Faculty Profiles - OTSUKA Fumio

Superior ophthalmic vein thrombosis associated with severe facial trauma: a case report. Reviewed International journal

Momoko Mishima, Tetsuya Yumoto, Hiroaki Hashimoto, Takao Yasuhara, Atsuyoshi Iida, Kohei Tsukahara, Keiji Sato, Toyomu Ugawa, Fumio Otsuka, Yoshihito Ujike

Journal of medical case reports 9 244 - 244 2015.10

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

INTRODUCTION: Superior ophthalmic vein thrombosis is a rare entity, but is associated with significant morbidities. We describe a case in which superior ophthalmic vein thrombosis occurred shortly after severe facial trauma. CASE PRESENTATION: A 77-year-old Japanese man was transferred to our tertiary hospital after a motor vehicle accident. Le Fort III facial bone fractures and a minor cerebral contusion were detected. Follow-up computed tomography scans detected dilatation of his left superior ophthalmic vein on day 3 and thrombosis on day 12; however, no causative carotid cavernous fistula was observed. As he did not present with any symptoms other than slight conjunctival congestion, a conservative management strategy was adopted along with anticoagulant therapy against deep venous thrombosis. The superior ophthalmic vein thrombosis resolved spontaneously and the conjunctival congestion also improved. CONCLUSIONS: Superior ophthalmic vein thrombosis should be taken into consideration and managed properly after severe facial injuries, and further investigation of its cause is necessary to prevent morbidities.

DOI： 10.1186/s13256-015-0737-y

Mutual effects of melatonin and activin on induction of aldosterone production by human adrenocortical cells. Reviewed International journal

Takayuki Hara, Fumio Otsuka, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Takeshi Hosoya, Eri Nakamura, Tomohiro Terasaka, Motoshi Komatsubara, Hirofumi Makino

The Journal of steroid biochemistry and molecular biology 152 8 - 15 2015.8

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

Melatonin has been reported to suppress adrenocorticotropin (ACTH) secretion in the anterior pituitary and cortisol production in the adrenal by different mechanisms. However, the effect of melatonin on aldosterone production has remained unknown. In this study, we investigated the role of melatonin in the regulation of aldosterone production using human adrenocortical H295R cells by focusing on the activin system expressed in the adrenal. Melatonin receptor MT1 mRNA and protein were expressed in H295R cells and the expression levels of MT1 were increased by activin treatment. Activin increased ACTH-induced, but not angiotensin II (Ang II)-induced, aldosterone production. Melatonin alone did not affect basal synthesis of either aldosterone or cortisol. However, melatonin effectively enhanced aldosterone production induced by co-treatment with ACTH and activin, although melatonin had no effect on aldosterone production induced by Ang II in combination with activin. These changes in steroidogenesis became apparent when the steroid production was evaluated by the ratio of aldosterone/cortisol. Melatonin also enhanced dibutyryl-AMP-induced aldosterone/cortisol levels in the presence of activin, suggesting a functional link to the cAMP-PKA pathway for induction of aldosterone production by melatonin and activin. In accordance with the data for steroids, ACTH-induced, but not Ang II-induced, cAMP synthesis was also amplified by co-treatment with melatonin and activin. Furthermore, the ratio of ACTH-induced mRNA level of CYP11B2 compared with that of CYP17 was amplified in the condition of treatment with both melatonin and activin. In addition, melatonin increased expression of the activin type-I receptor ALK-4 but suppressed expression of inhibitory Smads6/7, leading to the enhancement of Smad2 phosphorylation. Collectively, the results showed that melatonin facilitated aldosterone production induced by ACTH and activin via the cAMP-PKA pathway. The results also suggested that mutual enhancement of melatonin and activin receptor signaling is involved in the induction of aldosterone output by adrenocortical cells.

