18 results on '"Vales T"'
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2. Recalls, Drugs and Consumer Products
- Author
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Gad, S.C., primary and Vales, T., additional
- Published
- 2014
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3. A Symmetric Random Walk defined by the Time-One Map of a Geodesic Flow
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Carrasco, Pablo D. and Vales, T��lio
- Subjects
37C40, 37D30, 60K37, 37H99 ,FOS: Mathematics ,Dynamical Systems (math.DS) - Abstract
In this note we consider a symmetric random walk defined by a $(f,f^{-1})$ Kalikow type system, where $f$ is the time-one map of the geodesic flow corresponding to an hyperbolic manifold. We provide necessary and sufficient conditions for the existence of an stationary measure for the walk that is equivalent to the volume in the corresponding unit tangent bundle. Some dynamical consequences for the random walk are deduced in these cases., Final version incorporating the reviewer suggestions. To be published in Discrete and Continuous Dynamical Systems. 18 pages, 1 fig
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- 2020
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4. Fumonisin Toxicity and Sphingolipid Biosynthesis
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Merrill, A. H., primary, Wang, E., additional, Vales, T. R., additional, Smith, E. R., additional, Schroeder, J. J., additional, Menaldino, D. S., additional, Alexander, C., additional, Crane, H. M., additional, Xia, J., additional, Liotta, D. C., additional, Meredith, F. I., additional, and Riley, R. T., additional
- Published
- 1996
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5. Programa de seguimiento de niños prematuros desde el punto de vista terapéutico y educativo
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Rico Vales, T., Herencia Solano, C., García Martín, A., González Castro, S., Puyol Buil, P.J., and Torres Mohedas, J.
- Subjects
Atención multidisciplinar ,Preterm ,Multidisciplinary care ,Development ,Desarrollo ,Child ,Niños ,Prematuridad - Abstract
Las necesidades de los niños prematuros son atendidas, además de por sus familias, desde diferentes servicios. Si queremos que esta atención sea adecuada, dichos servicios deben coordinarse y llevar conjuntamente programas preventivos. El programa de seguimiento de los niños nacidos prematuros en Móstoles (Madrid) se enmarca en esta coordinación imprescindible. Pretendemos mostrar cómo se desarrolla la coordinación y qué aporta cada unidad o servicio, así como transmitir la importancia que tiene el seguimiento conjunto partiendo de una colaboración que empezó hace una década; aportamos los datos más relevantes de los resultados obtenidos. Families of preterm infants need the collaboration of different services to take care of these children. These services must coordinate to give the adequate care, implementing together preventive programs. The preterm infants´ follow up program of Móstoles (Madrid) takes into account this essential coordination. We explain how this coordination develops, what it adds to each service and the importance the joint follow up has, starting from a collaboration that has started a decade ago. We show the most relevant data of the obtained results.
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- 2010
6. Amnionruptur bei monochorialer diamnioter Geminigravidiät
- Author
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Schlembach, D, primary, Neukamm, S, additional, Hahn, N von, additional, Vales, T, additional, and Hantschmann, P, additional
- Published
- 2012
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7. Amnionruptur bei monochorialer diamnioter Geminigravidiät
- Author
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Neukamm, S, primary, Hahn, N von, additional, Vales, T, additional, Schlembach, D, additional, and Hantschmann, P, additional
- Published
- 2012
- Full Text
- View/download PDF
8. Programa de seguimiento de niños prematuros desde el punto de vista terapéutico y educativo
- Author
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Rico Vales, T., primary, Herencia Solano, C., additional, García Martín, A., additional, González Castro, S., additional, Puyol Buil, P.J., additional, and Torres Mohedas, J., additional
- Published
- 2010
- Full Text
- View/download PDF
9. List of Contributors
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Abdolahi, A., Abdolghaffari, A.H., Abdollahi, M., Achanzar, W.E., Acquisto, N.M., Adatsi, F.K., Adekola, F.A., Agarwal, D., Aizawa, H., Akbar Malekirad, A., Allen, J.A., Allison, B., Alonso Blazquez, N., Altkorn, R., Amanlou, M., Amini, M., Anand, S.S., Andres, S.A., Angelini, D.J., Angelo, G., Api, A.M., Apte, U., Armendáriz, C.R., Asha, S., Atlason, P., Attene-Ramos, M.S., Austin, C.P., Babich, M.A., Badanthadka, M., Baeeri, M., Baer, K.N., Baghaei, A., Bahadar, H., Balali-Mood, B., Balali-Mood, M., Bale, A.S., Ballantyne, B., Banasik, M., Banks, C.N., Banton, M., Baran, K.P., Barata, C., Barefoot, A.C., Barlow, S.M., Barr, D.B., Barrueto, F., Barton, C., Barton, N., Battalora, M., Bayrami, Z., Bazl, R., Beckett, R.D., Bečková, V., Beedanagari, S., Behboudi, A.F., Beilke, L.D., Beltrán, E.M., Benson, A., Bergamo, L., Bergueiro, J., Berman, F.W., Betharia, S., Bhattacharya, S., Biglar, M., Biswas, S., Black, A.T., Bloomhuff, A.B., Bloomquist, J.R., Bolduc, D.L., Bolger, P.M., Bolt, H.M., Bonventre, J.A., Borek, H.A., Borghoff, S.J., Borzelleca, J.F., Botelho, M.C., Boxall, A.B.A., Bradford, H., Brady, P.M., Broderick, M., Brown, D.A., Brown, J., Bruce, R.D., Brugge, D., Brugger, K.E., Bryant, M.A., Bucklin, M.H., Burns-Naas, L.A., Burr, S.A., Caballero, J.M., Cai, Z., Calabrese, E.J., Calvo, M., Cammack, J., Campbell, A., Canedy, T., Cantrell, F.L., Caquet, T., Carbonell, G., Carlson-Lynch, H., Carmichael, N., Carmo, H., Carr, D., Carrington, C.D., Carvalho, F., Carvalho, M., Casa-Resino, I. de