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1. Low-dose orthotopic cancer implantation permits measurement of longitudinal functional changes associated with cachexia.

Author

Roy I, Binder-Markey B, Willbanks A, Sychowski D, Phipps T, Barber A, McAllister D, D'Andrea D, Franz CK, Pichika R, Dwinell MB, and Lieber RL

Subjects
Animals, Mice, Disease Models, Animal, Male, Cell Line, Tumor, Neoplasms complications, Neoplasms physiopathology, Muscular Atrophy physiopathology, Hand Strength physiology, Female, Cachexia physiopathology, Muscle, Skeletal physiopathology
Abstract

Progressive functional decline is a key element of cancer-associated cachexia. Major barriers to translating preclinical therapies into the clinic include lack of cancer models that accurately mimic functional decline, which develops over time, and use of nonspecific measures, like grip strength, as surrogates for physical function. In this study, we aimed to extend the survival and longevity of a cancer model, to investigate cachexia-related function at the basic science level. Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-ras LSL.G12D/+ ; Trp53 R172H/+ ; Pdx-1-Cre (KPC)-derived cells. One hundred twenty-eight animals in this new model were assessed for cachexia syndrome phenotype using a battery of anatomical, biochemical, and behavioral techniques. We extended the survival of the KPC orthotopic model to 8-9 wk postimplantation using a relatively low 100-cell dose of DT10022 KPC cells ( P < 0.001). In this low-dose orthotopic (LO) model, progressive muscle wasting was detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 wk postimplantation compared with controls ( P < 0.001). Gait speed in LO animals declined as early as 2 wk postimplantation, whereas grip strength change was a late event. Principal component and regression analyses revealed distinct cachectic and noncachectic animal populations, which we leveraged to show that the gait speed decline was specific to cachexia ( P < 0.01), whereas grip strength decline was not ( P = 0.19). Gait speed represents an accurate surrogate for cachexia-related physical function as opposed to grip strength. NEW & NOTEWORTHY Previous studies of cancer-induced cachexia have been confounded by the relatively rapid death of animal subjects. Using a lower dose of cancer cells in combination with a battery of behavioral, structural, histological, and biochemical techniques, we show that gait speed is actually the best indicator of functional decline due to cachexia. Future studies are required to define the underlying physiological basis of these findings.

Published
2024
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2. Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.