DOI： 10.1016/j.jsbmb.2015.04.012

A Rare Cause of Esophageal Ulcers. Reviewed International journal

Masaya Iwamuro, Takao Tsuzuki, Fumio Otsuka

Gastroenterology 149 ( 1 ) 31 - 2 2015.7

Atypical Onset of Eosinophilic Granulomatosis with Polyangitis in a Patient with Long-term Well-controlled Bronchial Asthma Reviewed

Satoshi Akao, Hideharu Hagiya, Kou Hasegawa, Takahiro Nada, Eri Nakamura, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Kentaro Deguchi, Fumio Otsuka

JOURNAL OF GENERAL AND FAMILY MEDICINE 16 ( 2 ) 99 - 102 2015.6

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

Eosinophillic glanuromatosis with polyangitis (EGPA) usually occurs in patients with a recent history (usually less than 10 years) of uncontrolled bronchial asthma. Here we describe a case of EGPA that occurred in a 68-year-old female who had well-controlled bronchial asthma for 17 years. A leukotriene receptor antagonist that had been prescribed one week before onset might have triggered the disease. Our case shows that there is a wide spectrum of clinical characteristics of EGPA, making diagnosis difficult in a primary care setting.

Gastric pseudopolyposis formed after recovery from gastric gangrene. Reviewed International journal

Masaya Iwamuro, Yoshihisa Hanayama, Fumio Otsuka, Hiroyuki Okada

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 47 ( 6 ) e9 - E9 2015.6

皮疹の再燃を繰り返しCD8陽性Terminally differentiated effector memory cellの増加を認めた薬剤性過敏症症候群(DIHS)の一例

青江伯規, 今田昌秀, 高橋孝英, 榊原佳奈枝, 日野佳弥, 狩山由貴, 渡部俊幸, 岡田健, 大塚文男

日本検査血液学会雑誌 16 ( 学術集会 ) S99 - S99 2015.6

Complication of chronic eosinophilic pneumonia in an elderly patient with Sjögren syndrome. Reviewed

Koichi Waseda, Hideharu Hagiya, Yoshihisa Hanayama, Tomohiro Terasaka, Kosuke Kimura, Takao Tsuzuki, Kou Hasegawa, Takahiro Nada, Eri Nakamura, Kazutoshi Murakami, Eisei Kondo, Fumio Otsuka

Acta medica Okayama 69 ( 2 ) 123 - 7 2015.4

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

An 81-year-old Japanese male with primary Sjogren syndrome (pSS) developed a low-grade fever and productive cough which were refractory to antibiotic therapy. Based on the high level of eosinophils observed in his bronchial alveolar lavage, he was diagnosed with chronic eosinophilic pneumonia (CEP) and successfully treated by oral prednisolone. Interstitial lung diseases associated with pSS (pSS-ILDs) usually present as nonspecific interstitial pneumonia or usual interstitial pneumonia; therefore, the present case is extremely unique in that the patient's condition was complicated with CEP. A diagnosis of advanced gallbladder cancer was made in the patient's clinical course, suggesting the advisability of a whole-body workup in cases of pSS, especially in elderly patients.

Interaction of pituitary hormones and expression of clock genes modulated by bone morphogenetic protein-4 and melatonin. Reviewed International journal

Naoko Tsukamoto-Yamauchi, Tomohiro Terasaka, Yasumasa Iwasaki, Fumio Otsuka

Biochemical and biophysical research communications 459 ( 1 ) 172 - 7 2015.3

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

Functional interaction of clock genes and pituitary hormones was investigated by focusing on bone morphogenetic protein (BMP)-4 and melatonin actions in anterior pituitary cells. A significant correlation between the mRNA expression of proopiomelanocortin (POMC) and Per2 was revealed in serial cultures of corticotrope AtT20 cells. Knockdown of Per2 expression by siRNA in AtT20 cells resulted in a significant reduction of POMC mRNA level with or without corticotropin-releasing hormone (CRH) stimulation. Treatments with BMP-4 and melatonin, both of which suppress POMC expression, reduced Per2 mRNA as well as protein levels in AtT20 cells. On the other hand, in lactosomatotrope GH3 cells, an expressional correlation was found between prolactin (PRL) and Clock mRNA levels, which was attenuated in the presence of forskolin treatment. The siRNA-mediated knockdown of Clock expression, but not that of Bmal1, significantly reduced PRL mRNA levels in GH3 cells. Interestingly, Clock mRNA and protein levels did not fluctuate with melatonin, BMP-4 or forskolin treatment, although Bmal1 expression was significantly increased by forskolin treatment. Collectively, a significant correlation between the expression of POMC and Per2 and that between PRL and Clock were uncovered in corticotrope and lactosomatotrope cells, respectively. Per2 expression was inhibited by POMC modulators including melatonin and BMP-4, while Clock expression was steadily maintained. Thus, the effects of melatonin and BMP-4 on clock gene expression may imply differential stability of circadian rhythms of adrenocorticotropin (ACTH) and PRL secreted from the anterior pituitary.

