研究者総覧

河野 由美 (コウノ ユミ)

  • 総合周産期母子医療センター 新生児発達部 教授
Last Updated :2021/12/08

研究者情報

ホームページURL

J-Global ID

研究キーワード

  • 早産   低出生体重児   神経発達予後   新生児   胎児   精神発達   dioxin   lactation   喫煙   臍帯血   DNAメチル化   

研究分野

  • ライフサイエンス / 胎児医学、小児成育学
  • ライフサイエンス / 胎児医学、小児成育学

経歴

  • 2014年  自治医科大学医学部准教授

研究活動情報

論文

  • Yumi Kono, Naohiro Yonemoto, Hidehiko Nakanishi, Shigeharu Hosono, Shinya Hirano, Satoshi Kusuda, Masanori Fujimura
    American journal of perinatology 2021年02月 
    OBJECTIVE:  We examined the effects of maternal hypertensive disorders of pregnancy (HDP) on the mortality and neurodevelopmental outcomes in preterm very low birth weight (VLBW) infants (BW ≤1,500 g) based on their intrauterine growth status and gestational age (GA). STUDY DESIGN:  We included singleton VLBW infants born at <32 weeks' gestation registered in the Neonatal Research Network Japan database. The composite outcomes including death, cerebral palsy (CP), and developmental delay (DD) at 3 years of age were retrospectively compared among three groups: appropriate for GA (AGA) infants of mothers with and without HDP (H-AGA and N-AGA) and small for GA (SGA) infants of mothers with HDP (H-SGA). The adjusted odds ratios (AOR) and 95% confidence intervals (CI) stratified by the groups of every two gestational weeks were calculated after adjusting for the center, year of birth, sex, maternal age, maternal diabetes, antenatal steroid use, clinical chorioamnionitis, premature rupture of membranes, non-life-threatening congenital anomalies, and GA. RESULTS:  Of 19,323 eligible infants, outcomes were evaluated in 10,192 infants: 683 were H-AGA, 1,719 were H-SGA, and 7,790 were N-AGA. Between H-AGA and N-AGA, no significant difference was observed in the risk for death, CP, or DD in any GA groups. H-AGA had a lower risk for death, CP, or DD than H-SGA in the 24 to 25 weeks group (AOR: 0.434, 95% CI: 0.202-0.930). The odds for death, CP, or DD of H-SGA against N-AGA were found to be higher in the 24 to 25 weeks (AOR: 2.558, 95% CI: 1.558-3.272) and 26 to 27 weeks (AOR: 1.898, 95% CI: 1.427-2.526) groups, but lower in the 30 to 31 weeks group (AOR: 0.518, 95% CI: 0.335-0.800). CONCLUSION:  There was a lack of follow-up data; however, the outcomes of liveborn preterm VLBW infants of mothers with HDP depended on their intrauterine growth status and GA at birth. KEY POINTS: · The effects of HDP on preterm low birth weight infants need to be further examined.. · The outcomes were not different between AGA infants with and without maternal HDP.. · The outcomes of SGA infants with maternal HDP were dependent on their GA..
  • Yumi Kono
    Clinical and Experimental Pediatrics 64 313 - 321 2020年11月 [査読有り][招待有り]
  • Yume Suzuki, Yumi Kono, Takahiro Hayakawa, Hironori Shimozawa, Miyuki Matano, Yukari Yada, Neonatal Research Network Japan
    PLoS ONE 13 6 2018年06月 [査読有り][通常論文]
     
    Background: Although late-onset circulatory collapse (LCC) is widely recognized in Japan, its etiology and the reason for center variation in its incidence remain unclear. This study's objectives were to identify the perinatal and neonatal factors related to LCC and to estimate the factors related to the center variation in the incidence of LCC. Methods: Extremely preterm infants born between 2008 and 2012 who were registered in the database of the Neonatal Research Network, Japan were retrospectively analyzed. LCC was defined as a clinical diagnosis of LCC and the administration of steroids. We first identified the factors that were significantly related to LCC. We then examined the cause of the center variation in the incidence of LCC, using the standardized incidence ratios (SIRs) of LCC and individual factors. Results: The factors significantly associated with LCC included low gestational age (odds ratio [OR]: 1.13), small for date (OR: 1.43), male sex (OR: 1.26), antenatal steroid use (OR: 1.19), respiratory distress syndrome (OR: 1.25), chronic lung disease at 36 weeks (OR: 1.16), periventricular leukomalacia (PVL) (OR: 2.57), necrotizing enterocolitis (OR: 0.59), retinopathy of prematurity (ROP) (OR: 1.73), high-frequency oscillating ventilation (HFOV) use (OR: 1.31), parenteral nutrition (OR: 1.38), and red blood cell (RBC) transfusion (OR: 1.94). The SIR of LCC ranged from 0.05 to 2.94, and was positively correlated with SIRs of PVL, ROP, HFOV use and RBC transfusion. Conclusion: PVL, ROP, HFOV use and RBC transfusion were found to be correlated with the center variation in the incidence of LCC.
  • Hidehiko Nakanishi, Hideyo Suenaga, Atsushi Uchiyama, Yumi Kono, Satoshi Kusuda, On behalf of the Neonatal Research Network, Japan
    Journal of Perinatology 1 - 10 2018年04月 [査読有り][通常論文]
     
    Objectives: To determine the trends in mortality and the prevalence of abnormal neurodevelopmental outcomes among preterm Japanese infants. Study design: A retrospective multicenter cohort of 30,793 preterm infants born at a gestational age ≤32 weeks, between 2003 and 2012, in the Neonatal Research Network, Japan, was evaluated in the primary analysis. Finally, 13,661 infants were followed-up until 3 years of age and evaluated for neurodevelopmental outcomes, including cerebral palsy (CP), home oxygen therapy (HOT) use, and visual, hearing, and cognitive impairments. Multivariable logistic regression analysis was performed to determine the risk-adjusted trends in mortality and long-term neurodevelopmental outcomes. Results: The trends in overall mortality (adjusted odds ratio, (AOR): 0.92 95% confidence interval, (CI): 0.89–0.94), the prevalence of CP (AOR: 0.95, 95% CI: 0.92–0.98), HOT use (AOR: 0.84, 95% CI: 0.75–0.93), and visual (AOR: 0.84, 95% CI: 0.81–0.87) and hearing impairments (AOR: 0.78, 95% CI: 0.63–0.97) showed a significant downward trend, while cognitive impairment showed no significant changes (AOR: 1.02, 95% CI: 0.99–1.05). Intravenous hyperalimentation was significantly correlated with visual impairment (AOR 0.74, 95% CI 0.59–0.91). Early establishment of enteral feeding was associated with improved long-term outcomes. Conclusions: Mortality was improved, and this did not lead to increased risks for abnormal neurodevelopmental outcomes. Nutritional support might improve long-term neurodevelopmental outcomes.
  • Kono Y, Yonemoto N, Nakanishi H, Kusuda S, Fujimura M
    BMJ paediatrics open 2 1 e000211  2018年 [査読有り][通常論文]
  • Yumi Kono, Naohiro Yonemoto, Satoshi Kusuda, Shinya Hirano, Osuke Iwata, Kyoko Tanaka, Jun Nakazawa
    BRAIN & DEVELOPMENT 38 4 377 - 385 2016年04月 [査読有り][通常論文]
     
