46 results on '"Kananen, K."'
Search Results
2. The effect of ascorbic acid during biopsy and cryopreservation on viability of bovine embryos produced in vivo
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Korhonen, K., Julkunen, H., Kananen, K., Bredbacka, P., Tiirikka, T., Räty, M., Vartia, K., Kaimio, I., Kontinen, A., Halmekytö, M., Vilkki, J., Peippo, J., and Lindeberg, H.
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- 2012
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3. Evidence for Multiple Teosinte Hybrid Zones in Central Mexico
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Sanchez-Gonzalez JdJ, Kananen K, John Doebley, David E. Hufnagel, Matthew B. Hufford, and Jeffrey C. Glaubitz
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education.field_of_study ,Taxon ,Hybrid zone ,Genus ,Range (biology) ,Evolutionary biology ,Population ,Biology ,education ,Isolation by distance ,Local adaptation ,Hybrid - Abstract
1SummaryHybrid zones provide an excellent opportunity for studying population dynamics and whether hybrid genetic architectures are locally adaptive. The genus Zea contains many diverse wild taxa collectively called teosinte.Zea maysssp.parviglumis, the lowland progenitor of maize (Zea maysssp.mays), and its highland relativeZea maysssp.mexicanalive parapatrically and, while putative hybrids have been identified in regions of range overlap, these have never been deeply explored.Here we use a broadly sampled SNP data set to identify and confirm 112 hybrids betweenZea maysssp.parviglumisandZea maysssp.mexicana, mostly clustered in three genetically and geographically distinct hybrid groups in Central Mexico.These hybrid groups inhabit intermediate environments relative to parental taxa. We demonstrate that these individuals are true hybrids and not products of isolation by distance or ancestral to parviglumis and mexicana. This work expands on previous studies, clearly identifying hybrid zones inZea, genetically characterizing hybrid groups, and showing what appear to be unique genetic architectures of hybridization in distinct hybrid groups.With the potential for local adaptation, variable hybrid zone dynamics, and differential architectures of hybridization, we present these teosinte hybrids and parental taxa as a promising model system for studying hybridization and hybrid zones.
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- 2021
4. Serum osteoprotegerin and receptor activator of nuclear factor-κB ligand (RANKL) concentrations in allogeneic stem cell transplant-recipients: a role in bone loss?
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Kananen, K., Volin, L., Laitinen, K., Ruutu, T., and Välimäki, M. J.
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- 2006
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5. Serum osteoprotegerin and receptor activator of nuclear factor-IoB ligand (RANKL) concentrations in allogeneic stem cell transplant-recipients: a role in bone loss?
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Kananen, K., Volin, L., Laitinen, K., Ruutu, T., and Valimaki, M.J.
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Osteoporosis -- Causes of ,Osteoporosis -- Care and treatment ,Stem cells -- Transplantation ,Stem cells -- Complications and side effects ,Health - Abstract
Byline: K. Kananen (1), L. Volin (2), K. Laitinen (3), T. Ruutu (2), M. J. Valimaki (1) Keywords: Osteoporosis; Osteoprotegerin; sRANKL; Stem cell transplantation Abstract: Purpose: Osteoporosis is a long-term complication of allogeneic stem cell transplantation (SCT). Receptor activator of nuclear factor-IoB ligand (RANKL) increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A deficiency of OPG or an excess of RANKL may contribute to post-SCT bone loss. Methods: Serum OPG and soluble RANKL (sRANKL) concentrations were determined in 30 patients who received calcium, vitamin D and sex steroids -- with or without pamidronate -- prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to those in healthy controls. Results: Despite all treatments patients lost bone at the hip. At baseline, serum OPG was similar in patients and controls in the two patient groups it increased by 26--27% at 6 months post-SCT (p=0.002--0.028) and over the control level (p=0.002). Serum sRANKL concentrations were also similar in patients and controls at baseline. In those patients receiving pamidronate sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in 28 additional patients who did not receive pamidronate, at a median of 122 days after SCT. In this latter group, OPG but not sRANKL concentrations were clearly elevated (p< 0.001) in comparison to healthy controls. In conclusion, the present study fails to support the view that an excess of sRANKL or a deficiency of OPG would have a substantial impact on bone loss in SCT-recipients. Conclusion: Serum sRANKL concentrations may be modulated by bisphosphonates. Author Affiliation: (1) Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, 00290, Helsinki, Finland (2) Division of Haematology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (3) Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland Article History: Registration Date: 11/11/2005 Received Date: 30/06/2005 Accepted Date: 09/11/2005 Online Date: 31/12/2005
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- 2006
6. Recovery of bone mass and normalization of bone turnover in long-term survivors of allogeneic bone marrow transplantation
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Kananen, K, Volin, L, Tähtelä, R, Laitinen, K, Ruutu, T, and Välimäki, MJ
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- 2002
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7. Impact of in vitro fertilization of bovine oocytes with sex-sorted frozen--thawed spermatozoa on developmental kinetics, quality and sex ratio of developing embryos
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Peippo, J., Räty, M., Korhonen, K., Eronen, M., Kananen, K., Hurme, T., Halmekytö, M., and Mäki-Tanila, A.
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- 2010
8. Tuberoosiskleroosi - suomalainen diagnoosi- ja seurantasuositus
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Metsähonkala L, Alapulli H, Arvio M, Hiippala A, Hodgson U, Immonen A, Kananen K, Karvonen M, Kataja J, Kälviäinen R, Leppävirta J, Lähdesmäki T, Nisen H, Pöyhönen M, Vanninen R, Vasara K, Vieira P, and School of Medicine / Clinical Medicine
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Tuberoosiskleroosia sairastavat potilaat tarvitsevat systemaattista, monen erikoisalan seurantaa läpi elämän. Tavoitteena on haitallisten tai jopa hengenvaarallisten elinmuutosten varhainen toteaminen ja hoito. Epilepsian tehokkaalla hoidolla ja kehityksen oikea-aikaisella tuella pyritään vaikuttamaan potilaiden kehitysennusteeseen ja neuropsykiatristen häiriöiden esiintymiseen. Tässä suosituksessa esitetään diagnosointi- ja seurantavaiheessa tarvittavat tutkimukset ja niiden toteutus, jossa hyödynnetään sekä erikoissairaanhoidon että perusterveydenhuollon palveluja., published version, peerReviewed
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- 2017
9. Koskikunnostusten vaikutukset ekosysteemipalveluihin kalastajien, melojien ja ranta-asukkaiden näkökulmasta Kiiminki-, Koston- ja Simojoella
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Kananen, K. (Kirsi)
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Geography - Abstract
Ihminen on vaikuttanut virtavesiin lähes koko historiansa ajan. Virtavesiä on muokattu mm. valjastamalla koskia sähköntuotantoon ja ruoppaamalla koskia taloudellisten tekijöiden vuoksi. Muokkaus on kaventanut virtavesien biodiversiteettiä. Tämä on johtanut tuottavuuden laskuun ja vaikuttanut kykyyn tuottaa ekosysteemipalveluita. Suomessa virtavesiä on muokattu lähinnä tukinuiton ja vesivoimatuotannon tarpeisiin. Virtavesikunnostukset ovat korjaavaa vesirakentamistoimintaa. Niiden avulla pyritään parantamaan joen nykyistä tilaa kohti luonnonmukaisempaa. Kunnostuksia on tehty pitkään lähinnä kalataloudellisista lähtökohdista. Joen muita käyttäjäryhmiä tai sosiaalisia seikkoja ei ole huomioitu samalla tavalla. Kunnostusvaikutusten arvioinnissa tarvitaan enemmän kokonaisvaltaista tutkimusta, jossa myös sosiaalinen näkökulma on aiempaa enemmän mukana. Tämän tutkielman tarkoituksena on tarkastella kysely- ja haastatteluaineiston kautta, kuinka virkistyskäyttäjät ja ranta-asukkaat kokevat ekosysteemipalveluiden muutoksen kolmella joella Pohjois-Suomessa. Lisäksi tarkastellaan, ovatko kunnostukset onnistuneet sekä mitä hyötyjä ja haittoja kunnostuksilla on eri käyttäjäryhmien näkökulmasta. Tutkielmassa käsitellään virtavesien ekosysteemipalveluita ja erityisesti kulttuuripalveluita, johon kuuluu merkittävänä osana virkistyspalvelut. Aineisto koostui melojien haastatteluista (n=10) sekä ranta-asukkaiden ja kalastajien kyselyistä (n= asukkaat 302 ja kalastajat 380). Vastauksia palautui yhteensä 682, jolloin vastausprosentti oli 31. Koskikunnostukset ovat edistäneet ranta-asukkaiden, kalastajien ja melojien kulttuuripalveluita, mutta tuotantopalveluihin kuuluvissa kalasaaliissa ei ole tapahtunut toivottua muutosta. Koskien kalastettavuus ja kalastuspaikat ovat käyttäjien mielestä parantuneet, mikä on vaikuttanut virkistyskäyttömahdollisuuksiin. Maisema koettiin muuttuneen kauniimmaksi ja luonnonmukaisemmaksi sekä äänimaisema miellyttävämmäksi. Tämä on todennäköisesti vaikuttanut myös asumisviihtyvyyteen, jonka koettiin parantuneen. Edellytykset virkistäytymiselle ovat yleisesti parantuneet ranta-asukkaiden ja kalastajien näkökulmasta, mutta jokien välillä oli eroavaisuuksia näiden kokemisessa. Toisaalta kulttuuripalveluiden hyödyntämismahdollisuudet ovat osittain vaikeutuneet. Uimisen harrastaminen on hieman hankaloitunut sekä koskissa kahlaaminen ja kalastaminen ovat joidenkin mielestä vaikeutuneet pyörivien kivien ja kuoppien takia. Kiveäminen ja uoman leventäminen ovat vaikeuttaneet melomista vähäisen veden aikaan. Melominen on voinut muuttua paikoin jopa mahdottomaksi. Osa melojista arvioi kuitenkin melomisen muuttuneen mielenkiintoisemmaksi. Kunnostukset eivät ole yleensä vaikuttaneet ranta-asukkaiden ja melojien vierailutottumuksiin, kun taas kalastajat ovat hieman lisänneet kalastusta kunnostusten jälkeen. Virkistyskäyttäjien ja ranta-asukkaiden mukaan jokiuoman kunnostukset eivät ole yksistään riittävä keino joen ekologisen tilan, virkistyskäytön ja asumisviihtyvyyden parantamiseksi. Heidän mielestään valuma-aluetasolla tarvitaan kokonaisvaltaisempaa ongelman hallintaa ja mm. turvetuotannon vaikutusten vähentämistä.