la, Cash, L.J., Castranova, V., Cesnaitis, R., Chadwick, K.D., Chakraborty, P., Chan, P.P.K., Chang, S., Chapin, R.E., Chateauvieux, S., Chattopadhyay, A., Chaumot, A., Chen, G., Chen, X., Chesser, R.K., Chilakapati, J., Chojnacka, K., Chou, K., Christoforidis, J., Clark, A.K., Clewell, H.J., Clough, S.R., Coelho, P.C.S., Coggins, C.R.E., Cohen, S.M., Cole, S.D., Corcoran, G.B., Cornu, C., Corsini, E., Cory-Slechta, D.A., Costa, C., Costa, L.G., Costa, S., Covaci, A., Cowden, J., Cumpston, K.L., Curfman, E., Czerczak, S., Daam, M.A., Dahlstrom, D.L., Darracq, M.A., Darwich, A.S., Das, S.R., Davis, J.A., de la Casa Resino, I., de la Torre, A.H., de Lourdes Bastos, M., del Río, E., de Marcellus, S., Demers, P.A., de Peyster, A., Derakhshani, M., Desai, S.N., de San Andrés Larrea, M.I., Descotes, J., Devi, S.S., Devlin, J.J., de Voogt, P., Devriese, L., DeWoskin, R.S., de Zwart, D., Diederich, M., Dieter, H.H., Di Guardo, A., Đikić, D., Dincer, I., Dissanayake, V., DiZio, S.M., Dodd-Butera, T., Doke, D., Dorsey, R.M., Dougherty, M.M., Dourson, M.L., Drake, V.J., Duffus, J.H., Dumancas, G.G., Dumbacher, J.P., DuTeaux, S.B., Dydek, S.T., Dykens, J.A., Eagle, S.R., Eastmond, D.A., Easton, J.D., Eidemiller, B.J., Eisen, E.A., Emami, A., Emami, S., Embry, M.R., Emswiler, M.P., Erraguntla, N.K., Escribano, M., Espín, S., Estevan, C., Estévez, J., Etemad, L., Everson, G.W., Ewers, L.M., Fain, J.H., Fan, A.M., Farris, F.F., Farshchi, A., Fatoki, O.S., Feakes, D., Feasel, M., Fedoruk, M.J., Feitshans, I.L., Fent, G.M., Fernández-Tajes, J., Fernández, Á.J.G., Fernández, C., Fernández Rodríguez, M.D., Ferrari, B., Fidalgo, J., Fields, A., Finch, G.L., Finizio, A., Finnveden, G., Fitzgerald, L., Foroumadi, A., Fuentes, D., Gad, K., Gad, S.C., Gad, S.E., Gadagbui, B., Gammon, D.W., García-Fernández, A.J., García Gómez, M.C., Gardner, D.E., Garrard, A., Garric, J., Gautam, G., Geffard, O., Genter, M.B., Gevaart-Durkin, A., Ghafouri, N., Ghazali, A.R., Ghoreishi, K., Ghosh, B., Gilbert, S.G., Giordano, G., Giouleme, O., Gironés, M.C.L.R., Gobba, F., Goel, S., Gohari, A.R., Gohlke, J.M., Golbabaei, S., Gold, S.C., Gómez-López, V.M., Gómez-Ramírez, P., González-Canga, A., González, G.L., Goodman, J.E., Gordon, E., Gordon, T., Gorodetsky, R., Gray, J.P., Green, M.D., Greim, H., Griffiths, J.C., Groth, C.M., Guedes de Pinho, P., Gupta, N., Gupta, R.C., Gutiérrez, A.J., Guy, R.C., Haber, L.T., Hacatoglu, K., Hahn, K., Haines, J.A., Hakkinen, P.J., Hall, E.J., Hall, G.J., Hall, V.R., Hambright, K.D., Handler, J.A., Hansen, D.K., Hanson, K.M., Hanson, M., Hardison, L.S., Hardisson, A., Harper, S.L., Hartmann, A.C., Hartung, T., Hartwig, A., Hassani, S., Hatlelid, K.M., Hayes, A.W., Hayes, A.N., Heidari, M.R., Henderson, J., Henriksen, B., Hernández-Moreno, D., Hertzberg, R.C., Hesterberg, T., Heyndrickx, M., Hicks, D., Hikkaduwa Koralege, R.S., Hilburn, M.E., Hinderliter, P., Hines, E.P., Hirakawa, B., Hirata, C.M., Ho, S., Hobson, D.W., Hoffmann, S., Holloway, A.C., Holstege, C.P., Holstege, E., Hon, S.L., Honeycutt, M., Hong, S., Hoover, M.D., Hopf, N.B., Hopp, A.G., Horiguchi, H., Hosseini-Tabatabaei, A., Hosseini, A., Hostetler, M.A., Hsu, C.H., Huang, F.X., Hulla, J.E., Hultén, P., Hultin, M.L., Hurst, H.E., Iannucci, A., Inayat-Hussain, S.H., Inselman, A.L., Iskander, J., Jabbour, R.E., Jaberidoost, M., Jacobs, M., Jamei, M., Jamison, K.P., Janes, M., Janz, D.M., Jazayeri, S.B., Jenkins, A., Jiang, M., Jin, N., John, K., Jones, L., Jones, P.D., Jordan, S.A., Jurado, A.S., Kalapos, M.P., Kamrin, M.A., Kapp, R.W., Karami-Mohajeri, S., Karanth, S., Karimi, G., Katz, S.A., Kem, W.R., Kempegowda, P., Kennedy, G.L., Kester, J.E., Khaksar, M.R., Kharabaf, S., Khoobi, M., Kiersma, M.E., Kilpinen, J.M., Kim, D.H., Kim, S.T., Kimbrough, R.D., Klein, S.J., Knechtges, P.L., Knuckles, T.L., Knudsen, T.B., Korrapati, M.C., Koshlukova, S.E., Kovacic, P., Kraft, A., Krafts, K., Krishnan, P., Kruger, C.L., Kubic, A., Kulkarni, S., Kwok, E.S.C., Laffon, B., Lagadic, L., Lambert, C.E., Landolph, J.R., Lange, R.W., Lank, P., Lari, P., Lasley, W., Lawana, V., Lazo, C.R., Ledrich, M.-L., Le Goff, F., Lein, P.J., Leung, H.-W., Leung, Y.L., Lewandowski, T.A., Li, X., Liesivuori, J., Lim, L., Limaye, P., Lin, H.H., Lin, S.C., Litovitz, T., Liu, F., Liu, J., Lloyd-Smith, M., Lo, J.C.Y., Loccisano, A.E., Logan, P., López, S., Lord-Garcia, J., Lotti, M., Luschützky, E., Mahdaviani, P., Maier, A., Makhaeva, G.F., Malátová, I., Malekirad, A.A., Manayi, A., Mangas, I., Mangino, M., Mangipudy, R.S., Maples, R.D., Marcel, B.J., Marigómez, I., Marraffa, J.M., Martínez-López, E., Mathews, S.M., Maxim, L.D., Maxwell-Stuart, P.G., Mayor, A., McClane, B.A., McCoole, M.D., McCormick, D.B., McGregor, D., McKee, J.M., McMartin, K., Meek, B., Megharaj, M., Mehendale, H.M., Mehrpour, O., Mendes, A., Méndez, J., Menn, F.