sequences of leukocyte extravasation might aid development of novel therapeutic strategies. Leukocyte extravasation is initiated by interaction of selectins with appropriate carbohydrate ligands. Lack of P-selectin expression leads to decreased contact hypersensitivity responses. Yet, it remains unclear if this is due to inhibition of leukocyte extravasation to the skin or due to interference with initial immune activation in lymph nodes. In line with previous data, we here report a decreased contact hypersensitivity response, induced by 2,4,-dinitrofluorobenzene (DNFB), in P-selectin-deficient mice. Eliciting an immune reaction towards DNFB in wild-type mice, followed by adoptive transfer to P-selectin-deficient mice, had no impact on inflammatory response in recipients. This was significantly reduced in wild-type recipient mice adoptively transferred with DNFB immunity generated in P-selectin-deficient mice. To investigate if platelet or endothelial P-selectin was involved, mice solely lacking platelet P-selectin expression generated by bone marrow transplantation were used. Adoptive transfer of immunity from wild-type mice reconstituted with P-selectin-deficient bone marrow led to a decrease of inflammatory response. Comparing this decrease to the one observed using P-selectin-deficient mice, no differences were observed. Our observations indicate that platelet, not endothelial, P-selectin contributes to generation of immunity in DNFB-induced contact hypersensitivity. PMID:20056837

Ludwig, Ralf J.; Bergmann, Peri; Garbaraviciene, Jurate; Stebut, Esther von; Radeke, Heinfried H.; Gille, Jens; Diehl, Sandra; Hardt, Katja; Henschler, Reinhard; Kaufmann, Roland; Pfeilschifter, Josef M.; Boehncke, Wolf-Henning

2010-01-01

243

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

PubMed Central

Background Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Methods Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca2+]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Results Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24 hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca2+]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. Conclusions The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in suppression of hypersensitivity reaction. PMID:25302070

2014-01-01

244

Distinct roles of the pepper hypersensitive induced reaction protein gene CaHIR1 in disease and osmotic stress, as determined by comparative transcriptome and proteome analyses  

Microsoft Academic Search

A Capsicum \\u000a annuum hypersensitive induced reaction protein1 (CaHIR1) was recently proposed as a positive regulator of hypersensitive cell death\\u000a in plants. Overexpression of CaHIR1 in transgenic Arabidopsis plants conferred enhanced resistance against the hemi-biotrophic Pseudomonas syringae pv. tomato (Pst) and the biotrophic Hyaloperonospora parasitica. Infection by avirulent Pseudomonas strains carrying avrRpm1 or avrRpt2 caused enhanced resistance responses in transgenic plants,

Ho Won Jung; Chae Woo Lim; Sung Chul Lee; Hyong Woo Choi; Cheol Ho Hwang; Byung Kook Hwang

2008-01-01

245

Hypersensitivity to laminaria: a case report and review of literature.  

PubMed

We report a case of laminaria hypersensitivity treated with diphenhydramine and corticosteroids. A literature review identified 10 previously reported cases, with 8 recognized as anaphylaxis, and good outcomes with corticosteroids and antihistamines despite limited epinephrine utilization. Laminaria hypersensitivity is likely IgE mediated with an increased anaphylaxis risk with prior exposure. PMID:25595541

Sierra, Tania; Figueroa, Melissa M; Chen, Katherine T; Lunde, Britt; Jacobs, Adam

2015-04-01

246

Diagnosis and Management of Hypersensitivity Reactions Caused by Oxaliplatin  

Microsoft Academic Search

Hypersensitivity reactions to oxaliplatin have been increasing since its introduction at the end of the 1990s, but allergy tests with antineoplastic drugs are rarely used to aid diagnosis. We describe 5 cases in which hypersensitivity reactions to oxaliplatin after several courses of chemotherapy were managed by allergy testing and desensitization. Skin prick tests were negative at 1 mg\\/mL in all

T Herrero; P Tornero; S Infante; V Fuentes; MN Sánchez; M De Barrio; ML Baeza

247

Accuracy of a Pharmacovigilance Algorithm in Diagnosing Drug Hypersensitivity Reactions  

Microsoft Academic Search

Background: This study was performed to evaluate the diagnostic accuracy of a pharmacovigilance algo- rithm in patients with 1 or more histories suggestive of drug hypersensitivity. Methods: We performed a retrospective analysis of a clinic case series. We analyzed patients with suspected clinical reactions of drug hypersensitivity. Patients with severe skin reactions were excluded. Patients with his- tory of drug

Said Benahmed; Marie-Christine Picot; Francine Dumas; Pascal Demoly

2005-01-01

248

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. PMID:22242170

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

2012-01-01

249

Modulation of Picryl Chloride-Induced Contact Hypersensitivity Reaction in Mice by Nitric Oxide  

Microsoft Academic Search

We have studied the possible involvement of nitric oxide (NO) in the contact hypersensitivity reaction. A bisphasic response of ear swelling was observed at 2 h (early phase) and 24 h (late phase) after application of the antigen to picryl chloride (PCl)-sensitized CBA\\/J mice. Intravenous injection of NO synthase inhibitor, Ng -nitro-L-arginine methyl ester (L-NAME), at the time of PCl

Hideki Morita; Mika Hori; Yukto Kitano

1996-01-01

250

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

PubMed

Despite its relevance, protein regulation, metabolic adjustment, and the physiological status of plants under drought is not well understood in relation to the role of nitrogen fixation in nodules. In this study, nodulated alfalfa plants were exposed to drought conditions. The study determined the physiological, metabolic, and proteomic processes involved in photosynthetic inhibition in relation to the decrease in nitrogenase (N(ase)) activity. The deleterious effect of drought on alfalfa performance was targeted towards photosynthesis and N(ase) activity. At the leaf level, photosynthetic inhibition was mainly caused by the inhibition of Rubisco. The proteomic profile and physiological measurements revealed that the reduced carboxylation capacity of droughted plants was related to limitations in Rubisco protein content, activation state, and RuBP regeneration. Drought also decreased amino acid content such as asparagine, and glutamic acid, and Rubisco protein content indicating that N availability limitations were caused by N(ase) activity inhibition. In this context, drought induced the decrease in Rubisco binding protein content at the leaf level and proteases were up-regulated so as to degrade Rubisco protein. This degradation enabled the reallocation of the Rubisco-derived N to the synthesis of amino acids with osmoregulant capacity. Rubisco degradation under drought conditions was induced so as to remobilize Rubisco-derived N to compensate for the decrease in N associated with N(ase) inhibition. Metabolic analyses showed that droughted plants increased amino acid (proline, a major compound involved in osmotic regulation) and soluble sugar (D-pinitol) levels to contribute towards the decrease in osmotic potential (?(s)). At the nodule level, drought had an inhibitory effect on N(ase) activity. This decrease in N(ase) activity was not induced by substrate shortage, as reflected by an increase in total soluble sugars (TSS) in the nodules. Proline accumulation 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 N(2) 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. PMID:20797998

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

2011-01-01

251

Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw  

USGS Publications Warehouse

Permafrost contains an estimated 1672????????Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 ??C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. ?? 2011 Macmillan Publishers Limited. All rights reserved.

MacKelprang, R.; Waldrop, M.P.; Deangelis, K.M.; David, M.M.; Chavarria, K.L.; Blazewicz, S.J.; Rubin, E.M.; Jansson, J.K.

2011-01-01

252

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. PMID:23269925

Van Aken, Olivier; Whelan, James

2012-01-01

253

Radiocontrast media hypersensitivity in the Asia Pacific region  

PubMed Central

Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region. PMID:24809018

Lee, Suh-Young; Lim, Kyoung-Whan

2014-01-01

254

Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent.  

PubMed

Hypersensitivity pneumonitis (HP), an inflammatory lung disease, develops after repeated exposure to inhaled particulate antigen and is characterized by a vigorous T helper type 1-mediated immune response, resulting in the release of IL-12 and interferon (IFN)-?. These T helper type 1 cytokines may participate in the pathogenesis of HP. Stachybotrys chartarum (SC) is a dimorphic fungus implicated in a number of respiratory illnesses, including HP. Here, we have developed a murine model of SC-induced HP that reproduces pathology observed in human HP and hypothesized that toll receptor-like 9 (TLR9)-mediated dendritic cell responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice sensitized and challenged with 10(6) SC spores develop granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of neutrophils and CD4(+) and CD8(+) T cells. SC sensitization and challenge resulted in robust pulmonary expression of tumor necrosis factor-?, IL-12, and IFN-?. SC-mediated granulomatous inflammation required IFN-? and was TLR9 dependent, because TLR9(-/-) mice displayed reduced peribronchial inflammation, decreased accumulation and/or activation of polymorphonuclear (PMN) and CD4(+) and CD8(+) T cells, and reduced lung expression of type 1 cytokines and chemokines. T-cell production of IFN-? was IL-12 dependent. Our studies suggest that TLR9 is critical for dendritic cell-mediated development of a type 1 granulomatous inflammation in the lung in response to SC. PMID:21982832

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

2011-12-01

255

Stachybotrys chartarum-Induced Hypersensitivity Pneumonitis Is TLR9 Dependent  

PubMed Central

Hypersensitivity pneumonitis (HP), an inflammatory lung disease, develops after repeated exposure to inhaled particulate antigen and is characterized by a vigorous T helper type 1-mediated immune response, resulting in the release of IL-12 and interferon (IFN)-?. These T helper type 1 cytokines may participate in the pathogenesis of HP. Stachybotrys chartarum (SC) is a dimorphic fungus implicated in a number of respiratory illnesses, including HP. Here, we have developed a murine model of SC-induced HP that reproduces pathology observed in human HP and hypothesized that toll receptor-like 9 (TLR9)-mediated dendritic cell responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice sensitized and challenged with 106 SC spores develop granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of neutrophils and CD4+ and CD8+ T cells. SC sensitization and challenge resulted in robust pulmonary expression of tumor necrosis factor-?, IL-12, and IFN-?. SC-mediated granulomatous inflammation required IFN-? and was TLR9 dependent, because TLR9?/? mice displayed reduced peribronchial inflammation, decreased accumulation and/or activation of polymorphonuclear (PMN) and CD4+ and CD8+ T cells, and reduced lung expression of type 1 cytokines and chemokines. T-cell production of IFN-? was IL-12 dependent. Our studies suggest that TLR9 is critical for dendritic cell-mediated development of a type 1 granulomatous inflammation in the lung in response to SC. PMID:21982832

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

2011-01-01

256

Hypersensitivity to ticks and Lyme disease risk.  

PubMed

Although residents of Lyme disease-endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%-31%) reported > or = 1 tick bites, and 17% (95% CI 13%-21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%-26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94-0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease. PMID:15705320

Burke, Georgine; Wikel, Stephen K; Spielman, Andrew; Telford, Sam R; McKay, Kathleen; Krause, Peter J

2005-01-01

257

[Hypersensitivity pneumonitis caused by a home humidifier].  

PubMed

A 33-year-old man was admitted complaining of a fever, dyspnea, and a dry cough almost every night since December of 1992. He had been using an ultrasonic humidifier at home. The chest CT scan and roentgenogram showed bilateral reticulonodular shadows. After admission, the symptoms resolved spontaneously. These findings were suggestive of hypersensitivity pneumonitis. After analysis of fluid obtained by bronchoalveolar lavage and of a specimen obtained by transbronchial biopsy, "humidifier lung" was diagnosed. Ten species of microorganisms were isolated from the water left in the patient's humidifier. On precipitation and complement fixation tests of the patients serum, the results were positive for three of those microorganisms: Flavobacterium multivorum, Yersinia pseudotuberculosis, and Aureobacterium liquefaciens. The titer on the complement fixation test increased immediately after a provocation test. The laboratory results suggest that at least one of these three microorganisms was the causative antigen in this case. PMID:8538084

Hagiwara, S; Ishii, Y; Sugiyama, Y; Kitamura, S

1995-09-01

258

Nutritional management of pediatric food hypersensitivity.  

PubMed

The diagnosis and management of food allergy requires attention to several important dietary issues. Successful exclusion of identified dietary allergens requires extensive education regarding the interpretation of ingredient labels of commercial products and an appreciation for issues of cross-contact in settings such as restaurants and commercial manufacturing. Once a food or food group is eliminated, attention must be focused on potential dietary insufficiencies resulting from these exclusions. These dietary issues are also central to the successful use of diagnostic elimination diets and physician-supervised oral food challenges. This review provides a framework for the dietary management of food hypersensitivity in infants and children both for short-term diagnostic and long-term therapeutic purposes. In addition, approaches for maternal dietary restriction for breastfed infants with food allergy and the introduction of solid foods to atopic infants are reviewed. PMID:12777605

Mofidi, Shideh

2003-06-01

259

Pain hypersensitivity mechanisms at a glance  

PubMed Central

There are two basic categories of pain: physiological pain, which serves an important protective function, and pathological pain, which can have a major negative impact on quality of life in the context of human disease. Major progress has been made in understanding the molecular mechanisms that drive sensory transduction, amplification and conduction in peripheral pain-sensing neurons, communication of sensory inputs to spinal second-order neurons, and the eventual modulation of sensory signals by spinal and descending circuits. This poster article endeavors to provide an overview of how molecular and cellular mechanisms underlying nociception in a physiological context undergo plasticity in pathophysiological states, leading to pain hypersensitivity and chronic pain. PMID:23828645

Gangadharan, Vijayan; Kuner, Rohini

2013-01-01

260

Diagnostic yield of specific inhalation challenge in hypersensitivity pneumonitis.  

PubMed

Reliable methods are needed to diagnose hypersensitivity pneumonitis. The aim of the study was to establish the diagnostic yield of specific inhalation challenge (SIC) in patients with hypersensitivity pneumonitis. All patients with suspected hypersensitivity pneumonitis in whom SIC was performed (n=113) were included. SIC was considered positive when patients showed a decrease of >15% in forced vital capacity (FVC) or >20% in diffusing capacity of the lung for carbon dioxide, or a decrease of 10% to 15% in FVC accompanied by a temperature increase of 0.5°C within 24 h of inhalation of the antigen. SIC was positive to the agents tested in 68 patients: 64 received a diagnosis of hypersensitivity pneumonitis and SIC results were considered false-positive in the remaining four patients. In the SIC-negative group (n=45), 24 patients received a diagnosis of hypersensitivity pneumonitis and SIC results were considered false-negative, and 21 patients were diagnosed with other respiratory diseases. The sensitivity and specificity of the test were 72.7% and 84%, respectively. Having hypersensitivity pneumonitis caused by an antigen other than birds or fungi predicted a false-negative result (p=0.001). In hypersensitivity pneumonitis, positive SIC testing virtually confirms the diagnosis, whereas negative testing does not rule it out, especially when the antigenic sources are not birds or fungi. PMID:25142480

Muñoz, Xavier; Sánchez-Ortiz, Mónica; Torres, Ferran; Villar, Ana; Morell, Ferran; Cruz, María-Jesús

2014-12-01

261

Delayed type hypersensitivity: current theories with an historic perspective.  

PubMed

Although the delayed type hypersensitivity (DTH) reaction was discovered over 100 years ago, the exact nature of the reaction has been the subject of contentious debate over the years. The reaction was discovered in 1882 by Robert Koch, but it was not until the 1940s that Landsteiner and Chase proved that the reaction was mediated by the cellular and not the humoral arm of the immune system. The first DTH reaction described used only the tuberculin antigen (tuberculin reaction), but the definition was later expanded to include cell mediated reactions to other bacterial and viral antigens, responses to pure protein with adjuvant or haptens, and host responses to allograft. The DTH skin test is used to test if prior exposure to an antigen has occurred. When small quantities of antigen are injected dermally, a hallmark response is elicited which includes induration, swelling and monocytic infiltration into the site of the lesion within 24 to 72 hours. This reaction has been shown to be absolutely dependent on the presence of memory T cells. Both the CD4+ and CD8+ fractions of cells have been shown to modulate a response. Contemporary debate regarding the reaction is focused on the role of the Th1 and Th2 cells originally discovered by Mosmann. It has been postulated that the Th1 cell is the "inducer" of a DTH response since it secretes interferon gamma (IFN ), a potent stimulator of macrophages, while the Th2 cell is either not involved or acting as a downregulator of the cell mediated immune response. Despite the early experimental success of this theory, experiments have shown that Th2 cells may be involved in certain types of proinflammatory cell mediated immunity. This review focuses on the nature of the different forms of DTH that can be elicited and the different experimental evidence that has led to the current theories regarding DTH and its role in cell mediated immunity. PMID:10673450

Black, C A

1999-05-01

262

Age-related differences in response regulation as revealed by functional MRI  

Microsoft Academic Search

This fMRI study studied age-related differences in neural activities during response regulation. Twenty-one male participants from two age groups, a younger group and an older group (mean ages: 29.9 and 65.2 years, respectively), were scanned while performing a task with response compatibility manipulation. They were presented with a sequence of arrowheads that pointed either upward or downward. In the “Response

Tatia M. C. Lee; John X. Zhang; Chetwyn C. H. Chan; Kenneth S. L. Yuen; L. W. Chu; Raymond T. F. Cheung; Y. S. Chan; Peter T. Fox; Jia-Hong Gao

2006-01-01

263

Stromal Transcriptional Profiles Reveal Hierarchies of Anatomical Site, Serum Response and Disease and Identify Disease Specific Pathways  

PubMed Central

Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through _3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts. PMID:25807374

Parsonage, Greg N.; Legault, Holly M.; O’Toole, Margot; Pearson, Mark J.; Thomas, Andrew M.; Scheel-Toellner, Dagmar; Raza, Karim; Buckley, Christopher D.; Falciani, Francesco

2015-01-01

264

HLA-B*5701 testing to predict abacavir hypersensitivity.  