    Aim: To assess the developmental characteristics of very low-birth-weight (VLBW) infants using the Kyoto Scale of Psychological Development (KSPD) and to compare with those using the Bayley Scales, third edition (Bayley III).Methods: KSPD and Bayley III were performed on 124 Japanese VLBW infants at 18 months of corrected age at a 2-week interval by trained psychologists. The relationships between KSPD and Bayley III in corresponding pairs: Cognitive Adaptive (C-A) developmental quotient (DQ) and cognitive composite (Cog) scores, Language Social (L-S) DQ and language composite (Lang) scores, and Postural Motor (P-M) DQ and motor composite (Mot) scores were analyzed.Results: The means [SD] of C-A DQ, L-S DQ, P-M DQ, and overall DQ of KSPD were 94 [15], 90 [17], 89 [15], and 93 [14], respectively. The means [SD] of the Cog, Lang, and Mot scores of Bayley III were 96 [13], 84 [12], and 91 [12], respectively. The DQ of KSPD strongly correlated with the corresponding composite score of Bayley III; Spearman rank correlations between the Cog score and C-A DQ, the Lang score and L-S DQ, and the Mot score and P-M DQ were 0.65, 0.71 and 0.55, respectively. The selected cut-off of the Cog score of <85 accurately identified development delay, defined by KSPD, with sensitivity of 100% and specificity of 85%.Conclusion: Although absolute value of the Bayley III score may not represent the degree of impairment, the developmental characteristics on KSPD well correlated with those on Bayley III. The developmental outcomes of Japanese VLBW infants were verified by the two tests. (c) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
  • Prakesh S. Shah, Kei Lui, Gunnar Sjörs, Lucia Mirea, Brian Reichman, Mark Adams, Neena Modi, Brian A. Darlow, Satoshi Kusuda, Laura San Feliciano, Junmin Yang, Stellan Håkansson, Rintaro Mori, Dirk Bassler, Josep Figueras-Aloy, Shoo K. Lee, Nadia Badawi, Peter Marshall, Paul Craven, Karen Simmer, Jacqueline Stack, Dan Casalaz, Elizabeth Carse, Lucy Cooke, Vijay Shingde, David Cartwright, Rod Hunt, Charles Kilburn, Peter Dargaville, Kei Lui, Mary Paradisis, Ingrid Rieger, Carl Kuschel, Andrew Numa, Hazel Carlisle, Guan Koh, Chad Andersen, Melissa Luig, Nicola Austin, Roland Broadbent, Lindsay Mildenhall, Malcolm Battin, David Bourchier, Vaughan Richardson, Anne Synnes, Nicole Rouvinez-Bouali, Bruno Piedboeuf, Barbara Bulleid, Wendy Yee, Nalini Singhal, Adele Harrison, Cherrie Tan-Dy, Sandesh Shivananda, Kenneth Tan, Andrew James, Molly Seshia, Keith Barrington, Francine Lefebvre, Doug McMillan, Wayne Andrews, Lajos Kovacs, Kimberly Dow, Maxine Clarke, Patricia Riley, Prakesh Shah, Arne Ohlsson, Khalid Aziz, Abraham Peliowski, Zenon Cieslak, Todd Sorokan, Zarin Kalapesi, Abraham Ninan, Koravangattu Sankaran, Daniel Faucher, Keith Barrington, Gerarda Cronin, Roderick Canning, Orlando da Silva, David Lee, Cecil Ojah, Michael Dunn, Eli Heymann, Shmuel Zangen, Amir Kushnir, Francis Mimouni, David Bader, Avi Rothschild, Zipora Strauss, Clari Felszer, Jamalia Jeryes, Smadar Even Tov-Friedman, Benjamin Bar-Oz, Michael Feldman, Nizar Saad, Orna Flidel-Rimon, Meir Weisbrod, Daniel Lubin, Ita Litmanovitz, Shraga Blazer, Eric Shinwell, Leah Sirota, Yousif Nijim, Francis Mimouni, Agneta Golan, Dror Mandel, Vered Fleisher-Sheffer, David Kohelet, Lev Bakhrakh, Satoshi Hattori, Shohei Konishi, Takasuke Amizuka, Takeo Kasai, Ritsuko Takahasi, Hirokazu Arai, Maki Sato, Yayoi Miyazono, Junichi Shimizu, Hiroshi Suzumura, Yumi Kono, Takahiro Inoue, Hiroshi Miyabayashi, Hisanori Sobajima, Rika Ishiguro, Hiroyuki Sato, Satsuki Totsu, Nozomi Ishii, Shigeharu Hosono, Mika Shiraishi, Humihiro Miura, Atsushi Nakao, Hitoshi Yoda, Mitsumasa Shimizu, Kazuo Seki, Yasuhumi Itani, Keiji Suzuki, Atsushi Nemoto, Tomohiko Nakamura, Masaki Wada, Yoshihisa Nagayama, Osamu Numata, Takeshi Futatani, Yasuhisa Ueno, Kazuyuki Iwai, Yoshinori Kono, Shigeru Ooki, Yusuke Nakazawa, Chizuko Suzuki, Taihei Tanaka, Motoki Bonno, Kenji Nakamura, Minako Kihara, Hiroyuki Sano, Atsushi Shiraishi, Atsushi Ohashi, Hiroyuki Ichiba, Kiyoaki Sumi, Seiji Yoshimoto, Yukihiro Takahashi, Takahiro Okutani, Masumi Miura, Fumihide Kato, Shinichi Watabe, Misao Kageyama, Rie Fukuhara, Michiko Hayashitani, Keiko Hasegawa, Kosuke Koyano, Shoko Kobayashi, Shinosuke Akiyoshi, Yusei Nakata, Takeshi Kanda, Hisano Tadashi, Hiroshi Kanda, Masaki Nakamura, Naoko Matsumoto, Masayuki Ochiai, Mikihiro Aoki, Akihiko Kawase, Koichi Iida, Chie Ishihara, Moriyasu Kohama, Ma José Fernández Seara, José Ma Fraga Bermúdez, Andrés Martínez Gutiérrez, María Mercedes Martínez Ayúcar, Carolina Vizcaíno Díaz, José Luis Quiles Durá, María González Santacruz, Ma Anne Feret Siguile, Adela Rodríguez Fernández, Belén Fernández Colomer, Enrique García López, Josep Figuera Aloy, Francesc Botet Mussons, Israel Anquela Sanz, Gemma Ginovart Galiana, Elisenda Moliner Calderon, Antonio Natal Pujol, Alicia Mirada Vives, Martín Iriondo Sanz, Roser Porta, Eva Capdevila Cogul, Laura Castells Vilella, Bruno Alonso Álvarez, José María Montero Macarro, Ana R. Barrio Sacristán, Ma Jesús López Cuesta, Ortiz Tardío, Eugenia Valls Sánchez Puerta, Isabel Benavente Fernández, Juan Mena Romero, María Dolores Martinez Gimenez, Ramón Aguilera Olmos, Ricardo Tosca Segura, Juana Ma Guzmán Cabañas, Ma Dolores Huertas Muñoz, Alberto Trujillo, Luis Fidel Moltó Ripoll, José Antonio Hurtado Suazo, Ana Elena Aldea Romero, Luis Paisán Grisolía, Ana Isabel Garrido Ocana, Eduardo Garcia Soblechero, Ma Yolanda Ruiz del Prado, Inés Esteba Díez, Gema E. González-Luis, Fermín García-Muñoz Rodrigo, Emilio Álvaro Iglesias, Fernando Fernandez Calvo, Eduard Solé Mir, Jordi Garcia Martí, Roberto Ortiz Movilla, Lucía Cabanillas Vilaplana, Marta García San Miguel, Isabel Llana Martín, María Fernández Díaz, Jesús Pérez Rodríguez, Sofía Salas, Carmen Muñoz Labian, Carmen González Armengod, Laura Domingo Comeche, Tomás Sánchez Tamayo, Manuel García del Río, José Ángel Alonso Gallego, José María Lloreda Garcia, Javier Vilas González, Ocampo, Nieves Balado Insunza, Pilar García González, Mercedes Granero Asencio, Antonia López Sanz, Carmen Macías Díaz, Araceli Ferrari Cortés, Pedro Amadeo Fuster Jorge, Santiago López Mendoza, Sabina Romero Ramírez, Ma del Mar Albújar Font, Alicia de Ureta Huertas, Antonio Arroyos Plana, Javier Estañ Capell, Vicente Roqués, F. Morcillo, Sara Marín, María Fernanda Omaña, Gabriel Saitua Iturriaga, Jiri Kofron, Katarina Strand Brodd, Andreas Odlind, Lars Alberg, Sofia Arwehed, Eva Engström, Anna Kasemo, Charlotte Ekelund, Lars Åhman, Fredrik Ingemarsson, Laura Österdahl, Pernilla Thurn, Eva Albinsson, Bo Selander, Fredrik Lundberg, Ingela Heimdahl, Ola Hafström, Erik Wejryd, Johanna Kuusima-Löfbom, Ellen-Elisabeth Lund, Annelie Thorén, Boubou Hallberg, Eva Berggren Broström, Torbjörn Hertzberg, Björn Stjernstedt, Johan Robinson, Aijaz Farooqi, Erik Normann, Magnus Fredriksson, Anders Palm, Åsa Hedblom, Kenneth Sjöberg, Leif Thorbjörnsson, Andreas Ohlin, Rein Florell, Agneta Smedsaas-Löfvenberg, Philipp Meyer, Claudia Anderegg, Sven Schulzke, Mathias Nelle, Bendicht Wagner, Walter Bär, Grégoire Kaczala, Riccardo E. Pfister, Jean-François Tolsa, Matthias Roth, Thomas M. Berger, Bernhard Laubscher, Andreas Malzacher, John P. Micallef, Lukas Hegi, Dirk Bassler, Romaine Arlettaz, Vera Bernet, Santanu Bag, Jonathan Kefas, Oliver Rackham, Arumugavelu Thirumurgan, Bill Yoxall, Tim McBride, Delyth Webb, Laweh Amegavie, Ahmed Hassan, Priyadarshan Ambadkar, Mark Dyke, Seif Babiker, Susan Rubin, Amanda Ogilvy-Stuart, Nagesh Panasa, Paul Settle, Jonathan Moise, Ngozi Edi-Osagie, Carrie Heal, Jacqeline Birch, Abdul Hasib, Aung Soe, Niraj Kumar, Hamudi Kisat, Vimal Vasu, Meera Lama, Richa Gupta, Chris Rawlingson, Tim Wickham, Karin Schwarz, Van Sommen, Sara Watkin, Aashish Gupta, Narendra Aladangady, Imdad Ali, Lesley Alsford, Khalid Mannan, Ebel Rainer, Nicholas Wilson, Mark Thomas, Ramnik Mathur, Michele Cruwys, Sunit Godambe, Sunit Godambe, Timothy Watts, Jauro Kuna, John Chang, Jon Filkin, Charlotte Huddy, Ruth Shephard, Krzystof Zieba, Patti Rao, Andrew Currie, Andrew Currie, Azhar Manzoor, Munir Ahmed, Phil Simmons, Julie Nycyk, Phil Simmons, Andrew Gallagher, Chrisantha Halahakoon, Sanjeev Deshpande, Anand Mohite, Kate Palmer, Alan Gibson, Mehdi Garbash, Mithilesh Lal, Majd Abu-Harb, Mehdi Garbash, Róisín McKeon-Carter, Michael Selter, Paul Munyard, Vaughan Lewis, Mala Raman, Graham Whincup, Abdus Mallik, Philip Amess, Charles Godden, Philip Amess, Peter Reynolds, Indranil Misra, Naveen Shettihalli, Peter De Halpert, Sanjay Salgia, Rekha Sanghavi, Ruth Wigfield, Abby Deketelaere, Minesh Khashu, Michael Hall, Charlotte Groves, Nick Brown, Nick Brennan, Katia Vamvakiti, Mal Ratnayaka, Simon Pirie, Stephen Jones, Paul Mannix, David Harding, Megan Eaton, Karin Schwarz, David Gibson, Lawrence Miall, David Gibson
    Journal of Pediatrics 177 144 - 152.e6 2016年 [査読有り][通常論文]
     