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- 2014
10. A randomized phase II study of stem cell mobilization with cyclophosphamide+G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma
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Silvennoinen, R, primary, Anttila, P, additional, Säily, M, additional, Lundan, T, additional, Heiskanen, J, additional, Siitonen, T M, additional, Kakko, S, additional, Putkonen, M, additional, Ollikainen, H, additional, Terävä, V, additional, Kutila, A, additional, Launonen, K, additional, Räsänen, A, additional, Sikiö, A, additional, Suominen, M, additional, Bazia, P, additional, Kananen, K, additional, Selander, T, additional, Kuittinen, T, additional, Remes, K, additional, and Jantunen, E, additional
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- 2015
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11. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes
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Parving, Hh, Brenner, Bm, Mcmurray, Jj, de Zeeuw, D, Haffner, Sm, Solomon, Sd, Chaturvedi, N, Persson, F, Desai, As, Nicolaides, M, Richard, A, Xiang, Z, Brunel, P, Pfeffer, Ma, Viberti, G, Lachin, Jm, Zinman, B, Pedersen, Tr, Villamil, As, Juncos, L, Prager, R, Verpooten, G, Zanella, Mt, Leiter, L, Pan, C, Wang, H, Botero, R, Cifkova, R, Christiansen, Js, Groop, Ph, Marre, M, Haller, H, Nickenig, G, Siamopoulos, K, Gero, L, Maggioni, A, Remuzzi, G, Katayama, Ss, Kim, Sg, Petrulioniene, Z, Lok, D, Kooy, A, Jorde, R, Medina, F, Polonia, J, Wong, Ks, Dukat, A, Rayner, Bl, Ruilope, L, Weiss, L, Wuethrich, R, Sheu, W, Sritara, P, Comlekci, A, Bilous, R, Toto, R, Jamerson, K, Carillo, E, Orias, M, Kuschnir, E, Rusculleda, M, Garcia, S, Farias, E, Lema, L, Hominal, M, Montaña, O, Sala, J, Diaz, M, Piskorz, D, Vita, N, Litwak, L, Sinay, I, Marin, M, Massari, P, Majul, C, Aizemberg, D, Azize, Gm, Bartolacci, I, Reboredo, A, Vico, M, Milesi, R, Sessa, H, Wassermann, A, Margulis, F, Zangroniz, P, Watschinger, B, Toplak, H, Paulweber, B, Drexel, H, Francesconi, C, Foeger, B, Mayer, G, Braun, Rk, Brath, H, Gaal, Lv, Niepen, Pv, Persu, A, Vercammen, C, Vriese, Ad, Coucke, F, Mathieu, C, Fery, F, Treille, S, Meeus, G, Acker, Kv, Scheen, A, Tits, J, Ruige, J, Krzesinski, Jm, Hollanders, G, Liénart, F, Dendale, P, Quinonez, M, Arnouts, P, Vanuytsel, J, Zanella, M, Mion D., Jr, Forti, A, Almeida, F, Cunha, R, de Paula RB, Brandao, A, Rocha, J, Krieger, E, Feitosa, G, Saraiva, J, Martin, J, Hissa, Mn, Schmid, H, Felicio, J, Sgarbi, J, Oigman, W, Bowering, K, Garceau, C, Berlingieri, Jc, Weisnagel, Sj, Hardin, P, Powell, C, Turcot, R, Muirhead, N, Aronson, R, Barima, Yt, Steele, Aw, Pandey, S, Woo, V, Cha, J, Dattani, D, Godin, C, Gupta, M, Saunders, K, Tellier, G, Ting, R, Tobe, S, Chouinard, G, Schlosser, R, Khandwala, H, Ekoe, Jm, Harris, Sb, Pichette, V, Lachance, P, Ooi, Tc, Tildesley, H, Barrett, B, Cournoyer, S, Lu, J, Zhang, H, Liu, X, Yan, S, Qi, X, Li, Q, Li, H, Lv, X, Yang, J, Sun, N, Xia, W, Wang, N, Tong, N, Mei, C, Gu, S, Zhang, J, Chen, X, Li, L, Su, B, Wang, L, Qiu, M, Wu, X, Liu, Z, Jia, W, Xu, G, Dong, J, Zhu, D, Zhang, M, Yan, J, Liu, B, Chen, J, Fu, J, Yan, L, Zhan, X, Zhong, L, Yang, T, Ma, J, Xu, M, Xu, X, Shi, B, Ji, Q, Zhong, H, He, R, Yuan, Z, Zhou, Z, Lin, H, Yang, W, Ke, Y, Hong, T, Franco, C, Casas, L, Triana, A, Jaramillo, C, Hernandez, E, Barrera, C, Blanco, D, Stipal, R, Widimsky, P, Dohnalova, L, Komroskova, M, Kvapil, M, Belobradkova, J, Tesar, V, Vodnansky, P, Kocourkova, B, Lervang, Hh, Perrild, H, Rossing, P, Oestergaard, O, Juhl, H, Thorsteinsson, B, Snorgaard, O, Urhammer, S, Egstrup, K, Tikkanen, T, Helin, K, Rinne, J, Lahtela, J, Strand, J, Valtonen, E, Saari, M, Kananen, K, Savela, K, Blacher, J, Aldigier, Jc, Zaoui, P, Fauvel, Jp, Gouet, D, Valensi, Pe, Charpentier, G, Marechaud, R, Penfornis, A, Ovize, M, Kovalchuck, Aa, Dellanna, F, Schoen, N, Groeschel, W, Eickhoff, F, Hanefeld, M, Merke, J, Rambausek, M, Zimmermann, U, Stuetz, W, Vosskuehler, A, Hevendehl, G, Schax, U, Lehmann, G, Haack, A, Hilgenberg, J, Klausmann, G, Adelberger, V, Gessner, S, Fiesselmann, A, Oerter, E, Hohenstatt, T, Groeschel, A, Behnke, T, Sisting, Rt, Schoch, D, Bieler, T, Schleyer, S, Altes, U, Klepzig, C, Rudofsky, G, Mueller, G, Burkhardt, F, Reschke, K, Senftleber, I, Wiesweg, Ck, Herrmann, Hj, Brandstetter, R, Segner, A, Schmitt, H, Rippert, R, Goebel, R, Schreibmueller, F, Pencz, I, Ott, P, Migdalis, I, Pappas, S, Pagkalos, E, Yalouris, A, Tsapas, A, Maltezos, E, Tentolouris, N, Papadakis, I, Ioannidis, G, Goumenos, D, Corona, V, Gonzalez, R, Haase, F, Monterroso, V, Sánchez, V, Turcios, E, Wyss, F, Arango, Jl, Bako, B, Deak, L, Dömötör, E, Dudas, M, Fulop, T, Kiss, I, Koranyi, L, Lengyel, Z, Nyirati, G, Oroszlan, T, Aniko, S, Vörös, P, Kapocsi, J, Wittmann, I, Paragh, G, Abraham, G, Tandon, N, Thomas, N, Mohan, V, Sahay, R, Sethi, B, Rao, V, Kumar, S, Chowdhury, S, Dharmalingam, M, Seshiah, V, Bantwal, G, Viswanathan, V, Yajnik, C, Adhikari, P, Krishnan, U, Varthakavi, P, Hiremath, J, Bhattacharyya, A, Dani, S, Modi, Kk, Glorioso, N, Morosetti, M, Veglio, Franco, Perticone, F, Dotta, F, Quarello, F, Sesti, G, Aiello, A, D'Ospina, A, Giordano, C, Novo, S, Santoro, A, Ferri, C, Capuano, V, Trimarco, B, Tonolo, G, Villa, G, De Pellegrin, A, Zanette, G, Federici, M, Aucello, G, Piatti, P, Vinciguerra, A, Mannarino, E, Taddei, S, Filetti, S, Grandaliano, G, Marchionni, N, Lambiase, C, Locatelli, F, Scanferla, F, Lembo, G, Leotta, S, Mos, L, Calatola, P, Fogari, R, David, S, Pedrinelli, R, Pignone, Am, Cozzolino, D, Bevilacqua, Mt, Catena, C, Del Prato, S, Cerasola, G, Frontoni, S, Falcone, C, Porta, A, Bonora, E, Cocchi, R, Fucili, A, Frisinghelli, A, Volpe, M, Carugo, S, Gambardella, S, Spagnuolo, V, Maglia, G, D'Angelo, Ar, Corsi, A, Limone, Pp, Guarnieri, A, Ghigo, Ezio, Ronchi, E, Ravera, M, Scioli, Ga, Sekiguchi, M, Aoki, S, Ogawa, Y, Seino, H, Onishi, Y, Tojo, A, Narimiya, M, Iwaita, Y, Takeda, H, Shimizu, H, Yamada, T, Kojima, S, Zushi, S, Kaneko, S, Matsumoto, A, Kajiyama, S, Fujita, H, Shikata, K, Tone, A, Matsubayashi, S, Tanaka, S, Sekigami, T, Tatsukawa, Y, Abe, N, Kawahara, K, Kasahara, H, Maeda, Y, Suzuki, Y, Okamoto, H, Tachi, K, Yamada, K, Uzu, T, Itou, T, Fukui, T, Kim, S, Kim, Y, Cho, W, Kwak, I, Chae, D, Oh, H, Ha, S, Shin, Y, Cha, D, Kang, S, Lim, C, Song, J, Kwon, Y, Badariene, J, Labutiniene, Ip, Zabuliene, L, Poteliuniene, V, Miglinas, M, van den Meiracker AH, Gregoor, Pj, Luik, Aj, van Loon BJ, Feenstra, Hj, Kaasjager, Ha, Viergever, Pp, Woittiez, Aj, van Bemmel, T, Lieverse, Ag, Simsek, S, Gaillard, Ca, van der Zwaan, C, Lok, Dj, Spiering, W, Nierop, Pr, Baggen, Mg, Leendert, Rj, de Jong, A, Leurs, Pb, Vincent, Hh, Wins, Eh, Voors, Aa, Ronner, E, Heeg, Je, van Hal JM, Boermans, T, Feis, Wl, Mostard, G, Bakker, Rc, Dunselman, Ph, Skeie, S, Istad, H, Skjelvan, G, Gronert, J, Tomala, T, Gudnason, S, Torvik, Dt, Risberg, K, Abedini, S, Cabrera, W, Medina, B, Herrada, B, Saavedra, A, Polonia, Dj, Providencia, Dl, Carvalho, D, Vasconcelos, Mp, da Silva GF, Branco, P, Gil, Dv, da Costa AG, da Silva PM, Arez, L, Martins, L, Birne, R, Dzuponova, J, Surovcikova, M, Culak, J, Filipova, S, Andre, I, Stevlik, J, Uhliar, R, Fabryova, L, Benacka, J, Koleny, D, Szentivanyi, M, Spisak, V, Pella, D, Pastrnakova, E, Martinka, E, Chua, T, Lau, T, Ng, Tg, Yeoh, Ly, Bhana, Sa, Rayner, B, Wellmann, H, Amod, A, Ranjith, N, Ahmed, F, Rheeder, P, Makan, H, Naicker, P, Podgorski, G, De Teresa, E, Olivan, J, Fernandez, Vl, Povedano, St, Terns, M, Ricart, W, Gonzalez, Jm, Fernandez, P, Parreño Lde, T, Redon, J, Parra, J, Calvo, C, Lopez, I, Puig, Jg, Calle, A, Garcia, Jc, Lopez, Jm, Jimenez, Ml, Fraile, B, Perez, Js, Nadal, Jj, Guija, E, Calviño, J, Barrios, V, Iglesias, Jn, Armario, P, Garcia, M, Aranda, P, Brotons, C, Gomez, P, Catelao, Am, Cusachs, Ar, Sarro, M, Martinez, V, dell Valle MH, Trias, F, Comas, A, Salvador, N, Martinez, F, Hernandez, F, Martinez, J, Mateos, C, Peral, Jl, Tolosana, J, Sobrino, J, Isart, J, Vizcaino, J, Vega, Ff, Zamorano, Jl, Bacariza, M, Soubriet, A, Fernández Cruz, A, Querejeta, R, Leira, Vm, Iglesias, Fe, Ibrik, O, Martin, D, Nanclares, Ms, Mediavilla, Jd, Galceran, Jm, Lopez, A, Muros, T, Pascual, J, Casalla, F, Tornero, F, Fernandez, G, Pettersson, P, Olsen, H, Franke, F, Stroembom, U, Furuland, H, Larnefelt, H, Allemann, Y, Krapf, R, Gerber, P, Munger, R, Hayoz, D, Graf, Hj, Burnier, M, Petrillo, A, Batt, R, Constam, En, Moccetti, T, Bianda, T, Rickli, H, Bulliard, C, Wu, Kd, Lin, Sh, Wu, Cj, Sheu, Wh, Su, Sl, Chen, Sc, Chou, Cw, Lee, Ct, Yang, Tc, Chen, Hc, Sukonthasarn, A, Sriratanasathavorn, C, Eiam Ong, S, Supasyndh, O, Chanchairujira, T, Kitiyakara, C, Arici, M, Usalan, C, Guneri, S, Koc, M, Kalender, B, Ates, K, Gurgun, C, Araz, M, Demirbas, B, Biernacki, W, Calvert, J, Eavis, P, Kerrane, J, Litchfield, J, Middleton, A, Roberts, J, Simpson, H, Charles, H, Jardine, A, Fisher, M, Banerjee, D, Gallen, I, Gnudi, L, Harvey, J, O'Hare, P, Vora, J, Winocour, P, Soran, H, Browne, D, Darko, D, Mancebo, Jg, de Roa ER, Antepara, N, Carrillo, E, Berrizbeitia, M, Guevara, L, Pernalete, N, Ontiveros, C, Zigrang, W, Blakney, E, Rosenblit, P, Weinstein, R, Klaff, L, Lipetz, R, Busick, E, Tung, P, Cooperman, M, Michael, S, Sun, Ch, Hart, T, Maddux, A, Bowden, R, East, C, Arakaki, R, Villafuerte, B, Mamish, Z, Mendez, R, Connery, L, Nour, K, Wynne, A, Busch, R, Zamora, B, Sachson, R, Prasad, J, Lasala, G, Smith, M, Fitz Patrick, D, Ruiz Rivera, L, Barranco, E, Solomon, R, Woolley, A, Brown, C, Freedman, Z, Schmidt, S, Pollock, J, Ruddy, M, Kopyt, Np, Bazzi, A, Horowitz, B, Feng, W, Wahl, T, Duprez, D, Gilbert, J, Steigerwalt, S, Jacqmein, J, Gorton, S, 3rd, Allison J., Pino, J, Lock, J, Leimbach, W, Anderson, J, Beacom, M, Craig, W, Gorson, D, Kerstein, H, Segal, S, Downey, H, Ledger, G, Mcgill, J, Gabriel, J, Nolen, T, Levinson, L, Williams, T, Levenson, D, Lerman, S, Minehart, C, Agarwal, N, Verma, S, Valitutto, M, Demetry, K, Mersey, J, Koeper, D, Fanti, P, Eng, G, Grimm, R, Fagan, T, Bajaj, M, Katz, L, Portnay, G, Altschuller, A, Desai, V, Bilazarian, S, Ipp, E, Rodelas, R, Burstein, D, Berg, J, Velez, J, Lund, R, Rekhi, A, Martin, E, Robertson, D, Singh, N, Narayan, P, Moustafa, M, Lanier, D, Seidner, M, Phillips, A, Vaughters, B, Sprague, A, Swartz, S, Lopez, R, Kumar, J, Bressler, P, Sadler, L, Wise, J, Kilbane, A., and Groningen Kidney Center (GKC)
