研究者詳細 - 小笠原　徳子

論文 - 小笠原　徳子

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Bob1 limits cellular frequency of T-follicular helper cells

Keiji Yamashita, Koji Kawata, Hiroshi Matsumiya, Ryuta Kamekura, Sumito Jitsukawa, Tomonori Nagaya, Noriko Ogasawara, Ken-ichi Takano, Terufumi Kubo, Sachiko Kimura, Katsunori Shigehara, Tetsuo Himi, Shingo Ichimiya

EUROPEAN JOURNAL OF IMMUNOLOGY ( WILEY ) 46 ( 6 ) 1361 - 1370 2016年06月 [査読有り]

T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B-cell lymphoma-6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(-/-) mice were much higher than those inwild-type (WT) mice. In addition, expansion of Tfh cells within Bob1(-/-)CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T-cell-intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(-/-) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3-induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1-related mechanism to restrict numerical frequency against stimulation of TCRs.

DOI PubMed

Outcomes of visually impaired patients who received cochlear implantations

Kenichi Takano, Aya Kaizaki, Etsuko Saikawa, Ayami Konnno, Noriko Ogasawara, Tetsuo Himi

AURIS NASUS LARYNX ( ELSEVIER SCI LTD ) 43 ( 3 ) 242 - 246 2016年06月 [査読有り]

Objective: Patients with multiple sensory deficits, including hearing loss and visual impairment, present a unique problem. We evaluated the clinical outcomes of cochlear implantation in patients with severe to profound sensorineural hearing loss and visual impairment. Methods: We retrospectively reviewed eight patients with severe sensorineural hearing loss and visual impairment who underwent cochlear implantation at our institution between 1993 and 2014. The follow-up period was between 2 and 20 years. We evaluated the case histories, etiologies of hearing loss and visual impairment, pre- and postoperative pure-tone thresholds, speech perception rates after CI using the Japanese CD speech discrimination scoring system (CI-2004 test) for words and sentences, and pre- and postoperative communication means. Postoperative speech discrimination scores were compared between patients with and without visual impairment who underwent cochlear implantation. Results: The outcomes of cochlear implantation were good in all patients, with seven showing the ability to hold a conversation with others. The average proportion of correct answers for words and sentences in the CI-2004 test was 72.3 +/- 19.1% and 86.0 +/- 16.1%, respectively, for the patients with visual impairment and 62.1 +/- 21.7% and 78.5 +/- 20.9%, respectively, for those without visual impairment (based on auditory senses only). There were no significant differences in results between the patients with and without visual impairment. Conclusions: Cochlear implantation is important for the rehabilitation of patients with severe auditory loss and visual impairment. Medical staff members require additional skills to perform auditory evaluations and rehabilitate patients with multiple sensory deficits. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI PubMed

Congenital microtia treated at Sapporo Medical University Hospital: Clinical characteristics and associated anomalies

Noriko Ogasawara, Sumito Jitsukawa, Nozomi Takahashi, Kenichi Takano, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 12 - 16 2016年 [査読有り]

Seventy-three children who underwent plastic surgery for their external ear malformations between December 2010 and May 2013 at the Sapporo Medical University Hospital were evaluated. The predominance of right-sided malformation (62%) in males (71%) was similar to that reported previously, but the number of bilateral cases (9.3%) was lower than that in previous reports. We classified patients' ears using Marx's classification. The pure-tone average (average air conduction thresholds measured at 500, 1,000 and 2,000 Hz) was used as the representative value for the hearing level, which was compared with a patient's Marx classification. We evaluated the facial nerve position using high-resolution computed tomography scans. A thorough understanding of anatomical variations and complications, as well as performing appropriate treatments, is required for otolaryngologists to effectively manage congenital microtia.

