Roles of Fukutin, the Gene Responsible for Fukuyama-Type Congenital Muscular Dystrophy, in Neurons: Possible Involvement in Synaptic Function and Neuronal Migration

Fukutin is a gene responsible for Fukuyama-type congenital muscular dystrophy (FCMD), accompanying ocular and brain malformations represented by cobblestone lissencephaly. Fukutin is related to basement membrane formation via the glycosylation of α-dystoglycan (α-DG), and astrocytes play a crucial role in the pathogenesis of the brain lesion. On the other hand, its precise function in neurons is unknown. In this experiment, the roles of fukutin in mature and immature neurons were examined using brains from control subjects and FCMD patients and cultured neuronal cell lines. In quantitative PCR, the expression level of fukutin looked different depending on the region of the brain examined. A similar tendency in DG expression appears to indicate a relation between fukutin and α-DG in mature neurons. An increase of DG mRNA and core α-DG in the FCMD cerebrum also supports the relation. In immunohistochemistry, dot-like positive reactions for VIA4-1, one of the antibodies detecting the glycosylated α-DG, in Purkinje cells suggest that fukutin is related to at least a post-synaptic function via the glycosylation of α-DG. As for immature neurons, VIA4-1 was predominantly positive in cells before and during migration with expression of fukutin, which suggest a participation of fukutin in neuronal migration via the glycosylation of α-DG. Moreover, fukutin may prevent neuronal differentiation, because its expression was significantly lower in the adult cerebrum and in differentiated cultured cells. A knockdown of fukutin was considered to induce differentiation in cultured cells. Fukutin seems to be necessary to keep migrating neurons immature during migration, and also to support migration via α-DG

Involvement of 4-hydroxy-2-nonenal Accumulation in Multiple System Atrophy

Recent studies have suggested implications for α-synuclein cytotoxicity in the pathomechanism of multiple system atrophy (MSA). Given in vitro evidence that α-synuclein generates oxidative stress, it is proposed that lipid peroxidation may be accelerated in MSA. To address this issue, we performed an immunohistochemical analysis of protein-bound 4-hydroxy-2-nonenal (P-HNE) in sections of archival, formalin-fixed, paraffin-embedded pontine materials of eight sporadic MSA patients and eight age-matched control subjects. In the MSA cases, P-HNE immunoreactivity was localized in all of the neuronal cytoplasmic inclusions and glial cytoplasmic inclusions, both of them identified with α-synuclein and ubiquitin. It was also detectable in reactive astrocytes and phagocytic microglia but undetectable in activated microglia. By contrast, P-HNE immunoreactivity in the control cases was only very weak or not at all in the parenchyma including neurons and glia. The present results provide in vivo evidence that HNE participates in α-synuclein-induced cytotoxicity and neuroinflammation in MSA