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Male ,Hyperkalemia ,CARDIOVASCULAR MORTALITY ,BLOOD-PRESSURE ,Angiotensin-Converting Enzyme Inhibitors ,Type 2 diabetes ,GLOMERULAR-FILTRATION-RATE ,DOUBLE-BLIND ,chemistry.chemical_compound ,Fumarates ,cardiovascular disease ,Renin ,Treatment Failure ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,610 Medicine & health ,diabetes ,Medicine (all) ,Hazard ratio ,aliskiren ,diabete ,trial clinico ,Liter ,General Medicine ,Middle Aged ,hypertension ,Cardiovascular Diseases ,Combination ,HEART-FAILURE ,Drug Therapy, Combination ,Female ,Kidney Diseases ,type 2 diabetes ,medicine.symptom ,Type 2 ,medicine.medical_specialty ,Patient Dropouts ,Urology ,Hypokalemia ,Aliskiren ,chronic kidney disease ,Placebo ,Angiotensin Receptor Antagonists ,LEFT-VENTRICULAR DYSFUNCTION ,Drug Therapy ,Double-Blind Method ,Diabetes Mellitus ,medicine ,Humans ,CONVERTING-ENZYME INHIBITORS ,Antihypertensive Agents ,Aged ,Amides ,Diabetes Mellitus, Type 2 ,Follow-Up Studies ,business.industry ,medicine.disease ,Confidence interval ,Surgery ,Blood pressure ,MYOCARDIAL-INFARCTION ,chemistry ,SYSTOLIC DYSFUNCTION ,FOLLOW-UP ,business - Abstract
BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P = 0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, = 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P CONCLUSIONS The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.)
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- 2012
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12. A randomized phase II study of stem cell mobilization with cyclophosphamide + G-CSF versus G-CSF alone after lenalidomide-based induction in multiple myeloma
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Silvennoinen, R., primary, Anttila, P., additional, Säily, M., additional, Lundan, T., additional, Heiskanen, J., additional, Siitonen, T.M., additional, Kakko, S., additional, Putkonen, M., additional, Ollikainen, H., additional, Terävä, V., additional, Kutila, A., additional, Launonen, K., additional, Räsänen, A., additional, Sikiö, A., additional, Suominen, M., additional, Bazia, P., additional, Kananen, K., additional, Selander, T., additional, Kuittinen, T., additional, Remes, K., additional, and Jantunen, E., additional
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- 2015
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13. Male gender explains increased birthweight in children born after transfer of blastocysts.
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Kaartinen, N. M., Kananen, K. M., Rodriguez-Wallberg, K. A., Tomás, C. M., Huhtala, H. S. A., Tinkanen, H. I., and Huhtala, H Sa
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BLASTOCYST , *EMBRYO transfer , *BIRTH weight , *HUMAN in vitro fertilization , *RETROSPECTIVE studies , *CASE-control method , *SELECTION bias (Statistics) , *COMPARATIVE studies , *CULTURE media (Biology) , *FERTILIZATION in vitro , *FREEZING , *RESEARCH methodology , *MEDICAL cooperation , *INDUCED ovulation , *RESEARCH , *SEX distribution , *EVALUATION research ,SEX differences (Biology) - Abstract
Study Question: Does extended embryo culture have a different effect on the birthweight of girls and boys?Summary Answer: The mean birthweight of boys born after fresh and frozen-thawed blastocyst transfer was increased compared with those born after cleavage stage embryo transfer. This effect was not detected among girls.What Is Known Already: Previous studies indicate that newborns from frozen-thawed cleavage stage embryos may present with a higher weight than newborns from fresh embryo transfers. With regard to fresh embryos, newborns after a blastocyst transfer have been reported as having higher birthweights than newborns from cleavage stage embryos.Study Design, Size, Duration: Retrospective multicentre case-control cohort study. All IVF/ICSI treatments were performed in the time-period from January 2008 to March 2014.Participants/materials, Setting, Methods: Birthweight of singletons born at full-term (≥37 weeks), after fresh or frozen blastocyst embryo transfers (n = 277), were compared with weights of children born after fresh or frozen cleavage stage embryo transfers (Day 2-3) (n = 277). The cases and controls were matched by delivery week, and by gender. Data of IVF/ICSI treatments, and the treatments' outcomes were collected and analysed.Main Results and the Role Of Chance: The birthweight after a fresh blastocyst transfer was significantly higher (mean 3530.6 g) than that after a transfer of cleavage stage embryos (mean 3418.8 g; weight difference 111.8 g, P = 0.047). The weights of newborns after frozen-thawed blastocyst transfers (mean 3647.5 g) and the frozen-thawed cleavage stage embryo transfers (mean 3650.9 g), were similar (weight difference 3.4 g, P = 0.95). The boys born after transfer of frozen-thawed blastocysts had a significantly higher birthweight (mean 3767.9 g) than girls (3525.2 g; weight difference 242.7 g, P = 0.002), whereas the difference of birthweights between genders was only 13.5 g in cleavage stage (P = 0.863). The same effect was seen after fresh blastocyst transfers (weight difference 211.5 g, P = 0.011), but not after fresh Day 2-3 embryo transfers (weight difference 53.6 g, P = 0.478).Limitations, Reasons For Caution: The study material was large enough to detect differences between birthweights as a whole, but a larger study group would confirm these new findings. To avoid selection bias, the next possible control candidate, fulfilling the selection criteria, was included for matching cases and controls. We have matched the cases and controls by gender and gestational week at birth, with an aim to reduce their impact as confounding factors.Wider Implications Of the Findings: Our findings of a similar weight at birth of newborns after frozen-thawed blastocysts and frozen-thawed cleavage stage embryos, when matching for age and duration of pregnancy, are novel. The gender of the newborn has an impact on the birthweight, and the extended embryo culture increases the weight difference between the genders, which is a new finding as well.Study Funding/competing Interests: The study was funded by the Fertility Society of Finland. [ABSTRACT FROM AUTHOR]- Published
- 2015
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14. P08—Quality of Life did not Worsen for 7 Years in Enzyme-Replacement Therapy Recipients with Fabry Disease
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Kantola, I., primary, Hietaharju, A., additional, Taurio, J., additional, Kananen, K., additional, Kantola, T., additional, and Viikari, J., additional
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- 2012
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15. Effects of Serum-FreeIn VitroMaturation of Bovine Oocytes on Subsequent Embryo Development and Cell Allocation in Two Developmental Stages of Day 7 Blastocysts
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Korhonen, K, primary, Kananen, K, additional, Ketoja, E, additional, Matomäki, J, additional, Halmekytö, M, additional, and Peippo, J, additional
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- 2010
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16. Direct conversion receiver RFIC for CDMA-2000
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Hafizi, M., primary, Feng, S., additional, Fu, T.L., additional, Ruth, B., additional, Schwab, R., additional, Schulze, K., additional, Karlsen, P., additional, Gu, Q., additional, Narhi, O., additional, Kananen, K., additional, and Wakeham, C., additional
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- 2003
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17. A randomized phase II study of stem cell mobilization with cyclophosphamide+G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma
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Silvennoinen, R, Anttila, P, Säily, M, Lundan, T, Heiskanen, J, Siitonen, T M, Kakko, S, Putkonen, M, Ollikainen, H, Terävä, V, Kutila, A, Launonen, K, Räsänen, A, Sikiö, A, Suominen, M, Bazia, P, Kananen, K, Selander, T, Kuittinen, T, Remes, K, and Jantunen, E
- Abstract
The most common means of mobilizing autologous stem cells is G-CSF alone or combined with cyclophosphamide (CY) to obtain sufficient CD34+cells for one to two transplants. There are few prospective, randomized studies investigating mobilization regimens in multiple myeloma (MM), especially after lenalidomide-based induction. We designed this prospective, randomized study to compare low-dose CY 2 g/m2+G-CSF (arm A) and G-CSF alone (arm B) after lenalidomide-based up-front induction in MM. Of the 80 initially randomized patients, 69 patients were evaluable, 34 and 35 patients in arms A and B, respectively. The primary end point was the proportion of patients achieving a yield of ⩾3 × 106/kg CD34+cells with 1−2 aphereses, which was achieved in 94% and 77% in arms A and B, respectively (P=0.084). The median number of aphereses needed to reach the yield of ⩾3 × 106/kg was lower in arm A than in arm B (1 vs 2, P=0.035). Two patients needed plerixafor in arm A and five patients in arm B (P=0.428). Although CY-based mobilization was more effective, G-CSF alone was successful in a great majority of patients to reach the defined collection target after three cycles of lenalidomide-based induction.
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- 2016
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18. Gonadectomy permits adrenocortical tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene: evidence for negative autoregulation of the inhibin alpha-subunit gene.
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Kananen, K, primary, Markkula, M, additional, Mikola, M, additional, Rainio, E M, additional, McNeilly, A, additional, and Huhtaniemi, I, additional
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- 1996
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19. Pituitary and ovarian expression of the endogenous follicle-stimulating hormone (FSH) subunit genes and an FSH β-subunit promoter-driven herpes simplex virus thymidine kinase gene in transgenic mice; specific partial ablation of FSH-producing cells by antiherpes treatment
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Markkula, M, primary, Kananen, K, additional, Klemi, P, additional, and Huhtaniemi, I, additional
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- 1996
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20. Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines.