PubMed

Abacavir is a nucleoside reverse transcriptase inhibitor used for combination antiretroviral therapy for treating human immunodeficiency virus (HIV) infection. An adverse effect from abacavir is a treatment-limiting hypersensitivity reaction, which can be severe and potentially life-threatening. Abacavir-induced hypersensitivity reaction has been associated with the presence of the major histocompatibility complex class I allele HLA-B*5701. A screening test for the HLA-B*5701 allele can assist clinicians to identify patients who are at risk of developing a hypersensitivity reaction to abacavir. PMID:21151380

Ma, Joseph D; Lee, Kelly C; Kuo, Grace M

2010-01-01

265

Carbamazepine-induced hypersensitivity syndrome in chronic schizophrenia.  

PubMed

Drug-induced hypersensitivity syndrome is a clinically important issue. We report a case of carbamazepine-induced hypersensitivity syndrome in a 35-year-old schizophrenia patient. This patient had no previous food or medication allergy history and presented a negative test result of HLA-B*1502 genotype. After 19 days exposure of carbamazepine, high fever up to 39.4 °C, leucopenia (1670/mm3), proteinuria and bilateral lung field infiltration were developed. These clinically significant physical conditions resolved after discontinuing carbamazepine. The importance of genetic susceptibility other than HLA-B*1502 should not be overlooked in drug-induced hypersensitivity syndrome. PMID:23153842

Pan, Chan-Wei; Yu, Chi-Hua; Liao, Ding-Lieh

2013-01-01

266

Successful Desensitization of a Patient with Rituximab Hypersensitivity  

PubMed Central

Rituximab is a monoclonal antibody which targets CD20 in B cells that is used for the treatment of CD20 positive oncologic and hematologic malignancies. Rituximab causes hypersensitivity reactions during infusions. The delay of treatment or loss of a highly efficient drug can be prevented by rapid drug desensitization method in patients who are allergic to rituximab. We report a low grade B cell non-Hodgkin lymphoma patient with rituximab hypersensitivity successfully treated with rapid drug desensitization. In experienced centers, drug desensitization is a novel modality to break through in case of hypersensitivity that should be considered. PMID:25685566

Ataca, Pinar; Atilla, Erden; Kendir, Resat; Bavbek, Sevim; Ozcan, Muhit

2015-01-01

267

Azathioprine hypersensitivity presenting as septic shock with encephalopathy  

PubMed Central

We present a case of azathioprine hypersensitivity presenting as septic shock with associated encephalopathy. The patient was presented with rapid onset of fever, hypotension, confusion and a rapidly declining conscious level. He was admitted to the intensive care unit where he received numerous invasive investigations and treatments with broad-spectrum antibiotics, antivirals and antifungals. All microbial cultures were negative. The patient—consistent with azathioprine hypersensitivity—made a spontaneous recovery after 7?days. The case shows that a time line of drug initiation is a key part of the medical history and consideration of azathioprine hypersensitivity could avoid unnecessary interventions and excessive antimicrobial use. PMID:23513015

James, Antonia; Blagojevic, Jelena; Benham, Stuart W; Cornall, Richard; Frater, John

2013-01-01

268

Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children  

ERIC Educational Resources Information Center

Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

2010-01-01

269

Conditioned fear as revealed by magnitude of startle response to an auditory stimulus  

Microsoft Academic Search

Male rats were trained on buzzer-shock presentations. In 15 animals, conditions produced a conditioned pain response; in the controls, conditions reduced or prevented formation of fear. The experimental group showed a significant progressive increase, extinction and spontaneous recovery in the average startle response whereas the controls changed but little.

Judson S. Brown; Harry I. Kalish; I. E. Farber

1951-01-01

270

The Pupillary Light Response Reveals the Focus of Covert Visual Attention  

PubMed Central

The pupillary light response is often assumed to be a reflex that is not susceptible to cognitive influences. In line with recent converging evidence, we show that this reflexive view is incomplete, and that the pupillary light response is modulated by covert visual attention: Covertly attending to a bright area causes a pupillary constriction, relative to attending to a dark area under identical visual input. This attention-related modulation of the pupillary light response predicts cuing effects in behavior, and can be used as an index of how strongly participants attend to a particular location. Therefore, we suggest that pupil size may offer a new way to continuously track the focus of covert visual attention, without requiring a manual response from the participant. The theoretical implication of this finding is that the pupillary light response is neither fully reflexive, nor under complete voluntary control, but is instead best characterized as a stereotyped response to a voluntarily selected target. In this sense, the pupillary light response is similar to saccadic and smooth pursuit eye movements. Together, eye movements and the pupillary light response maximize visual acuity, stabilize visual input, and selectively filter visual information as it enters the eye. PMID:24205144

Mathôt, Sebastiaan; van der Linden, Lotje; Grainger, Jonathan; Vitu, Françoise

2013-01-01

271

Cefazolin tolerance does not predict ceftriaxone hypersensitivity: unique side chains precipitate anaphylaxis.  

PubMed

A 48-year-old woman with a questionable history of an unspecified ceftriaxone allergy was treated with cefazolin for surgical antibiotic prophylaxis. After she tolerated cefazolin therapy for 4 days, the medical staff concluded that her allergy history was inaccurate, and she was treated with intravenous ceftriaxone for suspected nosocomial pneumonia. Approximately 10 minutes after the start of the infusion, the patient experienced anaphylaxis. Initial symptoms of oral angioedema and laryngopharyngeal constriction progressed to dyspnea, tachypnea, hypotension, and tachycardia, all of which quickly resolved after immediate treatment with hydrocortisone, diphenhydramine, and epinephrine. Skin testing with cefazolin, cefepime, and ceftriaxone revealed that the likely allergic determinant mediating the patient's hypersensitivity reaction was the unique ceftriaxone R2 side chain and not the beta-lactam ring, which initially was suspected by the physician. Immunoglobulin E-mediated hypersensitivity reactions to cephalosporins may occur due to antibody complexes with the beta-lactam ring or various cephalosporin side chains. Misconceptions regarding the nature of cephalosporin allergies complicate antibiotic selection for patients with questionable allergy histories and may lead to inappropriate drug reexposure and anaphylaxis. Detailed understanding of the antigenic determinants that mediate hypersensitivity reactions is essential for clinicians to avoid type 1 reactions in patients with a suspected allergy to cephalosporins. PMID:15162902

Poston, Sara A; Jennings, Heath R; Poe, Kevin L

2004-05-01

272

Role of soluble guanylate cyclase in the trigeminal subnucleus caudalis in capsaicin-induced muscle hypersensitivity.  

PubMed

Nitric oxide (NO) produces its effects by activating soluble guanylate cyclase (sGC). In the present study, we investigated the potential role of sGC in the subnucleus caudalis (Vc) in mediating masseter hypersensitivity under acute inflammatory condition in male Sprague-Dawley rats. First, our Western blot analysis revealed that sGC protein is reliably detected in the Vc. Subsequent immunohistochemical studies demonstrated that neuronal cell bodies in the superficial laminae of the Vc positively stained for sGC. Astrocytes in deeper lamina of the Vc also showed sGC immunoreactivity. We then tested whether intrathecal administration of sGC inhibitors, methylene blue (MB), and ODQ, in the Vc, attenuates masseter hypersensitivity induced by intramuscular injection of capsaicin. Intrathecal MB or ODQ significantly blocked the capsaicin-induced reduction of mechanical threshold to noxious stimulation of the masseter. These data indicate that the NO-sGC pathway in the Vc is involved in mediating orofacial muscle hypersensitivity under acute inflammatory conditions. PMID:17980861

Ro, Jin Y; Lee, Jongseok; Capra, Norman F; Zhang, Youping

2007-12-12

273

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

PubMed Central

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

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

2015-01-01

274

Evidence for oesophageal visceral hypersensitivity and aberrant symptom referral in patients with globus.  

PubMed

We tested the hypotheses that globus patients demonstrate oesophageal visceral hypersensitivity and aberrant viscerosomatic referral of oesophageal stimuli. Oesophageal visceral perception was assessed by oesophageal balloon distension and electrical stimulation in nine patients with globus and compared with 11 healthy controls. Oesophageal perception and pain thresholds were determined. Subjects recorded the area of thoracic viscerosomatic referral on a body map in response to each stimulus. All the patients reported their first sensation at balloon volumes between 2 and 6 mL whereas controls reported their first sensation at volumes between 3 and 14 mL (P = 0.03). All the patients reported pain at balloon volumes between 5 and 12 mL whereas controls experienced pain at volumes between 8 and 20 mL (P = 0.001). In response to electrical stimulation to the oesophagus patients and controls demonstrated comparable sensory thresholds. In response to oesophageal balloon distension seven of nine patients, but no controls, referred the sensation to the region at or above the suprasternal notch (P = 0.001). Similarly, significant differences in viscerosomatic referral pattern were observed in response to oesophageal electrical stimulation (P = 0.03). Patients with globus demonstrate oesophageal visceral hypersensitivity to mechanical distension. The differential responses to stretch and electrical stimuli may indicate that the hypersensitivity is a peripheral, rather than central, phenomenon. The aberrant referral of oesophageal sensations in response to both mechanical and electrical stimulation supports the hypothesis that referral of symptoms to the neck might be a central phenomenon. PMID:19422528

Chen, C L; Szczesniak, M M; Cook, I J

2009-11-01

275

Common garden experiments reveal uncommon responses across temperatures, locations, and species of ants  

E-print Network

of ants Shannon L. Pelini1,2 , Sarah E. Diamond3 , Heidi MacLean4 , Aaron M. Ellison1 , Nicholas J and spatial variation in responses to warming. Such experiments are useful for deter- mining if geographically

Sanders, Nathan J.

276

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

E-print Network

that initiates a well-characterized signaling cascade in cells exposed to ionizing radiation (IR). However response (DDR) complexes is unknown. We combined SILAC-based tandem mass spectrometry and a subcellular

277

BCL-2 family genetic profiling reveals microenvironment-specific determinants of chemotherapeutic response  

E-print Network

The Bcl-2 family encompasses a diverse set of apoptotic regulators that are dynamically activated in response to various cell-intrinsic and -extrinsic stimuli. An extensive variety of cell culture experiments have identified ...

Pritchard, Justin Robert

278

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

E-print Network

, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed biology of disease Keywords: glucose homeostasis; insulin sensitivity; metabolic profiling This is an open. Introduction Glucose homeostasis is a complex physiologic process invol- ving the orchestration of multiple

279

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

280

Clustering by Plasma Lipoprotein Profile Reveals Two Distinct Subgroups with Positive Lipid Response to Fenofibrate Therapy  

PubMed Central

Fibrates lower triglycerides and raise HDL cholesterol in dyslipidemic patients, but show heterogeneous treatment response. We used k-means clustering to identify three representative NMR lipoprotein profiles for 775 subjects from the GOLDN population, and study the response to fenofibrate in corresponding subgroups. The subjects in each subgroup showed differences in conventional lipid characteristics and in presence/absence of cardiovascular risk factors at baseline; there were subgroups with a low, medium and high degree of dyslipidemia. Modeling analysis suggests that the difference between the subgroups with low and medium dyslipidemia is influenced mainly by hepatic uptake dysfunction, while the difference between subgroups with medium and high dyslipidemia is influenced mainly by extrahepatic lipolysis disfunction. The medium and high dyslipidemia subgroups showed a positive, yet distinct lipid response to fenofibrate treatment. When comparing our subgroups to known subgrouping methods, we identified an additional 33% of the population with favorable lipid response to fenofibrate compared to a standard baseline triglyceride cutoff method. Compared to a standard HDL cholesterol cutoff method, the addition was 18%. In conclusion, by using constructing subgroups based on representative lipoprotein profiles, we have identified two subgroups of subjects with positive lipid response to fenofibrate therapy and with different underlying disturbances in lipoprotein metabolism. The total subgroup with positive lipid response to fenofibrate is larger than subgroups identified with baseline triglyceride and HDL cholesterol cutoffs. PMID:22719863

Parnell, Laurence D.; Lai, Chao-Qiang; Ordovás, José M.; de Graaf, Albert A.; van Ommen, Ben; Arnett, Donna K.

2012-01-01

281

Current trends in screening across ethnicities for hypersensitivity to abacavir.  

PubMed

Abacavir is a potent nucleoside analog reverse transcriptase inhibitor approved for the treatment of HIV infection. Approximately 5-8% of Caucasian patients receiving abacavir develop a hypersensitivity reaction, characterized by rash, fever and, occasionally, multisystemic involvement. Rechallenge with the drug can be fatal. The discovery of the mechanisms involved in this hypersensitivity reaction and the identification of tools for its prediction are the subject of this review. The most relevant finding is the recognition of a strong association between one specific haplotype at the HLA complex type I, HLA-B*5701, and the abacavir hypersensitivity reaction. The heterogeneity in the prevalence of HLA-B*5701 across distinct ethnicities accounts for differences in the risk of abacavir hypersensitivity reactions in distinct populations. PMID:18855539

Rodriguez-Nóvoa, Sonia; Soriano, Vincent

2008-10-01

282

Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity  

PubMed Central

Dentin hypersensitivity (DH) is a relatively common painful condition among dental problems. Although many studies have been performed regarding the diagnosis and treatment of DH, dental practitioners are still confused about the definite diagnosis and treatment.The use of lasers as a treatment for dentin hypersensitivity was first introduced in 1985.Laser treatment in dentin hypersensitivity is an interesting and controversial issue and many investigations have been done on its mechanism of action, advantages, and unclear points.The present literature review tries to go over the definition, diagnosis, etiology , predisposing factors, various laser types in the treatment of DH alone or in combination with topical desensitizing agents. Since a certain treatment has not yet introduced for dentin hypersensitivity, a combination of laser therapy and topical desensitizing factors ,can increase the success of the treatment compared with either treatments alone. PMID:25606300

Asnaashari, Mohammad; Moeini, Masoumeh

2013-01-01

283

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2012 CFR

...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

2012-04-01

284

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2013 CFR

...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

2013-04-01

285

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2011 CFR

...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

2011-04-01

286

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2014 CFR

...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

2014-04-01

287

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

PubMed

A 63-year-old man with multiple liver metastases from gastric cancer was treated with S-1 plus cisplatin; however, the number of multiple liver metastases increased. The patient received paclitaxel(PTX)treatment, but a hypersensitivity reaction occurred after administering the second dose; therefore, he received docetaxel treatment. A hypersensitivity reaction occurred after administering the first dose of docetaxel; therefore, he received irinotecan treatment. However, irinotecan administration was stopped because of severe diarrhea and weight reduction. Subsequently, at the patient's request, nab-PTX treatment was initiated by administering a premedication regimen of dexamethasone(8mg)and chlorpheniramine(10mg); no hypersensitivity reactions were reported thereafter. Nab-PTX is a contraindication; however, it might be possible to use nab-PTX for treating patients with PTX hypersensitivity. PMID:25131878

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

2014-07-01

288

Hypersensitivity to biological agents-updated diagnosis, management, and treatment.  

PubMed

Biological agents are used in the treatment of neoplastic, autoimmune, and inflammatory diseases and their clinical applications are becoming broader. Following their increased utilization, hypersensitivity reactions linked to these drugs have become more frequent, sometimes preventing the use of first-line therapies. The clinical presentation of hypersensitivity reactions to biological agents ranges from mild cutaneous manifestations to life-threatening reactions. In this scenario, rapid desensitization is a groundbreaking procedure that enables selected patients to receive the full treatment dose in a safe way, in spite of their immediate hypersensitivity reaction to the drug, and protects them against anaphylaxis. The aim of this review is to update and discuss some of the main biological agents used in clinical practice (rituximab, trastuzumab, cetuximab, ofatumumab, tocilizumab, brentuximab, omalizumab, and tumor necrosis factor alpha inhibitor agents) and their associated hypersensitivity reactions, including clinical presentations, diagnosis, and treatment in the acute setting. In addition, novel management options with rapid desensitization are presented. PMID:25754718

Galvão, Violeta Régnier; Castells, Mariana C

2015-01-01

289

Transcriptome analysis of sorbic acid-stressed Bacillus subtilis reveals a nutrient limitation response and indicates plasma membrane remodeling  

Microsoft Academic Search

The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses

Alex Ter Beek; Bart J. F. Keijser; Andre Boorsma; Anna Zakrzewska; Rick Orij; Gertien J. Smits

2008-01-01

290

Aspririn and nonsteroidal anti-inflammatory drug hypersensitivity  

Microsoft Academic Search

Acetylsalicylic acid (ASA) or aspirin and nonsteroidal anti-inflammatory drug (NSAID) sensitivities encompass a diverse group\\u000a of both pharmacological and hypersensitivity reactions. Conventionally, hypersensitivities include aspirin-exacerbated respiratory\\u000a disease (AERD), ASA-induced urticaria, and anaphylaxis. With an increasing prevalence of coronary artery disease in an aging\\u000a population, aspirin continues to play a significant role in cardiac prophylaxis in a large patient population. Invariably,

James S. W. Kong; Suzanne S. Teuber; M. Eric Gershwin

2007-01-01

291

Assessing Hypersensitive Narcissism: A Reexamination of Murray's Narcism Scale  

Microsoft Academic Search

A new measure of hypersensitive narcissism was derived by correlating the items of H. A. Murray's (1938) Narcism Scale with an MMPI-based composite measure of covert narcissism. In three samples of college students (totalN= 403), 10 items formed a reliable measure: the Hypersensitive Narcissism Scale (HSNS). The new HSNS and the MMPI-based composite showed similar patterns of correlations with the

Holly M. Hendin; Jonathan M. Cheek

1997-01-01

292

Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update  

PubMed Central

After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal anti-inflammatory drugs are the second cause of hypersensitivity to drugs. Acute manifestations affect the respiratory tract (aspirin exacerbated respiratory disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis). Correct diagnosis and treatment in order to prevent unnecessary morbidity and the potential risk of death from these severe reactions, and to provide proper medical advice on future drug use frequently requires the participation of allergology specialists familiar with these clinical conditions.