-M., Meyer, S.A., Michalak, I., Míguez-Santiyán, M.P., Mikulewicz, M., Milanez, S., Mileson, B.E., Miller, G.W., Miller, S.J., Miller, S.M., Millner, G.C., Minarchick, V.C., Miracle, A.L., Mirajkar, N.S., Mirkes, P.E., Mitra, M.S., Mody, V., Mogl, S., Mohammadirad, A., Mojica, E.-R.E., Molander, L., Molina López, A.M., Momen-Heravi, F., Montague, P., Monteiro, J.P., Monticelli, F., Morceau, F., Moreno, M., Morgan, B.W., Mortensen, S.R., Moser, V.C., Moshiri, M., Mostafalou, S., Moyer, R.A., Mumy, K.L., Munday, R., Murdianti, B.S., Murray, A., Murray, T.M., Murta, T.L., Nadri, H., Naidu, R., Naile, J.E., Naistat, D.M., Nakajima, T., Nalliah, R.E., Nance, P., Nathan, S., Navarro, L., Navas, I.M., Nelson, L.S., Nerin, C., Newsted, J., Nikfar, S., Nili-Ahmadabadi, A., Nobay, F., Nony, P., Nurkiewicz, T.R., Oi, M., Okoro, H.K., Oliveira, P.A., Olsen, L.R., Oropesa Jiménez, A.L., Othumpangat, S., Pablos, M.V., Pakulska, D., Pakzad, M., Pallasch, E.M., Pamies, D., Parihar, H.S., Parmar, M.S., Parod, R.J., Paschos, P., Patterson, J., Patterson, T.J., Patterson, T.A., Paulo Teixeira, J., Pawlaczyk, A., Pearson, M.A., Pellerano, M.B., Pellizzato, F., Perales, C.M., Peredy, T., Pereira, J., Pérez-López, M., Peri, R., Persad, A.S., Persson, H., Perwaiz, S., Peterson, M.K., Pham, P.J., Pham, T., Philip, B.K., Pichery, C., Pickett, A.J., Piña, B., Pinkerton, K.E., Pleus, R.C., Podder, S., Poirier, M.C., Pomerleau, A.C., Pope, C., Posthuma, L., Potting, J., Pournourmohammadi, S., Pravasi, S.D., Preston, R.J., Prusakov, P.A., Punja, M., Puran, A.C., Purcell, M.M., Qian, L., Qozi, M., Quintana, P.J.E., Rabiei, M., Radulovic, L.L., Rahmani, N., Rajabi, M., Raman, P., Ramasahayam, S., Ramos-Peralonso, M.J., Rankin, G.O., Rao, C.V., Rao, P.S., Rashedinia, M., Rath, A.D., Ray, D.E., Ray, S.D., Reed, N.R., Remião, F., Rezaee, R., Rezvanfar, M.A., Rezvani, N., Rhomberg, L.R., Riar, N.K., Rice, G., Richardson, J.R., Richardson, R.J., Richter, P., Rider, G., Rivera, H.L., Robbens, J., Roberts, D.J., Roberts, L.G., Robinson, P.J., Robles, H., Rodgers, B.E., Rodgers, K., Rodriguez, Y.R., Rodriguez Fernández, C., Roede, J.R., Rogawski, M.A., Rojo, L., Romano, J.A., Rose, S.R., Rosen, M.A., Rossol, M., Rostami–Hodjegan, A., Rourke, J.L., Roy, R., Roy, S.S., Rozman, K.K., Rubin, A.L., Rubio, C., Ruch, R.J., Rumbeiha, W.K., Rushton, W., Sabzevari, O., Saeedi, M., Saeid, A., Saeidnia, S., Saghir, S.A., Saili, K.S., Salem, H., Salvago, M.R. Moyano, Salvatore, J.R., San Andrés Larrea, M.D., San Andrés Larrea, M.I., Sarazan, R.D., Sardari, S., Sasaki, T., Sawant, S.P., Schaeffer, V., Schep, L.J., Schlesinger, R.B., Schneider, S.M., Schreffler, S.M., Schultz, M.M., Schwartz, M., Schwela, D., Scott, A.L., Scott, B.R., Scribner, K., Seabury, R.W., Seco, B., Seeley, M., Seifert, J., Sellamuthu, R., Serex, T.L., Sexton, K., Shadnia, S., Shafiee, A., Shah, I., Shankar, K., Sheets, L.P., Sheppard, L., Shiotsuka, R.N., Shirley, S., Shojaei Saadi, H.A., Sibbald, K.N., Sidell, F.R., Siegrist, M., Simmons, J.E., Sinal, C.J., Singh, P., Skoglund, R., Skonberg, C., Slaughter, R.J., Sledge, C.L., Slothower, J.D., Smith, M., Smith, M.T., Snider, D.B., Snyman, R.G., Sobanska, M., Sogorb, M.Á., Soler-Rodríguez, F., Solgi, R., Solomon, K.R., Somanathan, R., Sonawane, B.R., Song, X., Soni, M.G., Sorensen, J., Soucy, N.V., Southard, R.J., Spainhour, C.B., Spencer, P.S., Spiller, H.A., Spoelhof, B., Stanard, B., Stanek, L.W., Stapleton, P.A., Stedeford, T., Steidl-Nichols, J., Stephens, M., Steyn, N.P., Stickney, J., Stohs, S.J., Stone, D., Stool, D., Stork, C.M., Strohm, B., Stromberg, P.E., Sullivan, D.W., Sullivan, M.R., Sultatos, L.G., Suryanarayanan, A., Syed, I., Szabo, D.T., Szynkowska, M.I., Takacs, Z., Talaska, G., Talbot, P., Tanguay, R.L., Tarazona, J.V., Teixeira, J.P., Temple, N.J., Temple, W.A., Tena, A., Teuschler, L.K., Thackaberry, E.A., Thakore, K.N., Theodorakis, C., Thompson, R.E., Thornton, S.L., Ting, D., Tirmenstein, M.A., Touwaide, A., Towne, T.G., Traven, S.A., Tritscher, A., Troendle, M., Trosko, J.E., Tsai, W.-T., Tsai-Turton, M., Tsatsakis, A., Tsitsimpikou, C., Tsubura, A., Tsuda, T., Tyl, R.W., Udarbe Zamora, E.M., Utell, M.J., Vahabzadeh, M., Vaidya, V.S., Valdiglesias, V., Valentovic, M.A., Valerio, L.G., Vales, T., Vandenberg, L.N., van den Brink, P.J., van der Kolk, J., Van Vleet, T.R., van Vliet, E., Varga, J., Venkateswarlu, K., Verslycke, T., Versonnen, B., Verstraete, K., Vighi, M., Vilanova, E., Vincent, L., Vincent, M., Visser, R., Volger, B., von Stackelberg, K., Vulimiri, S.V., Wahl, M., Walker, N.J., Walker, T.D., Wallace, D.R., Wang, C., Wang, G.S., Wanna-Nakamura, S.C., Watson, R.E., Wattenberg, E.V., Wax, P.M., Weaver, J.A., Webber, N.R., Weber, J.A., Weber, L.P., Weinrich, A.J., Weiss, B., Wennberg, A., Wernke, M.J., Weston, A., Wexler, P., White, L.D., Whittaker, M.H., Wiedenfeld, H., Wiegand, T.J., Wikoff, D.S., Wild, C.P., Will, Y., Willett, C., Willhite, C.C., Willis, A., Willis, K., Wills, B.K., Wilson, B.W., Wittliff, J.L., Wojcinski, Z.W., Wolfe, M.S., Wood, C.S., Woodall, G.M., Woolley, A., Xia, M., Ximba, B.J., Yan, B., Yanagiba, Y., Yang, D., Yang, N., Yoon, M., Yorifuji, T., Yoshizawa, K., Young, R.A., Zamor, R.M., and Zhao, Q.J.
