Faculty Profiles - OTSUKA Fumio

Papers - OTSUKA Fumio

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Serum leptin correlates with serum uric acid but not serum testosterone in non-obese male adolescents

T Ogura 1, K Matsuura, F Otsuka, A Imai, C Tsukamoto, Y Mimura, Y Iwasaki, K Tobe

Res. Commun. Mol. Pathol. Pharmacol. 107 ( 1-2 ) 55-64 - 64 2000.1

Language：English Publishing type：Research paper (scientific journal) Publisher：P J D PUBLICATIONS LTD

To identify the serum factors that affect circulating leptin levels, we measured the serum concentrations of leptin, testosterone (T), estradiol (E), serum alanine aminotransferase, total cholesterol and uric acid (UA) in healthy male adolescents (age, 18.3 +/- 0.1 years, n=96). We also measured body mass index (BMI), percent body fat and thickness of skin fold to assess the effect of body constitution on serum leptin level. Since serum concentration of leptin significantly correlated with BMI (r=0.820, p<0.001), we analyzed the relation-ship between leptin/BMI ratio (L/BMI) and serum parameters. Analysis of data of subjects with normal serum T level showed a significant inverse correlation between L/BMI and serum T levels (n=96, r=-0.294, p<0.005), but no such correlation was present among non-obese subjects (n=70) with BMI of +/- 20% of normal (22 kg/m(2)). There was no correlation between L/BMI and serum E level. Serum UA level significantly correlated with L/BMI in both the test group (n=96, r=0.520, p<0.001) and non-obese subjects (r=0.369, p<0.005). Stepwise multiple regression analysis showed that UA independently and significantly influenced serum leptin levels in both the test and control groups. Our results demonstrate that T weakly influences serum leptin concentration, and that UA concentrations strongly influences serum leptin in healthy male adolescents independent of their obesity level.

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Pseudomalabsorption of Levothyroxine. A Case Report.

DAISUKE OGAWA, FUMIO OTSUKA, YUKARI MIMURA, AKIKO UENO, HIROO HASHIMOTO, MASAYUKI KISHIDA, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 47 ( 1 ) 45 - 50 2000

Hyperthyroidism in a Patient with TSH-Producing Pituitary Adenoma Coexisting with Thyroid Papillary Adenocarcinoma.

MASAYUKI KISHIDA, FUMIO OTSUKA, HIDEO KATAOKA, KAZUAKI YOKOTA, TETSUYA OISHI, TAKAYOSHI YAMAUCHI, HIROYOSHI DOIHARA, TAKASHI TAMIYA, YUKARI MIMURA, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 47 ( 6 ) 731 - 738 2000

Significant Gene Expression of Insulin-Like Growth Factor II and Proliferating Cell Nuclear Antigen in a Rapidly Growing Recurrent Pituitary ACTH-Secreting Adenoma

Kozo Hashimoto, Isao Nagano, Koichi Asaba, Mari Inoue, Tatsuya Nishioka, Toshihiro Takao, Takahito Nakajo, Takahisa Mori, Masahiro Kurisaka, Fumio Otsuka

Hormone Research in Paediatrics 54 ( 4 ) 198 - 202 2000

Publishing type：Research paper (scientific journal) Publisher：S. Karger AG

Background: We quantified the expression of various growth-related factors in an adrenocorticotropic hormone (ACTH)-secreting adenoma that had recurred very rapidly as invasive macroadenoma. Methods/Results: A 43-year-old woman underwent successful transsphenoidal surgery for Cushing’s disease. Seven years later, she was admitted to our ward for further endocrine examinations. In spite of a very high plasma ACTH level, the serum cortisol level was normal. Discrepancies between ACTH and cortisol levels were detected on the basis of diurnal rhythms, dexamethasone suppression tests, and corticotropin-releasing hormone test. The patient showed no clinical features of Cushing’s disease. Magnetic resonance imaging of the pituitary showed an almost empty sella, and no microadenoma was found. These results, along with those of Sephadex column gel filtration and high-performance liquid chromatography of plasma-immunoreactive ACTH, suggested that the patient’s residual corticotrophs secreted biologically inactive ACTH. Two years later, the patient suddenly developed diplopia and right abducens nerve palsy. She was slightly moonfaced and centrally obese. Her plasma ACTH and serum and urinary free cortisol levels were elevated, although discrepancies between ACTH and cortisol still existed. Magnetic resonance imaging revealed a large pituitary mass with suprasellar and cavernous sinus extensions. The tumor was excised, and the proopiomelanocortin gene and the expression of growth-related factors were analyzed. No mutations were found in the ACTH-coding region of the proopiomelanocortin gene. A significant expression of insulin-like growth factor II and proliferating cell nuclear antigen mRNAs was demonstrated. A high MIB-1 antibody labeling index was also detected in the adenoma tissue, suggesting high Ki-67 expression. Conclusion: These growth- and proliferation-related factors might be involved in the rapid growth and aggressiveness of this patient’s pituitary adenoma.