DOI PubMed

Clinical review of cochlear implantation performed at sapporo medical university hospital

Noriko Ogasawara, Kenichi Takano, Tomoko Shintani, Etsuko Saikawa, Nozomi Takahashi, Fumie Ito, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 1 - 6 2016年 [査読有り]

More than 20 years have passed since cochlear implantation (CI) was first introduced in Japan. We began CI at the Sapporo Medical University Hospital in 1988 since then, up to the first half of 2015, we have performed CI on 280 ears. In patients aged less than and those aged over 18 years, 121 and 159 ears, respectively, have undergone surgery. This report presents typical cases of CI, such as an adult case, a bilateral case, a case where both hearing and vision were impaired, a pediatric case, a case with multiple handicaps, a case with a genetic mutation leading to severe hearing loss, and a complicated case. In addition, complications with CI cases experienced during extended follow-up periods are also summarized.

DOI PubMed

Accessory parotid gland tumors: A series of 4 cases

Takuya Kakuki, Kenichi Takano, Makoto Kurose, Atsushi Kondo, Tsuyoshi Okuni, Noriko Ogasawara, Tetsuo Himi

Ear, Nose and Throat Journal ( Medquest Communications LLC ) 95 ( 7 ) E35 - 8 2016年 [査読有り]

Accessory parotid gland tumors are clinically rare, and their management remains unclear. In this article, we describe our experience with 4 patients-2 males and 2 females, aged 13 to 66 years-who were diagnosed with an accessory parotid gland tumor. All patients presented with an asymptomatic midcheek swelling, and all underwent fine-needle aspiration biopsy, ultrasonography, computed tomography, and magnetic resonance imaging. A standard parotidectomy was performed on all patients. Postoperatively, 2 patients were found to have a malignant tumor, while the other 2 had a pleomorphic adenoma. No patient experienced any obvious facial nerve injuries postoperatively, and no recurrences were observed. We discuss the preoperative evaluation, treatment, and prognosis of these tumors, and we briefly describe the literature. The first choice of treatment for accessory parotid gland tumors is surgical resection. In our experience, a standard parotidectomy approach is safe and cosmetically appealing.

PubMed

A novel nonsense mutation in the NOG gene causes familial NOG-related symphalangism spectrum disorder.

Kenichi Takano, Noriko Ogasawara, Tatsuo Matsunaga, Hideki Mutai, Akihiro Sakurai, Aki Ishikawa, Tetsuo Himi

Human genome variation 3 16023 - 16023 2016年 [査読有り] [国際誌]

The human noggin (NOG) gene is responsible for a broad spectrum of clinical manifestations of NOG-related symphalangism spectrum disorder (NOG-SSD), which include proximal symphalangism, multiple synostoses, stapes ankylosis with broad thumbs (SABTT), tarsal-carpal coalition syndrome, and brachydactyly type B2. Some of these disorders exhibit phenotypes associated with congenital stapes ankylosis. In the present study, we describe a Japanese pedigree with dactylosymphysis and conductive hearing loss due to congenital stapes ankylosis. The range of motion in her elbow joint was also restricted. The family showed multiple clinical features and was diagnosed with SABTT. Sanger sequencing analysis of the NOG gene in the family members revealed a novel heterozygous nonsense mutation (c.397A>T; p.K133*). In the family, the prevalence of dactylosymphysis and hyperopia was 100% while that of stapes ankylosis was less than 100%. Stapes surgery using a CO2 laser led to a significant improvement of the conductive hearing loss. This novel mutation expands our understanding of NOG-SSD from clinical and genetic perspectives.

DOI PubMed

Relationship between otitis media and epithelial function in the lymphoepithelium of pediatric adenoids

Noriko Ogasawara, Keisuke Yamamoto, Kenichi Takano, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 33 - 39 2016年 [査読有り]

Nose- or nasopharynx-associated lymphoid tissue (NALT) has a unique role that is distinct from that of other lymphoid tissues. During upper airway mucosal immune response, NALT induces a variety of responses, including cytokine and chemokine production and innate immune response, to establish acquired immunity. NALT consists of epithelial cells, epithelium-associated lymphoid tissues such as IgA-committed B cells, innate lymphocytes, T helper cells and dendritic cells. Intranasal immunization has recently been shown to effectively induce a proactive immune response in the local mucosa in addition to a systemic immune response. A variety of factors can cause otitis media, including Eustachian tube dysfunction, inflammation, allergy and viral and bacterial infections. However, the detailed pathogenesis of otitis media is not yet completely understood. In this report, we provide evidence suggesting that adenoid tissue as a component of NALT in children may play an important role in inducing innate immunity following viral infection.

