89 research outputs found
The Effect of Lobbying in an Economy with Firm Heterogeneity and Unemployment : Searching for an Optimal Tariff Policy
本稿では、生産性が異質な企業と失業が存在する経済において、ロビー活動が厚生にどのような影響を及ぼすかを検討する。このため、Melitz (2003) を基礎として、企業のロビー活動と失業を明示的に示したモデルを構築する。ロビー活動は、経済全体の雇用と賃金に影響を与え、そのどちらの効果が大きいかによって、厚生に与える影響が異なることが明らかになった。このモデルを用いて、ロビー活動が関税率に与える影響を明らかにし、また、その結果、厚生がどのように変化するのかについて明らかにすることが残された課題である
A Novel RNA Synthesis Inhibitor, STK160830, Has Negligible DNA-Intercalating Activity for Triggering A p53 Response, and Can Inhibit p53-Dependent Apoptosis
RNA synthesis inhibitors and protein synthesis inhibitors are useful for investigating whether biological events with unknown mechanisms require transcription or translation; however, the dependence of RNA synthesis has been difficult to verify because many RNA synthesis inhibitors cause adverse events that trigger a p53 response. In this study, we screened a library containing 9600 core compounds and obtained STK160830 that shows anti-apoptotic effects in irradiated wild-type-p53-bearing human T-cell leukemia MOLT-4 cells and murine thymocytes. In many of the p53-impaired cells and p53-knockdown cells tested, STK160830 did not show a remarkable anti-apoptotic effect, suggesting that the anti-apoptotic activity is p53-dependent. In the expression analysis of p53, p53-target gene products, and reference proteins by immunoblotting, STK160830 down-regulated the expression of many of the proteins examined, and the downregulation correlated strongly with its inhibitory effect on cell death. mRNA expression analyses by qPCR and nascent RNA capture kit revealed that STK160830 showed a decreased mRNA expression, which was similar to that induced by the RNA synthesis inhibitor actinomycin D but differed to some extent. Furthermore, unlike other RNA synthesis inhibitors such as actinomycin D, p53 accumulation by STK160830 alone was negligible, and a DNA melting-curve analysis showed very weak DNA-intercalating activity, indicating that STK160830 is a useful inhibitor for RNA synthesis without triggering p53-mediated damage responses
Hemangiopericytoma in the sacrococcygeal space: a case report
<p>Abstract</p> <p>Introduction</p> <p>A hemangiopericytoma is a rare, soft-tissue tumor of vascular origin derived from a pericyte of Zimmerman, which is a modified smooth muscle cell that surrounds the small blood vessels. Hemangiopericytomas can occur wherever there are vascular capillaries. However, there are no previous reports of a hemangiopericytoma in the sacrococcygeal space.</p> <p>Case presentation</p> <p>We describe the first reported case of a hemangiopericytoma found in the sacrococcygeal space. A 47-year-old Japanese woman presented with a palpable tumor on the left side of her anus. Preoperative imaging indicated that the tumor was in the sacrococcygeal space without invasion of other organs. A complete resection was performed via a parasacral incision. The histological and immunohistochemical staining patterns supported the diagnosis of a hemangiopericytoma.</p> <p>Conclusion</p> <p>A complete resection without piecemeal excision is the best way to treat a hemangiopericytoma. Recognizing the presence of a hemangiopericytoma in the sacrococcygeal space requires appropriate surgery.</p
A novel transgenic chimaeric mouse system for the rapid functional evaluation of genes encoding secreted proteins
A major challenge of the post-genomic era is the functional characterization of anonymous open reading frames (ORFs) identified by the Human Genome Project. In this context, there is a strong requirement for the development of technologies that enhance our ability to analyze gene functions at the level of the whole organism. Here, we describe a rapid and efficient procedure to generate transgenic chimaeric mice that continuously secrete a foreign protein into the systemic circulation. The transgene units were inserted into the genomic site adjacent to the endogenous immunoglobulin (Ig) κ locus by homologous recombination, using a modified mouse embryonic stem (ES) cell line that exhibits a high frequency of homologous recombination at the Igκ region. The resultant ES clones were injected into embryos derived from a B-cell-deficient host strain, thus producing chimaerism-independent, B-cell-specific transgene expression. This feature of the system eliminates the time-consuming breeding typically implemented in standard transgenic strategies and allows for evaluating the effect of ectopic transgene expression directly in the resulting chimaeric mice. To demonstrate the utility of this system we showed high-level protein expression in the sera and severe phenotypes in human EPO (hEPO) and murine thrombopoietin (mTPO) transgenic chimaeras
ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation
