Researchers Database


    CenterforCommunityMedicineDepartmentofPublicHealth Professor
Last Updated :2021/12/07

Researcher Information


J-Global ID

Research Interests

  • 公衆衛生学   疫学   川崎病   難治性疾患   嗅覚   細胞・組織   好酸球   

Published Papers

  • 自治医科大学女性卒業生を対象とした就業継続に関する調査結果
    牧野伸子, 仲摩恵美, 吉村成子, 竹内三春, 雲井悠里, 河原奈麻美, 石川由紀子, 牧野伸二, 松村正巳
    月刊地域医学 30 (6) 462 - 466 2017/06 [Refereed][Not invited]
  • Analysis of Neuroblastoma Mortality Rates before and after the Cessation of the Mass Screening Program According to Vital Statistics of Japan Data
    Makino N, Nakamura Y, Ikeda H, Oka A
    Epidemiol: Open Access 7 (2) 161 - 165 2017 [Refereed][Not invited]
  • Nobuko Makino, Yosikazu Nakamura, Mayumi Yashiro, Ryusuke Ae, Satoshi Tsuboi, Yasuko Aoyama, Takao Kojo, Ritei Uehara, Kazuhiko Kotani, Hiroshi Yanagawa
    Journal of Epidemiology 25 (3) 239 - 245 1349-9092 2015 [Refereed][Not invited]
    Background: The number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan. We have therefore characterized the latest epidemiological information on KD. Methods: The 22nd nationwide survey of KD, which targeted patients diagnosed with KD in 2011 and 2012, was conducted in 2013 and included a total of 1983 departments and hospitals. In order to report on all patients with KD during the 2 survey years, we targeted hospitals of 100 beds or more with pediatric departments, or specialized pediatric hospitals. Results: From a total of 1420 hospitals and departments (71.6% response rate), 26 691 KD patients were reported (12 774 in 2011 and 13 917 in 2012 15 442 males and 11 249 females). The annual incidence rates were 243.1 per 100 000 population aged 0 to 4 years in 2011 and 264.8 in 2012. The number of cases of KD recorded in 2012 was the highest ever reported in Japan. The incidence rate of complete cases was also the highest ever reported in Japan and contributed to the increase in the rate of total cases in recent years. The number of patients diagnosed per month peaked in January, and additional peaks were noted during summer months, although these peaks were lower than those seen in winter. Age-specific incidence rate showed a monomodal distribution with a peak in the latter half of the year in which patients were born. Conclusions: The number of patients and the incidence rate of KD in Japan continue to increase. A similar trend has also been seen for patients with complete KD.
  • Nobuko Makino, Seiji Madoiwa, Tsukasa Ohmori, Kazuo Katoh, Shigeo Ookawara, Takeharu Kanazawa, Osamu Matsuo, Masumi Ichikawa, Jun Mimuro, Keiichi Ichimura, Yoichi Sakata
    INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY 3 (6) 458 - 467 2042-6976 2013/06 [Refereed][Not invited]
    Background Tissue type plasminogen activator (tPA) functions as a fibrinolytic factor in the blood and has unique roles in the nervous system. However, the role of tPA in the olfactory epithelium (OE) is still unclear. Generally, surgical ablation of the olfactory bulb (bulbectomy) triggers degeneration followed by regeneration of OE. In this experimental study, we investigated the role of tPA in OE regeneration. Methods Wild-type (WT) mice and tPA-knockout (tPA-/-) mice were subjected to bulbectomy. Reverse-transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemical examination was done to detect tPA expression in the olfactory bulb and OE. Cellular proliferation and apoptosis was also monitored in the OE. Results Before bulbectomy, tPA was found to be expressed in the olfactory bulb and OE. OE degenerated to a similar extent in both strains between 0 and 3 days after bulbectomy. However, OE was thicker and contained more cells in tPA-/- mice than in WT mice at 7 days after bulbectomy. Moreover, the number of apoptotic bodies was reduced and the number of proliferating cells was increased in the OE of tPA-/- mice compared to WT mice, after bulbectomy. Transmission electron microscopy revealed continuous degeneration of the OE for up to 7 days after bulbectomy in WT mice. In contrast, we observed some intact olfactory vesicles and almost normal supporting cells in the OE of tPA-/- mice, at 7 days after bulbectomy. Conclusion The current findings show that the tPA-plasmin system plays an inhibitory role in the regulation of regeneration in the OE.