    Objective To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. Study design We included 58 004 infants born weighing < 1500 g at 240–316 weeks' gestation from databases in Australia/New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the United Kingdom. We compared a composite outcome (mortality or any of grade ≥3 peri-intraventricular hemorrhage, periventricular echodensity/echolucency, bronchopulmonary dysplasia, or treated retinopathy of prematurity) between each country and all others by using standardized ratios and pairwise using logistic regression analyses. Results Despite differences in population coverage, included neonates were similar at baseline. Composite outcome rates varied from 26% to 42%. The overall mortality rate before discharge was 10% (range: 5% [Japan]-17% [Spain]). The standardized ratio (99% CIs) estimates for the composite outcome were significantly greater for Spain 1.09 (1.04-1.14) and the United Kingdom 1.16 (1.11-1.21), lower for Australia/New Zealand 0.93 (0.89-0.97), Japan 0.89 (0.86-0.93), Sweden 0.81 (0.73-0.90), and Switzerland 0.77 (0.69-0.87), and nonsignificant for Canada 1.04 (0.99-1.09) and Israel 1.00 (0.93-1.07). The adjusted odds of the composite outcome varied significantly in pairwise comparisons. Conclusions We identified marked variations in neonatal outcomes between countries. Further collaboration and exploration is needed to reduce variations in population coverage, data collection, and case definitions. The goal would be to identify care practices and health care organizational factors, which has the potential to improve neonatal outcomes.
  • Ken Miyazaki, Madoka Furuhashi, Kaoru Ishikawa, Koji Tamakoshi, Kazutoshi Hayashi, Akihiko Kai, Hiroshi Ishikawa, Nao Murabayashi, Tomoaki Ikeda, Yumi Kono, Satoshi Kusuda, Masanori Fujimura
    JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 29 2 331 - 337 2016年01月 [査読有り][通常論文]
     
