Stratospheric aerosol increase after eruption of Pinatubo observed with lidar and aureolemeter

An increase in the amount of stratospheric aerosol due to the Pinatubo eruption (June 12-15, 1991, 15.14 deg N, 120.35 deg E) was observed from the end of June, 1991 by a lidar in NIES (National Institute for Environmental Studies), Tsukuba (36.0 deg N, 140.1 deg E). After large fluctuations in summer of 1991, the amount of the aerosols increased in mid-September as a result of enhanced transportation from the subtropical region. In autumn and winter of 1991, dense aerosol layers were continuously observed. Aureolemeter (scanning spectral radiometer) measurements were also carried out with lidar measurements and columnar size distribution of stratospheric aerosols was estimated for some cases. Collaborative measurements with the lidar and aureolemeter provided some information on height distribution of the surface area of aerosols in late 1991

Epitope Characterization of an Aromatase Monoclonal Antibody Suitable for the Assessment of Intratumoral Aromatase Activity

Immunohistochemistry is one of the most suitable methods for the detection of intratumoral aromatase in order to identify patients who may respond to aromatase inhibitor therapy in hormone-dependent breast cancer. Previous studies showed statistically significant correlation between results of immnuohistochemistry and biochemical analysis in carcinoma components stained by aromatase monoclonal antibody 677. In this study, determination of the antigenic peptides recognized by aromatase antibodies through epitope mapping, combined with the new knowledge on aromatase-reductase interaction, provide insights for understanding various immunostaining patterns using different aromatase antibodies. Our studies on aromatase-reductase interaction also provided critical information on how aromatase and reductase interact with each other on the endoplasmic reticulum membrane, and identified key residues, including K108 of aromatase, that are involved in the interaction with reductase. Through epitope mapping and taking into consideration the interference with aromatase immunohistochemical staining by NADPH-cytochrome P450 reductase, we demonstrated that monoclonal antibody 677 is a suitable antibody for an assessment of intratumoral aromatase activity in breast cancer patients for making clinical management decisions. These results also provide valuable information to identify new aromatase antibodies for immunohistochemical diagnosis of hormone-dependent breast cancer in future

Aromatase expression and outcomes in the P024 neoadjuvant endocrine therapy trial

Background Expression of aromatase by malignant breast epithelial cells and/or the surrounding stroma implies local estrogen production that could influence the outcome of endocrine therapy for breast cancer. Methods A validated immunohistochemical assay for aromatase was applied to samples from the P024 neoadjuvant endocrine therapy trial that compared tamoxifen and letrozole. The presence of aromatase expression by tumor or stromal cells was correlated with tumor response, treatment induced changes in proliferation index (Ki67), relapse-free survival (RFS) and breast cancer-specific survival (BCSS). Results Tumor and stromal aromatase expression were highly correlated (P = 0.0001). Tumor cell aromatase, as a semi-continuous score, also correlated with smaller tumor size at presentation (P = 0.01) higher baseline ER Allred score (P = 0.006) and lower Ki67 levels (P = 0.003). There was no significant relationship with clinical response or treatment-induced changes in Ki67. However, in a Cox multivariable model that incorporated a post-treatment tumor profile (pathological T stage, N stage, Ki67 and ER status of the surgical specimen), the presence of tumor aromatase expression at baseline sample remained a favorable independent prognostic biomarker for both RFS (P = 0.01, HR 2.3, 95% CI 1.2–4.6 for absent expression) and BCSS (P = 0.008, HR 3.76, 95% CI 1.4–10.0). Conclusions Autocrine estrogen synthesis may be most characteristic of smaller, more indolent and ER-rich breast cancers with lower baseline growth rates. However, response to endocrine treatment may not depend on whether the estrogenic stimulus has a local versus systemic source

The farnesoid X receptor regulates transcription of 3 beta-hydroxysteroid dehydrogenase type 2 in human adrenal cells

