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Given the importance of collocational knowledge for second language learning, how collocation learning can be facilitated is an important question. The present study examined the effects of three different practice schedules on collocation learning: node massed, collocation massed, and collocation spaced. In the node-massed schedule, three collocations for the same node verb were studied on the same day. In the collocation-massed schedule, three collocations for the same node verb were studied in different weeks. In the collocation-spaced schedule, participants encountered multiple collocations for the same node verb within a single day; at the same time, multiple collocations for the same node verb were repeated each week. To examine whether the knowledge of studied collocations could be transferred to unstudied collocations containing the same node, posttests included novel collocations that were not encountered during the treatment. Results suggested that the collocation-spaced schedule led to the largest gains for both studied and unstudied collocations.

17α-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by pathogenic mutations in CYP17A1. Impaired 17α-hydroxylase and 17,20-lyase activities typically induce hypertension, hypokalemia, sexual infantilism, and amenorrhea. Most patients with 17OHD are diagnosed in adolescence. Here, we report a female (46, XX) patient with 17OHD who was diagnosed at the age of 67 years. Genetic analysis was performed using direct DNA sequencing of polymerase chain reaction (PCR) products and multiplex ligation-dependent probe amplification (MLPA) analysis. Direct DNA sequencing revealed a homozygous c.1039C>T in CYP17A1, corresponding to a p.R347C amino acid change. MLPA probe signals showed that the ‍CYP17A1 mutation was present in the homozygous carrier state. The patient's dehydroepiandrosterone sulfate and androstenedione levels were extremely low, despite elevated adrenocorticotropic hormone (ACTH) and normal cortisol levels. A corticotropin-releasing hormone (CRH) test showed no response of cortisol, despite a normal response of ACTH. Rapid ACTH injection resulted in elevations in the deoxycorticosterone, corticosterone, aldosterone, and 17-hydroxypregnenolone levels, but not in the cortisol level. These results suggested that 17α-hydroxylase/17,20-lyase activities were partially impaired. Computed tomography revealed bilateral adrenal hyperplasia and a hypoplastic uterus. A high basal plasma ACTH level and a discrepancy between ACTH and cortisol responses in a CRH test may provide a definitive diagnostic clue for this ‍disease.

McCune-Albright syndrome (MAS) is a rare disorder. MAS is classically defined by the occurrence of fibrous dysplasia, café-au-lait skin macules, and precocious puberty. In addition to precocious puberty, other hyperfunctioning endocrinopathies may occur. We evaluated hypothalamic-pituitary-adrenal function in two cases of typical MAS associated with fibrous dysplasia and growth hormone excess. Pituitary adenoma or hyperplasia was not detected by magnetic resonance imaging. Hormonal data showed normal or low cortisol levels, despite high ACTH levels in the blood. A high ratio of circulating ACTH to cortisol was found in the two cases. Insulin tolerance and CRH tests showed hyper-responses of ACTH and an insufficient increase in cortisol levels. No involvement of 11β-HSD1 by GH excess was suggested because basal levels of ACTH and cortisol showed no changes, even after therapy for acromegaly by somatostatin analogues. Patients with Cushing's disease cases of pituitary macroadenoma can have high circulating ACTH precursor levels, and elevated ACTH precursors have been observed in ectopic ACTH syndrome. Autonomous cortisol excess was excluded by the level of midnight cortisol and the level of cortisol after a low-dose dexamethasone suppression test in the two cases. Finally, the gel filtration profiles of immunoreactive ACTH contents showed the presence of aberrant ACTH precursors. To the best of our knowledge, there have been no reports of MAS associated with aberrant ACTH precursors. Our findings in these cases emphasize that attention should be to secretion of inactive ACTH precursors in MAS.

Pembrolizumab, or anti-programmed death receptor 1 antibody, is an immune checkpoint inhibitor that can cause immune-related adverse events. We herein report for the first time the progression of hypopituitarism and hypothyroidism after treatment with pembrolizumab in a patient with adrenal metastasis of non-small-cell lung cancer. Severe primary hypothyroidism occurred three weeks after the first administration of pembrolizumab. Four months after the discontinuation of pembrolizumab, isolated adrenocorticotropic hormone (ACTH) deficiency was noted. Corticotropin-releasing hormone and rapid ACTH tests performed repeatedly showed that the patient's pituitary and adrenal function had been gradually deteriorating. It is important to diagnose adrenal insufficiency without delay in order to prevent adrenal crisis.

