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981.
Sung Hee Um Melanie Sticker-Jantscheff Gia Cac Chau Kristina Vintersten Matthias Mueller Yann-Gael Gangloff Ralf H. Adams Jean-Francois Spetz Lynda Elghazi Paul T. Pfluger Mario Pende Ernesto Bernal-Mizrachi Albert Tauler Matthias H. Tsch?p George Thomas Sara C. Kozma 《The Journal of clinical investigation》2015,125(7):2736-2747
Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased β cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic β cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore β cell size or insulin levels in S6K1–/– embryos, suggesting that loss of S6K1 leads to an intrinsic β cell lesion. Consistent with this hypothesis, reexpression of S6K1 in β cells of S6K1–/– mice restored embryonic β cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic β cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced β cell growth and eventual development of T2DM later in life. 相似文献
982.
Efficacy and safety of deferasirox estimated by serum ferritin and labile plasma iron levels in patients with aplastic anemia,myelodysplastic syndrome,or acute myeloid leukemia with transfusional iron overload 下载免费PDF全文
983.
Ga Eun Park Cheol-In Kang Yu Mi Wi Jae-Hoon Ko Woo Joo Lee Ji Yong Lee Sun Young Cho Young Eun Ha Doo Ryeon Chung Kyong Ran Peck Jae-Hoon Song 《Antimicrobial agents and chemotherapy》2015,59(9):5830-5833
Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp. 相似文献
984.
985.
986.
987.
Sung‐Bum Kang Young Min Ju Sang Jin Lee Anthony Atala James J. Yoo 《Journal of tissue engineering and regenerative medicine》2015,9(7):838-846
Tissue‐engineered muscle has been proposed as a means of repairing volumetric muscle defects to restore anatomical and functional recovery. We have previously demonstrated that denervated muscle, which is analogous to engineered muscle construct, can be reinnervated by direct transplantation of host nerve (neurotization) in a rat model. However, the use of this approach is not possible if the length of host nerve is inadequate and cannot be mobilized to the insertion site of the engineered muscle. In this study we investigated whether neurotization coupled with nerve guidance channels would increase the regeneration of neuromuscular junctions (NMJs) in completely denervated muscle and encourage neurofunctional recovery. Seventy‐two Lewis rats were evaluated in three groups, a normal control group (n = 8), a denervated group (n = 32) and a neurotization coupled with nerve guidance group (n = 32). Neurofunctional behaviour and histological evaluations were performed at 4, 8, 12 and 20 weeks postoperatively. Extensor postural thrust (EPT) and compound muscle action potential (CMAP) amplitude were significantly improved in the nerve guidance group when compared with the denervated group, even though these values were different from those of the normal control group at 20 weeks postoperation. Regeneration of axons and NMJs was demonstrated histologically in the nerve guidance group. Neurotization coupled with nerve guidance channels leads to regeneration of axons and NMJs in completely denervated muscle. To our knowledge, this is the first report to show that nerve guidance can allow re‐innervation in denervated muscle containing long‐gap nerve injuries. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
988.
989.
Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study 下载免费PDF全文
990.
Insang Hwang Donghoon Lim Young Beom Jeong Seung Chol Park Jun Hwa Noh Dong Deuk Kwon Taek Won Kang 《Asian journal of andrology》2015,17(5):811-814
Only 54% of prostate cancer cases in Korea are localized compared with 82% of cases in the US. Furthermore, half of Korean patients are upgraded after radical prostatectomy (41.6%–50.6%). We investigated the risk factors for upgrading and/or upstaging of low-risk prostate cancer after radical prostatectomy. We retrospectively reviewed the medical records of 1159 patients who underwent radical prostatectomy at five hospitals in Honam Province. Preoperative data on standard clinicopathological parameters were collected. The radical prostatectomy specimens were graded and staged and we defined a “worsening prognosis” as a Gleason score ≥ 7 or upstaging to ≥ pT3. Multivariate logistic regression models were used to assess factors associated with postoperative pathological upstaging. Among the 1159 patients, 324 were classified into the clinically low-risk group, and 154 (47.5%) patients were either upgraded or upstaged. The multivariable analysis revealed that the preoperative serum prostate-specific antigen level (odds ratio [OR], 1.131; 95% confidence interval [CI], 1.007–1.271; P= 0.037), percent positive biopsy core (OR: 1.018; 95% CI: 1.002–1.035; P= 0.032), and small prostate volume (≤30 ml) (OR: 2.280; 95% CI: 1.351–3.848; P= 0.002) were predictive of a worsening prognosis. Overall, 47.5% of patients with low-risk disease were upstaged postoperatively. The current risk stratification criteria may be too relaxed for our study cohort. 相似文献