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21.
Kuramitsu M Sato-Otsubo A Morio T Takagi M Toki T Terui K Wang R Kanno H Ohga S Ohara A Kojima S Kitoh T Goi K Kudo K Matsubayashi T Mizue N Ozeki M Masumi A Momose H Takizawa K Mizukami T Yamaguchi K Ogawa S Ito E Hamaguchi I 《Blood》2012,119(10):2376-2384
Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes. 相似文献
22.
Noriyuki Fuku Seijiro Mori Haruka Murakami Yuko Gando Heying Zhou Hideki Ito Masashi Tanaka Motohiko Miyachi 《Geriatrics & Gerontology International》2012,12(2):292-297
Aim: Sarcopenia is the significant degenerative loss of skeletal muscle mass and strength associated with aging, and it is one of the components of frailty. We previously reported an association between the 29C>T polymorphism in the transforming growth factor‐β1 gene (rs1800470) and the prevalence of vertebral fractures in subjects with postmenopausal osteoporosis. The association was not attributable to bone mineral density, which suggests that polymorphism influences some aspects of bone quality that affects strength and/or frailty rather than bone strength itself. Thus, we examined the relationship between genetic polymorphism and lean body mass in a Japanese population. Methods: A total of 479 adults comprising 143 men and 336 women, age 23 to 85 years, participated in the present study. Fat‐free mass was measured by dual energy X‐ray absorptiometry, and the relative skeletal muscle index was calculated as the ratio of appendicular (sum of arms and legs) fat‐free mass to the square of height. Results: Total, leg, and appendicular fat‐free mass as well as the relative skeletal muscle index were significantly lower in male subjects with CT/TT genotypes compared to those with CC genotype. Female subjects did not show any genotype‐dependent differences when analyzed as a group, but when those without menstruation (postmenopausal women) were analyzed, arm fat‐free mass was significantly lower in the CT/TT genotypes than in the CC genotype. Conclusions: T allele of the 29C>T polymorphism in the transforming growth factor‐β1 gene might be a risk factor of sarcopenia in a Japanese population. Geriatr Gerontol Int 2012; 12: 292–297. 相似文献
23.
Kazuma Murakami Haruka Kato Mizuho Hanaki Yoko Monobe Ken-ichi Akagi Taiji Kawase Kenji Hirose Kazuhiro Irie 《RSC advances》2020,10(33):19506
Protein persulfidation plays a role in redox signaling as an anti-oxidant. Dimers of amyloid β42 (Aβ42), which induces oxidative stress-associated neurotoxicity as a causative agent of Alzheimer''s disease (AD), are minimum units of oligomers in AD pathology. Met35 can be susceptible to persulfidation through its substitution to homoCys residue under the condition of oxidative stress. In order to verify whether persulfidation has an effect in AD, herein we report a chemical approach by synthesizing disulfide dimers of Aβ42 and their evaluation of biochemical properties. A homoCys-disulfide dimer model at position 35 of Aβ42 formed a partial β-sheet structure, but its neurotoxicity was much weaker than that of the corresponding monomer. In contrast, the congener with an alkyl linker generated β-sheet-rich 8–16-mer oligomers with potent neurotoxicity. The length of protofibrils generated from the homoCys-disulfide dimer model was shorter than that of its congener with an alkyl linker. Therefore, the current data do not support the involvement of Aβ42 persulfidation in Alzheimer''s disease.Our data do not support the Aβ42 persulfidation hypothesis in Alzheimer''s etiology because the neurotoxicity of the homoCys-disulfide-Aβ42 dimer was very weak. 相似文献
24.
Soyoung Park Haruka Matsui Koyuki Fukumoto Ji Hye Yum Hiroshi Sugiyama 《RSC advances》2020,10(16):9717
Histidine is a versatile amino acid residue that plays a critical role in the active sites of many metalloenzymes. DNA is an attractive biomolecular scaffold owing to its chemical and thermal stability and easy accessibility. Herein, we report histidine-conjugated DNA oligonucleotides, which were synthesized by combining DNA alphabets and natural metal-binding amino acids, as novel biohybrid materials and demonstrate their use as molecular depots for various metal ions. Moreover, histidine-conjugated DNA oligonucleotides could be successfully used in asymmetric catalysis (up to 90% conversion and 95% ee) as DNA metalloenzymes and in 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) oxidation reactions as horseradish-peroxidase (HRP)-mimicking DNAzymes with suitable metal cofactors. Nature-inspired histidine-DNA hybrids will become an attractive strategy to construct fine-tuned coordination environments as an alternative to bioremediation and the development of multimetal enzymes.Histidine is a versatile amino acid residue that plays a critical role in the active sites of many metalloenzymes. 相似文献
25.