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Kananen, K, primary, Markkula, M, additional, Rainio, E, additional, Su, J G, additional, Hsueh, A J, additional, and Huhtaniemi, I T, additional
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- 1995
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21. A 10 bit low-power CMOS D/A converter with on-chip gain error compensation.
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Henriques, B.G., Kananen, K., Franca, J.E., and Rapeli, J.
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- 1995
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22. Effects of Serum-Free In Vitro Maturation of Bovine Oocytes on Subsequent Embryo Development and Cell Allocation in Two Developmental Stages of Day 7 Blastocysts.
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Korhonen, K., Kananen, K., Ketoja, E., Matomäki, J., Halmekyt, M., and Peippo, J.
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BLASTOCYST , *CRYOPRESERVATION of organs, tissues, etc. , *FATTY acids , *VITAMIN B complex , *SERUM albumin - Abstract
Contents Maturation of oocytes and the subsequent outcome of the in vitro production (IVP) are affected by the composition of in vitro maturation (IVM) medium. To determine the use of serum interfering with effects of single molecules, we aimed at developing simplified IVM medium. The experimental IVM media were: (1) M199-medium supplemented with hormones and serum (control), (2) as 1 but serum was substituted with fatty acid-free serum albumin (FAFBSA) and (3) M199-medium without hormonal and serum supplementation (M199). The quality of embryos was assessed on day 7 by morphology and cryotolerance, as well as by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) and differential staining. Results showed that the nuclear maturation was suppressed in M199 group alone. Embryo cleavage and development rates, and the proportion of quality 1 blastocysts were lower in the FAFBSA and M199 groups compared to the control. Differences in the cell allocation of fresh embryos were observed at the blastocyst stage, but not at the expanded blastocyst stage. The control group blastocysts had larger number of cells allocated to the inner cell mass (ICM), and the FAFBSA group blastocysts larger apoptotic cell proportion compared to the blastocysts derived from other groups. After cryopreservation, the reduction of ICM proportion and increase of apoptotic cell proportion of embryos were equal between the experimental groups. In conclusion, exclusion of serum from the IVM media reduces embryo development and may cause perturbations in blastocyst development. Differences in the cell allocation of blastocysts between IVM media may appear only when the developmental stages are taken into account. [ABSTRACT FROM AUTHOR]
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- 2010
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23. Stable transfection of the rat follicle-stimulating hormone receptor complementary DNA into an immortalized murine Sertoli cell line
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Eskola, V., Ryhaanen, P., Savisalo, M., Rannikko, A., Kananen, K., Sprengel, R., and Huhtaniemi, I.
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- 1998
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24. The mouse inhibin a-subunit promoter directs SV40 T-antigen to Leydig cells in transgenic mice
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Kananen, K., Markkula, M., El-Hefnawy, T., Zhang, F.-P., Paukku, T., Su, J.-G. J., Hsueh, A. J. W., and Huhtaniemi, I.
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- 1996
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25. A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes
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van Zuydam, Natalie R, Ahlqvist, Emma, Sandholm, Niina, Deshmukh, Harshal, Rayner, N William, Abdalla, Moustafa, Ladenvall, Claes, Ziemek, Daniel, Fauman, Eric, Robertson, Neil R, Mckeigue, Paul M, Valo, Erkka, Forsblom, Carol, Harjutsalo, Valma, Perna, Annalisa, Rurali, Erica, Marcovecchio, M Loredana, Igo, Robert P, Salem, Rany M, Perico, Norberto, Lajer, Maria, Käräjämäki, Annemari, Imamura, Minako, Kubo, Michiaki, Takahashi, Atsushi, Sim, Xueling, Liu, Jianjun, van Dam, Rob M, Jiang, Guozhi, Tam, Claudia H T, Luk, Andrea O Y, Lee, Heung Man, Lim, Cadmon K P, Szeto, Cheuk Chun, Wing Yee, So, Chan, Juliana C N, Ang, Su Fen, Dorajoo, Rajkumar, Wang, Ling, Clara, Tan Si Hua, Mcknight, Amy-Jayne, Duffy, Seamus, Pezzolesi, Marcus G, Marre, Michel, Gyorgy, Beata, Hadjadj, Samy, Hiraki, Koivula, S, Uggeldahl, T, Forslund, T, Halonen, A, Koistinen, A, Koskiaho, P, Laukkanen, M, Saltevo, J, Tiihonen, M, Forsen, M, Granlund, H, Jonsson, Ac, Nyroos, B, Kinnunen, P, Orvola, A, Salonen, T, Vähänen, A, Paldanius, Kr, Riihelä, M, Ryysy, L, Laukkanen, Kh, Nyländen, P, Sademies, A, Anderson, S, Asplund, B, Byskata, U, Liedes, P, Kuusela, M, Virkkala, T, Nikkola, A, Ritola, E, Niska, Tm, Saarinen, H, Oukko-Ruponen, Se, Virtanen, T, Lyytinen, Va, Kari, Ph, Simonen, T, Kaprio, Sa, Kärkkäinen, J, Rantaeskola, B, Kääriäinen, Tp, Haaga, J, Pietiläinen, Al, Klemetti, S, Nyandoto, T, Rontu, E, Satuli-Autere, S, Toivonen, Kr, Lansimaki, Hv, Ahonen, R, Ivaska-Suomela, M, Jauhiainen, A, Laine, Mm, Pellonpää, T, Puranen, R, Airas, Ma, Laakso, J, Rautavaara, K, Erola, Rm, Jatkola, E, Lönnblad, Tr, Malm, A, Mäkelä, J, Rautamo, E, Hentunen, P, Lagerstam, J, Feodoroff, M, Gordin, D, Heikkilä, O, Hietala, K, Fagerudd, J, Korolainen, M, Kyllönen, L, Kytö, J, Lindh, S, Pettersson-Fernholm, K, Rosengård-Bärlund, M, Sandelin, A, Thorn, L, Tuomikangas, J, Vesisenaho, T, Wadén, J, Sipilä, V, Kalliomäki, Ft, Koskelainen, J, Nikkanen, R, Savolainen, N, Sulonen, H, Valtonen, E, Norvio, L, Hämäläinen, A, Toivanen, E, Parta, Ja, Pirttiniemi, I, Aranko, S, Ervasti, S, Kauppinen-Mäkelin, R, Kuusisto, A, Leppälä, T, Nikkilä, K, Pekkonen, L, Jokelainen, Ks, Kananen, K, Karjalainen, M, Kemppainen, P, Mankinen, Am, Reponen, A, Sankari, M, Suominen, P, Lappalainen, A, Liimatainen, M, Santaholma, J, Aimolahti, A, Huovinen, E, Ilkka, V, Lehtimäki, M, Pälikkö-Kontinen, E, Vanhanen, A, Koskinen, E, Siitonen, T, Huttunen, E, Ikäheimo, R, Karhapää, P, Kekäläinen, P, Laakso, M, Lakka, T, Lampainen, E, Moilanen, L, Tanskanen, S, Niskanen, L, Tuovinen, U, Vauhkonen, I, Voutilainen, E, Rcw, Ma, Chan, Jcn, Huang, Y, Lan, Hy, Lok, S, Tomlinson, B, Tsui, Skw, Yu, W, Yip, Kyl, Chan, Tf, Fan, X, So, Wy, Szeto, Cc, Tang, N, Luk, Ao, Tian, X, Jiang, G, Tam, Cht, Lee, Hm, Lim, Ckp, Chan, Kkh, Xie, F, Acw, Ng, Cheung, Gpy, Yeung, Mw, Mai, S, Zhang, S, Yu, P, Weng, M, Maxwell, Ap, Mcknight, Aj, Savage, Da, Walker, J, Thomas, S, Viberti, Gc, Boulton, Ajm, Marshall, S, Demaine, Ag, Millward, Ba, Bain, Sc, Sandholm, N, Forsblom, C, Harjutsalo, V, Mäkinen, Vp, Ahola, Aj, Dahlström, E, Lehto, M, Lithovius, R, Panduru, Nm, Parkkonen, M, Saraheimo, M, Söderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, Lm, Tolonen, N, Groop, Ph, Mckay, Gj, Salem, Rm, Isakova, T, Palmer, C, Guiducci, C, Taylor, A, Mirel, Db, Williams, Ww, Hirschhorn, Jn, Florez, Jc, Brennan, Ep, Sadlier, Dm, Martin, F, Godson, C, Mayer, L, Gubitosi-Klug, R, Bourne, P, Schutta, M, Lackaye, Me, Gregory, Ns, Kruger, D, Jones, Jk, Bhan, A, Golden, E, Aiello, L, Larkin, M, Nathan, D, Ziegler, G, Caulder, S, Pittman, C, Luttrell, L, Lopes-Virella, M, Johnson, M, Gunyou, K, Bergenstal, R, Vittetoe, B, Sivitz, W, Flaherty, N, Bantle, J, Hitt, S, Goldstein, D, Hainsworth, D, Cimino, L, Orchard, T, Wigley, C, Dagogo-Jack, S, Strowig, S, Raskin, P, Barnie, A, Zinman, B, Fahlstrom, R, Palmer, J, Harth, J, Driscoll, M, Mcdonald, C, Lipps Hagan, J, May, M, Levandoski, L, White, N, Gatcomb, P, Tamborlane, W, Adelman, D, Colson, S, Molitch, M, Lorenzi, G, Mudaliar, S, Johnsonbaugh, S, Miller, R, Canady, J, Schade, D, Bernal, Ml, Malone, J, Morrison, A, Martin, C, Herman, W, Pop-Busui, R, Cowie, C, Leschek, E, Cleary, P, Lachin, J, Braffett, B, Steffes, M, Arends, V, Blodi, B, Danis, R, Lawrence, D, Wabers, H, Soliman, E, Zhang, Zm, Campbell, C, Hensley, S, Keasler, L, Mark, M, Albertini, M, Boustany, C, Ehlgen, A, Gerl, M, Huber, J, Schölch, C, Zimdahl-Gelling, H, Groop, L, Agardh, E, Ahlqvist, E, Ajanki, T, Al Maghrabi, N, Almgren, P, Apelqvist, J, Bengtsson, E, Berglund, L, Björckbacka, H, Blom-Nilsson, U, Borell, M, Burström, A, Cilio, C, Cinthio, M, Dreja, K, Dunér, P, Engelbertsen, D, Fadista, J, Gomez, M, Goncalves, I, Hedblad, B, Hultgårdh, A, Johansson, Me, Kennbäck, C, Kravic, J, Ladenvall, C, Lernmark, Å, Lindholm, E, Ling, C, Luthman, H, Melander, O, Neptin, M, Nilsson, J, Nilsson, P, Nilsson, T, Nordin, G, Orho-Melander, M, Ottoson-Laakso, E, Persson, A, Persson, M, Persson, Må, Postma, J, Pranter, E, Rattik, S, Sterner, G, Tindberg, L, Wigren, M, Zetterqvist, A, Åkerlund, M, Ostling, G, Kanninen, T, Ahonen-Bishopp, A, Eliasson, A, Herrala, T, Tikka-Kleemola, P, Hamsten, A, Betsholtz, C, Björkholm, A, Foroogh, F, Genové, G, Gertow, K, Gigante, B, He, B, Leander, K, Mcleod, O, Nastase-Mannila, M, Patrakka, J, Silveira, A, Strawbridge, R, Tryggvason, K, Vikström, M, Ohrvik, J, Österholm, Am, Thorand, B, Gieger, C, Grallert, H, Ludwig, T, Nitz, B, Schneider, A, Wang-Sattler, R, Zierer, A, Remuzzi, G, Benigni, A, Donadelli, R, Lesti, Md, Noris, M, Perico, N, Perna, A, Piras, R, Ruggenenti, P, Rurali, E, Dunger, D, Chassin, L, Dalton, N, Deanfield, J, Horsford, J, Rice, C, Rudd, J, Walker, N, Whitehead, K, Wong, M, Colhoun, H, Adams, F, Akbar, T, Belch, J, Deshmukh, H, Dove, F, Ellingford, A, Farran, B, Ferguson, M, Henderson, G, Houston, G, Khan, F, Leese, G, Liu, Y, Livingstone, S, Looker, H, Mccann, M, Mcgurnaghan, S, Morris, A, Newton, D, Pearson, E, Reekie, G, Smith, N, Shore, A, Aizawa, K, Ball, C, Bellenger, N, Casanova, F, Frayling, T, Gates, P, Gooding, K, Hattersley, A, Ling, R, Mawson, D, Shandas, R, Strain, D, Thorn, C, Smith, U, Hammarstedt, A, Häring, H, Pedersen, O, Sesti, G, Fagerholm, E, Toppila, I, Valo, E, Salomaa, V, Havulinna, A, Kristiansson, K, Okamo, P, Peltola, T, Perola, M, Pietilä, A, Ripatti, S, Taimi, M, Ylä-Herttuala, S, Babu, M, Dijkstra, M, Gurzeler, E, Huusko, J, Kholová, I, Merentie, M, Poikolainen, M, Mccarthy, M, Groves, C, Juliusdottir, T, Karpe, F, Lagou, V, Rayner, W, Robertson, N, van Zuydam, N, Cobelli, C, Di