Recent studies have shown that the adrenal cortex expresses high levels of farnesoid X receptor (FXR), but its function remains not known. Herein, using microarray technology, we tried to identify candidate FXR targeting genes in the adrenal glands, and showed that FXR regulates 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) expression in human adrenocortical cells. We further demonstrated that FXR stimulated HSD3B2 promoter activity and have defined the cis-element responsible for FXR regulation of HSD3B2 transcription. Transfection of H295R adrenocortical cells with FXR expression vector effectively increased FXR expression levels and additional treatment with chenodeoxycholic acid (CDCA) caused a 25-fold increase in the mRNA for organic solute transporter alpha (OSTα), a known FXR target gene. HSD3B2 mRNA levels also increased following CDCA treatment in a concentration-dependent manner. Cells transfected with a HSD3B2 promoter construct and FXR expression vector responded to CDCA with a 20-fold increase in reporter activity compared to control. Analysis of constructs containing sequential deletions of the HSD3B2 promoter suggested a putative regulatory element between -166 and -101. Mutation of an inverted repeat between -137 and -124 completely blocked CDCA/FXR induced reporter activity. Chromatin immunoprecipitation assays further confirmed the presence of a FXR response element in the HSD3B2 promoter. In view of the emerging role of FXR agonists as therapeutic treatment of diabetes and certain liver diseases, the effects of such agonists on other FXR expressing tissues should be considered. Our findings suggest that in human adrenal cells, FXR increases transcription and expression of HSD3B2. Alterations in this enzyme would influence the capacity of the adrenal gland to produce corticosteroids

表層海水中溶存酸素の高精度連続観測

大気・海洋間の二酸化炭素や酸素の交換量と，その時空間変動要因や，大気中の温室効果ガスの動態を解明するための一環として，表層海水中溶存酸素の高精度連続観測に取り組んでいる．海洋地球研究船「みらい」では，表層海水連続測定装置により，水温・塩分の測定に加え，世界中で広く利用されているAADI社製OPTODEによる溶存酸素，および，蛍光光度計によるクロロフィルaの測定が行われてきた．OPTODEは時間安定性が優れており，連続観測に適していると考えられているが，応答時間が遅い（カタログによれば67%応答時間は20℃で23秒）という問題があった．そこで，船舶CTDO観測で培った高精度溶存酸素測定技術に基づき，2012年度から表層海水連続測定装置に応答時間が早いJFE Advantech社製RINKOを追加した．溶存酸素検出膜の適切なエイジングと標準ガスを用いたセンサー出力値の線形化，および，時間ドリフト補正用の溶存酸素の分析値を取得することで，溶存酸素の高精度連続観測を実現し，北極海，ベーリング海，西部太平洋，南大洋の広範囲でデータを蓄積した．従来のOPTODEと新たに導入したRINKOの比較から，RINKOに比べてOPTODEは約8分遅れて応答していることや，北極海などでの塩分の短時間での大きな変化に対応してOPTODEが不自然に大きく応答することが明らかになった．さらに，RINKOの技術を応用し，センサーを用いた酸素法による基礎生産量の測定を試みている．これらのデータを総合的に解析し，表層海水中の溶存酸素の時空間変動特性を把握し，変動要因の解明を目指す．BE13-19講演要旨 / ブルーアース2013（2013年3月14日～15日, 東京海洋大学品川キャンパス）http://www.godac.jamstec.go.jp/darwin/cruise/mirai/mr12-e03/

Multiple noncoding exons 1 of nuclear receptors NR4A family (nerve growth factor-induced clone B, Nur-related factor 1 and neuron-derived orphan receptor 1) and NR5A1 (steroidogenic factor 1) in human cardiovascular and adrenal tissues

金沢大学医薬保健研究域医学系Objective: Nuclear receptors are involved in a wide variety of functions, including aldosteronogenesis. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. Methods: We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5′-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs). Results: In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5′-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues. Conclusion: NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins