Dual regulation of ETTIN (ARF3) gene expression by AS1-AS2, which maintains the DNA methylation level, is involved in stabilization of leaf adaxial-abaxial partitioning in Arabidopsis.

Leaf primordia are generated at the periphery of the shoot apex, developing into flat symmetric organs with adaxial-abaxial polarity, in which the indeterminate state is repressed. Despite the crucial role of the ASYMMETRIC LEAVES1 (AS1)-AS2 nuclear-protein complex in leaf adaxial-abaxial polarity specification, information on mechanisms controlling their downstream genes has remained elusive. We systematically analyzed transcripts by microarray and chromatin immunoprecipitation assays and performed genetic rescue of as1 and as2 phenotypic abnormalities, which identified a new target gene, ETTIN (ETT)/AUXIN RESPONSE FACTOR3 (ARF3), which encodes an abaxial factor acting downstream of the AS1-AS2 complex. While the AS1-AS2 complex represses ETT by direct binding of AS1 to the ETT promoter, it also indirectly activates miR390- and RDR6-dependent post-transcriptional gene silencing to negatively regulate both ETT and ARF4 activities. Furthermore, AS1-AS2 maintains the status of DNA methylation in the ETT coding region. In agreement, filamentous leaves formed in as1 and as2 plants treated with a DNA methylation inhibitor were rescued by loss of ETT and ARF4 activities. We suggest that negative transcriptional, post-transcriptional and epigenetic regulation of the ARFs by AS1-AS2 is important for stabilizing early leaf partitioning into abaxial and adaxial domains.

Papillary thyroid carcinoma in one of identical twin patients with Pendred syndrome.

Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, a partial defect in iodide organification, and dyshormonogenetic goiter. Several cases of Pendred syndrome with follicular thyroid carcinomas were reported previously. Here we report identical twin patients with Pendred syndrome, who had thyroid tumors with distinct histopathological findings. 34-year-old identical twins with congenital deafness and goiter were referred to our hospital with complaint of neck discomfort. The genetic testing showed that these twin patients were compound heterozygotes carrying the same two mutations in the Pendred's syndrome (PDS / SLC26A4) gene (c2168A > G and ins2110GCTGG), which confirmed the diagnoses of Pendred syndrome. They underwent thyroidectomy. Histological examination of the thyroid tumors resected from these twin patients revealed follicular variant of papillary thyroid carcinoma, and diffuse and nodular goiter without any evidence of malignancy, respectively. To our knowledge, the former is the first case of follicular variant of papillary thyroid carcinoma in Pendred Syndrome.

Coronary computed tomography angiography-based coronary risk stratification in subjects presenting with no or atypical symptoms.

BACKGROUND: Coronary computed tomography angiography (CTA) findings of positive vessel remodeling and low-attenuation plaque, referred to as computed tomography-verified high-risk plaque (CT-HRP), have been reported to be associated with the development of subsequent acute coronary syndromes. The aim of this study was to examine the usefulness of coronary CTA for coronary risk re-stratification of patients with asymptomatic and atypical chest symptoms. METHODS AND RESULTS: A total of 1,139 subjects (M/F 602/537; mean age, 61.5±9.3 years) who were either asymptomatic or presented with atypical chest symptoms underwent coronary 64- or 320-slice multidetector computed tomography angiography and Agatston score. Age, sex, coronary risk factors, including hypertension, diabetes mellitus (DM), dyslipidemia, and smoking were investigated as predictors for CT-HRP on multivariate analysis using logistic regression analysis. CT-HRP was observed in 72 patients (6.3%). Based on Framingham risk scores (FRS), CT-HRP was observed in 0/94 subjects (0.0%) in the low-risk group, 35/806 (4.3%) in the intermediate-risk group, and 37/239 (15.5%) in the high-risk group. On logistic regression analysis significant predictors for CT-HRP in intermediate- and high-risk subjects were male sex (odds ratio [OR] 2.829; 95% confidence interval [CI] 1.460-5.479, P=0.0021), DM (OR 2.418; 95% CI 1.420-4.116, P=0.0011), and current smoking (OR 1.922; 95% CI 1.096-3.371, P=0.0160). CT-HRP prevalence for Agatston scores >500 and >250 was lower in the intermediate- and high-risk groups, respectively. CONCLUSIONS: In asymptomatic subjects and those presenting with atypical chest pain who have a more than an intermediate risk, coronary CTA is contributory to FRS. Male sex, DM and smoking were independent predictors of vulnerable plaque in the more than intermediate-risk group.