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- 2014
- Full Text
- View/download PDF
10. Acylation of naturally occurring and synthetic 1-deoxysphinganines by ceramide synthase. Formation of N-palmitoyl-aminopentol produces a toxic metabolite of hydrolyzed fumonisin, AP1, and a new category of ceramide synthase inhibitor.
- Author
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Humpf, H U, Schmelz, E M, Meredith, F I, Vesper, H, Vales, T R, Wang, E, Menaldino, D S, Liotta, D C, and Merrill, A H
- Abstract
Fumonisin B1 (FB1) is the predominant member of a family of mycotoxins produced by Fusarium moniliforme (Sheldon) and related fungi. Certain foods also contain the aminopentol backbone (AP1) that is formed upon base hydrolysis of the ester-linked tricarballylic acids of FB1. Both FB1 and, to a lesser extent, AP1 inhibit ceramide synthase due to structural similarities between fumonisins (as 1-deoxy-analogs of sphinganine) and sphingoid bases. To explore these structure-function relationships further, erythro- and threo-2-amino, 3-hydroxy- (and 3, 5-dihydroxy-) octadecanes were prepared by highly stereoselective syntheses. All of these analogs inhibit the acylation of sphingoid bases by ceramide synthase, and are themselves acylated with Vmax/Km of 40-125 for the erythro-isomers (compared with approximately 250 for D-erythro-sphinganine) and 4-6 for the threo-isomers. Ceramide synthase also acylates AP1 (but not FB1, under the conditions tested) to N-palmitoyl-AP1 (PAP1) with a Vmax/Km of approximately 1. The toxicity of PAP1 was evaluated using HT29 cells, a human colonic cell line. PAP1 was at least 10 times more toxic than FB1 or AP1 and caused sphinganine accumulation as an inhibitor of ceramide synthase. These studies demonstrate that: the 1-hydroxyl group is not required for sphingoid bases to be acylated; both erythro- and threo-isomers are acylated with the highest apparent Vmax/Km for the erythro-analogs; and AP1 is acylated to PAP1, a new category of ceramide synthase inhibitor as well as a toxic metabolite that may play a role in the diseases caused by fumonisins.
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- 1998
11. Sphingolipid biosynthesis de novo by rat hepatocytes in culture. Ceramide and sphingomyelin are associated with, but not required for, very low density lipoprotein secretion.
- Author
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Merrill, A H, Lingrell, S, Wang, E, Nikolova-Karakashian, M, Vales, T R, and Vance, D E
- Abstract
Sphingolipids are constituents of liver and lipoproteins, but relatively little is known about their synthesis and secretion. Incubation of rat hepatocytes with [14C]- or [3H]serine labeled the long-chain base backbones of mainly ceramide and sphingomyelin. Most of the labeled sphingolipids were associated with the cells; however, 1-5% (the majority of which was ceramide) was released into the medium as part of very low density lipoproteins (VLDL). Since this is the first report that lipoproteins contain ceramide, lipoproteins were isolated from rat plasma, and the ceramide contents were (per mg of protein): 6.5 nmol for VLDL (d < 1.018), 0.6 nmol for low density lipoproteins (1.018 < d < 1.063), 0.2 nmol for high density lipoproteins (1.063 < d < 1.18), and 0.1 nmol for the albumin fraction; the lipoproteins also contained 0.1-0.4 nmol of free sphingosine/mg of protein. A number of factors affected the secretion of radiolabeled sphingolipids: 1) addition of palmitic acid, but not stearic or oleic acid, enhanced secretion due to an increase in long-chain base synthesis de novo. 2) Choline deficiency caused a 42% reduction in the secretion of radiolabeled sphingomyelin, but this was due to an effect on VLDL secretion rather than a decrease in sphingolipid synthesis. Removal of choline was examined because previous studies (Yao, Z. M., and Vance, D. E. (1988) J. Biol. Chem. 263, 2998-3004) have shown that choline deficiencies depress phosphatidylcholine synthesis and lipoprotein secretion. 3) Incubation of the cells with fumonisin B1, a mycotoxin inhibitor of sphinganine (sphingosine) N-acyltransferase, reduced overall sphingolipid synthesis and secretion by 90%, but had no effect on the secretion of apoB, phosphatidylcholine, or cholesterol. All together, these findings demonstrate that rat hepatocytes synthesize ceramide and sphingomyelin de novo and incorporate them into both cellular membranes and secreted VLDL, but normal sphingolipid synthesis is not required for lipoprotein secretion.
- Published
- 1995
12. Regulation of lipid biosynthesis in Saccharomyces cerevisiae by fumonisin B1.
- Author
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Wu, W I, McDonough, V M, Nickels, J T, Ko, J, Fischl, A S, Vales, T R, Merrill, A H, and Carman, G M
- Abstract
The regulation of lipid biosynthesis in the yeast Saccharomyces cerevisiae by fumonisin B1 was examined. Fumonisin B1 inhibited the growth of yeast cells. Cells supplemented with fumonisin B1 accumulated free sphinganine and phytosphingosine in a dose-dependent manner. The cellular concentration of ceramide was reduced in fumonisin B1-supplemented cells. Ceramide synthase activity was found in yeast cell membranes and was inhibited by fumonisin B1. Fumonisin B1 inhibited the synthesis of the inositol-containing sphingolipids inositol phosphorylceramide, mannosylinositol phosphorylceramide, and mannosyldiinositol phosphorylceramide. Fumonisin B1 also caused a decrease in the synthesis of the major phospholipids synthesized via the CDP-diacylglycerol-dependent pathway and the synthesis of neutral lipids. The effects of fumonisin B1 and sphingoid bases on the activities of enzymes in the pathways leading to the synthesis of sphingolipids, phospholipids, and neutral lipids were also examined. Other than ceramide synthase, fumonisin B1 did not affect the activities of any of the enzymes examined. However, sphinganine and phytosphingosine inhibited the activities of inositol phosphorylceramide synthase, phosphatidylserine synthase, and phosphatidate phosphatase. These are key enzymes responsible for the synthesis of lipids in yeast. The data reported here indicated that the biosynthesis of sphingolipids, phospholipids and neutral lipids was coordinately regulated by fumonisin B1 through the regulation of lipid biosynthetic enzymes by sphingoid bases.
