Requirement of Gαq/Gα11 Signaling in the Preservation of Mouse Intestinal Epithelial Homeostasis

Background & AimsProliferation, differentiation, and morphogenesis of the intestinal epithelium are tightly regulated by a number of molecular pathways. Coordinated action of intestine is achieved by gastrointestinal hormones, most of which exert these actions through G-protein–coupled receptors. We herein investigated the role of Gαq/11-mediated signaling in intestinal homeostasis.MethodsIntestinal tissues from control (Gnaqflox/floxGna11+/+), Int-Gq knock-out (KO) (VilCre+/-Gnaqflox/floxGna11+/+), G11 KO (Gnaqflox/floxGna11-/-), and Int-Gq/G11 double knock-out (DKO) (VilCre+/-Gnaqflox/floxGna11-/-) mice were examined by microscopy, transmission electron microscopy, and immunohistochemistry. The effect of Gαq/11-mediated signaling was studied in the cell lineage, proliferation, and apoptosis. Dextran sodium sulfate (DSS) colitis was induced to study the role of Gαq/11 in colon.ResultsPaneth cells were enlarged, increased in number, and mislocalized in Int-Gq/G11 DKO small intestine. Paneth cells also reacted with PAS and Muc2 antibody, indicating an intermediate character of Paneth and goblet cells. The nuclear β-catenin, T-cell factor 1, and Sox9 expression were reduced severely in the crypt base of Int-Gq/G11 DKO intestine. Proliferation was activated in the crypt base and apoptosis was enhanced along the crypt. Int-Gq/G11 DKO mice were susceptible to DSS colitis. Proliferation was inhibited in the crypt of unaffected and regenerative areas. Cystic crypts, periodic acid–Schiff–positive cells, and Muc2-positive cells were unusually observed in the ulcerative region.ConclusionsThe Gαq/11-mediated pathway plays a pivotal role in the preservation of intestinal homeostasis, especially in Paneth cell maturation and positioning. Wnt/β-catenin signaling was reduced significantly in the crypt base in Gαq/G11-deficient mice, resulting in the defective maturation of Paneth cells, induction of differentiation toward goblet cells, and susceptibility to DSS colitis

Reactivation from latency displays HIV particle budding at plasma membrane, accompanying CD44 upregulation and recruitment

<p>Abstract</p> <p>Background</p> <p>It has been accepted that HIV buds from the cell surface in T lymphocytes, whereas in macrophages it buds into intracellular endosomes. Recent studies, on the other hand, suggest that HIV preferentially buds from the cell surface even in monocytic cells. However, most studies are based on observations in acutely infected cells and little is known about HIV budding concomitant with reactivation from latency. Such studies would provide a better understanding of a reservoir for HIV.</p> <p>Results</p> <p>We observed HIV budding in latently infected T lymphocytic and monocytic cell lines following TNF-α stimulation and examined the upregulation of host factors that may be involved in particle production. Electron microscopy analysis revealed that reactivation of latently infected J1.1 cells (latently infected Jurkat cells with HIV-1) and U1 cells (latently infected U937 cells with HIV-1) displayed HIV particle budding predominantly at the plasma membrane, a morphology that is similar to particle budding in acutely infected Jurkat and U937 cells. When mRNA expression levels were quantified by qRT-PCR, we found that particle production from reactivated J1.1 and U1 cells was accompanied by CD44 upregulation. This upregulation was similarly observed when Jurkat and U937 cells were acutely infected with HIV-1 but not when just stimulated with TNF-α, suggesting that CD44 upregulation was linked with HIV production but not with cell stimulation. The molecules in endocytic pathways such as CD63 and HRS were also upregulated when U1 cells were reactivated and U937 cells were acutely infected with HIV-1. Confocal microscopy revealed that these upregulated host molecules were recruited to and accumulated at the sites where mature particles were formed at the plasma membrane.</p> <p>Conclusion</p> <p>Our study indicates that HIV particles are budded at the plasma membrane upon reactivation from latency, a morphology that is similar to particle budding in acute infection. Our data also suggest that HIV expression may lead to the upregulation of certain host cell molecules that are recruited to sites of particle assembly, possibly coordinating particle production.</p

Studies on Antiandrogenic Agents. Synthesis of 16β-Ethyl-19-nortestosterone

金沢大学大学院医学系研究科　The mixture of enol acetates (II and III) of 16-acetyl-estrone-3-methyl ether underwent hydrogenolysis under high pressure (100kg/cm^2) of hydrogen in the presence of Raney Ni to form the 16β-ethyl-17β-ol compound (X) in high yield. The mechanism of hydrogenolysis was discussed. This facile and stereoselective introduction of 16β-ethyl and 17β-hydroxy groups was applied to the synthesis of 16β-ethyl-19-nortestosterone (TSAA-291,XIX), which shows strong antiandrogenic activity