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

2010-01-01

293

A World Allergy Organization International Survey on Diagnostic Procedures and Therapies in Drug Allergy/Hypersensitivity  

PubMed Central

Objective To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). Methods A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009. Results Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro–specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens–Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. Conclusions Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies. PMID:23268453

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

2011-01-01

294

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

SciTech Connect

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

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

2010-06-25

295

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity  

PubMed Central

Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive. PMID:18400801

Audicana, M. Teresa; Kennedy, Malcolm W.

2008-01-01

296

Differential reproductive responses to stress reveal the role of life-history strategies within a species  

PubMed Central

Life-history strategies describe that ‘slow’- in contrast to ‘fast’-living species allocate resources cautiously towards reproduction to enhance survival. Recent evidence suggests that variation in strategies exists not only among species but also among populations of the same species. Here, we examined the effect of experimentally induced stress on resource allocation of breeding seabirds in two populations with contrasting life-history strategies: slow-living Pacific and fast-living Atlantic black-legged kittiwakes. We tested the hypothesis that reproductive responses in kittiwakes under stress reflect their life-history strategies. We predicted that in response to stress, Pacific kittiwakes reduce investment in reproduction compared with Atlantic kittiwakes. We exposed chick-rearing kittiwakes to a short-term (3-day) period of increased exogenous corticosterone (CORT), a hormone that is released during food shortages. We examined changes in baseline CORT levels, parental care and effects on offspring. We found that kittiwakes from the two populations invested differently in offspring when facing stress. In response to elevated CORT, Pacific kittiwakes reduced nest attendance and deserted offspring more readily than Atlantic kittiwakes. We observed lower chick growth, a higher stress response in offspring and lower reproductive success in response to CORT implantation in Pacific kittiwakes, whereas the opposite occurred in the Atlantic. Our findings support the hypothesis that life-history strategies predict short-term responses of individuals to stress within a species. We conclude that behaviour and physiology under stress are consistent with trade-off priorities as predicted by life-history theory. We encourage future studies to consider the pivotal role of life-history strategies when interpreting inter-population differences of animal responses to stressful environmental events. PMID:24089339

Schultner, J.; Kitaysky, A. S.; Gabrielsen, G. W.; Hatch, S. A.; Bech, C.

2013-01-01

297

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

PubMed Central

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

2013-01-01

298

Simultaneous dual-task performance reveals parallel response selection after practice  

NASA Technical Reports Server (NTRS)

E. H. Schumacher, T. L. Seymour, J. M. Glass, D. E. Kieras, and D. E. Meyer (2001) reported that dual-task costs are minimal when participants are practiced and give the 2 tasks equal emphasis. The present research examined whether such findings are compatible with the operation of an efficient response selection bottleneck. Participants trained until they were able to perform both tasks simultaneously without interference. Novel stimulus pairs produced no reaction time costs, arguing against the development of compound stimulus-response associations (Experiment 1). Manipulating the relative onsets (Experiments 2 and 4) and durations (Experiments 3 and 4) of response selection processes did not lead to dual-task costs. The results indicate that the 2 tasks did not share a bottleneck after practice.

Hazeltine, Eliot; Teague, Donald; Ivry, Richard B.

2002-01-01

299

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 PMID:22808006

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

2012-01-01

300

Common garden experiments reveal uncommon responses across temperatures, locations, and species of ants  

PubMed Central

Population changes and shifts in geographic range boundaries induced by climate change have been documented for many insect species. On the basis of such studies, ecological forecasting models predict that, in the absence of dispersal and resource barriers, many species will exhibit large shifts in abundance and geographic range in response to warming. However, species are composed of individual populations, which may be subject to different selection pressures and therefore may be differentially responsive to environmental change. Asystematic responses across populations and species to warming will alter ecological communities differently across space. Common garden experiments can provide a more mechanistic understanding of the causes of compositional and spatial variation in responses to warming. Such experiments are useful for determining if geographically separated populations and co-occurring species respond differently to warming, and they provide the opportunity to compare effects of warming on fitness (survivorship and reproduction). We exposed colonies of two common ant species in the eastern United States, Aphaenogaster rudis and Temnothorax curvispinosus, collected along a latitudinal gradient from Massachusetts to North Carolina, to growth chamber treatments that simulated current and projected temperatures in central Massachusetts and central North Carolina within the next century. Regardless of source location, colonies of A. rudis, a keystone seed disperser, experienced high mortality and low brood production in the warmest temperature treatment. Colonies of T. curvispinosus from cooler locations experienced increased mortality in the warmest rearing temperatures, but colonies from the warmest locales did not. Our results suggest that populations of some common species may exhibit uniform declines in response to warming across their geographic ranges, whereas other species will respond differently to warming in different parts of their geographic ranges. Our results suggest that differential responses of populations and species must be incorporated into projections of range shifts in a changing climate. PMID:23301168

Pelini, Shannon L; Diamond, Sarah E; MacLean, Heidi; Ellison, Aaron M; Gotelli, Nicholas J; Sanders, Nathan J; Dunn, Robert R

2012-01-01

301

Neuron-glia crosstalk gets serious: Role in pain hypersensitivity  

PubMed Central

Purpose of review Recent studies show that peripheral injury activates both neuronal and non-neuronal or glial components of the peripheral and central cellular circuitry. The subsequent neuron-glial interactions contribute to pain hypersensitivity. This review will briefly discuss novel findings that have shed light on the cellular mechanisms of neuron-glial interactions in persistent pain. Recent findings Two fundamental questions related to neuron-glial interactions in pain mechanisms have been addressed: 1) what are the signals that lead to central glial activation after injury and 2) how glial cells affect CNS neuronal activity and promote hyperalgesia. Summary Evidence indicates that central glial activation depends on nerve inputs from the site of injury and release of chemical mediators. Hematogenous immune cells may migrate/infiltrate to the brain and circulating inflammatory mediators may penetrate the blood brain barrier to participate in central glial responses to injury. Inflammatory cytokines such as IL-1? released from glia may facilitate pain transmission through its coupling to neuronal glutamate receptors. This bidirectional neuron-glial signaling plays a key role in glial activation, cytokine production and the initiation and maintenance of hyperalgesia. Recognition of the contribution of the mutual neuron-glial interactions to central sensitization and hyperalgesia prompts new treatment for chronic pain. PMID:18784481

Ren, Ke; Dubner, Ronald

2009-01-01

302

Hypersensitivity to Aeroallergens in Patients with Nasobronchial Allergy  

PubMed Central

ABSTRACT Background: Aeroallergens are the most common causes of allergy. Aim: The aim of this study was to determine hypersensitivity to aeroallergens in patients with nasobronchial allergy. Methods: This retrospective population study included 2254 patients with nasobronchial allergy, from late adolescents to adults. Their response to aeroallergens was assessed by skin prick tests. Results: More patients had rhinitis (72.7%), than asthma (27.6%). Although majority of patients were female, allergy is more common in men than in women (p<0.05). Both groups of patients had the greatest number of positive skin prick tests for Dermatophagoides pteronyssinus (27.5%) and weed pollens (21.9%), followed by grass (18.3%) and tree pollens (10.1%). Ragweed is the most common positive weed pollen in both groups, more in patients with rhinitis (p=0.022). The cocksfoot is the most common grass pollen in rhinitis group (15.3%), but meadow grass (12.6%) in asthma patients. Birch is the most common tree allergen in the both groups. Conclusions: More patients with nasobronchial allergy have rhinitis than asthma. Skin prick tests are usually positive for Dermatophagoides pteronyssinus and weed pollens, followed by grass and tree pollens, and they are more common positive in patients with rhinitis than asthma. PMID:24937928

Balaban, Jagoda; Bijelic, Radojka; Milicevic, Snjezana

2014-01-01

303

Visceral hypersensitivity and intolerance symptoms in lactose malabsorption.  

PubMed

Lactose malabsorption is not always associated with intolerance symptoms. The factors responsible for symptom onset are not yet completely known. As differences in visceral sensitivity may play a role in the pathogenesis of functional symptoms, we evaluated whether an alteration of visceral sensitivity is present in subjects with lactose intolerance. Thirty subjects, recruited regardless of whether they were aware of their capacity to absorb lactose, underwent an evaluation of intestinal hydrogen production capacity by lactulose breath test, followed by an evaluation of lactose absorption by hydrogen breath test after lactose administration and subsequently an evaluation of recto-sigmoid sensitivity threshold during fasting and after lactulose administration, to ascertain whether fermentation modifies intestinal sensitivity. The role of differences in gastrointestinal transit was excluded by gastric emptying and mouth-to-caecum transit time by (13)C-octanoic and lactulose breath tests. Lactulose administration induced a significant reduction of discomfort threshold in subjects with lactose intolerance but not in malabsorbers without intolerance symptoms or in subjects with normal lactose absorption. Perception threshold showed no changes after lactulose administration. Severity of symptoms in intolerant subjects was significantly correlated with the reduction of discomfort thresholds. Visceral hypersensitivity should be considered in the induction of intolerance symptoms in subjects with lactose malabsorption. PMID:17973635

Di Stefano, M; Miceli, E; Mazzocchi, S; Tana, P; Moroni, F; Corazza, G R

2007-11-01

304

Rapid response to habitat restoration by the perennial Primula veris as revealed by demographic monitoring  

Microsoft Academic Search

The demography of Primula veris, a typical species of the species-rich Mesobromion grasslands, was investigated at two contrasting habitats in Eastern Belgium. Both a forested site and a clear-cut parcel were part of formerly larger calcareous grassland areas. By monitoring the demographic response of the target species, this study attempts to clarify the differences in fecundity, growth and survival between

Patrick Endels; Hans Jacquemyn; Rein Brys; Martin Hermy

2005-01-01

305

Quantitative Phosphoproteomics Reveals the Role of Protein Arginine Phosphorylation in the Bacterial Stress Response*  

PubMed Central

Arginine phosphorylation is an emerging protein modification implicated in the general stress response of Gram-positive bacteria. The modification is mediated by the arginine kinase McsB, which phosphorylates and inactivates the heat shock repressor CtsR. In this study, we developed a mass spectrometric approach accounting for the peculiar chemical properties of phosphoarginine. The improved methodology was used to analyze the dynamic changes in the Bacillus subtilis arginine phosphoproteome in response to different stress situations. Quantitative analysis showed that a B. subtilis mutant lacking the YwlE arginine phosphatase accumulated a strikingly large number of arginine phosphorylations (217 sites in 134 proteins), however only a minor fraction of these sites was increasingly modified during heat shock or oxidative stress. The main targets of McsB-mediated arginine phosphorylation comprise central factors of the stress response system including the CtsR and HrcA heat shock repressors, as well as major components of the protein quality control system such as the ClpCP protease and the GroEL chaperonine. These findings highlight the impact of arginine phosphorylation in orchestrating the bacterial stress response. PMID:24263382

Schmidt, Andreas; Trentini, Débora Broch; Spiess, Silvia; Fuhrmann, Jakob; Ammerer, Gustav; Mechtler, Karl; Clausen, Tim

2014-01-01

306

Shadow response in the blind cavefish Astyanax reveals conservation of a functional pineal eye.  

PubMed

The blind cavefish Astyanax mexicanus undergoes bilateral eye degeneration during embryonic development. Despite the absence of light in the cave environment, cavefish have retained a structurally intact pineal eye. We show here that contrary to visual degeneration in the bilateral eyes, the cavefish pineal eye has conserved the ability to detect light. Larvae of two different Astyanax cavefish populations and the con-specific sighted surface-dwelling form (surface fish) respond similarly to light dimming by shading the pineal eye. As a response to shading, cavefish larvae swim upward vertically. This behavior resembles that of amphibian tadpoles rather than other teleost larvae, which react to shadows by swimming downward. The shadow response is highest at 1.5-days post-fertilization (d.p.f.), gradually diminishes, and is virtually undetectable by 7.5 d.p.f. The shadow response was substantially reduced after surgical removal of the pineal gland from surface fish or cavefish larvae, indicating that it is based on pineal function. In contrast, removal of one or both bilateral eye primordia did not affect the shadow response. Consistent with its light detecting capacity, immunocytochemical studies indicate that surface fish and cavefish pineal eyes express a rhodopsin-like antigen, which is undetectable in the degenerating bilateral eyes of cavefish larvae. We conclude that light detection by the pineal eye has been conserved in cavefish despite a million or more years of evolution in complete darkness. PMID:18203983

Yoshizawa, Masato; Jeffery, William R

2008-02-01

307

Shadow response in the blind cavefish Astyanax reveals conservation of a functional pineal eye  

PubMed Central

SUMMARY The blind cavefish Astyanax mexicanus undergoes bilateral eye degeneration during embryonic development. Despite the absence of light in the cave environment, cavefish have retained a structurally intact pineal eye. We show here that contrary to visual degeneration in the bilateral eyes, the cavefish pineal eye has conserved the ability to detect light. Larvae of two different Astyanax cavefish populations and the con-specific sighted surface-dwelling form (surface fish) respond similarly to light dimming by shading the pineal eye. As a response to shading, cavefish larvae swim upward vertically. This behavior resembles that of amphibian tadpoles rather than other teleost larvae, which react to shadows by swimming downward. The shadow response is highest at 1.5-days post-fertilization (d.p.f.), gradually diminishes, and is virtually undetectable by 7.5 d.p.f. The shadow response was substantially reduced after surgical removal of the pineal gland from surface fish or cavefish larvae, indicating that it is based on pineal function. In contrast, removal of one or both bilateral eye primordia did not affect the shadow response. Consistent with its light detecting capacity, immunocytochemical studies indicate that surface fish and cavefish pineal eyes express a rhodopsin-like antigen, which is undetectable in the degenerating bilateral eyes of cavefish larvae. We conclude that light detection by the pineal eye has been conserved in cavefish despite a million or more years of evolution in complete darkness. PMID:18203983

Yoshizawa, Masato; Jeffery, William R.

2013-01-01

308

How We Know It Hurts: Item Analysis of Written Narratives Reveals Distinct Neural Responses to Others'  

E-print Network

to Others' Physical Pain and Emotional Suffering Emile Bruneau*, Nicholas Dufour, Rebecca Saxe Department and suffering of others. In the current study, we directly compared neural responses to others' physical pain and emotional suffering by presenting participants (n = 41) with 96 verbal stories, each describing

Saxe, Rebecca

309

Tomato Transcriptional Changes in Response to Clavibacter michiganensis subsp. michiganensis Reveal  

E-print Network

, causing bacterial wilt and canker disease in tomato (Solanum lycopersicum). Host responses to gram a Role for Ethylene in Disease Development1[W] Vasudevan Balaji, Maya Mayrose, Ofra Sherf, Jasmine Jacob-positive bacteria and molecular mechanisms associated with the development of disease symptoms caused by Cmm

Sessa, Guido

310

The pupil response reveals increased listening effort when it is difficult to focus attention.  

PubMed

Recent studies have shown that prior knowledge about where, when, and who is going to talk improves speech intelligibility. How related attentional processes affect cognitive processing load has not been investigated yet. In the current study, three experiments investigated how the pupil dilation response is affected by prior knowledge of target speech location, target speech onset, and who is going to talk. A total of 56 young adults with normal hearing participated. They had to reproduce a target sentence presented to one ear while ignoring a distracting sentence simultaneously presented to the other ear. The two sentences were independently masked by fluctuating noise. Target location (left or right ear), speech onset, and talker variability were manipulated in separate experiments by keeping these features either fixed during an entire block or randomized over trials. Pupil responses were recorded during listening and performance was scored after recall. The results showed an improvement in performance when the location of the target speech was fixed instead of randomized. Additionally, location uncertainty increased the pupil dilation response, which suggests that prior knowledge of location reduces cognitive load. Interestingly, the observed pupil responses for each condition were consistent with subjective reports of listening effort. We conclude that communicating in a dynamic environment like a cocktail party (where participants in competing conversations move unpredictably) requires substantial listening effort because of the demands placed on attentional processes. PMID:25732724

Koelewijn, Thomas; de Kluiver, Hilde; Shinn-Cunningham, Barbara G; Zekveld, Adriana A; Kramer, Sophia E

2015-05-01

311

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. PMID:21695167

Otálora-Luna, Fernando; Dickens, Joseph C.

