Publications (20)49.26 Total impact
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Article: Gender difference in association between polymorphism of serotonin transporter gene regulatory region and anxiety
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ABSTRACT: OBJECTIVE: The objective of this study was to verify the hypothesis that variation of the serotonin transporter gene promoter region (5-HTTLPR) is associated with sensitivity to stress. METHODS: Genotyping of 5-HTTLPR and evaluation of emotional states were performed on 194 participants. Participants' emotional states were evaluated using the Perceived-Stress Scale (PSS), the State-Trait Anxiety Inventory (STAI), and the Self-rating Depression Scale (SDS). RESULTS: There was significant GenderxGenotype interaction in STAI (state, P<.05; trait, P<.05). Females with the l/s genotype showed higher anxiety than those with the s/s genotype in both state and trait anxiety. Oppositely, males with the s/s genotype showed higher anxiety than those with the l/s genotype. CONCLUSION: On all emotional scales, females with the l/s genotype showed high scores, contrary to males with the same genotype. Therefore, our results suggest that 5-HTTLPR l allele may be one pathway that activates negative emotion in females but acts contrary in males.Journal of psychosomatic research. 01/2006; 60(1):91-7. -
Article: Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder.
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ABSTRACT: A high association between type 2 diabetes mellitus and depressive illness has been reported. Insulin resistance during depressive illness might contribute to the linkage between depression and type 2 diabetes. To determine whether the genetic polymorphisms of the tyrosine hydroxylase ([TH] HUMTH01) and insulin (INS-VNTR) genes contribute to insulin resistance in depressive illness, we analyzed the association between the polymorphisms and insulin resistance in 41 Japanese patients with depressive disorder, 204 normal control subjects, 161 cohort subjects with normal glucose tolerance (NGT) and without depressive symptomatology, and 59 NGT subjects with depressive symptomatology. The depressive patients had a significantly lower insulin sensitivity index (SI) than the control subjects (P= .016). Depressive NGT subjects had a significantly higher homeostasis model assessment (HOMA) insulin resistance index [HOMA(R)] than the nondepressive NGT subjects (P < .0001). The depressive patients and NGT subjects had more HUMTH01 allele 7 (TH7) than the controls and nondepressive NGT subjects. SI was significantly lower in patients with the TH7/7 homozygote versus patients with the other genotypes and the controls. TH7 was associated with higher HOMA(R) as compared with the other alleles in the NGT subjects. Insulin resistance was associated with depressive disorders. The HUMTH01 and INS-VNTR were associated with insulin resistance and depressive symptoms.Metabolism 09/2000; 49(9):1145-9. · 2.66 Impact Factor -
Article: Insulin resistance in patients with depression and its changes in the clinical course of depression: a report on three cases using the minimal model analysis.
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ABSTRACT: It has been reported that depression and diabetes mellitus often occur together, and insulin resistance has been observed in patients with depression. For further understanding of the relationship of depression to insulin resistance, three patients with depression were given the oral glucose tolerance test (OGTT) and the frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis before and after antidepressant treatment. Depressive patients showed decreased glucose tolerance, enhanced insulin secretion, and diminished insulin sensitively during OGTT and FSIGT. These abnormalities were resolved after their recovery from depression without changes in body weight or diet.Internal Medicine 04/1999; 38(3):257-60. · 0.94 Impact Factor -
Article: Secretory mechanisms of growth hormone (GH)-releasing peptide-, GH-releasing hormone-, and thyrotropin-releasing hormone-induced GH release in patients with acromegaly.