  • Momoko Dokai, Seiji Madoiwa, Atsushi Yasumoto, Yuji Kashiwakura, Akira Ishiwata, Asuka Sakata, Nobuko Makino, Tsukasa Ohmori, Jun Mimuro, Yoichi Sakata
    THROMBOSIS RESEARCH 128 (3) 283 - 292 0049-3848 2011/09 [Refereed][Not invited]
    Neutrophil elastase released from activated neutrophils contributes in combating bacterial infection. While chronic inflammation results in anemia and decreased bone marrow activities, little is known about the effect of neutrophil elastase on hematological cell growth in severe inflammatory states. Here, we demonstrated that alpha 1-antitrypsin, a physiological inhibitor of neutrophil elastase, functions as a regulator for cell growth by neutralizing neutrophil elastase activity in lipopolysaccharide-primed hematological cells. HL-60 cells were resistant to neutrophil elastase, as they also expressed alpha 1-antitrypsin. The growth of HL-60 cells transduced with a LentiLox-short hairpin alpha 1-antitrypsin vector was significantly suppressed by neutrophil elastase or lipopolysaccharide. When CD34(+) progenitor cells were differentiated towards a granulocytic lineage, they concomitantly expressed neutrophil elastase and alpha 1-antitrypsin and prevented neutrophil elastase-induced growth inhibition. These results suggest that granulocytes might protect themselves from neutrophil elastase-induced cellular damage by efficiently neutralizing its activity through the simultaneous secretion of endogenous alpha 1-antitrypsin. (C) 2011 Elsevier Ltd. All rights reserved.
  • Nobuko Makino, Shigeo Ookawara, Kazuo Katoh, Yasushi Ohta, Masumi Ichikawa, Keiichi Ichimura
    CHEMICAL SENSES 34 (2) 171 - 179 0379-864X 2009/02 [Refereed][Not invited]
    Transmission electron microscopy was used to study the responses of the supporting cells of the olfactory epithelium at 1-5 days after surgical ablation of the olfactory bulb (bulbectomy). In intact olfactory epithelium, lamellar smooth endoplasmic reticulum and rod-shaped mitochondria were distinctly observed in the supporting cells. On the first day after bulbectomy, bending of the microvilli and an increase in the smooth endoplasmic reticulum were observed. Cristae of the mitochondria became obscure, and the density of the mitochondrial matrix decreased. On the second day after bulbectomy, the number of microvilli decreased, broad cytoplasmic projections that contained cytoplasmic organelles protruded into the luminal side, and the mitochondria were swollen. On the fifth day after bulbectomy, microvilli seemed to be normal and some cells had large cytoplasmic projections that protruded toward the lumen of the nasal cavity. Within the cytoplasmic projections of the supporting cells, a large lamellar and reticular-shaped smooth endoplasmic reticulum was evident. Mitochondria exhibited almost normal morphology. The current findings demonstrate that morphological changes occur in the supporting cells after bulbectomy. This new evidence hypothesizes that these changes represent events that contribute to the regeneration of the olfactory epithelium after bulbectomy.
  • Y Ohta, M Takanosawa, C Matumoto, N Makino, S Ishimoto, K Ichimura
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 111 (10) 909 - 911 0003-4894 2002/10 [Refereed][Not invited]
    Glucocorticoids (GCs) are commonly prescribed for treatment of olfactory dysfunction. However, the effects of GCs on olfactory epithelium are not well known. We investigated the effects of high-dose GCs on proliferating cells of olfactory epithelium. Five adult male rats (300 g) received a single daily subcutaneous dose of vehicle containing 0.3 mg dexamethasone (DEX) for 9 days (DEX+ group), and a control group received vehicle alone (DEX- group). We compared sections from the two groups for numbers of Ki67-positive cells. The mean number of Ki67-positive cells per 500 olfactory epithelial cells was 9.6 for the DEX+ group and 58 for the DEX- group (significant difference). We conclude that high-dose GC suppressed proliferation of olfactory epithelium. We suggest that high-dose GC suppresses cytokines and growth factors, resulting in secondary suppression of proliferating ability.