DOI： 10.1016/j.bbrc.2015.02.100

Regulatory role of BMP-9 in steroidogenesis by rat ovarian granulosa cells. Reviewed International journal

Takeshi Hosoya, Fumio Otsuka, Eri Nakamura, Tomohiro Terasaka, Kenichi Inagaki, Naoko Tsukamoto-Yamauchi, Takayuki Hara, Kishio Toma, Motoshi Komatsubara, Hirofumi Makino

The Journal of steroid biochemistry and molecular biology 147 85 - 91 2015.3

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

BMPs expressed in the ovary differentially regulate steroidogenesis by granulosa cells. BMP-9, a circulating BMP, is associated with cell proliferation, apoptosis and differentiation in various tissues. However, the effects of BMP-9 on ovarian function have yet to be elucidated. Here we investigated BMP-9 actions on steroidogenesis using rat primary granulosa cells. BMP-9 potently suppressed FSH-induced progesterone production, whereas it did not affect FSH-induced estradiol production by granulosa cells. The effects of BMP-9 on FSH-induced steroidogenesis were not influenced by the presence of oocytes. FSH-induced cAMP synthesis and FSH-induced mRNA expression of steroidogenic factors, including StAR, P450scc, 3βHSD2 and FSHR, were suppressed by treatment with BMP-9. BMP-9 mRNA expression was detected in granulosa cells but not in oocytes. BMP-9 readily activated Smad1/5/8 phosphorylation and Id-1 transcription in granulosa cells. Analysis using ALK inhibitors indicated that BMP-9 actions were mediated via type-I receptors other than ALK-2, -3 and -6. Furthermore, experiments using extracellular domains (ECDs) for BMP type-I and -II receptor constructs revealed that the effects of BMP-9 were reversed by ECDs for ALK-1 and BMPRII. Thus, the functional receptors for BMP-9 in granulosa cells were most likely to be the complex of ALK-1 and BMPRII. Collectively, the results of the present study showed that BMP-9 can affect luteinization and that there are two possible sources of BMP-9, serum and granulosa cells in the ovary.

DOI： 10.1016/j.jsbmb.2014.12.007

Lemierre syndrome involving external jugular vein. Reviewed International journal

Hideharu Hagiya, Yuto Haruki, Fumio Otsuka

Acute medicine & surgery 2 ( 1 ) 64 - 68 2015.1

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

Case: A 74-year-old woman with a week-long history of cold symptoms was diagnosed with Lemierre syndrome that involved her left external jugular vein. Outcome: The patient was successfully treated with 4 weeks of antibiotics and anticoagulant treatment. Typical cases of Lemierre syndrome involve only the internal jugular vein. The external jugular vein is anatomically distant from the pharyngolaryngeal space and usually does not receive blood or lymphatic flow from there. Thus, Lemierre syndrome ordinarily does not involve the external jugular vein and clinical characteristics of external jugular vein-involving Lemierre syndrome have not been uncovered, mainly due to its rarity. Based on our review, it would not much differ from those of typical cases. Conclusion: Considering the potential severity and mortality, more attention should be paid to this potentially fatal disease that may demonstrate atypical manifestation, as shown in this case. Accumulation of cases would be needed for further understanding.

DOI： 10.1002/ams2.61

Disseminated streptococcal endophthalmitis in two diabetic patients. Reviewed

Hideharu Hagiya, Kotaro Aoki, Kazuhiro Tateda, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 10 ) 1317 - 8 2015

A paraganglioma in a hypertensive patient with unilateral renal hypoplasia. Reviewed

Tomohiro Terasaka, Hideharu Hagiya, Kosuke Kimura, Takahiro Nada, Eri Nakamura, Yoshihisa Hanayama, Hitoshi Sugiyama, Yasuyuki Kobayashi, Hiroyuki Yanai, Fumio Otsuka

Acta medica Okayama 69 ( 2 ) 119 - 22 2015

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

We report the case of a 46-year-old hypertensive Japanese female with renal insufficiency related to unilateral renal hypoplasia. The patient was found to have developed paraganglioma in the retroperitoneal space over a 5-year period. Catecholamine-producing tumors are not usually recognized as conditions associated with renal hypoplasia. Our long-term observation of the patient eventually led us to the diagnosis of paraganglioma. In hypertensive patients with chronic kidney disease, not only the renin-angiotensin-aldosterone system but also catecholamine activity may be involved, particularly in the patients whose cases are complicated with unilateral renal hypoplasia.

