Faculty Profiles - OTSUKA Fumio

Neck schwannoma mimicking a thyroid tumor.

Kosuke Oka, Masaya Iwamuro, Fumio Otsuka

Journal of general and family medicine 18 ( 6 ) 473 - 474 2017.12

Hypersensitivity Pneumonitis Caused by a Home Ultrasonic Humidifier Contaminated with Candida guilliermondii.

Akemi Ando, Hideharu Hagiya, Takahiro Nada, Kosuke Kimura, Koichi Waseda, Kammei Rai, Yoshihisa Hanayama, Fumio Otsuka

Internal medicine (Tokyo, Japan) 56 ( 22 ) 3109 - 3112 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

We herein report the first documented case of acute hypersensitivity pneumonitis in which Candida guilliermondii was the possible causative organism. A young Japanese woman presented to our hospital with relapsing respiratory symptoms accompanied by high fever. A detailed interview revealed that the onset of the symptoms occurred shortly after using a humidifier in her home. Her symptoms showed spontaneous improvement soon after admission, and an examination of her bronchoalveolar lavage fluid revealed the specific infiltration of inflammatory cells, which predominantly consisted of lymphocytes. Precipitin testing showed a positive reaction to C. guilliermondii, which was isolated from the home humidifier. Repeated history taking is essential for diagnosing occult respiratory disorders.

DOI： 10.2169/internalmedicine.9055-17

Regulation of gonadotropins by urocortin 2 in gonadotropic tumor LβT2 cells

Kazunori Kageyama, Shingo Murasawa, Kanako Niioka, Fumio Otsuka, Hiroko Yagi, Makoto Daimon

Neuroscience Letters 660 63 - 67 2017.11

Reply to "The Difficulty in Administering Appropriate Antimicrobial Therapy for Stenotrophomonas maltophilia Bacteremia".

Hirotaka Ebara, Hideharu Hagiya, Yuto Haruki, Eisei Kondo, Fumio Otsuka

Internal medicine (Tokyo, Japan) 56 ( 20 ) 2817 - 2817 2017.10

Multiple abscesses caused by repetitive intramuscular injections.

Ko Harada, Naoko Kashihara, Masaya Iwamuro, Fumio Otsuka

Journal of general and family medicine 18 ( 5 ) 301 - 302 2017.10

Perimandibular abscess associated with bisphosphonate-related osteonecrosis of the jaw. Reviewed

Kazuki Ocho, Masaya Iwamuro, Hideharu Hagiya, Soichiro Ibaragi, Fumio Otsuka

Journal of general and family medicine 18 ( 5 ) 305 - 306 2017.10

The Clinical and Hormonal Characteristics of Primary Adrenal Lymphomas: The Necessity of Early Detection of Adrenal Insufficiency. Reviewed

Ko Harada, Kosuke Kimura, Masaya Iwamuro, Tomohiro Terasaka, Yoshihisa Hanayama, Eisei Kondo, Eiko Hayashi, Tadashi Yoshino, Fumio Otsuka

Internal medicine (Tokyo, Japan) 56 ( 17 ) 2261 - 2269 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Objective To analyze the clinical and endocrine characteristics of patients with primary adrenal lymphoma.
Patients We retrospectively reviewed the cases of five patients with primary adrenal lymphoma who were treated in our hospital between April 2004 and March 2015. We investigated the characteristics of the clinical and pathological findings, treatment, prognosis and complications of adrenal insufficiency.
Results Adrenal insufficiency, which was confirmed by the laboratory data at the initial presentation, was observed in two cases. One case was complicated by relative adrenal insufficiency during a course of chemotherapy. The plasma adrenaline and urinary adrenaline levels were decreased in four cases and three cases, respectively. Diffusion MRI was radiologically diagnostic. In all of the cases, the patients were pathologically diagnosed with diffuse large-B cell lymphoma and were treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like chemotherapy. Two patients received central nervous system prophylaxis with high-dose methotrexate. Four of the patients survived and one patient died during the follow-up period.
Conclusion The early detection of adrenal insufficiency and the administration of an appropriate dose of hydrocortisone are necessary during the course of chemotherapy as well as at the initial manifestation. The exclusion of adrenal dysfunction prior to invasive diagnostic procedures, such as CT-guided needle biopsy, is also critical.

