Kobayashi, Sakiko

写真a

Affiliation

Research Centers and Institutes, Health Center (Hiyoshi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)
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Academic Background 【 Display / hide 】

  • 1992.04
    -
    1998.03

    Keio University, 医学部, 医学科

    University, Graduated

  • 2000.04
    -
    2004.03

    Keio University, 医学部

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 医学博士, Keio University, Coursework, 2005.02

    Ubc9 interacts with chicken ovalbumin upstream promoter-transcription factor I and represses receptor-dependent transcription.

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Research Areas 【 Display / hide 】

  • Life Science / Nephrology

  • Life Science / Metabolism and endocrinology

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Papers 【 Display / hide 】

  • Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    Sankoda A., Suzuki H., Imaizumi M., Yoshihara A., Kobayashi S., Katai M., Hamada K., Hidaka Y., Yoshihara A., Nakamura H., Kubota S., Kakita-Kobayashi M., Iwase A., Sugiyama T., Ota E., Arata N.

    Thyroid 34 ( 4 ) 519 - 530 2024.04

    ISSN  10507256

    　View Summary

    Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

  • Ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastoma

    Mikoshiba T., Sekimizu M., Saito S., Nakamura S., Nagai R., Kawaida M., Kurihara I., Kobayashi S., Ozawa H.

    Endocrine-Related Cancer 31 ( 9 )  2024

    ISSN  13510088

    　View Summary

    Olfactory neuroblastomas rarely secrete adrenocorticotropic hormone, leading to ectopic adrenocorticotropic hormone syndrome. However, the prevalence, timing, and triggers of ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastomas remain unclear. This study aimed to investigate these factors and conduct a literature review. Fifteen patients with olfactory neuroblastomas who underwent surgery at our institution were included. The prevalence of ectopic adrenocorticotropic hormone syndrome development was assessed by evaluating adrenocorticotropic hormone expression using immunohistochemistry. Furthermore, 26 patients with olfactory neuroblastomas who developed ectopic adrenocorticotropic hormone syndrome from previous reports were reviewed. Among the 15 patients, three (20%) showed adrenocorticotropic hormone-positive tumor cells at the time of initial surgery, and two (13%) developed ectopic adrenocorticotropic hormone syndrome. The timing of developing ectopic adrenocorticotropic hormone syndrome was 2.5 and 10 years following the initial treatment of olfactory neuroblastoma. Based on the literature review, nine patients with recurrent and metastatic olfactory neuroblastoma developed ectopic adrenocorticotropic hormone syndrome after the initial surgery, of whom, three had confirmed disease after developing ectopic adrenocorticotropic hormone syndrome, three developed during disease progression, two developed after receiving chemotherapy, and one developed after undergoing a biopsy. The timing of ectopic adrenocorticotropic hormone syndrome was 2.5–15 years after initial treatment. Our study revealed that acknowledging olfactory neuroblastomas can manifest as ectopic adrenocorticotropic hormone syndrome with a certain low prevalence is crucial. Moreover, our study speculated that tumor stimulation, such as biopsy or chemotherapy, as well as disease progression, could trigger ectopic adrenocorticotropic hormone syndrome onset. Thus, olfactory neuroblastomas can develop into ectopic adrenocorticotropic hormone syndrome, even long after the initial treatment.

  • Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification

    Jo R., Shibata H., Kurihara I., Yokota K., Kobayashi S., Murai-Takeda A., Mitsuishi Y., Hayashi T., Nakamura T., Itoh H.

    Hypertension Research 46 ( 1 ) 19 - 31 2023.01

    ISSN  09169636

    　View Summary

    This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. Liquid chromatography–tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295–307. Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus.

  • Lysine-specific demethylase 1 as a corepressor of mineralocorticoid receptor

    Kohata N., Kurihara I., Yokota K., Kobayashi S., Murai-Takeda A., Mitsuishi Y., Nakamura T., Morisaki M., Kozuma T., Torimitsu T., Kawai M., Itoh H.

    Hypertension Research 45 ( 4 ) 641 - 649 2022.04

    ISSN  09169636

    　View Summary

    Mineralocorticoid receptor (MR) and its ligand aldosterone play a central role in controlling blood pressure by promoting sodium reabsorption in the kidney. Coregulators are recruited to regulate the activation of steroid hormone receptors. In our previous study, we identified several new candidates for MR coregulators through liquid chromatography-tandem mass spectrometry analysis using a biochemical approach. Lysine-specific demethylase 1 (LSD1) was identified as a candidate. The relationship between LSD1 and salt-sensitive hypertension has been reported; however, the role of MR in this condition is largely unknown. Here, we investigated the functions of LSD1 as a coregulator of MR. First, a coimmunoprecipitation assay using HEK293F cells showed specific interactions between MR and LSD1. A chromatin immunoprecipitation study demonstrated LSD1 recruitment to the gene promoter of epithelial Na+ channel (ENaC), a target gene of MR. Reduced LSD1 expression by treatment with shRNA potentiated the hormonal activation of ENaC and serum/glucocorticoid-regulated kinase 1, another target gene of MR, indicating that LSD1 is a corepressor of MR. In an animal study, mice with kidney-specific LSD1 knockout (LSD1flox/floxKSP-Cre mice) developed hypertension after a high-salt diet without elevation of aldosterone levels, which was counteracted by cotreatment with spironolactone, an MR antagonist. In conclusion, our in vitro and in vivo studies demonstrated that LSD1 is a newly identified corepressor of MR.

