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排序方式: 共有842条查询结果,搜索用时 15 毫秒
821.
Shintaro Hirata Kazuyoshi Saito Satoshi Kubo Shunsuke Fukuyo Yasushi Mizuno Shigeru Iwata Masao Nawata Norifumi Sawamukai Kazuhisa Nakano Kunihiro Yamaoka Yoshiya Tanaka 《Arthritis research & therapy》2013,15(5):R135
Introduction
Evidences of biologics-free disease control after discontinuing adalimumab (ADA) in rheumatoid arthritis (RA) patients in clinical practice have not been sufficiently investigated. Purpose of this study is to investigate whether disease activity score 28 (DAS28)- erythrocyte sedimentation rate (ESR) remission was preserved after discontinuation of ADA in patients with RA.Methods
This is an observational but not a randomized controlled study. Among 197 RA patients who initiated with combination of ADA with concomitant MTX, 69 (35%) acquired DAS28 (ESR) < 2.6 for at least 24 weeks. Of those 69 patients, 51 went on ADA discontinuation with their consent, and finally 50 of those with follow-up of > 24 weeks were evaluated. The effect of discontinuing ADA on clinical disease activity, functional disability and radiographic progression were evaluated by DAS28 (ESR), the clinical disease activity index (CDAI) and the simplified disease activity index (SDAI), by a health assessment questionnaire-disability index (HAQ-DI) and by the modified total Sharp score (mTSS), respectively.Results
The mean age of the participants was 59.5 years with the mean disease duration of 7.1 years. Out of the 50 patients, 29 (58%) were maintained in DAS28 (ESR) < 2.6 at 24 weeks after discontinuing ADA. A logistic regression analysis showed that DAS28 (ESR) at baseline significantly predicted a DAS28 (ESR) < 2.6 maintained after discontinuation of ADA, and a receiver-operating characteristic (ROC) analysis showed that the cut-off value of DAS28 (ESR) at discontinuation was 2.16. The mean HAQ-DI at six months after discontinuing ADA was 0.1 in patients who kept in DAS28 (ESR) < 2.6, and 94.9% (37/39) showed no evidence of radiographic progression (> 0.5 per year of a change in mTSS) at 1 year.Conclusions
It was possible to maintain DAS28 (ESR) < 2.6 after discontinuation of ADA without functional and radiographic progression and very low DAS28 (ESR) at the discontinuation was associated with successful ADA-free DAS28 (ESR) < 2.6 in patients with RA.Trial registration
University Hospital Medical Information Network Identifier: UMIN000006669. 相似文献822.
Mechanistic studies on depurination and apurinic site chain breakage in oligodeoxyribonucleotides. 总被引:2,自引:2,他引:0
Products formed from defined oligodeoxyribonucleotide tetramers (oligonucleotides) by depurination at pH 5.0 and 90 degrees C followed by chain breakage at the resulting apurinic sites (AP sites) were assigned by reversed phase HPLC. Through kinetic analysis, rate constants of depurination and subsequent chain breakage reactions were measured. Depurination of the oligonucleotides with purine bases locating at the terminal positions was several times faster than those with purines at the internal ones. The pKa values for the N7 of the G residues and the activation energies of the depurination were essentially independent of the position of the bases. The frequency factor was found to be responsible for the observed difference of the depurination rates. In contrast, the chain breakage by beta-elimination was several times faster for the AP sites formed at the internal positions than those at the 5'-terminal positions. It is suggested that an electron withdrawing phosphate group attached to the 5'-side of an AP site facilitates the chain cleavage. 相似文献
823.
824.
Tadashi Toyama Noritaka Maeda Manabu Murashita Yong-Cheol Chang Shintaro Kikuchi 《Biodegradation》2010,21(2):157-165
A novel bacterium capable of utilizing 2-sec-butylphenol as the sole carbon and energy source, Pseudomonas sp. strain MS-1, was isolated from freshwater sediment. Within 30 h, strain MS-1 completely degraded 1.5 mM 2-sec-butylphenol in basal salt medium, with concomitant cell growth. A pathway for the metabolism of 2-sec-butylphenol by strain MS-1 was proposed on the basis of the identification of 3 internal metabolites—3-sec-butylcatechol, 2-hydroxy-6-oxo-7-methylnona-2,4-dienoic acid, and 2-methylbutyric acid—by gas chromatography-mass spectrometry
analysis. Strain MS-1 degraded 2-sec-butylphenol through 3-sec-butylcatechol along a meta-cleavage pathway. Degradation experiments with various alkylphenols showed that the degradability of alkylphenols by strain
MS-1 depended strongly on the position (ortho ≫ meta = para) of the alkyl substitute, and that strain MS-1 could degrade 2-alkylphenols with various sized and branched alkyl chain (o-cresol, 2-ethylphenol, 2-n-propylphenol, 2-isopropylphenol, 2-sec-butylphenol, and 2-tert-butylphenol), as well as a dialkylphenol (namely, 6-tert-butyl-m-cresol). 相似文献
825.
