Tan\u27itsu chaneru zatsuon yokusei shuho ni kansuru kenkyu

制度:新 ; 報告番号:甲3553号 ; 学位の種類:博士(工学) ; 授与年月日:2012/3/15 ; 早大学位記番号:新589

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization.BackgroundAnaphylatoxin C5a mediates inflammatory responses through interaction with a specific C5a receptor (C5aR), the expression of which is thought to be restricted to peripheral blood leukocytes. Although the presence of C5aR on cultured mesangial cells and tubular epithelial cells has recently been documented, the tissue distribution of C5aR in diseased kidney has not yet been determined.MethodsImmunohistochemistry and nonradioactive in situ hybridization for C5aR were performed in 34 tissue samples of kidneys from patients with various renal diseases, including 4 with minimal change nephrotic syndrome (MCNS), 5 with membranous nephropathy (MN), and 25 with mesangial proliferative glomerulonephritis (mesGN; 15 patients with IgA nephropathy, 5 with non-IgA mesGN, and 5 with lupus nephritis). Normal portions of surgically resected kidney served as the control.ResultsIn normal kidneys, C5aR protein was detected in tubular epithelial cells, while C5aR mRNA was detected in a few glomerular cells, tubular epithelial cells, and vascular endothelial and smooth muscle cells. In MCNS, the distribution of C5aR protein and mRNA was similar to that in normal kidneys. In MN and mesGN, C5aR protein and mRNA were detected in mesangial cells, glomerular epithelial and endothelial cells, Bowman's capsule cells, tubular cells, infiltrating cells, and vascular endothelial and smooth muscle cells. The glomerular expression of C5aR mRNA and protein correlated positively with the degree of mesangial hypercellularity and mesangial matrix expansion in mesGN. In the tubulointerstitium, interstitial expression of C5aR mRNA correlated positively with the degree of tubular atrophy and interstitial broadening in mesGN. Furthermore, the interstitial expression of C5aR mRNA correlated positively with the level of serum creatinine.ConclusionsOur results indicate that renal cells produce C5aR and that activation of C5a/C5aR pathway on renal cells may be involved in tissue injury in mesGN

Localization of an hTERT repressor region on human chromosome 3p21.3 using chromosome engineering

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA. The reactivation of telomerase activity by aberrant upregulation/expression of its catalytic subunit hTERT is a major pathway in human tumorigenesis. However, regulatory mechanisms that control hTERT expression are largely unknown. Previously, we and others have demonstrated that the introduction of human chromosome 3, via microcell-mediated chromosome transfer (MMCT), repressed transcription of the hTERT gene. These results suggested that human chromosome 3 contains a regulatory factor(s) involved in the repression of hTERT. To further localize this putative hTERT repressor(s), we have developed a unique experimental approach by introducing various truncated chromosome 3 regions produced by a novel chromosomal engineering technology into the renal cell carcinoma cell line (RCC23 cells). These cells autonomously express ectopic hTERT (exohTERT) promoted by a retroviral LTR promoter in order to permit cellular division after repression of endogenous hTERT. We found a telomerase repressor region located within a 7-Mb interval on chromosome 3p21.3. These results provide important information regarding hTERT regulation and a unique method to identify hTERT repressor elements

Juvenile hormone synthesis and signaling disruption triggering male offspring induction and population decline in cladocerans (water flea): Review and adverse outcome pathway development

Juvenile hormone (JH) are a family of multifunctional hormones regulating larval development, molting, metamorphosis, reproduction, and phenotypic plasticity in arthropods. Based on its importance in arthropod life histories, many insect growth regulators (IGRs) mimicking JH have been designed to control harmful insects in agriculture and aquaculture. These JH analogs (JHAs) may also pose hazards to nontarget species by causing unexpected endocrine-disrupting (ED) effects such as molting and metamorphosis defects, larval lethality, and disruption of the sexual identity. This critical review summarizes the current knowledge of the JH-mediated effects in the freshwater cladoceran crustaceans such as Daphnia species on JHA-triggered endocrine disruptive outputs to establish a systematic understanding of JHA effects. Based on the current knowledge, adverse outcome pathways (AOPs) addressing the JHA-mediated ED effects in cladoceran leading to male offspring production and subsequent population decline were developed. The weight of evidence (WoE) of AOPs was assessed according to established guidelines. The review and AOP development aim to present the current scientific understanding of the JH pathway and provide a robust reference for the development of tiered testing strategies and new risk assessment approaches for JHAs in future ecotoxicological research and regulatory processes.publishedVersionacceptedVersio

Relationship between mitochondrial DNA polymorphism and postnatal growth of Japanese beef cattle