Author

Abu-Shawareb H, Acree R, Adams P, Adams J, Addis B, Aden R, Adrian P, Afeyan BB, Aggleton M, Aghaian L, Aguirre A, Aikens D, Akre J, Albert F, Albrecht M, Albright BJ, Albritton J, Alcala J, Alday C, Alessi DA, Alexander N, Alfonso J, Alfonso N, Alger E, Ali SJ, Ali ZA, Allen A, Alley WE, Amala P, Amendt PA, Amick P, Ammula S, Amorin C, Ampleford DJ, Anderson RW, Anklam T, Antipa N, Appelbe B, Aracne-Ruddle C, Araya E, Archuleta TN, Arend M, Arnold P, Arnold T, Arsenlis A, Asay J, Atherton LJ, Atkinson D, Atkinson R, Auerbach JM, Austin B, Auyang L, Awwal AAS, Aybar N, Ayers J, Ayers S, Ayers T, Azevedo S, Bachmann B, Back CA, Bae J, Bailey DS, Bailey J, Baisden T, Baker KL, Baldis H, Barber D, Barberis M, Barker D, Barnes A, Barnes CW, Barrios MA, Barty C, Bass I, Batha SH, Baxamusa SH, Bazan G, Beagle JK, Beale R, Beck BR, Beck JB, Bedzyk M, Beeler RG, Beeler RG, Behrendt W, Belk L, Bell P, Belyaev M, Benage JF, Bennett G, Benedetti LR, Benedict LX, Berger RL, Bernat T, Bernstein LA, Berry B, Bertolini L, Besenbruch G, Betcher J, Bettenhausen R, Betti R, Bezzerides B, Bhandarkar SD, Bickel R, Biener J, Biesiada T, Bigelow K, Bigelow-Granillo J, Bigman V, Bionta RM, Birge NW, Bitter M, Black AC, Bleile R, Bleuel DL, Bliss E, Bliss E, Blue B, Boehly T, Boehm K, Boley CD, Bonanno R, Bond EJ, Bond T, Bonino MJ, Borden M, Bourgade JL, Bousquet J, Bowers J, Bowers M, Boyd R, Boyle D, Bozek A, Bradley DK, Bradley KS, Bradley PA, Bradley L, Brannon L, Brantley PS, Braun D, Braun T, Brienza-Larsen K, Briggs R, Briggs TM, Britten J, Brooks ED, Browning D, Bruhn MW, Brunner TA, Bruns H, Brunton G, Bryant B, Buczek T, Bude J, Buitano L, Burkhart S, Burmark J, Burnham A, Burr R, Busby LE, Butlin B, Cabeltis R, Cable M, Cabot WH, Cagadas B, Caggiano J, Cahayag R, Caldwell SE, Calkins S, Callahan DA, Calleja-Aguirre J, Camara L, Camp D, Campbell EM, Campbell JH, Carey B, Carey R, Carlisle K, Carlson L, Carman L, Carmichael J, Carpenter A, Carr C, Carrera JA, Casavant D, Casey A, Casey DT, Castillo A, Castillo E, Castor JI, Castro C, Caughey W, Cavitt R, Celeste J, Celliers PM, Cerjan C, Chandler G, Chang B, Chang C, Chang J, Chang L, Chapman R, Chapman TD, Chase L, Chen H, Chen H, Chen K, Chen LY, Cheng B, Chittenden J, Choate C, Chou J, Chrien RE, Chrisp M, Christensen K, Christensen M, Christiansen NS, Christopherson AR, Chung M, Church JA, Clark A, Clark DS, Clark K, Clark R, Claus L, Cline B, Cline JA, Cobble JA, Cochrane K, Cohen B, Cohen S, Collette MR, Collins GW, Collins LA, Collins TJB, Conder A, Conrad B, Conyers M, Cook AW, Cook D, Cook R, Cooley JC, Cooper G, Cope T, Copeland SR, Coppari F, Cortez J, Cox J, Crandall DH, Crane J, Craxton RS, Cray M, Crilly A, Crippen JW, Cross D, Cuneo M, Cuotts G, Czajka CE, Czechowicz D, Daly T, Danforth P, Danly C, Darbee R, Darlington B, Datte P, Dauffy L, Davalos G, Davidovits S, Davis P, Davis J, Dawson S, Day RD, Day TH, Dayton M, Deck C, Decker C, Deeney C, DeFriend KA, Deis G, Delamater ND, Delettrez JA, Demaret R, Demos S, Dempsey SM, Desjardin R, Desjardins T, Desjarlais MP, Dewald EL, DeYoreo J, Diaz S, Dimonte G, Dittrich TR, Divol L, Dixit SN, Dixon J, Do A, Dodd ES, Dolan D, Donovan A, Donovan M, Döppner T, Dorrer C, Dorsano N, Douglas MR, Dow D, Downie J, Downing E, Dozieres M, Draggoo V, Drake D, Drake RP, Drake T, Dreifuerst G, Drury O, DuBois DF, DuBois PF, Dunham G, Durocher M, Dylla-Spears R, Dymoke-Bradshaw AKL, Dzenitis B, Ebbers C, Eckart M, Eddinger S, Eder D, Edgell D, Edwards MJ, Efthimion P, Eggert JH, Ehrlich B, Ehrmann P, Elhadj S, Ellerbee C, Elliott NS, Ellison CL, Elsner F, Emerich M, Engelhorn K, England T, English E, Epperson P, Epstein R, Erbert G, Erickson MA, Erskine DJ, Erlandson A, Espinosa RJ, Estes C, Estabrook KG, Evans S, Fabyan A, Fair J, Fallejo R, Farmer N, Farmer WA, Farrell M, Fatherley VE, Fedorov M, Feigenbaum E, Fehrenbach T, Feit M, Felker B, Ferguson W, Fernandez JC, Fernandez-Panella A, Fess S, Field JE, Filip CV, Fincke JR, Finn T, Finnegan SM, Finucane RG, Fischer M, Fisher A, Fisher J, Fishler B, Fittinghoff D, Fitzsimmons P, Flegel M, Flippo KA, Florio J, Folta J, Folta P, Foreman LR, Forrest C, Forsman A, Fooks J, Foord M, Fortner R, Fournier K, Fratanduono DE, Frazier N, Frazier T, Frederick C, Freeman MS, Frenje J, Frey D, Frieders G, Friedrich S, Froula DH, Fry J, Fuller T, Gaffney J, Gales S, Le Galloudec B, Le Galloudec KK, Gambhir A, Gao L, Garbett WJ, Garcia A, Gates C, Gaut E, Gauthier P, Gavin Z, Gaylord J, Geddes CGR, Geissel M, Génin F, Georgeson J, Geppert-Kleinrath H, Geppert-Kleinrath V, Gharibyan N, Gibson J, Gibson C, Giraldez E, Glebov V, Glendinning SG, Glenn S, Glenzer SH, Goade S, Gobby PL, Goldman SR, Golick B, Gomez M, Goncharov V, Goodin D, Grabowski P, Grafil E, Graham P, Grandy J, Grasz E, Graziani FR, Greenman G, Greenough JA, Greenwood A, Gregori G, Green T, Griego JR, Grim GP, Grondalski J, Gross S, Guckian J, Guler N, Gunney B, Guss G, Haan S, Hackbarth J, Hackel L, Hackel R, Haefner C, Hagmann C, Hahn KD, Hahn S, Haid BJ, Haines BM, Hall BM, Hall C, Hall GN, Hamamoto M, Hamel S, Hamilton CE, Hammel BA, Hammer JH, Hampton G, Hamza A, Handler A, Hansen S, Hanson D, Haque R, Harding D, Harding E, Hares JD, Harris DB, Harte JA, Hartouni EP, Hatarik R, Hatchett S, Hauer AA, Havre M, Hawley R, Hayes J, Hayes J, Hayes S, Hayes-Sterbenz A, Haynam CA, Haynes DA, Headley D, Heal A, Heebner JE, Heerey S, Heestand GM, Heeter R, Hein N, Heinbockel C, Hendricks C, Henesian M, Heninger J, Henrikson J, Henry EA, Herbold EB, Hermann MR, Hermes G, Hernandez JE, Hernandez VJ, Herrmann MC, Herrmann HW, Herrera OD, Hewett D, Hibbard R, Hicks DG, Higginson DP, Hill D, Hill K, Hilsabeck T, Hinkel DE, Ho DD, Ho VK, Hoffer JK, Hoffman NM, Hohenberger M, Hohensee M, Hoke W, Holdener D, Holdener F, Holder JP, Holko B, Holunga D, Holzrichter JF, Honig J, Hoover D, Hopkins D, Berzak Hopkins LF, Hoppe M, Hoppe ML, Horner J, Hornung R, Horsfield CJ, Horvath J, Hotaling D, House R, Howell L, Hsing WW, Hu SX, Huang H, Huckins J, Hui H, Humbird KD, Hund J, Hunt J, Hurricane OA, Hutton M, Huynh KH, Inandan L, Iglesias C, Igumenshchev IV, Ivanovich I, Izumi N, Jackson M, Jackson J, Jacobs SD, James G, Jancaitis K, Jarboe J, Jarrott LC, Jasion D, Jaquez J, Jeet J, Jenei AE, Jensen J, Jimenez J, Jimenez R, Jobe D, Johal Z, Johns HM, Johnson D, Johnson MA, Gatu Johnson M, Johnson RJ, Johnson S, Johnson SA, Johnson T, Jones K, Jones O, Jones M, Jorge R, Jorgenson HJ, Julian M, Jun BI, Jungquist R, Kaae J, Kabadi N, Kaczala D, Kalantar D, Kangas K, Karasiev VV, Karasik M, Karpenko V, Kasarky A, Kasper K, Kauffman R, Kaufman MI, Keane C, Keaty L, Kegelmeyer L, Keiter PA, Kellett PA, Kellogg J, Kelly JH, Kemic S, Kemp AJ, Kemp GE, Kerbel GD, Kershaw D, Kerr SM, Kessler TJ, Key MH, Khan SF, Khater H, Kiikka C, Kilkenny J, Kim Y, Kim YJ, Kimko J, Kimmel M, Kindel JM, King J, Kirkwood RK, Klaus L, Klem D, Kline JL, Klingmann J, Kluth G, Knapp P, Knauer J, Knipping J, Knudson M, Kobs D, Koch J, Kohut T, Kong C, Koning JM, Koning P, Konior S, Kornblum H, Kot LB, Kozioziemski B, Kozlowski M, Kozlowski PM, Krammen J, Krasheninnikova NS, Krauland CM, Kraus B, Krauser W, Kress JD, Kritcher AL, Krieger E, Kroll JJ, Kruer WL, Kruse MKG, Kucheyev S, Kumbera M, Kumpan S, Kunimune J, Kur E, Kustowski B, Kwan