2011-01-01

312

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. PMID:17555569

Martin, Samuel AM; Zou, Jun; Houlihan, Dominic F; Secombes, Christopher J

2007-01-01

313

Hypersensitivity pneumonitis: the dug-well lung.  

PubMed

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is caused by a variety of environmental agents and may present as occult respiratory illness. HP represents a potentially curable subgroup of interstitial lung disease. This study was designed to examine a group of patients with HP due to a unique mechanism of environmental exposure. Five patients with HP were retrospectively identified, from our hospital records, admitted during the period of March 2007 to February 2011 with history of exposure to dug wells. The mode of exposure was specified as multiple entries into a dug well for different reasons. Other modes of exposure were considered as criteria of exclusion. All of the five patients had subacute HP based on available clinical, radiographic, immunologic, and supportive evidence and exposure. There were additional allergic bronchopulmonary aspergillosis-like features in one patient who did not have antecedent asthma. The evaluation of patient records indicated a fungal etiology. The air and soil from selected wells were tested for fungal organisms. Both settings grew Aspergillus as the predominant species. This novel mechanism of HP is labeled "dug-well lung" because the disease was attributed to exposure to dug wells. Lung disease may result from exposure to a dug well. Farmers or mechanics, climbing down these damp wells for a multitude of reasons, are prone to develop HP. The public health care personnel and farming community should be made aware of this potential occupation-related health hazard. PMID:24169053

Sharma, Bharat Bhushan; Singh, Sheetu; Singh, Virendra

2013-01-01

314

Dentin hypersensitivity: Recent trends in management  

PubMed Central

Dentinal hypersensitivity (DH) is a common clinical condition usually associated with exposed dentinal surfaces. It can affect patients of any age group and most commonly affects the canines and premolars of both the arches. This article concisely reviews the patho-physiology, mechanism and clinical management of the DH. Treatment of DH should start with an accurate diagnosis. Differential diagnosis should be made and all other probable causes should be excluded. An often neglected phase of clinical management of DH is the identification and treatment of the causative factors of DH. By removing the etiological factors, the condition can be even prevented from occurring or recurring. There are various treatment modalities available which can be used at home or may be professionally applied. The “at home” desensitizing agents include toothpastes, mouthwashes or chewing gums and they act by either occluding the dentinal tubules or blocking the neural transmission. This article also discusses the recent treatment options like bioglass, Portland cement, lasers and casein phosphopeptide. PMID:21217949

Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

2010-01-01

315

Granulomas and giant cells in hypersensitivity pneumonitis.  

PubMed

Hypersensitivity pneumonitis (HP) is an immunologically mediated form of diffuse lung disease, with histopathologic features that include cellular bronchiolitis, interstitial pneumonia, poorly formed granulomas, isolated multinucleated giant cells (MNGCs), organizing pneumonia, and interstitial fibrosis. This study describes the clinical and histopathologic findings in a retrospective series of 40 consecutive patients diagnosed with HP at the Mayo Clinic in Rochester, MN, between 1997 and 2011. Because the literature indicates that granulomas and MNGCs are located in the interstitium, particular attention was given to their distribution. Of the 40 patients, 33 underwent surgical lung biopsy and 7 underwent lung transplantation. Thirty-eight (95%) patients had interstitial pneumonia; 37 (93%), cellular bronchiolitis; 32 (80%), nonnecrotizing granulomas; 31 (78%), isolated MNGCs; 34 (85%) organizing pneumonia, and 31 (78%); interstitial fibrosis. In 27 cases, the granulomas were within airspaces; and in 26, they were interstitial. In 25 cases, MNGCs were within airspaces; and in 24, they were interstitial. In 3 (8%) cases, both granulomas and MNGCs were seen only within airspaces. Interstitial fibrosis was centrilobular in 22 cases, resembled usual interstitial pneumonia in 18 cases, and resembled nonspecific interstitial pneumonia in 11 cases. The "classic triad" of bronchiolitis, interstitial pneumonia, and granulomas was seen in 29 (73%) cases and was most frequent in biopsy than explant specimens (P = .004). This study confirms that granulomas and MNGCs are not confined to the pulmonary interstitium in HP. PMID:25694347

Castonguay, Mathieu C; Ryu, Jay H; Yi, Eunhee S; Tazelaar, Henry D

2015-04-01

316

Severe dapsone hypersensitivity syndrome in a child  

PubMed Central

Dapsone (4,4'-diaminodiphenylsulfone, DDS), a potent anti-inflammatory agent, is widely used in the treatment of leprosy and several chronic inflammatory skin diseases. Dapsone therapy rarely results in development of dapsone hypersensitivity syndrome, which is characterized by fever, hepatitis, generalized exfoliative dermatitis, and lymphadenopathy. Here, we describe the case of an 11-year-old Korean boy who initially presented with high fever, a morbilliform skin rash, generalized lymphadenopathy, hepatosplenomegaly, and leukopenia after 6 weeks of dapsone intake. Subsequently, he exhibited cholecystitis, gingivitis, colitis, sepsis, aseptic meningitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, pneumonia, pleural effusions, peritonitis, bronchiectatic changes, exfoliative dermatitis, and acute renal failure. After 2 months of supportive therapy, and prednisolone and antibiotic administration, most of the systemic symptoms resolved, with the exception of exfoliative dermatitis and erythema, which ameliorated over the following 4 months. Agranulocytosis, atypical lymphocytosis, aseptic meningitis, and bronchiectatic changes along with prolonged systemic symptoms with exfoliative dermatitis were the most peculiar features of the present case. PMID:23807893

Choi, So Yoon; Hwang, Ho Yeon; Lee, Jung Hyun; Jang, Min Soo

2013-01-01

317

Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.  

PubMed

Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy. PMID:25604826

Biswas, Nidhan K; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N; Tripathy, Laxmi N; Basu, Sunandan K; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

2015-01-01

318

Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM  

PubMed Central

Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy. PMID:25604826

Biswas, Nidhan K.; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N.; Tripathy, Laxmi N.; Basu, Sunandan K.; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

2015-01-01

319

Adaptive responses reveal contemporary and future ecotypes in a desert shrub  

USGS Publications Warehouse

Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species–climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep clines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are needed to inform restoration and management planning. We propose four transfer zones in blackbrush that correspond to areas currently dominated by cool-adapted and warm-adapted ecotypes in each of the two ecoregions.

Richardson, Bryce A.; Kitchen, Stanley G.; Pendleton, Rosemary L.; Pendleton, Burton K.; Germino, Matthew J.; Rehfeldt, Gerald E.; Meyer, Susan E.

2014-01-01

320

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. PMID:24340192

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

2013-01-01

321

Adaptive responses reveal contemporary and future ecotypes in a desert shrub.  

PubMed

Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species-climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep dines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are needed to inform restoration and management planning. We propose four transfer zones in blackbrush that correspond to areas currently dominated by cool-adapted and warm-adapted ecotypes in each of the two ecoregions. PMID:24689151

Richardson, Bryce A; Kitchen, Stanley G; Pendleton, Rosemary L; Pendleton, Burton K; Germino, Matthew J; Rehfeldt, Gerald E; Meyer, Susan E

2014-03-01

322

Genome wide transcriptome analysis reveals ABA mediated response in Arabidopsis during gold (AuCl?4) treatment  

PubMed Central

The unique physico-chemical properties of gold nanoparticles (AuNPs) find manifold applications in diagnostics, medicine and catalysis. Chemical synthesis produces reactive AuNPs and generates hazardous by-products. Alternatively, plants can be utilized to produce AuNPs in an eco-friendly manner. To better control the biosynthesis of AuNPs, we need to first understand the detailed molecular response induced by AuCl?4 In this study, we carried out global transcriptome analysis in root tissue of Arabidopsis grown for 12- h in presence of gold solution (HAuCl4) using the novel unbiased Affymetrix exon array. Transcriptomics analysis revealed differential regulation of a total of 704 genes and 4900 exons. Of these, 492 and 212 genes were up- and downregulated, respectively. The validation of the expressed key genes, such as glutathione-S-transferases, auxin responsive genes, cytochrome P450 82C2, methyl transferases, transducin (G protein beta subunit), ERF transcription factor, ABC, and MATE transporters, was carried out through quantitative RT-PCR. These key genes demonstrated specific induction under AuCl4? treatment relative to other heavy metals, suggesting a unique plant-gold interaction. GO enrichment analysis reveals the upregulation of processes like oxidative stress, glutathione binding, metal binding, transport, and plant hormonal responses. Changes predicted in biochemical pathways indicated major modulation in glutathione mediated detoxification, flavones and derivatives, and plant hormone biosynthesis. Motif search analysis identified a highly significant enriched motif, ACGT, which is an abscisic acid responsive core element (ABRE), suggesting the possibility of ABA- mediated signaling. Identification of abscisic acid response element (ABRE) points to the operation of a predominant signaling mechanism in response to AuCl?4 exposure. Overall, this study presents a useful picture of plant-gold interaction with an identification of candidate genes involved in nanogold synthesis. PMID:25506348

Shukla, Devesh; Krishnamurthy, Sneha; Sahi, Shivendra V.

2014-01-01

323

Characterization of the immunogenetic basis of ultraviolet-B light effects on contact hypersensitivity induction.  

PubMed Central

Ultraviolet-B (UVB) light has proven to be deleterious to the skin immune system in mice, and one major consequence is impairment of the induction of contact hypersensitivity (CH) to haptens applied to UVB-exposed skin. It has been shown recently that the damaging effects of UVB on CH are mediated primarily by tumour necrosis factor-alpha (TNF-alpha). Moreover, not all strains of mice are equally susceptible to the deleterious effects of UVB. Mice that develop CH when hapten is applied to UVB-exposed skin are termed UVB-resistant (UVB-R), whereas mice that fail to acquire CH under these circumstances are termed UVB-susceptible (UVB-S). In the present experiments, we have characterized the UVB-susceptibility of numerous, genetically disparate inbred strains of mice by applying dinitrofluorobenzene (DNFB) epicutaneously to normal and to UVB-exposed body wall skin. The results indicate that the intensities of CH responses of these different strains were distributed in a bimodal fashion, with means at 92% and 28.5% of positive control responses. Among the strains with CH values distributed around the higher mean (i.e. UVB-R mice), the intensity of CH responses after UVB irradiation was uniformly greater than 75% of the intensity found among their positive controls. By contrast, among the strains with CH values distributed around the lower mean (i.e. UVB-S mice), the intensity of CH responses after UVB exposure was uniformly less than 60% of the intensity displayed by their positive controls. The phenotypic traits of UVB-S and UVB-R appear, therefore, to be genetically determined. To that end, we provide in this report additional evidence that UVB-S is a polygenically determined trait that is dictated by polymorphisms at a locus within H-2, and at the Lps locus. Resistance to UVB radiation is a recessive trait, and requires homozygosity of resistance alleles at one or both of the two participating loci, whereas UVB-S acts as a dominant trait. Among H-2 congenic strains of mice that are lipopolysaccharide (LPS)-sensitive (Lpsn), UVB radiation impaired the induction of CH to DNFB in all mice except those of the H-2d and H-2a haplotypes. Thus, UVB-susceptibility is dictated by alleles at two, independent genetic loci that can influence transcriptional and translational activity of the Tnf-alpha gene. The potential biological and medical meaning of regulatory polymorphisms governing TNF-alpha production in the skin may be revealed by the recent demonstration that UVB-susceptibility and UVB-resistance are phenotypic traits in humans.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8206509

Kurimoto, I; Streilein, J W

1994-01-01

324

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. 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

2014-01-01

325

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. PMID:24574395

Pérez-Cidoncha, Maite; Killip, Marian J.; Oliveros, Juan C.; Asensio, Víctor J.; Fernández, Yolanda; Bengoechea, José A.; Randall, Richard E.

2014-01-01

326

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates  

PubMed Central

Vertebrate innate immunity is the first line of defense against an invading pathogen and has long been assumed to be largely unspecific with respect to parasite/pathogen species. However, recent phenotypic evidence suggests that immunogenetic variation, i.e. allelic variability in genes associated with the immune system, results in host-parasite genotype-by-genotype interactions and thus specific innate immune responses. Immunogenetic variation is common in all vertebrate taxa and this reflects an effective immunological function in complex environments. However, the underlying variability in host gene expression patterns as response of innate immunity to within-species genetic diversity of macroparasites in vertebrates is unknown. We hypothesized that intra-specific variation among parasite genotypes must be reflected in host gene expression patterns. Here we used high-throughput RNA-sequencing to examine the effect of parasite genotypes on gene expression patterns of a vertebrate host, the three-spined stickleback (Gasterosteus aculeatus). By infecting naïve fish with distinct trematode genotypes of the species Diplostomum pseudospathaceum we show that gene activity of innate immunity in three-spined sticklebacks depended on the identity of an infecting macroparasite genotype. In addition to a suite of genes indicative for a general response against the trematode we also find parasite-strain specific gene expression, in particular in the complement system genes, despite similar infection rates of single clone treatments. The observed discrepancy between infection rates and gene expression indicates the presence of alternative pathways which execute similar functions. This suggests that the innate immune system can induce redundant responses specific to parasite genotypes. PMID:25254967

Haase, David; Rieger, Jennifer K.; Witten, Anika; Stoll, Monika; Bornberg-Bauer, Erich; Kalbe, Martin; Reusch, Thorsten B. H.

2014-01-01

327

Multivariate genetic analysis of plant responses to water deficit and high temperature revealed contrasting adaptive strategies.  

PubMed

How genetic factors control plant performance under stressful environmental conditions is a central question in ecology and for crop breeding. A multivariate framework was developed to examine the genetic architecture of performance-related traits in response to interacting environmental stresses. Ecophysiological and life history traits were quantified in the Arabidopsis thaliana Ler × Cvi mapping population exposed to constant soil water deficit and high air temperature. The plasticity of the genetic variance-covariance matrix (G-matrix) was examined using mixed-effects models after regression into principal components. Quantitative trait locus (QTL) analysis was performed on the predictors of genotype effects and genotype by environment interactions (G × E). Three QTLs previously identified for flowering time had antagonistic G × E effects on carbon acquisition and the other traits (phenology, growth, leaf morphology, and transpiration). This resulted in a size-dependent response of water use efficiency (WUE) to high temperature but not soil water deficit, indicating that most of the plasticity of carbon acquisition and WUE to temperature is controlled by the loci that control variation of development, size, growth, and transpiration. A fourth QTL, MSAT2.22, controlled the response of carbon acquisition to specific combinations of watering and temperature irrespective of plant size and development, growth, and transpiration rate, which resulted in size-independent plasticity of WUE. These findings highlight how the strategies to optimize plant performance may differ in response to water deficit and high temperature (or their combination), and how different G × E effects could be targeted to improve plant tolerance to these stresses. PMID:25246443

Vasseur, François; Bontpart, Thibaut; Dauzat, Myriam; Granier, Christine; Vile, Denis

2014-12-01

328

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. PMID:24808101

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

2014-01-01

329

Multivariate genetic analysis of plant responses to water deficit and high temperature revealed contrasting adaptive strategies  

PubMed Central

How genetic factors control plant performance under stressful environmental conditions is a central question in ecology and for crop breeding. A multivariate framework was developed to examine the genetic architecture of performance-related traits in response to interacting environmental stresses. Ecophysiological and life history traits were quantified in the Arabidopsis thaliana Ler×Cvi mapping population exposed to constant soil water deficit and high air temperature. The plasticity of the genetic variance–covariance matrix (G-matrix) was examined using mixed-effects models after regression into principal components. Quantitative trait locus (QTL) analysis was performed on the predictors of genotype effects and genotype by environment interactions (G×E). Three QTLs previously identified for flowering time had antagonistic G×E effects on carbon acquisition and the other traits (phenology, growth, leaf morphology, and transpiration). This resulted in a size-dependent response of water use efficiency (WUE) to high temperature but not soil water deficit, indicating that most of the plasticity of carbon acquisition and WUE to temperature is controlled by the loci that control variation of development, size, growth, and transpiration. A fourth QTL, MSAT2.22, controlled the response of carbon acquisition to specific combinations of watering and temperature irrespective of plant size and development, growth, and transpiration rate, which resulted in size-independent plasticity of WUE. These findings highlight how the strategies to optimize plant performance may differ in response to water deficit and high temperature (or their combination), and how different G×E effects could be targeted to improve plant tolerance to these stresses. PMID:25246443

Vasseur, François; Bontpart, Thibaut; Dauzat, Myriam; Granier, Christine; Vile, Denis

2014-01-01

330

Correlation of transcriptomic responses and metal bioaccumulation in Mytilus edulis L. reveals early indicators of stress.  