DOI： 10.1159/000053259

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Chronic Treatment with Angiotensin II Type 1 Receptor Antagonist Suppresses Glomerular Activator Protein–1 Activity in Salt–Sensitive Hypertensive Rats

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Minoru Sato, Hideo Kataoka, Jingo Kageyama, Hirofumi Makino

Kidney and Blood Pressure Research 23 ( 1 ) 35 - 41 2000

Publishing type：Research paper (scientific journal) Publisher：S. Karger AG

We examined the effects of angiotensin–converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor antagonist (AT1a) on the action of protooncogene c–fos in salt–sensitive hypertensive rats. Seven–week old Dahl salt–sensitive rats fed a high (8%)–salt diet were treated with ACEI, cilazapril (10 mg/kg) or AT1a, TCV–116 (1mg/ kg) every day for 6 weeks. The control animals were fed a low (0.3%)–salt diet. Systolic blood pressure gradually increased in high–salt–loaded rats and was higher than low–salt–treated rats throughout the study. However, both medications had no significant antihypertensive effect. After 6 weeks of therapy, glomerular mRNA and nuclear protein were extracted from the resected kidneys. Competitive reverse transcription–polymerase chain reaction showed a high level of glomerular c–fos mRNA in high–salt–loaded rats and that ACEI or AT1a treatment did not significantly change its level. Electrophoretic mobility shift assay demonstrated that treatment with AT1a significantly decreased the activator protein–1 (AP–1) binding activity in the glomerular nuclear extract compared to ACEI. Our findings suggest that, compared with ACEI treatment, long–term treatment with AT1a may contribute to attenuation of the glomerular injury in salt–sensitive hypertension by inhibiting AP–1 transcription activity independent of its antihypertensive effect.

DOI： 10.1159/000025952

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Sevoflurane anaesthesia causes a transient decrease in aquaporin-2 and impairment of urine concentration

K Morita, F Otsuka, T Ogura, M Takeuchi, S Mizobuchi, T Yamauchi, H Makino, M Hirakawa

British Journal of Anaesthesia 83 ( 5 ) 734 - 739 1999.11

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

Sevoflurane anaesthesia is occasionally associated with polyuria, but the exact mechanism of this phenomenon has not been clarified. Aquaporin-2 (AQP2) is an arginine vasopressin (AVP)-regulated water channel protein localized to the apical region of renal collecting duct cells and is involved in the regulation of water permeability. To elucidate the effect of sevoflurane anaesthesia on urine concentration and AQP2, we have compared serum and urinary concentrations of AVP, AQP2 and osmolar changes during sevoflurane and propofol anaesthesia. General anaesthesia was induced with sevoflurane or propofol in 30 patients for a variety of major surgical procedures. Blood and urine samples were obtained from patients at baseline, and 90 and 180 min after induction of anaesthesia. AVP and AQP2 concentrations were measured by radioimmunoassay. In both groups, plasma and urinary concentrations of AVP increased similarly during anaesthesia although plasma osmolality remained unchanged. Although urinary AQP2 excretion in the propofol group increased together with changes in plasma and urinary AVP, urinary AQP2 was significantly lower at 90 min in the sevoflurane group. Urine osmolality in the sevoflurane group also showed a transient but significant decrease in parallel with suppression of AQP2. Our data suggest that sevoflurane anaesthesia transiently produced an impaired AQP2 response to an increase in intrinsic AVP.

DOI： 10.1093/bja/83.5.734

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Quantitative analysis of growth-related factors in human pituitary adenomas

Fumio Otsuka, Takashi Tamiya, Takayoshi Yamauchi, Toshio Ogura, Takashi Ohmoto, Hirofumi Makino

Regulatory Peptides 83 ( 1 ) 31 - 38 1999.8

Long-term administration of adrenocorticotropin modulates the expression of IGF-I and TGF-β1mRNAs in the rat adrenal cortex

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Hideo Kataoka, Masayuki Kishida, Nobuyuki Miyatake, Yukari Mimura, Jingo Kageyama, Hirofumi Makino

Growth Hormone & IGF Research 9 ( 1 ) 41 - 51 1999.2

The Effects of Intrinsic Vasopressin on Urinary Aquaporin-2 Excretion and Urine Osmolality During Surgery Under General Anesthesia

Fumio Otsuka, Kiyoshi Morita, Mamoru Takeuchi, Takayoshi Yamauchi, Toshio Ogura, Kyouichi Sekine, Masakazu Miura, Masahisa Hirakawa, Hirofumi Makino

Anesthesia & Analgesia 88 ( 1 ) 181 - 187 1999.1

An Elderly Patient with Transient Diabetes Insipidus Associated with Lymphocytic Infundibulo-Neurohypophysitis.

MASAMI TAKAHASHI, FUMIO OTSUKA, TOMOKO MIYOSHI, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 46 ( 5 ) 741 - 746 1999

A case of idiopathic deep vein thrombosis improved with glucocorticoid therapy

F Otsuka, T Amano, H Uchida, T Ogura, H Makino

Haematologia (Budap) 29 ( 4 ) 305 - 312 1999

Giant Insulinoma in a Patient with Multiple Endocrine Neoplasia-Type I. A Case report.