TJT, Kyrala GA, Laffite S, Lafon M, LaFortune K, Lagin L, Lahmann B, Lairson B, Landen OL, Land T, Lane M, Laney D, Langdon AB, Langenbrunner J, Langer SH, Langro A, Lanier NE, Lanier TE, Larson D, Lasinski BF, Lassle D, LaTray D, Lau G, Lau N, Laumann C, Laurence A, Laurence TA, Lawson J, Le HP, Leach RR, Leal L, Leatherland A, LeChien K, Lechleiter B, Lee A, Lee M, Lee T, Leeper RJ, Lefebvre E, Leidinger JP, LeMire B, Lemke RW, Lemos NC, Le Pape S, Lerche R, Lerner S, Letts S, Levedahl K, Lewis T, Li CK, Li H, Li J, Liao W, Liao ZM, Liedahl D, Liebman J, Lindford G, Lindman EL, Lindl JD, Loey H, London RA, Long F, Loomis EN, Lopez FE, Lopez H, Losbanos E, Loucks S, Lowe-Webb R, Lundgren E, Ludwigsen AP, Luo R, Lusk J, Lyons R, Ma T, Macallop Y, MacDonald MJ, MacGowan BJ, Mack JM, Mackinnon AJ, MacLaren SA, MacPhee AG, Magelssen GR, Magoon J, Malone RM, Malsbury T, Managan R, Mancini R, Manes K, Maney D, Manha D, Mannion OM, Manuel AM, Manuel MJ, Mapoles E, Mara G, Marcotte T, Marin E, Marinak MM, Mariscal DA, Mariscal EF, Marley EV, Marozas JA, Marquez R, Marshall CD, Marshall FJ, Marshall M, Marshall S, Marticorena J, Martinez JI, Martinez D, Maslennikov I, Mason D, Mason RJ, Masse L, Massey W, Masson-Laborde PE, Masters ND, Mathisen D, Mathison E, Matone J, Matthews MJ, Mattoon C, Mattsson TR, Matzen K, Mauche CW, Mauldin M, McAbee T, McBurney M, Mccarville T, McCrory RL, McEvoy AM, McGuffey C, Mcinnis M, McKenty P, McKinley MS, McLeod JB, McPherson A, Mcquillan B, Meamber M, Meaney KD, Meezan NB, Meissner R, Mehlhorn TA, Mehta NC, Menapace J, Merrill FE, Merritt BT, Merritt EC, Meyerhofer DD, Mezyk S, Mich RJ, Michel PA, Milam D, Miller C, Miller D, Miller DS, Miller E, Miller EK, Miller J, Miller M, Miller PE, Miller T, Miller W, Miller-Kamm V, Millot M, Milovich JL, Minner P, Miquel JL, Mitchell S, Molvig K, Montesanti RC, Montgomery DS, Monticelli M, Montoya A, Moody JD, Moore AS, Moore E, Moran M, Moreno JC, Moreno K, Morgan BE, Morrow T, Morton JW, Moses E, Moy K, Muir R, Murillo MS, Murray JE, Murray JR, Munro DH, Murphy TJ, Munteanu FM, Nafziger J, Nagayama T, Nagel SR, Nast R, Negres RA, Nelson A, Nelson D, Nelson J, Nelson S, Nemethy S, Neumayer P, Newman K, Newton M, Nguyen H, Di Nicola JG, Di Nicola P, Niemann C, Nikroo A, Nilson PM, Nobile A, Noorai V, Nora RC, Norton M, Nostrand M, Note V, Novell S, Nowak PF, Nunez A, Nyholm RA, O'Brien M, Oceguera A, Oertel JA, Oesterle AL, Okui J, Olejniczak B, Oliveira J, Olsen P, Olson B, Olson K, Olson RE, Opachich YP, Orsi N, Orth CD, Owen M, Padalino S, Padilla E, Paguio R, Paguio S, Paisner J, Pajoom S, Pak A, Palaniyappan S, Palma K, Pannell T, Papp F, Paras D, Parham T, Park HS, Pasternak A, Patankar S, Patel MV, Patel PK, Patterson R, Patterson S, Paul B, Paul M, Pauli E, Pearce OT, Pearcy J, Pedretti A, Pedrotti B, Peer A, Pelz LJ, Penetrante B, Penner J, Perez A, Perkins LJ, Pernice E, Perry TS, Person S, Petersen D, Petersen T, Peterson DL, Peterson EB, Peterson JE, Peterson JL, Peterson K, Peterson RR, Petrasso RD, Philippe F, Phillion D, Phipps TJ, Piceno E, Pickworth L, Ping Y, Pino J, Piston K, Plummer R, Pollack GD, Pollaine SM, Pollock BB, Ponce D, Ponce J, Pontelandolfo J, Porter JL, Post J, Poujade O, Powell C, Powell H, Power G, Pozulp M, Prantil M, Prasad M, Pratuch S, Price S, Primdahl K, Prisbrey S, Procassini R, Pruyne A, Pudliner B, Qiu SR, Quan K, Quinn M, Quintenz J, Radha PB, Rainer F, Ralph JE, Raman KS, Raman R, Rambo PW, Rana S, Randewich A, Rardin D, Ratledge M, Ravelo N, Ravizza F, Rayce M, Raymond A, Raymond B, Reed B, Reed C, Regan S, Reichelt B, Reis V, Reisdorf S, Rekow V, Remington BA, Rendon A, Requieron W, Rever M, Reynolds H, Reynolds J, Rhodes J, Rhodes M, Richardson MC, Rice B, Rice NG, Rieben R, Rigatti A, Riggs S, Rinderknecht HG, Ring K, Riordan B, Riquier R, Rivers C, Roberts D, Roberts V, Robertson G, Robey HF, Robles J, Rocha P, Rochau G, Rodriguez J, Rodriguez S, Rosen MD, Rosenberg M, Ross G, Ross JS, Ross P, Rouse J, Rovang D, Rubenchik AM, Rubery MS, Ruiz CL, Rushford M, Russ B, Rygg JR, Ryujin BS, Sacks RA, Sacks RF, Saito K, Salmon T, Salmonson JD, Sanchez J, Samuelson S, Sanchez M, Sangster C, Saroyan A, Sater J, Satsangi A, Sauers S, Saunders R, Sauppe JP, Sawicki R, Sayre D, Scanlan M, Schaffers K, Schappert GT, Schiaffino S, Schlossberg DJ, Schmidt DW, Schmit PF, Smidt JM, Schneider DHG, Schneider MB, Schneider R, Schoff M, Schollmeier M, Schroeder CR, Schrauth SE, Scott HA, Scott I, Scott JM, Scott RHH, Scullard CR, Sedillo T, Seguin FH, Seka W, Senecal J, Sepke SM, Seppala L, Sequoia K, Severyn J, Sevier JM, Sewell N, Seznec S, Shah RC, Shamlian J, Shaughnessy D, Shaw M, Shaw R, Shearer C, Shelton R, Shen N, Sherlock MW, Shestakov AI, Shi EL, Shin SJ, Shingleton N, Shmayda W, Shor M, Shoup M, Shuldberg C, Siegel L, Silva FJ, Simakov AN, Sims BT, Sinars D, Singh P, Sio H, Skulina K, Skupsky S, Slutz S, Sluyter M, Smalyuk VA, Smauley D, Smeltser RM, Smith C, Smith I, Smith J, Smith L, Smith R, Smith R, Schölmerich M, Sohn R, Sommer S, Sorce C, Sorem M, Soures JM, Spaeth ML, Spears BK, Speas S, Speck D, Speck R, Spears J, Spinka T, Springer PT, Stadermann M, Stahl B, Stahoviak J, Stanley J, Stanton LG, Steele R, Steele W, Steinman D, Stemke R, Stephens R, Sterbenz S, Sterne P, Stevens D, Stevers J, Still CH, Stoeckl C, Stoeffl W, Stolken JS, Stolz C, Storm E, Stone G, Stoupin S, Stout E, Stowers I, Strauser R, Streckart H, Streit J, Strozzi DJ, Stutz J, Summers L, Suratwala T, Sutcliffe G, Suter LJ, Sutton SB, Svidzinski V, Swadling G, Sweet W, Szoke A, Tabak M, Takagi M, Tambazidis A, Tang V, Taranowski M, Taylor LA, Telford S, Theobald W, Thi M, Thomas A, Thomas CA, Thomas I, Thomas R, Thompson IJ, Thongstisubskul A, Thorsness CB, Tietbohl G, Tipton RE, Tobin M, Tomlin N, Tommasini R, Toreja AJ, Torres J, Town RPJ, Townsend S, Trenholme J, Trivelpiece A, Trosseille C, Truax H, Trummer D, Trummer S, Truong T, Tubbs D, Tubman ER, Tunnell T, Turnbull D, Turner RE, Ulitsky M, Upadhye R, Vaher JL, VanArsdall P, VanBlarcom D, Vandenboomgaerde M, VanQuinlan R, Van Wonterghem BM, Varnum WS, Velikovich AL, Vella A, Verdon CP, Vermillion B, Vernon S, Vesey R, Vickers J, Vignes RM, Visosky M, Vocke J, Volegov PL, Vonhof S, Von Rotz R, Vu HX, Vu M, Wall D, Wall J, Wallace R, Wallin B, Walmer D, Walsh CA, Walters CF, Waltz C, Wan A, Wang A, Wang Y, Wark JS, Warner BE, Watson J, Watt RG, Watts P, Weaver J, Weaver RP, Weaver S, Weber CR, Weber P, Weber SV, Wegner P, Welday B, Welser-Sherrill L, Weiss K, Wharton KB, Wheeler GF, Whistler W, White RK, Whitley HD, Whitman P, Wickett ME, Widmann K, Widmayer C, Wiedwald J, Wilcox R, Wilcox S, Wild C, Wilde BH, Wilde CH, Wilhelmsen K, Wilke MD, Wilkens H, Wilkins P, Wilks SC, Williams EA, Williams GJ, Williams W, Williams WH, Wilson DC, Wilson B, Wilson E, Wilson R, Winters S, Wisoff PJ, Wittman M, Wolfe J, Wong A, Wong KW, Wong L, Wong N, Wood R, Woodhouse D, Woodruff J, Woods DT, Woods S, Woodworth BN, Wooten E, Wootton A, Work K, Workman JB, Wright J, Wu M, Wuest C, Wysocki FJ, Xu H, Yamaguchi M, Yang B, Yang ST, Yatabe J, Yeamans CB, Yee BC, Yi SA, Yin L, Young B, Young CS, Young CV, Young P, Youngblood K, Yu J, Zacharias R, Zagaris G, Zaitseva N, Zaka F, Ze F, Zeiger B, Zika M, Zimmerman GB, Zobrist T, Zuegel JD, and Zylstra AB