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ABSTRACT: The GH secretory mechanism of GH-releasing hexapeptide (GHRP-6), GHRH, and TRH were studied in vivo and in vitro in seven patients with acromegaly. In an in vivo study, these patients showed clear GH responses to single administration of GHRP (four of four patients), GHRH (seven of seven patients), and TRH (seven of seven patients) and enhanced responses to GHRP plus GHRH (two of four patients) or TRH plus GHRH (six of six patients). In an in vitro dispersed cell study, the majority of patients examined also showed clear GH responses to GHRP (four of four patients), GHRH (six of six patients), and TRH (four of four patients) and an enhanced response to GHRP plus GHRH (three of three patients) or TRH plus GHRH (three of four patients). In one patient (no. 3), GHRP plus forskolin (adenylate cyclase activator), but not GHRP plus phorbol 12-myristate 13-acetate (protein kinase C activator), additively enhanced the GH response. Nordihydroguaiaretic acid (NDGA; inhibitor of arachidonic cascade) inhibited GH release induced by GHRP, TRH, GHRH, TRH plus GHRH, or GHRP plus GHRH, but did not inhibit basal GH secretion. In contrast, NDGA distinctly elevated intracellular cAMP levels in another patient (no. 7) when coadministered with GHRP, GHRH, or GHRP plus GHRH, whereas cAMP levels were not modified by single administration of GHRP and NDGA. The GH response to the combined administration of GHRP and GHRH was synergistic in this patient, but was additive in the other two patients. It is concluded that GHRP, TRH, and GHRH directly stimulate in vivo and in vitro GH release from human somatotropinomas, and GHRP and TRH mainly exert their action through activation of the phosphatidylinositol-protein kinase C pathway, whereas GHRH exerts its action through the adenylate cyclase-protein kinase A pathway. These three agents seem to release GH via the arachidonic cascade.Journal of Clinical Endocrinology & Metabolism 11/1998; 83(10):3578-83. · 6.50 Impact Factor -
Article: Plasma GH responses to GHRH, arginine, L-dopa, pyridostigmine, sequential administrations of GHRH and combined administration of PD and GHRH in Turner's syndrome.
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ABSTRACT: To investigate GH secretory capacities in patients with Turner's syndrome, GHRH, arginine, L-dopa and pyridostigmine (PD) were administered singly and GHRH was administered sequentially for 3 days. In addition, plasma GH and TSH responses to GHRH and TRH after pretreatment with PD were analyzed to investigate whether the hypothalamic cholinergic somatostatinergic system functioned normally. The maximal GH responses to GHRH, L-dopa and PD were significantly smaller in Turner's syndrome (no.=14) than in normal short children (NSC, no.=14). However, there was no difference in plasma GH responses to arginine between the two groups. In ten patients with Turner's syndrome, the plasma GH response to GHRH did not improve even after the sequential 3-day administrations. Although plasma GH and TSH responses to GHRH and TRH were significantly enhanced by the pretreatment of PD in NSC (no.=12), these responses were not enhanced in Turner's syndrome. Plasma GH response to GHRH in Turner's syndrome with normal body fat was still significantly lower than in NSC. It is therefore concluded that somatotroph sensitivity to GHRH is decreased in Turner's syndrome and that this may be due to the primary defects of the somatotrophs rather than to the increased body fat. In addition, the network of cholinergic-somatostatinergic systems seemed to be impaired in these patients, while the activity of hypothalamic somatostatin neurons was thought to be maintained.Journal of endocrinological investigation 03/1998; 21(2):72-7. · 1.57 Impact Factor -
Article: Hyper-insulin response in a patient with depression. Changes in insulin resistance during recovery from depression.
Diabetes Care 01/1998; 20(12):1924-5. · 8.09 Impact Factor -
Article: Brain-gut induction of heat shock protein (HSP) 70 mRNA by psychophysiological stress in rats.
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ABSTRACT: Restraint water-immersion stress-induced expression of heat shock protein (HSP)70 mRNA in the cerebral cortex and stomach of rats was evaluated by Northern blotting. Cerebral and gastric HSP70 mRNA significantly increased in the 6 h-stressed rats and the amount of mRNA measured as optical densities was highest in the 12 h-stressed rats. These data confirmed our previous observations and suggest that families of HSPs play a salient cytoprotective role in stress-vulnerable organs.Brain Research 06/1997; 757(1):146-8. · 2.73 Impact Factor -
Article: The inhibitory effects of growth hormone-releasing hormone (GHRH)-antagonist on GHRH, L-dopa, and clonidine-induced GH secretion in normal subjects.