    Objective: To evaluate the short- and long-term outcomes among very low birth weight (VLBW) preterm infants after histologic chorioamnionitis (HCA).Methods: We performed a retrospective analysis of 5849 single infants (birth weight <1500g) born at a gestational age between 22+0 and 33+6 weeks. Clinical data were obtained from the Neonatal Research Network Japan between 2003 and 2007. Multivariable logistic regression analyses were performed to assess the effect of HCA on short- and long-term outcome.Results: According to logistic regression analysis, HCA was associated with lower incidence of respiratory distress syndrome (odds ratio [OR]=0.54; p<0.001), increased chronic lung disease (OR=1.68; p<0.001) and sepsis (OR=1.71; p<0.001) and as a short-term outcomes. There was no significant association with intraventricular hemorrhage (OR=1.11; p=0.33), periventricular leukomalacia (OR=1.07; p=.070) and death before discharge (OR=0.97; p=0.084). HCA was associated with increased home oxygen therapy (OR=3.09; p<0.001), but not with cerebral palsy (CP; OR=0.91; p=0.63), develop quotient<70 (OR=1.27; p=0.17), visual impairment (OR=1.08; p=0.77), severe hearing impairment (OR=1.28; p=0.62) and death (OR=0.98; p=0.91) before three years of age.Conclusions: In this retrospective population-based study in Japan, HCA was not a risk factor for death, neurodevelopmental impairment and CP in VLBW three-year-old preterm infants.
  • Ken Miyazaki, Madoka Furuhashi, Kaoru Ishikawa, Koji Tamakoshi, Kazutoshi Hayashi, Akihiro Kai, Hiroshi Ishikawa, Nao Murabayashi, Tomoaki Ikeda, Yumi Kono, Satoshi Kusuda, Masanori Fujimura
    ARCHIVES OF GYNECOLOGY AND OBSTETRICS 292 6 1239 - 1246 2015年12月 [査読有り][通常論文]
     
    Purpose To evaluate the effect of antenatal corticosteroids (AC) therapy on short- and long-term outcomes among very low birth weight preterm infants after histologic chorioamnionitis (HCA). Methods We performed a retrospective analysis of 5240 single very low birth weight (VLBW) infants born at 22 + 0 and 33 + 6 weeks of gestation between 2003 and 2007, who registered to the Neonatal Research Network Japan. The effects of AC therapy on mortality, neurodevelopmental outcomes at 3 years of age and neonatal morbidities were analyzed in the groups with or without HCA using logistic regression analysis. Results In the study subjects, 840 were with HCA, 2734 were without HCA, and 1666 were excluded without data for HCA. AC therapy was significantly associated with decreasing mortality before 3 years of age; [0.52 (0.32-0.86)], [odds ratio (95 % confidence intervals]. There were no differences between the two groups regarding neurodevelopmental outcomes, including cerebral palsy [0.90 (0.41-1.99)], development quotient < 70 [0.93 (0.48-1.81)], visual impairment [0.46 (0.04-5.18)], and severe hearing impairment [4.00 (0.30-53.4)] in the group with HCA as well as without HCA. Regarding neonatal morbidities, AC therapy was associated with a lower incidence of respiratory distress syndrome [0.67 (0.50-0.91)], sepsis [0.62 (0.41-0.94)], late-onset adrenal insufficiency [0.62 (0.39-0.98)] and an increased incidence of chronic lung disease [1.62 (1.18-2.24)] in the group with HCA. In the group without HCA, AC therapy was associated with decreasing respiratory distress syndrome [0.60 (0.43-0.84)] and increasing chronic lung disease [1.34 (1.11-1.62)]. Conclusion AC therapy is significantly associated with reduced mortality before 3 years of age in VLBW infants with HCA, but not with neurodevelopmental outcomes, which was same as the results found in infants without HCA. AC therapy is recommended for women with suspected chorioamnionitis, as well as those without chorioamnionitis.
  • Hironori Shimozawa, Yumi Kono, Miyuki Matano, Yume Suzuki, Yasunori Koike, Yukari Yada, Takanori Yamagata, Naoto Takahashi
    PEDIATRICS INTERNATIONAL 57 6 1211 - 1214 2015年12月 [査読有り][通常論文]
     
    We studied the cytokine profile of two siblings with neonatal lupus erythematosus (NLE) born to a mother positive for serum anti-Ro and -La antibodies, who did not receive any medication during the two pregnancies. The first sibling was found to have complete atrioventricular block in utero and became severely ill after birth. He fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis on day 2. The second sibling did not have any fetal symptoms. He was generally stable after birth, but with typical skin rash. Laboratory data suggested that they both had hypercytokinemia during the neonatal period, requiring corticosteroid treatment. Interleukin (IL)-6, interferon-gamma, IL-8 and monocyte chemotactic protein-1 were elevated in both cases, while IL-12, IL-13 and IL-17 were elevated only in the second sibling. Comparison of the cytokine profiles suggests the potential roles of different cytokines in the onset and clinical manifestations of NLE.
  • Hidehiko Maruyama, Naohiro Yonemoto, Yumi Kono, Satoshi Kusuda, Masanori Fujimura
    PLOS ONE 10 9 e0139014  2015年09月 [査読有り][通常論文]
     
    IntroductionThis study aimed to assess whether weight growth velocity (WGV) predicts neurodevelopmental outcomes in extremely low birth weight infants (ELBWIs).MethodsSubjects were infants who weighed 501-1000 g at birth and were included in the cohort of the Neonatal Research Network of Japan (2003-2007). Patel's exponential model (EM) method was used to calculate WGV between birth and discharge. Assessment of predictions of death or neurodevelopmental impairment (NDI) was performed at 3 years of age based on the WGV score, which was categorized by per one increase in WGV. Multivariate logistic regression analysis was used to calculate adjusted odds ratios and their 95% confidence intervals (95%CI).ResultsIn the 2961 ELBWIs assessed, the median WGV was 10.5 g/kg/day (interquartile, 9.41-1.9). With the categorical approach, the adjusted odds ratios for death or NDI with WGV scores of 6 and 7 were 2.41 (95% CI, 1.60-3.62) and 1.81 (95% CI, 1.18-2.75), respectively, relative to the reference WGV score of 10. WGV scores >= 8 did not predict death or NDI.ConclusionsWGV scores <8 were significant predictors suggesting that values of WGV during hospitalization in a NICU are associated with neurodevelopmental outcomes. Further investigations is necessary to determine whether additional nutritional support may improve low WGV in ELBWIs.
  • Yumi Kono, Akira Oka, Hiroshi Tada, Kazuo Itabashi, Eiko Matsui, Yosikazu Nakamura
    EARLY HUMAN DEVELOPMENT 91 9 499 - 503 2015年09月 [査読有り][通常論文]
     