Abstract

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Published
2024
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3. Gait speed is a biomarker of cancer-associated cachexia decline and recovery.

Author

Roy I, Binder-Markey B, Sychowski D, Willbanks A, Phipps T, McAllister D, Bhakta A, Marquez E, D'Andrea D, Franz C, Pichika R, Dwinell MB, Jayabalan P, and Lieber RL

Abstract

Background: Progressive functional decline is a key element of cancer-associated cachexia. No therapies have successfully translated to the clinic due to an inability to measure and improve physical function in cachectic patients. Major barriers to translating pre-clinical therapies to the clinic include lack of cancer models that accurately mimic functional decline and use of non-specific outcome measures of function, like grip strength. New approaches are needed to investigate cachexia-related function at both the basic and clinical science levels., Methods: Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-ras LSL.G12D/+ ; Trp53 R172H/+ ; Pdx-1-Cre (KPC) derived cells. 128 animals in this new model were then assessed for muscle wasting, inflammation, and functional decline using a battery of biochemical, physiologic, and behavioral techniques. In parallel, we analyzed a 156-subject cohort of cancer patients with a range of cachexia severity, and who required rehabilitation, to determine the relationship between gait speed via six-minute walk test (6MWT), grip strength (hGS), and functional independence measures (FIM). Cachectic patients were identified using the Weight Loss Grading Scale (WLGS), Fearon consensus criteria, and the Prognostic Nutritional Index (PNI)., Results: Using a 100-cell dose of DT10022 KPC cells, we extended the survival of the KPC orthotopic model to 8-9 weeks post-implantation compared to higher doses used (p<0.001). In this Low-dose Orthotopic (LO) model, both progressive skeletal and cardiac muscle wasting were detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 weeks post-implantation compared to controls (p<0.001). Gait speed in LO animals declined as early 2 week post-implantation whereas grip strength change was a late event and related to end of life. Principle component analysis (PCA) revealed distinct cachectic and non-cachectic animal populations, which we leveraged to show that gait speed decline was specific to cachexia (p<0.01) while grip strength decline was not (p=0.19). These data paralleled our observations in cancer patients with cachexia who required rehabilitation. In cachectic patients (identified by WLGS, Fearon criteria, or PNI, change in 6MWT correlated with motor FIM score changes while hGS did not (r 2 =0.18, p<0.001). This relationship between 6MWT and FIM in cachectic patients was further confirmed through multivariate regression (r 2 =0.30, p<0.001) controlling for age and cancer burden., Conclusion: Outcome measures linked to gait are better associated with cachexia related function and preferred for future pre-clinical and clinical cachexia studies.

Published
2023
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4. Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment.

