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Stoffel E, Maier H, Riedl E, Bruggen MC, Reininger B, Schaschinger M, Bangert C, Guenova E, Stingl G, Brunner PM
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Analysis of anti-tumour necrosis factor-induced skin lesions reveals strong T helper 1 activation with some distinct immunological characteristics
BRITISH JOURNAL OF DERMATOLOGY 2018 MAY; 178(5):1151-1162
Background Psoriasiform and eczematous eruptions are the most common dermatological adverse reactions linked to anti-tumour necrosis factor (TNF)-alpha therapy. Yet, a detailed characterization of their immune phenotype is lacking. Objectives To characterize anti-TNF-alpha-induced inflammatory skin lesions at a histopathological, cellular and molecular level, compared with psoriasis, eczema (atopic dermatitis) and healthy control skin. Methods Histopathological evaluation, gene expression (quantitative real-time polymerase chain reaction) and computer-assisted immunohistological studies (TissueFAXS) were performed on 19 skin biopsies from patients with inflammatory bowel disease (n = 17) and rheumatoid arthritis (n = 2) with new-onset inflammatory skin lesions during anti-TNF-alpha-therapy. Results Although most biopsies showed a psoriasiform and/or spongiotic (eczematous) histopathological architecture, these lesions were inconsistent with either psoriasis or eczema on a molecular level using an established chemokine (C-C motif) ligand 27/inducible nitric oxide synthase classifier. Despite some differences in immune skewing depending on the specific histopathological reaction pattern, all anti-TNF-alpha-induced lesions showed strong interferon (IFN)-gamma activation, at higher levels than in psoriasis or eczema. IFN-gamma was most likely produced by CD3/CD4/Tbet-positive T helper 1 lymphocytes. Conclusions New-onset anti-TNF-alpha-induced eruptions previously classified as psoriasis or spongiotic dermatitis (eczema) exhibit a molecular profile that is different from either of these disorders.
Inquimbert P, Moll M, Latremoliere A, Tong CK, Whang J, Sheehan GF, Smith BM, Korb E, Athie MCP, Babaniyi O, Ghasemlou N, Yanagawa Y, Allis CD, Hof PR, Scholz J
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NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury
CELL REPORTS 2018 MAY 29; 23(9):2678-2689
Peripheral nerve lesions provoke apoptosis in the dorsal horn of the spinal cord. The cause of cell death, the involvement of neurons, and the relevance for the processing of somatosensory information are controversial. Here, we demonstrate in a mouse model of sciatic nerve injury that glutamate-induced neurodegeneration and loss of gamma-aminobutyric acid (GABA)ergic interneurons in the superficial dorsal horn promote the transition from acute to chronic neuropathic pain. Conditional deletion of Grin1, the essential subunit of N-methyl-D-aspartate-type glutamate receptors (NMDARs), protects dorsal horn neurons from excitotoxicity and preserves GABAergic inhibition. Mice deficient in functional NMDARs exhibit normal nociceptive responses and acute pain after nerve injury, but this initial increase in pain sensitivity is reversible. Eliminating NMDARs fully prevents persistent pain-like behavior. Reduced pain in mice lacking proapoptotic Bax confirmed the significance of neurodegeneration. We conclude that NMDAR-mediated neuron death contributes to the development of chronic neuropathic pain.
Jia MX, Lu H, Kong XP, Cheng-Mayer C, Wu XL
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Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques
VIRUSES-BASEL 2018 MAY; 10(5):? Article 262
Simian-human immunodeficiency virus (SHIV) infection provides a relevant animal model to study HIV-1 neutralization breadth. With previously identified SHIVSF162P3N infected rhesus macaques that did or did not develop neutralization breadth, we characterized the transmitted/founder viruses and initial autologous/homologous neutralizing antibodies in these animals. The plasma viral load and blood CD4 count did not distinguish macaques with and without breadth, and only one tested homologous envelope clone revealed a trend for macaques with breadth to favor an early homologous response. In two macaques with breadth, GB40 and FF69, infected with uncloned SHIVSF162P3N, multiple viral variants were transmitted, and the transmitted variants were not equal in neutralization sensitivity. The targets of initial autologous neutralizing antibodies, arising between 10 and 20 weeks post infection, were mapped to N462 glycan and G460a in gp120 V5 in GB40 and FF69, respectively. Although it is unclear whether these targets are related to later neutralization breadth development, the G460a target but not N462 glycan appeared more common in macaques with breadth than those without. Longitudinal plasmas revealed 2-3 sequential waves of neutralizing antibodies in macaques with breadth, implicating that 3 sequential envelope variants, if not more, may be required for the broadening of HIV-1 neutralizing antibodies.