- Published
- 1995
13. A User's Guide to the Encyclopedia of DNA Elements (ENCODE)
- Author
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Zhi Lu, Giltae Song, Troy W. Whitfield, Vishwanath R. Iyer, Teresa Vales, Angelika Merkel, Max Libbrecht, David Haussler, Ting Wang, Kristen Lee, Lingyun Song, Richard M. Myers, Alfonso Valencia, Rachel A. Harte, Xiaoqin Xu, Lucas D. Ward, Hazuki Takahashi, Nathan C. Sheffield, Thomas Derrien, Georgi K. Marinov, Eric D. Nguyen, Bernard B. Suh, Brian J. Raney, Richard Sandstrom, Thomas D. Tullius, Benoit Miotto, Alexander Dobin, Youhan Xu, Lukas Habegger, Ian Dunham, Brian A. Risk, Paul G. Giresi, Morgan C. Giddings, Hualin Xi, Anshul Kundaje, Robert S. Harris, Devin Absher, Peter J. Bickel, Yanbao Yu, Browen Aken, Colin Kingswood, Bryan R. Lajoie, Peter J. Good, Katrina Learned, Laura Elnitski, Shirley Pepke, Brandon King, Piero Carninci, Xinqiong Yang, Ghia Euskirchen, Kathryn Beal, Christelle Borel, Michael Muratet, Robert L. Grossman, David G. Knowles, Zarmik Moqtaderi, Veronika Boychenko, Steven P. Wilder, Michael L. Tress, Florencia Pauli, Alan P. Boyle, Andrea Tanzer, Philipp Kapranov, Serafim Batzoglou, Audra K. Johnson, Jun Neri, Nitin Bhardwaj, Elise A. Feingold, Venkat S. Malladi, Michael M. Hoffman, William Stafford Noble, Andrea Sboner, Mark Gerstein, Stephanie L. Parker, Jacqueline Dumais, Felix Schlesinger, Deborah R. Winter, Randall H. Brown, Thanh Truong, Rebecca F. Lowdon, Paolo Ribeca, Brooke Rhead, Peggy J. Farnham, Krista Thibeault, Terrence S. Furey, Donna Karolchik, Alec Victorsen, Xiaoan Ruan, Rehab F. Abdelhamid, Amy S. Nesmith, Jing Wang, Nicholas M. Luscombe, Alina R. Cao, Diane Trout, Teri Slifer, Peter E. Newburger, Cricket A. Sloan, Dimitra Lotakis, Stephen M. J. Searle, Ali Mortazavi, Alexandra Bignell, Alex Reynolds, Orion J. Buske, Chris Zaleski, Theresa K. Canfield, Ian Bell, Jin Lian, Vanessa K. Swing, Katalin Toth Fejes, Catherine Ucla, Robert E. Thurman, Jacqueline Chrast, Wei Lin, Tim Hubbard, Gary Saunders, Minyi Shi, Vihra Sotirova, Sherman M. Weissman, Jason D. Lieb, Richard Humbert, Kevin M. Bowling, Assaf Gordon, Tarjei S. Mikkelsen, Jing Leng, Thomas R. Gingeras, Fabian Grubert, Nader Jameel, Jost Vielmetter, Hannah Monahan, Preti Jain, Lindsay L. Waite, Tony Shafer, Joel Rozowsky, Michael Coyne, Brian Reed, M. Kay, Harsha P. Gunawardena, Ross C. Hardison, Gavin Sherlock, Alexandra Charos, Joseph D. Fleming, Ann S. Zweig, Jason Gertz, Rajinder Kaul, Xianjun Dong, Alexandre Reymond, Carrie A. Davis, Haiyan Huang, Chao Cheng, Marco Mariotti, Phil Lacroute, Jason A. Dilocker, Kenneth McCue, R. Robilotto, Stylianos E. Antonarakis, Sridar V. Chittur, Justin Jee, Barbara J. Wold, Sudipto K. Chakrabortty, Erica Dumais, Amartya Sanyal, Nathan Boley, Tianyuan Wang, Julien Lagarde, Anthony Kirilusha, Jonathan B. Preall, Kevin Roberts, Erika Giste, Hugo Y. K. Lam, Alvis Brazma, Gregory J. Hannon, Eric Rynes, Philippe Batut, Kevin Struhl, Margus Lukk, Manching Ku, Suganthi Balasubramanian, Sonali Jha, Jorg Drenkow, W. James Kent, Michael Snyder, Jie Wang, Anna Battenhouse, Charles B. Epstein, Rami Rauch, Christopher Shestak, John A. Stamatoyannopoulos, Gaurab Mukherjee, Cédric Howald, Tanya Kutyavin, Huaien Wang, Scott A. Tenenbaum, Wan Ting Poh, Kate R. Rosenbloom, Manolis Kellis, Pauline A. Fujita, Linfeng Wu, Anita Bansal, Molly Weaver, Linda L. Grasfeder, Peter J. Sabo, Qiang Li, Melissa S. Cline, Robert M. Kuhn, Darin London, Seth Frietze, Atif Shahab, Shane Neph, Damian Keefe, James B. Brown, Mark Diekhans, Webb Miller, Katherine Aylor Fisher, Jiang Du, Hadar H. Sheffer, Sarah Djebali, Frank Doyle, Nathan Lamarre-Vincent, Chia-Lin Wei, Laura A.L. Dillon, Jennifer Harrow, Robert C. Altshuler, Tyler Alioto, Raymond K. Auerbach, Adam Frankish, Rebekka O. Sprouse, Patrick J. Collins, E. Christopher Partridge, Zheng Liu, Yoichiro Shibata, Elliott H. Margulies, Abigail K. Ebersol, Kimberly A. Showers, Eric D. Green, Krishna M. Roskin, Job Dekker, Barbara N. Pusey, Ekta Khurana, Gilberto DeSalvo, Yijun Ruan, Hao Wang, Jainab Khatun, Henriette O'Geen, Alexej Abyzov, Brian Williams, Ryan M. McDaniell, Maya Kasowski, Manoj Hariharan, Felix Kokocinski, Gloria Despacio-Reyes, Zhancheng Zhang, Subhradip Karmakar, Ewan Birney, Koon-Kiu Yan, Xian Chen, Shinny Vong, Daniel Sobral, Nick Bild, Seul K.C. Kim, Timo Lassmann, Li Wang, Minerva E. Sanchez, Vaughan Roach, Theodore Gibson, Stephen C. J. Parker, Michael F. Lin, Patrick A. Navas, Laurence R. Meyer, Luiz O. F. Penalva, Bradley E. Bernstein, Kevin P. White, Emilie Aït Yahya Graison, Juan M. Vaquerizas, Sushma Iyengar, Kimberly M. Newberry, Akshay Bhinge, Xiaolan Zhang, Kim Bell, Yoshihide Hayashizaki, Lucas Lochovsky, Noam Shoresh, Hagen Tilgner, Philip Cayting, Dorrelyn Patacsil, Timothy E. Reddy, Eric Haugen, Katherine E. Varley, M. van Baren, Nathan D. Trinklein, Bum Kyu Lee, Tristan Frum, Marianne Lindahl-Allen, Timothy Durham, Roderic Guigó, Christopher W. Maier, Micha Sammeth, Debasish Raha, Timothy R. Dreszer, Benedict Paten, Robbyn Issner, Michael R. Brent, Kevin Y. Yip, Kim Blahnik, Jason Ernst, Zhiping Weng, Henry Amrhein, Arend Sidow, Javier