DOI PubMed

Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.

Shin Hashimoto, Soh Yamamoto, Noriko Ogasawara, Toyotaka Sato, Keisuke Yamamoto, Hiroshi Katoh, Toru Kubota, Tsukasa Shiraishi, Takashi Kojima, Tetsuo Himi, Hiroyuki Tsutsumi, Shin-Ichi Yokota

PloS one ( PUBLIC LIBRARY SCIENCE ) 11 ( 8 ) e0161793 2016年 [査読有り] [国際誌]

Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.

DOI PubMed

Cochlear implantation in children with cochlear malformation

Etsuko Saikawa, Kenichi Takano, Noriko Ogasawara, Chieko Tsubomatsu, Nozomi Takahashi, Hideaki Shirasaki, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 7 - 11 2016年 [査読有り]

Cochlear implantation (CI) has proven to be an effective treatment for severe bilateral sensorineural hearing loss (SNHL). Inner ear malformation is a rare anomaly and occurs in approximately 20% of cases with congenital SNHL. In cases with cochlear malformation, CI can be successfully performed in nearly all patients, the exceptions being those with complete labyrinthine and cochlear aplasia. It is important to evaluate the severity of inner ear deformity and other associated anomalies during the preimplantation radiological assessment in order to identify any complication that may potentially occur during the surgery and subsequent patient management.

DOI PubMed

Intrafamilial, Preferentially Mother-to-Child and Intraspousal, Helicobacter pylori Infection in Japan Determined by Mutilocus Sequence Typing and Random Amplified Polymorphic DNA Fingerprinting

Shin-ichi Yokota, Mutsuko Konno, Shin-ichi Fujiwara, Nariaki Toita, Michiko Takahashi, Soh Yamamoto, Noriko Ogasawara, Tsukasa Shiraishi

HELICOBACTER ( WILEY-BLACKWELL ) 20 ( 5 ) 334 - 342 2015年10月 [査読有り]

Background: The infection route of Helicobacter pylori has been recognized to be mainly intrafamilial, preferentially mother-to-child, especially in developed countries. To determine the transmission route, we examined whether multilocus sequence typing (MLST) was useful for analysis of intrafamilial infection. The possibility of intraspousal infection was also evaluated. Materials and Methods: Clonal relationships between strains derived from 35 index Japanese pediatric patients, and their family members were analyzed by two genetic typing procedures, MLST and random amplified polymorphic DNA (RAPD) fingerprinting. Results: Mostly coincident results were obtained by MLST and RAPD. By MLST, the allele of loci in the isolates mostly matched between the index child and both the father and mother for 9 (25.7%) of the 35 patients, between the index child and the mother for 25 (60.0%) of the 35 patients. Conclusions: MLST is useful for analyzing the infection route of H. pylori as a highly reproducible method. Intrafamilial, especially mother-to-children and sibling, infection is the dominant transmission route. Intraspousal infection is also thought to occur in about a quarter in the Japanese families.

DOI PubMed

Poly(I:C) induced microRNA-146a regulates epithelial barrier and secretion of proinflammatory cytokines in human nasal epithelial cells

Ryo Miyata, Takuya Kakuki, Kazuaki Nomura, Tsuyoshi Ohkuni, Noriko Ogasawara, Ken-ichi Takano, Takumi Konno, Takayuki Kohno, Norimasa Sawada, Tetsuo Himi, Takashi Kojima

EUROPEAN JOURNAL OF PHARMACOLOGY ( ELSEVIER SCIENCE BV ) 761 375 - 382 2015年08月 [査読有り]