Camillo, B, Finotello, F, Sambo, F, Toffolo, G, Trifoglio, E, Bellazzi, R, Barbarini, N, Bucalo, M, Larizza, C, Magni, P, Malovini, A, Marini, S, Mulas, F, Quaglini, S, Sacchi, L, Vitali, F, Ferrannini, E, Boldrini, B, Kozakova, M, Mari, A, Morizzo, C, Mota, L, Natali, A, Palombo, C, Venturi, E, Walker, M, Patrono, C, Pagliaccia, F, Rocca, B, Nuutila, P, Haukkala, J, Knuuti, J, Roivainen, A, Saraste, A, Mckeague, P, Colombo, M, Steckel-Hamann, B, Bokvist, K, Shankar, S, Thomas, M, Gan, Lm, Heinonen, S, Jönsson-Rylander, Ac, Momo, R, Schnecke, V, Unwin, R, Walentinsson, A, Whatling, C, Nogoceke, E, Pacheco, Gd, Formentini, I, Schindler, T, Tortoli, P, Bassi, L, Boni, E, Dallai, A, Guidi, F, Lenge, M, Matera, R, Ramalli, A, Ricci, S, Viti, J, Jablonka, B, Crowther, D, Gassenhuber, J, Hess, S, Hubschle, T, Juretschke, Hp, Rutten, H, Sadowski, T, Wohlfart, P, Brosnan, J, Clerin, V, Fauman, E, Hyde, C, Malarstig, A, Pullen, N, Tilley, M, Tuthill, T, Vangjeli, C, Linda T, Ziemek D., Ahluwalia, Tarunveer S, Almgren, Peter, Schulz, Christina-Alexandra, Orho-Melander, Marju, Linneberg, Allan, Christensen, Cramer, Witte, Daniel R, Grarup, Niels, Brandslund, Ivan, Melander, Olle, Paterson, Andrew D, Tregouet, David, Maxwell, Alexander P, Lim, Su Chi, Ronald C W, Ma, Tai, E Shyong, Maeda, Shiro, Lyssenko, Valeriya, Tuomi, Tiinamaija, Krolewski, Andrzej S, Rich, Stephen S, Hirschhorn, Joel N, Florez, Jose C, Dunger, David, Pedersen, Oluf, Hansen, Torben, Rossing, Peter, Remuzzi, Giuseppe, Brosnan, Mary Julia, Palmer, Colin N A, Groop, Per-Henrik, Colhoun, Helen M, Groop, Leif C, Mccarthy, Mark, I, Palombo, Carlo, Clinicum, Diabetes and Obesity Research Program, Research Programs Unit, Nefrologian yksikkö, Department of Medicine, Institute for Molecular Medicine Finland, Tiinamaija Tuomi Research Group, Endokrinologian yksikkö, Per Henrik Groop / Principal Investigator, Leif Groop Research Group, HUS Abdominal Center, HUS Internal Medicine and Rehabilitation, and Lee Kong Chian School of Medicine (LKCMedicine)
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0301 basic medicine ,Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,LOCI ,Genome-wide association study ,Type 2 diabetes ,Bioinformatics ,Kidney Failure ,0302 clinical medicine ,Genome-wide analysis ,80 and over ,Diabetic Nephropathies ,Renal Insufficiency ,Chronic ,Genome-wide analysis, Type 2 Diabetes ,Aged, 80 and over ,RISK ,INSULIN-RESISTANCE ,diabetes ,Diabetes ,STAGE RENAL-DISEASE ,Single Nucleotide ,Middle Aged ,Type 2 Diabetes ,SUSCEPTIBILITY GENES ,Adult ,Aged ,Case-Control Studies ,Diabetes Mellitus, Type 2 ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Kidney Failure, Chronic ,Polymorphism, Single Nucleotide ,Renal Insufficiency, Chronic ,OBESITY ,BIOLOGICAL PATHWAYS ,nephropathy ,Medical genetics ,Type 2 ,kidney ,medicine.medical_specialty ,Diabetic Nephropathies/epidemiology ,Settore BIO/14 - FARMACOLOGIA ,Renal Insufficiency, Chronic/complications ,NEPHROPATHY ,SNP ,030209 endocrinology & metabolism ,Nephropathy ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Diabetes mellitus ,Journal Article ,Diabetes Mellitus ,Internal Medicine ,medicine ,Medicine [Science] ,Polymorphism ,Diabetic Kidney Disease ,METAANALYSIS ,Genetic heterogeneity ,business.industry ,Diabetes Mellitus, Type 2/complications ,association ,Case-control study ,nutritional and metabolic diseases ,Kidney Failure, Chronic/complications ,FAT DISTRIBUTION ,medicine.disease ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Microalbuminuria ,genetic ,business - Abstract
Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD. ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore)
26. A 10 bit low-power CMOS D/A converter with on-chip gain error compensation
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Henriques, B.G., primary, Kananen, K., additional, Franca, J.E., additional, and Rapeli, J., additional
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27. Transgenic Mice Harboring a 38-aa Deletion Mutation in the a2(IX) Collagen Gene
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Peraelae, M., Saeaemaenen, A.-M., Markkula, M., Kananen, K., and Vuorio, E.
- Published
- 1996
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28. Induced ablation of gonadotropins in transgenic mice expressing Herpes simplex virus thymidine kinase under the FSH -subunit promoter
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Markkula, M., Kananen, K., Paukku, T., and Maennistoe, A.
- Published
- 1995
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29. Adaptive adjustment of significance thresholds produces large gains in microbial gene annotations and metabolic insights.
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Kananen K, Veseli I, Quiles Pérez CJ, Miller S, Eren AM, and Bradley PH
- Abstract
Gene function annotations enable microbial ecologists to make inferences about metabolic potential from genomes and metagenomes. However, even tools that use the same database and general approach can differ markedly in the annotations they recover. We compare three popular methods for identifying KEGG Orthologs, applying them to genomes drawn from a range of bacterial families that occupy different host-associated and free-living biomes. Our results show that by adaptively tuning sequence similarity thresholds, sensitivity can be substantially improved while maintaining accuracy. We observe the largest improvements when few reference sequences exist for a given protein family, and when annotating genomes from non-model organisms (such as gut-dwelling Lachnospiraceae). Our results suggest that straightforward heuristic adjustments can broadly improve microbial metabolic predictions.
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- 2024
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30. Healthy live birth following embryo transfer of a blastocyst of tetrapronuclear (4PN) origin: a case report.
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Bredbacka P, Capalbo A, Kananen K, Picchetta L, and Tomás C
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- Pregnancy, Humans, Female, Male, Fertilization in Vitro methods, Embryo Transfer, Genetic Testing methods, Aneuploidy, Blastocyst, Live Birth, Preimplantation Diagnosis methods
- Abstract
During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronuclei, one arising from the oocyte and the other from the male gamete. Embryos derived from zygotes with a pronuclei number other than two are assumed to possess a ploidy abnormality and their transfer is usually avoided owing to increased risk of implantation failure, miscarriage, and molar pregnancies. Nonetheless, the inclusion of genotyping data in preimplantation genetic testing has revealed that a normal diploid configuration is possible in embryos deriving from zygotes with an abnormal pronuclei number such as tripronuclear and one pronucleus. Here, we present a one-of-a-kind transfer of a tetrapronuclear-derived embryo that was discovered to be diploid and negative for other whole chromosome or segmental aneuploidies during preimplantation genetic testing using a targeted next-generation sequencing approach. The transfer resulted in the live birth of a healthy infant who is now 4 years old and has no apparent health or developmental impairments., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
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31. Association of body mass index and inflammatory dietary pattern with breast cancer pathologic and genomic immunophenotype in the nurses' health study.
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Asad S, Damicis A, Heng YJ, Kananen K, Collier KA, Adams EJ, Kensler KH, Baker GM, Wesolowski R, Sardesai S, Gatti-Mays M, Ramaswamy B, Eliassen AH, Hankinson SE, Tabung FK, Tamimi RM, and Stover DG
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- Humans, Female, Adolescent, Body Mass Index, Diet, Biomarkers, Genomics, Tumor Microenvironment, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Nurses
- Abstract
Background: Breast tumor immune infiltration is clearly associated with improved treatment response and outcomes in breast cancer. However, modifiable patient factors associated with breast cancer immune infiltrates are poorly understood. The Nurses' Health Study (NHS) offers a unique cohort to study immune gene expression in tumor and adjacent normal breast tissue, immune cell-specific immunohistochemistry (IHC), and patient exposures. We evaluated the association of body mass index (BMI) change since age 18, physical activity, and the empirical dietary inflammatory pattern (EDIP) score, all implicated in systemic inflammation, with immune cell-specific expression scores., Methods: This population-based, prospective observational study evaluated 882 NHS and NHSII participants diagnosed with invasive breast cancer with detailed exposure and gene expression data. Of these, 262 women (training cohort) had breast tumor IHC for four classic immune cell markers (CD8, CD4, CD20, and CD163). Four immune cell-specific scores were derived via lasso regression using 105 published immune expression signatures' association with IHC. In the remaining 620 patient evaluation cohort, we evaluated association of each immune cell-specific score as outcomes, with BMI change since age 18, physical activity, and EDIP score as predictors, using multivariable-adjusted linear regression., Results: Among women with paired expression/IHC data from breast tumor tissue, we identified robust correlation between novel immune cell-specific expression scores and IHC. BMI change since age 18 was positively associated with CD4+ (β = 0.16; p = 0.009), and CD163 novel immune scores (β = 0.14; p = 0.04) in multivariable analyses. In other words, for each 10 unit (kg/m
2 ) increase in BMI, the percentage of cells positive for CD4 and CD163 increased 1.6% and 1.4%, respectively. Neither physical activity nor EDIP was significantly associated with any immune cell-specific expression score in multivariable analyses., Conclusions: BMI change since age 18 was positively associated with novel CD4+ and CD163+ cell scores in breast cancer, supporting further study of the effect of modifiable factors like weight gain on the immune microenvironment., (© 2022. The Author(s).)- Published
- 2022
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32. Challenges and Gaps in Clinical Trial Genomic Data Management.
