Faculty Profiles - OTSUKA Fumio

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice. Reviewed International journal

Fumiya Ojima, Yuka Saito, Yukiko Tsuchiya, Maho Ogoshi, Hiroshi Fukamachi, Kenichi Inagaki, Fumio Otsuka, Sakae Takeuchi, Sumio Takahashi

Cell and tissue research 375 ( 3 ) 743 - 754 2019.3

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

We previously demonstrated that female Runx3 knockout (Runx3-/-) mice were anovulatory and their uteri were atrophic and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examine the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3-/- mouse ovaries, the numbers of primary and antral follicles were lower than those in wild-type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba and Inhbb) was also decreased in ovaries from the Runx3-/- mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3-/- mice than those in wt mice. Follicle-stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3-/- granulosa cells in culture but the mRNA level in Runx3-/- granulosa cells was lower than that in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin α subunit, FSHβ subunit and luteinizing hormone (LH) β subunit mRNA levels were decreased in Runx3-/- mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells.

DOI： 10.1007/s00441-018-2947-2

Interaction of ovarian steroidogenesis and clock gene expression modulated by bone morphogenetic protein-7 in human granulosa cells.

Satoko Nagao, Nahoko Iwata, Yoshiaki Soejima, Takaaki Takiguchi, Tamami Aokage, Yuka Kozato, Yasuhiro Nakano, Takahiro Nada, Toru Hasegawa, Fumio Otsuka

Endocrine journal 66 ( 2 ) 157 - 164 2019.2

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

A functional link between clock gene expression and ovarian steroidogenesis was studied using human granulosa KGN cells. Similarities between changes in the mRNA and protein expression levels of Bmal1 and Clock and those of Per2 and Cry1 were found in KGN cells after treatment with forskolin. Among the interrelationships between the expression levels of clock and steroidogenic factors, Clock mRNA had a strongly positive correlation with P450arom and a negative correlation with 3βHSD. Knockdown of Clock gene by siRNA resulted in a significant reduction of estradiol production by inhibiting P450arom expression, while it induced a significant increase of progesterone production by upregulating 3βHSD in KGN cells treated with forskolin. Moreover, BMP-7 had an enhancing effect on the expression of Clock mRNA and protein in KGN cells. Thus, the expression levels of Clock, being upregulated by forskolin and BMP-7, were functionally linked to estradiol production and progesterone suppression by human granulosa cells.

DOI： 10.1507/endocrj.EJ18-0423

Diagnostic FDG PET/CT findings in polymyalgia rheumatica. International journal

Y Otsuka, K Harada, F Otsuka

QJM : monthly journal of the Association of Physicians 112 ( 2 ) 139 - 140 2019.2

Auricle Pain Due to Tophi.

Yasuhiro Nakano, Fumio Otsuka

Internal medicine (Tokyo, Japan) 58 ( 3 ) 453 - 453 2019.2

Comparison of Two Electrosurgical Modes for Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms: A Prospective Randomized Study.

Yuusaku Sugihara, Keita Harada, Shohei Oka, Eriko Yasutomi, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada

Acta medica Okayama 73 ( 1 ) 81 - 84 2019.2

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

Endoscopic submucosal dissection (ESD) is reportedly one of the standard treatment strategies for large superficial colorectal neoplasms in Japan because of its high en bloc resection rate. A few technical issues regarding ESD should be considered, one of which is the selection of the Endo-cut I mode versus the Swift-coagulation mode as the electrosurgical unit mode setting during submucosal dissection. We seek to determine which of these two modes is more suitable for submucosal dissections of colorectal tumors with regard to procedure time and safety.

DOI： 10.18926/AMO/56463

A Remarkable Uptake of FDG in Huge Mediastinal Hashimoto's Goiter.

Kosuke Oka, Takeshi Hosoya, Naruto Taira, Fumio Otsuka

Internal medicine (Tokyo, Japan) 58 ( 2 ) 313 - 314 2019.1

A Case of Juvenile Hypertension Suggestive of Adrenomedullary Hyperplasia.

Yoshito Nishimura, Miho Yasuda, Kou Hasegawa, Fumio Otsuka

Internal medicine (Tokyo, Japan) 58 ( 2 ) 311 - 311 2019.1

Hyperthyroidism with Selective Immunoglobulin A Deficiency.

Ko Harada, Fumio Otsuka

Internal medicine (Tokyo, Japan) 58 ( 1 ) 145 - 146 2019.1

Actinomycosis-induced Trismus with Orbital Involvement.

Daisuke Omura, Kammei Rai, Nobuchika Kusano, Fumio Otsuka

Internal medicine (Tokyo, Japan) 58 ( 1 ) 153 - 154 2019.1

A marked goiter involved in Marine-Lenhart syndrome.

Kosuke Oka, Miho Yasuda, Tadahiko Shien, Fumio Otsuka

Journal of general and family medicine 20 ( 1 ) 37 - 38 2019.1

Pleomorphic parotid adenoma with Graves’hyperthyroidism．

Ogura-Ochi K, Otsuka F

J. Hosp. Gen. Med. 15 26 - 27 2019.1

Cognitive decline due to ectopic primary hyperparathyroidism. International journal

Yoshito Nishimura, Akira Yamamoto, Masahiro Takahara, Fumio Otsuka

Clinical case reports 6 ( 12 ) 2513 - 2514 2018.12

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

When you see a patient with cognitive dysfunction, hypercalcemia due to hyperparathyroidism is an important differential diagnosis. It is important to consider including chest computed tomography and 131I-MIBI SPECT examinations in patients with possible hyperparathyroidism and normal thyroid ultrasound.