Human nasal epithelial cells (HNECs) are important in the tight junctional barrier and innate immune defense protecting against pathogens invading via Toll-like receptors (TERs). MicroRNAs (miRNAs) I egulate expression of tight junctions as direct or indirect targeting genes and maintain the barrier Function. However, the roles of miRNAs in the epithelial barrier of HNECs via TLRs remain unknown. In the present study, to investigate the effects of miRNAs on the epithelial barrier of HNECs via TLRs, primary cultured HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs), were treated with the TLR3 ligand poly(I:C) and miRNA array analysis was performed. In the miRNA array of the cells treated with poly(I:C), upregulation of miR-187, -146a, -574, -4274, -4433, -4455 and -4750, and downregulation of miR-4785 by more than twofold compared to the control were observed. When control HNECs were treated with mimics and inhibitors of these miRNAs, an miR-146a mimic induced expression of tight junction proteins claudin-1, occludin and JAM-A together with an increase of the epithelial barrier function. The poly(I:C)-induced miR-146a was regulated via the distinct TLR3-mediatecl signal pathways PI3K, JNK and NE-kappa B. Furthermore, the miR-146a mimic prevented downregulation of claudin-1 and JAM-A and the secretion of proinflammatory cytokines IL-8 and TNF-alpha induced by poly (I:C) by targeting TRAFG. These findings indicate that, in HNECs, miRNA-146a plays crucial roles in maintenance of the tight junction barrier and innate immune defense protecting against invading pathogens. (C) 2015 Elsevier B.V. All rights reserved.

DOI PubMed

Vascular tumors of the external auditory canal: three case reports and a review of the literature

Keisuke Yamamoto, Noriko Ogasawara, Nobuhiko Seki, Nobuhiro Konno, Hiroshi Tsubota, Tetsuo Himi

SPRINGERPLUS ( SPRINGER INTERNATIONAL PUBLISHING AG ) 4 307 2015年07月 [査読有り]

Background: Benign vascular tumors are frequently found in the head and neck, however, such tumors of the external auditory canal are extremely rare. We report three cases of benign vascular tumors limited to the external auditory canal. Case description: A 50-year-old woman was diagnosed during an episode of ear fullness and hearing loss. A 10-year-old boy consulted our department about an episode of recurrent otorrhagia. A 20-year-old man found a bulge of his external auditory canal by chance. Complete surgical resection was performed for the first patient. The second patient underwent electro-coagulation of the lesion. In the third patient, to exclude the possibility of a malignant tumor, a biopsy was performed under local anesthesia. Histopathological analysis demonstrated the characteristic of vascular tumors. The lesion showed remarkable reduction during his treatment with antibiotics and cleaning. He remains under careful observation. Discussion and evaluation: In diagnosis, there is sometimes confusion between vascular tumors and malformations. Generally, vascular malformations can be differentiated from vascular tumors since they are present at birth and are generally stable. Conclusion: Decision making about treatment of benign vascular tumors is sometimes confusing because of the difficulty in diagnosis. We performed biopsy for only one of our three cases because we regard that informal biopsy should not be conducted for lesions with difficult hemostic conditions and locations.

DOI PubMed

Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma

Ryuta Karnekura, Katsunori Shigehara, Satsuki Miyajima, Sumito Jitsukawa, Koji Kawata, Keiji Yamashita, Tomonori Nagaya, Ayako Kumagai, Akinori Sato, Hiroshi Matsumiya, Noriko Ogasawara, Nobuhiko Seki, Kenichi Takano, Yasuo Kokai, Hiroki Takahashi, Tetsuo Himi, Shingo Ichimiya

CLINICAL IMMUNOLOGY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 158 ( 2 ) 204 - 211 2015年06月 [査読有り]

Allergic rhinitis (AR), the most common allergic disorder of the airway, is often accompanied by bronchial asthma. However, little is known about the mechanism by which AR advances to AR comorbid with bronchial asthma (AR + Asthma). To determine the pathophysiologic features of AR and AR + Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR + Asthma patients. The results showed polarization of Tfh2 cells within Tfh cell subsets in both AR and AR + Asthma cases. Interestingly, the %Breg cells in total B cells were decreased in AR cases and, more extensively, in AR + Asthma cases. Moreover, we found significant correlations of fractional exhaled nitricoxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that relative decrease in Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma. (C) 2015 The Authors. Published by Elsevier Inc.