臨地実習における看護学教員と実習指導者に関する研究動向と課題

本研究の目的は，臨地実習における看護学教員と実習指導者に関する論文を分析し，研究動向と課題を明らかに することである．医学中央雑誌Web. 版を用いて「臨地実習」「看護学教員」「実習指導者」をキーワードとした原 著論文の検索を行った．文献レビューシート一覧を作成し，研究の種類・デザイン，研究方法，研究内容等の分 析を行った．その結果，対象文献は54件であり，研究の種類は量的研究が50.0％と半数を占め，研究デザインは因 子探索研究が最も多く47.5％であった．研究対象者は，実習指導者が最も多く41.9％，研究者の所属は看護大学が 35.2％であった．対象文献を内容分析の手法を用いて分類した結果，【看護学教員と実習指導者の連携・協働に関 する研究】【臨地実習指導におけるやりがいや困難感に関する研究】【効果的な臨地実習指導の検討に関する研究】 【臨地実習の評価に関する研究】【実習指導者の資質向上に関する研究】の5つのカテゴリーで構成された．今後の 研究課題として，1．看護学教員と実習指導者のそれぞれが認識している役割についての研究，2．看護学教員と実 習指導者の異なる役割や専門性・視点の明確化，3．看護学教員と実習指導者の連携・協働のあり方，4．指導力や 教授活動への自己効力感を高めるための要因，5．学生からの臨地実習評価の蓄積と分析，6．実習指導者講習会の 効果の分析，の6つを得た．The aims of this research were to analyze published papers relating to nursing teachers and clinical instructors responsible for clinical practicums, and from the results clarify research trends and issues in this area. Original papers containing the keywords 'clinical practicum' (rinchijisshu), 'nursing teacher' (kangogakukyoin), and 'clinical instructor' (jisshushidosha) were identified in a literature search of Ichushi Web. A summary of the literature review was created and examined for aspects including research type, design, methods, and contents. In total 54 papers were reviewed. Among them, in terms of research type, 50% were based on quantitative research and, in terms of research design, 47.5% used factor analysis. The highest percentage of research, 41.9%, investigated clinical instructors, and 35.2% of the researchers belonged to colleges of nursing. Based on the content analysis results, the studies were classified into five categories:【 studies on cooperation between nursing teachers and clinical instructors】;【studies on the sense of reward and difficulties in clinical practicum guidance】;【 studies on effective guidance in clinical practicums】;【 studies on evaluation of clinical practicums】;【 and studies on improving the quality of clinical instructors】. Future topics for research were summarized in the following six areas: 1) research on the roles perceived by nursing teachers and by clinical instructors; 2) clarification of different roles, expertise, and perspectives for nursing teachers and clinical instructors; 3) desirable ways for nursing teachers and clinical instructors to cooperate; 4) factors for improving self-efficacy in leadership and teaching activities; 5) accumulation and analysis of students' evaluation of clinical practicum sessions; and 6) analysis of the effectiveness of clinical instructors' seminars

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Intensity-modulated radiation therapy for small cell carcinoma of the prostate: A case report

Small cell carcinomas (SCC) make up only 1% of malignancies of the prostate. Reports of several case series have described outcomes of surgery and chemotherapy for SCC of the prostate, but few reports address radiotherapy. We treated a case of SCC of the prostate with intensity-modulated radiation therapy (IMRT) consisting of 70[[ce:hsp sp="0.25"/]]Gy administered in 35 fractions followed by hormonal therapy using only luteinizing hormone-releasing hormone (LH-RH) agonist. The tumor volume decreased remarkably by 4 months after IMRT. The rapid decrease in tumor size of this SCC of the prostate seemed to suggest a similar high radiosensitivity to that of SCC of the lung, but the tumor increased rapidly thereafter within the radiation fields, and pelvic lymph node metastases had developed by 24 months after IMRT. By 28 months after IMRT, multiple lung metastases developed, and the patient died of SCC of the prostate 31 months after initial diagnosis

Liver-Type Fatty Acid-Binding Protein Attenuates Renal Injury Induced by Unilateral Ureteral Obstruction

Liver-type fatty-acid-binding protein (L-FABP), which has high affinity for long-chain fatty acid oxidation products, may be an effective endogenous antioxidant. To examine the role of L-FABP in tubulointerstitial damage, we used a unilateral ureteral obstruction (UUO) model. We established human L-FABP (hL-FABP) gene transgenic (Tg) mice and compared the tubulointerstitial pathology of the Tg mice (n = 23) with that of the wild-type (WT) mice (n = 23). Mice were sacrificed on days 2, 4, 5, or 7 after UUO. Although mouse L-FABP was not expressed in WT mice, hL-FABP was expressed in the proximal tubules of the Tg mice with UUO (UUO-Tg) and in sham-operated Tg mice. The expression of renal hL-FABP was significantly increased in UUO-Tg compared with sham-operated Tg mice. The number of macrophages (F4/80) infiltrating the interstitium and the level of expression of MCP-1 and MCP-3 were significantly lower in UUO-Tg kidneys compared with UUO-WT kidneys. In UUO-Tg kidneys, the degree of the tubulointerstitial injury and the deposition of type I collagen were significantly lower than that of UUO-WT kidneys. On day 7, lipid peroxidation product accumulated in the UUO-WT kidneys but not in that of UUO-Tg kidneys. In conclusion, renal L-FABP may reduce the oxidative stress in the UUO model, ameliorating tubulointerstitial damage