DOI： 10.18926/AMO/53341

An Insulinoma Discovered in a Patient with Diffusely Calcified Chronic Pancreatitis. Reviewed

Tomohiro Terasaka, Keiko Tsukamoto, Kenichi Inagaki, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 21 ) 2785 - 6 2015

Myopathy and eosinophilic pneumonia coincidentally induced by treatment with daptomycin. Reviewed

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Tomohiro Terasaka, Kosuke Kimura, Takahiro Nada, Eri Nakamura, Koichi Waseda, Yoshihisa Hanayama, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 5 ) 525 - 9 2015

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

A 34-year-old man with 22q11.2 deletion syndrome (DiGeorge syndrome) concurrently suffered from myopathy and eosinophilic pneumonia shortly after receiving daptomycin (DAP) for right-sided infective endocarditis. The simultaneous occurrence of these phenomena in relation to DAP therapy has not been previously well described. An allergic reaction was suspected as a possible etiology of these DAP-related complications. This case highlights the need for close observation in order to detect both musculoskeletal and respiratory disorders from the start of DAP therapy. Physicians should pay more attention to this new drug, which is expected to be frequently used in various clinical settings.

DOI： 10.2169/internalmedicine.54.3397

Hyperintense Lesion in the Pons in Intravascular Lymphoma. Reviewed

Masaya Iwamuro, Kosuke Kimura, Eisei Kondo, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 18 ) 2421 - 2 2015

Infective Internal Iliac Artery Aneurysm Caused by Campylobacter fetus. Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Kou Hasegawa, Yoshihisa Hanayama, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 16 ) 2021 - 4 2015

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

A 67-year-old man with a persistent high fever was diagnosed to have an infective aneurysm in his left internal iliac artery. A blood culture detected a gram-negative spiral rod that was first identified as Campylobacter fetus subsp. venerealis based on a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. However, the strain was finally confirmed to be Campylobacter fetus subsp. fetus based on a genetic analysis. The infection was successfully treated with emergency resection of the aneurysm, followed by 4 weeks of antibiotic therapy. Involvement of the peripheral artery is uncommon in cases of C. fetus-infective aneurysm. To figure out the epidemiology and pathogenicity of C. fetus infection, the accurate identification of the responsible organisms is essential.

DOI： 10.2169/internalmedicine.54.4845

A Nephrostomy-associated Urinary Tract Infection Caused by Elizabethkingia meningoseptica. Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Kou Hasegawa, Masaya Iwamuro, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 24 ) 3233 - 6 2015

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

We report a case of nephrostomy-associated urinary tract infection caused by Elizabethkingia meningoseptica that occurred in a patient with retroperitoneal fibrosis. Though conventional identification methods failed to detect the causative organism, it was identified on the basis of the complete sequencing of 16S rRNA. Four weeks of levofloxacin and minocycline administration successfully eradicated the infection. E. meningoseptica rarely causes urinary tract infections, and we believe that this is the first such case in which the isolate was genetically confirmed. The accurate identification of the organism is necessary for the provision of appropriate treatment and to obtain a better understanding of its epidemiology and pathogenicity.

DOI： 10.2169/internalmedicine.54.4998

Klebsiella oxytoca-producing IMP-1 Detected as the First Strain of Carbapenem-resistant Enterobacteriaceae in Our Hospital. Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Akira Yamamoto, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 22 ) 2939 - 41 2015

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

We herein report a case of Klebsiella oxytoca-producing IMP-1 that was detected as a first isolate of carbapenem-resistant Enterobacteriaceae (CRE) at our facility. Since K. oxytoca is an uncommon strain for CRE, we speculated that the resistant organism had already spread out inside the hospital. Metallo-β-lactamases promotes antibiotic resistance in Enterobacteriaceae, which potentially yields problematic issues in clinical settings. Active surveillance of antibiotic resistant strains is important and should be repeatedly highlighted. Furthermore, appropriate methods should be established to detect highly resistant strains.

DOI： 10.2169/internalmedicine.54.4965