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R, Zenoni F, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Roskas C, Trocino D, Tytgat M, Verbeke W, Vit M, Zaganidis N, Bakhshiansohi H, Bondu O, Brochet S, Bruno G, Caputo C, Caudron A, David P, Visscher S, Delaere C, Delcourt M, Francois B, Giammanco A, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Quertenmont L, Saggio A, Marono MV, Wertz S, Zobec J, Junior WL, Alves FL, Alves GA, Brito L, Silva G, Hensel C, Moraes A, Pol ME, Teles P, Das Chagas EB, Carvalho W, Chinellato J, Coelho, Costa EM, Silveira GG, Damiao DJ, De Souza S, Guativa LM, Malbouisson H, De Almeida M, Herrera C, Mundim L, Nogima H, Rosas LJ, Santoro A, Sznajder A, Thiel M, Manganote EJ, De Araujo FDS, Pereira A, Ahuja S, Bernardes CA, Tomei TRP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Abad DR, Vargas JC, Aleksandrov A, Hadjiiska R, Iaydjiev P, Marinov A, Misheva M, Rodozov M, Shopova M, Sultanov G, Dimitrov A, Litov L, Pavlov B, Petkov P, Fang W, Gao X, Yuan L, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Chen Y, Jiang CH, Leggat D, Liao H, Liu Z, Romeo F, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Yazgan E, Zhang H, Zhao J, Ban Y, Chen G, Li J, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Wang Y, Avila C, Cabrera A, Montoya CAC, Sierra LFC, Florez C, Hernandez CF, Alvarez JDR, Delgado MAS, Courbon B, Godinovic N, Lelas D, Puljak I, Cipriano PMR, Sculac T, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Kadija K, Mesic B, Starodumov A, Susa T, Ather MW, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Finger M, Finger M, Jarrin EC, Assran Y, Elgammal S, Khalil S, Bhowmik S, Dewanjee RK, Kadastik M, Perrini L, Raidal M, Veelken C, Eerola P, Kirschenmann H, Pekkanen J, Voutilainen M, Havukainen J, Heikkila JK, Jarvinen T, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Laurila S, Lehti S, Linden T, Luukka P, Maenpaa T, Siikonen H, Tuominen E, Tuominiemi J, Tuuva T, Besancon M, Couderc F, Dejardin M, 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Autermann C, Feld L, Kiesel MK, Klein K, Lipinski M, Preuten M, Schomakers C, Schulz J, Teroerde M, Wittmer B, Zhukov V, Albert A, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Knutzen S, Merschmeyer M, Meyer A, Millet P, Mukherjee S, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Teyssier D, Thuer S, Flugge G, Kargoll B, Kress T, Kunsken A, Muller T, Nehrkorn A, Nowack A, Pistone C, Pooth O, Stahl A, Martin MA, Arndt T, Asawatangtrakuldee C, Beernaert K, Behnke O, Behrens U, Martinez AB, Bin Anuar AA, Borras K, Botta V, Campbell A, Connor P, Contreras-Campana C, Costanza F, De Wit A, Pardos CD, Eckerlin G, Eckstein D, Eichhorn T, Eren E, Gallo E, Garcia JG, Geiser A, Luyando JMG, Grohsjean A, Gunnellini P, Guthoff M, Harb A, Hauk J, Hempel M, Jung H, Kasemann M, Keaveney J, Kleinwort C, Korol I, Krucker D, Lange W, Lelek A, Lenz T, Lipka K, Lohmann W, Mankel R, Melzer-Pellmann IA, Meyer AB, Meyer M, Missiroli M, Mittag G, Mnich J, Mussgiller A, Pitzl D, Raspereza A, Savitskyi M, Saxena P, Shevchenko R, Stefaniuk N, Tholen H, Van Onsem GP, Walsh R, Wen Y, Wichmann K, Wissing C, Zenaiev O, Aggleton R, Bein S, Blobel V, Vignali MC, Dreyer T, Garutti E, Gonzalez D, Haller J, Hinzmann A, Hoffmann M, Karavdina A, Kasieczka G, Klanner R, Kogler R, Kovalchuk N, Kurz S, Marconi D, Multhaup J, Niedziela M, Nowatschin D, Peiffer T, Perieanu A, Reimers A, Scharf C, Schleper P, Schmidt A, Schumann S, Schwandt J, Sonneveld J, Stadie H, Steinbrueck G, Stober FM, Stoever M, Troendle D, Usai E, Vanhoefer A, Vormwald B, Akbiyik M, Barth C, Baselga M, Baur S, Butz E, Caspart R, Chwalek T, Colombo F, Boer W, Dierlamm A, Faltermann