Herrero, Hui Gao, Stephen G. Landt, Pouya Kheradpour, Galt P. Barber, Gregory E. Crawford, Toby Hunt, HudsonAlpha Institute for Biotechnology [Huntsville, AL], ENCODE Project Consortium : Myers RM, Stamatoyannopoulos J, Snyder M, Dunham I, Hardison RC, Bernstein BE, Gingeras TR, Kent WJ, Birney E, Wold B, Crawford GE, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Mikkelsen TS, Kheradpour P, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Lin MF, Kellis M, Gingeras TR, Davis CA, Kapranov P, Dobin A, Zaleski C, Schlesinger F, Batut P, Chakrabortty S, Jha S, Lin W, Drenkow J, Wang H, Bell K, Gao H, Bell I, Dumais E, Dumais J, Antonarakis SE, Ucla C, Borel C, Guigo R, Djebali S, Lagarde J, Kingswood C, Ribeca P, Sammeth M, Alioto T, Merkel A, Tilgner H, Carninci P, Hayashizaki Y, Lassmann T, Takahashi H, Abdelhamid RF, Hannon G, Fejes-Toth K, Preall J, Gordon A, Sotirova V, Reymond A, Howald C, Graison E, Chrast J, Ruan Y, Ruan X, Shahab A, Ting Poh W, Wei CL, Crawford GE, Furey TS, Boyle AP, Sheffield NC, Song L, Shibata Y, Vales T, Winter D, Zhang Z, London D, Wang T, Birney E, Keefe D, Iyer VR, Lee BK, McDaniell RM, Liu Z, Battenhouse A, Bhinge AA, Lieb JD, Grasfeder LL, Showers KA, Giresi PG, Kim SK, Shestak C, Myers RM, Pauli F, Reddy TE, Gertz J, Partridge EC, Jain P, Sprouse RO, Bansal A, Pusey B, Muratet MA, Varley KE, Bowling KM, Newberry KM, Nesmith AS, Dilocker JA, Parker SL, Waite LL, Thibeault K, Roberts K, Absher DM, Wold B, Mortazavi A, Williams B, Marinov G, Trout D, Pepke S, King B, McCue K, Kirilusha A, DeSalvo G, Fisher-Aylor K, Amrhein H, Vielmetter J, Sherlock G, Sidow A, Batzoglou S, Rauch R, Kundaje A, Libbrecht M, Margulies EH, Parker SC, Elnitski L, Green ED, Hubbard T, Harrow J, Searle S, Kokocinski F, Aken B, Frankish A, Hunt T, Despacio-Reyes G, Kay M, Mukherjee G, Bignell A, Saunders G, Boychenko V, Van Baren M, Brown RH, Khurana E, Balasubramanian S, Zhang Z, Lam H, Cayting P, Robilotto R, Lu Z, Guigo R, Derrien T, Tanzer A, Knowles DG, Mariotti M, James Kent W, Haussler D, Harte R, Diekhans M, Kellis M, Lin M, Kheradpour P, Ernst J, Reymond A, Howald C, Graison EA, Chrast J, Tress M, Rodriguez JM, Snyder M, Landt SG, Raha D, Shi M, Euskirchen G, Grubert F, Kasowski M, Lian J, Cayting P, Lacroute P, Xu Y, Monahan H, Patacsil D, Slifer T, Yang X, Charos A, Reed B, Wu L, Auerbach RK, Habegger L, Hariharan M, Rozowsky J, Abyzov A, Weissman SM, Gerstein M, Struhl K, Lamarre-Vincent N, Lindahl-Allen M, Miotto B, Moqtaderi Z, Fleming JD, Newburger P, Farnham PJ, Frietze S, O'Geen H, Xu X, Blahnik KR, Cao AR, Iyengar S, Stamatoyannopoulos JA, Kaul R, Thurman RE, Wang H, Navas PA, Sandstrom R, Sabo PJ, Weaver M, Canfield T, Lee K, Neph S, Roach V, Reynolds A, Johnson A, Rynes E, Giste E, Vong S, Neri J, Frum T, Johnson EM, Nguyen ED, Ebersol AK, Sanchez ME, Sheffer HH, Lotakis D, Haugen E, Humbert R, Kutyavin T, Shafer T, Dekker J, Lajoie BR, Sanyal A, James Kent W, Rosenbloom KR, Dreszer TR, Raney BJ, Barber GP, Meyer LR, Sloan CA, Malladi VS, Cline MS, Learned K, Swing VK, Zweig AS, Rhead B, Fujita PA, Roskin K, Karolchik D, Kuhn RM, Haussler D, Birney E, Dunham I, Wilder SP, Keefe D, Sobral D, Herrero J, Beal K, Lukk M, Brazma A, Vaquerizas JM, Luscombe NM, Bickel PJ, Boley N, Brown JB, Li Q, Huang H, Gerstein M, Habegger L, Sboner A, Rozowsky J, Auerbach RK, Yip KY, Cheng C, Yan KK, Bhardwaj N, Wang J, Lochovsky L, Jee J, Gibson T, Leng J, Du J, Hardison RC, Harris RS, Song G, Miller W, Haussler D, Roskin K, Suh B, Wang T, Paten B, Noble WS, Hoffman MM, Buske OJ, Weng Z, Dong X, Wang J, Xi H, Tenenbaum SA, Doyle F, Penalva LO, Chittur S, Tullius TD, Parker SC, White KP, Karmakar S, Victorsen A, Jameel N, Bild N, Grossman RL, Snyder M, Landt SG, Yang X, Patacsil D, Slifer T, Dekker J, Lajoie BR, Sanyal A, Weng Z, Whitfield TW, Wang J, Collins PJ, Trinklein ND, Partridge EC, Myers RM, Giddings MC, Chen X, Khatun J, Maier C, Yu Y, Gunawardena H, Risk B, Feingold EA, Lowdon RF, Dillon LA, Good PJ, Harrow J, Searle S., Becker, Peter B, Broad Institute of MIT and Harvard, Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Department of Physics, Kellis, Manolis, Epstein, Charles B., Bernstein, Bradley E., Shoresh, Noam, Ernst, Jason, Mikkelsen, Tarjei Sigurd, Kheradpour, Pouya, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Ward, Lucas D., Altshuler, Robert Charles, Lin, Michael F., ENCODE Project Consortium, Antonarakis, Stylianos, and Miotto, Benoit
- Subjects