Author

Abu-Shawareb H, Acree R, Adams P, Adams J, Addis B, Aden R, Adrian P, Afeyan BB, Aggleton M, Aghaian L, Aguirre A, Aikens D, Akre J, Albert F, Albrecht M, Albright BJ, Albritton J, Alcala J, Alday C, Alessi DA, Alexander N, Alfonso J, Alfonso N, Alger E, Ali SJ, Ali ZA, Alley WE, Amala P, Amendt PA, Amick P, Ammula S, Amorin C, Ampleford DJ, Anderson RW, Anklam T, Antipa N, Appelbe B, Aracne-Ruddle C, Araya E, Arend M, Arnold P, Arnold T, Asay J, Atherton LJ, Atkinson D, Atkinson R, Auerbach JM, Austin B, Auyang L, Awwal AS, Ayers J, Ayers S, Ayers T, Azevedo S, Bachmann B, Back CA, Bae J, Bailey DS, Bailey J, Baisden T, Baker KL, Baldis H, Barber D, Barberis M, Barker D, Barnes A, Barnes CW, Barrios MA, Barty C, Bass I, Batha SH, Baxamusa SH, Bazan G, Beagle JK, Beale R, Beck BR, Beck JB, Bedzyk M, Beeler RG, Beeler RG, Behrendt W, Belk L, Bell P, Belyaev M, Benage JF, Bennett G, Benedetti LR, Benedict LX, Berger R, Bernat T, Bernstein LA, Berry B, Bertolini L, Besenbruch G, Betcher J, Bettenhausen R, Betti R, Bezzerides B, Bhandarkar SD, Bickel R, Biener J, Biesiada T, Bigelow K, Bigelow-Granillo J, Bigman V, Bionta RM, Birge NW, Bitter M, Black AC, Bleile R, Bleuel DL, Bliss E, Bliss E, Blue B, Boehly T, Boehm K, Boley CD, Bonanno R, Bond EJ, Bond T, Bonino MJ, Borden M, Bourgade JL, Bousquet J, Bowers J, Bowers M, Boyd R, Bozek A, Bradley DK, Bradley KS, Bradley PA, Bradley L, Brannon L, Brantley PS, Braun D, Braun T, Brienza-Larsen K, Briggs TM, Britten J, Brooks ED, Browning D, Bruhn MW, Brunner TA, Bruns H, Brunton G, Bryant B, Buczek T, Bude J, Buitano L, Burkhart S, Burmark J, Burnham A, Burr R, Busby LE, Butlin B, Cabeltis R, Cable M, Cabot WH, Cagadas B, Caggiano J, Cahayag R, Caldwell SE, Calkins S, Callahan DA, Calleja-Aguirre J, Camara L, Camp D, Campbell EM, Campbell JH, Carey B, Carey R, Carlisle K, Carlson L, Carman L, Carmichael J, Carpenter A, Carr C, Carrera JA, Casavant D, Casey A, Casey DT, Castillo A, Castillo E, Castor JI, Castro C, Caughey W, Cavitt R, Celeste J, Celliers PM, Cerjan C, Chandler G, Chang B, Chang C, Chang J, Chang L, Chapman R, Chapman T, Chase L, Chen H, Chen H, Chen K, Chen LY, Cheng B, Chittenden J, Choate C, Chou J, Chrien RE, Chrisp M, Christensen K, Christensen M, Christopherson AR, Chung M, Church JA, Clark A, Clark DS, Clark K, Clark R, Claus L, Cline B, Cline JA, Cobble JA, Cochrane K, Cohen B, Cohen S, Collette MR, Collins G, Collins LA, Collins TJB, Conder A, Conrad B, Conyers M, Cook AW, Cook D, Cook R, Cooley JC, Cooper G, Cope T, Copeland SR, Coppari F, Cortez J, Cox J, Crandall DH, Crane J, Craxton RS, Cray M, Crilly A, Crippen JW, Cross D, Cuneo M, Cuotts G, Czajka CE, Czechowicz D, Daly T, Danforth P, Darbee R, Darlington B, Datte P, Dauffy L, Davalos G, Davidovits S, Davis P, Davis J, Dawson S, Day RD, Day TH, Dayton M, Deck C, Decker C, Deeney C, DeFriend KA, Deis G, Delamater ND, Delettrez JA, Demaret R, Demos S, Dempsey SM, Desjardin R, Desjardins T, Desjarlais MP, Dewald EL, DeYoreo J, Diaz S, Dimonte G, Dittrich TR, Divol L, Dixit SN, Dixon J, Dodd ES, Dolan D, Donovan A, Donovan M, Döppner T, Dorrer C, Dorsano N, Douglas MR, Dow D, Downie J, Downing E, Dozieres M, Draggoo V, Drake D, Drake RP, Drake T, Dreifuerst G, DuBois DF, DuBois PF, Dunham G, Dylla-Spears R, Dymoke-Bradshaw AKL, Dzenitis B, Ebbers C, Eckart M, Eddinger S, Eder D, Edgell D, Edwards MJ, Efthimion P, Eggert JH, Ehrlich B, Ehrmann P, Elhadj S, Ellerbee C, Elliott NS, Ellison CL, Elsner F, Emerich M, Engelhorn K, England T, English E, Epperson P, Epstein R, Erbert G, Erickson MA, Erskine DJ, Erlandson A, Espinosa RJ, Estes C, Estabrook KG, Evans S, Fabyan A, Fair J, Fallejo R, Farmer N, Farmer WA, Farrell M, Fatherley VE, Fedorov M, Feigenbaum E, Feit M, Ferguson W, Fernandez JC, Fernandez-Panella A, Fess S, Field JE, Filip CV, Fincke JR, Finn T, Finnegan SM, Finucane RG, Fischer M, Fisher A, Fisher J, Fishler B, Fittinghoff D, Fitzsimmons P, Flegel M, Flippo KA, Florio J, Folta J, Folta P, Foreman LR, Forrest C, Forsman A, Fooks J, Foord M, Fortner R, Fournier K, Fratanduono DE, Frazier N, Frazier T, Frederick C, Freeman MS, Frenje J, Frey D, Frieders G, Friedrich S, Froula DH, Fry J, Fuller T, Gaffney J, Gales S, Le Galloudec B, Le Galloudec KK, Gambhir A, Gao L, Garbett WJ, Garcia A, Gates C, Gaut E, Gauthier P, Gavin Z, Gaylord J, Geissel M, Génin F, Georgeson J, Geppert-Kleinrath H, Geppert-Kleinrath V, Gharibyan N, Gibson J, Gibson C, Giraldez E, Glebov V, Glendinning SG, Glenn S, Glenzer SH, Goade S, Gobby PL, Goldman SR, Golick B, Gomez M, Goncharov V, Goodin D, Grabowski P, Grafil E, Graham P, Grandy J, Grasz E, Graziani F, Greenman G, Greenough JA, Greenwood A, Gregori G, Green T, Griego JR, Grim GP, Grondalski J, Gross S, Guckian J, Guler N, Gunney B, Guss G, Haan S, Hackbarth J, Hackel L, Hackel R, Haefner C, Hagmann C, Hahn KD, Hahn S, Haid BJ, Haines BM, Hall BM, Hall C, Hall GN, Hamamoto M, Hamel S, Hamilton CE, Hammel BA, Hammer JH, Hampton G, Hamza A, Handler A, Hansen S, Hanson D, Haque R, Harding D, Harding E, Hares JD, Harris DB, Harte JA, Hartouni EP, Hatarik R, Hatchett S, Hauer AA, Havre M, Hawley R, Hayes J, Hayes J, Hayes S, Hayes-Sterbenz A, Haynam CA, Haynes DA, Headley D, Heal A, Heebner JE, Heerey S, Heestand GM, Heeter R, Hein N, Heinbockel C, Hendricks C, Henesian M, Heninger J, Henrikson J, Henry EA, Herbold EB, Hermann MR, Hermes G, Hernandez JE, Hernandez VJ, Herrmann MC, Herrmann HW, Herrera OD, Hewett D, Hibbard R, Hicks DG, Hill D, Hill K, Hilsabeck T, Hinkel DE, Ho DD, Ho VK, Hoffer JK, Hoffman NM, Hohenberger M, Hohensee M, Hoke W, Holdener D, Holdener F, Holder JP, Holko B, Holunga D, Holzrichter JF, Honig J, Hoover D, Hopkins D, Berzak Hopkins L, Hoppe M, Hoppe ML, Horner J, Hornung R, Horsfield CJ, Horvath J, Hotaling D, House R, Howell L, Hsing WW, Hu SX, Huang H, Huckins J, Hui H, Humbird KD, Hund J, Hunt J, Hurricane OA, Hutton M, Huynh KH, Inandan L, Iglesias C, Igumenshchev IV, Izumi N, Jackson M, Jackson J, Jacobs SD, James G, Jancaitis K, Jarboe J, Jarrott LC, Jasion D, Jaquez J, Jeet J, Jenei AE, Jensen J, Jimenez J, Jimenez R, Jobe D, Johal Z, Johns HM, Johnson D, Johnson MA, Gatu Johnson M, Johnson RJ, Johnson S, Johnson SA, Johnson T, Jones K, Jones O, Jones M, Jorge R, Jorgenson HJ, Julian M, Jun BI, Jungquist R, Kaae J, Kabadi N, Kaczala D, Kalantar D, Kangas K, Karasiev VV, Karasik M, Karpenko V, Kasarky A, Kasper K, Kauffman R, Kaufman MI, Keane C, Keaty L, Kegelmeyer L, Keiter PA, Kellett PA, Kellogg J, Kelly JH, Kemic S, Kemp AJ, Kemp GE, Kerbel GD, Kershaw D, Kerr SM, Kessler TJ, Key MH, Khan SF, Khater H, Kiikka C, Kilkenny J, Kim Y, Kim YJ, Kimko J, Kimmel M, Kindel JM, King J, Kirkwood RK, Klaus L, Klem D, Kline JL, Klingmann J, Kluth G, Knapp P, Knauer J, Knipping J, Knudson M, Kobs D, Koch J, Kohut T, Kong C, Koning JM, Koning P, Konior S, Kornblum H, Kot LB, Kozioziemski B, Kozlowski M, Kozlowski PM, Krammen J, Krasheninnikova NS, Kraus B, Krauser W, Kress JD, Kritcher AL, Krieger E, Kroll JJ, Kruer WL, Kruse MKG, Kucheyev S, Kumbera M, Kumpan S, Kunimune J, Kustowski B, Kwan TJT, Kyrala GA, Laffite S, Lafon M, LaFortune K, Lahmann B, Lairson B, Landen OL, Langenbrunner J, Lagin L, Land T, Lane M, Laney D, Langdon AB, Langer SH, Langro A, Lanier NE, Lanier TE, Larson D, Lasinski BF, Lassle D, LaTray D, Lau G, Lau N, Laumann C, Laurence A, Laurence TA, Lawson J, Le HP, Leach RR, Leal L, Leatherland A, LeChien K, Lechleiter B, Lee A, Lee M, Lee T, Leeper RJ, Lefebvre E, Leidinger JP, LeMire B, Lemke RW, Lemos NC, Le Pape S, Lerche R, Lerner S, Letts S, Levedahl K, Lewis T, Li CK, Li H, Li J, Liao W, Liao ZM, Liedahl D, Liebman J, Lindford G, Lindman EL, Lindl JD, Loey H, London RA, Long F, Loomis EN, Lopez FE, Lopez H, Losbanos E, Loucks S, Lowe-Webb R, Lundgren E, Ludwigsen AP, Luo R, Lusk J, Lyons R, Ma T, Macallop Y, MacDonald MJ, MacGowan BJ, Mack JM, Mackinnon AJ, MacLaren SA, MacPhee AG, Magelssen GR, Magoon J, Malone RM, Malsbury T, Managan R, Mancini R, Manes K, Maney D, Manha D, Mannion OM, Manuel AM, Mapoles E, Mara G, Marcotte T, Marin E, Marinak MM, Mariscal C, Mariscal DA, Mariscal EF, Marley EV, Marozas JA, Marquez R, Marshall CD, Marshall FJ, Marshall M, Marshall S, Marticorena J, Martinez D, Maslennikov I, Mason D, Mason RJ, Masse L, Massey W, Masson-Laborde PE, Masters ND, Mathisen D, Mathison E, Matone J, Matthews MJ, Mattoon C, Mattsson TR, Matzen K, Mauche CW, Mauldin M, McAbee T, McBurney M, Mccarville T, McCrory RL, McEvoy AM, McGuffey C, Mcinnis M, McKenty P, McKinley MS, McLeod JB, McPherson A, Mcquillan B, Meamber M, Meaney KD, Meezan NB, Meissner R, Mehlhorn TA, Mehta NC, Menapace J, Merrill FE, Merritt BT, Merritt EC, Meyerhofer DD, Mezyk S, Mich RJ, Michel PA, Milam D, Miller C, Miller D, Miller DS, Miller E, Miller EK, Miller J, Miller M, Miller PE, Miller T, Miller W, Miller-Kamm V, Millot M, Milovich JL, Minner P, Miquel JL, Mitchell S, Molvig K, Montesanti RC, Montgomery DS, Monticelli M, Montoya A, Moody JD, Moore AS, Moore E, Moran M, Moreno JC, Moreno K, Morgan BE, Morrow T, Morton JW, Moses E, Moy K, Muir R, Murillo MS, Murray JE, Murray JR, Munro DH, Murphy TJ, Munteanu FM, Nafziger J, Nagayama T, Nagel SR, Nast R, Negres RA, Nelson A, Nelson D, Nelson J, Nelson S, Nemethy S, Neumayer P, Newman K, Newton M, Nguyen H, Di Nicola JG, Di Nicola P, Niemann C, Nikroo A, Nilson PM, Nobile A, Noorai V, Nora R, Norton M, Nostrand M, Note V, Novell S, Nowak PF, Nunez A, Nyholm RA, O'Brien M, Oceguera A, Oertel JA, Okui J, Olejniczak B, Oliveira J, Olsen P, Olson B, Olson K, Olson RE, Opachich YP, Orsi N, Orth CD, Owen M, Padalino S, Padilla E, Paguio R, Paguio S, Paisner J, Pajoom S, Pak A, Palaniyappan S, Palma K, Pannell T, Papp F, Paras D, Parham T, Park HS, Pasternak A, Patankar S, Patel MV, Patel PK, Patterson R, Patterson S, Paul B, Paul M, Pauli E, Pearce OT, Pearcy J, Pedrotti B, Peer A, Pelz LJ, Penetrante B, Penner J, Perez A, Perkins LJ, Pernice E, Perry TS, Person S, Petersen D, Petersen T, Peterson DL, Peterson EB, Peterson JE, Peterson JL, Peterson K, Peterson RR, Petrasso RD, Philippe F, Phipps TJ, Piceno E, Ping Y, Pickworth L, Pino J, Plummer R, Pollack GD, Pollaine SM, Pollock BB, Ponce D, Ponce J, Pontelandolfo J, Porter JL, Post J, Poujade O, Powell C, Powell H, Power G, Pozulp M, Prantil M, Prasad M, Pratuch S, Price S, Primdahl K, Prisbrey S, Procassini R, Pruyne A, Pudliner B, Qiu SR, Quan K, Quinn M, Quintenz J, Radha PB, Rainer F, Ralph JE, Raman KS, Raman R, Rambo P, Rana S, Randewich A, Rardin D, Ratledge M, Ravelo N, Ravizza F, Rayce M, Raymond A, Raymond B, Reed B, Reed C, Regan S, Reichelt B, Reis V, Reisdorf S, Rekow V, Remington BA, Rendon A, Requieron W, Rever M, Reynolds H, Reynolds J, Rhodes J, Rhodes M, Richardson MC, Rice B, Rice NG, Rieben R, Rigatti A, Riggs S, Rinderknecht HG, Ring K, Riordan B, Riquier R, Rivers C, Roberts D, Roberts V, Robertson G, Robey HF, Robles J, Rocha P, Rochau G, Rodriguez J, Rodriguez S, Rosen M, Rosenberg M, Ross G, Ross JS, Ross P, Rouse J, Rovang D, Rubenchik AM, Rubery MS, Ruiz CL, Rushford M, Russ B, Rygg JR, Ryujin BS, Sacks RA, Sacks RF, Saito K, Salmon T, Salmonson JD, Sanchez J, Samuelson S, Sanchez M, Sangster C, Saroyan A, Sater J, Satsangi A, Sauers S, Saunders R, Sauppe JP, Sawicki R, Sayre D, Scanlan M, Schaffers K, Schappert GT, Schiaffino S, Schlossberg DJ, Schmidt DW, Schmitt MJ, Schneider DHG, Schneider MB, Schneider R, Schoff M, Schollmeier M, Schölmerich M, Schroeder CR, Schrauth SE, Scott HA, Scott I, Scott JM, Scott RHH, Scullard CR, Sedillo T, Seguin FH, Seka W, Senecal J, Sepke SM, Seppala L, Sequoia K, Severyn J, Sevier JM, Sewell N, Seznec S, Shah RC, Shamlian J, Shaughnessy D, Shaw M, Shaw R, Shearer C, Shelton R, Shen N, Sherlock MW, Shestakov AI, Shi EL, Shin SJ, Shingleton N, Shmayda W, Shor M, Shoup M, Shuldberg C, Siegel L, Silva FJ, Simakov AN, Sims BT, Sinars D, Singh P, Sio H, Skulina K, Skupsky S, Slutz S, Sluyter M, Smalyuk VA, Smauley D, Smeltser RM, Smith C, Smith I, Smith J, Smith L, Smith R, Sohn R, Sommer S, Sorce C, Sorem M, Soures JM, Spaeth ML, Spears BK, Speas S, Speck D, Speck R, Spears J, Spinka T, Springer PT, Stadermann M, Stahl B, Stahoviak J, Stanton LG, Steele R, Steele W, Steinman D, Stemke R, Stephens R, Sterbenz S, Sterne P, Stevens D, Stevers J, Still CB, Stoeckl C, Stoeffl W, Stolken JS, Stolz C, Storm E, Stone G, Stoupin S, Stout E, Stowers I, Strauser R, Streckart H, Streit J, Strozzi DJ, Suratwala T, Sutcliffe G, Suter LJ, Sutton SB, Svidzinski V, Swadling G, Sweet W, Szoke A, Tabak M, Takagi M, Tambazidis A, Tang V, Taranowski M, Taylor LA, Telford S, Theobald W, Thi M, Thomas A, Thomas CA, Thomas I, Thomas R, Thompson IJ, Thongstisubskul A, Thorsness CB, Tietbohl G, Tipton RE, Tobin M, Tomlin N, Tommasini R, Toreja AJ, Torres J, Town RPJ, Townsend S, Trenholme J, Trivelpiece A, Trosseille C, Truax H, Trummer D, Trummer S, Truong T, Tubbs D, Tubman ER, Tunnell T, Turnbull D, Turner RE, Ulitsky M, Upadhye R, Vaher JL, VanArsdall P, VanBlarcom D, Vandenboomgaerde M, VanQuinlan R, Van Wonterghem BM, Varnum WS, Velikovich AL, Vella A, Verdon CP, Vermillion B, Vernon S, Vesey R, Vickers J, Vignes RM, Visosky M, Vocke J, Volegov PL, Vonhof S, Von Rotz R, Vu HX, Vu M, Wall D, Wall J, Wallace R, Wallin B, Walmer D, Walsh CA, Walters CF, Waltz C, Wan A, Wang A, Wang Y, Wark JS, Warner BE, Watson J, Watt RG, Watts P, Weaver J, Weaver RP, Weaver S, Weber CR, Weber P, Weber SV, Wegner P, Welday B, Welser-Sherrill L, Weiss K, Widmann K, Wheeler GF, Whistler W, White RK, Whitley HD, Whitman P, Wickett ME, Widmayer C, Wiedwald J, Wilcox R, Wilcox S, Wild C, Wilde BH, Wilde CH, Wilhelmsen K, Wilke MD, Wilkens H, Wilkins P, Wilks SC, Williams EA, Williams GJ, Williams W, Williams WH, Wilson DC, Wilson B, Wilson E, Wilson R, Winters S, Wisoff J, Wittman M, Wolfe J, Wong A, Wong KW, Wong L, Wong N, Wood R, Woodhouse D, Woodruff J, Woods DT, Woods S, Woodworth BN, Wooten E, Wootton A, Work K, Workman JB, Wright J, Wu M, Wuest C, Wysocki FJ, Xu H, Yamaguchi M, Yang B, Yang ST, Yatabe J, Yeamans CB, Yee BC, Yi SA, Yin L, Young B, Young CS, Young CV, Young P, Youngblood K, Zacharias R, Zagaris G, Zaitseva N, Zaka F, Ze F, Zeiger B, Zika M, Zimmerman GB, Zobrist T, Zuegel JD, and Zylstra AB