Correlation coefficients (r) between mitochondrial DNA (mtDNA) haplotypes, maternal lineage (ML), birth weight (BWT), preweaning average daily gain (PREADG), weaning weight (WT6), post weaning average daily gain (POSTADG) and yearling weight (WT12) were computed in Japanese Black beef cattle within the same herd and management. The objective was to study the relationship between maternal and postnatal growth traits and to investigate if postnatal growth of calves to yearling age could be accurately predicted from mtDNA genotype at an early age. Blood samples and phenotypic records from 129 cattle which were part of a QTL mapping herd were utilized. mtDNA from the displacement-loop (D-loop) region (496 bp) was genotyped and classified into sub-groups 2 and 3 haplotypes and sequenced. General linear models procedure was utilized to adjust for genetic and non-genetic effects on postnatal growth traits. Simple and multiple linear regressions were fitted to predict postnatal growth traits from mtDNA haplotypes and the coefficients of determination (R2 ) were computed. Results revealed 19 maternal lineages and four mtDNA types (1, 11, 73 and a new hitherto unreported one). There were strong, positive and highly significant (P0.05) ranging from -0.05 to 0.1. Prediction of postnatal growth from mtDNA yielded very low R2 values ranging from 0.002 for BWT to 0.019 for WT6. The addition of ML, sub-group 2 and sub-group 3 haplotype information did not lead to any appreciable improvement in prediction accuracy. It was concluded that mtDNA polymorphism has no significant association with postnatal growth from birth to yearling age, and by implication, nuclear rather than cytoplasmic DNA, is most likely responsible for genetic variation observed in postnatal growth of Japanese Black cattle. Therefore, mtDNA genotyping at an early age has no bearing on future growth performance of calves

Oligomerization of Hepatitis C Virus Core Protein is Crucial for Interaction with the Cytoplasmic Domain of E1 Envelope Protein

Hepatitis C virus (HCV) contains two membrane-associated envelope glycoproteins, E1 and E2, which assemble as a heterodimer in the endoplasmic reticulum (ER). In this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the E1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the ER membrane: the conventional type I membrane topology and a polytopic topology in which the protein spans the ER membrane twice with an intervening cytoplasmic loop (amino acid residues 288 to 360). We also demonstrate that the E1 glycoprotein is able to associate with the HCV core protein, but only upon oligomerization of the core protein in the presence of tRNA to form capsid-like structures. Yeast two-hybrid and immunoprecipitation analyses reveal that oligomerization of the core protein is promoted by amino acid residues 72 to 91 in the core. Furthermore, the association between the E1 glycoprotein and the assembled core can be recapitulated using a fusion protein containing the putative cytoplasmic loop of the E1 glycoprotein. This fusion protein is also able to compete with the intact E1 glycoprotein for binding to the core. Mutagenesis of the cytoplasmic loop of E1 was used to define a region of four amino acids (residues 312 to 315) that is important for interaction with the assembled HCV core. Taken together, our studies suggest that interaction between the self-oligomerized HCV core and the E1 glycoprotein is mediated through the cytoplasmic loop present in a polytopic form of the E1 glycoprotein

看護学生と受持ち患児の母親との関係形成に向けた効果的支援の検討 : 母親とのかかわりの中で困惑した場面に焦点を当てて

本研究の目的は,小児看護学実習において看護学生の受持ち患児の母親との関係形成に向けた支援方法を見出すことである.28名の看護学生の受持ち患児の母親とのかかわりの中で困惑した場面から困惑した内容に焦点をあて,内容の類似性からカテゴリー化を行った.分析の結果,【母親が抱く思い・ストレスに対する認知と対応】,【母親のネガティブな態度】,【看護学生の知識・経験不足】,【母親との言語的コミュニケーション】の4つのカテゴリーが抽出された.看護学生は母親とのかかわりに困惑しながらも,母親のおかれている状況や思いに近づき,自分自身を内省していた.そこで教員は,母親の抱く思いが患児の病状の変化とともに複雑に表出されることの意味を学生に問い,理解できるように導くことが必要である.そして,学生の知識の確認や援助の工夫を促し,学生が自信をもって不安なく看護を提供できるように配慮し支援していくことの必要性が示唆された

小児看護学実習において母親との関係形成のために看護学生がとる行動の実態

本研究の目的は,小児看護学実習において看護学生が受け持ち患児の母親との関係形成のために心がけている行動の実態を明らかにすることである.そこで,看護学生がとる行動に焦点をあて,内容の類似性からカテゴリー化を行った.その結果,125コード,17サブカテゴリーから【母親の疲労に対する援助を行う】【母親とコミュニケーションを図る】【礼儀・マナーを守る】【患児に関心を示す】【看護技術・知識を提供する】の5カテゴリーが抽出された.看護学生は患児や母親との対話を大切にしながらも母親の意思を尊重するなど支持的態度を示したり,母親の心身の疲労を軽減したりするための援助を行うことが母親からの信頼を得るきっかけになると捉え行動していた.さらに,礼節をわきまえながら患児およびその母親と積極的に関わろうと努力し,学生として看護の専門的知識や技術を提供することを心がけていることが明らかとなった