Conference Activities & Talks

  • Epidemiology of Kawasaki disease in Japan: The etiology of Kawasak disease investigated from epidemiology  [Invited]
    Nobuko Makino
    The 21st International Epidemiological Association World Congress of Epidemiology  2017/08


  • MADOIWA Seiji, MAKINO Nobuko, OHMORI Tsukasa, MIMURO Jun, SAKATA Yoichi  Japanese Journal of Thrombosis and Hemostasis  24-  (5)  485  -490  2013  [Not refereed][Not invited]
  • NISHINO Hiroshi, TAKANOSAWA Minako, OTA Yasushi, ISHIKAWA Toshio, KIMURA Tokitugu, IKEDA Saeko, SEJIMA Takayuki, MAKINO Nobuko, SAITOU Tizu, ICHIMURA Keiichi  日本鼻科学会会誌  47-  (1)  16  -20  2008/04  [Not refereed][Not invited]
  • Koichi Abe, Hiroshi Nishino, Nobuko Makino, Kazuhiro Ishikawa, Kotaro Ishikawa, Keiko Imai, Keiichi Ichimura  Journal of Otolaryngology of Japan  110-  (1)  13  -19  2007  [Not refereed][Not invited]
    Arytenoid cartilage dislocation is a known complication of tracheal intubation and is also a type of laryngeal injury. Although spontaneous recovery has been reported, most patients require reduction via pharyngoscopy under general or neuroleptic anesthesia, and some must be treated by open reduction such as laryngoplasty. We report 8 cases of arytenoid cartilage dislocation between August 2003 and August 2004. Excluding 3 patients who recovered spontaneously, we conducted reduction under local anesthesia as an ambulatory procedure in the other 5 with anterior dislocation, i.e., 2 men and 3 women aged 53 to 75 years old. Of these 5, dislocation occurred after tracheal intubation in 4, and in 1 after wearing a laryngeal mask. The outcome was favorable in all 5. Surgery was conducteded after a fiberscope was inserted nasally and a urethral balloon catheter was inserted via the other nasal cavity under topical anesthesia with 4% lidocaine for both nasal cavities and the larynx. While monitoring the larynx, we expanded the balloon and pulled it away from the glottis. The expanded balloon was then placed at the arytenoid region for a few seconds. This procedure was repeated several times to achieve reduction. Three patients recovered well within 1 to 2 weeks of the first reduction, while 2 requierd a second reduction because of insufficient improvement after the first. These two both showed improved vocal cord movement and recovery from hoarseness within 1 to 2 weeks after the second reduction. We conducted 7 reductions without complications in any patient. Our approach is usable in the ambulatory setting, and is simple, minimally invasive, and effective. We consider it to be useful treatment for anterior arytenoid cartilage dislocation.
  • Yasushi Ohta, Keiju Tsubaki, Masanori Yamamoto, Nobuko Makino, Toshio Ishikawa, Keiichi Ichimura  Journal of Otolaryngology of Japan  109-  (3)  157  -162  2006  [Not refereed][Not invited]
    Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery. The condition is usually complicated by asthma, and many eosinophils are present in the sinus mucosa. One conservative treatment method is the administration of glucocorticoids locally or systematically. To evaluate the efficacy and tolerability of intranasal fluticasone propionate for the treatment of chronic sinusitis with eosinophils, seven patients with chronic sinusitis with eosinophils were treated over a 12-week period using a fluticasone propionate aqueous nasal spray (800μg per day in each nostrilz). The Symptons of 7 patients, especially nasal discharge and nasal obstructions, improved and an expanded air space was observed on paranasal CT images. The percent of drug systemically available after intranasal administration varied by less than 1% for intranasal fluticasone propionate. Therefore, even if intranasal fluticasone propionate is administerved at double the usual dose, it is unlikely to cause systemic side effects. Fluticasone propionate aqueous nasal spray at double the usual dose is effective for the treatment of chronic sinusitis with eosinophils.
  • MAKINO Nobuko, OHTA Yasushi, ISHIKAWA Toshio, ICHIMURA Keiichi  日本鼻科学会会誌  44-  (2)  123  -126  2005/08  [Not refereed][Not invited]
  • Nobuko Makino, Yasushi Ohta, Toshio Ishikawa, Keiichi Ichimura  Journal of Otolaryngology of Japan  108-  (5)  528  -532  2005  [Not refereed][Not invited]
    Purpose: To evaluate the systemic effects of intranasal steroid drops in patients with dysosmia. Cases and Methods: Intranasal steroid drops were administered for 12 weeks to 23 patients with dysosmia, and their plasma cortisol and adrenocorticotropic hormone (ACTH) values were measured before and after treatment. Improvement in dysosmia was judged based on the standerd olfactory test and the patients' symptoms. Results: The post-treatment plasma cortisol levels ranged from 0.1 to 25.0μg/dl (5.4±5.9μg/dl), and the post-treatment plasma ACTH levels ranged from 5.0 to 55.0pg/ml (13.8±11.7pg/ml). After treatment, the 23 cases were divided into two groups: 14 cases (60.9%) with a decline in cortisol and/or ACTH level, and 9 patients (39.1%) with normal plasma cortisol and ACTH levels. Improvement in dysosmia was found in 4 patients (28.6%) in the former group and 4 patients (44.4%) in the latter group. The difference in percentage of patients who improved was not significant between the groups. Conclusions: We conclude that the direct topical effect of intranasal steroid drops on the olfactory mucosa may have been the principal reason for the improvement in the patients' dysosmia.
  • 市村 恵一, 太田 康, 丹生 健一, 石川 敏夫, 高野澤 美奈子, 牧野 伸子, 安井 理絵, 近藤 健二, 松本 千織  日本鼻科学会会誌  43-  (1)  92  -94  2004/04  [Not refereed][Not invited]
  • ICHIMURA Keiichi, ISHIKAWA Kazuhiro, TAKANOSAWA Minako, SEJIMA Takayuki, SATO Takae, MAKINO Nobuko, ISIKAWA Toshio, OHTA Yasushi, ISHIDA Takashi  日本鼻科学会会誌  42-  (2)  138  -145  2003/08  [Not refereed][Not invited]
  • ICHIMURA Keiichi, SEJIMA Takayuki, OHTA Yasushi, MAKINO Nobuko  日本鼻科学会会誌  41-  (2)  149  -155  2002/06  [Not refereed][Not invited]
  • MAKINO Nobuko, OHTA Yasushi, ICHIMURA Keiichi  日本鼻科学会会誌  41-  (2)  162  -166  2002/06  [Not refereed][Not invited]

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