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51.
Tone Y Toma T Toga A Sakakibara Y Wada T Yabe M Kusafuka H Yachie A 《Modern rheumatology / the Japan Rheumatism Association》2012,22(1):45-51
Most reported cases of familial Mediterranean fever (FMF) involve missense mutations of MEFV concentrated within exon 10. We experienced two independent pedigrees of a unique variant in the MEFV gene that might cause excessive exon 2 skipping due to enhanced alternative splicing. In this study, we tried to elucidate
the molecular mechanism of the MEFV variant as a cause of the FMF phenotype. Peripheral blood was obtained from volunteers and two patients with homozygous c.910G>A
variant of the MEFV gene. MEFV messenger RNA (mRNA) expression patterns in mononuclear cells and granulocytes were compared using forward and reverse primers
from exons 1 and 3, respectively. Expression profiles of pyrin were examined by transfecting wild-type and variant MEFV genes into HEK293T cells. Expression of normal-sized mRNA was extremely reduced in these patients, whereas that of aberrant
short mRNA, deleting exon 2 (Δex2), was significantly increased. Immunohistochemical and immunoblotting analyses revealed
a truncated immunoreactive pyrin protein in cells transfected with Δex2 cDNA. The MEFV gene c.910G>A variant results in accelerated aberrant splicing with abnormal protein size, presumably leading to anomalous
pyrin function. This is the first report to show that an MEFV variant other than missense mutation is responsible for the FMF phenotype. 相似文献
52.
Kojima T Kaneko A Hirano Y Ishikawa H Miyake H Oguchi T Takagi H Yabe Y Kato T Ito T Terabe K Fukaya N Kanayama Y Shioura T Funahashi K Hayashi M Kato D Matsubara H Fujibayashi T Kojima M Ishiguro N;TBC 《Modern rheumatology / the Japan Rheumatism Association》2012,22(3):339-345
Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future. 相似文献
53.
Joan Gimenez-Dejoz Kousuke Tsuchiya Ayaka Tateishi Yoko Motoda Takanori Kigawa Yasuhisa Asano Keiji Numata 《RSC advances》2020,10(30):17582
Almost all natural proteins are composed exclusively of l-amino acids, and this chirality influences their properties, functions, and selectivity. Proteases can recognize proteins composed of l-amino acids but display lower selectivity for their stereoisomers, d-amino acids. Taking this as an advantage, d-amino acids can be used to develop polypeptides or biobased materials with higher biostability. Chemoenzymatic peptide synthesis is a technique that uses proteases as biocatalysts to synthesize polypeptides, and d-stereospecific proteases can be used to synthesize polypeptides incorporating d-amino acids. However, engineered proteases with modified catalytic activities are required to allow the incorporation of d-amino acids with increased efficiency. To understand the stereospecificity presented by proteases and their involvement in polymerization reactions, we studied d-aminopeptidase. This enzyme displays the ability to efficiently synthesize poly d-alanine-based peptides under mild conditions. To elucidate the mechanisms involved in the unique specificity of d-aminopeptidase, we performed quantum mechanics/molecular mechanics simulations of its polymerization reaction and determined the energy barriers presented by the chiral substrates. The enzyme faces higher activation barriers for the acylation and aminolysis reactions with the l-stereoisomer than with the d-substrate (10.7 and 17.7 kcal mol−1 higher, respectively). The simulation results suggest that changes in the interaction of the substrate with Asn155 influence the stereospecificity of the polymerization reaction.We studied the molecular mechanism of d-aminopeptidase for the synthesis of polypeptides incorporating d-amino acids. 相似文献
54.
Bungo Otsuki Mitsuru Takemoto Keiichi Kawanabe Yasunari Awa Haruhiko Akiyama Shunsuke Fujibayashi Takashi Nakamura Shuichi Matsuda 《International orthopaedics》2013,37(6):1033-1038
Purpose
Curved peri-acetabular osteotomy (CPO) produces excellent clinical results, but the surgical procedure is technically demanding, and severe complications related to the osteotomy have been reported. To provide a safe, accurate surgical procedure, we have developed a novel method for setting the cutting line and direction. We have designed and made a custom cutting guide for individual patients. The purpose of the study was to evaluate the efficacy of this new method and cutting guide.Methods
The cutting line was designed on a full-scale three-dimensional plaster model made from computed tomography (CT) data for each case. The surface of each plaster model was colour-coded according to the distance from the centre of the femoral head. A custom cutting guide was designed based on this cutting line on the workstation. A titanium custom cutting guide was fabricated using rapid prototyping technology. The cutting guide directed the cutting direction of the osteotome. We evaluated the outcomes for seven consecutive hips in seven patients who underwent CPO using the system between April and December 2011. All peri-operative complications were recorded. The accuracy of the cutting line was evaluated using CT data obtained two weeks after the operation.Results
There were no major complications related to the osteotomy such as posterior column fracture or intra-articular osteotomy. The actual cutting line corresponded almost exactly to the planned cutting line in all cases.Conclusions
The colour-coded plaster model and the custom cutting guide were effective for avoiding severe complications associated with a CPO. 相似文献55.