17α-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by pathogenic mutations in CYP17A1. Impaired 17α-hydroxylase and 17,20-lyase activities typically induce hypertension, hypokalemia, sexual infantilism, and amenorrhea. Most patients with 17OHD are diagnosed in adolescence. Here, we report a female (46, XX) patient with 17OHD who was diagnosed at the age of 67 years. Genetic analysis was performed using direct DNA sequencing of polymerase chain reaction (PCR) products and multiplex ligation-dependent probe amplification (MLPA) analysis. Direct DNA sequencing revealed a homozygous c.1039CT in CYP17A1, corresponding to a p.R347C amino acid change. MLPA probe signals showed that the CYP17A1 mutation was present in the homozygous carrier state. The patient's dehydroepiandrosterone sulfate and androstenedione levels were extremely low, despite elevated adrenocorticotropic hormone (ACTH) and normal cortisol levels. A corticotropin-releasing hormone (CRH) test showed no response of cortisol, despite a normal response of ACTH. Rapid ACTH injection resulted in elevations in the deoxycorticosterone, corticosterone, aldosterone, and 17-hydroxypregnenolone levels, but not in the cortisol level. These results suggested that 17α-hydroxylase/17,20-lyase activities were partially impaired. Computed tomography revealed bilateral adrenal hyperplasia and a hypoplastic uterus. A high basal plasma ACTH level and a discrepancy between ACTH and cortisol responses in a CRH test may provide a definitive diagnostic clue for this disease.

Background: McCune-Albright syndrome (MAS) is a rare disorder. MAS is caused by an activating postzygotic somatic mutation in the GNAS, and, is classically defined by the occurrence of fibrous dysplasia (FD), café-au-lait skin macules, and precocious puberty. Autonomous GH and/or PRL production in MAS has been reported. However, there have been no reports of ACTH excess in MAS. Method: Plasma ACTH and serum cortisol (F) levels were assessed using electrochemiluminescence immunoassays (Eclusys ACTHTM and Eclusys Cortisol IITM, respectively; Roche Diagnostics K.K., Tokyo, Japan).Clinical Cases: Case1; 42-year-old man showed craniofacial deformities and suffered from multiple bone fractures. He was diagnosed with FD at the age of 23 years. Café-au-lait macules were found on his back. He had slightly acromegaloid features. He showed no cushingoid features. Pituitary adenoma or hyperplasia was not detected by MRI. The diagnosis of GH excess was confirmed by no suppression of serum GH levels by a 75-g oral glucose tolerance test (nadir GH: 2.34 ng/mL) and an elevated serum IGF-I level (307 ng/mL; normal range: 92-257 ng/mL). The patient was treated with monthly subcutaneous lanreotide injection and then GH excess was well controlled. Basal ACTH and F levels in blood were 40.6-63.4 pg/mL and 8.0-10.5 μg/dL, respectively. The urinary free cortisol (UFC) level was 53 μg/day. Autonomous F excess was excluded by the level of midnight F (1.2 μg/dL) and the level of F (0.2 μg/dL) after a low-dose (1 mg) dexamethasone suppression test (DST). Case2; A 32-year-old man was diagnosed with MAS and gigantism at the Pediatrics Department at the age of 5 years. Treatment of GH excess was well controlled by monthly octreotide depot. He had no acromegaloid features and no cushingoid features. Café-au-lait macules were observed from the left flank to the back. Pituitary adenoma or hyperplasia was not detected by MRI. Basal ACTH and F levels in blood were 35.5-73.1 pg/mL and 7.0-11.7 μg/dL, respectively. The UFC level was 61 μg/day. Autonomous F excess was excluded by the level of F (