    Objective: The aim of this study was to elucidate the association between psychosocial and behavioral problems in children at school age and dioxin level in breast milk or estimated dioxin exposure CEDE) through breastfeeding in the general Japanese population. Methods: Dioxin level of breast milk at 1 month of age and breastfeeding ratio through the first year of life were used to calculate the EDE of infants born in 1998-2005 in Japan. The Japanese Social Difficulties Questionnaire (SDQ) for the assessment of children's behavior was sent by mail to mothers whose breast milk underwent the dioxin survey, at the time when their infants were aged 6-13 years. Results: The study subjects were 175 pairs of mothers and their first infants (79 boys, 96 girls). The mean total dioxin levels of breast milk were 18.3 and 19.8 (pgTEQ/g fat) and EDEs were 16.4 and 19.6 (ngTEQ/kg/year) in boys and girls, respectively. In linear multiple regression analyses after adjusting for age at SDQ maternal age, birth weight and maternal smoking habit, dioxin level in breast milk was not significantly related to the total difficulties score (TDS) of SDQ in boys, B = 2.29 (95% CI -7.60-12.18), or in girls, B = 1.04 (95% CI -9.24-7.15). EDE correlated to the TDS in neither boys, B = 0.99 (95% CI 4.14-2.15), nor girls, B = 1.08 (95% CI -2.69-4.85). Conclusion: No evidence was found of a correlation between perinatal dioxin exposure and behavioral and psychosocial problems of children measured by SDQ. These results support the benefits of recommending breastfeeding. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Ryou Kawamata, Yume Suzuki, Yukari Yada, Yasunori Koike, Yumi Kono, Naoto Takahashi
    PEDIATRICS INTERNATIONAL 57 4 614 - 619 2015年08月 [査読有り][通常論文]
     
    BackgroundThe pathogenesis of abdominal symptoms in premature infants with hypothyroxinemia is not understood; therefore, we investigated changes in gut hormones before and after levothyroxine sodium (T4-Na) supplementation in preterm infants with abdominal symptoms and hypothyroxinemia. MethodsIn eight preterm study subjects and 14 gestational age-matched controls, fasting serum concentration of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin and ghrelin was measured using a bead array system. ResultsSerum GLP-1, GIP and PYY in the subjects before T4-Na supplementation were lower than in controls at age 2 weeks. After improvement of abdominal symptoms and free thyroxine, serum levels of the three gut hormones in the subjects were increased and were not different from those in the control patients. ConclusionsIn preterm infants with abdominal symptoms, serum GLP-1, GIP and PYY might be related to thyroid function.
  • Takahashi N, Takahashi K, Kobayashi M, Yada Y, Koike Y, Kono Y
    Cytokine 73 1 101 - 107 2015年05月 [査読有り][通常論文]
     
    Background: The clinical significance of TGF beta isoforms in cord blood is not well understood. Methods: We obtained cord blood samples from 37 term infants and 85 preterm infants who were born in several clinical settings. The serum levels of 3 TGF beta isoforms and of the other 17 cytokines in cord blood were investigated using cytometric bead array technology. Results: Very high levels of TGF beta 1and TGF beta 2 isoforms compared to the level of other cytokines were found; mean levels were 44,180 and 1871 pg/mL, respectively. The levels of all 3 isoforms of TGF beta were significantly correlated with birth weight, and the levels of TGF beta 1 and TGF beta 3 were correlated with gestational age. The levels of TGF beta 1 and beta 2 isoforms were strongly correlated with each other, but not with levels of other cytokines. The levels of TGF beta 1 and TGF beta 2 were ignificantly higher in male infants and significantly lower in infants with fetal growth restriction. The prevalence of chronic lung disease was related to a low level of TGF beta 1, and that of patent ductus arteriosus was related to a high level of TGF beta 1 in preterm infants. Conclusions: TGF beta 1 and TGF beta 2 appeared to play a significant role in physiological and pathological conditions in the fetus. TGF beta isoform levels appear to be regulated independently of those of other cytokines and do not appear to be influenced by inflammation in the fetal period. The role of TGF beta 3 in cord blood and the postnatal chronological changes of the TGF beta isoforms should be investigated in the future. 0 2015 Elsevier Ltd. All rights reserved.
  • Hiroshi Ishikawa, Ken Miyazaki, Tomoaki Ikeda, Nao Murabayashi, Kazutoshi Hayashi, Akihiko Kai, Kaoru Ishikawa, Yoshihiro Miyamoto, Kunihiro Nishimura, Yumi Kono, Satoshi Kusuda, Masanori Fujimura
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 12 4 295 - 300 2015年 [査読有り][通常論文]
     
    Aim: To evaluate the effect of antenatal corticosteroids (ANS) on short-and long-term outcomes in small-for-gestational age (SGA) infants. Methods: A retrospective database analysis was performed. A total of 1,931 single infants (birth weight <1,500 g) born at a gestational age between 22 weeks and 33 weeks 6 days who were determined to be SGA registered in the Neonatal Research Network Database in Japan between 2003 and 2007 were evaluated for short-term outcome and long-term outcome. Results: ANS was administered to a total of 719 infants (37%) in the short-term outcome evaluation group and 344 infants (36%) in the long-term outcome evaluation group. There were no significant differences between the ANS group and the no-ANS group for primary short-term outcome (adjusted odds ratio (OR) 0.73; 95% confidence interval (CI) 0.45-1.20; P-value 0.22) or primary long-term outcome (adjusted OR 0.69; 95% CI 0.40-1.17; P-value 0.17). Conclusions: Our results show that ANS does not affect short-or long-term outcome in SGA infants when the birth weight is less than 1500 g. This study strongly suggests that administration of ANS resulted in few benefits for preterm FGR fetuses.
  • Kawamata R, Suzuki Y, Yada Y, Koike Y, Kono Y, Yada T, Takahashi N
    Journal of pediatric endocrinology & metabolism : JPEM 2014年02月 [査読有り][通常論文]
  • Nozomi Ishii, Yumi Kono, Naohiro Yonemoto, Satoshi Kusuda, Masanori Fujimura
    PEDIATRICS 132 1 62 - 71 2013年07月 [査読有り][通常論文]
     
    OBJECTIVE: To provide instructive information on death and neurodevelopmental outcomes of infants born at 22 and 23 weeks' gestational age. METHODS: The study cohort consisted of 1057 infants born at 22 to 25 weeks in the Neonatal Research Network, Japan. Neurodevelopmental impairment (NDI) at 36 to 42 months' chronological age was defined as any of the following: cerebral palsy, hearing impairment, visual impairment, and a developmental quotient <70. A systematic review was performed by using databases of publications of cohort studies with neonatal and neurodevelopmental outcomes at 22 and 23 weeks. RESULTS: Numbers and incidences (%) of infants with death or NDI were 60 (80%) at 22 weeks and 156 (64%) at 23 weeks. In logistic regression analysis, gestational ages of 22 weeks (odds ratio [OR]: 5.40; 95% confidence interval [CI]: 2.48-11.76) and 23 weeks (OR: 2.14; 95% CI: 1.38-3.32) were associated with increased risk of death or NDI compared with 24 weeks, but a gestational age of 25 weeks (OR: 0.65; 95% CI: 0.45-0.95) was associated with decreased risk of death or NDI. In the systematic review, the medians (range) of the incidence of death or NDI in 8 cohorts were 99% (90%-100%) at 22 weeks and 98% (67%-100%) at 23 weeks. CONCLUSIONS: Infants born at 22 and 23 weeks' gestation were at higher risk of death or NDI than infants at born at 24 weeks. However, outcomes were improved compared with those in previous studies. There is a need for additional discussions on interventions for infants born at 22 or 23 weeks' gestation.
  • Satohiko Yanagisawa, Kosaku Maeda, Yuko Tazuke, Yuki Tsuji, Insu Kubota, Yasunori Koike, Yukari Yada, Yumi Kono, Naoto Takahashi, Shigeki Matsubara
    Journal of Obstetrics and Gynaecology Research 39 5 974 - 978 2013年05月 [査読有り][通常論文]
     