DOI PubMed

当科における2歳未満の人工内耳埋込術症例の検討

高野賢一, 才川悦子, 小笠原徳子, 高橋希, 氷見徹夫

小児耳鼻咽喉科 ( 日本小児耳鼻咽喉科学会 ) 36 ( 2 ) 221 - 221 2015年04月

アレルギー性気道疾患の病態形成における濾胞ヘルパーT細胞と制御性B細胞の役割

亀倉隆太, 重原克則, 實川純人, 小笠原徳子, 高野賢一, 氷見徹夫, 一宮慎吾

アレルギー ( (一社)日本アレルギー学会 ) 64 ( 3-4 ) 570 - 570 2015年04月

当科における人工内耳埋め込み術の術後合併症に関する検討

小笠原徳子, 才川悦子, 高野賢一, 新谷朋子, 氷見徹夫

Otology Japan ( (一社)日本耳科学会 ) 25 ( 1 ) 51 - 57 2015年02月

当科では1988年から人工内耳埋め込み術を行っている。導入から25年以上が経過し、これまでに経験した術後合併症についてその原因と対策を検討することを目的として後ろ向き調査を行った。1988年から2013年5月までに札幌医科大学病院耳鼻咽喉科にて人工内耳埋め込み術を施行した248耳を調査対象とした。術後合併症を「人工内耳埋め込み術後に何らかの追加の診療・治療・処置を必要とした症状」と定義し、診療録からの記載をもとに検討した。結果として248耳中、92耳(37%)に何らかの術後合併症を認めた。観血的治療を必要とした重度合併症は12耳(4%)であった。人工内耳機器は時代により変遷しており、手術方法、適応基準、適応年齢に変化が生じてきている。これまでの報告と同様に、きめ細かな配慮を丁寧に行い、手術実施医療機関において長期の経過観察を行うことが合併症の減少につながると考えられた。(著者抄録)

当科における中等度難聴児の検討

今野綾美, 才川悦子, 新谷朋子, 小笠原徳子, 海崎文, 吉野真代, 北川可恵, 氷見徹夫

Audiology Japan ( (一社)日本聴覚医学会 ) 57 ( 5 ) 447 - 448 2014年10月

3歳以降に診断をうけた中等度・高度難聴症例の検討

才川悦子, 新谷朋子, 小笠原徳子, 高橋希, 海崎文, 吉野真代, 今野綾美, 北川可恵, 氷見徹夫

Audiology Japan ( (一社)日本聴覚医学会 ) 57 ( 5 ) 445 - 446 2014年10月

Cochlear implantation in a patient with Paget's disease

Kenichi Takano, Etsuko Saikawa, Noriko Ogasawara, Tetsuo Himi

AMERICAN JOURNAL OF OTOLARYNGOLOGY ( W B SAUNDERS CO-ELSEVIER INC ) 35 ( 3 ) 408 - 410 2014年05月 [査読有り]

Paget's disease of the temporal bone can cause hearing loss that eventually develops into profound deafness. However, the treatment options for hearing loss associated with Paget's disease are limited. Thus far, only 3 cases of cochlear implantation in patients with Paget's disease have been reported. In this study, we describe a 62-year-old woman who underwent cochlear implantation for progressive bilateral sensorineural hearing loss. The patient gained useful open-set speech perception over a 5-year postoperative period. Cochlear implantation can be beneficial in patients with profound hearing loss associated with Paget's disease. (C) 2014 Elsevier Inc. All rights reserved.

DOI PubMed

A clinical study of stapes fixation

Kenichi Takano, Tsuyoshi Okuni, Noriko Ogasawara

Otolaryngology - Head and Neck Surgery (Japan) 86 ( 2 ) 171 - 177 2014年02月

We analyzed the result of stapes surgery patients including otosclerosis (56 ears) and congenital foot plate ankylosis (15 ears) between 1999 and 2011 in our hospital. The success rates of hearing improvement according to the statement of Otological Society of Japan were 92.6% at otosclerosis and 92.0% at congenital foot plate ankylosis. One revision case of otosclerosis showed an extensive incus erosion during revision surgery. In mixed congenital auditory ossicular malformation with especially stapes footplate fixation, the preoperative diagnosis might be difficult and requiring unexpected procedures with a poor hearing outcome.

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