Objective The regulation of food intake is a major research area in the study of obesity, which plays a key role in the development of metabolic syndrome. Gene targeting studies have clarified the roles of hypothalamic neurons in feeding behavior, but the deletion of a gene has a long-term effect on neurophysiology. Our understanding of short-term changes such as appetite under physiological conditions is therefore still limited. Methods Targeted recombination in active populations (TRAP) is a newly developed method for labeling active neurons by using tamoxifen-inducible Cre recombination controlled by the promoter of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), a member of immediate early genes. Transgenic mice for TRAP were fasted overnight, re-fed with normal diet, and injected with 4-hydroxytamoxifen 1 h after the refeeding to label the active neurons. The role of labeled neurons was examined by expressing excitatory or inhibitory designer receptors exclusively activated by designer drugs (DREADDs). The labeled neurons were extracted and RNA sequencing was performed to identify genes that are specifically expressed in these neurons. Results Fasting-refeeding activated and labeled neurons in the compact part of the dorsomedial hypothalamus (DMH) that project to the paraventricular hypothalamic nucleus. Chemogenetic activation of the labeled DMH neurons decreased food intake and developed place preference, an indicator of positive valence. Chemogenetic activation or inhibition of these neurons had no influence on the whole-body glucose metabolism. The labeled DMH neurons expressed prodynorphin (pdyn), gastrin-releasing peptide (GRP), cholecystokinin (CCK), and thyrotropin-releasing hormone receptor (Trhr) genes. Conclusions We identified a novel cell type of DMH neurons that can inhibit food intake and promote feeding-induced positive valence. Our study provides insight into the role of DMH and its molecular mechanism in the regulation of appetite and emotion., Graphical abstract Image 1, Highlights • Fasting-refeeding activates a subset of neurons in the dorsomedial hypothalamus (DMH). • Chemogenetic inhibition of the DMH neurons increases food intake. • Chemogenetic activation of the DMH neurons inhibits food intake and promotes positive valence. • The DMH neurons express pdyn, GRP, CCK and Trhr genes.

The present study investigated the effects of two types of core-image-based basic verb learning approaches: the learner-centered and the teacher-centered approaches. The learner-centered approach was an activity in which participants found semantic relationships among several definitions of each basic target verb through a picture-elucidated card game. By contrast, the teacher-centered approach involved explicit instruction from the teacher explaining how several definitions of the basic target verbs are interrelated. A total of 241 Japanese EFL (English as a foreign language) junior high school students acted as participants in this comparative study to determine the superior approach. At the end of the treatment period, a short questionnaire was distributed. A two-way repeated measures analysis of variance (ANOVA) revealed that the learner-centered approach was more effective than the teacher-centered approach with regard to both retention rates for learned definitions and accuracy rates for novel definitions of the basic target verbs. The results of paired t-tests for the questionnaire also support these findings. Considering the results, it can be argued that basic verbs may be best taught through a learner-centered collaborative approach, with conventional teacher-centered explicit instruction as a supplement.

Objective: Acromegaly is associated with metabolic and neoplastic complications, but successful treatment of acromegaly can sometimes result in growth hormone deficiency (GHD). Nonalcoholic fatty liver disease may develop in GHD, although there are few reports of such cases after cured acromegaly.Methods: We report the case of a 41-year-old woman with nonalcoholic steatohepatitis associated with GHD after surgical cure of acromegaly.Results: Growth hormone (GH) replacement therapy improved serum triglyceride, hyaluronic acid, and type IV collagen levels as well as liver function and quality of life. Computed tomography (CT) showed reduced volumes of both visceral and subcutaneous fat and an increased liver/spleen CT attenuation value.Conclusion: Cured acromegalic patients should be carefully examined if GHD and associated metabolic disorders arise. Appropriate diagnosis of GHD and prompt treatment with GH replacement should ameliorate liver dysfunction and the metabolic changes associated with GHD.Abbreviations: ALT = alanine aminotransferase AST = aspartate aminotransferase BMI = body mass index CT = computed tomography GH = growth hormone GHD = growth hormone deficiency HbA1c = glycated hemoglobin IGF-1 = insulin-like growth factor 1 NAFLD = nonalcoholic fatty liver disease NASH = nonalcoholic steatohepatitis OGTT = oral glucose tolerance test rhGH = recombinant human GH