Prediction of late (24-hour) radioactive iodine uptake using early (3-hour) uptake values in Japanese patients with Graves' disease.

Measurement of 24-hour radioactive iodine uptake (RAIU), which is commonly used to calculate the dose of radioiodine (RI) therapy, cannot be accomplished in a single day. The purpose of this study was to predict 24-hour RAIU from 3-hour RAIU in Japanese patients with Graves' disease, and to investigate other factors that could be used to predict 24-hour RAIU. A total of 66 Japanese patients (14 men and 52 women; age, 17-83 years) with Graves' disease who had undergone both 3-hour and 24-hour ¹²³I RAIU measurements between January 2006 and September 2011 were included in this study. Stepwise multiple regression analyses were performed in order to identify factors that could be used to predict 24-hour RAIU. The investigated factors were gender, age, thyroid volume, TSH, free thyroxine (FT4), free triiodothyronine (FT3), serum creatinine, second generation assay TSH receptor antibody (TRAb2), antithyroid drugs discontinuation period (ADP), iodine restriction period and 3-hour RAIU. The ADP was converted to an ordinal scale ADP score (ADPS) for multiple regression analyses. Multiple regression analyses showed that 3-hour RAIU (P < 0.001), FT3 (P < 0.001) and ADPS (P < 0.001) were statistically significant predictive factors of 24-hour RAIU. The relationship between 24-hour RAIU (LU) and 3-hour RAIU (EU), FT3 and ADPS was: LU = 11.5 + 29.1 × log10 EU + 23.0 × log10 FT3 - 2.7 × ADPS (r = 0.82, P < 0.001). The present results indicate that prediction of LU from EU, FT3 and ADPS is feasible in Japanese patients with Graves' disease.

ACTH response to desmopressin in a patient with acromegaly; expression of corticotropin-releasing factor, urocortins and vasopressin V1b receptor in GH-producing pituitary adenoma.

GH-producing pituitary adenomas frequently co-produce other certain anterior pituitary hormones, such as prolactin (PRL). In contrast, GH-producing adenomas which express all of corticotropin-releasing factor (CRF), urocorin1 (Ucn1) and urocortin3 (Ucn3) have not been reported. A 39-year-old woman was admitted for evaluation of the pituitary tumor. The diagnosis of acromegaly was confirmed by elevated serum GH and IGF-I levels, and the absence of GH suppression by oral glucose tolerance test. ACTH response to desmopressin (DDAVP) was observed (plasma ACTH levels increased from 13.9 to 50.4 pg/ml at 90 min). Although it is known that ACTH response to DDAVP is considerably useful for the diagnosis of ACTH-dependent Cushing's syndrome, the diagnosis of Cushing's disease was not supported by the criteria. The patient underwent transsphenoidal resection of the pituitary tumor. Immunohistological examination confirmed a GH- and PRL-producing adenoma, whereas ACTH was negative. ACTH response to DDAVP disappeared after tumor removal. To determine the cause of preoperative ACTH response to DDAVP, we examined expression of CRF family peptides and vasopressin V1b receptor in the pituitary adenoma by immunohistochemistry. Immunohistochemistry revealed positive immunostaining for CRF, Ucn1, Ucn3 and vasopressin V1b receptor in the adenoma. These observations raised the possibility that DDAVP caused an ACTH response, perhaps via the paracrine effects of tumor-derived CRF and Ucn1. When ACTH response to DDAVP is observed in patients with pituitary tumor, not only the direct effect of DDAVP on ACTH secretion, but also a possible involvement of CRF and/or urocortins expressed in the pituitary adenoma, should be considered.

Sunitinib-induced thyrotoxicosis followed by persistent hypothyroidism with shrinkage of thyroid volume.