PubMed

Marine biomonitoring programs in the U.S. and Europe have historically relied on monitoring tissue concentrations of bivalves to monitor contaminant levels and ecosystem health. By integrating 'omic methods with these tissue residue approaches we can uncover mechanistic insight to link tissue concentrations to potential toxic effects. In an effort to identify novel biomarkers and better understand the molecular toxicology of metal bioaccumulation in bivalves, we exposed the blue mussel, Mytilus edulis L., to sub-lethal concentrations (0.54 ?M) of cadmium, lead, and a Cd+Pb mixture. Metal concentrations were measured in gill tissues at 1, 2, and 4 weeks, and increased linearly over the 4 week duration. In addition, there was evidence that Pb interfered with Cd uptake in the mixture treatment. Using a 3025 sequence microarray for M. edulis, we performed transcriptomic analysis, identifying 57 differentially expressed sequences. Hierarchical clustering of these sequences successfully distinguished the different treatment groups demonstrating that the expression profiles were reproducible among the treatments. Enrichment analysis of gene ontology terms identified several biological processes that were perturbed by the treatments, including nucleoside phosphate biosynthetic processes, mRNA metabolic processes, and response to stress. To identify transcripts whose expression level correlated with metal bioaccumulation, we performed Pearson correlation analysis. Several transcripts correlated with gill metal concentrations including mt10, mt20, and contig 48, an unknown transcript containing a wsc domain. In addition, three transcripts directly involved in the unfolded protein response (UPR) were induced in the metal treatments at 2 weeks and were further up-regulated at 4 weeks. Overall, correlation of tissue concentrations and gene expression responses indicates that as mussels accumulate higher concentrations of metals, initial stress responses are mobilized to protect tissues. However, given the role of UPR in apoptosis, it serves as an early indicator of stress, which once overwhelmed will result in adverse physiological effects. PMID:25016106

Poynton, Helen C; Robinson, William E; Blalock, Bonnie J; Hannigan, Robyn E

2014-10-01

331

Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression.  

PubMed

Adaptive changes in gene expression are thought to contribute to dependence, addiction and other behavioral responses to chronic ethanol abuse. DNA array studies provide a nonbiased detection of networks of gene expression changes, allowing insight into functional consequences and mechanisms of such molecular responses. We used oligonucleotide arrays to study nearly 6000 genes in human SH-SY5Y neuroblastoma cells exposed to chronic ethanol. A set of 42 genes had consistently increased or decreased mRNA abundance after 3 days of ethanol treatment. Groups of genes related to norepinephrine production, glutathione metabolism, and protection against apoptosis were identified. Genes involved in catecholamine metabolism are of special interest because of the role of this pathway in mediating ethanol withdrawal symptoms (physical dependence). Ethanol treatment elevated dopamine beta-hydroxylase (DBH, EC 1.14.17.1) mRNA and protein levels and increased releasable norepinephrine in SH-SY5Y cultures. Acute ethanol also increased DBH mRNA levels in mouse adrenal gland, suggesting in vivo functional consequences for ethanol regulation of DBH. In SH-SY5Y cells, ethanol also decreased mRNA and secreted protein levels for monocyte chemotactic protein 1, an effect that could contribute to the protective role of moderate ethanol consumption in atherosclerotic vascular disease. Finally, we identified a subset of genes similarly regulated by both ethanol and dibutyryl-cAMP treatment in SH-SY5Y cells. This suggests that ethanol and cAMP signaling share mechanistic features in regulating a subset of ethanol-responsive genes. Our findings offer new insights regarding possible molecular mechanisms underlying behavioral responses or medical consequences of ethanol consumption and alcoholism. PMID:11093800

Thibault, C; Lai, C; Wilke, N; Duong, B; Olive, M F; Rahman, S; Dong, H; Hodge, C W; Lockhart, D J; Miles, M F

2000-12-01

332

Virus-encoded TLR ligands reveal divergent functional responses of mononuclear phagocytes in pathogenic SIV infection  

PubMed Central

The role of mononuclear phagocytes in the pathogenesis or control of HIV infection is unclear. Here, we monitored the dynamics and function of dendritic cells (DC) and monocytes/macrophages in rhesus macaques acutely infected with pathogenic SIVmac251 with and without antiretroviral therapy (ART). SIV infection was associated with monocyte mobilization and recruitment of plasmacytoid DC (pDC) and macrophages to lymph nodes which did not occur with ART treatment. SIVmac251 single-stranded RNA encoded several uridine-rich sequences that were potent TLR7/8 ligands in mononuclear phagocytes of naive animals, stimulating myeloid DC (mDC) and monocytes to produce TNF-? and pDC and macrophages to produce both TNF-? and IFN-?. Following SIV infection pDC and monocytes/macrophages rapidly became hyporesponsive to stimulation with SIV-encoded TLR ligands and influenza virus, a condition that was reversed by ART. The loss of pDC and macrophage function was associated with a profound but transient block in the capacity of lymph node cells to secrete IFN-? upon stimulation. In contrast to pDC and monocytes/macrophages, mDC increased TNF-? production in response to stimulation following acute infection. Moreover, SIV-infected rhesus macaques with stable infection had increased mDC responsiveness to SIV-encoded TLR ligands and influenza virus at set-point, whereas animals that progressed rapidly to AIDS had reduced mDC responsiveness. These findings indicate that SIV encodes immunostimulatory TLR ligands and that pDC, mDC and monocytes/macrophages respond to these ligands differently as a function of SIV infection. The data also suggest that increased responsiveness of mDC to stimulation following SIV infection may be beneficial to the host. PMID:23338235

Wonderlich, Elizabeth R.; Wijewardana, Viskam; Liu, Xiangdong; Barratt-Boyes, Simon M.

2013-01-01

333

Problem gamblers exhibit reward hypersensitivity in medial frontal cortex during gambling.  

PubMed

Problem gambling (PG) is increasingly conceptualized as an addiction akin to substance abuse, rather than an impulse control disorder, however the mechanism of addiction remains unclear. Neuroimaging investigations have supported a "reward deficiency" hypothesis for PG by suggesting a blunted response to gambling, particularly in the striatum. Here we describe electrophysiological evidence of a hypersensitive response to gambling feedback in problem gamblers. Previous research in healthy participants has shown that feedback during gambling tasks triggers stereotypical neural responses including the Feedback-Related Mediofrontal Negativity (FRN), the feedback-related P300, and an increase in induced theta-band (4-8 Hz) power. We tested the theory that abnormal feedback processing characterizes brain activity in problem gamblers while gambling. EEG was recorded from non-gamblers and self-identified gamblers as they engaged in a computerized version of the Iowa Gambling Task. Feedback about valence (win vs. loss) triggered a FRN in both groups, but in gamblers this was preceded by an early-latency hypersensitive fronto-central difference to feedback. This early FRN was correlated with gambling severity and was localized to medial frontal cortex using distributed source imaging (CLARA). Gamblers also differed in responses to risk, showing a blunted P300 component and less EEG power in the theta band. Here we suggest that a more nuanced interpretation of reward deficiency is called for with respect to PG. For certain aspects of brain function, gamblers may exhibit hypersensitivity to reward feedback more akin to drug sensitization than reward deficiency. Our results also suggest that the neurologically normal brain employs dissociable systems in the processing of feedback from tasks involving risky decision making. PMID:21982697

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

2011-11-01

334

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. PMID:22438501

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

2012-01-01

335

The TRPM8 channel forms a complex with the 5-HT(1B) receptor and phospholipase D that amplifies its reversal of pain hypersensitivity.  

PubMed

Effective relief from chronic hypersensitive pain states remains an unmet need. Here we report the discovery that the TRPM8 ion channel, co-operating with the 5-HT(1B) receptor (5-HT(1B)R) in a subset of sensory afferents, exerts an influence at the spinal cord level to suppress central hypersensitivity in pain processing throughout the central nervous system. Using cell line models, ex vivo rat neural tissue and in vivo pain models, we assessed functional Ca(2+) fluorometric responses, protein:protein interactions, immuno-localisation and reflex pain behaviours, with pharmacological and molecular interventions. We report 5-HT(1B)R expression in many TRPM8-containing afferents and direct interaction of these proteins in a novel multi-protein signalling complex, which includes phospholipase D1 (PLD1). We provide evidence that the 5-HT(1B)R activates PLD1 to subsequently activate PIP 5-kinase and generate PIP2, an allosteric enhancer of TRPM8, achieving a several-fold increase in potency of TRPM8 activation. The enhanced activation responses of synaptoneurosomes prepared from spinal cord and cortical regions of animals with a chronic inflammatory pain state are inhibited by TRPM8 activators that were applied in vivo topically to the skin, an effect potentiated by co-administered 5-HT(1B)R agonists and attenuated by 5-HT(1B)R antagonists, while 5-HT(1B)R agents alone had no detectable effect. Corresponding results are seen when assessing reflex behaviours in inflammatory and neuropathic pain models. Control experiments with alternative receptor/TRP channel combinations reveal no such synergy. Identification of this novel receptor/effector/channel complex and its impact on nociceptive processing give new insights into possible strategies for enhanced analgesia in chronic pain. PMID:24269608

Vinuela-Fernandez, Ignacio; Sun, Liting; Jerina, Helen; Curtis, John; Allchorne, Andrew; Gooding, Hayley; Rosie, Roberta; Holland, Pamela; Tas, Basak; Mitchell, Rory; Fleetwood-Walker, Sue

2014-04-01

336

Menthol suppresses laryngeal C-fiber hypersensitivity to cigarette smoke in a rat model of gastroesophageal reflux disease: the role of TRPM8.  

PubMed

Patients with gastroesophageal reflux disease (GERD) display enhanced laryngeal reflex reactivity to stimuli that may be due to sensitization of the laryngeal C-fibers by acid and pepsin. Menthol, a ligand of transient receptor potential melastatin-8 (TRPM8), relieves throat irritation. However, the possibility that GERD induces laryngeal C-fiber hypersensitivity to cigarette smoke (CS) and that menthol suppresses this event has not been investigated. We delivered CS into functionally isolated larynxes of 160 anesthetized rats. Laryngeal pH 5-pepsin treatment, but not pH 5-denatured pepsin, augmented the apneic response to CS, which was blocked by denervation or perineural capsaicin treatment (a procedure that blocks the conduction of C fibers) of the superior laryngeal nerves. This augmented apnea was partially attenuated by capsazepine [an transient receptor potential vanilloid 1 (TRPV1) antagonist], SB-366791 (a TRPV1 antagonist), and HC030031 [a transient receptor potential ankyrin 1 (TRPA1) antagonist] and was completely prevented by a combination of TRPV1 and TRPA1 antagonists. Local application of menthol significantly suppressed the augmented apnea and this effect was reversed by pretreatment with AMTB (a TRPM8 antagonist). Our electrophysiological studies consistently revealed that laryngeal pH 5-pepsin treatment increased the sensitivity of laryngeal C-fibers to CS. Likewise, menthol suppressed this laryngeal C-fiber hypersensitivity and its effect could be reversed by pretreatment with AMTB. Our results suggest that laryngeal pH 5-pepsin treatment increases sensitivity to CS of both TRPV1 and TRPA1, which are presumably located at the terminals of laryngeal C-fibers. This sensory sensitization leads to enhanced laryngeal reflex reactivity and augmentation of the laryngeal C-fiber responses to CS, which can be suppressed by menthol acting via TRPM8. PMID:25539933

Liu, Bi-Yu; Lin, Yu-Jung; Lee, Hung-Fu; Ho, Ching-Yin; Ruan, Ting; Kou, Yu Ru

2015-03-01

337

Comparative transcriptome analysis reveals novel roles of the Ras and cyclic AMP signaling pathways in environmental stress response and antifungal drug sensitivity in Cryptococcus neoformans.  

PubMed

The cyclic AMP (cAMP) pathway plays a central role in the growth, differentiation, and virulence of pathogenic fungi, including Cryptococcus neoformans. Three upstream signaling regulators of adenylyl cyclase (Cac1), Ras, Aca1, and Gpa1, have been demonstrated to control the cAMP pathway in C. neoformans, but their functional relationship remains elusive. We performed a genome-wide transcriptome analysis with a DNA microarray using the ras1Delta, gpa1Delta, cac1Delta, aca1Delta, and pka1Delta pka2Delta mutants. The aca1Delta, gpa1Delta, cac1Delta, and pka1Delta pka2Delta mutants displayed similar transcriptome patterns, whereas the ras1Delta mutant exhibited transcriptome patterns distinct from those of the wild type and the cAMP mutants. Interestingly, a number of environmental stress response genes are modulated differentially in the ras1Delta and cAMP mutants. In fact, the Ras signaling pathway was found to be involved in osmotic and genotoxic stress responses and the maintenance of cell wall integrity via the Cdc24-dependent signaling pathway. Notably, the Ras and cAMP mutants exhibited hypersensitivity to a polyene drug, amphotericin B, without showing effects on ergosterol biosynthesis, which suggested a novel method of antifungal combination therapy. Among the cAMP-dependent gene products that we characterized, two small heat shock proteins, Hsp12 and Hsp122, were found to be involved in the polyene antifungal drug susceptibility of C. neoformans. PMID:20097740

Maeng, Shinae; Ko, Young-Joon; Kim, Gyu-Bum; Jung, Kwang-Woo; Floyd, Anna; Heitman, Joseph; Bahn, Yong-Sun

2010-03-01

338

Analysis of Global Gene Expression in Brachypodium distachyon Reveals Extensive Network Plasticity in Response to Abiotic Stress  

PubMed Central

Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium. PMID:24489928

Priest, Henry D.; Fox, Samuel E.; Rowley, Erik R.; Murray, Jessica R.; Michael, Todd P.; Mockler, Todd C.

2014-01-01

339

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. 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

2014-01-01

340

Functional analysis of the Arabidopsis PLDZ2 promoter reveals an evolutionarily conserved low-Pi-responsive transcriptional enhancer element  

PubMed Central

Plants have evolved a plethora of responses to cope with phosphate (Pi) deficiency, including the transcriptional activation of a large set of genes. Among Pi-responsive genes, the expression of the Arabidopsis phospholipase DZ2 (PLDZ2) is activated to participate in the degradation of phospholipids in roots in order to release Pi to support other cellular activities. A deletion analysis was performed to identify the regions determining the strength, tissue-specific expression, and Pi responsiveness of this regulatory region. This study also reports the identification and characterization of a transcriptional enhancer element that is present in the PLDZ2 promoter and able to confer Pi responsiveness to a minimal, inactive 35S promoter. This enhancer also shares the cytokinin and sucrose responsive properties observed for the intact PLDZ2 promoter. The EZ2 element contains two P1BS motifs, each of which is the DNA binding site of transcription factor PHR1. Mutation analysis showed that the P1BS motifs present in EZ2 are necessary but not sufficient for the enhancer function, revealing the importance of adjacent sequences. The structural organization of EZ2 is conserved in the orthologous genes of at least eight families of rosids, suggesting that architectural features such as the distance between the two P1BS motifs are also important for the regulatory properties of this enhancer element. PMID:22210906

Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Acevedo-Hernández, Gustavo J.; Pérez-Torres, Claudia-Anahí; Caballero-Pérez, Juan; Herrera-Estrella, Luis

2012-01-01

341

Application of xCELLigence RTCA Biosensor Technology for Revealing the Profile and Window of Drug Responsiveness in Real Time.  

PubMed

The xCELLigence technology is a real-time cellular biosensor, which measures the net adhesion of cells to high-density gold electrode arrays printed on custom-designed E-plates. The strength of cellular adhesion is influenced by a myriad of factors that include cell type, cell viability, growth, migration, spreading and proliferation. We therefore hypothesised that xCELLigence biosensor technology would provide a valuable platform for the measurement of drug responses in a multitude of different experimental, clinical or pharmacological contexts. In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1) not only if cells respond to a particular drug, but (2) the window of drug responsiveness. The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay. In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time. PMID:25893878

Kho, Dan; MacDonald, Christa; Johnson, Rebecca; Unsworth, Charles P; O'Carroll, Simon J; Mez, Elyce du; Angel, Catherine E; Graham, E Scott

2015-01-01

342

Global Transcriptome Analysis in Influenza-Infected Mouse Lungs Reveals the Kinetics of Innate and Adaptive Host Immune Responses  

PubMed Central

An infection represents a highly dynamic process involving complex biological responses of the host at many levels. To describe such processes at a global level, we recorded gene expression changes in mouse lungs after a non-lethal infection with influenza A virus over a period of 60 days. Global analysis of the large data set identified distinct phases of the host response. The increase in interferon genes and up-regulation of a defined NK-specific gene set revealed the initiation of the early innate immune response phase. Subsequently, infiltration and activation of T and B cells could be observed by an augmentation of T and B cell specific signature gene expression. The changes in B cell gene expression and preceding chemokine subsets were associated with the formation of bronchus-associated lymphoid tissue. In addition, we compared the gene expression profiles from wild type mice with Rag2 mutant mice. This analysis readily demonstrated that the deficiency in the T and B cell responses in Rag2 mutants could be detected by changes in the global gene expression patterns of the whole lung. In conclusion, our comprehensive gene expression study describes for the first time the entire host response and its kinetics to an acute influenza A infection at the transcriptome level. PMID:22815957

Srivastava, Barkha; Schulze, Annika; Novoselova, Natalia; Geffers, Robert; Schughart, Klaus

2012-01-01

343

High-fat taste challenge reveals altered striatal response in women recovered from bulimia nervosa: A pilot study  

PubMed Central

Objectives Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) tend to have disordered thinking and eating behaviours in regards to fat containing foods. This is the first study to investigate neuronal pathways that may contribute to altered fat consumption in eating disordered patients. Methods We used functional magnetic resonance imaging (fMRI) to compare responses to a high-fat cream stimulus, water, and a non-caloric viscous stimulus (CMC) to control for response to viscosity in individuals recovered from AN (N = 15), BN (N = 14) and a healthy control sample (CW, N = 18). Results An interaction analysis (ANOVAR) comparing the three groups (AN, BN, CW) and the three conditions (cream, CMC, water) revealed significant differences in the left anterior ventral striatum (AVS). A post hoc analysis displayed a higher magnitude of response for the contrast cream/water in BN compared to AN or CW and for the contrast CMC/water in BN compared to AN. Conclusions BN showed an exaggerated AVS response for the cream/water contrast in comparison to AN or CW. Moreover, BN showed an exaggerated AVS response for the CMC/water contrast in comparison to AN. These findings support the possibility that BN have an altered hedonic and/or motivational drive to consume fats. PMID:22540408

RADELOFF, DANIEL; WILLMANN, KATHRIN; OTTO, LISA; LINDNER, MICHAEL; PUTNAM, KAREN; VAN LEEUWEN, SARA; KAYE, WALTER H; POUSTKA, FRITZ; WAGNER, ANGELA

2015-01-01

344

The combined effect of salinity and heat reveals a specific physiological, biochemical and molecular response in tomato plants.  