Abstract

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Published
2022
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5. Comparative genome analyses suggest a hemibiotrophic lifestyle and virulence differences for the beech bark disease fungal pathogens Neonectria faginata and Neonectria coccinea.

Author

Salgado-Salazar C, Skaltsas DN, Phipps T, and Castlebury LA

Subjects
Europe, Genome, Fungal, Genomics, Hypocreales, Life Style, North America, Plant Bark, Virulence genetics, Fagus genetics
Abstract

Neonectria faginata and Neonectria coccinea are the causal agents of the insect-fungus disease complex known as beech bark disease (BBD), known to cause mortality in beech forest stands in North America and Europe. These fungal species have been the focus of extensive ecological and disease management studies, yet less progress has been made toward generating genomic resources for both micro- and macro-evolutionary studies. Here, we report a 42.1 and 42.7 mb highly contiguous genome assemblies of N. faginata and N. coccinea, respectively, obtained using Illumina technology. These species share similar gene number counts (12,941 and 12,991) and percentages of predicted genes with assigned functional categories (64 and 65%). Approximately 32% of the predicted proteomes of both species are homologous to proteins involved in pathogenicity, yet N. coccinea shows a higher number of predicted mitogen-activated protein kinase genes, virulence determinants possibly contributing to differences in disease severity between N. faginata and N. coccinea. A wide range of genes encoding for carbohydrate-active enzymes capable of degradation of complex plant polysaccharides and a small number of predicted secretory effector proteins, secondary metabolite biosynthesis clusters and cytochrome oxidase P450 genes were also found. This arsenal of enzymes and effectors correlates with, and reflects, the hemibiotrophic lifestyle of these two fungal pathogens. Phylogenomic analysis and timetree estimations indicated that the N. faginata and N. coccinea species divergence may have occurred at ∼4.1 million years ago. Differences were also observed in the annotated mitochondrial genomes as they were found to be 81.7 kb (N. faginata) and 43.2 kb (N. coccinea) in size. The mitochondrial DNA expansion observed in N. faginata is attributed to the invasion of introns into diverse intra- and intergenic locations. These first draft genomes of N. faginata and N. coccinea serve as valuable tools to increase our understanding of basic genetics, evolutionary mechanisms and molecular physiology of these two nectriaceous plant pathogenic species., (Published by Oxford University Press on behalf of Genetics Society of America 2021. This work is written by US Government employees and is in the public domain in the US.)

Published
2021
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6. [Fungal keratitis: A 5-year monocentric retrospective study on Reunion Island].

Author

Hoarau G, Albrieux M, Martin-Phipps T, Zitte-Zehler K, Borry L, Peytral J, Garcia-Hermoso D, and Picot S

Subjects
Adult, Aged, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Corneal Injuries complications, Corneal Injuries microbiology, Eye Infections, Fungal drug therapy, Eye Infections, Fungal microbiology, Female, Fusariosis drug therapy, Fusariosis epidemiology, Fusariosis microbiology, Hospitals, University statistics & numerical data, Humans, Keratitis drug therapy, Keratitis microbiology, Male, Middle Aged, Retrospective Studies, Reunion epidemiology, Voriconazole therapeutic use, Wound Infection epidemiology, Wound Infection microbiology, Eye Infections, Fungal epidemiology, Keratitis epidemiology
Abstract

Objectives: Fungal keratitis is rare in France, but could be a severe sight-threatening condition. Here, we aimed to describe the epidemiology of fungal keratitis in Réunion Island., Methods: In a retrospective study, we analyzed 13 culture-proven keratitis episodes, occurred between January 2013 and July 2017 in the ophthalmology ward of a University Hospital, Saint-Pierre. Twelve isolates were genotyped and antifungal susceptibility testing was performed., Results: Corneal abrasion caused by vegetable matter was the main predisposing factor. Stromal infiltration was observed in 12 patients. Six patients did not response to medical treatment, requiring surgical care, including two enucleations surgery. Fusarium solani (n = 6) and Fusarium dimerum (n = 4) were the main fungal species involved in fungal keratitis. Clinical failures were more prevalent with F. solani infections. The lowest minimal inhibitory concentrations for Fusarium sp. were observed with voriconazole and amphotericin B., Conclusion: In Reunion Island, the epidemiology of fungal keratitis is characterized by the predominance of Fusarium species, potentially involved in visual loss. This pattern is consistent with the epidemiology usually observed in tropical areas., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Published
2018
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7. QUEST®: A Data-Driven Collaboration to Improve Quality, Efficiency, Safety, and Transparency in Acute Care.

Author

Crimmins MM, Lowe TJ, Barrington M, Kaylor C, Phipps T, Le-Roy C, Brooks T, Jones M, and Martin J

Subjects
Cost-Benefit Analysis, Hospitalization economics, Humans, Patient Safety economics, Patient Satisfaction, Program Evaluation, United States, Cooperative Behavior, Hospitalization statistics & numerical data, Patient Safety statistics & numerical data, Quality Improvement
Abstract

Background: In 2008 Premier (Premier, Inc., Charlotte, North Carolina) began its Quality, Efficiency, and Safety with Transparency (QUEST®) collaborative, which is an acute health care organization program focused on improving quality and reducing patient harm., Methods: Retrospective performance data for QUEST hospitals were used to establish trends from the third quarter (Q3; July–September) of 2006 through Q3 2015. The study population included past and present members of the QUEST collaborative (N = 356), with each participating hospital considered a member. The QUEST program engages with member hospitals through a routine-coaching structure, sprints, minicollaboratives, and face-to-face meetings., Results: Cost and efficiency data showed reductions in adjusted cost per discharge for hospitals between Q3 2013 (mean, $8,296; median, $8,459) and Q3 2015 (mean, $8,217; median, $7,895). Evidence-based care (EBC) measures showed improvement from baseline (Q3 2006; mean, 77%; median, 79%) to Q3 2015 (mean, 95%; median, 96%). Observed-to-expected (O/E) mortality improved from 1% to 22% better-than-expected outcomes on average. The QUEST safety harm composite score showed moderate reduction from Q1 2009 to Q3 2015, as did the O/E readmission rates--from Q1 2010 to Q3 2015--with improvement from a 5% to an 8% better-than-expected score., Conclusion: Quantitative and qualitative evaluation of QUEST collaborative hospitals indicated that for the 2006-2015 period, QUEST facilities reduced cost per discharge, improved adherence with evidence-based practice, reduced safety harm composite score, improved patient experience, and reduced unplanned readmissions.

Published
2016
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8. Effectiveness of a mobile diabetic retinopathy screening campaign to encourage diabetics to undergo regular ophthalmic follow-up.

Author

Creuzot-Garcher C, Martin-Phipps T, Beynat J, Astruc K, Brassac K, and Bron AM

Subjects
Aged, Female, Follow-Up Studies, Humans, Male, Photography, Program Evaluation, Retrospective Studies, Continuity of Patient Care statistics & numerical data, Diabetic Retinopathy diagnosis, Health Promotion, Mass Screening, Mobile Health Units statistics & numerical data, Office Visits statistics & numerical data, Ophthalmology statistics & numerical data
Abstract

Aim: To evaluate the effectiveness of a mobile diabetic retinopathy (DR) screening campaign with a non-mydriatic camera to encourage diabetics to undergo a subsequent ophthalmic follow-up., Methods: Diabetic patients who underwent free DR screening with a non-mydriatic fundus camera were given the recommendation to have an ophthalmic visit, in a time frame suited to the DR stage or in case abnormalities in the macula, the optic nerve or intra-ocular pressure were detected. The photographs were performed by a trained orthoptist. The date of the visit to their ophthalmologist and the report of this consultation were recorded., Results: During 5 annual campaigns, 4,699 diabetics were screened. Of the 1,573 ophthalmic examinations recommended at the screening, 1,241 (79%) were actually conducted. A total of 623 new cases of DR were found in the course of this screening campaign, with a fair concordance between the diagnosis suggested at screening and the examination by the ophthalmologist (κ = 0.48)., Conclusion: Information and recommendations given during DR screening helped to reintroduce patients to a regular ophthalmic follow-up, at least in the short term., (© 2014 S. Karger AG, Basel.)

