Expression of visual and nonvisual opsins in American chameleon

AbstractWe previously characterized five visual opsin genes of American chameleon (Anolis carolinensis). Here we report its nonvisual opsin gene orthologous to the chicken pineal gland-specific opsin (P-opsin) gene. In the pure-cone American chameleon retina, all visual opsins including rod opsin are expressed. In both pineal and parietal eye, three visual opsins as well as P-opsin are expressed. Although opsins are detected in the pineal glands of a wide variety of vertebrates, Southern analysis suggests that the P-opsin gene is used mainly by birds and reptiles

The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNALys3 packaging into human immunodeficiency virus type-1 particles

AbstractHuman immunodeficiency virus type-1 (HIV-1) requires the packaging of human tRNALys3 as a primer for effective viral reverse transcription. Previously, we reported that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) suppresses the packaging efficiency of tRNALys3. Although the binding of GAPDH to Pr55gag is important for the suppression mechanism, it remains unclear which domain of GAPDH is responsible for the interaction with Pr55gag. In this study, we show that Asp256, Lys260, Lys263 and Glu267 of GAPDH are important for the suppression of tRNALys3 packaging. Yeast two-hybrid analysis demonstrated that the C-terminal domain of GAPDH (151–335) interacts with both the matrix region (MA; 1–132) and capsid N-terminal domain (CA-NTD; 133–282). The D256R, K263E or E267R mutation of GAPDH led to the loss of the ability to bind to wild-type (WT) MA, and the D256R/K260E double mutation of GAPDH resulted in the loss of detectable binding activity to WT CA-NTD. In contrast, R58E, Q59A or Q63A of MA, and E76R or R82E of CA-NTD abrogated the interaction with the C-terminal domain of GAPDH. Multiple-substituted GAPDH mutant (D256R/K260E/K263E/E267R) retained the oligomeric formation with WT GAPDH in HIV-1 producing cells, but the incorporation level of the hetero-oligomer was decreased in viral particles. Furthermore, the viruses produced from cells expressing the D256R/K260E/K263E/E267R mutant restored tRNALys3 packaging efficiency because the mutant exerted a dominant negative effect by preventing WT GAPDH from binding to MA and CA-NTD and improved the reverse transcription. These findings indicate that the amino acids Asp256, Lys260, Lys263 and Glu267 of GAPDH is essential for the mechanism of tRNALys3-packaging suppression and the D256R/K260E/K263E/E267R mutant of GAPDH acts in a dominant negative manner to suppress tRNALys3 packaging

Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth

Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth. Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins. Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively. Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state

Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway

<p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.</p> <p>Methods</p> <p>The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.</p> <p>Results</p> <p>We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α₂, integrin α₄, and integrin α₅and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).</p> <p>Conclusions</p> <p>The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.</p

Experimental Studies for Application of the Fixed Lung as an Oxygenator

科学研究費補助金研究成果報告書研究種目: 一般研究(C)研究期間: 1994～1995課題番号: 06671336研究代表者: 藤野 昇三（滋賀医科大学・医学部・助手）研究代表者: 森 渥視（滋賀医科大学・医学部・教授）研究分担者: 朝倉 庄志（滋賀医科大学・医学部・助手）研究分担者: 岡田 慶夫（滋賀医科大学・学長）研究分担者: 手塚 則明（滋賀医科大学・医学部・医員