PubMed

Many studies have described the response mechanisms of plants to salinity and heat applied individually; however, under field conditions some abiotic stresses often occur simultaneously. Recent studies revealed that the response of plants to a combination of two different stresses is specific and cannot be deduced from the stresses applied individually. Here, we report on the response of tomato plants to a combination of heat and salt stress. Interestingly, and in contrast to the expected negative effect of the stress combination on plant growth, our results show that the combination of heat and salinity provides a significant level of protection to tomato plants from the effects of salinity. We observed a specific response of plants to the stress combination that included accumulation of glycine betaine and trehalose. The accumulation of these compounds under the stress combination was linked to the maintenance of a high K(+) concentration and thus a lower Na(+) /K(+) ratio, with a better performance of the cell water status and photosynthesis as compared with salinity alone. Our findings unravel new and unexpected aspects of the response of plants to stress combination and provide a proposed list of enzymatic targets for improving crop tolerance to the abiotic field environment. PMID:24028172

Rivero, Rosa M; Mestre, Teresa C; Mittler, Ron; Rubio, Francisco; Garcia-Sanchez, Francisco; Martinez, Vicente

2014-05-01

345

Super-resolution microscopy reveals protein spatial reorganization in early innate immune responses.  

SciTech Connect

Over the past decade optical approaches were introduced that effectively break the diffraction barrier. Of particular note were introductions of Stimulated Emission/Depletion (STED) microscopy, Photo-Activated Localization Microscopy (PALM), and the closely related Stochastic Optical Reconstruction Microscopy (STORM). STORM represents an attractive method for researchers, as it does not require highly specialized optical setups, can be implemented using commercially available dyes, and is more easily amenable to multicolor imaging. We implemented a simultaneous dual-color, direct-STORM imaging system through the use of an objective-based TIRF microscope and filter-based image splitter. This system allows for excitation and detection of two fluorophors simultaneously, via projection of each fluorophor's signal onto separate regions of a detector. We imaged the sub-resolution organization of the TLR4 receptor, a key mediator of innate immune response, after challenge with lipopolysaccharide (LPS), a bacteria-specific antigen. While distinct forms of LPS have evolved among various bacteria, only some LPS variations (such as that derived from E. coli) typically result in significant cellular immune response. Others (such as from the plague bacteria Y. pestis) do not, despite affinity to TLR4. We will show that challenge with LPS antigens produces a statistically significant increase in TLR4 receptor clusters on the cell membrane, presumably due to recruitment of receptors to lipid rafts. These changes, however, are only detectable below the diffraction limit and are not evident using conventional imaging methods. Furthermore, we will compare the spatiotemporal behavior of TLR4 receptors in response to different LPS chemotypes in order to elucidate possible routes by which pathogens such as Y. pestis are able to circumvent the innate immune system. Finally, we will exploit the dual-color STORM capabilities to simultaneously image LPS and TLR4 receptors in the cellular membrane at resolutions at or below 40nm.

Carson, Bryan D.; Aaron, Jesse S.; Timlin, Jerilyn Ann

2010-10-01

346

Transcriptome Analysis Reveals Crosstalk of Responsive Genes to Multiple Abiotic Stresses in Cotton (Gossypium hirsutum L.)  

PubMed Central

Abiotic stress is a major environmental factor that limits cotton growth and yield, moreover, this problem has become more and more serious recently, as multiple stresses often occur simultaneously due to the global climate change and environmental pollution. In this study, we sought to identify genes involved in diverse stresses including abscisic acid (ABA), cold, drought, salinity and alkalinity by comparative microarray analysis. Our result showed that 5790, 3067, 5608, 778 and 6148 transcripts, were differentially expressed in cotton seedlings under treatment of ABA (1?M ABA), cold (4°C), drought (200mM mannitol), salinity (200mM NaCl) and alkalinity (pH=11) respectively. Among the induced or suppressed genes, 126 transcripts were shared by all of the five kinds of abiotic stresses, with 64 up-regulated and 62 down-regulated. These common members are grouped as stress signal transduction, transcription factors (TFs), stress response/defense proteins, metabolism, transport facilitation, as well as cell wall/structure, according to the function annotation. We also noticed that large proportion of significant differentially expressed genes specifically regulated in response to different stress. Nine of the common transcripts of multiple stresses were selected for further validation with quantitative real time RT-PCR (qRT-PCR). Furthermore, several well characterized TF families, for example, WRKY, MYB, NAC, AP2/ERF and zinc finger were shown to be involved in different stresses. As an original report using comparative microarray to analyze transcriptome of cotton under five abiotic stresses, valuable information about functional genes and related pathways of anti-stress, and/or stress tolerance in cotton seedlings was unveiled in our result. Besides this, some important common factors were focused for detailed identification and characterization. According to our analysis, it suggested that there was crosstalk of responsive genes or pathways to multiple abiotic or even biotic stresses, in cotton. These candidate genes will be worthy of functional study under diverse stresses. PMID:24224045

Zhu, Ya-Na; Shi, Dong-Qiao; Ruan, Meng-Bin; Zhang, Li-Li; Meng, Zhao-Hong; Liu, Jie; Yang, Wei-Cai

2013-01-01

347

Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome.  

PubMed

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

Feng, Bin; La, Jun Ho; Schwartz, Erica S; Gebhart, G F

2012-05-15

348

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

PubMed Central

Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization. Conclusions: Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved. Citation: Sutton BC; Opp MR. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization. SLEEP 2014;37(3):515-524. PMID:24587574

Sutton, Blair C.; Opp, Mark R.

2014-01-01

349

Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans  

SciTech Connect

It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased inflammatory cells and IgE, but the others did not. • The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. • Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.

Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

2013-08-15

350

Failure analysis of porcupine quills under axial compression reveals their mechanical response during buckling.  

PubMed

Porcupine quills are natural structures formed by a thin walled conical shell and an inner foam core. Axial compression tests, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR) were all used to compare the characteristics and mechanical properties of porcupine quills with and without core. The failure mechanisms that occur during buckling were analyzed by scanning electron microscopy (SEM), and it was found that delamination buckling is mostly responsible for the decrease in the measured buckling stress of the quills with regard to predicted theoretical values. Our analysis also confirmed that the foam core works as an energy dissipater improving the mechanical response of an empty cylindrical shell, retarding the onset of buckling as well as producing a step wise decrease in force after buckling, instead of an instantaneous decrease in force typical for specimens without core. Cell collapse and cell densification in the inner foam core were identified as the key mechanisms that allow for energy absorption during buckling. PMID:25123434

Torres, Fernando G; Troncoso, Omar P; Diaz, John; Arce, Diego

2014-11-01

351

Auditory brainstem response recovery in the dolphin as revealed by double sound pulses of different frequencies.  

PubMed

Recovery of auditory brainstem responses (ABR) in a bottlenose dolphin was studied in conditions of double-pip stimulation when two stimuli in a pair differed in frequency and intensity. When the conditioning and test stimuli were of equal frequencies, the test response was markedly suppressed at short interstimulus intervals; complete recovery appeared at intervals from about 2 ms (when two stimuli were of equal intensity) to 10-20 ms (when the conditioning stimulus exceeded the test by up to 40 dB). When the two stimuli were of different frequencies, the suppression diminished and was almost absent at a half-octave difference even if the conditioning stimulus exceeded the test one by 40 dB. Frequency-dependence curves (ABR amplitude dependence on frequency difference between the two stimuli) had equivalent rectangular bandwidth from +/-0.2 oct at test stimuli of 20 dB above threshold to +/-0.5 oct at test stimuli of 50 dB above threshold. PMID:11681398

Popov, V V; Supin AYa; Klishin, V O

2001-10-01

352

Analysis of Natural Variation in Bermudagrass (Cynodon dactylon) Reveals Physiological Responses Underlying Drought Tolerance  

PubMed Central

Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass and one of the most drought tolerant species. Dissecting the natural variation in drought tolerance and physiological responses will bring us powerful basis and novel insight for plant breeding. In the present study, we evaluated the natural variation of drought tolerance among nine bermudagrass varieties by measuring physiological responses after drought stress treatment through withholding water. Three groups differing in drought tolerance were identified, including two tolerant, five moderately tolerant and two susceptible varieties. Under drought stress condition, drought sensitive variety (Yukon) showed relative higher water loss, more severe cell membrane damage (EL), and more accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA), while drought tolerant variety (Tifgreen) exhibited significantly higher antioxidant enzymes activities. Further results indicated that drought induced cell injury in different varieties (Yukon, SR9554 and Tifgreen) exhibited liner correlation with leaf water content (LWC), H2O2 content, MDA content and antioxidant enzyme activities. Additionally, Tifgreen plants had significantly higher levels of osmolytes (proline level and soluble sugars) when compared with Yukon and SR9554 under drought stress condition. Taken together, our results indicated that natural variation of drought stress tolerance in bermudagrass varieties might be largely related to the induced changes of water status, osmolyte accumulation and antioxidant defense system. PMID:23285294

Cheng, Zhangmin; Ye, Tiantian; Chan, Zhulong

2012-01-01

353

Hepatic gene expression profiling reveals protective responses in Atlantic salmon vaccinated against furunculosis  

PubMed Central

Background Furunculosis, a disease caused with gram negative bacteria Aeromonas salmonicida produces heavy losses in aquaculture. Vaccination against furunculosis reduces mortality of Atlantic salmon but fails to eradicate infection. Factors that determine high individual variation of vaccination efficiency remain unknown. We used gene expression analyses to search for the correlates of vaccine protection against furunculosis in Atlantic salmon. Results Naïve and vaccinated fish were challenged by co-habitance. Fish with symptoms of furunculosis at the onset of mass mortality (LR - low resistance) and survivors (HR - high resistance) were sampled. Hepatic gene expression was analyzed with microarray (SFA2.0 - immunochip) and real-time qPCR. Comparison of LR and HR indicated changes associated with the protection and results obtained with naïve fish were used to find and filter the vaccine-independent responses. Genes involved in recruitment and migration of immune cells changed expression in both directions with greater magnitude in LR. Induction of the regulators of immune responses was either equal (NFkB) or greater (Jun) in LR. Expression levels of proteasome components and extracellular proteases were higher in LR while protease inhibitors were up-regulated in HR. Differences in chaperones and protein adaptors, scavengers of reactive oxygen species and genes for proteins of iron metabolism suggested cellular and oxidative stress in LR. Reduced levels of free iron and heme can be predicted in LR by gene expression profiles with no protection against pathogen. The level of complement regulation was greater in HR, which showed up-regulation of the components of membrane attack complex and the complement proteins that protect the host against the auto-immune damages. HR fish was also characterized with up-regulation of genes for proteins involved in the protection of extracellular matrix, lipid metabolism and clearance of endogenous and exogenous toxic compounds. A number of genes with marked expression difference between HR and LR can be considered as positive and negative correlates of vaccine protection against furunculosis. Conclusion Efficiency of vaccination against furunculosis depends largely on the ability of host to neutralize the negative impacts of immune responses combined with efficient clearance and prevention of tissue damages. PMID:19878563

Škugor, Stanko; Jørgensen, Sven Martin; Gjerde, Bjarne; Krasnov, Aleksei

2009-01-01

354

A possible link between sinusitis and lower airway hypersensitivity: the role of Staphylococcal enterotoxin B  

PubMed Central

Background and aims The prevalence of asthma has been keeping arising with unknown etiology. The cumulative evidence indicates that chronic rhinosinusitis (CRS) closely relates to asthma, but the detailed mechanisms remain unclear. The present study aimed to take insight into the role of Staphylococcus enterotoxin B (SEB) in a possible association between CRS and asthma. Methods 38 patients with both CRS and asthma underwent functional endoscopic sinus surgery. Serum specific IgE and cytokines, clinical symptoms of CRS and asthma were evaluated before and after the surgery. Peripheral blood mononuclear cells (PBMCs) were separated from the patients and cultured. Th2 response of the cultured PBMCs in the presence or absence of specific antigens and SEB was evaluated. Results Besides the improvement of CRS symptoms, amelioration of asthma was also observed in the patients with both CRS and asthma after the sinus surgery. The preoperatively elevated Th2 cytokines, IL-4 and IL-5, normalized postoperatively. Th2 response was generated with separated PBMCs in the presence of specific antigens. SEB was required for maintaining Th2 response in these separated PBMCs. Conclusion The present results indicate that a possible link exists between CRS and lower airway hypersensitivity. Sinusitis derived SEB may play a role in sustaining Th2 responses in the low airway hypersensitivity related to sinusitis. PMID:16677400

Liu, Tao; Wang, Bin-Quan; Yang, Ping-Chang

2006-01-01

355

Metabolic profiling reveals local and systemic responses of host plants to nematode parasitism.  

PubMed

The plant parasitic beet cyst nematode Heterodera schachtii induces syncytial feeding structures in Arabidopsis roots. The feeding structures form strong sink tissues that have been suggested to be metabolically highly active. In the present study, metabolic profiling and gene targeted expression analyses were performed in order to study the local and systemic effects of nematode infection on the plant host. The results showed increased levels of many amino acids and phosphorylated metabolites in syncytia, as well as high accumulation of specific sugars such as 1-kestose that do not accumulate naturally in Arabidopsis roots. A correlation-based network analysis revealed highly activated and coordinated metabolism in syncytia compared to non-infected control roots. An integrated analysis of the central primary metabolism showed a clear coherence of metabolite and transcript levels, indicating transcriptional regulation of specific pathways. Furthermore, systemic effects of nematode infection were demonstrated by correlation-based network analysis as well as independent component analysis. 1-kestose, raffinose, alpha,alpha-trehalose and three non-identified analytes showed clear systemic accumulation, indicating future potential for diagnostic and detailed metabolic analyses. Our studies open the door towards understanding the complex remodelling of plant metabolism in favour of the parasitizing nematode. PMID:20374527

Hofmann, Julia; El Ashry, Abd El Naser; Anwar, Shahbaz; Erban, Alexander; Kopka, Joachim; Grundler, Florian

2010-06-01

356

Metabolic profiling reveals local and systemic responses of host plants to nematode parasitism  

PubMed Central

The plant parasitic beet cyst nematode Heterodera schachtii induces syncytial feeding structures in Arabidopsis roots. The feeding structures form strong sink tissues that have been suggested to be metabolically highly active. In the present study, metabolic profiling and gene targeted expression analyses were performed in order to study the local and systemic effects of nematode infection on the plant host. The results showed increased levels of many amino acids and phosphorylated metabolites in syncytia, as well as high accumulation of specific sugars such as 1-kestose that do not accumulate naturally in Arabidopsis roots. A correlation-based network analysis revealed highly activated and coordinated metabolism in syncytia compared to non-infected control roots. An integrated analysis of the central primary metabolism showed a clear coherence of metabolite and transcript levels, indicating transcriptional regulation of specific pathways. Furthermore, systemic effects of nematode infection were demonstrated by correlation-based network analysis as well as independent component analysis. 1-kestose, raffinose, ?,?-trehalose and three non-identified analytes showed clear systemic accumulation, indicating future potential for diagnostic and detailed metabolic analyses. Our studies open the door towards understanding the complex remodelling of plant metabolism in favour of the parasitizing nematode. PMID:20374527

Hofmann, Julia; El Ashry, Abd El Naser; Anwar, Shahbaz; Erban, Alexander; Kopka, Joachim; Grundler, Florian

2010-01-01

357

Plant root transcriptome profiling reveals a strain-dependent response during Azospirillum-rice cooperation  