N, Freund B, Friese R, Giffels M, Harrendorf MA, Hartmann F, Heindl SM, Husemann U, Kassel F, Kudella S, Mildner H, Mozer MU, Muller T, Plagge M, Quast G, Rabbertz K, Schroeder M, Shvetsov I, Sieber G, Simonis HJ, Ulrich R, Wayand S, Weber M, Weiler T, Williamson S, Woehrmann C, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Kyriakis A, Loukas D, Topsis-Giotis I, Karathanasis G, Kesisoglou S, Panagiotou A, Saoulidou N, Tziaferi E, Kousouris K, Papakrivopoulos I, Evangelou I, Foudas C, Gianneios P, Katsoulis P, Kokkas P, Mallios S, Manthos N, Papadopoulos I, Paradas E, Strologas J, Triantis FA, Tsitsonis D, Csanad M, Filipovic N, Pasztor G, Suranyi O, Veres GI, Bencze G, Hajdu C, Horvath D, Hunyadi A, Sikler F, Veszpremi V, Vesztergombi G, Vami TA, Beni N, Czellar S, Karancsi J, Makovec A, Molnar J, Szillasi Z, Bartok M, Raics P, Trocsanyi ZL, Ujvari B, Choudhury S, Komaragiri JR, Bahinipati S, Mal P, Mandal K, Nayak A, Sahoo DK, Sahoo N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chawla R, Dhingra N, Gupta R, Kaur A, Kaur M, Kaur S, Kumar R, Kumari P, Mehta A, Sharma S, Singh JB, Walia G, Kumar A, Shah A, Bhardwaj A, Chauhan S, Choudhary BC, Garg RB, Keshri S, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma R, Bhardwaj R, Bhattacharya R, Bhattacharya S, Bhawandeep U, Bhowmik D, Dey S, Dutt S, Dutta S, Ghosh S, Majumdar N, Modak A, Mondal K, Mukhopadhyay S, Nandan S, Purohit A, Rout PK, Roy A, Chowdhury SR, Sarkar S, Sharan M, Singh B, Thakur S, Behera PK, Chudasama R, Dutta D, Jha V, Kumar V, Mohanty AK, Netrakanti PK, Pant LM, Shukla P, Topkar A, Aziz T, Dugad S, Mahakud B, Mitra S, Mohanty GB, Sur N, Sutar B, Banerjee S, Bhattacharya S, Chatterjee S, Das P, Guchait M, Jain S, Kumar S, Maity M, Majumder G, Mazumdar K, Sarkar T, Wickramage N, Chauhan S, Dube S, Hegde V, Kapoor A, Kothekar K, Pandey S, Rane A, Sharma S, Chenarani S, Tadavani EE, Etesami SM, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Calabria C, Colaleo A, Creanza D, Cristella L, De Filippis N, De Palma M, Di Florio A, Errico F, Fiore L, Iaselli G, Lezki S, Maggi G, Maggi M, Marangelli B, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Sharma A, Silvestris L, Venditti R, Verwilligen P, Zito G, Abbiendi G, Battilana C, Bonacorsi D, Borgonovi L, Braibant-Giacomelli S, Campanini R, Capiluppi P, Castro A, Cavallo FR, Chhibra SS, Codispoti G, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Iemmi F, Marcellini S, Masetti G, Montanari A, Navarria FL, Perrotta A, Rossi AM, Rovelli T, Siroli GP, Tosi N, Albergo S, Costa S, Di Mattia A, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Chatterjee K, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Latino G, Lenzi P, Meschini M, Paoletti S, Russo L, Sguazzoni G, Strom D, Viliani L, Benussi L, Bianco S, Fabbri F, Piccolo D, Primavera F, Calvelli V, Ferro F, Ravera F, Robutti E, Tosi S, Benaglia A, Beschi A, Brianza L, Brivio F, Ciriolo V, Dinardo ME, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Malberti M, Malvezzi S, Manzoni RA, Menasce D, Moroni L, Paganoni M, Pauwels K, Pedrini D, Pigazzini S, Ragazzi S, de Fatis TT, Buontempo S, Cavallo N, Di Guida 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Lee J, Yu I, Dudenas V, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Zolkapli Z, Reyes-Almanza R, Ramirez-Sanchez G, Duran-Osuna MC, Castilla-Valdez H, La Cruz-Burelo E, La Cruz ID, Rabadan-Trejo RI, Lopez-Fernandez R, Guisao J, Sanchez-Hernandez A, Moreno S, Barrera C, Valencia F, Eysermans J, Pedraza I, Ibarguen HA, Estrada C, Pineda A, Krofcheck D, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Saddique A, Shah MA, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Szleper M, Zalewski