Sunitinib, a tyrosine kinase inhibitor, has been approved for the treatment of cancers, such as advanced renal cell carcinoma (RCC). On the other hand, sunitinib treatment is known to induce thyroid dysfunction in a substantial proportion of patients treated for advanced RCC; in fact, hypothyroidism is a frequent complication. However, little is known about sunitinib-induced thyrotoxicosis and destructive thyroiditis. Here, we report a patient with RCC who developed transient overt thyrotoxicosis followed by hypothyroidism due to sunitinib treatment. A 58-year-old woman, who had been treated with chronic thyroiditis, was diagnosed as having left RCC with bone metastasis to the rib. The patient underwent resection of the left kidney and the bone metastasis lesion. However, 3 months later, bone metastasis to the rib recurred, and sunitinib treatment was started. At 6 weeks of sunitinib therapy, the patient developed transient thyrotoxicosis, followed by persistent hypothyroidism. In the thyrotoxic phase, the patient was diagnosed as having destructive thyroiditis based on an increased thyroglobulin level, a low radioactive iodine uptake, increased free thyroxine level, and suppressed thyroid-stimulating hormone level. The thyroid volume in the hypothyroid phase was 68% of that in the thyrotoxic phase. In conclusion, the present report suggests that sunitinib-induced persistent hypothyroidism may be a consequence of preceding destructive thyroiditis with transient thyrotoxicosis. The decreased volume of the thyroid during the hypothyroid phase indicates irreversible organ damage in the present patient, thereby resulting in persistent hypothyroidism. Thus, periodic surveillance of thyroid function is mandatory during sunitinib therapy.

Familial Dysalbuminemic Hyperthyroxinemia in a Japanese Man Caused by a Point Albumin Gene Mutation (R218P).

Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant disease caused by mutation in the albumin gene that produces a condition of euthyroid hyperthyroxinemia. In patients with FDH, serum-free thyroxine (FT4) and free triiodothyronine (FT3) concentrations as measured by several commercial methods are often falsely increased with normal thyrotropin (TSH). Therefore, several diagnostic steps are needed to differentiate TSH-secreting tumor or generalized resistance to thyroid hormone from FDH. We herein report a case of a Japanese man born in Aomori prefecture, with FDH caused by a mutant albumin gene (R218P). We found that a large number of FDH patients reported in Japan to date might have been born in Aomori prefecture and have shown the R218P mutation. In conclusion, FDH needs to be considered among the differential diagnoses in Japanese patients born in Aomori prefecture and showing normal TSH levels and elevated FT4 levels.

Nanoscopic Structural Investigation of Physically Cross-Linked Nanogels Formed from Self-Associating Polymers.

The detailed structure of a nanogel formed by self-association of cholesterol-bearing pullulans (CHPs) was determined by contrast variation small-angle neutron scattering. The decomposition of scattering intensities into partial scattering functions of each CHP nanogel component, i.e., pullulan, cholesterol, and the cross-term between the pullulan and the cholesterol, allows us to investigate the internal structure of the nanogel. The effective spherical radius of the skeleton formed by pullulan chains was found to be 8.1 ± 0.3 nm. In the CHP nanogel, there are about 19 cross-linking points where a cross-linking point is formed by aggregation of trimer cholesterol molecules, and the spatially inhomogeneous distribution of the cross-linking points in the nanogel can be represented by the mass fractal dimension of 2.6. The average radius of gyration of the partial chains can also be determined to be 1.7 ± 0.1 nm by analyzing the extracted cross-correlation between the cross-linker and the tethered polymer chain quantitatively, and the size agrees with the value assuming random distribution of the cross-linkers on the chains. As the result, the complex structure of the nanogels is coherently revealed at the nanoscopic level.

Neutron diffraction of ice in hydrogels.

