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71.
Miwako Saikusa Naganori Nao Chiharu Kawakami Shuzo Usuku Tadayoshi Sasao Takahiro Toyozawa Makoto Takeda Ichiro Okubo 《Microbiology and immunology》2017,61(11):507-512
72.
Yasuyuki Kourogi Kenji Ogata Norito Takamura Jin Tokunaga Nao Setoguchi Mitsuhiro Kai Emi Tanaka Susumu Chiyotanda 《Theoretical biology & medical modelling》2017,14(1):8
Background
When administering vancomycin hydrochloride (VCM), the initial dose is adjusted to ensure that the steady-state trough value (Css-trough) remains within the effective concentration range. However, the Css-trough (population mean method predicted value [PMMPV]) calculated using the population mean method (PMM) often deviate from the effective concentration range. In this study, we used the generalized linear mixed model (GLMM) for initial dose planning to create a model that accurately predicts Css-trough, and subsequently assessed its prediction accuracy.Methods
The study included 46 subjects whose trough values were measured after receiving VCM. We calculated the Css-trough (Bayesian estimate predicted value [BEPV]) from the Bayesian estimates of trough values. Using the patients’ medical data, we created models that predict the BEPV and selected the model with minimum information criterion (GLMM best model). We then calculated the Css-trough (GLMMPV) from the GLMM best model and compared the BEPV correlation with GLMMPV and with PMMPV.Results
The GLMM best model was {[0.977?+?(males: 0.029 or females: -0.081)]?×?PMMPV?+?0.101?×?BUN/adjusted SCr – 12.899?×?SCr adjusted amount}. The coefficients of determination for BEPV/GLMMPV and BEPV/PMMPV were 0.623 and 0.513, respectively.Conclusion
We demonstrated that the GLMM best model was more accurate in predicting the Css-trough than the PMM.73.
Satomi Okano Ryosuke Tanaka Akie Okayama Etsushi Tsuchida Fumikatsu Nohara Nao Suzuki Toshio Okamoto Ken Nagaya Satoru Takahashi Hiroshi Azuma 《Journal of medical case reports》2017,11(1):359
Background
Basal meningoceles are rare congenital defects and often clinically occult until they result in life-threatening complications. Therefore, it is important to know the diagnostic clues to early diagnosis.Case presentation
We describe three cases of congenital basal meningocele in a 3-year-old Japanese boy, a 1-month-old Japanese baby boy, and a 10-month-old Japanese baby girl. One of our patients died of sepsis due to traumatic rupture of the meningocele during nasal suction. His meningocele remained undiagnosed until it resulted in the fatal complication. The other patients underwent surgical repair without any complications. Their meningoceles were complicated by midfacial anomalies including cleft palate and hypertelorism, or a sign of nasal obstruction such as snoring.Conclusions
These clinical features may be a clue to the early diagnosis of congenital basal meningocele, which enables its safe preoperative management and provides an opportunity for surgical repair before the condition results in serious complications.74.
The availability of human stem cells heralds a new era for modeling normal and pathologic tissues and developing therapeutics. For example, the in vitro recapitulation of normal and aberrant neurogenesis holds significant promise as a tool for de novo modeling of neurodevelopmental and neurodegenerative diseases. Translational applications include deciphering brain development, function, pathologies, traditional medications, and drug discovery for novel pharmacotherapeutics. For the latter, human stem cell-based assays represent a physiologically relevant and high-throughput means to assess toxicity and other undesirable effects early in the drug development pipeline, avoiding late-stage attrition whilst expediting proof-of-concept of genuine drug candidates. Here we consider the potential of human embryonic, adult, and induced pluripotent stem cells for studying neurological disorders and preclinical drug development. 相似文献
75.
Reiko Sakaguchi Takashi Endoh Seigo Yamamoto Kazuki Tainaka Kenji Sugimoto Nobutaka Fujieda Shigeki Kiyonaka Yasuo Mori Takashi Morii 《Bioorganic & medicinal chemistry》2009,17(20):7381-7386
A fluorescent sensor for the detection of inositol-1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4, was constructed from a split PH domain and a single circularly permuted GFP. A structure-based design was conducted to transduce a ligand-induced subtle structural perturbation of the split PH domain to an alteration in the population of the protonated and the deprotonated states of the GFP chromophore. Excitation of each distinct absorption band corresponding to the protonated or the deprotonated state of GFP resulted an increase and a decrease, respectively, in the intensity of emission spectra upon addition of Ins(1,3,4,5)P4 to the split PH domain-based sensor. The Ins(1,3,4,5)P4 sensor retained the ligand affinity and the selectivity of the parent PH domain, and realized the ratiometric fluorescence detection of Ins(1,3,4,5)P4. 相似文献
76.