Buntaro Zempo Shinji Kanda Kataaki Okubo Yasuhisa Akazome Yoshitaka Oka 《The Journal of comparative neurology》2013,521(8):1760-1780
Estrogen and androgen play crucial roles in coordinating reproductive functions through estrogen receptors (ERs) and androgen receptors (ARs), respectively. These receptors are considered important for regulation of the hypothalamo‐pituitary‐gonadal (HPG) axis. Despite their biological importance, the distribution of sex steroid receptors has not been fully analyzed anatomically in the teleost brain. The teleosts have many characteristic features, which allow unique approaches toward an understanding of the regulatory mechanisms of reproductive functions. Medaka serves as a good model system for studying the mechanisms by which steroid receptor‐mediated systems are regulated, because 1) their breeding conditions can be easily manipulated; 2) we can take advantage of the genome database; and 3) molecular genetic tools, such as transgenic techniques, are applicable. We analyzed the distribution of ERα, ERβ1, ERβ2, ARα, and ARβ mRNA by in situ hybridization in the brain of female medaka. We found that all subtypes of ERs and ARs were expressed in the following nuclei: the dorsal part of the ventral telencephalic area (Vd), supracommissural part of the ventral telencephalic area (Vs), postcommissural part of the ventral telencephalic area (Vp), preoptic area (POA), and nucleus ventralis tuberis (NVT). These regions are known to be involved in the regulation of sexual behavior (Vd, Vs, Vp, POA) or the HPG axis (NVT). These ER‐ and/or AR‐expressing neurons may regulate sexual behavior or the HPG axis according to their axonal projections. Future analysis should be targeted to the neurons described in the present study to extend our understanding of the central regulatory mechanisms of reproduction. J. Comp. Neurol. 521:1760–1780, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
56.
Candidate selection for quadrant‐based focal ablation through a combination of diffusion‐weighted magnetic resonance imaging and prostate biopsy 下载免费PDF全文
57.
Fujibayashi Y 《Nihon rinsho. Japanese journal of clinical medicine》2007,65(2):199-203
Molecular imaging research is "to advance our understanding of biology and medicine through noninvasive in vivo investigation of cellular molecular events involved in normal and pathologic processes". This is considered to be useful for holistic understanding of life, a missing viewpoint in recent life sciences. Principle of molecular imaging is a combination of well-designed molecular probe and external detection system. Research on new combination will bring us new insights of life, as well as powerful tools for the development of new drug/therapeutic approach. 相似文献
58.
59.
Satoshi Kano MD PhD Ryuichi Hayashi MD Akihiro Homma MD PhD Kazuto Matsuura MD PhD Kengo Kato MD PhD Kazuyoshi Kawabata MD PhD Nobuya Monden MD PhD Yasuhisa Hasegawa MD PhD Tetsuro Onitsuka MD PhD Yasushi Fujimoto MD PhD Shigemichi Iwae MD PhD Kenji Okami MD PhD Takashi Matsuzuka MD PhD Kunitoshi Yoshino MD PhD Masato Fujii MD PhD 《Head & neck》2014,36(11):1567-1572
60.
Kazuomi Kario Masafumi Nishizawa Mari Kiuchi Arihiro Kiyosue Fumishi Tomita Hiroshi Ohtani Yasuhisa Abe Hideyo Kuga Satoshi Miyazaki Takatoshi Kasai Makiko Hongou Takanori Yasu Jin Kuramochi Yoshihiro Fukumoto Satoshi Hoshide Ichiro Hisatome 《Journal of clinical hypertension (Greenwich, Conn.)》2021,23(2):334
Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio‐ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (–2.9 and –2.5 mg/dl; both p < 0.001) and morning home systolic BP (–3.6 and –5.1 mm Hg; both p < 0.01) after 24 weeks'' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin‐creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (–20.8%; p = 0.021), but not febuxostat (–8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks'' treatment. 相似文献