ERAL1, a homologue of Era protein in Escherichia coli, is a member of conserved GTP-binding proteins with RNA-binding activity. Depletion of prokaryotic Era inhibits cell division without affecting chromosome segregation. Previously, we isolated ERAL1 protein as one of proteins which were associated with mitochondrial transcription factor A by using immunoprecipitation. In this study, we analysed the localization and function of ERAL1 in mammalian cells. ERAL1 was localized in mitochondrial matrix and associated with mitoribosomal proteins including the 12S rRNA. siRNA knockdown of ERAL1 decreased mitochondrial translation, caused redistribution of ribosomal small subunits and reduced 12S rRNA. The knockdown of ERAL1 in human HeLa cells elevated mitochondrial superoxide production and slightly decreased mitochondrial membrane potential. The knockdown inhibited the growth of HeLa cells with an accumulation of apoptotic cells. These results suggest that ERAL1 is localized in a small subunit of the mitochondrial ribosome, plays an important role in the small ribosomal constitution, and is also involved in cell viability
Greater Efficacy and Improved Endothelial Dysfunction in Untreated Type 2 Diabetes with Liraglutide versus Sitagliptin
Objective:The incretin hormone glucagon-like peptide 1 (GLP-1) and its analogs, including the glucagonlike peptide 1 receptor agonist liraglutide, use a simple once-daily regimen and can be easily introduced in the outpatient setting. We compared treatment with liraglutide monotherapy and dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy in patients with untreated type 2 diabetes( T2DM).Methods:This study included 40 outpatients with untreated T2DM who were randomized to receive liraglutide (0.9 mg/day, n=24) or DPP-4 inhibitors (n=16:sitagliptin, 50 mg/day) as initial treatment for 6 months. Glycemic control, urinalysis, blood pressure, body weight, lipid levels, vascular endothelial function, and inflammatory factors were assessed before and after treatment.Results:Significant improvement was observed in HbA1c and fasting blood glucose levels after treatment in both groups;improvements in the liraglutide group were significantly better than in the sitagliptin group. Only the liraglutide group demonstrated significant improvements in blood pressure, low-density lipoprotein cholesterol levels, urinary albumin excretion, flow-mediated dilatation, and high-sensitivity C-reactive protein levels. Linear regression analysis demonstrated a significant negative relation between change in flow-mediated dilatation and high-sensitivity C-reactive protein levels.Conclusion:Liraglutide provided significant glycemic control and improved blood pressure, lipid levels, endothelial function, and inflammatory factors in untreated T2DM. In addition to its impact on blood glucose levels, liraglutide may have beneficial effects on the cardiovascular system in patients with T2DM
コウレイシャ 2 ガタ トウニョウビョウ カンジャ ニ オケル ニンチ キノウ チョウサ ト ソノ カンレン インシ ニ ツ イテ
目的:2型糖尿病は,認知症発症との関連が報告されている.そこで実際の高齢者2型糖尿病患者において,認知機能が低下している患者の頻度を調査し,また認知機能に影響を与える因子を検討した.方法:2014年2月?4月の間に,入院加療を行った糖尿病多発合併症や心血管病の既往がない2型糖尿病患者64名のうち,60歳以上の高齢者で,臨床研究に同意した35名(男性:23名,女性:12名)を対象とし,Mini-Mental State Examination(MMSE)にて認知機能を評価した.認知機能(MMSE score)と年齢,血糖コントロール(HbA1c),血圧,脂質,喫煙歴,糖尿病罹患歴,動脈硬化の指標として,Cardio Ankle Vascular Index(CAVI)に対する相関を検討した.結果:高齢者糖尿病のうち31.4%に認知機能の低下が疑われた.またそれは,年齢,糖尿病罹患歴,CAVI値にMMSE値は単相関を認め,重回帰分析では,糖尿病罹患歴とCAVI値が有意な影響を与えている因子であった.結論:高齢者2型糖尿病における認知機能は,罹患歴や動脈硬化が影響を与える事が示唆され,中年期からの糖尿病管理や動脈硬化抑制が老年期の認知機能障害の発生と関連する可能性が示唆された.Objective:Type 2 diabetes is reportedly associated with the risk of developing dementia. Hence, we surveyed elderly patients with type 2 diabetes to investigate the actual level of cognitive function decline and examine factors that affect cognitive function. Methods:From among 64 patients with type 2 diabetes who underwent inpatient treatment in the Department of Endocrinology and Metabolism of Dokkyo Medical University between February and April 2014, we selected as study subjects 35 patients aged ? 60 years(23 men and 12 women)who had no history of multiple diabetic complications or cardiovascular disease. The Mini-Mental State Examination(MMSE)was used to assess cognitive function. The correlations of cognitive function(MMSE score) with age, glycemic control(HbA1c), blood pressure, fat, smoking, diabetes history, and cardio-ankle vascular index (CAVI)as an index of arteriosclerosis were investigated. Results:Cognitive function decline was suspected in 31.4% of the elderly patients with diabetes. Simple correlations were found between MMSE score and age, diabetes history, and CAVI score. In particular, diabetes history and CAVI score were identified as significant risk factors in a multivariate analysis. Conclusion:Our results suggest that disease history and arteriosclerosis may affect the cognitive function of elderly patients with type 2 diabetes, and that diabetes management and arteriosclerosis control from middle age may be associated with cognitive function in old age
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