    Aim: Assisted reproductive technology (ART) has increased the incidences of multiple gestations and low birth weights, which frequently warrant pediatric surgery. ART may have also increased the rate of birth defects. In this study, we aimed to determine whether infants conceived after ART required neonatal surgery more frequently compared with naturally conceived infants. Material and Methods: Our study population comprised 1891 infants (160 ART (+) and 1731 ART (-)) who were admitted to our neonatal intensive care unit during a 5-year period (January 2006-December 2010) of these, 198 infants (9 ART (+) and 189 ART (-)), with diseases requiring surgery, were referred to pediatric surgeons (consultation cases).We examined the following: (i) factors potentially increasing the requirement for surgery (ii) frequency of birth defects and (iii) maternal factors that may increase the need for surgery. Results: A significantly higher incidence of multiple gestation and low birth weight was observed in the ART (+) group than the ART (-) group. However, ART did not yield a higher rate of surgery and birth defects: overall, the rate of surgery was 4% (7/160) in the ART (+) group and 8% (143/1731) in the ART (-) group. Of 198 consultation cases, the percentage of infants actually requiring surgery was approximately the same in the ART (+) group (7/9 [78%]) and the ART (-) group (143/189 [76%]). Conclusion: Infants conceived after ART comprised a small proportion of neonatal surgery cases, and did not require surgery more frequently. © 2013 The Authors.
  • Karin Kojima, Naoto Takahashi, Yukari Yada, Yasunori Koike, Miyuki Matano, Yumi Kono, Mariko Y. Momoi
    PEDIATRICS INTERNATIONAL 54 3 409 - 412 2012年06月 [査読有り][通常論文]
  • Yumi Kono, Jun Mishina, Naohiro Yonemoto, Satoshi Kusuda, Masanori Fujimura
    PEDIATRICS INTERNATIONAL 53 6 1051 - 1058 2011年12月 [査読有り][通常論文]
     
    Background: The aim of this study was to describe and compare neurodevelopmental outcomes with birthweight (BW) groups at 250-g intervals of very-low-birthweight (VLBW) infants at 3 years of age in a multicenter cohort in Japan. Methods: A total of 3104 VLBW infants born in 2003 and 2004 registered in a NICU-network database were followed in the study. Neurodevelopmental impairment (NDI) was defined as any of the following impairments: cerebral palsy, unilateral or bilateral blindness, severe hearing impairment, or developmental delay; a developmental quotient (DQ) <70 measured using the Kyoto Scale of Psychological Development test or judged by physicians in infants without the test. Results: A total of 257 infants died and follow-up data were obtained from 1826 infants. Of the 1826 infants, 155 (8.5%) had cerebral palsy, 25 (1.4%) had visual impairment, and 12 (0.7%) had hearing impairment. Of the 1197 infants in whom DQ was measured, 184 (15.4%) had DQ < 70. The proportion of NDI in the evaluated infants was 19.2% (n = 350), ranging from 11.9% (BW 1251-1500 g) to 42.0% (BW <= 500 g). Odds ratios (95% CI) of NDI or death against the group BW 1251-1500 g were 20.62 (13.29-31.97) in BW <= 500 g, 7.25 (5.45-9.64) in BW 501-750 g, 2.85 (2.12-3.82) in BW 751-1000 g and 1.18 (0.85-1.64) in BW 1001-1250 g. Conclusion: The increasing proportion of NDI or death, an indicator of adverse outcome, was associated with decrement in the BW of the groups. Although we have to consider a bias due to loss of follow-up data, the incidence of NDI was similar to previous overseas cohort studies despite the higher survival proportion in our study.
  • Yumi Kono, Jun Mishina, Naohiro Yonemoto, Satoshi Kusuda, Masanori Fujimura
    PEDIATRICS INTERNATIONAL 53 6 930 - 935 2011年12月 [査読有り][通常論文]
     
    Background: The aim of the present study was to explore the relationships among neonatal morbidity, interventions and death or adverse neurodevelopmental outcomes in very low-birthweight (VLBW) infants. Methods: Subjects were infants with birthweight 21500 g who were cared for in the tertiary neonatal intensive care units in Japan. Multiple logistic regression analysis was performed to examine the odds ratios (OR) and 95% confidence intervals (CI) of neonatal factors for death or cerebral palsy (CP) and death or developmental delay (developmental quotient < 70 or delay judged by physicians) at 3 years of age after adjusting for biological and prenatal variables. Results: Of the 3104 subjects, 257 died and 1826 were evaluated at 3 years of age. Cystic periventricular leukomalacia (PVL; OR, 23.9; 95% CI: 11.0-51.7), gastrointestinal perforation (OR, 8.5; 95% CI: 2.8-25.4), intraventricular hemorrhage (IVH) grade 3 or 4 (OR, 3.1; 95% CI: 1.3-7.2) and sepsis (OR, 2.6; 95% CI: 1.4-4.8) were neonatal factors significantly associated with an increased risk of death or CP. Significant correlates with death or developmental delay were cystic PVL (OR, 7.9; 95% CI: 3.7-16.8), gastrointestinal perforation (OR, 6.3; 95% CI: 1.9-20.8), sepsis (OR, 2.8; 95% CI: 1.6-4.8), IVH grade 3 or 4 (OR, 2.6; 95% CI: 1.2-5.7), chronic lung disease at 36 weeks of corrected gestational age (OR, 1.6; 95% CI: 1.1-2.4) and treatment for retinopathy of prematurity (ROP; OR, 1.5; 95% CI: 1.0-2.3). Conclusion: Cystic PVL, gastrointestinal perforation, IVH and sepsis correlated with both death or CP and death or developmental delay in VLBW infants. Chronic lung disease at 36 weeks and treatment for ROP were associated with death or developmental delay, but not with death or CP.
  • Kawamata R, Takahashi N, Yada Y, Koike Y, Kono Y, Momoi MY
    Pediatrics international : official journal of the Japan Pediatric Society 53 386 - 388 3 2011年06月 [査読有り][通常論文]
  • 【周産期医療の向上を目指して-予知・予防・治療とシステムの最前線-[新生児編]】新しい新生児医療システム 新生児臨床研究ネットワークNRN(neonatal research network)
    藤村 正哲, 平野 慎也, 楠田 聡, 森 臨太郎, 河野 由美, 青谷 裕文
    母子保健情報 62 81 - 87 (福)恩賜財団母子愛育会 2010年11月
  • Maho Ichikawa, Naoto Takahashi, Yukari Yada, Yasunori Koike, Ryou Kawamata, Yumi Kono, Yoko Honma, Shigeru Yotsumoto, Mariko Y. Momoi
    Pediatrics 126 1 e247 - e250 2010年07月 [査読有り][通常論文]
     
    We present here the unusual case of a male newborn infant who showed progressive severe cholestasis. The infant's gestational age was 37 weeks, and his birth weight was 2134 g. His serum level of direct bilirubin gradually increased from the 6th day of life and reached 257.5 μmol/L on the 22nd day of life. We could not find any cause for his cholestasis, but his serum level of ferritin was extremely elevated at 9211.0 ng/mL. Because we felt that his clinical condition might be related to hypercytokinemia caused by an immunologic reaction, steroid pulse therapy and cyclosporine were administered. His condition improved, and his direct bilirubin and ferritin levels declined. From the investigation of his cytokine profile, we found a preferentially elevated level of serum interleukin 17 (IL-17) (96.1 pg/mL) and high level of chemokines IL-8 and macrophage inflammatory protein 1β. The IL-17 level gradually decreased to 7.5 pg/mL by the 124th day of life. The infant was successfully discharged from the children's hospital but later developed epilepsy at 11 months and asthma at 1 year, 2 months of age. Although we have not yet reached a definitive diagnosis, this case may be the first to show a relationship between cholestasis and an elevated serum IL-17 level in the neonatal period. Copyright © 2010 by the American Academy of Pediatrics.
  • Koji Yokoyama, Naoto Takahashi, Yukari Yada, Yasunori Koike, Ryou Kawamata, Ritei Uehara, Yumi Kono, Yoko Honma, Mariko Y. Momoi
    EARLY HUMAN DEVELOPMENT 86 3 187 - 191 2010年03月 [査読有り][通常論文]
     
    Background: Magnesium sulfate (MgSO(4)) has been used as a tocolytic agent in cases of refractory preterm labor. Prolonged maternal administration of MgSO(4) may induce bone demineralization in the neonate. However, the effects of MgSO(4) on serum biochemistry related to bone metabolism in neonates remain unclear. Aim: To assess the effects of prolonged maternal administration of MgSO(4) on fetuses and neonates. Study design: This retrospective case-control study examined 167 neonates. Cases comprised 58 neonates whose mothers had received intravenous MgSO(4) administration for > 5 days. Neonatal serum levels of magnesium (Mg), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were reviewed. We also investigated whether subject neonates showed appearance of osteopenia at the metaphyseal lines on radiography at birth. Results: Mean serum Mg and P levels were significantly higher, and Ca levels were significantly lower, in cases than in controls at birth. Mean serum ALP level was 1188.5 IU/l in cases, significantly higher than that in controls at birth. Bone abnormalities were noted on radiography in 2 subjects. By 3 weeks old, serum ALP levels did not differ significantly between cases and controls. Logistic regression analysis revealed maternal administration of MgSO(4) and multiple pregnancies were significantly related to serum ALP level in neonates at birth. Conclusion: Prolonged maternal administration of MgSO(4) significantly affects neonatal serum biochemistry related to bone metabolism. Potential long-term adverse effects on neonates and how Mg affects fetal bone metabolism in utero need to be investigated in future studies. (c) 2010 Elsevier Ireland Ltd. All rights reserved.
  • Yumi Kono, Jun Mishina, Noriko Sato, Toyoko Watanabe, Yoko Honma
    Pediatrics International 50 1 23 - 28 2008年02月 [査読有り][通常論文]
     
    Background: The objective of the present study was to describe developmental profiles of very low-birthweight (VLBW) infants compared by birthweight, because those of infants with birthweight < 750 g might be different from other VLBW infants. Methods: VLBW infants from four medical centers were followed at each site with the same protocol at 18 months' corrected age. The protocol by the Society for the Study of Follow up for High-Risk Infants, which includes a standardized developmental test, the Kyoto Scale of Psychological Development (KSPD), was used. Five hundred and sixty-four VLBW infants without neurological or neurosensory impairment were divided into four groups using 250 g birthweight intervals and outcomes were compared between the four groups. Results: Developmental characteristics of extremely low-birthweight infants (birthweight < 750 g) in comparison with other VLBW infants were as follows: (i) more infants were judged clumsy in their fine motor skills (ii) fewer were able to speak meaningful words although they were able to understand oral simple orders (iii) developmental quotients (DQ) of KSPD was significantly lower and (iv) more infants were judged as hyperactive. Conclusion: Developmental profiles of VLBW infants without major handicaps at 18 months' corrected age correlated significantly with their birthweight sequence. These results provide useful information on developmental outcomes of VLBW infants. © 2008 Japan Pediatric Society.
  • Yumi Kono, Jun Mishina, Tomoko Takamura, Hitoshi Hara, Izumi Sakuma, Satoshi Kusuda, Hiroshi Nishida
    Journal of Perinatal Medicine 35 5 447 - 454 2007年10月 [査読有り][通常論文]
     
    Aim: To evaluate factors affecting survival and long-term outcome of extremely premature infants and to determine whether small for gestational age (SGA) status is an additional risk factor. Methods: Survival was analyzed in 193 infants born between 23 and 27 weeks of gestational age (GA) and compared between SGA (n=43) and appropriate for gestational age (AGA) infants. Long-term outcome was assessed in 123 infants at six years of chronological age by neurological evaluation and cognitive tests. Results: The long-term survival rates were 72.1% for SGA and 84.0% for AGA infants. Significant independent factors affecting survival were GA (OR 1.79 for one week advance, 95% CI 1.36-2.34) and SGA (OR 0.42, 95% CI 0.18-0.997) in comparison with AGA. There were no significant differences in rates of cerebral palsy or mental retardation, 12.0% and 24.0% in SGA, 14.3% and 17.3% in AGA, respectively. Fifty-two percent of SGA and 70% of AGA infants had intact long-term outcome. The perinatal factor found to affect the intact long-term outcome was RDS with surfactant therapy (OR 0.17, 95% CI 0.07-0.45). Conclusion: SGA status as well as short gestation had significant effects on survival. Respiratory complications after birth had a larger detrimental effect on long-term outcome than whether the infant was SGA or AGA. ©2007 by Walter de Gruyter.
  • Yumi Kono, Shin'ichi Okada, Yusaku Tazawa, Susumu Kanzaki, Tetsuo Mura, Etsuko Ueta, Eiji Nanba, Yuzuru Otsuka
    Pediatrics International 44 5 481 - 487 2002年 [査読有り][通常論文]
     
