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Objective: Conventional diagnostic methods are limited in their ability to differentiate destructive thyroiditis from Graves’ disease. We hypothesised that serum diiodotyrosine (DIT ) and monoiodotyrosine (MIT) levels could be biomarkers for differentiating destructive thyroiditis from Graves’ disease. Design: Patients with destructive thyroiditis (n = 13) and Graves’ disease (n = 22) were enrolled in this cross-sectional study. Methods: We assayed the serum DIT and MIT levels using liquid chromatogr aphy-tandem mass spectrometry. A receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of the serum DIT and MIT levels as biomarkers for differentiating destr uctive thyroiditis from Graves’ disease. Results: The serum DIT and MIT levels were significantly higher in patien ts with destructive thyroiditis than in those with Graves’ disease. The ROC curve analysis showed that the se rum DIT levels (≥359.9 pg/mL) differentiated destructive thyroiditis from Graves’ disease, significantly, with 100.0% sensitivity and 95.5% specificity (P < 0.001). The diagnostic accuracy of the serum MIT levels (≥119.4 pg/mL) was not as high as that of the serum DIT levels (s ensitivity, 84.6%; specificity, 77.3%; P = 0.001). Conclusions: The serum DIT levels may serve as a novel diagnostic biomarker for differentiating destructive thyroiditis from Graves’ disease. [ABSTRACT FROM AUTHOR]

The specialized multilayered pollen wall plays multiple roles to ensure normal microspore development. The major components of the pollen wall (e.g. sporopollenin and lipidic precursors) are provided from the tapetum. Material export from the endoplasmic reticulum (ER) is mediated by coat protein complex II (COPII) vesicles. The Arabidopsis thaliana genome encodes seven homologs of SEC23, a COPII component. However, the functional importance of this diversity remains elusive. Here, we analyzed knockout and knockdown lines for AtSEC23A and AtSEC23D, two of the A. thaliana SEC23 homologs, respectively. Single atsec23a and atsec23d mutant plants, despite normal fertility, showed an impaired exine pattern. Double atsec23ad mutant plants were semi-sterile and exhibited developmental defects in pollen and tapetal cells. Pollen grains of atsec23ad had defective exine and intine, and showed signs of cell degeneration. Moreover, the development of tapetal cells was altered, with structural abnormalities in organelles. AtSEC23A and AtSEC23D exhibited the characteristic localization pattern of COPII proteins and were highly expressed in the tapetum. Our work suggests that AtSEC23A and AtSEC23D may organize pollen wall development and exine patterning by regulating ER export of lipids and proteins necessary for pollen wall formation. Also, our results shed light on the functional heterogeneity of SEC23 homologs. [ABSTRACT FROM AUTHOR]

Hydrocarbon contamination introduced during point, line and map analyses in a field emission electron probe microanalysis (FE-EPMA) was investigated to enable reliable quantitative analysis of trace amounts of carbon in steels. The increment of contamination on pure iron in point analysis is proportional to the number of iterations of beam irradiation, but not to the accumulated irradiation time. A combination of a longer dwell time and single measurement with a liquid nitrogen (LN2) trap as an anti-contamination device (ACD) is sufficient for a quantitative point analysis. However, in line and map analyses, contamination increases with irradiation time in addition to the number of iterations, even though the LN2 trap and a plasma cleaner are used as ACDs. Thus, a shorter dwell time and single measurement are preferred for line and map analyses, although it is difficult to eliminate the influence of contamination. While ring-like contamination around the irradiation point grows during electron-beam irradiation, contamination at the irradiation point increases during blanking time after irradiation. This can explain the increment of contamination in iterative point analysis as well as in line and map analyses. Among the ACDs, which are tested in this study, specimen heating at 373 K has a significant contamination inhibition effect. This technique makes it possible to obtain line and map analysis data with minimum influence of contamination. The above-mentioned FE-EPMA data are presented and discussed in terms of the contamination-formation mechanisms and the preferable experimental conditions for the quantification of trace carbon in steels. [ABSTRACT FROM AUTHOR]

Context: Adrenal crisis is an endocrine emergency that requires prompt diagnosis and treatment. However, the clinical features and practice patterns of treatment for adrenal crisis are not completely understood. Objective: To investigate patient characteristics, comorbidities and treatments of adrenal crisis. Methods: We conducted a cross-sectional study of patients who received intravenous glucocorticoids for adrenal crisis at admission from 1 July 2007 to 31 March 2014, using a national inpatient database in Japan. Results: Among approximately 34 million inpatients in the database, we identified 799 patients diagnosed with adrenal crisis and coexisting primary or secondary adrenal insufficiency at admission. The median (interquartile range) age was 58 (28–73) years, and the overall in-hospital mortality was 2.4% (19 of 799 patients). The most common comorbidity at admission was infections excluding pneumonia and gastroenteritis (15.0%). There were 68 (8.5%) patients with gastroenteritis, and no deaths occurred among these patients. The patients with secondary adrenal insufficiency showed significantly higher proportions of admission to ICU, extracellular fluid resuscitation, insulin therapy and catecholamine use than the patients with primary adrenal insufficiency. There were no significant between-group differences in mortality rate and variation in intravenous glucocorticoids (short-acting glucocorticoid, hydrocortisone; moderate-acting glucocorticoid, prednisolone or methylprednisolone; long-acting glucocorticoid, dexamethasone or betamethasone). Of the 19 dead patients, 15 were aged above 60 years, 12 had impaired consciousness at admission and 13 received insulin therapy. Conclusions: Clinicians should be aware that older patients with impaired consciousness and diabetes mellitus are at relatively high risk of death from adrenal crisis. [ABSTRACT FROM AUTHOR]