The ancestral insulin/relaxin peptide superfamily member relaxin-3 is an important regulator of food intake and behaviors related to anxiety and motivation. Relaxin family peptide receptor 1 (RXFP1) and RXFP3 are expressed in the rat hypothalamic paraventricular nucleus (PVN). Corticotropin-releasing factor (CRF) is produced in the PVN in response to stressors and promotes adrenocorticotropic hormone secretion from the anterior pituitary. We hypothesized that relaxin-3 directly regulates Crf expression in the hypothalamus and investigated its effect on Crf expression in cultured hypothalamic 4B cells. Relaxin-3 increased Crf mRNA levels and stimulated Crf promoter activity. Both protein kinase A and C pathways contributed to relaxin-3-induced Crf promoter activity. Rxfp1 and Rxfp3 mRNA and their proteins were expressed in cultured hypothalamic 4B cells. Relaxin-3 decreased Rxfp1 mRNA and protein levels and increased Rxfp3 mRNA and protein levels. These results suggested that the action of relaxin-3 in cultured hypothalamic 4B cells may be regulated through both RXFP1 and RXFP3.

Summary Patients with Cushing’s syndrome and excess exogenous glucocorticoids have an increased risk for venous thromboembolism, as well as arterial thrombi. The patients are at high risk of thromboembolic events, especially during active disease and even in cases of remission and after surgery in Cushing’s syndrome and withdrawal state in glucocorticoid users. We present a case of Cushing’s syndrome caused by adrenocorticotropic hormone-secreting lung carcinoid tumor. Our patient developed acute mesenteric ischemia after video-assisted thoracoscopic surgery despite administration of sufficient glucocorticoid and thromboprophylaxis in the perioperative period. In addition, our patient developed hepatic infarction after surgical resection of the intestine. Then, the patient was supported by total parenteral nutrition. Our case report highlights the risk of microthrombi, which occurred in our patient after treatment of ectopic Cushing’s syndrome. Guidelines on thromboprophylaxis and/or antiplatelet therapy for Cushing’s syndrome are acutely needed. Learning points: The present case showed acute mesenteric thromboembolism and hepatic infarction after treatment of ectopic Cushing’s syndrome. Patients with Cushing’s syndrome are at increased risk for thromboembolic events and increased morbidity and mortality. An increase in thromboembolic risk has been observed during active disease, even in cases of remission and postoperatively in Cushing’s syndrome. Thromboprophylaxis and antiplatelet therapy should be considered in treatment of glucocorticoid excess or glucocorticoid withdrawal.

Objective: Cystic pheochromocytomas can become enlarged without abdominal symptoms and can potentially be confused with other abdominal cystic tumors.Methods: We report here a case of a 45-mm cystic pheochromocytoma that was initially considered a pancreatic cystic tumor. The patient had a 4-year history of treatment for hypertension and occasional headaches. Left cystic pheochromocytoma was diagnosed based on excessive catecholamine levels, 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy.Results: Left adrenalectomy ameliorated the patient's hypertension and headache. Pathologic findings showed an enlarged cyst with an irregular, thick wall adherent to the normal adrenal tissues.Conclusion: A large cystic pheochromocytoma can be misdiagnosed as a large pancreatic cystic tumor. CT and magnetic resonance imaging (MRI) are less important in excluding the possibility of pheochromocytoma than biochemical evaluation. When adrenal glands are not identified on CT or MRI, 18F-FDG PET/CT or 123I-MIBG scintigraphy should be considered.

Objective: Adrenal venous sampling (AVS) is the most reliable test to distinguish between unilateral and bilateral primary aldosteronism (PA). However, AVS is invasive, risky, and expensive, and alternative diagnostic methods are desirable. This study aimed to investigate the diagnostic power of saline infusion test (SIT) to distinguish between unilateral and bilateral PA. Design: Retrospective database analysis. Subjects and Methods: We selected 111 patients with PA diagnosed by confirmatory tests who underwent both SIT and successful AVS. Thirty-two patients had lateralized ratio (LR) over 4.0 and 79 patients had LR less than 4.0. Multiple regression analysis and receiver operating characteristic (ROC) analysis were used to examine whether the SIT had good diagnostic power to distinguish between patients with high LR and those with low LR. Results: The patients with high LR had significantly lower serum potassium levels (P