Yoshimatsu M Kitaura H Fujimura Y Kohara H Morita Y Eguchi T Yoshida N 《Archives of oral biology》2012,57(1):36-43
ObjectiveInterleukin (IL)-12 is an important cytokine for innate and adaptive immunity. We previously reported that IL-12 inhibits tumour necrosis factor (TNF)-α-mediated osteoclast formation by inducing apoptosis. We also reported that TNF-α plays an important role in mechanical loading-induced osteoclast formation and bone resorption during orthodontic tooth movement. In this study, we investigated the effects of IL-12 on mechanical tooth movement in mice.DesignA Ni–Ti closed coil spring was inserted between the upper incisors and the upper left first molar in mice. IL-12 was injected locally adjacent to the first molar every other day during the experimental period, at doses varying from 0 to 1.5 μg/day. After 12 days, the animals were killed and their jaws were processed for histological evaluation using tartrate-resistant acid phosphatase (TRAP) and TdT-mediated dUTP-biotin nick end-labelling (TUNEL) staining, and measurements of the root resorption area.ResultsIn the IL-12-treated mice, tooth movement and root resorption appeared to be reduced. In TUNEL-stained sections, many apoptotic cells were recognized on the pressure side in the IL-12-treated mice.ConclusionsOur findings suggest that IL-12 inhibits not only mechanical tooth movement, but also root resorption during orthodontic tooth movement. These findings may arise through apoptosis induced by IL-12. 相似文献
26.
Hiroaki Hanada Junko Imanaga Aoi Yoshiiwa Tomoya Yoshikawa Yoshihiro Tanaka Jusen Tsuru Ayako Inoue Yoshinobu Ishitobi Shizuko Okamoto Masayuki Kanehisa Yoshihiro Maruyama Taiga Ninomiya Haruka Higuma Koichi Isogawa Tsuyoshi Kawasaki Toshio Fujioka Jotaro Akiyoshi 《International journal of geriatric psychiatry》2013,28(7):756-765
27.
Matsukawa Y Miyabe T Sawamura H Higa M Yamane N Urasoko A Endo R 《Rinsho byori. The Japanese journal of clinical pathology》2007,55(7):611-618
The fully automated microbial system, RAISUS (Nissui Pharmaceutical, Tokyo, Japan) can provide antimicrobial susceptibility test results for the isolates of Haemophilus influenzae. It is known that viable cell concentrations (colony forming unit/ml) of H. influenzae significantly vary depending on the incubation period. For the rapid reporting of antimicrobial susceptibility test results, we evaluated optimal cell density when we prepared the cell suspension using the early-harvested (6 hour incubation) cells for RAISUS. A total of 180 clinical isolates, comprising of 33 ampicillin-susceptible isolates, 114 beta-lactamase negative but ampicillin-resistant isolates and 33 beta-lactamase positive and amoxicillin/clavulanic acid susceptible or -resistant isolates, were included. All the isolates were genetically defined according to the detection of TEM gene and specific mutation (s) in fts I gene. The isolates were incubated on chocolate agar plates for 6 hours, and then the cell suspensions were prepared and adjusted to 0.5, 0.25 and 0.125 McFarland standards through serially dilutions. The respective cell suspensions were tested by the RAISUS AST panels. The % agreements between RAISUS and Clinical and Laboratory Standards Institute standard microdilutions in ampicillin category interpretations were 66.7%(McFarland 0.5), 77.8% (McFarland 0.25) and 83.9%(McFarland 0.125). When the McFarland 0.125 cell suspensions were inoculated, the majority of discrep ant interpretations were minor errors (15.0%) and the occurrence of major error was 3.4%. There was no very major error throughout the study. Essential agreement in MIC determinations (with or within +/- 1 doubling dilution) for 11 beta-lactam antimicrobial agents tested improved to 95.2% by McFarland 0.125 when compared to 77.4% by McFarland 0.5. It was also demonstrated that the viable cell concentrations prepared from 6 hour incubation cultures were 2.5 to 6.5 times higher than those from 22 hour-incubations. With these results, it can be concluded that the early harvested cell suspension of H. influenzae is applicable to RAISUS antimicrobial susceptibility test with lower cell density (McFarland 0.125). With this adjustment, the antimicrobial susceptibility test for H. influenzae will be completed by RAISUS within 26 hours after primary isolation. 相似文献
28.
Taguchi Kumiko Bessho Nanami Hida Mari Narimatsu Haruka Matsumoto Takayuki Kobayashi Tsuneo 《Naunyn-Schmiedeberg's archives of pharmacology》2018,391(10):1075-1083
Naunyn-Schmiedeberg's Archives of Pharmacology - Abnormal G protein-coupled receptor kinase 2 (GRK2) accumulation has a crucial role in the development of insulin resistance and diabetes.... 相似文献
29.
Nami Ogawa Takashi Mori Ichiro Fujishima Hidetaka Wakabayashi Masataka Itoda Kenjiro Kunieda Takashi Shigematsu Shinta Nishioka Haruka Tohara Minoru Yamada Sumito Ogawa 《Journal of the American Medical Directors Association》2018,19(6):516-522