Nao Odajima Tomoko Betsuyaku Katsura Nagai Chinatsu Moriyama Da-Hong Wang Tomoko Takigawa Keiki Ogino Masaharu Nishimura 《Respiratory research》2010,11(1):183
Background
Catalase is preferentially expressed in bronchiolar and alveolar epithelial cells, and acts as an endogenous antioxidant enzyme in normal lungs. We thus postulated epithelial damage would be associated with a functional deficiency of catalase during the development of lung fibrosis.Methods
The present study evaluates the expression of catalase mRNA and protein in human interstitial pneumonias and in mouse bleomycin-induced lung injury. We examined the degree of bleomycin-induced inflammation and fibrosis in the mice with lowered catalase activity.Results
In humans, catalase was decreased at the levels of activity, protein content and mRNA expression in fibrotic lungs (n = 12) compared to control lungs (n = 10). Immunohistochemistry revealed a decrease in catalase in bronchiolar epithelium and abnormal re-epithelialization in fibrotic areas. In C57BL/6J mice, catalase activity was suppressed along with downregulation of catalase mRNA in whole lung homogenates after bleomycin administration. In acatalasemic mice, neutrophilic inflammation was prolonged until 14 days, and there was a higher degree of lung fibrosis in association with a higher level of transforming growth factor-β expression and total collagen content following bleomycin treatment compared to wild-type mice.Conclusions
Taken together, these findings demonstrate diminished catalase expression and activity in human pulmonary fibrosis and suggest the protective role of catalase against bleomycin-induced inflammation and subsequent fibrosis. 相似文献77.
78.
Aoki W Kitahara N Miura N Morisaka H Yamamoto Y Kuroda K Ueda M 《Journal of biochemistry》2011,150(4):431-438
Candida albicans is a commensal organism, but causes life-threatening infections in immunocompromised patients. Certain factors such as yeast-hyphae transition and hydrolytic enzymes are suggested as virulence attributes of C. albicans. Among them, 10 types of secreted aspartic protease (SAP) genes have received particular attention as a major virulence gene family. However, their full functional repertoire, including its biochemical properties, remains to be elucidated. Hence, we purified all Sap isozymes using Pichia pastoris and comprehensively determined and compared their biochemical properties. While optimum pH of Sap7 was 6.5 and that of Sap8 was 2.5, presence of other Sap isozymes functioning within a broad range of optimum pH could allow C. albicans to survive and cause infections in various tissues. The substrate specificities of Sap isozymes were analysed by using FRETS-25Xaa libraries. Sap7 and Sap10 showed high substrate specificity, while other Sap isozymes had broad substrate specificities. Principal component analysis revealed that the 10 Sap isozymes were clustered into 3 distinct groups in terms of their substrate specificities. Interestingly, Sap4-6, which are coproduced in the hyphal form, were clustered as the same group, indicating that they may target similar host proteins. These results will lead to further understanding of C. albicans pathogenicity. 相似文献
79.
Disruption of cell–extracellular matrix interaction causes epithelial cells to undergo apoptosis called anoikis, and resistance to anoikis has been suggested to be a critical step for cancer cells to metastasize. EphA2 is frequently overexpressed in a variety of human cancers, and recent studies have found that overexpression of EphA2 contributes to malignant cellular behavior, including resistance to anoikis, in several different types of cancer cells. Here we show that Ephexin4, a guanine nucleotide exchange factor for the small GTPase RhoG that interacts with EphA2, plays an important role in the regulation of anoikis. Knockdown of Ephexin4 promoted anoikis in HeLa cells, and experiments using a knockdown-rescue approach showed that activation of RhoG, phosphatidylinositol 3-kinase (PI3K), and Akt was required for the Ephexin4-mediated suppression of anoikis. Indeed, Ephexin4 knockdown caused a decrease in RhoG activity and Akt phosphorylation in HeLa cells cultured in suspension. In addition, Ephexin4 was involved in the EphA2-mediated suppression of anoikis. Taken together, these results suggest that Ephexin4 mediates resistance to anoikis through activation of RhoG and PI3K downstream of EphA2. 相似文献
80.
Kawakami E Kinouchi N Adachi T Ohsawa Y Ishimaru N Ohuchi H Sunada Y Hayashi Y Tanaka E Noji S 《Development, growth & differentiation》2011,53(1):48-54
Small interfering RNA (siRNA)-mediated silencing of gene expression is rapidly becoming a powerful tool for molecular therapy. However, the rapid degradation of siRNAs and their limited duration of activity require efficient delivery methods. Atelocollagen (ATCOL)-mediated administration of siRNAs is a promising approach to disease treatment, including muscular atrophy. Herein, we report that ATCOL-mediated systemic administration of a myostatin-targeting siRNA into a caveolin-3-deficient mouse model of limb-girdle muscular dystrophy 1C (LGMD1C) induced a marked increase in muscle mass and a significant recovery of contractile force. These results provide evidence that ATCOL-mediated systemic administration of siRNAs may be a powerful therapeutic tool for disease treatment, including muscular atrophy. 相似文献