  • Remission of Angiographically Confirmed Minocycline-induced Renal Polyarteritis Nodosa: A Case Report and Literature Review

    Yokota K., Kurihara I., Nakamura T., Nakatsuka S., Miyashita K., Kobayashi S., Murai-Takeda A., Sone M., Itoh H.

    Internal Medicine 61 ( 1 ) 103 - 110 2022

    ISSN  09182918

    　View Summary

    A 23-year-old man presented with severe hypertension. Based on his history of minocycline treatment for over three years and clinical symptoms, such as myalgias and renovascular hypertension with multiple intrarenal aneurysms, he was diagnosed with minocycline-induced renal polyarteritis nodosa (PAN). After minocycline treatment cessation and management of the hypertension, his blood pressure, renin-aldosterone levels, and urinary protein levels gradually improved. Seven and a half years later, repeated angiography found that the aneurysms had resolved. This is the first report in English describing a case of minocycline-induced renal PAN that was reversed functionally and morphologically without steroids or immunosuppressive drugs.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • 原発性アルドステロン症の確定診断における経口食塩負荷試験および立位フロセミドレニン刺激試験の有用性の検討

    村井　彩乃、柴田　洋孝、小林　佐紀子、須田　徳子、横田　健一、栗原　勲、本間　桂子、太田　敦美。林　晃一、齊藤　郁夫、猿田　享男

    第78回日本内分泌学会 (東京) , 

    2005.07
    , 

    Oral presentation (general)

  • 副腎腫瘍症例におけるＡＣＴＨ負荷血中17-hydroxyprogesterone（17OHP)および尿中pregnanetriolonr(Ptl)の検討

    小林　佐紀子、柴田　洋孝、本間　桂子、須田　徳子、横田　健一、村井　彩乃、栗原　勲、林　晃一、齊藤　郁夫、猿田　享男

    第78回日本内分泌学会 (東京) , 

    2005.07
    , 

    Oral presentation (general)

  • COUP-TFI and transcriptional coregulators in adrenal cortical steroidogenesis

    Shibata Hirotaka, Kurihara Isao, Kobayashi Sakiko, Ikeda Yayoi, Yokota Kenichi, Saito Ikuo, Rainey William, White Perrin, Saruta Takao

    The 2nd International Nuclear Receptor Meeting, 

    2003.03
    , 

    Oral presentation (invited, special)

  • 核内受容体COUP-TFに結合する新規転写共役因子CIP-1のクローニング

    Kobayashi Sakiko, Shibata Hirotaka, Kurihara Isao, Hayashi Matsuhiko, Saitou Ikuo, Saruta Takao

    第75回日本内分泌学会学術総会, 

    2002.06
    , 

    Oral presentation (general)

  • Urinary 18-hydroxycortisol level may be a useful clinical marker for differential diagnosis between aldosterone-producing adrenocortical adenoma and hyperplasia

    Shibata Hirotaka, Homma Keiko, Kurihara Isao, Kobayashi Sakiko, Chiba Hiroshi, Kurosawa Takao, Takeshita Eiko, Saito Ikuo, Hayashi Matsuhiko, Saruta Takao

    International Congress of Internal Medicine, 

    2002.05
    , 

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 新規転写共役因子LSD１のMR活性制御及び食塩感受性高血圧発症における意義の解明

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • The role of TET2 in mineralocorticoid receptor mediated transcription through epigenetic mechanisms and development of hypertension

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

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Awards 【 Display / hide 】

  • Young Investigator Travel Grant Award (YIA)

    2015, 国際甲状腺学会

  • 若手奨励賞

    2013.02, 臨床甲状腺学会

  • 第7回東京アルドステロンアワード

    2006

  • Travel Grant Award

    2006, 米国内分泌学会

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Courses Taught 【 Display / hide 】

  • PATHOPHYSIOLOGICAL ISSUES IN CHRONIC CARE

    2022

  • LECTURE SERIES, INTERNAL MEDICINE (NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM)

    2022

  • LECTURE SERIES, INTERNAL MEDICINE

    2022

  • LECTURE SERIES, INTERNAL MEDICINE (NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM)

    2021

  • LECTURE SERIES, INTERNAL MEDICINE

    2021

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Courses Previously Taught 【 Display / hide 】

  • 甲状腺

    Keio University

    2017.04
    -
    2018.03
    , 

    Spring Semester, Lecture, Within own ｆaculty, 100people

    甲状腺

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