P, Bunkowski K, Byszuk A, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Pyskir A, Walczak M, Bargassa P, Silva CDCE, Francesco A, Faccioli P, Galinhas B, Gallinaro M, Hollar J, Leonardo N, Iglesias L, Nemallapudi MV, Seixas J, Strong G, Toldaiev O, Vadruccio D, Varela J, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Lanev A, Malakhov A, Matveev 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Saltzberg D, Schnaible C, Valuev V, Bouvier E, Burt K, Clare R, Ellison J, Gary JW, Shirazi SMAG, Hanson G, Karapostoli G, Kennedy E, Lacroix F, Long OR, Negrete MO, Paneva MI, Si W, Wang L, Wei H, Wimpenny S, Yates BR, Branson JG, Cittolin S, Derdzinski M, Gerosa R, Gilbert D, Hashemi B, Holzner A, Klein D, Kole G, Krutelyov V, Letts J, Masciovecchio M, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Wood J, Wuerthwein F, Yagil A, Porta GZ, Amin N, Bhandari R, Bradmiller-Feld J, Campagnari C, Citron M, Dishaw A, Dutta V, Sevilla MF, Gouskos L, Heller R, Incandela J, Ovcharova A, Qu H, Richman J, Stuart D, Suarez I, Yoo J, Anderson D, Bornheim A, Bunn J, Lawhorn JM, Newman HB, Nguyen TQ, Pena C, Spiropulu M, Vlimant JR, Wilkinson R, Xie S, Zhang Z, Zhu RY, Andrews MB, Ferguson T, Mudholkar T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Weinberg M, Cumalat JP, Ford WT, Jensen F, Johnson A, Krohn M, Leontsinis S, Macdonald E, Mulholland T, Stenson K, Ulmer KA, Wagner SR, Alexander J, Chaves J, Cheng Y, Chu J, Datta A, Dittmer S, Mcdermott K, Mirman N, Patterson JR, Quach D, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Tan SM, Tao Z, Thom J, Tucker J, Wittich P, Zientek M, Abdullin S, Albrow M, Alyari M, Apollinari G, Apresyan A, Apyan A, Banerjee S, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Canepa A, Cerati GB, Cheung HWK, Chlebana F, Cremonesi M, Duarte J, Elvira VD, Freeman J, Gecse Z, Gottschalk E, Gray L, Green D, Gruenendahl S, Gutsche O, Hanlon J, Harris RM, Hasegawa S, Hirschauer J, Hu Z, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Lammel S, Lincoln D, Lipton R, Liu M, Liu T, De Sa RL, Lykken J, Maeshima K, Magini N, Marraffino JM, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, O'Dell V, Pedro K, Prokofyev O, Rakness G, Ristori L, Savoy-Navarro A, Schneider B, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strait J, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Wu W, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Field RD, Furic IK, Gleyzer SV, Joshi BM, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Mitselmakher G, Shi K, Sperka D, Terentyev N, Thomas L, Wang J, Wang S, Yelton J, Joshi YR, Linn S, Markowitz P, Rodriguez JL, Ackert A, Adams T, Askew A, Hagopian S, Hagopian V, Johnson KF, Kolberg T, Martinez G, Perry T, Prosper H, Saha A, Santra A, Sharma V, Yohay R, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Noonan D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Cavanaugh R, Chen X, Evdokimov O, Gerber CE, Hangal DA, Hofman DJ, Jung K, Kamin J, Gonzalez IDS, Tonjes MB, Varelas N, Wang H, Wu Z, Zhang J, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Maksimovic P, Roskes J, Sarica U, Swartz M, Xiao M, You C, Al-bataineh A, Baringer P, Bean A, Boren S, Bowen J, Castle J, Khalil S, Kropivnitskaya A, Majumder D, Mcbrayer W, Murray M, Rogan C, Royon C, Sanders S, Schmitz E, Takaki JDT, Wang Q, Ivanov A, Kaadze K, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Rebassoo F, Wright D, Baden A, Baron O, Belloni A, Eno SC, Feng Y, Ferraioli C, Hadley NJ, Jabeen S, Jeng GY, Kellogg RG, Kunkle J, Mignerey AC, Ricci-Tam F, Shin YH, Skuja A, Tonwar SC, Abercrombie D, Allen B, Azzolini V, Barbieri R, Baty A, Bauer G, Bi R, Brandt S, Busza W, Cali IA, D'Alfonso