Neutron diffraction patterns for deuterated poly-N,N,-dimethylacrylamide (PDMAA) hydrogels were measured from 10 to 300 K to investigate the structure and properties of water in the gels. Diffraction peaks observed below 250 K indicate the existence of ice in the hydrogels. Some diffraction peaks from the ice are at lower diffraction angles than those in ordinary hexagonal ice (Ih). These shifts in peaks indicate that the lattice constants of the a and c axes in the ice are about 0.29 and 0.3% higher than those in ice Ih, respectively. The results show that bulk low-density ice can exist in PDMAA hydrogels. The distortions in the lattice structure of ice imply significant interactions between water molecules and the surrounding polymer chains, which play an important role in the chemical and mechanical properties of the hydrogel.

Prevalence of anomalous origin of coronary artery detected by multi-detector computed tomography at one center.

BACKGROUND: Anomalous origin of coronary artery (AOCA) has been described by coronary angiography or autopsy. However the actual prevalence of such abnormalities is unknown. Multi-detector computed tomography (MDCT) offers the possibility to visualize AOCA non-invasively. The purpose of this study was to report the prevalence AOCA by MDCT. METHODS AND RESULTS: In 5869 consecutive subjects who underwent coronary MDCT (Aquilion 64, Toshiba Medical Systems Corporation, Otowara, Japan) at one center, the prevalence of AOCA was 89 (1.52%) patients. The most common abnormality (33 cases, 0.56%) was the origin of the coronary artery or branch from the opposite or non-coronary sinus. The right coronary arteries (RCA) arising from the left coronary artery sinus (LCS) was observed in 27 cases (0.46%). Vascular cross-sectional area of such RCA arising from LCS was significantly smaller in 11 patients with angina than in 10 patients without symptoms [3.02 (1.68-7.67) mm² vs 5.93 (2.54-12.04) mm² p < 0.05]. The left coronary artery arising from the non-coronary sinus was observed in 2 cases (0.03%), and the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCX) arising from the right coronary sinus was observed in 4 cases (0.07%). Single coronary arteries were found in 5 cases (0.09%). Fifteen patients (0.26%) presented multiple coronary ostia, all of 15 (0.26%) had the LAD and LCX separately arising from the left coronary sinus. High take off was found in 36 cases (0.60%). CONCLUSION: MDCT can accurately detect and characterize the type of AOCA.

Significance of PQ interval in acquisition of coronary multidetector row computed tomography.

BACKGROUND: Since image quality obtained in the mid-diastolic [or slow filling (SF)] phase is generally superior to end-systolic image in coronary multidetector row computed tomography (MDCT), low heart rate (HR) comprises the most important factor for acquisition of high-quality images. However, despite HR <70 and optimum breath-hold, sometimes high quality images cannot be obtained in SF. We assessed the significance of PQ interval in acquisition of coronary MDCT. METHODS AND RESULTS: Of 541 consecutive patients who underwent coronary MDCT, 7 patients with incomplete breath-hold, 62 HR ≥70, and 70 arrhythmias were excluded. The remaining 402 patients (M: 222, 66±11 years), including 38 with first-degree atrioventricular block (1° AVB, PQ >200 ms) were evaluated. RR and PQ were measured on electrocardiogram and systolic and SF phase with 4-chamber cine cardiac computed tomography. SF significantly (p<0.0001) correlated with RR (SF=-471+0.720RR, r=0.887) in all subjects. The SF of without 1° AVB (292±97 ms) was significantly (p<0.0147) longer than that of with 1° AVB (251±121 ms), although RR was not significantly different between the two groups. The SF/RR of without 1° AVB (27.2±6.1%) was also significantly (p<0.0001) higher than that of with 1° AVB (22.7±8.0%). The coefficient of correlation between (RR-PQ) and SF [r=0.915, p<0.0001, SF=-362+0.742(RR-PQ)] was significantly (p<0.034) higher than that of correlation between RR and SF in all subjects. The SF of rank A image quality was significantly longer than that of rank B (p<0.0001) or rank C (p=0.0042). In critical HR (60-69 bpm), the optimum phase was ES in 7/139 patients without 1° AVB, and SF in 3/13 patients with 1° AVB (chi(2), p<0.0416). CONCLUSION: Since SF depends on (RR-PQ), if PQ is long in critical HR, it might be difficult to reconstruct high quality images in the SF phase.

ECG-edit function in multidetector-row computed tomography coronary arteriography for patients with arrhythmias.