Published
2014
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9. Mitochondrial genome sequences reveal deep divergences among Anopheles punctulatus sibling species in Papua New Guinea.

Author

Logue K, Chan ER, Phipps T, Small ST, Reimer L, Henry-Halldin C, Sattabongkot J, Siba PM, Zimmerman PA, and Serre D

Subjects
Animals, Genotype, Humans, Molecular Sequence Data, Papua New Guinea, Sequence Analysis, DNA, Anopheles classification, Anopheles genetics, Genetic Variation, Genome, Mitochondrial, Phylogeny
Abstract

Background: Members of the Anopheles punctulatus group (AP group) are the primary vectors of human malaria in Papua New Guinea. The AP group includes 13 sibling species, most of them morphologically indistinguishable. Understanding why only certain species are able to transmit malaria requires a better comprehension of their evolutionary history. In particular, understanding relationships and divergence times among Anopheles species may enable assessing how malaria-related traits (e.g. blood feeding behaviours, vector competence) have evolved., Methods: DNA sequences of 14 mitochondrial (mt) genomes from five AP sibling species and two species of the Anopheles dirus complex of Southeast Asia were sequenced. DNA sequences from all concatenated protein coding genes (10,770 bp) were then analysed using a Bayesian approach to reconstruct phylogenetic relationships and date the divergence of the AP sibling species., Results: Phylogenetic reconstruction using the concatenated DNA sequence of all mitochondrial protein coding genes indicates that the ancestors of the AP group arrived in Papua New Guinea 25 to 54 million years ago and rapidly diverged to form the current sibling species., Conclusion: Through evaluation of newly described mt genome sequences, this study has revealed a divergence among members of the AP group in Papua New Guinea that would significantly predate the arrival of humans in this region, 50 thousand years ago. The divergence observed among the mtDNA sequences studied here may have resulted from reproductive isolation during historical changes in sea-level through glacial minima and maxima. This leads to a hypothesis that the AP sibling species have evolved independently for potentially thousands of generations. This suggests that the evolution of many phenotypes, such as insecticide resistance will arise independently in each of the AP sibling species studied here.

Published
2013
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10. PCR-free method detects high frequency of genomic instability in prostate cancer.

Author

Makridakis NM, Phipps T, Srivastav S, and Reichardt JK

Subjects
Aged, Cloning, Molecular, Humans, Male, Middle Aged, Polymerase Chain Reaction, DNA Mutational Analysis methods, Genomic Instability, Prostatic Neoplasms genetics
Abstract

Most studies of tumor instability are PCR-based. PCR-based methods may underestimate mutation frequencies of heterogeneous tumor genomes. Using a novel PCR-free random cloning/sequencing method, we analyzed 100 kb of total genomic DNA from blood lymphocytes, normal prostate and tumor prostate taken from six individuals. Variations were identified by comparison of the sequence of the cloned fragments with the nr-database in Genbank. After excluding known polymorphisms (by comparison to the NCBI dbSNP), we report a significant over-representation of variants in the tumors: 0.66 variations per kilobase of sequence, compared with the corresponding normal prostates (0.14 variations/kb) or blood (0.09 variations/kb). Extrapolating the observed difference between tumor and normal prostate DNA, we estimate 1.8 million somatic (de novo) alterations per tumor cell genome, a much higher frequency than previous measurements obtained by mostly PCR-based methods in other tumor types. Moreover, unlike the normal prostate and blood, most of the tumor variations occur in a specific motif (P = 0.046), suggesting common etiology. We further report high tumor cell-to-cell heterogeneity. These data have important implications for selecting appropriate technologies for cancer genome projects as well as for understanding prostate cancer progression.

Published
2009
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12. Pelvic lordosis and alignment in spondylolisthesis.

Author

Jackson RP, Phipps T, Hales C, and Surber J

Subjects
Adolescent, Adult, Aged, Female, Humans, Lordosis classification, Lordosis complications, Male, Middle Aged, Observer Variation, Radiography, Reference Values, Reproducibility of Results, Retrospective Studies, Sacrum diagnostic imaging, Spondylolisthesis complications, Terminology as Topic, Lordosis diagnostic imaging, Pelvic Bones diagnostic imaging, Spine diagnostic imaging, Spondylolisthesis diagnostic imaging
Abstract

Study Design and Objectives: Pelvic morphology and lumbopelvic lordosis were measured on standing radiographs of 75 patients with greater than 10% L5-S1 spondylolytic spondylolisthesis. The findings were compared with those of 75 volunteers to determine significant differences between the two groups., Summary of Background Data: Etiology of isthmic (lytic) spondylolisthesis remains uncertain. Causation appears to be multifactorial. The relationship between pelvic morphology and spondylolisthesis deserves additional study., Methods: Both groups had a standing lateral radiograph of the thoracolumbar spine and pelvis taken that included both hips. Three radiographic angles for pelvic morphology (pelvisacral, pelvic incidence, and pelvic lordosis) were measured by two observers. Each offered similar reliability. Measurement of the pelvic lordosis angle by the pelvic radius technique required fewer steps. It also allowed calculation of the combined angles comprising both the pelvic morphology component for lordosis (the constant pelvic lordosis angle) and the lordosis in the lumbar spine (the variable lumbar lordosis from T12-S1) that should complement the fixed pelvic lordosis (the complementary lumbopelvic lordosis). Mean values and statistical correlations were then computed for each group and compared., Results: The mean slippage for patients was 30% (range, 11-85%), with 34 patients (45%) having Grade I slips, 32 (43%) having Grade II slips, and nine (12%) having Grade III and IV slips. The mean measurements between patients and volunteers were significantly different (P < 0.01) for lumbar lordosis, pelvic lordosis, and lumbopelvic lordosis. Subgroups of patients with increasingly larger slips (Grade I-III) had significantly smaller mean angles for pelvic lordosis., Conclusions: The pelvic and lumbopelvic parameters studied were different in patients compared with controls. The contribution of the pelvis to lordosis was significantly smaller in the subgroups of patients with increasingly larger grades of spondylolisthesis. Pelvic morphology may play a role in the development of spondylolisthesis. Measurement of the combined lumbar and pelvic (lumbopelvic) lordosis on standing radiographs is important.

Published
2003
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13. Neuroendocrine carcinoma of the skin (Merkel cell carcinoma) in a black.

Author

Anderson LL, Phipps TJ, and McCollough ML

Subjects
Black People, Buttocks, Carcinoma, Merkel Cell pathology, Carcinoma, Merkel Cell ultrastructure, Humans, Immunohistochemistry, Male, Microscopy, Electron, Middle Aged, Skin Neoplasms pathology, Skin Neoplasms ultrastructure, Carcinoma, Merkel Cell ethnology, Skin Neoplasms ethnology
Abstract

Neuroendocrine carcinoma of the skin is an uncommon, small-cell neoplasm most commonly found on white, sun-exposed skin. Diagnosis by clinical and histologic means may be difficult. Immunohistochemical and ultrastructural analysis are often required. Because of the aggressive nature of neuroendocrine carcinoma of the skin, prompt diagnosis and treatment are essential. We present the rare occurrence of a neuroendocrine carcinoma of the skin on sun protected skin in a black. Clinical, histologic, immunohistochemical, and ultrastructural features are reviewed, and therapeutic options are discussed.

Published
1992
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14. Protection of macaques with a simian immunodeficiency virus envelope peptide vaccine based on conserved human immunodeficiency virus type 1 sequences.

Author

Shafferman A, Jahrling PB, Benveniste RE, Lewis MG, Phipps TJ, Eden-McCutchan F, Sadoff J, Eddy GA, and Burke DS

Subjects
Amino Acid Sequence, Animals, Antibodies, Viral analysis, Base Sequence, Biological Evolution, Enzyme-Linked Immunosorbent Assay, HIV-1 genetics, Macaca mulatta, Molecular Sequence Data, Neutralization Tests, Oligonucleotide Probes, Polymerase Chain Reaction, Sequence Homology, Nucleic Acid, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Immunodeficiency Virus genetics, Simian Immunodeficiency Virus isolation & purification, Viral Envelope Proteins genetics, HIV-1 immunology, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus immunology, Viral Envelope Proteins immunology, Viral Vaccines
Abstract

This report describes the vaccination of rhesus macaques with peptides selected from regions of the simian immunodeficiency virus (SIV) envelope that are hydrophilic, immunoreactive, and highly homologous with corresponding conserved envelope sequences of the human immunodeficiency virus (HIV). The peptides, produced as beta-galactosidase fusion proteins, induced virus-neutralizing and peptide-specific antibodies. After challenge with virulent virus, controls became virus positive and developed gradually rising antibody titers to SIV over 63 weeks. Immunized macaques developed a postchallenge anamnestic response to SIVenv antigens within 3-6 weeks followed by a gradual, fluctuating decline in SIV antibody titers and partial or total suppression of detectable SIV. Virus suppression correlated with prechallenge neutralizing antibody titers. Although the average CD4+ cell count in the blood of immunized macaques remained constant, the control macaques exhibited a progressive decrease developing about week 55 after challenge. The conserved nature of the HIV and SIV peptides and the similar humoral immunoreactivity in the respective hosts suggest that homologous HIV peptides may be important components of a successful immunization strategy.