うつ病の治療中にアカシジアとジスキネジアを呈した一例

症例は60歳代男性，15年前より当科にてうつ病，アルコール依存症として治療していた．２年前より町内会の仕事で多大なストレスを感じ，１年前より身体不調から仕事を退職した．その後，過剰な飲酒が始まり，精神科病院に入院しアルコール依存症の治療が行われ，その際にオランザピンが投与された．その後は断酒ができていたが，町内会での大きな役割が回ってくる不安感からイライラ感が強くなり，オランザピンの増量，クロルプロマジンへの変更などを行ったが精神症状は改善せず，薬剤変更１ヶ月後より終日じっとしていられないアカシジア様症状と，舌が勝手に動く口舌ジスキネジア様症状，首下がり症状が出現した．抗精神病薬を中止したが症状改善せず，次第に食事摂取困難となり体重が減少，状態悪化のため当科入院となった．入院後，薬剤調整による抗うつ治療を行ったが改善なく，希死念慮の増悪を認めたため修正型電気けいれん療法（modified-electroconvulsive therapy: m-ECT）の適応と考えられ，全13回のm-ECT を施行した．m-ECT 施行により精神症状，アカシジア，ジスキネジア，首下がりが徐々に改善し，最終的には病状が著明に改善した．本症例のジスキネジアは薬剤性としては発現が急であり，また首下がりの症状を伴っていたため，パーキンソン病の存在が疑われた．頭部MRI，ドパミントランスポーターシンチグラフィでは異常はなかったが，MIBG 心筋シンチグラフィではFDG 集積の低下を認めた．入院時軽度の左右差のあるパーキンソニズムがあり，筋電図にて頸部伸展筋ミオパチーと診断された．以上から身体症状の原因は，臨床症状発現前のパーキンソン病を背景とする抗精神病薬の副作用であると考えられた．アカシジア，ジスキネジアは薬剤性に起因するものが多数であるが，その他の疾病の有無を注意深く観察することが必要であると考えられた．Here, we present a case study of a man in his sixties, under treatment for depression and alcoholism at our department for the past 15 years. 2 years ago, he began to experience high stress levels that he attributed to his work at the neighborhood association. One year after that, he retired from his job because of poor health. After his retirement, he began to consume alcohol excessively. Subsequently, he was admitted to our hospital and was treated for alcoholism with the antipsychotic drug olanzapine. Although he achieved abstinence, his frustration gradually increased because of the stress associated with his prominent role in his neighborhood association several months ahead. Therefore, he was administered a higher dose of olanzapine, which was then changed to chlorpromazine. However, his psychological symptoms did not improve. After about one month, he began to display symptoms of akathisia, characterized by an inability to stay still throughout the day. Additionally, his tongue began to move involuntarily, which is a common symptoms of dyskinesia. He also presented with the dropped head syndrome. His symptoms did not improve upon termination of antipsychotic drugs. He was subsequently hospitalized because of gradually decreasing appetite and weight. Because the antidepressant treatment had no effect and his suicidal feelings had exacerbated, he was subjected to 13 rounds of modified-electroconvulsive therapy (m-ECT). His mental condition improved and the akathisia, dyskinesia, and dropped head symptom decreased gradually. Parkinson’s disease would not have likely caused dyskinesia without long term medication with dopaminergic drugs. Additionally, because dyskinesia generally appears several years after initiation of antipsychotics therapy, dyskinesia in our case could not have occurred due to antipsychotic drugs in acute course of the symptoms. Head MRI and dopamine transporter scintigraphy did not show any abnormalities. In contrast, metaiodobenzylguanidine (MIBG) scintigraphy showed a decrease heart/mediastinum ratio (H/M ratio). He had been recognized as showing symptoms of parkinsonism with a slight laterality when he was initially hospitalized, and his EMG showed neck extensor myopathy, which is a characteristic of Parkinson’s disease. Thus, his physical symptoms were likely a side effect of short-term use of antipsychotic drugs for preclinical Parkinson’s disease. The most common cause of akathisia and dyskinesia is antipsychotics drug use, however it is necessary to check carefully for other diseases as well

Return migration after Disasters : A Case study of 2011 Fukushima Dai-ichi Nuclear Power Plant Accident.

We investigate what are the factors that influence people’s intent to return after disasters by a literature survey, and conduct an empirical analysis on return migration by using a unique survey of Fukushima evacuees to determine the factors that influence their decision to return after a disaster. We also conduct a simulation of the number of evacuees who intend to return. The result found that the number of returnees encouraged by this decontamination was 12,882, less than 8% of the total evacuees, while the decontamination cost per returnee was 3.36 million USD.本研究は，平成29年度関西大学研究教育高度化促進費「災害移民に関する国際的研究連携体制の構築」（研究代表者：永松伸吾）の成果である