Corticotropin-releasing factor (CRF) is involved in a variety of physiological functions including regulation of hypothalamo–pituitary–adrenal axis activity during stressful periods. Urocortins (Ucns) are known to be members of the CRF family peptides. CRF has a high affinity for CRF receptor type 1 (CRF 1 receptor). Both Ucn2 and Ucn3 have very high affinity for CRF receptor type 2 (CRF 2 receptor) with little or no binding affinity for the CRF 1 receptor. Gonadotropin-releasing hormone (GnRH) is known to be involved in the regulation of the stress response. Gonadotropin-inhibitory hormone (GnIH) neurons interact directly with GnRH neurons, and the action of GnIH is mediated by a novel G-protein coupled receptor, Gpr147. This study aimed to explore the possible function of CRF family peptides and the regulation of GnRH mRNA in hypothalamic GnRH cells. Both mRNA and protein expression of the CRF 1 receptor and CRF 2 receptor were found in hypothalamic GnRH N39 cells. CRF suppressed GnRH mRNA levels via the CRF 1 receptor, while Ucn2 increased the levels via the CRF 2 receptor. Both CRF and Ucn2 increased Gpr147 mRNA levels. The results indicate that CRF and Ucn2 can modulate GnRH mRNA levels via each specific CRF receptor subtype. Finally, CRF suppressed GnRH protein levels, while Ucn2 increased the levels. Differential regulation of GnRH by CRF family peptides may contribute to the stress response and homeostasis in GnRH cells.

Objective: Fulminant type 1 diabetes mellitus (FT1DM), a distinct subtype of type 1 diabetes, is characterized by a rapid onset of severe hyperglycemia and diabetic ketoacidosis (DKA). DKA sometimes induces severe rhabdomyolysis, which causes renal failure, and it requires permanent hemodialysis (HD), especially in elderly patients. Some cases of FT1DM progress to rhabdomyolysis-induced acute kidney injury (AKI). Methods: We report the case of an 81-year-old male with rhabdomyolysis-induced AKI, the oldest patient reported to date, associated with acute FT1DM onset. Results: Although the patient required HD, he was successfully withdrawn from HD within 2 months. Conclusion: Even in such advanced age patients, prompt renal replacement therapy gives the prospect for recovering kidney function and circumvents the need for permanent renal replacement therapy. Abbreviations: AKI acute kidney injury CHDF continuous hemodiafiltration CK creatinine kinase DKA diabetic ketoacidosis FT1DM fulminant type 1 diabetes mellitus HD hemodialysis HLA human leukocyte antigen RRT renal replacement therapy

SummaryACTH-dependent Cushing's syndrome includes Cushing's disease and ectopic ACTH syndrome (EAS). The differential diagnosis of Cushing's disease from EAS in cases of ACTH-dependent Cushing's syndrome is a challenging problem. We report here a case of EAS with an unknown source of ACTH secretion. Extensive imaging procedures, involving computed tomography (neck to pelvis), pituitary magnetic resonance imaging, and whole-body18F-fluorodeoxyglucose-positron emission tomography, failed to reveal the source of ACTH secretion. Intermittent administration of bromocriptine, a short-acting and nonselective dopamine agonist, has afforded adequate suppression of plasma ACTH and cortisol levels over the long term.Learning pointsTumor excision is the primary treatment for EAS. However, when surgery is impossible, medical therapy is needed to treat hypercortisolism.In cases where the source of ACTH secretion is unknown, inhibitors of steroidogenesis, such as metyrapone, mitotane, ketoconazole, and etomidate, are mostly used to suppress cortisol secretion.Medications that suppress ACTH secretion are less effective, therefore less popular, as standard treatments.In the present case, short-term treatment with dopamine agonists was effective for the long-term suppression of both ACTH and cortisol levels.

Flow near riverbank erosion was examined to investigate mechanism of bank erosion through experimental study of flow field of model bank erosion shape in the authors' previous study. This paper presents prediction of flow field near bank erosion. A numerical model is developed to compute two dimensional flow velocity and water depth for different model bank erosion shapes. The purpose of this study is to reproduce measured flow field of the model bank erosion shape. Curvilinear coordinate system is used in this analysis to obtain the bank erosion shape appropriately. The model could predict the flow field inside bank erosion for small erosion surface angle (equal or less then 4 degrees) with higher accuracy. It is also able to reproduce flow field inside erosion part for larger erosion surface angle (8degrees), but absolute value of the computed velocity is larger than the measured velocity.