Published
1991
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15. Survey of H2-antagonist usage in acute upper gastrointestinal hemorrhage.

Author

Bhatt BD, Meriano FV, Phipps TL, Ho H, and Zuckerman MJ

Subjects
Adult, Aged, Aged, 80 and over, Drug Utilization, Female, Gastrointestinal Hemorrhage epidemiology, Humans, Male, Middle Aged, Cimetidine therapeutic use, Drug Prescriptions statistics & numerical data, Gastrointestinal Hemorrhage drug therapy, Ranitidine therapeutic use
Abstract

H2-antagonists are frequently used in the management of upper gastrointestinal (UGI) hemorrhage despite their lack of proven efficacy. In order to determine the pattern of H2-antagonist usage for this indication, we retrospectively reviewed the charts of 137 patients admitted with acute UGI bleeding over a 1-year period at two teaching hospitals in West Texas. An H2-antagonist was ordered in 89% of patients (77%) intravenous, 12% oral). It was administered within 2 h of admission in 25% of these patients, within 4 h in 54%, and within 8 h in 78%. An H2-antagonist was ordered among the initial six orders in 49% and among the initial 10 orders in 77% of patients. Considering orders for specific therapies, an H2-antagonist was in the initial three orders in 60% of patients and among the initial six orders in 97%. Of the patients who were prescribed an H2-antagonist and who also had upper endoscopy, the drug was ordered prior to endoscopy in 86%. This review of H2-antagonist usage in the management of acute UGI bleeding has identified a prescribing pattern of writing for these drugs early in the sequence of order writing, with the drugs being given early in the course of hospitalization.

Published
1990
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16. Enzyme-linked immunosorbent assay for Pseudomonas aeruginosa exotoxin A.

Author

Schultz WW, Phipps TJ, and Pollack M

Subjects
Hemagglutination Inhibition Tests, Humans, Pseudomonas Infections microbiology, Enzyme-Linked Immunosorbent Assay, Exotoxins analysis, Immunoenzyme Techniques, Pseudomonas aeruginosa analysis
Abstract

An enzyme-linked immunosorbent assay (ELISA) is described for Pseudomonas aeruginosa exotoxin A. A double antibody sandwich method was used, employing polyvinyl microtiter plates as the solid phase, a primary coat of monospecific rabbit antitoxin serum, an outer layer composed of a horseradish peroxidase-sheep antitoxin immunoglobulin G conjugate, and an ortho-phenylene-diamine substrate. Absorbance (optical density) of hydrolyzed end product was read spectrophotometrically at 492 nm. ELISA detected as little as 30 pg (0.3 ng/ml) of purified toxin, and absorbance was linear over a 20-fold or greater concentration range. Toxin was demonstrated in culture filtrates from 42 of 48 (88%) consecutive clinical P. aeruginosa isolates compared with 37 of 48 (77%) positive by hemagglutination inhibition. Results of the two assays correlated closely (r = 0.82, P less than 0.001). Specificity was confirmed by neutralizability of ELISA activity with monospecific antitoxin. ELISA was thus a sensitive, specific, and quantifiable technique for the assay of P. aeruginosa exotoxin A in both purified and crude culture materials.

Published
1979
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17. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes.

Author

Gendelman HE, Orenstein JM, Martin MA, Ferrua C, Mitra R, Phipps T, Wahl LA, Lane HC, Fauci AS, and Burke DS

Subjects
Cells, Cultured, Cytopathogenic Effect, Viral, DNA, Viral analysis, HIV Seropositivity pathology, Humans, Lymphocytes microbiology, Macrophages drug effects, Macrophages microbiology, Proviruses analysis, Recombinant Proteins pharmacology, Colony-Stimulating Factors pharmacology, HIV isolation & purification, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear ultrastructure, Virus Cultivation methods
Abstract

Monocytes were maintained in tissue culture for greater than 3 mo in media supplemented with rCSF-1. These cultures provided susceptible target cells for isolation and propagation of virus from PBMC of HIV-infected patients. HIV isolated into monocytes readily infected other rCSF-1-treated monocytes but only inefficiently infected PHA-stimulated lymphoblasts. Similarly, laboratory HIV strains passaged in T cell lines or virus isolated from patients' leukocytes into PHA-stimulated lymphoblasts inefficiently infected rCSF-1-treated monocytes. Persistent, low-level virion production was detected in macrophage culture fluids by reverse transcriptase activity or HIV antigen capture through 6-7 wk. Marked changes in cell morphology with cell death, syncytia, and giant cell formation were observed in monocyte cultures 2 wk after infection, but at 4-6 wk, all cells appeared morphologically normal. However, the frequency of infected cells in these cultures at 6 wk was 60-90% as quantified by in situ hybridization with HIV RNA probes or by immunofluorescence with AIDS patients' sera. Ultrastructural analysis by EM also showed a high frequency of infected cells; virtually all HIV budded into and accumulated within cytoplasmic vacuoles and virus particles were only infrequently associated with the plasma membrane. Retention of virus within macrophages and the macrophage tropism of HIV variants may explain mechanisms of both virus persistence and dissemination during disease.

Published
1988
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18. Effects of ibuterol, a beta-2 adrenergic prodrug, on intraocular pressure.

Author

Phipps TL, Potter DE, and Rowland JM

Subjects
Animals, Aqueous Humor drug effects, Blood Pressure drug effects, Colforsin pharmacology, Male, Rabbits, Terbutaline pharmacology, Intraocular Pressure drug effects, Prodrugs pharmacology, Terbutaline analogs & derivatives
Abstract

Ibuterol, a prodrug of terbutaline, was approximately 100 times more potent than terbutaline in producing ocular hypotension in the treated eye of normal and sympathectomized (SX) rabbits. In normal rabbits, ibuterol produced no change in IOP of the contralateral eye whereas in unilaterally SX rabbits a rise in IOP occurred in the SX (contralateral) eye when the normal eye was treated with ibuterol. Ibuterol also suppressed ocular hypertension induced by water loading and delayed the IOP recovery rate although its onset of action was delayed. Aqueous flow was increased significantly at 1 hr after ibuterol in fluorophotometric studies in normal rabbits. Pretreatment with forskolin antagonized rather than enhanced ibuterol-induced ocular hypotension. Pretreatment with diclofenac failed to suppress the development of tachyphylaxis to the ocular hypotensive effect of ibuterol. Although ibuterol is an effective ocular hypotensive agent in rabbits, the effects of this agent on aqueous flow are complex and tachyphylaxis to the ocular hypotensive effect develops fairly rapidly.

Published
1986
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19. Cytoplasmic assembly and accumulation of human immunodeficiency virus types 1 and 2 in recombinant human colony-stimulating factor-1-treated human monocytes: an ultrastructural study.

Author

Orenstein JM, Meltzer MS, Phipps T, and Gendelman HE

Subjects
Acquired Immunodeficiency Syndrome microbiology, Acquired Immunodeficiency Syndrome pathology, Cells, Cultured, Colony-Stimulating Factors pharmacology, Humans, Immunohistochemistry, Macrophages ultrastructure, Monocytes ultrastructure, Recombinant Proteins pharmacology, Time Factors, HIV growth & development, Macrophages microbiology, Monocytes microbiology, Virus Replication drug effects
Abstract

Recombinant human colony-stimulating factor-1-treated human peripheral blood-derived monocytes-macrophages are efficient host cells for recovery of the human immunodeficiency virus (HIV) from blood leukocytes of patients with acquired immunodeficiency syndrome. These cells can be maintained as viable monolayers for intervals exceeding 3 months. Infection with HIV resulted in virus-induced cytopathic effects, accompanied by relatively high levels of released progeny virus, followed by a prolonged low-level release of virus from morphologically normal cells. In both acutely and chronically infected monocytes, viral particles were seen budding into and accumulating within cytoplasmic vacuoles. The number of intravacuolar virions far exceeded those associated with the plasma membrane, especially in the chronic phase, and were concentrated in the perinuclear Golgi zone. In many instances, the vacuoles were identified as Golgi elements. Fusion of virus-laden vacuoles with primary lysosomes were rare. The pattern of cytoplasmic assembly of virus was observed with both HIV types 1 and 2 and in brain macrophages of an individual with acquired immunodeficiency syndrome encephalopathy. Immunoglobulin-coated gold beads added to acutely infected cultures were segregated from the vacuoles containing virus; relatively few beads and viral particles colocalized. The assembly of HIV virions within vacuoles of macrophages is in contrast to the exclusive surface assembly of HIV by T lymphocytes. Intracytoplasmic virus hidden from immune surveillance in monocytes-macrophages may explain, in part, the persistence of HIV in the infected human host.

Published
1988
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