    Background: The aim of this study was to assess the response to dioxin-induced oxidative stress in neonates via lactation in the model we have described previously. Methods: Maternal rats were treated with a single dose of 50 or 100 μmol/kg 1,2,3,4-tetrachlorodibenzo-p-dioxin (TCDD) on the first day postpartum (day 1). Messenger RNA levels of the key anti-oxidant enzymes (AOE), phospholipid hydroperoxide-glutathione peroxidase (PH-GPx), cellular-glutathione peroxidase (cell-GPx), copper-zinc superoxide dismutase (CuZn SOD), manganese superoxide dismutase (Mn SOD) and catalase (CAT) in the neonatal and maternal livers were determined by a competitive reverse transcription-polymerase chain reaction method. Results: Lactational transfer of 1,2,3,4-TCDD induced an inhibition of PH-GPx and cell-GPx mRNA in the neonatal liver on day 2 to 68 (P < 0.01) and 62% (P < 0.05) of the control at 100 μmol/kg, respectively. Both GPx mRNA returned to control levels on day 6 and thereafter increased to levels higher than the controls on day 10. In the dam rat, 10 days after the treatment, no remarkable change of PH-GPx or cell-GPx mRNA was observed. Copper-zinc superoxide dismutase and CAT mRNA of neonates on day 2 were also suppressed at 100 μmol/kg and then slightly increased on day 10. However, Mn SOD mRNA was not suppressed, but increased to a 2.1-fold level of the control (P < 0.05) on day 10 with 100 μmol/kg 1,2,3,4-TCDD. Conclusion: Quantitative analysis of AOE mRNA showed that PH-GPx and cell-GPx mRNA, as well as CuZn SOD and CAT mRNA in the neonatal liver were suppressed for a short period of time by 1,2,3,4-TCDD exposure via lactation. Dioxin induced oxidative stress by lactational transfer may alter pretranslation regulation of protective AOE in neonates.
  • Yumi Kono, Shin'Ichi Okada, Yusaku Tazawa, Susumu Kanzaki, Tetsuo Mura, Etsuko Ueta, Eiichi Nanba, Yuzuru Otsuka
    Pediatrics International 43 5 458 - 464 2001年 [査読有り][通常論文]
     
    Background and Methods: The aim of this study was to assess the effect of lactational exposure to dioxins in neonates on the cytochrome P450 1A1 (CYP1A1) induction in the level of gene expression. Maternal rats were treated with a single dose of 50 or 100 μmol/kg 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD), a low potent congener of dioxins, on the first day post-partum (day 1). Induction of CYP1A1 mRNA expression was quantitatively analyzed by the competitive reverse transcription-polymerase chain reaction (RT-PCR) method. Results: The CYP1A1 mRNA was detectable at extremely low amounts in the liver of control neonates and mothers. The mRNA ratios of CYP1A1 to β-actin in neonates were dose-dependently increased by the treatment of 1,2,3,4-TCDD of their mothers. Its peak occurred on day 6 and was sustained at the same level on day 10. Increases of the ratio with 100 μmol/kg 1,2,3,4-TCDD on day 2, 6 and 10 were 26-, 40- and 40-fold of the appropriate controls, respectively. These levels paralleled the activity of ethoxyresorufin-o-deethylase, representing CYP1A mediated monooxygenase. In the mother, the mRNA ratio was increased only to threefold of the control, 10 days after treatment. Conclusion: Current RT-PCR procedure enabled to assess both constitutive and induced levels of CYP1A1 mRNA in the neonatal rat livers. Although the dose of 1,2,3,4-TCDD selected in this study was about 5000 times higher than the daily intake of dioxins in breast-fed infants, CYP1A1 mRNA was highly induced for a longer period of time in neonatal rats receiving 1,2,3,4-TCDD via lactation than the treated maternal rats.
  • Jasper Zu Putlitz, Eve A. Roberts, Stefan Wieland, Yumi Kono, Hubert E. Blum
    Virus Research 52 2 177 - 182 1997年12月 [査読有り][通常論文]
     
    Transient transfection and in vitro infection experiments were performed to characterize replication and antigen synthesis of the hepatitis B virus (HBV) in human hepatocyte lines HH29 and HHY41, derived from normal liver tissue. These liver cell lines are capable of supporting HBV replication and gene expression at levels similar to the human hepatoma cell line HuH-7. Strikingly, a very tight adhesion of HBV to the outer cell membrane of HH29 and HHY41 was observed under conditions that removed HBV to undetectable levels from HuH-7 hepatoma cells. However, no productive HBV infection could be established in these cells as determined by the absence of viral transcripts and de novo antigen synthesis. In conclusion, the human hepatocyte cell lines HH29 and HHY41 may be useful to study important aspects of late steps in the replication of HBV, but appear to lack certain cellular components that play a pivotal role during early steps of the viral life cycle.
  • Yumi Kono, Maki Fukunaga, Kazuo Shikari, Hideo Akiyoshi
    Tohoku Journal of Experimental Medicine 181 1 9 - 18 1997年01月 [査読有り][通常論文]
     
    The effects of cytochalasin B and colchicine on the structure and function of bile canaliculi were studied in neonatal rat hepatocytes in primary culture. Cellular contacts of neonatal hepatocytes were not as tight as those of adult hepatocytes. There was no remarkable difference in the ultrastructure of bile canaliculi between neonatal and adult hepatocytes. Neonatal hepatocytes treated with cytochalasin B were round in shape and aggregated in groups of several cells. Actin filaments stained by rhodamine-phalloidin were disrupted and condensed at the cell periphery or around dilated bile canaliculi. Markedly-dilated bile canaliculi with less microvilli were observed by transmission electron microscopy while the secretory function of horseradish peroxidase, which was used as a marker for uptake, transport and secretion into bile canaliculi, were maintained. The lumen of dilated bile canaliculi was found close to the undersurfaces of hepatocytes by scanning electron microscopy after turning over the cultured cells. By colchicine treatment the filamentous structure of microtubules in neonatal hepatocytes disappeared. The ultrastructure of the bile canaliculi was not affected by the treatment, but transport and secretion of horseradish peroxidase into bile canaliculi were inhibited. The development of strict cellular polarity in neonatal hepatocytes may be suppressed in neonatal hepatocytes however, cholestatic agents which rearrange the cytoskeleton caused the same morphological or functional changes of bile canaliculi as in adult hepatocytes.
  • Yumi Kono, Eve A. Roberts
    Biochemical and Biophysical Research Communications 220 3 628 - 632 1996年03月 [査読有り][通常論文]
     
    Liver-specific functions were examined in two novel human hepatocyte lines established from normal liver tissue (HH29, HHY41) and one human hepatoma line (Hep G2), cultured either in a collagen gel sandwich configuration or on plain plastic dishes. At confluence, levels of albumin and a-fetoprotein mRNA were markedly increased in all lines cultured in the collagen gel sandwich over those on plastic, while levels of mRNA for mitochondrial elongation factor (EFTU), a ubiquitous enzyme, were equivalent. Secretion of albumin by cells cultured in the collagen gel sandwich was significantly increased in parallel with the abundance of albumin mRNA. Hepatocytes in the collagen gel sandwich configuration secreted α-fetoprotein of a higher molecular weight in addition to α-fetoprotein of standard molecular weight. The three-dimensional configuration of the collagen gel sandwich enhances the expression of liver-specific functions of human hepatocytes from continuous cell lines, probably by preserving proper cellular polarity in vitro.

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