826.
Kortaro Tanaka M.D. Yasuo Fukuuchi Shintaro Gomi Shutaro Takashima Ban Mihara Toshitaka Shirai Shigeru Nogawa Hiroyuki Nozaki Eiichiro Nagata Taro Kondo 《Neurochemical research》1995,20(9):1007-1012
The correlation between regional phorbol ester binding and cerebral blood flow (CBF) was evaluated in the gerbil brain after 2-hour unilateral common carotid artery occlusion [3H]phorbol 12, 13-dibutyrate (PDBu) was used as a specific ligand for estimating the translocation of protein kinase C (PKC), and CBF was determined by the [14C]iodoantipyrine method. A quantitative autoradiographic method permitted concurrent measurement of these two parameters in the same brain. In the ischemia group of the animals, statistically significant, inverse correlations were noted between the CBF and PDBu binding in the hippocampus (CA1 and CA3 regions and dentate gyrus), the caudate-putamen and lateral nuclei of the thalamus. In these regions, the PDBu binding increased progressively as CBF fell below 35–40 ml/100 g/min. On the other hand, the PDBu binding in the cerebral cortices did not show any significant changes even when CBF was decreased to below 35 ml/100 g/min. The above data suggest that (1) the translocation of PKC to the cell membrane may be regionally specific in response to ischmia and may remain in the regions particularly vulnerable to ischemia such as the hippocampus, caudate-putamen and lateral nuclei of the thalamus in the early ischemic phase; (2) the threshold of CBF below which PKC begins to translocate to the cell membrane in the above regions, may be 35–40 ml/100 g/min in 2-hour ischemia. 相似文献
827.
Butyric acid is one of the major extracellular metabolites of periodontopathic Gram-negative bacteria. We previously demonstrated that butyric acid induced apoptosis in human T cells. In the present study, we examined the interaction between butyric acid and TNF-α in Jurkat T-cell apoptosis. Simultaneous treatment with TNF-α enhanced butyric acid-induced apoptosis by promoting caspase activity more than was achieved by either reagent alone. We examined which genes were associated with the increased susceptibility to TNF-α caused by butyric acid, and revealed that expression of cFLIP decreased with increased concentrations of butyric acid. Furthermore, exogenous expression of cFLIP protein suppressed the enhancing effect by TNF-α in the apoptosis. These results suggest that butyric acid downregulates cFLIP expression and increases the susceptibility to TNF-α by activating caspases via the death receptor signal. 相似文献
828.
Fluorescein mercuric acetate causes the unwinding of DNA and binds to the separated bases. This unwinding process can be followed by measuring absorption changes of this reagent. For untreated calf thymus DNA, the initial rate was very slow, and the shape of the kinetic curve was sigmoidal. When double-strand breaks of DNA were produced by DNase II treatment or sonication, the initial rate increased and the sigmoidal character disappeared. The initial rate was shown to be proportional to the concentration of helix ends. From this relation the rate of unwinding was estimated to be 2.0 base pairs/sec at 1.0 × 10?5M fluorescein mercuric acetate and 25°C. DNase I treatment, which produces single-strand breaks and a smaller number of double-strand breaks, also increased the initial rate. However, this increase was due only to the double-strand breaks, that is, single-strand breaks had no significant effect on the initial rate. Also, uv irradiation increased the initial rate linearly with uv dose, at least up to 2 × 105 erg/mm2, suggesting that this increase is due to photoproducts other than usual pyrimidine dimers. We discuss the usefulness of this kinetic method in structural studies of DNA. 相似文献
829.
Shintaro Seto Sohkichi Matsumoto Kunio Tsujimura Yukio Koide 《Microbiology and immunology》2010,54(3):170-174
M.tb is an intracellular pathogen which survives within the phagosomes of host macrophages by inhibiting their fusion with lysosomes. Here, it has been demonstrated that a lysosomal glycoprotein, CD63, is recruited to the majority of M.tb phagosomes, while RILP shows limited localization. This is consistent with the author's findings that CD63, but not RILP, is recruited to the phagosomes in macrophages expressing the dominant negative form of Rab7. These results suggest that M.tb phagosomes selectively fuse with endosomes and lysosomes to escape killing activity while acquiring nutrients. 相似文献
830.
Hiromi Ii Naoki Yokoyama Shintaro Yoshida Kae Tsutsumi Shinji Hatakeyama Takashi Sato Keiichi Ishihara Satoshi Akiba 《PloS one》2009,4(12)
Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A2 (IVA-PLA2), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA2-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA2-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA2-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA2-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA2-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E2, which has a fat storage effect, was lower in IVA-PLA2-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA2 alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA2 metabolites, such as prostaglandin E2. IVA-PLA2 could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease. 相似文献