野生下におけるスズキLateolabrax japonicusのエネルギー収支に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 佐藤 克文, 東京大学教授 大竹 二雄, 東京大学准教授 山川 卓, 東京大学准教授 北川 貴士, 名城大学教授 新妻 靖章University of Tokyo(東京大学

Design and Development of Mapping Exercise between Concept Map and Image Figure

概念マップを命題単位でイメージ図と対応付ける学習活動として，(1) イメージ図選択活動と(2) イメージ図組立活動，の二つの活動を演習として実現するソフトウェアシステムを設計・開発し，小学校理科での授業実践を通して評価した．概念間の関係として表現されている概念マップを視覚的な意味をもった構成要素とその空間配置として表現されたイメージ図と対応付けることは，知識の精緻化の一つとなりえる．正誤判定を伴ってこの対応付けを実現するためには，概念マップが命題レベルで正誤判定されている必要があるが，このためにキットビルド概念マップを用いている．授業実践を通して，この対応付け演習が児童及び教諭に有用な学習活動と認識されたこと，対象課題についての理解促進に貢献すること，を示唆する結果が得られた

Optimal Temperature of Graft Preservation after ex Vivo Gene Transfer in Lung Isografts

The aim of this study was to determine the optimal temperature of graft preservation after ex vivo gene transfer to rat lung isografts. Left lungs were harvested and infused with cationic lipid/LacZ-DNA complex via the pulmonary artery, and the grafts were stored for 4h. The grafts (n＝7) were allocated into groups IﾝIV according to the storage temperature:4℃, 10℃, 16℃, and 23℃, respectively. Forty-eight h after orthotopic transplantation, the arterial blood gas was analyzed and the peak airway pressure (PAP) and the level of LacZ protein production in the grafts were measured by reverse transcription polymerase chain reaction. After reperfusion, the grafts were stained with hematoxylin and eosin. The grafts in groups III and IV showed more deterioration as evidenced by decreased arterial oxygen tension, increased PAP, and predominant infiltration of inflammatory cells compared with groups I and II. The level of LacZ production was significantly lower in group I than in groups IIﾝIV. The optimal temperature of lung graft preservation after ex vivo gene transfer was determined to be 10℃, balancing considerations of lung injury and efficiency of transgene expression.</p

Characterization of the human herpesvirus 6A U23 gene

AbstractHuman herpesvirus 6 (HHV-6), which replicates abundantly in T cells, belongs to the Roseolovirus genus within the betaherpesvirus subfamily. Members of the Roseolovirus genus encode seven unique genes, U20, U21, U23, U24, U24A, U26, and U100. The present study focused on one of these, U23, by analyzing the characteristics of its gene product in HHV-6A-infected cells. The results indicated that the U23 protein was expressed at the late phase of infection as a glycoprotein, but was not incorporated into virions, and mostly stayed within the trans Golgi network (TGN) in HHV-6A-infected cells. Furthermore, analysis using a U23-defective mutant virus showed that the gene is nonessential for viral replication in vitro

Decarboxylative C-C Bond Cleavage Reactions via Oxapalladacycles

In the presence of Pd(0) catalyst and triethylborane, 3-hydroxy-4-pentenoic acids undergo C-C bond cleavage reactions via oxapalladacyclopentanones to provide conjugated dienes with evolution of carbon dioxide

Gastric Carcinoid with Hypergastrinemia: Report of Three Cases

We report 3 cases of gastric carcinoids with hypergastrinemia. Case 1: A 60-year-old man had a 2 cm carcinoid of the stomach and underwent partial resection. Involvement of the muscularis propria and lymph nodes metastasis were observed microscopically. Follow-up gastroscopy revealed another carcinoid lesion and total gastrectomy was performed. Case 2: A 67-year-old woman with multiple carcinoids of the entire stomach underwent antrectomy. No growth of residual tumors has been detected so far. Case 3: A 61-year-old man had a tumor near the esophagogastric junction and underwent total gastrectomy. Carcinoid component was diffusely intermingled with adenocarcinoma in the tumor and invaded into the subserosa. In all 3 cases, the serum gastrin level was high and atrophic gastritis was microscopically observed. Carcinoid tumor in Case 3 was different from those in Cases 1 and 2 and interestingly, gastric carcinoid with hypergastrinemia showed various types of appearance

Incidence and associated factors of sudden unexpected death in advanced cancer patients: A multicenter prospective cohort study