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ABSTRACT: The relative inhibitory potency of GHRH-Antagonist (GHRH-Ant) to GHRH(1-44)NH2 and mechanism of L-dopa- or clonidine-induced GH release were studied in seven normal subjects using GHRH-Ant. One hundred micrograms of GHRH-Ant (iv for 75 min) did not inhibit plasma GH responses to bolus injection of 100 micrograms and 10 micrograms GHRH or simultaneous infusion of 5 micrograms GHRH (iv for 75 min). However, 200 micrograms GHRH-Ant (iv for 75 min) significantly inhibited GH release, which was induced by simultaneous infusion of 5 micrograms GHRH. Although 100 micrograms GHRH-Ant could not significantly inhibit L-dopa-induced GH release, 200 micrograms GHRH-Ant almost completely inhibited the response. Similarly, the same dose of GHRH-Ant markedly inhibited the GH-releasing activity of clonidine. It is concluded that the inhibitory potency of GHRH-Ant on GHRH(1-44)NH2 is relatively weak (about 1/60 in molar base), and that L-dopa- or clonidine-induced GH release seems to be mediated by the release of hypothalamic GHRH.Journal of Clinical Endocrinology & Metabolism 06/1996; 81(5):1952-5. · 6.50 Impact Factor -
Article: Plasma GH responses to human GHRH-antagonist in normal subjects.
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ABSTRACT: The effect of GHRH-antagonist [(N-Ac-Tyr1, D-Arg2) GRF-(1-29)-NH2] on plasma GH morning and evening secretion was evaluated in 14 normal subjects (10 males, 4 females, aged 19-25 years). Plasma GH was determined using a high sensitivity IRMA kit (detection limit, 0.006 micrograms/l). After intravenous infusion of GHRH-antagonist (100 micrograms/100 ml saline over 75 min) in the morning, plasma GH remained constant during the 150 min post-infusion (N = 6). In contrast, when GHRH-antagonist was administered in the evening, plasma GH showed a clear and gradual decrease through the initial 90 min and returned to baseline levels at 150 min. Plasma GH values were also significantly lower from 75 min to 135 min when compared to physiological fluctuations in plasma GH (P < 0.05). Other anterior pituitary hormones remained unaffected by GHRH-antagonist. In conclusion, our data suggest that evening basal GH secretion, but not morning GH secretion, is maintained by endogenous GHRH.European Journal of Endocrinology 01/1996; 134(1):67-72. · 3.42 Impact Factor -
Article: Psychophysiological stress induces heat shock cognate protein (HSC) 70 mRNA in the cerebral cortex and stomach of rats.
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ABSTRACT: Families of 70 kDa heat shock proteins have essential roles in cellular coping to noxious stimuli. However, their roles in psychophysiological stress have not been precisely clarified. We tested our hypothesis that heat shock cognate protein (HSC)70 messenger RNA would increase in stress-vulnerable organs under psychophysiological stress. In control rats, cerebral HSC70 mRNAs were constitutively expressed while gastric HSC70 mRNAs were scarcely identified. Restraint-water immersion stress significantly increased the level of cerebral HSC70 mRNAs for 6 h and 12 h. Stress for 6 h with recovery for 6 h induced more gastric HSC70 mRNA levels than that without recovery, while stress for 12 h expressed the highest gastric HSC70 mRNA levels. Hypothermia, induced by water immersion, excluded a possible role of hyperthermia in inducing HSC70 mRNA. Our results point to a crucial cytoprotective role for families of heat shock proteins in stress-vulnerable brain-gut link in mammals under psychophysiological stress.Brain Research 04/1995; 675(1-2):98-102. · 2.73 Impact Factor -
Article: Enhanced plasma GH responses to simultaneous administration of TRH and GHRH in patients with primary hypothyroidism.