M, Demiragli Z, Ceballos GG, Goncharov M, Harris P, Hsu D, Hu M, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Lee YJ, Levin A, Luckey PD, Maier B, Marini AC, Mcginn C, Mironov C, Narayanan S, Niu X, Paus C, Roland C, Roland G, Salfeld-Nebgen J, Stephans GSF, Sumorok K, Tatar K, Velicanu D, Wang J, Wang TW, Wyslouch B, Zhaozhong S, Benvenuti AC, Chatterjee RM, Evans A, Hansen P, Kalafut S, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Turkewitz J, Wadud MA, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Claes DR, Fangmeier C, Golf F, Suarez RG, Kamalieddin R, Kravchenko I, Monroy J, Siado JE, Snow GR, Stieger B, Dolen J, Godshalk A, Harrington C, Iashvili I, Nguyen D, Parker A, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Freer C, Hortiangtham A, Massironi A, Morse DM, Orimoto T, De Lima RT, Wamorkar T, Wang B, Wisecarver A, Wood D, Bhattacharya S, Charaf O, Hahn KA, Mucia N, Odell N, Schmitt MH, Sung K, Trovato M, Velasco M, Bucci R, Dev N, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Kellams N, Lannon K, Li W, Loukas N, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Siddireddy P, Smith G, Taroni S, Wayne M, Wightman A, Wolf M, Woodard A, Alimena J, Antonelli L, Bylsma B, Durkin LS, Flowers S, Francis B, Hart A, Hill C, Ji W, Ling TY, Luo W, Winer BL, Wulsin HW, Cooperstein S, Driga O, Elmer P, Hardenbrook J, Hebda P, Higginbotham S, Kalogeropoulos A, Lange D, Luo J, Marlow D, Mei K, Ojalvo I, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Malik S, Norberg S, Barker A, Barnes VE, Das S, Gutay L, Jones M, Jung AW, Khatiwada A, Miller DH, Neumeister N, Peng CC, Qiu H, Schulte JF, Sun J, Wang F, Xiao R, Xie W, Cheng T, Parashar N, Chen Z, Ecklund KM, Freed S, Geurts FJM, Guilbaud M, Kilpatrick M, Li W, Michlin B, Padley BP, Roberts J, Rorie J, Shi W, Tu Z, Zabel J, Zhang A, Bodek A, de Barbaro P, Demina R, Duh YT, Ferbel T, Galanti M, Garcia-Bellido A, Han J, Hindrichs O, Khukhunaishvili A, Lo KH, Tan P, Verzetti M, Ciesielski R, Goulianos K, Mesropian C, Agapitos A, Chou JP, Gershtein Y, Espinosa TAG, Halkiadakis E, Heindl M, Hughes E, Kaplan S, Elayavalli RK, Kyriacou S, Lath A, Montalvo R, Nash K, Osherson M, Saka H, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Delannoy AG, Heideman J, Riley G, Rose K, Spanier S, Thapa K, Bouhali O, Hernandez AC, Celik A, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Gilmore J, Huang T, Kamon T, Mueller R, Pakhotin Y, Patel R, Perloff A, Pernie L, Rathjens D, Safonov A, Tatarinov A, Akchurin N, Damgov J, Guio F, Dudero PR, Faulkner J, Gurpinar E, Kunori S, Lamichhane K, Lee SW, Mengke T, Muthumuni S, Peltola T, Undleeb S, Volobouev I, Wang Z, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Padeken K, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Barria P, Cox B, Hirosky R, Joyce M, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Wang Y, Wolfe E, Xia F, Harr R, Karchin PE, Poudyal N, Sturdy J, Thapa P, Zaleski S, Brodski M, Buchanan J, Caillol C, Carlsmith D, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Rekovic V, Ruggles T, Savin A, Smith N, Smith WH, Woods N
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Search for Heavy Neutral Leptons in Events with Three Charged Leptons in Proton-Proton Collisions at root s=13 TeV
PHYSICAL REVIEW LETTERS 2018 MAY 29; 120(22):? Article 221801