Alpha-naphthylisothiocyanate (ANIT) causes intrahepatic cholestasis by injuring biliary epithelial cells. Adaptive regulation of hepatobiliary transporter expression has been proposed to reduce liver injury during cholestasis. Recently, the oxidative stress transcription factor Nrf2 (nf-e2–related factor 2) was shown to regulate expression of hepatobiliary transporters. The purpose of this study was to determine whether ANIT-induced hepatotoxicity and regulation of hepatobiliary transporters are altered in the absence of Nrf2. For this purpose, wild-type and Nrf2-null mice were administered ANIT (75 mg/kg po). Surprisingly, ANIT-induced hepatotoxicity was similar in both genotypes at 48 h. Accumulation of bile acids in serum and liver was lower in Nrf2-null mice compared with wild-types treated with ANIT. Transporter mRNA profiles differed between wild-type and Nrf2-null mice after ANIT. Bsep (bile salt export pump), Mdr2 (multidrug resistance gene), and Mrp3 (multidrug resistance–associated protein) efflux transporters were increased by ANIT in wild-type, but not in Nrf2-null mice. In contrast, mRNA expression of two hepatic uptake transporters, Ntcp (sodium-taurocholate cotransporting polypeptide) and Oatp1b2 (organic anion transporting peptide), were decreased in both genotypes after ANIT, with larger declines in Nrf2-null mice. mRNA expression of the transcriptional repressor of Ntcp, small heterodimeric partner (SHP), was increased in Nrf2-null mice after ANIT. Furthermore, hepatocyte nuclear factor 1α (HNF1α), which regulates Oatp1b2, was downregulated in ANIT-treated Nrf2-null mice. Preferential upregulation of SHP and downregulation of HNF1α and uptake transporters likely explains why Nrf2-null mice exhibited similar injury to wild-types after ANIT. A subsequent study revealed that treatment of mice with the Nrf2 activator oltipraz protects against ANIT-induced histological injury. Despite compensatory changes in Nrf2-null mice to limit ANIT toxicity, pharmacological activation of Nrf2 may represent a therapeutic option for intrahepatic cholestasis. [ABSTRACT FROM AUTHOR]

The article focuses on the availability of a new series of Gateway Binary Vectors R4LlpGWB possessing the bialaphos resistance gene (bar) and the tunicamycin resistance gene that can be used as markers for promoter analysis in plants. It mentions that the vectors can be used as a useful tool for promoter analysis in pre-existing transgenic plants.