RNA, Messenger/genetics ,[SDV]Life Sciences [q-bio] ,Messenger ,Genoma humà ,Genome ,Medical and Health Sciences ,0302 clinical medicine ,Models ,ddc:576.5 ,Biology (General) ,Conserved Sequence ,Genetics ,0303 health sciences ,General Neuroscience ,RNA-Binding Proteins ,Genomics ,Biological Sciences ,Chromatin ,3. Good health ,[SDV] Life Sciences [q-bio] ,DNA-Binding Proteins ,Gene Components ,030220 oncology & carcinogenesis ,DNA methylation ,Encyclopedia ,HIV/AIDS ,Proteïnes de la sang -- Aspectes genètics ,General Agricultural and Biological Sciences ,Databases, Nucleic Acid ,Human ,Research Article ,Quality Control ,Process (engineering) ,QH301-705.5 ,1.1 Normal biological development and functioning ,Computational biology ,Biology ,ENCODE ,General Biochemistry, Genetics and Molecular Biology ,Chromatin/metabolism ,Vaccine Related ,03 medical and health sciences ,Databases ,Genetic ,Underpinning research ,Humans ,RNA, Messenger ,RNA-Binding Proteins/genetics/metabolism ,Vaccine Related (AIDS) ,Gene ,030304 developmental biology ,Internet ,General Immunology and Microbiology ,Nucleic Acid ,Agricultural and Veterinary Sciences ,Base Sequence ,Models, Genetic ,Genome, Human ,Prevention ,Human Genome ,Computational Biology ,DNA Methylation ,ENCODE Project Consortium ,Gene Expression Regulation ,DNA-Binding Proteins/genetics/metabolism ,RNA ,Human genome ,Immunization ,Generic health relevance ,Developmental Biology - Abstract
The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome., National Human Genome Research Institute (U.S.), National Institutes of Health (U.S.)
- Published
- 2011
14. Synthesis and Photophysical Properties of Tumor-Targeted Water-Soluble BODIPY Photosensitizers for Photodynamic Therapy.
- Author
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Khuong Mai D, Kang B, Pegarro Vales T, Badon IW, Cho S, Lee J, Kim E, and Kim HJ
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- Boron Compounds chemistry, Boron Compounds pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Click Chemistry, HeLa Cells, Humans, MCF-7 Cells, Neoplasms therapy, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Quantum Dots, Singlet Oxygen metabolism, Boron Compounds chemical synthesis, Lactose chemistry, Neoplasms metabolism, Photosensitizing Agents chemical synthesis
- Abstract
The synthesis of three water-soluble lactose-modified 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photosensitizers with tumor-targeting capabilities is reported, including an investigation into their photodynamic therapeutic activity on three distinct cancer cell lines (human hepatoma Huh7, cervical cancer HeLa, and breast cancer MCF-7 cell lines). The halogenated BODIPY dyes exhibited a decreased fluorescence quantum yield compared to their non-halogenated counterpart, and facilitated the efficient generation of singlet oxygen species. The synthesized dyes exhibited low cytotoxicities in the dark and high photodynamic therapeutic capabilities against the treated cancer cell lines following irradiation at 530 nm. Moreover, the incorporation of lactose moieties led to an enhanced cellular uptake of the BODIPY dyes. Collectively, the results presented herein provide promising insights for the development of photodynamic therapeutic agents for cancer treatment.
- Published
- 2020
- Full Text
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15. Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity.
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Song L, Zhang Z, Grasfeder LL, Boyle AP, Giresi PG, Lee BK, Sheffield NC, Gräf S, Huss M, Keefe D, Liu Z, London D, McDaniell RM, Shibata Y, Showers KA, Simon JM, Vales T, Wang T, Winter D, Zhang Z, Clarke ND, Birney E, Iyer VR, Crawford GE, Lieb JD, and Furey TS
- Subjects
- Base Sequence, Binding Sites, CCCTC-Binding Factor, Cell Differentiation genetics, Cell Line, Gene Expression Regulation, Humans, Protein Binding, Repressor Proteins metabolism, Transcription, Genetic, Transcriptional Activation, Chromatin metabolism, Chromosome Mapping, Regulatory Elements, Transcriptional, Sequence Analysis, DNA methods
- Abstract
The human body contains thousands of unique cell types, each with specialized functions. Cell identity is governed in large part by gene transcription programs, which are determined by regulatory elements encoded in DNA. To identify regulatory elements active in seven cell lines representative of diverse human cell types, we used DNase-seq and FAIRE-seq (Formaldehyde Assisted Isolation of Regulatory Elements) to map "open chromatin." Over 870,000 DNaseI or FAIRE sites, which correspond tightly to nucleosome-depleted regions, were identified across the seven cell lines, covering nearly 9% of the genome. The combination of DNaseI and FAIRE is more effective than either assay alone in identifying likely regulatory elements, as judged by coincidence with transcription factor binding locations determined in the same cells. Open chromatin common to all seven cell types tended to be at or near transcription start sites and to be coincident with CTCF binding sites, while open chromatin sites found in only one cell type were typically located away from transcription start sites and contained DNA motifs recognized by regulators of cell-type identity. We show that open chromatin regions bound by CTCF are potent insulators. We identified clusters of open regulatory elements (COREs) that were physically near each other and whose appearance was coordinated among one or more cell types. Gene expression and RNA Pol II binding data support the hypothesis that COREs control gene activity required for the maintenance of cell-type identity. This publicly available atlas of regulatory elements may prove valuable in identifying noncoding DNA sequence variants that are causally linked to human disease.