A search for a heavy neutral lepton N of Majorana nature decaying into a W boson and a charged lepton is performed using the CMS detector at the LHC. The targeted signature consists of three prompt charged leptons in any flavor combination of electrons and muons. The data were collected in proton-proton collisions at a center-of-mass energy of 13 TeV, with an integrated luminosity of 35.9 fb(-1). The search is performed in the N mass range between 1 GeV and 1.2 TeV. The data are found to be consistent with the expected standard model background. Upper limits are set on the values of vertical bar V-eN vertical bar(2) and vertical bar V-mu N vertical bar(2), where V-lN is the matrix element describing the mixing of N with the standard model neutrino of flavor l. These are the first direct limits for N masses above 500 GeV and the first limits obtained at a hadron collider for N masses below 40 GeV.
Glanzmann B, Moller M, Moncada-Velez M, Peter J, Urban M, van Helden PD, Hoal EG, de Villiers N, Glashoff RH, Nortje R, Bustamante J, Abel L, Casanova JL, Boisson-Dupuis S, Esser M, Kinnear CJ
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Autosomal Dominant IFN-gamma R1 Deficiency Presenting with both Atypical Mycobacteriosis and Tuberculosis in a BCG-Vaccinated South African Patient
JOURNAL OF CLINICAL IMMUNOLOGY 2018 MAY; 38(4):460-463
Pukhovskaya NM, Morozova OV, Vysochina NP, Belozerova NB, Bakhmetyeva SV, Zdanovskaya NI, Seligmand SJ, Ivanov LI
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Tick-borne encephalitis virus in arthropod vectors in the Far East of Russia
TICKS AND TICK-BORNE DISEASES 2018 MAY; 9(4):824-833
Isolates of tick-borne encephalitis virus (TBEV) from arthropod vectors (ticks and mosquitoes) in the Amur, the Jewish Autonomous and the Sakhalin regions as well as on the Khabarovsk territory of the Far East of Russia were studied. Different proportions of four main tick species of the family Ixodidae: Ixodes persulcatus P. Schulze, 1930; Haemaphysalis concinna Koch, 1844; Haemaphysalis japonica douglasi Nuttall et Warburton, 1915 and Dermacentor silvarum Olenev, 1932 were found in forests and near settlements. RT-PCR of TBEV RNA in adult ticks collected from vegetation in 1999-2014 revealed average infection rates of 7.9 +/- 0.7% in I. persulcatus, of 5.6 +/- 1.0% in H. concinna, of 2.0 +/- 2.0% in H. japonica, and of 1.3 +/- 1.3% in D. silvarum. Viral loads varied in a range from 10(2) to 10(9) TBEV genome-equivalents per a tick with the maximal values in I. persulcatus and H. japonica. Molecular typing using reverse transcription with subsequent real time PCR with subtype-specific fluorescent probes demonstrated that the Far Eastern (FE) subtype of TBEV predominated both in mono-infections and in mixed infection with the Siberian (Sib) subtype in I. persulcatus pools. TBEV strains of the FE subtype were isolated from I. persulcatus, H. concinna and from a pool of Aedes vexans mosquitoes. Ten TBEV strains isolated from I. persulcatus from the Khabarovsk territory and the Jewish Autonomous region between 1985 and 2013 cluster with the TBEV vaccine strain Sofjin of the FE subtype isolated from human brain in 1937. A TBEV strain from H. concinna collected in the Amur region (GenBank accession number KF880803) is similar to the vaccine strain 205 isolated in 1973 from I. persulcatus collected in the Jewish Autonomous region. The TBEV strain Lazo MP36 of the FE subtype isolated from a pool of A. vexans in the Khabarovsk territory in 2014 (KT001073) differs from strains isolated from 1) I. persulcatus (including the vaccine strain 205) and H. concinna; 2) mosquitoes [strain Malishevo (KJ744034) isolated in 1978 from Aedes vexans nipponii in the Khabarovsk territory]; and 3) human brain (including the vaccine strain Sofjin). Accordingly, in the far eastern natural foci, TBEV of the prevailing FE subtype has remained stable since 1937. Both Russian vaccines against TBE based on the FE strains (Sofjin and 205) are similar to the new viral isolates and might protect against infection.