大学生の成長の考察

大学の大衆化に伴い、大学入学者の基礎学力低下と並んで学習意欲の欠如および目的意識の希薄さが深刻化しており、大学全入学時代を迎え、問題の更なる顕在化が目前に迫っている。本論は、そうした環境下において大学の使命である学生の成長をいかに実現するかという現実の課題を取り上げる。研究の方法論に関する特徴の第1は、大学特に大学生を巡る諸問題について、互いに接触が少ない大学及び高等学校の関係者による共同討議である。具体的には、「高大連携で考える研究会」を設けて、意見交換並びに実態調査を行い、その成果を踏まえた。第2は、経営学分野におけるいくつかの新しい知見に着眼して、大学並びに学生が置かれている現状を分析し、いくつかの提言に結びつけようと試みた。経営学的アプローチとして、ステークホルダー論、顧客満足・顧客価値論、未来傾斜原理、学習地図といった論点を盛り込んだ。本論の構成は、次の通りである。まず第1部では、上述した経営学の視点による学生の飛躍的成長に向けた現状分析並びに課題と若干の提言を取り扱う。第2部では、「高大連携で考える研究会」の活動概要並びに得られた成果を報告する。第3部は全体の資料編であり、第1部で展開した各論の裏づけとなる各種資料並びに第2部で報告した研究会で用いた討論資料類を収録する。得られた知見は、次の3点である。第1に、大学をめぐる各種ステークホルダーの相互関係性を顧客連鎖の視点で整理したうえで、学生を主要な顧客として位置づけ、学生の戦略実現を大学が提供する教育サービスの最大の目的と指摘した。第2に、学生が未来に対していだく絶望感と渇望感を統一的に把握し、未来傾斜原理と組織内地図の視点から学生の成長を促進する要因を明らかにした。第3に、学生の成長を促進するうえで、内生要因と外生要因を整理して、学生の成長を促進する要因を明らかにした。学生の成長を促進するうえで、特に顧客である学生に対して教育サービスを提供する基本方針の確立、組織構成員としての自覚、自己の位置づけと居場所・自己評価・目標の発見と並んで、動機付けときっかけに対する具体的配慮・学生との信頼感の醸成の重要性の3点を指摘した点が重要である

Intralesional steroid infusion using a spray tube to prevent stenosis after endoscopic submucosal dissection of esophageal cancer

Background/Aims Intralesional steroid injections have been administered as prophylaxis for stenosis after esophageal endoscopic submucosal dissection. However, this method carries a risk of potential complications such as perforation because a fine needle is used to directly puncture the postoperative ulcer. We devised a new method of steroid intralesional infusion using a spray tube and evaluated its efficacy and safety. Methods Intralesional steroid infusion using a spray tube was performed on 27 patients who underwent endoscopic submucosal dissection for superficial esophageal cancer with three-quarters or more of the lumen circumference resected. The presence or absence of stenosis, complications, and the number of endoscopic balloon dilations (EBDs) performed were evaluated after treatment. Results Although stenosis was not observed in 22 of the 27 patients, five patients had stenosis and dysphagia requiring EBD. The stenosis in these five patients was relieved after four EBDs. No complications related to intralesional steroid infusion using the spray tube were observed. Conclusions Intralesional steroid infusion using a spray tube is a simple and safe technique that is adequately effective in preventing stenosis (clinical trial number, UMIN000037567)

A study on the scattering exposure dose in radiotherapy.

現代の医療のなかで癌治療において不可欠な存在となった放射線治療｡一方,放射線被曝はたとえわずかであってもリスクが伴い,厳しく規制されている｡ただし医療被曝はこの限りになく,過去においては癌患者に放射線治療をおこなう際の患部以外の被曝についてはあまり問題視されなかった｡これには癌の治療という前提に加え,長期生存の可能性が低く,存命中に晩発障害が発生することが低いと考えられていたからである｡しかし,集学的治療が確立した今後の放射線治療においては完治する放射線治療患者が多くなり,治癒後の余命が長くなることが予測される｡放射線被曝による確率的影響は閾値がなく,影響は当然現れるであろう｡そこで,放射線治療をおこなう際の患者の散乱線被曝線量,治療室内散乱線量,さらに高エネルギー放射線発生装置を取り扱うときに問題となっている中性子を測定した｡その結果,測定線量は治療患部外被曝,室内散乱線量ともに無視できない量であることがわかった｡中性子については,人体に影響がある線量は検出されなかったが,中性子の存在は室内物品の放射化の可能性を示唆するもので定期的な測定管理が必要である｡また,Ⅹ線撮影室用の防護衣による散乱線被曝の低減効果は放射線治療室では無意味であった｡In modern medicine, radiotherapy has proved indispensable in the treatment of cancer. However. radiation exposure is a health hazard. and is thus strictly regulated. In the past, incidental exposure was not considered to pose a considerable risk, and because radiotherapy was an effective treatment for cancer and because the possibility of the long-term survival was generally poor, the prevalence of radiation injury was thought to be low. In recent years, however, more patients are making complete recoveries, and it is believed that long-term survival is possible with future radiotherapy techniques. There is no threshold for the stochastic effects of radiation exposure, and thus such effects may be detected even at low levels. In the present study, we measured the radiation exposure due to scattered rays from the patient, incidental radiation levels in the radiotherapy room, and levels of neutron radiation. which is a problem when high-energy X-ray radiotherapy systems are used. The results showed that exposure due to scattered rays and incidental levels in the radiotherapy room cannot be dismissed. and that further investigation is warranted. As for neutron radiation, dosages were below those that are known to influence the human body, but regular measurement is necessary because it may induce radioactivity in otherwise benign equipment. In addition, a protective apron had no effect on the exposure due to scattered rays in the radiotherapy room

Pressure-induced superconductivity in AgxBi2-xSe3

We investigated the pressure dependence of electric transport and crystal structure of Ag-doped Bi2Se3. In the sample prepared by Ag doping of Bi2Se3, the Bi atom was partially replaced by Ag, i.e., Ag0.05Bi1.95Se3. X-ray diffraction patterns of Ag0.05Bi1.95Se3 measured at 0–30 GPa showed three different structural phases, with rhombohedral, monoclinic, and tetragonal structures forming in turn as pressure increased, and structural phase transitions at 8.8 and 24 GPa. Ag0.05Bi1.95Se3 showed no superconductivity down to 2.0 K at 0 GPa, but under pressure, superconductivity suddenly appeared at 11 GPa. The magnetic field (H) dependence of the superconducting transition temperature Tc was measured at 11 and 20.5 GPa, in order to investigate whether the pressure-induced superconducting phase is explained by either p-wave polar model or s-wave model