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- 2011
- Full Text
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16. Improved somatic embryo maturation in loblolly pine by monitoring ABA-responsive gene expression.
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Vales T, Feng X, Ge L, Xu N, Cairney J, Pullman GS, and Peter GF
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- DNA, Complementary, Gene Expression Profiling, Genes, Plant, Pinus taeda metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Abscisic Acid pharmacology, Gene Expression Regulation, Plant, Pinus taeda embryology, Pinus taeda genetics, Plant Growth Regulators pharmacology
- Abstract
During loblolly pine zygotic embryo development, increases in mRNAs for three ABA-responsive LEA-like genes coincided with the two developmental stage-specific peaks of endogenous ABA accumulation (Kapik et al. 1995). These ABA concentration profiles from zygotic embryo development were used to develop several tissue culture approaches that altered the exposure of somatic embryos to exogenous ABA. Elevating exogenous ABA at a time corresponding to mid-maturation improved the germination and resulted in more zygotic-like expression of selected genes in somatic embryos. Extending the time on maturation medium for a fourth month increased embryo yield, dry weight, and germination in high-and low-yield genotypes. Optimizing the amounts of embryogenic suspension, plated and exogenous ABA concentration increased from 22 to 66% in the early-stage bipolar embryos that developed to the cotyledonary stage.
- Published
- 2007
- Full Text
- View/download PDF
17. Abnormal formation of collagen cross-links in skin fibroblasts cultured from patients with Ehlers-Danlos syndrome type VI.
- Author
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Pasquali M, Still MJ, Vales T, Rosen RI, Evinger JD, Dembure PP, Longo N, and Elsas LJ
- Subjects
- Adolescent, Amino Acids metabolism, Ascorbic Acid pharmacology, Cells, Cultured, Child, Cross-Linking Reagents metabolism, Ehlers-Danlos Syndrome pathology, Female, Fibroblasts cytology, Fibroblasts drug effects, Humans, Hydroxylysine metabolism, Lysine metabolism, Pyridinium Compounds metabolism, Skin cytology, Skin drug effects, Skin metabolism, Collagen metabolism, Ehlers-Danlos Syndrome metabolism, Fibroblasts metabolism
- Abstract
Ehlers-Danlos syndrome type VI (EDS VI) is an autosomal recessive disorder of connective tissue characterized by hyperextensible, friable skin and joint hypermobility. Severe scoliosis and ocular fragility are present in some patients. This disease is caused by defective collagen lsyl hydroxylase, a vitamin C-dependent enzyme that converts lysyl residues to hydroxylysine on procollagen peptides. Hydroxylysine is essential for the formation of the covalent pyridinium cross-links pyridinoline (Pyr) and deoxypyridinoline (Dpyr), among mature collagen molecules. Pyr derives from three hydroxylysyl residues, whereas Dpyr derives from one lysyl and two hydroxylysyl residues. Patients with EDS VI have high urinary excretion of Dpyr, resulting in a high ratio of Dpyr-Pyr. In this study, we evaluate content and production of pyridinium cross-links in the skin and cultured fibroblasts from patients with EDS VI. The skin of normal controls contained both Pyr and Dpyr, with a marked predominance of Pyr as observed in normal urine. The skin of patients with EDS VI had reduced total content of pyridinium cross-links, with the presence of Dpyr but not Pyr. Long-term cultures of control fibroblasts produced both Pyr and Dpyr, with a pattern resembling that of normal skin. By contrast, cross-links were not detected in dermal fibroblasts cultured from patients with EDS VI. Vitamin C, which improves the clinical manifestations of some patients with EDS VI, decreased Dpyr accumulation though only minimally affecting Pyr content in control cells. By contrast, addition of vitamin C to fibroblasts from patients with EDS VI stimulated the formation of Dpyr more than that of Pyr and greatly increased total pyridinium cross-link formation. These results indicate that qualitative and quantitative alterations of pyridinium cross-links occur in skin and in cultured dermal fibroblasts of patients with EDS VI and may be responsible for their abnormal skin findings. The vitamin C-stimulated production of Dpyr and Pyr in fibroblasts from patients with EDS VI may explain at least in part the therapeutic effects of this vitamin in EDS VI.
- Published
- 1997
18. Selective suppression of cytochrome P-450 gene expression by interleukins 1 and 6 in rat liver.
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Morgan ET, Thomas KB, Swanson R, Vales T, Hwang J, and Wright K
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- Animals, Cells, Cultured, Dexamethasone pharmacology, Female, Gene Expression Regulation, Enzymologic drug effects, In Vitro Techniques, Liver metabolism, Male, RNA, Messenger genetics, Rats, Rats, Sprague-Dawley, Time Factors, Cytochrome P-450 Enzyme System genetics, Interleukin-1 pharmacology, Interleukin-6 pharmacology
- Abstract
Inflammatory stimuli suppress constitutive hepatic expression of the CYP2C11 and CYP2C12 genes in male and female rat livers, respectively. We have shown previously that injection of interleukin-1 (IL1), but not interleukin-6 (IL6), to female rats also suppresses CYP2C12. In the present study, we examined the effects of these cytokines on CYP2C12 expression in rat hepatocyte cultures, and their in vivo effects on expression of multiple cytochrome P-450 (P450) gene products in male rat livers. IL1 suppressed the expression of CYP2C12 mRNA and protein in hepatocytes cultured on Matrigel in the presence of growth hormone. No consistent effect of IL6 was observed. Maximal suppression of CYP2C12 mRNA after 24 h of IL1 treatment reached 12 and 32% of control levels in two separate experiments. The approximate ED50 for IL1 was 5 ng/ml. CYP2C12 protein was suppressed to 28% of control levels as early as 12 h after IL1 treatment. Injection of IL1, low doses of dexamethasone, or both, in male rats produced decreases in total P450, and in CYP3A2 and CYP2C11 mRNA and protein expression similar to effects previously seen for CYP2C12 expression in females. CYP2E1 mRNA and protein was significantly suppressed only by the combination of IL1 and dexamethasone. IL6 treatment of male rats down-regulated the CYP2C11 and CYP2E1 mRNAs at a dose of 4.5 micrograms/kg, which was lower than that required to induce haptoglobin mRNA, a prototype acute phase gene product. CYP2C11 protein content of the microsomes was also decreased by IL6 treatment, with a slower time-course than for suppression of its mRNA. No significant effects of IL6 treatment were seen on CYP3A2 mRNA or CYP3A2/1 proteins. These results demonstrate that IL1 and IL6 treatments in vivo differentially affect subsets of P450 gene products in rat liver.
- Published
- 1994
- Full Text
- View/download PDF
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