Galea S, Vaughan RD
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Moving Beyond the Cause Constraint: A Public Health of Consequence, May 2018
AMERICAN JOURNAL OF PUBLIC HEALTH 2018 MAY; 108(5):602-603
Dunphy MPS, Harding JJ, Venneti S, Zhang HW, Burnazi EM, Bromberg J, Omuro AM, Hsieh JJ, Mellinghoff IK, Staton K, Pressl C, Beattie BJ, Zanzonico PB, Gerecitano JF, Kelsen DP, Weber W, Lyashchenko SK, Kung HF, Lewis JS
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In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of F-18-(2S,4R)-4-Fluoroglutamine
RADIOLOGY 2018 MAY; 287(2):667-675
Purpose: To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods: This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq +/- 118, <100 mu g) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P < .05 was considered indicative of a statistically significant difference. Results: FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P = .07). Patients experienced no adverse effects. Conclusion: Preliminary human FGln PET trial results provide clinical validation of abnormal glutamine metabolism as a potential tumor biomarker for targeted radiotracer imaging in several different cancer types. (C)RSNA, 2018
Bucciol G, Cassiman D, Roskams T, Renard M, Hoffman I, Witters P, Schrijvers R, Schaballie H, Bosch B, Putti MC, Gheysens O, Knops N, Gewillig M, Mekahli D, Pirenne J, Meyts I
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Liver transplantation for very severe hepatopulmonary syndrome due to vitamin A-induced chronic liver disease in a patient with Shwachman-Diamond syndrome
ORPHANET JOURNAL OF RARE DISEASES 2018 MAY 2; 13(?):? Article 69
Vitamin A intoxication is a rare cause of liver disease, but the risk increases in patients with underlying liver dysfunction. We present a patient with Shwachman-Diamond Syndrome who developed liver fibrosis, portal hypertension and very severe hepatopulmonary syndrome as a consequence of chronic vitamin A intoxication. She underwent successful liver transplantation with complete resolution of the pulmonary shunting.
Li J, Casanova JL, Puel A
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Mucocutaneous IL-17 immunity in mice and humans: host defense vs. excessive inflammation
MUCOSAL IMMUNOLOGY 2018 MAY; 11(3):581-589
Interleukin (IL)-17A is a pro-inflammatory cytokine in mice and humans. It is recognized as a key factor for the protection of mice against various pathogens, but it also underlies pathogenic inflammatory responses in numerous mouse models. The inborn errors of IL-17A- and IL-17F-mediated immunity identified in humans in the last decade have revealed that IL-17A and IL-17F are key players in mucocutaneous immunity to Candida albicans, and, to a lesser extent, Staphylococcus aureus. By contrast, there is currently no genetic evidence for a causal link between excess of IL-17 and autoimmunity, autoinflammation, or allergy in humans. We discuss here the physiological and pathological roles of mouse and human IL-17A and IL-17F in host defense and excessive inflammation. We highlight recent advances in our understanding of the consequences of deficient or excessive IL-17 immunity at various mucocutaneous sites, including the oral cavity, skin, intestine, lungs, and vagina.