腎再生を担う細胞群の探索とその再生能力の限界

京都大学0048新制・論文博士博士(医学)乙第13330号論医博第2198号新制||医||1044(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 長船 健二, 教授 羽賀 博典, 教授 山下 潤学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

Endoplasmic Reticulum Stress-Related Inflammation and Cardiovascular Diseases

The endoplasmic reticulum (ER) is the site of synthesis and maturation of proteins designed for secretion or for localization on the cell membrane. Various types of stress from both inside and outside cells disturb ER function, thus causing unfolded or misfolded proteins to accumulate in the ER. To improve and maintain the ER functions against such stresses, the ER stress response pathway is activated. However, when the stress is prolonged or severe, apoptosis pathways are activated to remove damaged cells. It was recently reported that the ER stress pathway is also involved in the inflammatory response, whereby inflammation induces ER stress, and ER stress induces an inflammatory response. Therefore, the ER stress response pathway is involved in various diseases, including cardiovascular diseases such as atherosclerosis and ischemic diseases, in various ways. The ER stress pathway may represent a novel target for the treatment of these diseases

Interaction between Northern Coal Sack in the Cyg OB 7 cloud complex and the multiple super nova remnants including HB 21

We report possible interaction between multiple super nova remnants (SNRs) and Northern Coal Sack (NCS) which is a massive clump (~1000 Mo) in the Cyg OB 7 cloud complex and is forming a massive Class 0 object. We performed molecular observations of the 12CO(J=1-0), 13CO(J=1-0), and C18O(J=1-0) emission lines using the 45m telescope at the Nobeyama Radio Observatory, and we found that there are mainly four velocity components at Vlsr=-20, -6, -4, and 10 km/s. The -6 and -4 km/s components correspond to the systemic velocities of NCS and the Cygnus OB 7 complex, respectively, and the other velocity components originate from distinct smaller clouds. Interestingly, there are apparent correlations and anti-correlations among the spatial distributions of the four components, suggesting that they are physically interacting with one another. On a larger scale, we find that a group of small clouds belonging to the -20 and 10 km/s components are located along two different arcs around some SNRs including HB 21 which has been suggested to be interacting with the Cyg OB 7 cloud complex, and we also find that NCS is located right at the interface of the arcs. The small clouds are likely to be the gas swept up by the stellar wind of the massive stars which created the SNRs. We suggest that the small clouds alined along the two arcs recently encountered NCS and the massive star formation in NCS was triggered by the strong interaction with the small clouds.Comment: To appear in the Publications of the Astronomical Society of Japan (PASJ

キュウセイキ ビョウイン ニ キンムスル カンゴシ ノ リンリテキ ナヤミ ノ カンレン ヨウイン ノ ケントウ

本研究では、倫理的悩みを測定する尺度Nurse Questionnaire (ADULT) scaleをもとに作成した『改訂版 倫理的悩みの尺度－看護師版』を用いて、急性期病院に勤務する看護師の倫理的悩みについて検討した。近畿地方のA県と中部地方のB県にある340床以上の急性期病院22施設に対し研究協力依頼を行い、承諾が得られた6施設に勤務する看護師846名に質問紙調査の依頼を行い、そのうち443部の調査票を回収した（回収率52.4％）。各設問の無効回答率20％以上を除く405部の調査票を有効回答とした（有効回答率　48.1％）。その結果、年齢（F＝6.12，p<0.001）に有意な関係が見られ、「25歳未満」よりも「25歳～30歳未満」、「30歳～35歳未満」、「35歳以上」が倫理的悩みを多く認識し、倫理的悩みのスコア平均値が4.0以上であった項目は【3.患者にとって最良と思えなくても医療を続けてほしいという患者・家族の希望に沿うことがある】と【4.ただ死を先延ばしすることだと感じても救命行為を開始することがある】の主に2つの項目でともに高い値を示した。本研究において、患者家族との倫理的価値の相違から倫理的悩みを多く認識し、年齢の高い看護師は自己の経験より養われた倫理観や価値観を臨床現場に活かそうと模索するなかで、倫理的悩みとしての認識に繋がっていた。これらのことから、看護師への倫理教育では看護倫理のみでなく医療・工学・生命倫理など幅広い分野に基づいた教育が必要であり、臨床看護師への倫理教育のあり方について多くの課題が示唆された。This study examined the ethical concerns of nurses working in acute care hospitals using the "Revised Ethical Concerns Scale - Nurse Edition," which was developed based on the Nurse Questionnaire (ADULT) scale, a scale for measuring ethical concerns. Requests for research cooperation were made to 22 acute care hospitals with 340 or more beds in prefectures A in the Kinki region and B in the Chubu region. 846 nurses working at the 6 facilities that agreed to participate were asked to complete the questionnaire, of which 443 copies were collected (response rate 52.4%). Forty-five copies of the questionnaire were considered valid responses (valid response rate: 48.1%), excluding those with an invalid response rate of 20% or more for each question. The results showed a significant relationship with age (F=6.12, p<0.001), with "25-30 years old," "30-35 years old," and "35 years old or older" identifying more ethical concerns than "under 25 years old," and the items with a mean score of 4.0 or higher for ethical concerns were [3. Sometimes, the patient/family wishes for continued medical care even if it does not seem best for the patient] and [4. Sometimes, life-saving actions are initiated even if the patient/family feels that the action is merely postponing death] were the two main items with high values. In this study, nurses recognized many ethical concerns due to differences in ethical values with patients' families, and older nurses were seeking to apply the ethical views and values nurtured through their own experiences to clinical practice, which led to their recognition as ethical concerns. These findings suggest that ethics education for nurses needs to be based not only on nursing ethics but also on a wide range of fields, including medical, engineering, and bioethics, and that many issues need to be addressed in the education of ethics for clinical nurses.departmental bulletin pape