[Purpose] A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. [Methods] We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1–2 days; (b) surprise death, defined if the primary responsible palliative care physician answered “yes” to the question, “Were you surprised by the timing of the death?”; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)-defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia-modified Karnofsky PS ≥50. [Results] Among 1896 patients, the incidence of rapid decline death was the highest (30-day cumulative incidence: 16.8%, 95% CI: 14.8–19.0%), followed by surprise death (9.6%, 8.1–11.4%), unexpected death (9.0%, 7.5–10.8%), and PS-defined sudden death (6.4%, 5.2–8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. [Conclusion] Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4–16.8% according to the different definitions

A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene

Varicella-zoster virus (VZV), an alphaherpesvirus, establishes lifelong latent infection in the neurons of >90% humans worldwide, reactivating in one-third to cause shingles, debilitating pain and stroke. How VZV maintains latency remains unclear. Here, using ultra-deep virus-enriched RNA sequencing of latently infected human trigeminal ganglia (TG), we demonstrate the consistent expression of a spliced VZV mRNA, antisense to VZV open reading frame 61 (ORF61). The spliced VZV latency-associated transcript (VLT) is expressed in human TG neurons and encodes a protein with late kinetics in productively infected cells in vitro and in shingles skin lesions. Whereas multiple alternatively spliced VLT isoforms (VLTly) are expressed during lytic infection, a single unique VLT isoform, which specifically suppresses ORF61 gene expression in co-transfected cells, predominates in latently VZV-infected human TG. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency

Midkine promoter-based conditionally replicative adenovirus therapy for midkine-expressing human pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>To develop a novel therapeutic strategy for human pancreatic cancer using a midkine promoter-based conditionally replicating adenovirus.</p> <p>Methods</p> <p>We examined midkine mRNA expression and midkine protein expression by seven human pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, MIAPaCa-2, PANC-1, and Suit-2), as well as by non-cancerous pancreatic tissue and pancreatic cancers. Midkine promoter activity was measured in cancer cell lines by the dual luciferase reporter assay. Adenoviral transduction efficiency was assessed by fluorescent staining of cancer cell lines using adenovirus type 5 containing the green fluorescent protein gene (Ad5GFP). Replication of adenovirus type 5 containing the 0.6 kb midkne promoter (Ad5MK) was assessed by the detection of E1 protein in cancer cell lines. The cytotoxicity of Ad5MK for cancer cells was evaluated from the extent of growth inhibition after viral infection. Infection and replication were also assessed in nude mice with subcutaneous Suit-2 tumors by intratumoral injection of Ad5MK, Ad5GFP, or vehicle. E1a mRNA expression in the treated tumors and expression of the replication-specific adenoviral hexon protein were evaluated. Finally, the anti-tumor activity of Ad5MK against intraperitoneal xenografts of Suit-2 pancreatic cancer cells was examined after intraperitoneal injection of the virus.</p> <p>Results</p> <p>Both midkine mRNA expression and midkine protein expression were strong in AsPC-1 and CFPAC-1 cell liens, moderate in BxPC-3, HPAC, and Suit-2 cell lines, and weak in PANC-1 and MIAPaCa-2 cell lines. Expression of midkine mRNA was significantly stronger in pancreatic cancers than in non-cancerous pancreatic tissues. The relative luciferase activity mediated by the 0.6 kb midkne fragment in AsPC-1, PANC-1, and Suit-2 cell lines was approximately 6 to 20 times greater than that in midkne-negative MIAPaCa-2 cell lines. Pancreatic cancer cell lines exhibited a heterogeneous adenoviral transduction profile. E1A expression was higher in cell lines with strong midkine expression than in cell lines with weak midkine expression. Ad5MK showed much greater cytotoxicity for midkine-expressing Suit-2 and PANC-1 cell lines than for midkine-negative MIAPaCa-2 cell lines. In the Suit-2 subcutaneous xenograft model, expression of E1A was detected in Ad5MK-treated tumors, but not in untreated and Ad5GFP-treated tumors. In the Suit-2 intraperitoneal xenograft model, the Ad5MK group survived for significantly longer than the Ad5GFP, PBS, and untreated groups.</p> <p>Conclusion</p> <p>Ad5MK has an anti-tumor effect against human pancreatic cancer cell lines that express midkine mRNA. Midkine promoter-based conditionally replicative adenovirus might be a promising new gene therapy for pancreatic cancer.</p