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ABSTRACT: The mechanism of aberrant GH responses to TRH was indirectly evaluated in 7 patients with primary hypothyroidism. All patients showed GH response to TRH. When TRH was administered together with GHRH, the plasma GH response was much greater than after a single administration of TRH or GHRH (TRH+GHRH vs. TRH or GHRH: max. delta GH, 16.4 +/- 3.2 vs. 5.4 +/- 1.3 or 6.0 +/- 0.8 microgram/L; AUC, 1282.7 +/- 234.7 vs. 384.0 +/- 95.0 or 441.8 +/- 66.2, both P < 0.01). The combined administration of TRH and GHRH caused an additive, but not a synergistic, GH response. In contrast, 8 normal subjects showed neither any plasma GH response to TRH nor enhancement by TRH of GHRH-induced GH response following combined administration. It is concluded that the sites of action of TRH seemed to be different from GHRH in patients with primary hypothyroidism.Endocrine Journal 03/1995; 42(1):43-7. · 2.03 Impact Factor -
Article: The evaluation of hypothalamic somatostatin tone using pyridostigmine and thyrotropin releasing hormone in patients with acromegaly.
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ABSTRACT: To indirectly evaluate the hypothalamic somatostatin (SS) tone in patients with acromegaly, the effects of pyridostigmine (PD), a cholinesterase inhibitor which can inhibit hypothalamic SS secretion, on TRH-induced TSH secretion and the effects of SMS 201-995 on TSH or GH secretion were studied in acromegalic patients (31-69 yr, n = 10), normal young (21-24 yr, n = 7) and normal old male subjects (62-71 yr, n = 7). After pretreatment with PD (60 mg po, -30 min), normal young subjects showed significantly enhanced TSH responses to TRH (500 micrograms i.v., 0 min) compared to single administration of TRH, whereas normal old and acromegalic patients did not show such enhancement. Plasma TSH response to a single administration of TRH in acromegalic patients was significantly lower than that of normal young and old subjects. Although normal young and old subjects showed significantly enhanced GH responses to GHRH (100 micrograms i.v. at 0 min) after the pretreatment with PD (60 mg, -30 min), no such enhancement was observed in acromegalic patients. In contrast, the decrement in plasma TSH after SMS 201-995 administration was similar between normal subjects (5 young 5 old) and 7 acromegalic patients. Further, the maximal plasma GH decrement after administration was significantly greater in acromegalic patients than in the 5 normal young and 5 old subjects p < 0.01). In conclusion, hypothalamic SS tone does not appear to be elevated in acromegalic patients compared to normal young and probably old subjects.Journal of endocrinological investigation 06/1994; 17(5):313-21. · 1.57 Impact Factor -
Article: Enhanced GH responses to combined administration of GHRP and GHRH in patients with acromegaly.
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ABSTRACT: Plasma GH responses to GH-releasing peptide (GHRP) were studied in 11 patients with active acromegaly. Ten of these patients showed plasma GH increases to GHRP (100 micrograms i.v.), whereas every patient showed GH increases to TRH (500 micrograms i.v.) and GHRH (100 micrograms i.v.). When GHRP was administered together with GHRH to the 10 GHRP responders, plasma GH responses were synergistically enhanced. However, combined administration of GHRP and TRH did not enhance the response. The GH response pattern and mean time to the peak value were similar to TRH but were different from GHRH. There was no correlation in the maximum GH increment between GHRP and TRH or GHRP and GHRH. It is concluded that GHRP stimulated GH release in the majority of acromegaly patients. The mode of action of GHRP might be similar to TRH and different from GHRH, although the sites of action of GHRP seemed to be different from those of TRH and GHRH.Journal of Clinical Endocrinology & Metabolism 04/1994; 78(3):509-12. · 6.50 Impact Factor -
Article: Plasma GH response to the sequential 3 day administrations of GHRH followed by arginine infusion in patients with idiopathic GH deficiency and normal short children.
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ABSTRACT: To study the site of lesions in idiopathic growth hormone (GH) deficiency (IGHD), growth hormone releasing hormone (GHRH) was administered sequentially for 3 days to 19 patients with IGHD, 3 patients with GH deficiency (GHD) secondary to hypothalamic tumors, and 7 normal short children (NSC). GHRH (100 micrograms) was injected as a bolus on days 1 and 3, and was infused over 60 min on day 2. Of 19 patients with IGHD, 6 showed an improved GH response (group A), 5 a decreased response (group B) and the remaining 8 an unchanged response (group C) to sequential administration of GHRH. The response was unchanged in patients with secondary GHD or NSC. There was no significant correlation between the patterns of GH response and the findings on pituitary MR images or the delivery state at birth in IGHD patients. Ten patients with IGHD (4 of group A; 3 each of groups B & C) and 2 NSC showed much greater GH responses to arginine (0.5 g/kg i.v. for 30 min) injected with preceding GHRH than to arginine injected without preceding GHRH. These results indicate that hypothalamic lesions were primarily responsible for GH deficiency in about 60% of the patients with IGHD (groups A and B), and group C might have more severe hypothalamo-pituitary damages than the other groups. Hypothalamic somatostatin neurons seems to be functioning to a degree even in severe IGHD patients.The Tohoku Journal of Experimental Medicine 03/1993; 169(2):91-101. · 1.24 Impact Factor -
Article: Simultaneous administration of TRH and sulpiride caused additive but not synergistic PRL responses in normal subjects.