DOI： 10.1002/ccr3.1901

Changes in Serum Biochemical Markers in Relation to Chief Complaints and Aging in General Medicine.

Daisuke Omura, Asuka Sato, Kosuke Oka, Yoshihisa Hanayama, Hiroko Ogawa, Mikako Obika, Fumio Otsuka

Acta medica Okayama 72 ( 6 ) 553 - 562 2018.12

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

To clarify potential relationships between chief complaints of patients and laboratory data with a focus on aging-related changes, we retrospectively analyzed the data of 843 patients who visited a general medicine department for the first time. Their chief complaints were classified into 8 major symptoms: visceral pain, somatic pain, fever, cough, dizziness, fatigue, appetite loss, and edema. We compared the laboratory data obtained from the patients with complaints with the data of symptom-free (control) patients. The serum sodium and potassium levels in the fever group were decreased compared to those in the control group. In the fever group, the serum sodium level was inversely correlated with age. The ratio of serum urea nitrogen to creatinine (UN/Cr) was increased in the appetite-loss group. There were significant age-dependent increases in the UN/Cr ratio in the appetite-loss and edema groups. Of note, serum levels of free thyroxin were lower in the dizziness group compared to the control group. In addition, the free thyroxin level was inversely correlated with age in the dizziness group but not in the asymptomatic control group. Collectively, the results indicated that osmolality-related laboratory data are strongly associated with individual primary symptoms at the first visit regardless of the final diagnosis. The consideration of age-dependent changes of these markers is helpful for diagnosing latent disorders based on various primary symptoms.

DOI： 10.18926/AMO/56372

A Case of Diffuse Esophageal Spasm Treated with Peroral Endoscopic Myotomy.

Yuusaku Sugihara, Keita Harada, Ryo Kato, Kenji Yamauchi, Hiroyuki Sakae, Seiji Kawano, Sakiko Hiraoka, Yoshiro Kawahara, Fumio Otsuka, Hiroyuki Okada

Acta medica Okayama 72 ( 6 ) 595 - 600 2018.12

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

The indications for peroral endoscopic myotomy (POEM) have been expanded to include diffuse esophageal spasm (DES). A 67-year-old Japanese man presented with a 4-year history of dysphagia. Endoscopy and upper gastrography revealed abnormal peristaltic movements involving interruption of normal peristalsis, and a diverticulum located at the 2 o'clock esophageal position. High-resolution manometry indicated DES. POEM with a long (15 cm) myotomy was performed for the abnormal contractions, which subsequently disappeared along with dysphagia improvement. Our results suggest that esophageal motility disorders accompanying a diverticulum may be eliminated by POEM without treating the diverticulum itself. We speculate that POEM ameliorates esophageal diverticulum by reducing internal esophageal pressure.

DOI： 10.18926/AMO/56378

Clival Osteomyelitis with Cavernous Sinus Thrombosis Due to Fusobacterium nucleatum and Campylobacter rectus Induced by Tooth Extraction.

Kosuke Oka, Yasuhiro Nakano, Yosuke Sazumi, Tomo Michitani, Shigeru Horiguchi, Kazuki Ocho, Masaya Iwamuro, Fumio Otsuka

Internal medicine (Tokyo, Japan) 57 ( 22 ) 3325 - 3328 2018.11

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

A 70-year-old woman who had suffered from aseptic meningitis complained of chronic headache after dental treatment including tooth extraction. She developed a fever and respiratory failure. Based on chest computed tomography and head magnetic resonance imaging (MRI), she was diagnosed with osteomyelitis in the clivus accompanying moderate pituitary involvement, cavernous sinus thrombosis and septic pulmonary embolism. Both of the causal bacteria, Fusobacterium nucleatum and Campylobacter rectus, were isolated from her blood. Dual infection leading to clival osteomyelitis and cavernous sinus thrombosis has not been reported. It is important to perform enhanced MRI and blood culture for patients with chronic headache related to dental treatment.

DOI： 10.2169/internalmedicine.1025-18

Clinical relevance of low androgen to gastroesophageal reflux symptoms.

Ko Harada, Yoshihisa Hanayama, Miho Yasuda, Kou Hasegawa, Mikako Obika, Hitomi Kataoka, Koichi Itoshima, Ken Okada, Fumio Otsuka

Endocrine journal 65 ( 10 ) 1039 - 1047 2018.10

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

The aim of this study was to determine the relationships between free testosterone (FT) level and parameters including laboratory data and data from questionnaires and to determine symptoms leading to the detection of late onset hypogonadism (LOH). We retrospectively reviewed medical records of patients in whom serum FT was measured in our hospital. Aging Male Symptoms (AMS) score, self-rating depression scale (SDS) and frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) score were used for questionnaires. A total of 205 patients were included in the analysis (55.2 ± 15.6 years of age, mean ± SD). Among them, 119 patients (58.0%) had an FT level of less than 8.5 pg/mL, which fulfills the diagnostic criterion of LOH syndrome according to the clinical practice manual for LOH in Japan. It was revealed that FSSG score was inversely correlated to serum FT levels (r = -0.3395, p < 0.001), although SDS and AMS scales did not show significant correlations to FT levels. Our study revealed a high prevalence of LOH syndrome among patients in whom the majority complained of general symptoms. Although GERD symptoms are generally not considered to be typical symptoms of LOH, our study indicates that those symptoms might be clues for the detection of LOH.

DOI： 10.1507/endocrj.EJ18-0187