There is a possibility of cohesive soil being used as a material of riverbank. For this purpose, it is important to investigate and estimate the erosive resistance of cohesive soils against the stream flow. Several studies on the erosion of cohesive soils have been made in recent years. In previous studies, the dynamic processes of bank erosion have been clarified. We have accumulated the knowledge about mechanism and process of erosion in cross and longitudinal directions. However, the knowledge is not sufficient in estimating the erosion amount and erosion speed.The point of this paper is to examine the relation of flow velocity and erosion rate. Some hydraulic models were made to measure the flow velocity around eroded area in detail. One model reproduced faithfully the shape of erosion experiment to examine the longitudinal change in velocity, and another simplified the feature of overhanging bank to examine the effect of erosion angle. The important relations of flow characteristics and erosion mechanism are found as the consequence of those experiments.

The Fos- and Jun family proteins are immediate-early gene products, and the Fos/Jun heterodimer, activator protein-1 (AP-1), may be involved in the regulation of corticotropin-releasing factor (CRF) gene expression. FosB is a member of the Fos family proteins that is expressed in the paraventricular nucleus of the hypothalamus upon stress exposure, but it has not been clear whether FosB participates in the regulation of CRF gene expression. This study aimed to explore the effect of the FosB and cJun proteins on CRF gene expression in rat hypothalamic 4B cells. The levels of FosB mRNA and cJun mRNA increased following treatment with forskolin, phorbol-12-myristate-13-acetate (PMA), or A23187 in the hypothalamic cells. Overexpression of FosB or cJun potently increased CRF mRNA levels. Furthermore, downregulation of FosB or cJun suppressed the CRF gene expression induced by forskolin, PMA, or A23187. In addition, the basal CRF mRNA levels were partially reduced by cJun downregulation. These findings suggest that FosB, together with cJun, may mediate CRF gene expression in the hypothalamic cells.

Corticotropin-releasing factor (CRF) activates the pituitary-adrenal axis during stress, and shows anorectic effects via CRF type 1 receptors in the hypothalamus. Both urocortin (Ucn) 2 and Ucn3 also act as anorectic neuropeptides via CRF type 2 receptors. Leptin, a product of the obesity gene secreted mainly from adipose tissue, reduces food intake and increases energy expenditure. A possible interaction between leptin and CRF/Ucns has been suggested, as leptin can regulate expression and activation of CRF and Ucns in the hypothalamus. This study aimed to explore the possible function of leptin in the hypothalamus, and its effects in regulating CRF and Ucns. The study identified mRNA expression of the leptin receptor (Ob-R) and its subtypes, CRF, and Ucn2/3 in mouse hypothalamic N39 cells. Leptin stimulated signal transducer and activators of transcription type 3 (STAT3) phosphorylation, directly increased the mRNA levels of both CRF and Ucn2/3 in hypothalamic cells, and increased Ob-Rb mRNA levels. A Janus kinase inhibitor inhibited the leptin-mediated increase in STAT3 phosphorylation, and then the increases in CRF and Ucn2/3 mRNA levels. Leptin may contribute to a stress response or anorectic effect via the regulation of CRF and Ucn2/3 in the hypothalamus.

Objective: The purpose of this study was to investigate the diagnostic power of the adrenocorticotropin (ACTH) stimulation test in patients with primary aldosteronism (PA) and those with aldosterone-producing adenoma (APA). Design: This study was based on a retrospective database analysis. Subjects and methods: We assessed 158 hypertensive patients with a high plasma aldosterone-to-renin ratio (ARR) including 97 with at least one positive confirmatory test result who did not undergo surgery and comprised a “possible PA” group, 19 with negative results in all tests who were the “non-PA” group, and 41 diagnosed with APA following surgery who were the APA group. The “confirmed PA group” included APA patients and patients from the possible PA group showing both high ARR and hypokalemia. One case was diagnosed as a metastasis. Results: Receiver-operating characteristic (ROC) analysis showed that the diagnostic accuracy of ACTH test was not very effective in differentiating between APA patients and possible PA and non-PA patients. The optimal cut-off value of maximal plasma aldosterone concentration for differentiating between patient in the confirmed PA group and other patients showed moderate accuracy. Conclusions: The ACTH test may not be useful as a screening or confirmatory test, but the test may be useful for differentiating between patients with confirmed PA and the rest of the cohort. The positive finding of the ACTH test may at least support a higher likelihood of lateralizing on adrenal venous sampling.