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ABSTRACT: In order to study the mode of action of TRH and sulpiride in man, we administered TRH (500 micrograms, iv) and sulpiride (DA D2 receptor antagonist, 100 mg, im) simultaneously to 6 normal females (20-21 yr). Normal females showed significantly greater PRL increments and AUC in response to the combined administration compared to a single administration of each agent (P < 0.05-0.01), while the increment and AUC in response to the combination did not exceed the sum of those responses to a single administration. In contrast, the combined administration of TRH and sulpiride did not elicit an enhanced response of plasma TSH. These results indicate that the sites of action of TRH and sulpiride might be different from each other, and these agents work additively with no interaction in human lactotrophs.Endocrinologia japonica 10/1992; 39(5):465-8. -
Article: Plasma growth hormone (GH) responses to corticotropin-releasing hormone in patients with acromegaly--the effect of dexamethasone pretreatment and the comparison with GH responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and GH-releasing hormone.
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ABSTRACT: It has been reported that paradoxical GH responses to corticotropin-releasing hormone (CRH) occur in only few patients with acromegaly. However, we have observed such responses in 7 of 14 active acromegalic patients. Therefore, we have studied the GH responses to thyrotropin-releasing hormone (TRH) (500 micrograms, iv), gonadotropin-releasing hormone (LHRH) (100 micrograms, iv) and GH-releasing hormone (GHRH) (100 micrograms, iv) in these patients to examine the relationships between the GH responses to CRH and the responses to these hypothalamic hormones. Further, these patients received human CRH (1-41) NH2 (100 micrograms, iv) with or without dexamethasone (Dex) pretreatment (1 mg/100 ml saline, iv, from -30 to +30 min) to study the mechanism of CRH-induced GH secretion, and a perifusion experiment was performed using adenoma tissue obtained at surgery from one patient (10(-7) M CRH and TRH were added) to elucidate whether CRH acts directly at the pituitary level. Aberrant GH responses induced by CRH were found in 7 of 14 (50%) acromegalic patients (TRH responders: 10/13, 77%; LHRH responders: 2/9, 22%; GHRH responders: 10/12, 83%). In these patients, percent GH increment induced by CRH ranged from 81 to 144% (Mean +/- SE, 118 +/- 8%), and the GH peak (19 +/- 3 min) appeared as early as after TRH (23 +/- 4 min, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)Journal of endocrinological investigation 04/1992; 15(3):167-71. · 1.57 Impact Factor -
Article: The relation between pituitary magnetic resonance imaging findings and GH, TSH, PRL dynamics in patients with idiopathic GH deficiency.
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ABSTRACT: The relation between pituitary magnetic resonance imaging (MRI) findings and anterior pituitary function was studied in 36 patients with classic idiopathic GH deficiency. These patients were divided into three groups based on MRI findings which were compared with those of 14 normal short children; i.e. normal stalk (N = 6), narrowed stalk (N = 20), and transected stalk (N = 10). The transected and narrowed stalk groups showed significantly delayed TSH responses to TRH compared with the normal stalk group and with the normal short children. Further, the mean maximal TSH increment in the narrowed and transected stalk group was slightly greater than that in normal short children. In contrast, there were no differences in basal plasma GH and PRL levels and their responses to GHRH and TRH among the three groups. When the patients were divided into normal anterior pituitary and atrophic pituitary groups regardless of stalk changes or when they were divided into groups of stalk changes (narrowing and transection) with and without pituitary atrophy, no differences in GH, TSH and PRL dynamics between the groups were observed. These results indicate that pituitary thyrotrope functions, but not somatotrope and lactotrope functions, in patients with idiopathic GH deficiency are more closely correlated to stalk changes than to anterior pituitary changes observed on MRI.Acta endocrinologica 11/1991; 125(4):342-7. -
Article: Evidence for dopamine-related and TRH-related pituitary TSH and PRL pools in patients with prolactinoma.