HIDEO KATAOKA, FUMIO OTSUKA, TAKAYOSHI YAMAUCHI, MASAYUKI KISHIDA, MASAMI TAKAHASHI, TAKASHI TAMIYA, YUKARI MIMURA, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 46 ( 3 ) 429 - 435 1999

Treatment with a Ca2+ Channel Blocker, Barnidipine, Reduces Platelet-Derived Growth Factor B-Chain mRNA in Glomeruli of Spontaneously Hypertensive Rats

Masami Hashimoto, Takayoshi Yamauchi, Toshio Ogura, Tetsuya Oishi, Yukari Mimura, Fumio Otsuka, Naoki Kashihara, Hirofumi Makino

American Journal of Nephrology 19 ( 5 ) 615 - 621 1999

Publishing type：Research paper (scientific journal) Publisher：S. Karger AG

We investigated the effect of barnidipine hydrochloride, a Ca2+ channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-β1 in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR. The glomerular level of TGF-β1 mRNA expression was not affected by the treatment. Treatment with barnidipine significantly reduced the excretion of urinary protein. Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR.

DOI： 10.1159/000013511

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Congenital Adrenal Hyperplasia With Normokalemic Periodic Paralysis

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Hirofumi Makino

Archives of Neurology 55 ( 11 ) 1487 - 1487 1998.11

Renal c-fos expression induced by angiotensin II is enhanced in spontaneously hypertensive rats

Fumio Otsuka, Takayoshi Yamauchi, Toshio Ogura, Masami Takahashi, Jingo Kageyama, Hirofumi Makino

Life Sciences 63 ( 23 ) 2089 - 2095 1998.10

Hormonal characteristics of primary aldosteronism due to unilateral adrenal hyperplasia

Fumio Otsuka, F. Otsuka-Misunaga, S. Koyama, H. Yamanari, T. Ogura, T. Ohe, H. Makino

Journal of Endocrinological Investigation 21 ( 8 ) 531 - 536 1998.9

Cluster headache dependent upon octreotide injection

F Otsuka, J Kageyama, T Ogura, H Makino

Headache: The Journal of Head and Face Pain 38 ( 8 ) 629 - 631 1998.9

Effects of chronic inhibition of ACE and AT₁receptors on glomerular injury in Dahl salt-sensitive rats

Fumio Otsuka, Takayoshi Yamauchi, Hideo Kataoka, Yukari Mimura, Toshio Ogura, Hirofumi Makino

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274 ( 6 ) R1797 - R1806 1998.6

Language：English Publishing type：Research paper (scientific journal) Publisher：American Physiological Society

To elucidate the contribution of the renin-angiontensin system (RAS) to glomerular injury in salt-sensitive hypertension, we investigated the chronic effects of the angiotensin I-converting enzyme inhibitor cilazapril and the angiotensin II type 1-receptor antagonist (AT_1a) TCV-116 in Dahl-Iwai rats. Dahl salt-sensitive (S) rats receiving 8% salt diet for 6 wk were simultaneously treated with cilazapril ( n = 6), TCV-116 ( n = 6), or saline ( n = 14). The 8% salt diet markedly increased systolic blood pressure (SBP), urinary protein, and N-acetyl-β-glucosaminidase (NAG) excretion compared with 0.3% salt-treated S ( n = 6) or salt-resistant ( n = 6) rats. Although neither cilazapril nor TCV-116 reduced the elevated SBP, TCV-116 significantly lowered urinary protein and NAG excretion. Histologically, 8% salt treatment in S rats induced progressive sclerotic and proliferative glomerular changes, which were ameliorated by both drugs. TCV-116 increased the glomerular diameter. Immunofluorescence demonstrated the increased level of type III collagen in the mesangium of 8% salt-treated S rats, which was completely reversed by TCV-116. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that 8% salt treatment significantly increased the levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor B-chain and that TCV-116 significantly reduced the levels of PCNA and transforming growth factor-β1 (TGF-β1). Thus, although the chronic RAS-inhibition in salt-sensitive hypertension exerted a histologically renoprotective effect by both ways without lowering blood pressure, the RAS inhibition due to AT_1ahad more beneficial advantages of reducing proteinuria and attenuating the levels of glomerular TGF-β1 and extracellular matrix.

DOI： 10.1152/ajpregu.1998.274.6.r1797

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Effect of continuous infusion of vasopressin on glomerular growth response in spontaneously hypertensive rats

Kazushi Harada, Toshio Ogura, Takayoshi Yamauchi, Fumio Otsuka, Yukari Mimura, Masami Hashimoto, Tetsuya Oishi, Hirofumi Makino

Regulatory Peptides 74 ( 1 ) 11 - 18 1998.4

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

Vasopressin (VP) is thought to play an important role in the presser and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta 1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the II-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta 1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta 1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta 1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease. (C) 1998 Published by Elsevier Science B.V.

DOI： 10.1016/s0167-0115(98)00009-3

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Sheehan's syndrome of more than 30 years' duration: an endocrine and MRI study of 6 cases

Fumio Otsuka, Jingo Kageyama, Toshio ogura, Teruhiko Hattori, Hirofumi makino

Endocr. J. 45 451-458 1998.1

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