DOI： 10.2169/internalmedicine.8216-16

A regulatory role of androgen in ovarian steroidogenesis by rat granulosa cells. International journal

Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka

The Journal of steroid biochemistry and molecular biology 172 160 - 165 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of androgen on steroidogenesis, DHT enhanced the expression of progesterogenic factors and enzymes, including StAR, P450scc and 3βHSD, and cellular cAMP synthesis induced by FSH and IGF-I. Of note, treatment with DHT and IGF-I suppressed Smad1/5/8 phosphorylation and transcription of the BMP target gene Id-1, suggesting that androgen and IGF-I counteract BMP signaling that inhibits FSH-induced progesterone synthesis in rat granulosa cells. DHT was revealed to suppress the expression of BMP-6 receptors, consisting of ALK-2, ALK-6 and ActRII, while it increased the expression of inhibitory Smads in rat granulosa cells. In addition, IGF-I treatment upregulated androgen receptor (AR) expression and DHT treatment suppressed IGF-I receptor expression on rat granulosa cells. Collectively, the results indicate that androgen and IGF-I mutually interact and accelerate progesterone production, at least in part, by regulating endogenous BMP signaling in rat granulosa cells. Cooperative effects of androgen and IGF-I counteract endogenous BMP-6 activity in rat granulosa cells, which is likely to be functionally linked to the steroidogenic property shown in the PCOS ovary.

DOI： 10.1016/j.jsbmb.2017.07.002

Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells. Reviewed International journal

Kanako Ogura-Ochi, Satoshi Fujisawa, Nahoko Iwata, Motoshi Komatsubara, Yuki Nishiyama, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Jun Wada, Fumio Otsuka

Peptides 94 19 - 24 2017.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release. Melatonin receptor activation also suppressed BMP-4-induced prolactin expression by inhibiting phosphorylation of Smad and transcription of the BMP-target gene Id-1, while BMP-4 treatment upregulated MT2 expression. Melatonin receptor activation suppressed basal, BMP-4-induced and forskolin-induced cAMP synthesis; however, BtcAMP-induced prolactin mRNA expression was not affected by melatonin or ramelteon, suggesting that MT2 activation leads to inhibition of prolactin production through the suppression of Smad signaling and cAMP synthesis. Experiments using intracellular signal inhibitors revealed that the ERK pathway is, at least in part, involved in prolactin induction by GH3 cells. Thus, a new regulatory role of melatonin involving BMP-4 in prolactin secretion was uncovered in lactotrope GH3 cells.

DOI： 10.1016/j.peptides.2017.06.001

顕性クッシングを呈しメチラポンで加療中のAIMAHの2例

藤澤諭、稲垣兼一、西山悠紀、小松原基志、原孝行、細谷武史、当真貴志雄、越智可奈子、和田淳、大塚文男

日本内分泌学会雑誌 93 ( Suppl. Update ) 44 - 45 2017.6

Predictors of vasovagal reactions during preoperative autologous blood donation: a single-institution analysis.

Hisakazu Nishimori, Nobuharu Fujii, Keiko Fujii, Tohru Ikeda, Naomi Asano, Hiroaki Ogo, Miwa Yamakawa, Naoe Takagi, Fumio Otsuka, Kazuma Ikeda

International journal of hematology 105 ( 6 ) 812 - 818 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Studies examining risk factors associated with vasovagal reactions (VVRs) during autologous blood donations, especially in younger subjects, have been limited. The aim of the present study was to define risk factors for VVRs during preoperative autologous blood donation in patients, including those younger than 18 years old. We retrospectively analyzed 4192 autologous, preoperative blood donations between 2007 and 2015 at Okayama University Hospital. Eighty-seven (2.08%) of the patients experienced VVRs. VVRs occurred approximately three times as often in patients 0-17 years old (16/320, 5.0%) than in patients 18 years and older (71/3872, 1.8%). In particular, VVRs occurred more frequently in those 10-13 years old, and decreased with older age (P = 0.006). In a univariate analysis, younger age, lower body mass index, lower systolic blood pressure, lower body weight, lower total blood volume, female gender, first-time collection, and higher heart rate were associated with a higher incidence of VVRs. In a multivariate analysis, lower systolic blood pressure (P < 0.001), higher heart rate (P = 0.007), and first-time collection (P = 0.015), remained independent predictors of VVRs. These results emphasize the need for careful attention during blood collection.