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Asad S, Kananen K, Mueller KR, Symmans WF, Wen Y, Perou CM, Blachly JS, Chen J, Vincent BG, and Stover DG
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- Data Management, Humans, Clinical Trials as Topic, Genomics
- Abstract
Competing Interests: W. Fraser SymmansStock and Other Ownership Interests: ISIS Pharmaceuticals, Delphi Diagnostics, Eiger BioPharmaceuticalsConsulting or Advisory Role: MerckResearch Funding: Pfizer (Inst)Patents, Royalties, Other Intellectual Property: Intellectual property, Intellectual Property (expired)Uncompensated Relationships: Delphi DiagnosticsOpen Payments Link: https://openpaymentsdata.cms.gov/physician/256534 Charles M. PerouLeadership: GeneCentricStock and Other Ownership Interests: BioClassifier, GeneCentric, Reveal GenomicsConsulting or Advisory Role: BioClassifier, GeneCentric, NanoString Technologies, Veracyte, Reveal GenomicsPatents, Royalties, Other Intellectual Property: Royalties from PAM50 breast cancer gene patent application and from the lung gene signature patent James S. BlachlyConsulting or Advisory Role: AstraZeneca, AbbVie, Kite, a Gilead company, AstraZeneca, Astellas Pharma, Innate PharmaPatents, Royalties, Other Intellectual Property: Sequencing Technology patent pending (Inst)Travel, Accommodations, Expenses: Oxford Nanopore Technologies James ChenEmployment: TempusConsulting or Advisory Role: Syapse, TempusSpeakers' Bureau: Foundation MedicineResearch Funding: EisaiPatents, Royalties, Other Intellectual Property: MatchTX Benjamin G. VincentStock and Other Ownership Interests: GeneCentricConsulting or Advisory Role: GeneCentricResearch Funding: Merck (Inst) Daniel G. StoverThis author is a member of the JCO Clinical Cancer Informatics Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: NovartisNo other potential conflicts of interest were reported.
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- 2022
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33. RVD induction and autologous stem cell transplantation followed by lenalidomide maintenance in newly diagnosed multiple myeloma: a phase 2 study of the Finnish Myeloma Group.
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Luoma S, Anttila P, Säily M, Lundan T, Heiskanen J, Siitonen T, Kakko S, Putkonen M, Ollikainen H, Terävä V, Sankelo M, Partanen A, Launonen K, Räsänen A, Sikiö A, Suominen M, Bazia P, Kananen K, Lievonen J, Selander T, Pelliniemi TT, Ilveskero S, Huotari V, Mäntymaa P, Tienhaara A, Jantunen E, and Silvennoinen R
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- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Autografts, Bortezomib administration & dosage, Dexamethasone administration & dosage, Disease-Free Survival, Female, Finland, Humans, Male, Middle Aged, Survival Rate, Lenalidomide administration & dosage, Maintenance Chemotherapy, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Multiple Myeloma therapy, Stem Cell Transplantation
- Abstract
Autologous stem cell transplantation (ASCT) combined with novel agents is the standard treatment for transplant-eligible, newly diagnosed myeloma (NDMM) patients. Lenalidomide is approved for maintenance after ASCT until progression, although the optimal duration of maintenance is unknown. In this trial, 80 patients with NDMM received three cycles of lenalidomide, bortezomib, and dexamethasone followed by ASCT and lenalidomide maintenance until progression or toxicity. The primary endpoint was the proportion of flow-negative patients. Molecular response was assessed if patients were flow-negative or in stringent complete response (sCR). By intention to treat, the overall response rate was 89%. Neither median progression-free survival nor overall survival (OS) has been reached. The OS at 3 years was 83%. Flow-negativity was reached in 53% and PCR-negativity in 28% of the patients. With a median follow-up of 27 months, 29 (36%) patients are still on lenalidomide and 66% of them have sustained flow-negativity. Lenalidomide maintenance phase was reached in 8/16 high-risk patients but seven of them have progressed after a median of only 6 months. In low- or standard-risk patients, the outcome was promising, but high-risk patients need more effective treatment approach. Flow-negativity with the conventional flow was an independent predictor for longer PFS.
- Published
- 2019
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34. Real-world treatment outcomes in multiple myeloma: Multicenter registry results from Finland 2009-2013.
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Remes K, Anttila P, Silvennoinen R, Putkonen M, Ollikainen H, Terävä V, Sinisalo M, Kananen K, Schain F, Castren-Kortegangas P, Järvinen TM, Pisini M, Wahl F, Dixon T, and Leval A
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- Aged, Aged, 80 and over, Female, Finland, Humans, Kaplan-Meier Estimate, Middle Aged, Multiple Myeloma mortality, Registries, Retrospective Studies, Transplantation, Autologous, Treatment Outcome, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy
- Abstract
Outcomes for patients with multiple myeloma (MM) have improved with the advent of novel therapies, however, real-world evidence of outcomes in clinical practice is scarce. We conducted a multi-center registry study to build a reliable picture of treatment and patient outcomes in Finland. The aim of this study was also to understand any methodological challenges in assessing treatment outcomes using disease registry data., Methods: We carried out a retrospective, observational study using data from the national Finnish Hematology Registry (FHR) to provide real-world evidence of outcomes for all adult patients diagnosed with and treated for MM between 2009-2013 at one of the six regional hospitals, with at least six months of recorded follow-up. Patients were identified within the FHR by applying eligibility criteria of a diagnosis of MM and verifiable records of medical treatment and lines of treatment during the study period. Patients receiving allogenic stem cell transplantation were excluded from the cohort, as were individuals who only had monoclonal gammopathy of undetermined significance diagnosis and patients who had not initiated treatment during this period. Kaplan Meier curves were used to calculate overall survival and time to next treatment. Stratification was carried out by drug status (conventional/novel) and by autologous stem cell transplant (ASCT) status., Results: A total of 321 patients met the inclusion criteria and were included in this study. Overall survival (OS) was longest in patients who received first-line novel therapy and ASCT (median not reached during 60-month follow-up) versus 46.2 months for novel first-line therapy without ASCT and 25.6 months for first-line conventional therapy without ASCT. Similarly, median time to next treatment were 33.9 months, 12.6 months and 7.8 months, respectively., Conclusions: The adoption of novel treatments in MM in Finland has had substantial impact on patient outcomes. Given the reality of complex treatment combinations for MM and relatively low patient numbers, assessing individual treatment effectiveness will require substantial cohort sizes and advanced, collaborative analytics on an international scale., Competing Interests: KR has been a member of Advisory Boards for Abbvie, Celgene, Janssen-Cilag and Takeda and has received fees to attend Congresses from Abbvie, Amgen, Celgene, Janssen-Cilag, Sanofi, Takeda. PA has been a member of Advisory Boards for Amgen, Celgene, Janssen and Takeda and has received fees to attend Congresses from Amgen, Bristol-Meyers-Squibb, Celgene, Janssen, Roche, Sanofi, Takeda and Teva. RS has received research funding from Amgen, BMS, Celgene, Janssen-Cilag and Takeda and honoraria from the same companies (Advisory Board and presentations). MP has received honoraria from Amgen, Celgene, Janssen-Cilag and Takeda (Advisory Board and presentations). HO does not have any competing interests. VT does not have any competing interests. MS does not have any competing interests. KK has received financial support from Jansen to collect data for this study and travel grants from Amgen, Shire and Sanofi Genzyme. TJ, MaP, FS, PCK and AL are employees of Janssen, the funder of this research. FW does not have any competing interests. TD is a Director of JB Medical and has worked with, and been funded by, other pharmaceutical companies in the field of hematological cancer. The funder Janssen provided support in the form of salaries for authors AL, PCK, TMJ, FS, MaP. This was a company sponsored study conducted in collaboration with the Finnish researchers, where both parties were involved in the study design, analysis and publication as per ICMJE standards. Data collection was carried out at the Finnish hospitals, with financial support from the funder. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Janssen funded JB Medical Ltd to provide medical writing support, TD is a paid employee of JB Medical and carried out the work. JB Medical did not have any additional role in the study design, data collection and analysis or decision to publish. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2018
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35. Can repeated IVF-ICSI-cycles be avoided by using blastocysts developing from poor-quality cleavage stage embryos?
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Kaartinen N, Das P, Kananen K, Huhtala H, and Tinkanen H
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- Birth Rate, Cryopreservation, Embryo Culture Techniques, Family Characteristics, Female, Finland epidemiology, Hospitals, University, Humans, Infertility, Female pathology, Infertility, Male, Male, Outpatient Clinics, Hospital, Pregnancy, Pregnancy Rate, Retrospective Studies, Sperm Injections, Intracytoplasmic, Vitrification, Blastocyst pathology, Cleavage Stage, Ovum pathology, Ectogenesis, Embryo Transfer, Fertilization in Vitro, Infertility, Female therapy
- Abstract
In many clinics, good-quality embryos are selected for embryo transfer and cryopreservation at the cleavage stage, and poor-quality embryos are discarded. The aim of this retrospective study was to examine how many repeated IVF cycles could be avoided by culturing the cleavage stage poor-quality embryos to blastocyst stage and transferring them after vitrification and warming (604 IVF and intracytoplasmic sperm injection [IVF-ICSI] cycles were included). Poor-quality cleavage stage embryos not eligible for transfer or cryopreservation were cultured until day 5 or 6, and those developing to the blastocyst stage were vitrified. The rate of vitrified blastocysts and clinical pregnancy and delivery rate of the warmed blastocysts was evaluated. The effect of the extended culture on the cumulative delivery rate, and the number of avoided new treatment cycles was calculated. The surplus blastocysts resulted in clinical pregnancy, spontaneous abortion and delivery rates of 24.6%, 27.3% and 17.2% respectively. The use of surplus blastocysts raised cumulative delivery rate from 43% to 47% and 53 repeated new cycles were avoided. This study shows that the cumulative delivery rate can be increased, and repeated IVF-ICSI treatments avoided by using blastocysts developing from poor-quality cleavage stage embryos, which otherwise would have been discarded., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2015
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36. In vitro maturation supplements affect developmental competence of bovine cumulus-oocyte complexes and embryo quality after vitrification.
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Räty M, Ketoja E, Pitkänen T, Ahola V, Kananen K, and Peippo J
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- Animals, Biomarkers metabolism, Cattle, Embryonic Development, Excipients pharmacology, Female, Gene Expression, Glucose Transporter Type 1 genetics, Glucose Transporter Type 1 metabolism, Intercellular Signaling Peptides and Proteins pharmacology, Male, Oocytes physiology, Povidone pharmacology, Semen physiology, Blastocyst physiology, Cryopreservation methods, Cryopreservation veterinary, Culture Media pharmacology, Embryo Culture Techniques veterinary, Fertilization in Vitro methods, Fertilization in Vitro veterinary, In Vitro Oocyte Maturation Techniques methods, In Vitro Oocyte Maturation Techniques veterinary, Vitrification
- Abstract
Oocyte quality affects subsequent embryo development and quality. We examined the impact of bovine oocyte in vitro maturation (IVM) conditions on subsequent embryo yield, quality and cryosurvival. Cumulus-oocyte complexes (COCs) were sampled for cytological and gene expression analysis after IVM in TCM199 supplemented with 10% fetal bovine serum (FBS), 4 mg/ml of fatty-acid-free bovine serum albumin (FAFBSA), 4 mg/ml of polyvinylpyrrolidone (PVP), FAFBSA with epidermal growth factor (EGF, 100 ng/ml) and insulin-like growth factor 1 (IGF-I, 100 ng/ml) (FAFBSAGF), PVP with EGF and IGF-I (PVPGF) or PVP with single strength BME and MEM amino acids (PVPAA). The remaining COCs were fertilized. On day 7 (IVF=day 0) quality 1 blastocysts were vitrified or analyzed for glucose transporter 1 (Glut-1) expression levels. The remaining blastocysts (days 7-9) were evaluated for morphology and total cell counts. After warming, survival and hatching rates were evaluated followed by total cell counts and Glut-1 expression levels. Only PVPGF IVM resulted in embryo production rates comparable to those recorded with FBS IVM. Growth factors with FAFBSA and amino acids with PVP reduced embryo production rates whereas the effect of the growth factors with PVP was negligible. Insulin-like growth factor 2 binding protein 3 (IGF2BP3) and beta cell translocation gene 4 (BTG4) were revealed as potential candidates for oocyte developmental competence, and secreted protein, acidic and rich in cysteine (SPARC) for cumulus cell expansion. There were no differences among treatments in hatching rates of vitrified embryos after warming. However, total cell numbers and Glut-1 expression levels at 72 h were affected., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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37. Nephropathy advancing to end-stage renal disease: a novel complication of lysinuric protein intolerance.
