A high-fat diet aggravates tubulointerstitial but not glomerular lesions in obese Zucker rats

A high-fat diet aggravates tubulointerstitial but not glomerular lesions in obese Zucker ratsBackgroundDespite a large body of evidence that manipulation of dietary fat alters glomerular lesions, reports regarding the effects of dietary fat on tubulointerstitial lesions are limited. Obese Zucker rats (OZR) spontaneously develop glomerular and tubulointerstitial lesions in association with hyperlipidemia. We sought to elucidate the effects of dietary fat on glomerular and tubulointerstitial lesions in OZR versus lean Zucker rats (LZR) and to assess the involvement of macrophages in the development of these lesions.MethodsWe fed LZR and OZR either a low- (1%) or high-fat (20%) diet. After 30 weeks of the specified diet, the creatinine clearance (CCr) and renal histology as well as plasma lipid concentrations were examined. For morphological evaluation, glomerular sclerosis (GSI) and tubulointerstitial indices (TII) were each determined by a point-counting method. Infiltrating macrophages were stained immunohistochemically using an avidin-biotin complex technique.ResultsThe high-fat diet increased the plasma low-density lipoprotein concentration in OZR. Both low- and high-fat OZR groups had higher GSI and TII than LZR receiving either diet. The high-fat diet aggravated TII but not GSI or CCr in OZR; conversely, high fat intake worsened GSI and CCr but not TII in LZR. Tubulointerstitial macrophages were most prominent in the high-fat OZR group, followed by the low-fat OZR group. Glomerular macrophages were similar in number in all groups.ConclusionsThe manipulation of dietary fat has diverse effects on the kidney. A high-fat diet aggravated macrophage-mediated tubulointerstitial lesions in OZR, whereas in LZR, the diet induced glomerulosclerosis

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Simulation-based medical education in clinical skills laboratory

Clinical skills laboratories have been established in medical institutions as facilities for simulation-based medical education (SBME). SBME is believed to be superior to the traditional style of medical education from the viewpoint of the active and adult learning theories. SBME can provide a learning cycle of debriefing and feedback for learners as well as evaluation of procedures and competency. SBME offers both learners and patients a safe environment for practice and error. In a full-environment simulation, learners can obtain not only technical skills but also non-technical skills, such as leadership, team work, communication, situation awareness, decision-making, and awareness of personal limitations. SBME is also effective for integration of clinical medicine and basic medicine. In addition, technology-enhanced simulation training is associated with beneficial effects for outcomes of knowledge, skills, behaviors, and patient-related outcomes. To perform SBME, effectively, not only simulators including high-fidelity mannequin-type simulators or virtual-reality simulators but also full-time faculties and instructors as professionals of SBME are essential in a clinical skills laboratory for SBME. Clinical skills laboratory is expected to become an integrated medical education center to achieve continuing professional development, integrated learning of basic and clinical medicine, and citizens’ participation and cooperation in medical education

Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation

Mdm20 is an auxiliary subunit of the NatB complex, which includes Nat5, the catalytic subunit for protein N-terminal acetylation. The NatB complex catalyzes N-acetylation during de novo protein synthesis initiation; however, recent evidence from yeast suggests that NatB also affects post-translational modification of tropomyosin, which is involved in intracellular sorting of aggregated proteins. We hypothesized that an acetylation complex such as NatB may contribute to protein clearance and/or proteostasis in mammalian cells. Using a poly glutamine (polyQ) aggregation system, we examined whether the NatB complex or its components affect protein aggregation in rat primary cultured hippocampal neurons and HEK293 cells. The number of polyQ aggregates increased in Mdm20 over-expressing (OE) cells, but not in Nat5-OE cells. Conversely, in Mdm20 knockdown (KD) cells, but not in Nat5-KD cells, polyQ aggregation was significantly reduced. Although Mdm20 directly associates with Nat5, the overall cellular localization of the two proteins was slightly distinct, and Mdm20 apparently co-localized with the polyQ aggregates. Furthermore, in Mdm20-KD cells, a punctate appearance of LC3 was evident, suggesting the induction of autophagy. Consistent with this notion, phosphorylation of Akt, most notably at Ser473, was greatly reduced in Mdm20-KD cells. These results demonstrate that Mdm20, the so-called auxiliary subunit of the translation-coupled protein N-acetylation complex, contributes to protein clearance and/or aggregate formation by affecting the phosphorylation level of Akt indepenently from the function of Nat5

湖南説唱本研究

早大学位記番号:新7036早稲田大