DOI： 10.1007/s12185-017-2204-6

Successful treatment with glucocorticoid for secondary Fanconi syndrome caused by sarcoidosis. Reviewed International journal

Daisuke Omura, Hideharu Hagiya, Yoshihisa Hanayama, Kou Hasegawa, Hiroshi Morinaga, Atsue Kikuta, Hitomi Kataoka, Fumio Otsuka

Modern rheumatology 27 ( 3 ) 545 - 547 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

A 77-year-old female with renal dysfunction, hypercalcemia, and hypercalciuria was presented. Systemic investigations including renal biopsy showed that the patient had Fanconi syndrome secondary to renal sarcoidosis. Treatment with 25 mg per day of prednisolone was initiated and her condition improved. Complication of Fanconi syndrome in patients with sarcoidosis is extremely rare. Although the pathological mechanism is still unknown, corticosteroid therapy was effective for ameliorating proteinuria, glycosuria, hypercalciuria, and aminoaciduria.

DOI： 10.3109/14397595.2014.1002163

A unique acromegalic osteoarthropathy: manubriosternal joint arthritis. International journal

Satoshi Fujisawa, Fumio Otsuka

Clinical case reports 5 ( 5 ) 725 - 726 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Osteoarthritis of the manubriosternal joint can be found in patients with inflammatory arthritis. Acromegalic arthropathy is often found in the shoulders, wrists, knees, hips, and spine; however, attention should also be given to sternalgia as a complication of acromegalic involvement of the manubriosternal joint.

DOI： 10.1002/ccr3.913

Endoscopic Manifestations and Clinical Characteristics of Cytomegalovirus Infection in the Upper Gastrointestinal Tract.

Masaya Iwamuro, Eisei Kondo, Takehiro Tanaka, Hideharu Hagiya, Seiji Kawano, Yoshiro Kawahara, Fumio Otsuka, Hiroyuki Okada

Acta medica Okayama 71 ( 2 ) 97 - 104 2017.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

We retrospectively analyzed the cases of 14 patients (9 women, 5 men, mean age: 51.6 years) with cytomegalovirus (CMV) involvement in the esophagus, stomach, and/or duodenum diagnosed at a single center, to determine their endoscopic features and clinical backgrounds. Thirteen patients (92.9%) had hematologic disease; the other had rheumatoid arthritis. Of the former, 12 patients underwent allogeneic hematopoietic stem cell transplantation, and 9 of these patients had graft-versus-host disease (GVHD) before undergoing esophagogastroduodenoscopy (EGD). All 14 patients had been taking one or more immunosuppressive agents including cyclosporine (n=10), corticosteroids (n=9), mycophenolic acid (n=6), tacrolimus (n=3), and methotrexate (n=1). Tests for CMV antigenemia were positive in 11 patients (78.6%). EGD examinations revealed esophageal (n=3), gastric (n=9), and duodenal involvement (n=6). Macroscopically, esophageal lesions by CMV infection presented as redness (n=1), erosions (n=1), and ulcers (n=1). Gastric lesions manifested as redness (n=7), erosions (n=3), exfoliated mucosa (n=2), and verrucous erosions (n=1). Mucosal appearances in the duodenum varied: redness (n=2), ulcers (n=2), multiple erosions (n=2), single erosion (n=1), edema (n=1). CMV was detected even in the intact duodenal mucosa (n=1). In conclusion, physicians must recall the relevance of CMV infection when any mucosal alterations exist in the upper gastrointestinal tract of immunosuppressed patients.

DOI： 10.18926/AMO/54977

Idiopathic adult ileo-colonic intussusception.

Masaya Iwamuro, Takahiro Nada, Kosuke Kimura, Yoshihisa Hanayama, Fumio Otsuka

Journal of general and family medicine 18 ( 2 ) 94 - 95 2017.4

Lanthanum Deposition in the Stomach: Usefulness of Scanning Electron Microscopy for Its Detection.

Masaya Iwamuro, Haruo Urata, Takehiro Tanaka, Akemi Ando, Takahiro Nada, Kosuke Kimura, Kenji Yamauchi, Chiaki Kusumoto, Fumio Otsuka, Hiroyuki Okada

Acta medica Okayama 71 ( 1 ) 73 - 78 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

After having been treated with lanthanum carbonate administration for 4 years for hyperphosphatemia, a 75-year-old Japanese woman undergoing hemodialysis was diagnosed with lanthanum phosphate deposition in the stomach. The deposition, seen as white microgranules, was observed using esophagogastroduodenoscopy with magnifying observation. To the best of our knowledge, these are the minutest endoscopy images of lanthanum phosphate deposition in the gastric mucosa. Scanning electron microscopy (SEM) observation enabled easier identification of the deposited material, which was visible as bright areas. The present case suggests the usefulness of SEM observation in the detection of lanthanum phosphate deposition in the gastrointestinal tract.