Evaluation of Infliximab Effects on Gastrointestinal Bleeding in Crohn's Disease Using Double-Balloon Endoscopy

Tumor necrosis factor α plays an important role in the pathogenesis of Crohn's disease (CD). The effects of infliximab on gastrointestinal bleeding in CD have not yet been fully evaluated. Herein we describe three CD cases who presented with gastrointestinal bleeding and received infliximab treatment. In case 1, double-balloon endoscopy showed a large ulcer with several irregularly shaped ulcers in the terminal ileum; 8 weeks after infliximab administration, complete healing of all lesions was observed. In case 2, double-balloon endoscopy showed linear ulcers and mucosal edema in the jejunum and ileum; 5 weeks after infliximab administration, all lesions were decreased in size and were healed. In case 3, double-balloon endoscopy revealed ulcerations and stenosis in the terminal ileum; 12 weeks after infliximab administration, ulcer healing and an increased diameter of the ileal stenosis were observed. These three cases have been receiving ongoing infliximab maintenance therapy and are currently symptom-free. Infliximab thus appears to be useful for treatment of gastrointestinal bleeding in CD patients

Resectable hepatoblastoma with tumor thrombus extending into the right atrium after chemotherapy: A case report

AbstractHepatoblastoma with intraatrial tumor thrombus is relatively rare. We report a case of hepatoblastoma with tumor thrombus extending into the right atrium, which responded well to chemotherapy and was resected using extracorporeal circulation. A 4-year-old girl was referred to our hospital because of abdominal distention and tenderness. A computed tomography (CT) scan showed a large tumor occupying the left 3 segments of the liver with tumor thrombus extending into the right atrium. There was also a small intrahepatic metastasis in the right lobe of the liver. She was diagnosed with hepatoblastoma on the basis of the results of open biopsy. Neoadjuvant chemotherapy with an intense CDDP-based regimen was performed. The tumor responded well to chemotherapy, and intrahepatic metastasis became undetectable on CT scan, although the tumor thrombus remained in the right atrium. After 7 courses of chemotherapy, we performed resection using extracorporeal circulation. The postoperative course was uneventful, and adjuvant chemotherapy was started 10 days after the operation. Her serum alpha-fetoprotein (AFP) level decreased to the normal range, and she was free of disease for 1 year after the operation. Tumor resection using extracorporeal circulation can be performed safely and is justified in patients with intraatrial tumor thrombus

Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy

Background and Purpose: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. Methods: Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined. Results: Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. Conclusion: The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. © 2013 Kitano et al

Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy

There is a hot debate concerning actual amount of albumin filtered through glomeruli and reabsorbed at proximal tubules in normal kidneys and diabetic conditions. To overcome current technical problems, we generated a drug-inducible megalin knockout mouse line, megalin(lox/lox);Ndrg1-CreER[T2] (or iMegKO), whose protein reabsorption can be shut off anytime by tamoxifen (Tam). After Tam administration, renal megalin protein expression was reduced by 92% compared to wild-type C57BL/6J mice, and renal reabsorption of intravenously-injected retinol binding protein was almost completely abrogated. Urinary albumin excretion increased to 175 μg/day (0.460 mg/mg-creatinine), suggesting that this was the amount of total nephron albumin filtration. Glomerular sieving coefficient of albumin was 1.7 x 10[-5]. By comparing streptozotocin-induced, Tam-treated, diabetic STZ;iMegKO mice with non-STZ;iMegKO mice, we estimated that daily albumin filtration was increased by 1.9-fold, reabsorption was increased by 1.8-fold, and reabsorption efficiency was reduced to 86% by development of diabetes (versus 96% in control). Such abnormalities were well normalized after insulin treatment. Another type 1 diabetic model of Akita;iMegKO mice showed equivalent results. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy, bringing new insights into our understanding of renal albumin dynamics in hyperfiltration status of diabetic nephropath