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Tanner LM, Näntö-Salonen K, Niinikoski H, Jahnukainen T, Keskinen P, Saha H, Kananen K, Helanterä A, Metso M, Linnanvuo M, Huoponen K, and Simell O
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Citrulline blood, Creatinine blood, Cystatin C, Cystatins blood, Disease Progression, Female, Glomerular Filtration Rate, Humans, Infant, Kidney Diseases blood, Kidney Diseases pathology, Kidney Failure, Chronic surgery, Kidney Transplantation, Male, Middle Aged, Proteinuria etiology, Amino Acid Transport Disorders, Inborn complications, Kidney Diseases etiology, Kidney Failure, Chronic etiology, Lysine urine
- Abstract
Objective: To analyze systemically the prevalence of renal involvement in a cohort of Finnish patients with lysinuric protein intolerance (LPI) and to describe the course and outcome of end-stage renal disease in 4 patients., Study Design: The clinical information in a cohort of 39 Finnish patients with LPI was analyzed retrospectively., Results: Proteinuria was observed in 74% of the patients and hematuria was observed in 38% of the patients during follow-up. Elevated blood pressure was diagnosed in 36% of the patients. Mean serum creatinine concentration increased in 38% of the patients, and cystatin C concentration increased in 59% of the patients. Four patients required dialysis, and severe anemia with poor response to erythropoietin and iron supplementation also developed in these patients., Conclusions: Our findings suggest that renal function of patients with LPI needs to be carefully monitored, and hypertension and hyperlipidemia should be treated effectively. Special attention also should be paid to the prevention of osteoporosis and carnitine deficiency in the patients with end-stage renal disease associated with LPI. The primary disease does not prohibit treatment by dialysis and renal transplantation.
- Published
- 2007
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38. Risk factors for reduced areal bone mineral density in young adults with stem cell transplantation in childhood.
- Author
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Taskinen M, Kananen K, Välimäki M, Löyttyniemi E, Hovi L, Saarinen-Pihkala U, and Lipsanen-Nyman M
- Subjects
- Absorptiometry, Photon, Adolescent, Adult, Bone Resorption epidemiology, Bone Resorption metabolism, Child, Child, Preschool, Female, Femur Neck diagnostic imaging, Finland epidemiology, Hip diagnostic imaging, Humans, Incidence, Lumbar Vertebrae diagnostic imaging, Male, Prognosis, Retrospective Studies, Risk Factors, Bone Density physiology, Bone Resorption etiology, Stem Cell Transplantation adverse effects
- Abstract
Slightly, but significantly, reduced bone mineral density (BMD) has been detected as a late effect after stem cell transplantation (SCT) performed in childhood. The aim of the study was to evaluate the risk factors of reduced BMD after SCT in childhood. We evaluated areal BMD of 16 young adults (six males, 10 females), aged 21 yr (range 15-34) by dual-energy X-ray absorptiometry at the lumbar spine, at the femoral neck, in the total hip, and in the total body. Bone turnover rate was evaluated by markers of bone formation and resorption. Six of the 16 patients had reduced BMD with a Z-score of < or = -1 at least at one measurement site. Factors associated with reduced BMD were prepubertal status at transplant (p = 0.03), delayed pubertal growth (p = 0.03), pubertal onset gonadal hormone insufficiency (p = 0.02), and female sex (p = 0.02). Surprisingly, height in SDs and lumbar spine BMD correlated negatively (p = 0.008) in those with reduced bone mass, indicating that low areal density could not be due the small size of the vertebrae. Bone turnover markers were similar for those with normal and reduced BMD. In conclusion, 38% of the SCT long-term survivors had reduced areal BMD. Prepubertal status at transplant with pubertal onset gonadal hormone insufficiency and female sex predisposed to reduced bone mass after SCT performed in childhood.
- Published
- 2006
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39. Prevention of bone loss after allogeneic stem cell transplantation by calcium, vitamin D, and sex hormone replacement with or without pamidronate.
- Author
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Kananen K, Volin L, Laitinen K, Alfthan H, Ruutu T, and Välimäki MJ
- Subjects
- Adult, Aged, Bone Density, Bone Remodeling, Female, Humans, Male, Middle Aged, Pamidronate, Transplantation, Homologous, Calcium Carbonate administration & dosage, Diphosphonates therapeutic use, Gonadal Steroid Hormones therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hormone Replacement Therapy, Osteoporosis prevention & control, Vitamin D administration & dosage
- Abstract
Context: In controlled studies, bisphosphonates have been used to prevent bone loss after solid organ transplantations but not in conjunction with stem cell transplantation (SCT)., Objective: The objective of the study was to test whether additional iv pamidronate would prevent bone loss associated with SCT more effectively than the combination of calcium, vitamin D, and sex steroid replacement therapy alone., Setting: The study was carried out at the Helsinki University Central Hospital. PATIENTS, DESIGN, INTERVENTION: Ninety-nine adult recipients of allogeneic SCT were randomized by age and gender into two groups. In one group, the patients received 1000 mg calcium carbonate and 800 IU vitamin D daily, and females received estrogen and males received testosterone replacement therapy. In another group, the patients received the same treatments plus six iv infusions of 60 mg pamidronate before and 1, 2, 3, 6, and 9 months after SCT., Main Outcome Measures: Bone mineral density (BMD) of the lumbar spine and the upper femur, measured by dual-energy x-ray absorptiometry, and bone turnover markers were followed for 12 months., Results: In the pamidronate group, lumbar spine BMD remained stable but decreased in the other group by 2.9% at 12 months (P = 0.0084 between the groups over time). Total hip BMD reduced 5.1% in the pamidronate group and 7.8% in the other group by 12 months (P = 0.0015), and femoral neck BMD reduced 4.2 and 6.2%, respectively (P = 0.074). In the pamidronate group, serum type I procollagen amino-terminal propeptide (P = 0.032 between the groups over time) and urinary type I collagen amino-terminal telopeptide (P = 0.035) decreased 79 and 68% during the first 3 months, and remained lowered thereafter, but did not change in the other group., Conclusions: The recipients of allogeneic SCT receiving additional pamidronate sustain less bone loss than those treated with calcium, vitamin D, and sex steroid replacement alone. Despite all the efforts, however, bone loss is not totally abolished at the hip.
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- 2005
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40. Direct luteinizing hormone action triggers adrenocortical tumorigenesis in castrated mice transgenic for the murine inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene.
- Author
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Rilianawati, Paukku T, Kero J, Zhang FP, Rahman N, Kananen K, and Huhtaniemi I
- Subjects
- Adrenal Cortex Neoplasms physiopathology, Animals, Antigens, Polyomavirus Transforming genetics, Castration, Cell Transformation, Neoplastic genetics, Chorionic Gonadotropin pharmacology, Crosses, Genetic, DNA Replication drug effects, Female, Gonadal Steroid Hormones pharmacology, Gonadotropin-Releasing Hormone analogs & derivatives, Gonadotropin-Releasing Hormone toxicity, Gonadotropins, Pituitary deficiency, Granulosa Cell Tumor physiopathology, Humans, Leydig Cell Tumor physiopathology, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Mutant Strains, Mice, Transgenic, Neoplasms, Hormone-Dependent physiopathology, Organ Specificity, Ovarian Neoplasms physiopathology, Peptides genetics, Receptors, FSH analysis, Receptors, LH biosynthesis, Receptors, LH physiology, Recombinant Fusion Proteins physiology, Simian virus 40 physiology, Testicular Neoplasms physiopathology, Thecoma physiopathology, Tumor Cells, Cultured, Adrenal Cortex Neoplasms genetics, Antigens, Polyomavirus Transforming physiology, Granulosa Cell Tumor genetics, Inhibins, Leydig Cell Tumor genetics, Luteinizing Hormone pharmacology, Luteinizing Hormone physiology, Neoplasms, Hormone-Dependent genetics, Ovarian Neoplasms genetics, Peptides physiology, Promoter Regions, Genetic, Testicular Neoplasms genetics, Thecoma genetics
- Abstract
Transgenic (TG) mice, expressing the Simian Virus 40 T-antigen (Tag) under a 6-kb fragment of the murine inhibin alpha-subunit promoter (inh alpha p), develop gonadal tumors of granulosa/theca or Leydig cell origin. We showed previously that adrenocortical tumors develop if the TG mice are gonadectomized but never develop in intact animals. However, if functional gonadectomy was induced by GnRH antagonist treatment or by cross-breeding the TG mice into the hypogonadotropic hpg genetic background, neither gonadal nor adrenal tumors appeared. Since the most obvious difference between the gonadectomized and GnRH-antagonist-treated or Tag/hpg double mutant mice is the elevated gonadotropin secretion in the first group, we examined whether the adrenal tumorigenesis would be gonadotropin-dependent. Surprisingly, both the adrenal tumors and a cell line (C alpha 1) derived from one of them expressed highly functional LH receptors (LHR), as assessed by Northern hybridization, immunocytochemistry, ligand binding, and human CG (hCG)-stimulated cAMP and steroid production. No FSH receptor expression was found in the adrenal tumors by RT-PCR. hCG treatment of the C alpha 1 cells stimulated their proliferation, as measured by [3H]thymidine incorporation. This effect was related to hCG-stimulated steroidogenesis since progesterone, testosterone, and estradiol, at physiological concentrations, also stimulated the C alpha 1 cell proliferation. Different adrenocortical cells expressed initially LHR and Tag, whereas both were highly expressed in the tumor cells. In conclusion, the high level of functional LHR in the adrenal tumors indicates that this receptor can function as tumor promoter when ectopically expressed and stimulated by the ligand hormone.
- Published
- 1998
- Full Text
- View/download PDF
41. Suppression of gonadotropins inhibits gonadal tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene.
- Author
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Kananen K, Rilianawati, Paukku T, Markkula M, Rainio EM, and Huhtaniemi I
- Subjects
- Animals, Antigens, Polyomavirus Transforming analysis, Disease Models, Animal, Female, Gonadotropin-Releasing Hormone analogs & derivatives, Gonadotropin-Releasing Hormone pharmacology, Gonadotropins metabolism, Hormone Antagonists pharmacology, Hyperplasia, Leydig Cells chemistry, Leydig Cells pathology, Male, Mice, Mice, Transgenic, Ovarian Neoplasms blood, Ovarian Neoplasms genetics, Ovary pathology, Peptides analysis, Peptides blood, Pituitary Gland chemistry, Progesterone analysis, Progesterone blood, Promoter Regions, Genetic genetics, RNA, Messenger analysis, RNA, Messenger genetics, Testicular Neoplasms blood, Testicular Neoplasms genetics, Testis pathology, Testosterone analysis, Testosterone blood, Time Factors, Antigens, Polyomavirus Transforming genetics, Cell Transformation, Neoplastic drug effects, Cloning, Molecular, Gonadotropins antagonists & inhibitors, Inhibins, Ovarian Neoplasms pathology, Peptides genetics, Testicular Neoplasms pathology
- Abstract
We have previously developed a transgenic (TG) mouse model expressing the Simian virus 40 T-antigen (Tag), driven by a 6-kb fragment of the mouse inhibin alpha-subunit promoter (inh-alpha). The mice develop metastasizing gonadal tumors, of granulosa/theca or Leydig cell origin, with 100% penetrance by the age of 5-8 months. In the present study, we examined whether the appearance and growth of the gonadal tumors are dependent on gonadotropins. Gonadotropin suppression was achieved either by treatment of 3-month-old mice for 2-3 months with a GnRH antagonist (Cetrorelix, SB-75), or by cross-breeding the TG mice to the genetic background of the gonadotropin-deficient hypogonadal mutant mouse (hpg). Gonadal tumor growth was clearly inhibited by SB-75 treatment in one of the TG mouse lines (IT6-M), as indicated by the absence of macroscopically visible tumors and by reduced gonadal weights. Despite the suppressed gonadotropin secretion and Tag expression, hyperplasia of testicular Leydig, and ovarian stromal cells persisted in some of the treated mice. In another TG mouse line (IT6-F), with more aggressive tumorigenesis, the SB-75 treatment only partially inhibited gonadal tumor growth. None of the hypogonadotropic TG mice, homozygous for the hpg mutation, developed gonadal tumors. Their gonadal histology was indistinguishable from that of the non-TG hpg mice, suggesting total inhibition of gonadal tumorigenesis in the absence of gonadotropin stimulation. Tag expression and Leydig cell hyperplasia were apparent already in the postnatal TG mice but absent in those TG mice homozygous for the hpg mutation. In conclusion, the present results indicate that the gonadal tumorigenesis in our TG mouse model starts in early age as hyperplasia in specific somatic cells. Both this, and the subsequent malignant tumor growth, are gonadotropin dependent. A sufficient level of Tag expression, a prerequisite for gonadal tumorigenesis, only occurs upon gonadotropin stimulation.