DOI： 10.18926/AMO/54828

Combined Effects of Androgen and Growth Hormone on Osteoblast Marker Expression in Mouse C2C12 and MC3T3-E1 Cells Induced by Bone Morphogenetic Protein. Reviewed International journal

Kosuke Kimura, Tomohiro Terasaka, Nahoko Iwata, Takayuki Katsuyama, Motoshi Komatsubara, Ryota Nagao, Kenichi Inagaki, Fumio Otsuka

Journal of clinical medicine 6 ( 1 ) 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Osteoblasts undergo differentiation in response to various factors, including growth factors and steroids. Bone mass is diminished in androgen- and/or growth hormone (GH)-deficient patients. However the functional relationship between androgen and GH, and their combined effects on bone metabolism, remains unclear. Here we investigated the mutual effects of androgen and GH on osteoblastic marker expression using mouse myoblastic C2C12 and osteoblast-like MC3T3-E1 cells. Combined treatment with dihydrotestosterone (DHT) and GH enhanced BMP-2-induced expression of Runx2, ALP, and osteocalcin mRNA, compared with the individual treatments in C2C12 cells. Co-treatment with DHT and GH activated Smad1/5/8 phosphorylation, Id-1 transcription, and ALP activity induced by BMP-2 in C2C12 cells but not in MC3T3-E1 cells. The insulin-like growth factor (IGF-I) mRNA level was amplified by GH and BMP-2 treatment and was restored by co-treatment with DHT in C2C12 cells. The mRNA level of the IGF-I receptor was not significantly altered by GH or DHT, while it was increased by IGF-I. In addition, IGF-I treatment increased collagen-1 mRNA expression, whereas blockage of endogenous IGF-I activity using an anti-IGF-I antibody failed to suppress the effect of GH and DHT on BMP-2-induced Runx2 expression in C2C12 cells, suggesting that endogenous IGF-I was not substantially involved in the underlying GH actions. On the other hand, androgen receptor and GH receptor mRNA expression was suppressed by BMP-2 in both cell lines, implying the existence of a feedback action. Collectively the results showed that the combined effects of androgen and GH facilitated BMP-2-induced osteoblast differentiation at an early stage by upregulating BMP receptor signaling.

DOI： 10.3390/jcm6010006

Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions. Reviewed International journal

Motoshi Komatsubara, Takayuki Hara, Takeshi Hosoya, Kishio Toma, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Kenichi Inagaki, Jun Wada, Fumio Otsuka

The Journal of steroid biochemistry and molecular biology 165 ( Pt B ) 182 - 189 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Melatonin is functionally involved in the control of circadian rhythm and hormonal secretion. In the present study, we investigated the roles of melatonin in the interaction of catecholamine synthesis with adrenocortical steroids by focusing on bone morphogenetic protein (BMP)-4 expressed in the adrenal medulla using rat pheochromocytoma PC12 cells. Melatonin treatment significantly reduced the mRNA expression of catecholamine synthases, including the rate-limiting enzyme tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanine decarboxylase and dopamine-beta-hydroxylase expressed in PC12 cells. In accordance with changes in the expression levels of enzymes, dopamine production and CAMP synthesis determined in the culture medium and cell lysate were also suppressed by melatonin. The MT1 receptor, but not the MT2 receptor, was expressed in PC12 cells, and luzindole treatment reversed the inhibitory effect of melatonin on Th expression, suggesting that MT1 is a functional receptor for the control of catecholamine synthesis. Interestingly, melatonin enhanced the inhibitory effect of BMP-4 on Th mRNA expression in PC12 cells. Melatonin treatment accelerated BMP-4-induced phosphorylation of SMAD1/5/8 and transcription of the BMP target gene Id1. Of note, melatonin significantly upregulated Alk2 and Bmpr2 mRNA levels but suppressed inhibitory Smac16/7 expression, leading to the enhancement of SMAD1/5/8 signaling in PC12 cells, while BMP-4 did not affect Mt1 expression. Regarding the interaction with adrenocortical steroids, melatonin preferentially enhanced glucocorticoid-induced Th mRNA through upregulation of the glucocorticoid receptor and downregulation of Bmp4 expression, whereas melatonin repressed Th mRNA expression induced by aldosterone or androgen without affecting expression levels of the receptors for mineralocorticoid and androgen. Collectively, the results indicate that melatonin plays a modulatory role in catecholamine synthesis by cooperating with BMP-4 and glucocorticoid in the adrenal medulla. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jsbmb.2016.06.002