岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 147 2011 Clinical Usefulness of TSH Receptor Autoantibody Using Different Assay Systems 135 144 EN Yukari Mimura Toshio Ogura Fumio Otsuka 10.18926/bgeou/47111 Thyroid stimulating hormone receptor antibody (TRAb) plays an important role in Graves' disease (GD). A second-generation measurement system has been developed and we have gotten a benefit by the system clinically. In this study, we determined 4 kinds of TRAb in 42 GD patients using the current and second-generation measurement systems to investigate the differences between them. The secondgeneration measurement system exhibited higher positive rates and inhibition rates of thyroid stimulating hormone (TSH) binding than those of the current system. Furthermore, 42 patients with GD were classified into 4 groups by GD activity. The actual values of all TRAbs and positive rates exhibited a tendency to increase significantly with GD activity. Of significance, 2 TRAbs in the second-generation measurement system exhibited high positive rates. However, all actual values of patients did not necessarily agree with these tendencies. The values of TRAb-human detecting anti-human TSH receptors at an approximate cut-off value reflected GD activity more accurately than those of TRAb-CT detecting anti-porcine TSH receptor. This suggests the possibility of specific differences between TSH receptors and further studies are required to further examine these effects. No potential conflict of interest relevant to this article was reported.

Elsevier Ireland Ltd. Acta Medica Okayama 0303-7207 332 1-2 2011 Activities of bone morphogenetic proteins in prolactin regulation by somatostatin analogs in rat pituitary GH3 cells 163 169 EN Naoko Tsukamoto Fumio Otsuka Tomoko Miyoshi Kenichi Inagaki Eri Nakamura Jiro Suzuki Toshio Ogura Yasumasa Iwasaki Hirofumi Makino Involvement of the pituitary BMP system in the modulation of prolactin (PRL) secretion regulated by somatostatin analogs, including octreotide (OCT) and pasireotide (SOM230), and a dopamine agonist, bromocriptine (BRC), was examined in GH3 cells. GH3 cells are rat pituitary somato-lactotrope tumor cells that express somatostatin receptors (SSTRs) and BMP system molecules including BMP-4 and -6. Treatment with BMP-4 and -6 increased PRL and cAMP secretion by GH3 cells. The BMP-4 effects were neutralized by adding a BMP-binding protein Noggin. These findings suggest the activity of endogenous BMPs in augmenting PRL secretion by GH3 cells. BRC and SOM230 reduced PRL secretion, but OCT failed to reduce the PRL level. In GH3 cells activated by forskolin, BRC suppressed forskolin-induced PRL secretion with reduction in cAMP levels. OCT did not affect forskolin-induced PRL level, while SOM230 reduced PRL secretion and PRL mRNA expression induced by forskolin. BMP-4 treatment enhanced the reducing effect of SOM230 on forskolin-induced PRL level while BMP-4 did not affect the effects of OCT or BRC. Noggin treatment had no significant effect on the BRC actions reducing PRL levels by GH3 cells. However, in the presence of Noggin, OCT elicited an inhibitory effect on forskolin-induced PRL secretion and PRL mRNA expression, whereas the SOM230 effect on PRL reduction was in turn impaired. It was further found that BMP-4 and -6 suppressed SSTR-2 but increased SSTR-5 mRNA expression of GH3 cells. These findings indicate that Noggin rescues SSTR-2 but downregulates SSTR-5 by neutralizing endogenous BMP actions, leading to an increase in OCT sensitivity and a decrease in SOM230 sensitivity of GH3 cells. In addition, BMP signaling was facilitated in GH3 cells treated with forskolin. Collectively, these findings suggest that BMPs elicit differential actions in the regulation of PRL release dependent on cellular cAMP-PKA activity. BMPs may play a key role in the modulation of SSTR sensitivity of somato-lactotrope cells in an autocrine/paracrine manner. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 149 6 2008 Aldosterone breakthrough caused by chronic blockage of angiotensin II type 1 receptors in human adrenocortical cells: Possible involvement of bone morphogenetic protein-6 actions 2816 2825 EN Hiroyuki Otani Fumio Otsuka Kenichi Inagaki Jiro Suzuki Tomoko Miyoshi Yoshihiro Kano Junko Goto Toshio Ogura Hirofumi Makino Circulating aldosterone concentrations occasionally increase after initial suppression with angiotensin II (Ang II) converting enzyme inhibitors or Ang II type 1 receptor blockers (ARBs), a phenomenon referred to as aldosterone breakthrough. However, the underlying mechanism causing the aldosterone breakthrough remains unknown. Here we investigated whether aldosterone breakthrough occurs in human adrenocortical H295R cells in vitro. We recently reported that bone morphogenetic protein (BMP)-6, which is expressed in adrenocortical cells, enhances Ang II-but not potassium-induced aldosterone production in human adrenocortical cells. Accordingly, we examined the roles of BMP-6 in aldosterone breakthrough induced by long-term treatment with ARB. Ang II stimulated aldosterone production by adrenocortical cells. This Ang II stimulation was blocked by an ARB, candesartan. Interestingly, the candesartan effects on Ang II-induced aldosterone synthesis and CYP11B2 expression were attenuated in a course of candesartan treatment for 15 d. The impairment of candesartan effects on Ang II-induced aldosterone production was also observed in Ang II- or candesartanpretreated cells. Levels of Ang II type 1 receptor mRNA were not changed by chronic candesartan treatment. However, BMP-6 enhancement of Ang II- induced ERK1/2 signaling was resistant to candesartan. The BMP-6-induced Smad1, -5, and -8 phosphorylation, and BRE-Luc activity was augmented in the presence of Ang II and candesartan in the chronic phase. Chronic Ang II exposure decreased cellular expression levels of BMP-6 and its receptors activin receptor-like kinase-2 and activin type II receptor mRNAs. Cotreatment with candesartan reversed the inhibitory effects of Ang II on the expression levels of these mRNAs. The breakthrough phenomenon was attenuated by neutralization of endogenous BMP-6 and activin receptor-like kinase-2. Collectively, these data suggest that changes in BMP-6 availability and response may be involved in the occurrence of cellular escape from aldosterone suppression under chronic treatment with ARB. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 45 5 1991 Effects of beta-adrenergic blocking agents on specific binding of [3H]D-Ala2-Met5-enkephalinamide and [3H]naloxone. 295 299 EN Haruhiko Takayama Norio Ogawa Masato Asanuma Hiroshi Hirata Toshio Ogura Zensuke Ota Article 10.18926/AMO/32199 To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 55 5 2001 Serum total cholesterol of new students enrolled at Okayama University: trend during 1989-1998. 269 276 EN Toshio Ogura Kazuharu Matsuura Hisao Suzuki Masayuki Kishida Satoru Ikeda Chiaki Tsukamoto Ayumi Imai Kazuo Tobe Article 10.18926/AMO/32015 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 56 3 2002 Effect of change in body mass index on morbidity in non-obese university graduates. 149 158 EN Kazuo Tobe Toshio Ogura Chiaki Tsukamoto Hajime Inoue Jiro Arata Kazuharu Matsuura Article 10.18926/AMO/31718 To establish the actual serial changes in body weight in Japanese people and to elucidate the influence of changes in BMI on morbidity, we conducted a historical cohort study of university graduates from 1955 to 1990 using questionnaires and BMI data. The subjects of this study were 3,675 university graduates aged 26-62 years in whom BMI was determined at the time of enrollment in the university (Pre-BMI), 5 to 40 years earlier. Morbidity (one or more system diseases or obesity-related system diseases) was analyzed according to current age, sex, current BMI, deltaBMI (difference between current BMI and pre-BMI), and various lifestyle variables. The proportion of overweight subjects at enrollment to university was higher in recent male students compared to old students, but not in female graduates, and the BMI in both genders increased progressively after graduation, especially in recent male graduates. Pre-BMI correlated negatively and significantly with deltaBMI. The percentages of obese (BMI > or = 30 kg/m2) males and females were 1.6% and 0.5%, respectively, and high morbidity was observed in 56.1% and 42.2% of males and females, respectively. Stepwise regression analysis showed that in subjects with normal BMI at enrollment, prospective morbidity was dependent on ABMI in addition to age. Our results indicate that in subjects with normal body weight, prospective morbidity is determined by increment of ABMI, and suggest that maintenance of BMI at the late adolescence level is an important factor in preventing future disease. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 49 1 1995 Enhanced pressor response in spontaneously hypertensive rats induced by stimulation of vasopressin-V1 receptors. 