PubMed Central

Cooperation involving Plant Growth-Promoting Rhizobacteria results in improvements of plant growth and health. While pathogenic and symbiotic interactions are known to induce transcriptional changes for genes related to plant defense and development, little is known about the impact of phytostimulating rhizobacteria on plant gene expression. This study aims at identifying genes significantly regulated in rice roots upon Azospirillum inoculation, considering possible favored interaction between a strain and its original host cultivar. Genome-wide analyzes of Oryza sativa japonica cultivars Cigalon and Nipponbare were performed, by using microarrays, seven days post-inoculation with Azospirillum lipoferum 4B (isolated from Cigalon) or Azospirillum sp. B510 (isolated from Nipponbare) and compared to the respective non-inoculated condition. A total of 7384 genes were significantly regulated, which represent about 16% of total rice genes. A set of 34 genes is regulated by both Azospirillum strains in both cultivars, including a gene orthologous to PR10 of Brachypodium, and these could represent plant markers of Azospirillum-rice interactions. The results highlight a strain-dependent response of rice, with 83% of the differentially expressed genes being classified as combination-specific. Whatever the combination, most of the differentially expressed genes are involved in primary metabolism, transport, regulation of transcription and protein fate. When considering genes involved in response to stress and plant defense, it appears that strain B510, a strain displaying endophytic properties, leads to the repression of a wider set of genes than strain 4B. Individual genotypic variations could be the most important driving force of rice roots gene expression upon Azospirillum inoculation. Strain-dependent transcriptional changes observed for genes related to auxin and ethylene signaling highlight the complexity of hormone signaling networks in the Azospirillum-rice cooperation. PMID:25414716

Drogue, Benoît; Sanguin, Hervé; Chamam, Amel; Mozar, Michael; Llauro, Christel; Panaud, Olivier; Prigent-Combaret, Claire; Picault, Nathalie; Wisniewski-Dyé, Florence

2014-01-01

358

Proteomic Analysis of Urine Exosomes Reveals Renal Tubule Response to Leptospiral Colonization in Experimentally Infected Rats  

PubMed Central

Background Infectious Leptospira colonize the kidneys of reservoir (e.g. rats) and accidental hosts such as humans. The renal response to persistent leptospiral colonization, as measured by urinary protein biosignatures, has not been systematically studied. Urinary exosomes--bioactive membrane-bound nanovesicles--contain cell-state specific cargo that additively reflect formation all along the nephron. We hypothesized that Leptospira-infection will alter the content of urine exosomes, and further, that these Leptospira-induced alterations will hold clues to unravel novel pathways related to bacterial-host interactions. Methodology/Principal findings Exosome protein content from 24 hour urine samples of Leptospira-infected rats was compared with that of uninfected rats using SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Statistical models were used to identify significantly dysregulated proteins in Leptospira-infected and uninfected rat urine exosomes. In all, 842 proteins were identified by LC-MS/MS proteomics of total rat urine and 204 proteins associated specifically with exosomes. Multivariate analysis showed that 25 proteins significantly discriminated between uninfected control and infected rats. Alanyl (membrane) aminopeptidase, also known as CD13 topped this list with the highest score, a finding we validated by Western immunoblotting. Whole urine analysis showed Tamm-Horsfall protein level reduction in the infected rat urine. Total urine and exosome proteins were significantly different in male vs. female infected rats. Conclusions We identified exosome-associated renal tubule-specific responses to Leptospira infection in a rat chronic colonization model. Quantitative differences in infected male and female rat urine exosome proteins vs. uninfected controls suggest that urine exosome analysis identifies important differences in kidney function that may be of clinical and pathological significance. PMID:25793258

RamachandraRao, Satish P.; Matthias, Michael A.; Mondrogon, Chanthel-Kokoy; Aghania, Eamon; Park, Cathleen; Kong, Casey; Ishaya, Michelle; Madrigal, Assael; Horng, Jennifer; Khoshaba, Roni; Bounkhoun, Anousone; De Palma, Antonella; Agresta, Anna Maria; Awdishu, Linda; Naviaux, Robert K.; Vinetz, Joseph M.; Mauri, Pierluigi

2015-01-01

359

Phylogenetically Driven Sequencing of Extremely Halophilic Archaea Reveals Strategies for Static and Dynamic Osmo-response  

PubMed Central

Organisms across the tree of life use a variety of mechanisms to respond to stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms and phenotypes associated with osmoadaptation also play important roles in bacterial virulence, human health, agricultural production and many other biological systems. To improve understanding of osmoadaptive strategies, we have generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade whose members thrive in hypersaline environments and routinely experience drastic changes in environmental salinity) and analyzed these new genomes in combination with those from 21 previously sequenced haloarchaeal isolates. We propose a generalized model for haloarchaeal management of cytoplasmic osmolarity in response to osmotic shifts, where potassium accumulation and sodium expulsion during osmotic upshock are accomplished via secondary transport using the proton gradient as an energy source, and potassium loss during downshock is via a combination of secondary transport and non-specific ion loss through mechanosensitive channels. We also propose new mechanisms for magnesium and chloride accumulation. We describe the expansion and differentiation of haloarchaeal general transcription factor families, including two novel expansions of the TATA-binding protein family, and discuss their potential for enabling rapid adaptation to environmental fluxes. We challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. The combination of broad (17 genera) and deep (?5 species in four genera) sampling of a phenotypically unified clade has enabled us to uncover both highly conserved and specialized features of osmoadaptation. Finally, we demonstrate the broad utility of such datasets, for metagenomics, improvements to automated gene annotation and investigations of evolutionary processes. PMID:25393412

Tritt, Andrew; Larsen, David; Krusor, Megan; Yao, Andrew I.; Wu, Dongying; Madern, Dominique; Eisen, Jonathan A.; Darling, Aaron E.; Facciotti, Marc T.

2014-01-01

360

Effects of gait speed on stability of walking revealed by simulated response to tripping perturbation.  

PubMed

The objective of this work was to study stability of walking over a range of gait speeds by means of muscle-driven simulations. Fast walking has previously been related to high likelihood of falling due to tripping. Various measures of stability have shown different relationships between walking speed and stability. These measures may not be associated with tripping, so it is unclear whether the increase in likelihood of falling is explicable by an increase in instability. Here, stability with respect to a constant tripping perturbation was quantified as the immediate passive response of torso to the perturbation. Subject-specific muscle-driven simulations of eight young healthy subjects walking at four speeds, created by combining a generic musculoskeletal model with gait data, were analyzed. In the simulations, short perturbations were performed several times throughout the swing-phase by applying a constant backward force to the swing-foot of the model. Maxima of changes in the torso (angular) velocity components during the swing-phase were studied. These changes in the velocity components correlated with the walking speed as follows: anterior-posterior r=0.37 (p<0.05), vertical r=0.41 (p<0.05), and medio-lateral r=-0.40 (p<0.05). Of the angular velocity components, only the vertical component correlated statistically significantly with speed, r=0.52 (p<0.01). The weak and varying speed effects suggest that fast walking is not necessarily more unstable than slow walking, in the sense of response to a constant perturbation. PMID:24091248

Klemetti, Rudolf; Moilanen, Petro; Avela, Janne; Timonen, Jussi

2014-01-01

361

Proteomics analysis of urine reveals acute phase response proteins as candidate diagnostic biomarkers for prostate cancer.  

PubMed

Despite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p?Response Signaling pathway. Nine proteins with differential abundances were included in this pathway: AMBP, APOA1, FGA, FGG, HP, ITIH4, SERPINA1, TF and TTR. The expression pattern of 4 acute phase response proteins differed from the defined expression in the canonical pathway. The urine levels of TF, AMPB and HP were measured by immunoturbidimetry in an independent validation set. The concentration of AMPB in urine was significantly higher in PCa while levels of TF and HP were opposite (p?

Davalieva, Katarina; Kiprijanovska, Sanja; Komina, Selim; Petrusevska, Gordana; Zografska, Natasha Chokrevska; Polenakovic, Momir

2015-01-01

362

Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture.  

PubMed

We have used proteomic analyses to probe the responses induced by a pair of marine biotoxins, okadaic acid (OA) and gambierol (GB), added alone or in combination to a cultured cell line and carried out a preliminary investigation into the possible interactions between toxins possessing two different molecular mechanisms of action at a cellular level. When MCF-7 cells were treated with OA, we found that cellular levels of 30 proteins were significantly affected, including several isoforms of nonphosphorylated and phosphorylated hsp 27, as well as enzymes involved in the maintenance of nucleoside triphosphate pools and the control of redox states of the cell. When we repeated our analysis using GB, nine proteins were significantly affected, including some isoforms of nonphosphorylated hsp 27, as well as semenogelin-1, myosin-7, and the ATP synthase subunit delta. The combined addition of OA and GB to MCF-7 cells, in turn, affected 14 proteins, including some isoforms of nonphosphorylated and phosphorylated hsp 27, as well as myosin-7, the ATP synthase subunit delta, and enzymes involved in the control of redox states of the cell. If components affected by either OA or GB, as well as by the combined treatment, were classified according to the detected changes, two sets of data were obtained, including the components whose levels were found affected by the combined treatment, regardless of the effect observed after addition of only one agent, and those that had been found affected in cells that had been challenged with only one toxin but not when cells had been subjected to the combined treatment. Multiple patterns of responses to the toxin mixture were recorded in the two sets, consisting of both independent and interacting actions, among which we detected synergistic, similar, and antagonistic effects. PMID:19397276

Sala, Gian Luca; Ronzitti, Giuseppe; Sasaki, Makoto; Fuwa, Haruhiko; Yasumoto, Takeshi; Bigiani, Albertino; Rossini, Gian Paolo

2009-06-01

363

In Vivo Physiological and Transcriptional Profiling Reveals Host Responses to Clostridium difficile Toxin A and Toxin B  

PubMed Central

Toxin A (TcdA) and toxin B (TcdB) of Clostridium difficile cause gross pathological changes (e.g., inflammation, secretion, and diarrhea) in the infected host, yet the molecular and cellular pathways leading to observed host responses are poorly understood. To address this gap, we evaluated the effects of single doses of TcdA and/or TcdB injected into the ceca of mice, and several endpoints were analyzed, including tissue pathology, neutrophil infiltration, epithelial-layer gene expression, chemokine levels, and blood cell counts, 2, 6, and 16 h after injection. In addition to confirming TcdA's gross pathological effects, we found that both TcdA and TcdB resulted in neutrophil infiltration. Bioinformatics analyses identified altered expression of genes associated with the metabolism of lipids, fatty acids, and detoxification; small GTPase activity; and immune function and inflammation. Further analysis revealed transient expression of several chemokines (e.g., Cxcl1 and Cxcl2). Antibody neutralization of CXCL1 and CXCL2 did not affect TcdA-induced local pathology or neutrophil infiltration, but it did decrease the peripheral blood neutrophil count. Additionally, low serum levels of CXCL1 and CXCL2 corresponded with greater survival. Although TcdA induced more pronounced transcriptional changes than TcdB and the upregulated chemokine expression was unique to TcdA, the overall transcriptional responses to TcdA and TcdB were strongly correlated, supporting differences primarily in timing and potency rather than differences in the type of intracellular host response. In addition, the transcriptional data revealed novel toxin effects (e.g., altered expression of GTPase-associated and metabolic genes) underlying observed physiological responses to C. difficile toxins. PMID:23897615

D'Auria, Kevin M.; Kolling, Glynis L.; Donato, Gina M.; Warren, Cirle A.; Gray, Mary C.

2013-01-01

364

Immune response of the Caribbean sea fan, Gorgonia ventalina, exposed to an Aplanochytrium parasite as revealed by transcriptome sequencing  

PubMed Central

Coral reef communities are undergoing marked declines due to a variety of stressors including disease. The sea fan coral, Gorgonia ventalina, is a tractable study system to investigate mechanisms of immunity to a naturally occurring pathogen. Functional studies in Gorgonia ventalina immunity indicate that several key pathways and cellular components are involved in response to natural microbial invaders, although to date the functional and regulatory pathways remain largely un-described. This study used short-read sequencing (Illumina GAIIx) to identify genes involved in the response of G. ventalina to a naturally occurring Aplanochytrium spp. parasite. De novo assembly of the G. ventalina transcriptome yielded 90,230 contigs of which 40,142 were annotated. RNA-Seq analysis revealed 210 differentially expressed genes in sea fans exposed to the Aplanochytrium parasite. Differentially expressed genes involved in immunity include pattern recognition molecules, anti-microbial peptides, and genes involved in wound repair and reactive oxygen species formation. Gene enrichment analysis indicated eight biological processes were enriched representing 36 genes, largely involved with protein translation and energy production. This is the first report using high-throughput sequencing to characterize the host response of a coral to a natural pathogen. Furthermore, we have generated the first transcriptome for a soft (octocoral or non-scleractinian) coral species. Expression analysis revealed genes important in invertebrate innate immune pathways, as well as those whose role is previously un-described in cnidarians. This resource will be valuable in characterizing G. ventalina immune response to infection and co-infection of pathogens in the context of environmental change. PMID:23898300

Burge, Colleen A.; Mouchka, Morgan E.; Harvell, C. Drew; Roberts, Steven

2013-01-01

365

Immune response of the Caribbean sea fan, Gorgonia ventalina, exposed to an Aplanochytrium parasite as revealed by transcriptome sequencing.  

PubMed

Coral reef communities are undergoing marked declines due to a variety of stressors including disease. The sea fan coral, Gorgonia ventalina, is a tractable study system to investigate mechanisms of immunity to a naturally occurring pathogen. Functional studies in Gorgonia ventalina immunity indicate that several key pathways and cellular components are involved in response to natural microbial invaders, although to date the functional and regulatory pathways remain largely un-described. This study used short-read sequencing (Illumina GAIIx) to identify genes involved in the response of G. ventalina to a naturally occurring Aplanochytrium spp. parasite. De novo assembly of the G. ventalina transcriptome yielded 90,230 contigs of which 40,142 were annotated. RNA-Seq analysis revealed 210 differentially expressed genes in sea fans exposed to the Aplanochytrium parasite. Differentially expressed genes involved in immunity include pattern recognition molecules, anti-microbial peptides, and genes involved in wound repair and reactive oxygen species formation. Gene enrichment analysis indicated eight biological processes were enriched representing 36 genes, largely involved with protein translation and energy production. This is the first report using high-throughput sequencing to characterize the host response of a coral to a natural pathogen. Furthermore, we have generated the first transcriptome for a soft (octocoral or non-scleractinian) coral species. Expression analysis revealed genes important in invertebrate innate immune pathways, as well as those whose role is previously un-described in cnidarians. This resource will be valuable in characterizing G. ventalina immune response to infection and co-infection of pathogens in the context of environmental change. PMID:23898300

Burge, Colleen A; Mouchka, Morgan E; Harvell, C Drew; Roberts, Steven

2013-01-01

366

Levetiracetam following liver and kidney failure in late-onset anticonvulsant hypersensitivity syndrome.  

PubMed

Anticonvulsant hypersensitivity syndrome is an adverse drug reaction usually occurring from 1 to 8 weeks after exposure to antiepileptic drugs. It can threaten life by affecting the liver, kidneys, central nervous system or lungs. We present a 47-year-old patient treated with phenytoin, lamotrigine and clobazam for 7 years. He presented with hepatic and renal failure in relation to this syndrome demonstrated by renal biopsy. Prognosis was excellent due to an early diagnosis leading to cessation of the causative agents. Levetiracetam was started with a good response. PMID:24238830

Rodríguez-Osorio, X; Pardo, J; López-González, F J; Novoa, D; Pintos, E

2014-05-01

367

Comparative effects of various lead salts on delayed hypersensitivity in mice.  

PubMed

Intraperitoneal administration of lead acetate, lead carbonate, lead chloride, lead nitrate or lead oxide at 0.5 or 6 mg per kg per day on five consecutive days was found to produce diverging effects on delayed hypersensitivity to sheep erythrocytes in Balb/c mice according to the salt used. Lead carbonate, lead nitrate and lead oxide exerted immunosuppressing properties, while lead acetate and lead chloride enhanced this cell-mediated immune response. From these findings, it is concluded that lead immunotoxicity critically depends on which salt is present. PMID:6512164

Descotes, J; Evreux, J C; Laschi-Locquerie, A; Tachon, P

1984-10-01

368

Effects of variations in time and dose of diazepam injection on delayed hypersensitivity.  

PubMed

Administration of diazepam was suggested to exert immuno-suppressive properties in mice. In the present study, we explored the time and dose-dependence of diazepam effects on delayed hypersensitivity to sheep erythrocytes in Balb/c mice. DTH response was only depressed when diazepam was injected shortly after immunization and this effect on DTH induction was found with doses of 4 and 8 mg/kg ip while lower doses (0, 5, 1 and 2 mg/kg) remained ineffective. PMID:7184962

Descotes, J; Laschi, A; Tachon, P; Tedone, R; Evreux, J C

369

RNA-seq reveals regional differences in transcriptome response to heat stress in the marine snail Chlorostoma funebralis.  