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ABSTRACT: The sources of TSH, which was excessively released by sulpiride (dopamine D2 receptor antagonist), were studied in 15 female patients with PRL-secreting adenoma (18-43 years). Sequential 3-day administration of sulpiride (100 mg, im) was given to 12 patients with prolactinoma and 6 normal female subjects (19-24 years). Patients with prolactinoma showed much greater TSH responses than normal subjects on the first day. However, TSH responses to sulpiride disappeared on the 2nd and 3rd day in both groups. In contrast, plasma PRL responses to the 1st sulpiride administration were smaller in patients with prolactinoma than in normal subjects, and the response disappeared following the 2nd administration in both groups. When TRH (500 micrograms, iv) was administered 120 min after the 3rd sulpiride injection, TSH and PRL increments were not different from those before the sulpiride injection in both patients with prolactinoma (N = 6) and normal subjects (N = 6). Further, combined administration of sulpiride and TRH in 5 patients with prolactinoma clearly enhanced the TSH and PRL responses compared with the single administration of each agent. These results suggest that there may be two readily releasable pituitary TSH and PRL pools, i.e. one dopamine-related and the other TRH-related, in patients with prolactinoma and normal female subjects.Acta endocrinologica 06/1991; 124(5):545-52. -
Article: GHRH and TRH tests in patients with idiopathic and secondary GH deficiency--with special reference to GH response patterns to GHRH.
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ABSTRACT: To study whether patients with idiopathic GH deficiency (IGHD) show a delayed GH response pattern to GHRH, 42 patients with IGHD, 14 patients with hypothalamic tumor (2ry GHD), and 23 normal short children (NSC) were examined as to their GH response patterns to GHRH together with their TSH and PRL response patterns to TRH. After TRH injection, the mean time of the TSH peak in IGHD (67.5 +/- 6.5 min, n = 36) and 2ry GHD patients (81.7 +/- 14.8 min, n = 9) was clearly delayed comparing to that of NSC (29.1 +/- 2.9 min, n = 16; both p less than 0.01). Similarly, the mean time of the PRL peak in IGHD (38.3 +/- 3.6 min, n = 36) and 2ry GHD patients (39.5 +/- 5.8, n = 11) was significantly delayed comparing to NSC (22.0 +/- 3.5 min, both p less than 0.01). In IGHD patients, the delayed response pattern of TSH and PRL was more remarkable in patients who had breech delivery than in those with normal delivery. In contrast, the mean time of the GH peak was similar in IGHD (62.1 +/- 4.0 min, n = 41), 2ry GHD (64.1 +/- 8.1 min, n = 11) and NSC (58.0 +/- 6.1 min, n = 23). However, the decline from peak GH (120 min GH/peak GH) was significantly smaller in IGHD (54.3 +/- 4.2%) and 2ry GHD (60.7 +/- 7.3%) than in NSC (39.0 +/- 8.1%) (both p less than 0.05). Further, in IGHD patients plasma GH response was greater in patients with normal delivery than in those with breech and asphyxia delivery. These results seem to indicate: 1) the stimulus-secretion mechanism is different between somatotrophs and thyrotrophs or lactotrophs in man, 2) IGHD patients have hypothalamic lesions as well as pituitary lesions, 3) such hypothalamo-pituitary lesions in IGHD patients are greater in patients with abnormal delivery than in those with normal delivery.The Tohoku Journal of Experimental Medicine 04/1990; 160(3):189-202. · 1.24 Impact Factor -
Article: Increased Brain Histamine H1 receptor Binding in Patients with Anorexia Nervosa
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1992
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Tohoku University
- Division of Internal Medicine
Sendai-shi, Miyagi-ken, Japan
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