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are the two major regulatory peptides in the hypothalamic–pituitary–adrenal (HPA) axis. Glucagon-like peptide-1 (GLP-1), an important regulator of metabolism or energy homeostasis, is implicated in the regulation of the HPA axis in response to stress and may act directly on CRF and AVP neurons. To elucidate the direct regulation of CRF and AVP genes by GLP-1 in the hypothalamus, we examined the effect of GLP-1 in hypothalamic 4B cells, which show the characteristics of hypothalamic paraventricular nucleus neurons. The mRNA of GLP-1 receptor was detected in 4B cells by RT-PCR. GLP-1 significantly stimulated both CRF and AVP mRNA levels. Cells were transfected with CRF or AVP promoter to examine the activity of each promoter. GLP-1 directly stimulated the activities of both CRF and AVP promoters in hypothalamic 4B cells. Basal promoter activities of both CRF and AVP were increased in higher glucose medium. In addition, CRF and AVP promoter activities were increased by GLP-1 in standard or low glucose medium but not in higher glucose medium. An equimolar concentration of metabolically inactive l -glucose failed to mimic the effect of d -glucose, indicating that the event was caused by changes in glucose levels and not by hyperosmolality. Together, these data suggest that GLP-1 would contribute to stress responses through activation of CRF and AVP genes in the hypothalamic cells. Hyperglycemia may be one of the stressors enhancing the syntheses of CRF and AVP in the hypothalamus.

2-Chloro-1-azaazulene-3-carbaldehyde (1a) reacted with pyridine, followed by a reacion with piperidine to give 2-amino-1-azaazulene-3-carbaldehyde (1b) in excellent yield. Compound 1b was also obtained by a Vilsmeier–Haack reaction of 2-amino-1-azaazulene. Acetylation of 1b yielded a 2-acetylamino derivative, whereas methylation gave a 1-methylated compound. Reactions of 1b with hydrazines and alkylamines gave the corresponding hydrazones and Schiff bases, respectively, in excellent yields. The reactions of 1b with active methylene compounds gave 1,10-diazabenz[a]azulen-2(1H)-one derivatives. The reaction of 1b with guanidine gave pyrimidine-fuzed 1-azaazulene.

This pilot study made comparisons on image-based basic verb learning through learner and teacher-centred approaches. To this purpose, 121 Japanese EFL junior high school students participated. In a learner-centred activity, they just engaged in a card game in which they were able to pay attention to relationships between situational images and forms of the targeted basic verbs. In a teacher-centred instruction, the participants were explicitly taught how given definitions of another basic verb were motivated semantically from situational-images. Immediately after each treatment, post-tests were administered. A week after each immediate post-test, delayed post-tests were given. Analysis of the results found that only high proficiency learners were capable of image-based basic verb learning through either the card game activity or the explicit instruction alone. Considering the results and a SLA model, the authors concluded that image-based basic verb learning should be implemented through learner-centred activity first, followed by teacher-centred explicit instruction.

The tribological properties of a Co-Cr thin film were greatly improved by surface oxidation. According to surface analyses, a Cr-rich oxidized region in which Cr is oxidized to Cr/sub 2/O/sub 3/ was formed near the surface of the film. This region plays an important role in improving the mechanical durability of the film. However, when the oxidation is carried out for a long time, a thick Co-rich oxidized region grows on the Cr-rich oxidized one. As a result, the durability deteriorates. >

In order to improve the reproduced output of a Co-Cr perpendicular magnetic recording medium, a very thin ( approximately 10 nm) soft magnetic underlayer such as a Permalloy film was inserted between the recording layer and the substrate. An evaluation using a ring-type head showed that the reproduced output of the Co-Cr medium was greatly increased by the underlayer without any deterioration in its high-density recording characteristics. The increase is attributed to the decrease of the demagnetizing field acting on the recorded magnetization, which is caused by the establishment of horseshoe magnetization modes in the vicinity of recording transition regions. >