PubMed

To investigate the role of gene expression in adaptation of marine ectotherms to different temperatures, we examined the transcriptome-wide thermal stress response in geographically separated populations of the intertidal snail Chlorostoma funebralis. Snails from two southern (heat tolerant) and two northern (heat sensitive) populations were acclimated to a common thermal environment, exposed to an environmentally relevant thermal stress and analysed using RNA-seq. Pooling across all populations revealed 306 genes with differential expression between control and heat-stressed samples, including 163 significantly upregulated and 143 significantly downregulated genes. When considered separately, regional differences in response were widely apparent. Heat shock proteins (Hsps) were upregulated in both regions, but the magnitude of response was significantly greater in northern populations for most Hsp70s, while the southern populations showed greater upregulation for approximately half of the Hsp40s. Of 177 stress-responsive genes in northern populations, 55 responded to heat stress only in northern populations. Several molecular chaperones and antioxidant genes that were not differentially expressed in southern populations showed higher expression under control conditions compared with northern populations. This suggests that evolution of elevated expression of these genes under benign conditions preadapts the southern populations to frequent heat stress and contributes to their higher thermal tolerance. These results indicate that evolution has resulted in different transcriptome responses across populations, including upregulation of genes in response to stress and preadaptation of genes in anticipation of stress (based on evolutionary history of frequent heat exposure). The relative importance of the two mechanisms differs among gene families and among populations. PMID:25524431

Gleason, Lani U; Burton, Ronald S

2015-02-01

370

Tomato transcriptional changes in response to Clavibacter michiganensis subsp. michiganensis reveal a role for ethylene in disease development.  

PubMed

Clavibacter michiganensis subsp. michiganensis (Cmm) is a gram-positive actinomycete, causing bacterial wilt and canker disease in tomato (Solanum lycopersicum). Host responses to gram-positive bacteria and molecular mechanisms associated with the development of disease symptoms caused by Cmm in tomato are largely unexplored. To investigate plant responses activated during this compatible interaction, we used microarray analysis to monitor changes in host gene expression during disease development. This analysis was performed at 4 d postinoculation, when bacteria were actively multiplying and no wilt symptoms were yet visible; and at 8 d postinoculation, when bacterial growth approached saturation and typical wilt symptoms were observed. Of the 9,254 tomato genes represented on the array, 122 were differentially expressed in Cmm-infected plants, compared with mock-inoculated plants. Functional classification of Cmm-responsive genes revealed that Cmm activated typical basal defense responses in the host, including induction of defense-related genes, production and scavenging of free oxygen radicals, enhanced protein turnover, and hormone synthesis. Cmm infection also induced a subset of host genes involved in ethylene biosynthesis and response. After inoculation with Cmm, Never ripe (Nr) mutant plants, impaired in ethylene perception, and transgenic plants with reduced ethylene synthesis showed significant delay in the appearance of wilt symptoms, compared with wild-type plants. The retarded wilting in Nr plants was a specific effect of ethylene insensitivity, and was not due to altered expression of defense-related genes, reduced bacterial populations, or decreased ethylene synthesis. Taken together, our results indicate that host-derived ethylene plays an important role in regulation of the tomato susceptible response to Cmm. PMID:18245454

Balaji, Vasudevan; Mayrose, Maya; Sherf, Ofra; Jacob-Hirsch, Jasmine; Eichenlaub, Rudolf; Iraki, Naim; Manulis-Sasson, Shulamit; Rechavi, Gideon; Barash, Isaac; Sessa, Guido

2008-04-01

371

Inhibitory effect of the selective serotonin 5-HT? receptor antagonist ramosetron on duodenal acidification-induced gastric hypersensitivity in rats.  

PubMed

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are both functional gastrointestinal disorders and frequently co-occur in patients. While one cause of FD appears to be gastric hypersensitivity, whether the hypersensitivity is affected by IBS treatments remains unclear, given the lack of appropriate animal models for testing. Here, we established an experimental model of duodenal acidification-induced gastric hypersensitivity in conscious rats. The model involved duodenal acidification induced by the infusion of hydrochloric acid into the proximal duodenum, with the nociceptive response being determined as the change in mean arterial pressure (MAP) during gastric distension via an indwelling latex balloon. Using our model we evaluated the effects of duodenal acidification, increased distension pressure, and orally administered therapeutic agents for IBS with diarrhea (IBS-D). Duodenal acidification enhanced the pressor response during gastric distension, and pretreatment with the opioid ?-receptor agonist fedotozine (10mg/kg, intra-arterial) inhibited the pressor response. Pressure levels of 15-60 mm Hg increased MAP in response to gastric distension. The serotonin 5-HT3 receptor antagonist ramosetron (30 ?g/kg) inhibited MAP increase induced by duodenal acidification, with no other IBS-D therapeutic agents showing any effect. In contrast, the serotonin 5-HT3 receptor agonist m-chlorophenylbiguanide (1mg/kg) significantly enhanced the pressor response during gastric distension. These findings indicate that the serotonin 5-HT3 receptor plays a key role in duodenal acidification-induced gastric hypersensitivity in rats, suggesting that ramosetron may reduce FD symptoms by ameliorating sensitized gastric perception. PMID:24632457

Nakata-Fukuda, Mari; Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Uchiyama, Yasuo

2014-05-15

372

Modifying Behavioral Phenotypes in Fmr1 KO Mice: Genetic Background Differences Reveal Autistic-Like Responses  

PubMed Central

Scientific Abstract Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild-type mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD-1). Male Fmr1 knockout and wild-type littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic-like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic-like traits. PMID:21268289

Spencer, Corinne M.; Alekseyenko, Olga; Hamilton, Shannon M.; Thomas, Alexia M.; Serysheva, Ekaterina; Yuva-Paylor, Lisa A.; Paylor, Richard

2010-01-01

373

Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage.  

PubMed

Nuclear functions including gene expression, DNA replication and genome maintenance intimately rely on dynamic changes in chromatin organization. The movements of chromatin fibers might play important roles in the regulation of these fundamental processes, yet the mechanisms controlling chromatin mobility are poorly understood owing to methodological limitations for the assessment of chromatin movements. Here, we present a facile and quantitative technique that relies on photoactivation of GFP-tagged histones and paired-particle tracking to measure chromatin mobility in live cells. We validate the method by comparing live cells to ATP-depleted cells and show that chromatin movements in mammalian cells are predominantly energy dependent. We also find that chromatin diffusion decreases in response to DNA breaks induced by a genotoxic drug or by the ISceI meganuclease. Timecourse analysis after cell exposure to ionizing radiation indicates that the decrease in chromatin mobility is transient and precedes subsequent increased mobility. Future applications of the method in the DNA repair field and beyond are discussed. PMID:25501817

Liu, Jing; Vidi, Pierre-Alexandre; Lelièvre, Sophie A; Irudayaraj, Joseph M K

2015-02-01

374

Systems-Scale Analysis Reveals Pathways Involved in Cellular Response to Methamphetamine  

PubMed Central

Background Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced. Methodology/Results We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis/contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level. Conclusion Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions. PMID:21533132

Sun, Lijie; Li, Hong-Mei; Seufferheld, Manfredo J.; Walters, Kent R.; Margam, Venu M.; Jannasch, Amber; Diaz, Naomi; Riley, Catherine P.; Sun, Weilin; Li, Yueh-Feng; Muir, William M.; Xie, Jun; Wu, Jing; Zhang, Fan; Chen, Jake Y.; Barker, Eric L.; Adamec, Jiri; Pittendrigh, Barry R.

2011-01-01

375

Revealing Real-Time Emotional Responses: a Personalized Assessment based on Heartbeat Dynamics  

PubMed Central

Emotion recognition through computational modeling and analysis of physiological signals has been widely investigated in the last decade. Most of the proposed emotion recognition systems require relatively long-time series of multivariate records and do not provide accurate real-time characterizations using short-time series. To overcome these limitations, we propose a novel personalized probabilistic framework able to characterize the emotional state of a subject through the analysis of heartbeat dynamics exclusively. The study includes thirty subjects presented with a set of standardized images gathered from the international affective picture system, alternating levels of arousal and valence. Due to the intrinsic nonlinearity and nonstationarity of the RR interval series, a specific point-process model was devised for instantaneous identification considering autoregressive nonlinearities up to the third-order according to the Wiener-Volterra representation, thus tracking very fast stimulus-response changes. Features from the instantaneous spectrum and bispectrum, as well as the dominant Lyapunov exponent, were extracted and considered as input features to a support vector machine for classification. Results, estimating emotions each 10 seconds, achieve an overall accuracy in recognizing four emotional states based on the circumplex model of affect of 79.29%, with 79.15% on the valence axis, and 83.55% on the arousal axis. PMID:24845973

Valenza, Gaetano; Citi, Luca; Lanatá, Antonio; Scilingo, Enzo Pasquale; Barbieri, Riccardo

2014-01-01

376

Genomic and proteomic analysis of transcription factor TFII-I reveals insight into the response to cellular stress  

PubMed Central

The ubiquitously expressed transcription factor TFII-I exerts both positive and negative effects on transcription. Using biotinylation tagging technology and high-throughput sequencing, we determined sites of chromatin interactions for TFII-I in the human erythroleukemia cell line K562. This analysis revealed that TFII-I binds upstream of the transcription start site of expressed genes, both upstream and downstream of the transcription start site of repressed genes, and downstream of RNA polymerase II peaks at the ATF3 and other stress responsive genes. At the ATF3 gene, TFII-I binds immediately downstream of a Pol II peak located 5 kb upstream of exon 1. Induction of ATF3 expression increases transcription throughout the ATF3 gene locus which requires TFII-I and correlates with increased association of Pol II and Elongin A. Pull-down assays demonstrated that TFII-I interacts with Elongin A. Partial depletion of TFII-I expression caused a reduction in the association of Elongin A with and transcription of the DNMT1 and EFR3A genes without a decrease in Pol II recruitment. The data reveal different interaction patterns of TFII-I at active, repressed, or inducible genes, identify novel TFII-I interacting proteins, implicate TFII-I in the regulation of transcription elongation and provide insight into the role of TFII-I during the response to cellular stress. PMID:24875474

Fan, Alex Xiucheng; Papadopoulos, Giorgio L.; Hossain, Mir A.; Lin, I.-Ju; Hu, Jianhong; Tang, Tommy Ming; Kilberg, Michael S.; Renne, Rolf; Strouboulis, John; Bungert, Jörg

2014-01-01

377

Physiological and proteomic analyses of leaves from the halophyte Tangut Nitraria reveals diverse response pathways critical for high salinity tolerance  

PubMed Central

Soil salinization poses a serious threat to the environment and agricultural productivity worldwide. Studies on the physiological and molecular mechanisms of salinity tolerance in halophytic plants provide valuable information to enhance their salt tolerance. Tangut Nitraria is a widely distributed halophyte in saline–alkali soil in the northern areas of China. In this study, we used a proteomic approach to investigate the molecular pathways of the high salt tolerance of T. Nitraria. We analyzed the changes in biomass, photosynthesis, and redox-related enzyme activities in T. Nitraria leaves from plant seedlings treated with high salt concentration. Comparative proteomic analysis of the leaves revealed that the expression of 71 proteins was significantly altered after salinity treatments of T. Nitraria. These salinity-responsive proteins were mainly involved in photosynthesis, redox homeostasis, stress/defense, carbohydrate and energy metabolism, protein metabolism, signal transduction, and membrane transport. Results showed that the reduction of photosynthesis under salt stress was attributed to the down-regulation of the enzymes and proteins involved in the light reaction and Calvin cycle. Protein–protein interaction analysis revealed that the proteins involved in redox homeostasis, photosynthesis, and energy metabolism constructed two types of response networks to high salt stress. T. Nitraria plants developed diverse mechanisms for scavenging reactive oxygen species (ROS) in their leaves to cope with stress induced by high salinity. This study provides important information regarding the salt tolerance of the halophyte T. Nitraria. PMID:25713577

Cheng, Tielong; Chen, Jinhui; Zhang, Jingbo; Shi, Shengqing; Zhou, Yanwei; Lu, Lu; Wang, Pengkai; Jiang, Zeping; Yang, Jinchang; Zhang, Shougong; Shi, Jisen

2015-01-01

378

Glycocapture-assisted global quantitative proteomics (gagQP) reveals multiorgan responses in serum toxicoproteome.  

PubMed

Blood is an ideal window for viewing our health and disease status. Because blood circulates throughout the entire body and carries secreted, shed, and excreted signature proteins from every organ and tissue type, it is thus possible to use the blood proteome to achieve a comprehensive assessment of multiple-organ physiology and pathology. To date, the blood proteome has been frequently examined for diseases of individual organs; studies on compound insults impacting multiple organs are, however, elusive. We believe that a characterization of peripheral blood for organ-specific proteins affords a powerful strategy to allow early detection, staging, and monitoring of diseases and their treatments at a whole-body level. In this paper we test this hypothesis by examining a mouse model of acetaminophen (APAP)-induced hepatic and extra-hepatic toxicity. We used a glycocapture-assisted global quantitative proteomics (gagQP) approach to study serum proteins and validated our results using Western blot. We discovered in mouse sera both hepatic and extra-hepatic organ-specific proteins. From our validation, it was determined that selected organ-specific proteins had changed their blood concentration during the course of toxicity development and recovery. Interestingly, the peak responding time of proteins specific to different organs varied in a time-course study. The collected molecular information shed light on a complex, dynamic, yet interweaving, multiorgan-enrolled APAP toxicity. The developed technique as well as the identified protein markers is translational to human studies. We hope our work can broaden the utility of blood proteomics in diagnosis and research of the whole-body response to pathogenic cues. PMID:23540550

Sun, Bingyun; Utleg, Angelita G; Hu, Zhiyuan; Qin, Shizhen; Keller, Andrew; Lorang, Cynthia; Gray, Li; Brightman, Amy; Lee, Denis; Alexander, Vinita M; Ranish, Jeffrey A; Moritz, Robert L; Hood, Leroy

2013-05-01

379

Spectral reconstruction of phase response curves reveals the synchronization properties of mouse globus pallidus neurons  

PubMed Central

The propensity of a neuron to synchronize is captured by its infinitesimal phase response curve (iPRC). Determining whether an iPRC is biphasic, meaning that small depolarizing perturbations can actually delay the next spike, if delivered at appropriate phases, is a daunting experimental task because negative lobes in the iPRC (unlike positive ones) tend to be small and may be occluded by the normal discharge variability of a neuron. To circumvent this problem, iPRCs are commonly derived from numerical models of neurons. Here, we propose a novel and natural method to estimate the iPRC by direct estimation of its spectral modes. First, we show analytically that the spectral modes of the iPRC of an arbitrary oscillator are readily measured by applying weak harmonic perturbations. Next, applying this methodology to biophysical neuronal models, we show that a low-dimensional spectral reconstruction is sufficient to capture the structure of the iPRC. This structure was preserved reasonably well even with added physiological scale jitter in the neuronal models. To validate the methodology empirically, we applied it first to a low-noise electronic oscillator with a known design and then to cortical pyramidal neurons, recorded in whole cell configuration, that are known to possess a monophasic iPRC. Finally, using the methodology in conjunction with perforated-patch recordings from pallidal neurons, we show, in contrast to recent modeling studies, that these neurons have biphasic somatic iPRCs. Biphasic iPRCs would cause lateral somatically targeted pallidal inhibition to desynchronize pallidal neurons, providing a plausible explanation for their lack of synchrony in vivo. PMID:23966679

Atherton, Jeremy F.; Surmeier, D. James

2013-01-01

380

Different responses to heat shock stress revealed heteromorphic adaptation strategy of Pyropia haitanensis (Bangiales, Rhodophyta).  

PubMed

Pyropia has a unique heteromorphic life cycle with alternation stages between thallus and conchocelis, which lives at different water temperatures in different seasons. To better understand the different adaptation strategies for temperature stress, we tried to observe comparative biochemical changes of Pyropia haitanensis based on a short term heat shock model. The results showed that: (1) At normal temperature, free-living conchocelis contains significantly higher levels of H2O2, fatty acid-derived volatiles, the copy number of Phrboh and Phhsp70 genes,the activities of NADPH oxidase and floridoside than those in thallus. The released H2O2 and NADPH oxidase activity of conchocelis were more than 7 times higher than those of thallus. The copy number of Phrboh in conchocelis was 32 times that in thallus. (2) After experiencing heat shock at 35°C for 30 min, the H2O2 contents, the mRNA levels of Phrboh and Phhsp70, NADPH oxidase activity and the floridoside content in thallus were all significantly increased. The mRNA levels of Phrboh increased 5.78 times in 5 min, NADPH oxidase activity increased 8.45 times in 20 min. (3) Whereas, in conchocelis, the changes in fatty acids and their down-stream volatiles predominated, significantly increasing levels of saturated fatty acids and decreasing levels of polyunsaturated fatty acids occurred, and the 8-carbon volatiles were accumulated. However, the changes in H2O2 content and expression of oxidant-related genes and enzymatic activity were not obvious. Overall, these results indicate that conchocelis maintains a high level of active protective apparatus to endure its survival at high temperature, while thallus exhibit typical stress responses to heat shock. It is concluded that Pyropia haitanensis has evolved a delicate strategy for temperature adaptation for its heteromorphic life cycle. PMID:24709783

Luo, Qijun; Zhu, Zhenggang; Zhu, Zhujun; Yang, Rui; Qian, Feijian; Chen, Haimin; Yan, Xiaojun

2014-01-01