Alpha-naphthyl isothiocyanate (ANIT) is a hepatotoxicant that produces acute intrahepatic cholestasis in rodents. Farnesoid X receptor (FXR) and pregnane X receptor (PXR) are two major bile acid sensors in liver. The purpose of this study was to characterize the regulation of hepatic transporters by FXR and PXR during ANIT-induced liver injury. Wild-type, FXR-null, and PXR-null mice were administered ANIT (75 mg/kg, po) and evaluated 48 h later for hepatotoxicity and messenger RNA (mRNA) expression of basolateral uptake (sodium taurocholate–cotransporting polypeptide, organic anion transporting polypeptide [Oatp] 1a1, Oatp1a4, Oatp1b2) and efflux transporters (organic solute transporter [Ost] α, Ostβ, multidrug resistance–associated protein [Mrp] 3, Mrp4), as well as canalicular transporters (bile salt export pump [Bsep], Mrp2, multidrug resistance protein 2 [Mdr2], ATPase, class I, type 8B, member 1 [Atp8b1]). Livers from wild-type and PXR-null mice had comparable multifocal necrosis 48 h after ANIT. However, ANIT-treated FXR-null mice have fewer and smaller necrotic foci than wild-type mice but had scattered single-cell hepatocyte necrosis throughout the liver. Serum alanine transaminase, alkaline phosphatase (ALP), and direct bilirubin were increased in all genotypes, with higher ALP levels in FXR-null mice. Serum and liver unconjugated bile acids were higher in ANIT-treated FXR-null mice than the other two genotypes. ANIT induced mRNA expression of Mdr2, Bsep, and Atp8b1 in wild-type and PXR-null mice but failed to upregulate these genes in FXR-null mice. mRNA expression of uptake transporters declined in livers of all genotypes following ANIT treatment. ANIT increased Ostβ and Mrp3 mRNA in livers of wild-type and PXR-null mice but did not alter Ostβ mRNA in FXR-null mice. In conclusion, FXR deficiency enhances susceptibility of mice to ANIT-induced liver injury, likely a result of impaired induction of hepatobiliary efflux transporters and subsequent hepatic accumulation of unconjugated bile acids. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid and perfluorodecanoic acid (PFDA) are commonly used as emulsifiers and surfactants in fluoropolymer manufacturing and are known peroxisome proliferator–activated receptor alpha (PPARα) agonists. PPARα activation induces β- and ω-oxidation enzymes such as Cyp4a14 and acyl-CoA oxidase, which are a likely cause of subsequent oxidative stress and peroxisome proliferation. Conversely, NF-E2-related factor-2 (Nrf2) is a transcription factor that protects against oxidative stress and inflammation by regulating several detoxification and xenobiotic transporter genes. Because PFDA markedly induces hepatic metabolism and oxidative stress, we hypothesized that PFDA exposure would increase expression of hepatic efflux multidrug resistance–associated protein (Mrp) transporters. A single PFDA dose (80 mg/kg) administered to mice increased hepatic Mrp3 (fourfold) and Mrp4 (31-fold) mRNA expression. Upregulation of Mrp3 and Mrp4 correlated with elevated serum-conjugated bilirubin and bile acids, respectively. To determine the mechanism of Mrp3 and Mrp4 induction, PFDA was administered to Nrf2-null mice, PPARα-null mice, and mice pretreated with gadolinium chloride, a Kupffer cell–depleting chemical capable of inhibiting the inflammatory cytokine response. In both PPARα- and Nrf2-null mice, maximal induction of Mrp3 and Mrp4 mRNA after PFDA administration was attenuated. Gadolinium chloride pretreatment reduced serum and hepatic tumor necrosis factor-α levels after PFDA treatment, as well as Mrp4 mRNA expression by 30%, suggesting that Kupffer cell–derived mediators may contribute to Mrp induction. Thus, after PFDA administration, the liver mounts a compensatory hepatoprotective response via PPARα and Nrf2, markedly increasing Mrp3 and Mrp4 expression, with corresponding increases in serum of known Mrp3 and Mrp4 substrates. [ABSTRACT FROM AUTHOR]

To estimate the productivity and grazing impact of a common appendicularian species Oikopleura dioica in Tokyo Bay, monthly observations on its abundance and vertical distribution were conducted during 2000. The abundance peaked in February and October, but was low during summer. Seasonal fluctuations in productivity were similar to those of the abundance, with maximum values of 92, 134 and 508 mg C m−2 day−1 for somatic, new house and discarded house productivity in October and 206 mg C m−2 day−1 for fecal pellet productivity in February, respectively. The averaged biomass of O. dioica was only 2.5% of that of copepods; however, the secondary productivity of the former corresponded to 12.4% of the latter. Daily grazing impact on particulate organic carbon ranged from 0.05% to 5%, which is close to the impact by copepods. These results imply that in Tokyo Bay, where small copepods and jellyfish are abundant, O. dioica is an important component of the ecosystem because it bridges between small primary producers and higher consumers. [ABSTRACT FROM AUTHOR]

Hepatic ischemia-reperfusion (IR) injury during liver transplantation can lead to cholestasis and remote organ dysfunction. Multidrug resistance–associated proteins (Mrps) are efflux transporters known to transport a diverse set of substrates, such as amphipathic chemicals, organic anions, and endogenous molecules. The purpose of this study was to determine the effect of hepatic IR injury on the expression of Mrps in rat liver and kidney. Male Sprague-Dawley rats were subjected to 60 min of partial hepatic ischemia. At various times after reperfusion (0, 3, 6, 24, and 48 h), the ischemic lobes were harvested as well as kidneys. RNA and protein expression of Mrps in livers and kidneys were determined by the branched DNA method, Western blot analysis, and tissue immunofluorescence. Mrp2 mRNA and protein expression in livers decreased after IR. Conversely, Mrp2 mRNA and protein expression in kidneys increased after IR. Mrp3 mRNA expression, and Mrp4 mRNA and protein expression in kidneys transiently increased after IR. The intensity of immunofluorescent staining of Mrp2 corresponded to changes in Mrp2 expression in livers and kidneys after IR as detected by Western blot analysis and was localized to the apical membrane domain in both tissues. These results demonstrate that after hepatic IR, downregulation of hepatic Mrp2 and upregulation of renal Mrp2 occur. These decreases in hepatic Mrp2 may contribute to cholestasis, yet increases in kidney may protect from oxidative stress and/or inflammation after hepatic IR. [ABSTRACT FROM AUTHOR]