- Published
- 1997
- Full Text
- View/download PDF
42. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera.
- Author
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Hämäläinen KM, Kananen K, Auriola S, Kontturi K, and Urtti A
- Subjects
- Absorption, Animals, Aqueous Humor metabolism, Chromatography, High Pressure Liquid, Diffusion Chambers, Culture, Epithelium metabolism, Female, Male, Mass Spectrometry, Molecular Weight, Porosity, Rabbits, Cell Membrane Permeability physiology, Conjunctiva metabolism, Cornea metabolism, Pharmaceutic Aids pharmacokinetics, Polyethylene Glycols pharmacokinetics, Sclera metabolism
- Abstract
Purpose: To characterize quantitatively the paracellular permeation routes in rabbit cornea, conjunctiva, and sclera using polyethylene glycol (PEG) oligomers., Methods: Corneal, conjunctival, and scleral tissues from New Zealand white rabbits were tested individually in a modified two-chamber Ussing apparatus with the mixture of PEGs with mean molecular weights 200, 400, 600, and 1000 in glutathione bicarbonated Ringer's solution buffer on the donor side of the chamber. The samples and standards were analyzed with high-performance liquid chromatography-thermospray mass spectrometry method. The pore sizes and the pore densities of the corneal and conjunctival epithelia were calculated using an effusion-like approach., Results: The conjunctival and scleral tissues were 15 to 25 times more permeable than the cornea and the molecular size affected the conjunctival permeability less than that of the cornea. The palpebral and bulbar conjunctivas had equal permeabilities. The scleral permeability was approximately half of that in the conjunctiva and approximately 10 times more than in the cornea. The conjunctival epithelia had 2 times larger pores and 16 times higher pore density than the cornea. The total paracellular space in the conjunctiva was estimated to be 230 times greater than that in the cornea., Conclusions: The conjunctival epithelium, due to its higher membrane permeability and larger absorptive and intercellular space surface areas, is the most viable route for ocular delivery of peptides and oligonucleotides.
- Published
- 1997
43. Pituitary and ovarian expression of the endogenous follicle-stimulating hormone (FSH) subunit genes and an FSH beta-subunit promoter-driven herpes simplex virus thymidine kinase gene in transgenic mice; specific partial ablation of FSH-producing cells by antiherpes treatment.
- Author
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Markkula M, Kananen K, Klemi P, and Huhtaniemi I
- Subjects
- Acyclovir pharmacology, Animals, Cell Death, DNA Primers genetics, Female, Follicle Stimulating Hormone metabolism, Follicle Stimulating Hormone, beta Subunit, Ganciclovir pharmacology, Gene Expression, Glycoprotein Hormones, alpha Subunit genetics, Mice, Ovary anatomy & histology, Ovary drug effects, Pituitary Gland drug effects, Polymerase Chain Reaction, Promoter Regions, Genetic, RNA, Messenger analysis, Simplexvirus drug effects, Simplexvirus enzymology, Simplexvirus genetics, Follicle Stimulating Hormone genetics, Mice, Transgenic metabolism, Ovary metabolism, Pituitary Gland metabolism, Thymidine Kinase genetics
- Abstract
The ovarian expression of the endogenous follicle-stimulating hormone beta-subunit (FSH beta) and common alpha-subunit (C alpha) genes, and a herpes simplex virus thymidine kinase (tk) transgene, driven by a 2.3 kb bovine FSH beta promoter, was studied in normal and transgenic (tg) mice, tk functions not only as a neutral reporter that enables the study of the promoter function but also as an exogenously inducible toxigene. Reverse transcription-PCR followed by Southern blot hybridization with a nested probe was used to show the expression of the gene at the mRNA level. Common alpha-subunit mRNA was detected in the pituitary gland and ovaries of normal adult mice. We have previously detected endogenous FSH beta and tg tk mRNAs in the mouse pituitary, testis and ovary. In this study, the cellular localization of the corresponding proteins was visualized by immunocytochemistry. In normal mouse ovaries a positive reaction with FSH beta and C alpha antisera was seen in some of the corpora lutea and most prominently in the interstitial cells. A positive reaction with the tk antiserum was seen in the same cell types of tg mouse ovaries, but not in those of non-tg mice. Cell-ablation-inducing treatment (gancyclovir, 20 mg/kg per day, for 14 days) of tg female mice reduced pituitary FSH concentrations by 52% (P < 0.05) but did not affect pituitary LH or plasma gonadotropins compared with non-tg females treated in the same way. A longer period of cell ablation induction (acyclovir 400 mg/kg per day, for 21 days) reduced not only pituitary but also plasma FSH concentrations (55 and 57% respectively; P < 0.05) without affecting LH. This treatment also reduced ovarian weight by 38% (P < 0.01). In conclusion, our results show first that the endogenous FSH beta and C alpha proteins are produced in the mouse ovary. Hence, endogenously synthesized FSH or its subunits may have a role in the paracrine regulation of ovarian function. Secondly, the FSH beta promoter directs the expression of tg tk in the pituitary gonadotrope cells, as shown by specific but partial ablation of FSH-producing cells after induction by gancyclovir and acyclovir. In the ovary, tk protein was localized to the same compartments as the endogenous gonadotropin subunit proteins. This further confirms our finding of ovarian expression of the FSH subunit genes.
- Published
- 1996
- Full Text
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44. Tissue distribution and phenotypic consequences of different type X collagen gene constructs in transgenic mice.
- Author
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Eerola I, Elima K, Markkula M, Kananen K, and Vuorio E
- Subjects
- Animals, Cartilage embryology, Cartilage metabolism, Chickens, Connective Tissue embryology, Connective Tissue metabolism, Introns, Mice, Mice, Transgenic, Mutagenesis, Organ Specificity, Promoter Regions, Genetic, RNA, Messenger biosynthesis, Recombinant Proteins biosynthesis, beta-Galactosidase biosynthesis, Collagen biosynthesis, Collagen genetics
- Published
- 1996
- Full Text
- View/download PDF
45. A 252 bp upstream region of the rat spermatocyte-specific hst70 gene is sufficient to promote expression of the hst70-CAT hybrid gene in testis and brain of transgenic mice.
- Author
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Widłak W, Markkula M, Krawczyk Z, Kananen K, and Huhtaniemi I
- Subjects
- Animals, Base Sequence, Chloramphenicol O-Acetyltransferase biosynthesis, DNA Primers, HSP70 Heat-Shock Proteins biosynthesis, Male, Mice, Mice, Transgenic, Molecular Sequence Data, Polymerase Chain Reaction, Recombinant Fusion Proteins biosynthesis, Sequence Homology, Nucleic Acid, Brain metabolism, Gene Expression, HSP70 Heat-Shock Proteins genetics, Multigene Family, Rats genetics, Regulatory Sequences, Nucleic Acid, Spermatocytes metabolism, Testis metabolism
- Abstract
The rat hst70 gene belongs to a heat shock hsp70 multigene family and its expression has been detected so far solely in spermatocytes. To investigate the cis-elements responsible for testis-specific expression of the hst70 gene we produced several lines of transgenic mice carrying fragments of the 5'-flanking regions of the hst70 gene fused to the chloramphenicol acetyltransferase (CAT) reporter gene. Hybrid genes of series B were constructed such that, besides the 780 bp, 343 bp and 163 bp 5'-flanking region these plasmids contained no other sequences of the hst70 gene. In hybrid genes of series D the CAT gene was ligated to 343 bp and 252 bp 5'-flanking regions together with the 57 bp of the 5'-end nontranslated (leader) sequences of the hst70 gene. We found that in 780/B, 343/B, 343/D and 252/D adult mice the transgene was specifically and highly expressed in testes. In developing testes the high CAT activity appeared in transgenic mice aged 3 weeks and older. None of the three 163/B transgenic lines exhibited CAT activity in any tissue analyzed. In all CAT expressing lines a weak but significant CAT activity (up to 5% of that in testis) was detected also in the brain. RNase protection assay confirmed that the endogenous hst70 gene transcripts are present in testis as well as in brain of nontransgenic rats and mice. Our data show that the cis-regulatory sequences responsible for testis-specific and developmentally regulated expression of the hst70 gene are localized within the 252 bp region 5' to the gene and neither the 5'-end nor 3'-end nontranslated sequences of the gene are important for this specificity.
- Published
- 1995
- Full Text
- View/download PDF
46. Induced ablation of gonadotropins in transgenic mice expressing herpes simplex virus thymidine kinase under the FSH beta-subunit promoter.
- Author
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Markkula M, Kananen K, Paukku T, Männistö A, Loune E, Fröjdman K, Pelliniemi LJ, and Huhtaniemi I
- Subjects
- Acyclovir pharmacology, Animals, Base Sequence, DNA analysis, DNA chemistry, DNA genetics, DNA Primers chemistry, Female, Follicle Stimulating Hormone analysis, Follicle Stimulating Hormone blood, Ganciclovir pharmacology, Gene Expression Regulation, Enzymologic drug effects, Gonadotropins genetics, Gonadotropins physiology, Growth Hormone analysis, Luteinizing Hormone analysis, Luteinizing Hormone blood, Male, Mice, Mice, Transgenic, Molecular Sequence Data, Pituitary Gland chemistry, Polymerase Chain Reaction, Pregnancy, Prolactin analysis, Testis enzymology, Thymidine Kinase analysis, Thyrotropin analysis, Follicle Stimulating Hormone genetics, Gonadotropins metabolism, Promoter Regions, Genetic genetics, Simplexvirus enzymology, Thymidine Kinase genetics
- Abstract
Suppression of gonadotropins was induced by gancyclovir or acyclovir treatment in transgenic mice carrying 2.3 kb of bovine follicle-stimulating hormone beta (FSH beta) promoter fused to Herpes simplex virus thymidine kinase (tk) coding sequence. Transgenic tk and endogenous FSH beta were immunohistochemically co-localized in the same pituitary cells. In adult castrated transgenic males, gancyclovir treatment reduced plasma FSH (30%, P < 0.001). In intact juvenile gancyclovir treated mice, the reduction of pituitary FSH, and in males also of plasma FSH, was greater (50-70%, P < 0.05-0.01). A concomitant suppression of luteinizing hormone (LH) (50%, P < 0.01) was observed in female pups. The most pronounced reduction of gonadotropins was observed in newborn transgenic pups treated in utero with acyclovir. Both males and females had significantly lower pituitary levels of FSH (75-55%), LH (80-90%) or both (P < 0.05-0.01). Less pronounced decreases (30-40%, P < 0.01) were observed in plasma FSH. No apparent defects were seen in the testes of the transgenic, acyclovir treated, newborn pups. This mouse model is applied to study the dynamics of the gonadotropes and the role of gonadotropins in the maturation of the reproductive functions.
- Published
- 1995
- Full Text
- View/download PDF
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