BACKGROUND: ECG-gating is necessary for cardiac computed tomography, but is not suitable for arrhythmias, so the aim of this study was to evaluate the usefulness of the ECG-edit function for this purpose. METHODS AND RESULTS: Of 1,221 patients undergoing 64-row multidetector-row computed tomography coronary angiography (coronary MDCT), 123 patients (28 atrial fibrillation (Af), 39 premature atrial contractions (PAC), 42 premature ventricular contractions (PVC), 3 PAC + PVC, 10 sinus arrhythmias (SA), and a second-degree atrioventricular block (2 degrees AVB)) had arrhythmias necessitating the ECG-edit function. Short R-R interval was deleted and mid-diastolic phases were selected from the long R-R intervals using the "R+absolute time" method. In the present study, the reconstructed images were evaluated using a triple-grade scale A-C, representing excellent, acceptable, and unacceptable image quality. Image quality, categorized as A, B and C, respectively, was 50%, 36% and 14% for the 28 patients with Af; 56%, 36% and 8% for the 39 PAC patients, and 65%, 33% and 2% in the 42 PVC patients. None of the scans of the PAC + PVC, SA, and 2 degrees AVB patients was ranked as C. CONCLUSIONS: The ECG-edit function is useful for reconstructing coronary MDCT images in many arrhythmias, and provides clinically acceptable images in most cases.

Selective OD bond dissociation of HOD: photodissociation of vibrationally excited HOD in the 5nu(OD) state.

Exclusively selective OD bond dissociation of HOD has been demonstrated by the ultraviolet photodissociation at 243.1 nm through the fourth overtone state of the OD stretching mode (5nu(OD)). Branching ratio between the OH and OD bond dissociation channels has been determined by detecting H and D atoms, utilizing a (2+1) resonance-enhanced multiphoton ionization (REMPI) process. The OD bond dissociation has been solely observed with the branching ratio phi(D+OH)/phi(H+OD)>12, which has been determined by the detection limit for the H atom. Time-dependent wave-packet calculations reveal two important features for the highly selective OD bond dissociation: (1) strong local-mode character of the 5nu(OD) state and (2) limitation of the total excitation energy lower than the saddle point between the OH and OD dissociation channels in the A state. Additionally, the recoil velocity and angular distribution of the nascent D atom are roughly evaluated by analyzing the Doppler-resolved REMPI spectrum. Based on these results, the dynamics of the selective OD dissociation has been discussed in detail.

[Relationship between redox state of whole arterial blood glutathione and left ventricular function after acute myocardial infarction].

OBJECTIVES: To investigate the role of oxidative stress in left ventricular function after acute myocardial infarction. METHODS: We studied 41 patients with acute myocardial infarction (30 men and 11 women, mean age 61.7 +/- 11.6 years) with Thrombolysis in Myocardial Infarction grade 3 recanalization of occluded coronary arteries within 12 hr after onset. Cardiac catheterization was performed at the time of admission and before discharge. Three markers for oxidative stress were measured: plasma lipid hydroperoxide, plasma creatol and whole arterial blood glutathione at the time of admission. RESULTS: Mean time from onset to recanalization was 5.2 +/- 0.6 hr. The patients were divided into two groups according to the changes in left ventricular wall motion (LVWM); patients who showed improvement in LVWM and those without improvement. There were no significant differences in age, sex, coronary risk factors, severity of coronary artery disease, time from onset to recanalization or ejection fraction between two groups. Maximum creatine kinase and C-reactive protein levels in patients without LVWM improvement were significantly higher than in patients with improvement. Plasma levels of lipid hydroperoxide and creatol did not differ significantly between two groups. On the other hand, reduced glutathione/oxidized glutathione ratio in arterial blood in patients without LVWM improvement was significantly lower than in patients with LVWM improvement (69.8 +/- 3.4 vs 85.5 +/- 2.9, p < 0.05). CONCLUSIONS: Our results suggest that whole arterial blood glutathione is more oxidized in acute myocardial infarction patients without LVWM improvement than in patients with improvement. Redox state of arterial blood can be a predicting factor for left ventricular function after acute myocardial infarction.