53 59 EN Takayoshi Yamauchi Toshio Ogura Tetsuya Oishi Kazushi Harada Masami Hashimoto Yukari Mimura Naoko Asano Zensuke Ota Jingo Kageyama Article 10.18926/AMO/30419 To elucidate the effect of the arginine vasopressin (AVP) system in vivo, especially V1 and V2 activity, on blood pressure, we measured the acute changes in blood pressure and heart rate after AVP, OPC-21,268 (a V1 receptor antagonist), and OPC-31,260 (a V2 receptor antagonist) were injected intravenously in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of 15 weeks. Compared with the control period, single injection of AVP 5 ng/kg significantly increased systolic blood pressure in WKY rats without a concomitant increase in heart rate, but there was no significant increase in blood pressure in SHR. In contrast, single injection of either OPC-21,268 3 mg/kg or OPC-31,260 3 mg/kg did not affect blood pressure or heart rate in either SHR or WKY rats. Injection of AVP after the administration of OPC-31,260 induced a greater increase in blood pressure in SHR than in WKY rats, whereas injection of AVP after the administration of OPC-21,268 did not induce any clear increase in blood pressure in SHR or WKY rats. These results suggest that SHR have enhanced pressor activity mediated by V1 receptors and that this increase may be due to an increase in their number. In conclusion, enhancement of V1 activity may contribute to the development of high blood pressure in SHR. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 49 5 1995 Diuretic effect of cilazapril and dopamine system in the spontaneously hypertensive rat. 247 252 EN Hitoshi Watanabe Toshio Ogura Masaharu Hosoya Norikazu Nishida Zensuke Ota Article 10.18926/AMO/30400 To assess the role of the kidney dopamine system on the diuretic state induced by angiotensin-converting enzyme (ACE) inhibitors, we examined the changes in urinary excretion and plasma level of dopamine, and kidney dopamine receptors in spontaneously hypertensive rats (SHR) treated with cilazapril, an ACE inhibitor. We administered cilazapril 10 mg/kg orally to 13-week-old SHR daily for 21 days (CILAZA group). Systolic blood pressure was significantly decreased in the CILAZA group on Day 6 compared with that in vehicle-treated SHR (control group). The urine volume was three- to fivefold higher in the CILAZA group, and total urinary dopamine secretion was also increased compared with the control group. There was no significant difference in affinity and number of kidney dopamine receptors between the CILAZA and the control groups. In conclusion, the diuretic effect caused by cilazapril is partly mediated by inhibition of the water reabsorption via the increase of dopamine production in the kidney. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 49 4 1995 Effect of vasopressin V1- and V2-receptor stimulation on blood pressure in DOCA-salt hypertensive rats. 187 194 EN Yukari Mimura Toshio Ogura Takayoshi Yamauchi Fumio Otsuka Tetsuya Oishi Kazushi Harada Masami Hashimoto Zensuke Ota Article 10.18926/AMO/30375 We recently reported that stimulation of the arginine vasopressin (AVP) V1-receptor enhanced the pressor response in spontaneously hypertensive rats (SHR). In the present study, we investigated acute changes in systolic blood pressure (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1-receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats (control) to determine whether the pressor effect is specific to SHR or is present in other hypertensive animal models. SBP increased significantly in DOCA rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR. Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP or HR. SBP tended to increase when AVP was administered after injection of OPC-31260. HR increased significantly 15 min after the combined treatment with OPC-31260 and AVP in DOCA rats compared with control rats. SBP did not change significantly when AVP was administered after injection of OPC-21268 in DOCA or control rats, but HR decreased significantly from 1 to 4 min after injection of AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not enhance the pressor response in the DOCA rat, which is a model of volume-dependent hypertension, suggesting that the AVP system, especially V1-receptor, is not as important in the development or maintenance of hypertension in DOCA rats as in SHR. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 5-6 1994 腎性貧血に対するエリスロポエチンの維持投与法の検討 655 661 EN Tosio Ogura Yoshio Nagake Hirofumi Makino Toshinori Haramoto Mitsuhito Matsumoto Makoto Hiramatsu Yasuaki Mino Shigeaki Nishimura Kazuhi Taniai Isao Kumagai Kiichi Komoto Yoshiaki Takehisa Umeharu Matsuura Yoshihiko Suga Zensuke Ota The beneficial effect of recombinant human erythropoietin (EPO) for renal anemia in patients with chronic hemodialysis has been esthablishel. EPO is reported to be effective against renal anemia when adeministered at a dose 3,000 units three times a week. However, only a few studies have been made on the therapy to maintain the anemia-improving effect of EPO. In the present study, we performed EPO maintenance therapy on 22 hemodialysis patients with renal anemia. EPO was initialy administered at a dose of 3,000 units three times a week, and maintenance therapy was initiated after 12 weeks of treatment. The patients were divided into two groups, with EPO being administered at a dose of 1,500 units twice a week to one group and three times a week to the other. The duration of maintenance therapy was set at eight weeks. The anemia-improving effect of EPO was found to be satisfactorily maintained in both groups and no significant difference was noted between them. According, it may be better to use the lower dose regimen of 1,500 units twice a week for the maintenance therapy of renal anemia. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 3-4 1994 エリスロポエチン投与による貧血改善と透析効率の変化に関する検討 253 259 EN Hirohumi Makino Yoshio Nagake Toshio Ogura Toshinori Haramoto Mitsuhito Matsumoto Makoto Haramatsu Yasuaki Mino Shigeaki Nishimura Kazuhi Taniai Isao Kumagai Kiichi Komoto Yoshiaki Takehisa Umeharu Matsuura Yoshihiko Suga Zensuke Ota The administration of recombinant human erythropoietin (EPO) has considerably improved renal anemia in benodialysis patients. However, there is a possibility that plasma flow will decrease and cause a reduction of hemodialysis effciency after the improvement of anemia. In the present study, we examined the influence of the improvement of anemia EPO administration on the efficiency of dialysis in 44 hemodialysis patients with renal anemia (21 males and 23 females ; mean age : 59.5±14.6 years). Epo was administered at a dose of 3,000 units three times a week and the duration of treatment was generally 12 weeks. EPO treatment significantly improved anemia. However, the blood urea nitrogen, creatinine, and uric acid levels before and after dialysis as well as the potassium and phosporus levels before dialysis showed no significant changes after the improvement of renal anemia. Accordingly. it is unnecessary to take any specific measures to improve the efficiency of dialysis after treating renal anemia with EPO. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 111 3-8 1999 病院基盤の訪問看護ステーションの問題点 ―患者67名からの検討― 85 93 EN Yukari Mimura Hirofumi Makino Youko Oka Kimiko Watanabe Hifumi Kanami Kazuhiko Moriwaki Eriko Katayama Hiromichi Fujiwara Takazi Sadakane Yoshiyuki Satou Ippei Hayashi Kamehiro Satou Toshio Ogura We investigated the curent status of home nursing in our instiution, and visiting nurses' station "chime", to clarify current problems and possible improvements in home care service. A large number of the subjects were aged, and had various diseases usually involving cerebrovascular disorder. Patients requiring medical treatment comprised less than half, and it was considered that support was strong in the current home nursing siuation, particulrly. We examined the age status of persons who looked after the patients, and tce burden on women who provided care. Furthemore, problems with the prenent visit nursing syntem were evaluated by an anonymous questionnaire survey of patients and their attendants. Many of the subjects were worried or troubled about what to do about exacerbation or sudden chages of he patients' condition, the health of the caretakers, and the tight schedule of the caretakers'　life. Based on the results of this questionnaire, we would like to improve the cooperation among members the visting nurse staff including doctors, and physiotherapists so that each of them may better play their roles and provide more appropriate nursing based on the wishes and needs of indvidual patients patients and their caretakers rather than those of the uniform service. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1989 Developmental Change of Kidney Receptor for Atrial Natriuretic Factor in Spontaneously Hypertensive Rat EN No potential conflict of interest relevant to this article was reported.