共查询到17条相似文献,搜索用时 180 毫秒
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研究分析老、中、青年肾移植患者服用普乐可复天数、总胆红素、尿酸的三维图像,使临床指标形象化显现,为预测疾病提供信息。将60岁以上老年患者、40~59岁中年患者与小于40岁青年患者分三组,采用MATLAB7.0做三维图像,分析图像特征并且对老年、中年、青年组图像进行比较。三维图像显示出各项指标间存在内在关系与个体差异。体内指标与服药天数相关,体内指标对临床预防疾病具有重要意义。 相似文献
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采用数字三维图像剖析研究老、中、青年肾移植患者服用普乐可复剂量(FK506)后体内白蛋白、血红蛋白、红细胞个体差异较大的特征,使患者临床用药形象化显现,为个体用药提供信息。将老年患者(>60a)、中年患者(40-59a)与青年患者(<40a)分组,采用MATLAB7.0做三维图像,分析图像特征并且比较白蛋白、血红蛋白、红细胞的各组图像。三维图像显示出三项指标间存在内在关系与个体差异很大。三项体内指标与年龄相关,三项指标对临床个体用药指导具有重要意义。 相似文献
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研究不同年龄的肾移植患者服用环孢素A与百令胶囊的合用药时,患者年龄与体内血红蛋白、红细胞的相关三维图像,为临床合理用药提供信息,使临床血常规指标形象化显现。方法:将合用环孢素A、百令胶囊的老年、中年、青年患者的年龄与用药后的红细胞、血红蛋白指标分为三组,采用MATLAB做三维图像、分析图像特征并对比分析老年组、中年组与青年组的图像异同。结果:三维图像显示出各项指标间存在内在关系与个体差异。结论:环孢素与百令胶囊的合用对老、中、青年肾移植者的红细胞、血红蛋白指标有不同影响。 相似文献
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对100例老年患者的临床资料进行分析,并与同期住院发现的25~45岁青年肺结核100例比较,可见①老年患者易形成高危易感人群;②老年患者病程较长;③误诊率高;④老年患者以Ⅳ型为主,因此就诊时应加以注意。 相似文献
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目的了解临床药师在老年病科的临床药学服务,提升药学服务质量,增强患者的治疗效果,减少患者用药风险,提高患者对医疗服务的满意度。方法对平顶山市医院老年病科的临床医师、临床药师和部分患者进行调查,采用访谈法获取相应的资料,并对老年病科临床药师药学服务进行分析和探究。结果在平顶山某医院的老年病科的临床药学服务有一定程序化的服务,对临床治疗效果起到了作用。在老年病科临床医师对临床药师提出的用药建议有较高的采纳率。针对临床药师提出的调整剂量的采纳率达到84.2%,对于提出的调换药物的建议的采纳率是76.9%,对停用药物的意见采纳率为83.3%。患者的入院前用药依从性较好的占总科室住院患者人数的71.7%,出院前用药依从性较好的人数占科内总人数的81.5%。结论临床药师在审核医嘱和参与病例讨论中所提出的用药建议,给临床医师带来了很大的帮助,减少了药物的不合理使用,增加了患者用药的安全性和有效性。 相似文献
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服药依从性是指病人对医嘱的服从或遵守,充分的依从是病人完全服从医嘱用药及护嘱,并产生相关的有效作用。依从性不佳是指患者不能按医嘱坚持进行药物的自我管理,包括老年患者在用药时,出现多服、漏服、误服、不规则用药、使用非医嘱药。 相似文献
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肺癌是危害人体健康的恶性肿瘤之一,它主要发生在40岁以上的中老年人,但青年肺癌近年来有上升趋势.本文对40岁以下20例肺癌发生误诊的原因进行分析,以期对临床医务人员及广大患者强化防癌意识提供帮助. 相似文献
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孙方寿 《中国轮胎资源综合利用》2009,(12):22-26
我从事轮胎翻修与循环利用工作,是从70年代开始的,从此与翻胎工作结下不解之缘,到现在已有40个年头。我本人已从青年、中年,步入老年。在庆祝祖国60周年华诞之际,回忆过去,可以自豪的说,我从事利国利民的轮胎翻修与循环利用行业一点不后悔,还决定将余生奉献。 相似文献
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Pao-Jen Kuo Cheng-Shyuan Rau Shao-Chun Wu Chia-Wei Lin Lien-Hung Huang Tsu-Hsiang Lu Yi-Chan Wu Chia-Jung Wu Chia-Wen Tsai Ching-Hua Hsieh 《International journal of molecular sciences》2021,22(17)
Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction. 相似文献
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Stankunas K Bayle JH Havranek JJ Wandless TJ Baker D Crabtree GR Gestwicki JE 《Chembiochem : a European journal of chemical biology》2007,8(10):1162-1169
We recently reported that certain mutations in the FK506-rapamycin binding (FRB) domain disrupt its stability in vitro and in vivo (Stankunas et al. Mol. Cell, 2003, 12, 1615). To determine the precise residues that cause instability, we calculated the folding free energy (Delta G) of a collection of FRB mutants by measuring their intrinsic tryptophan fluorescence during reversible chaotropic denaturation. Our results implicate the T2098L point mutation as a key determinant of instability. Further, we found that some of the mutants in this collection were destabilized by up to 6 kcal mol(-1) relative to the wild type. To investigate how these mutants behave in cells, we expressed firefly luciferase fused to FRB mutants in African green monkey kidney (COS) cell lines and mouse embryonic fibroblasts (MEFs). When unstable FRB mutants were used, we found that the protein levels and the luminescence intensities were low. However, addition of a chemical ligand for FRB, rapamycin, restored luciferase activity. Interestingly, we found a roughly linear relationship between the Delta G of the FRB mutants calculated in vitro and the relative chemical rescue in cells. Because rapamycin is capable of simultaneously binding both FRB and the chaperone, FK506-binding protein (FKBP), we next examined whether FKBP might contribute to the protection of FRB mutants. Using both in vitro experiments and a cell-based model, we found that FKBP stabilizes the mutants. These findings are consistent with recent models that suggest damage to intrinsic Delta G can be corrected by pharmacological chaperones. Further, these results provide a collection of conditionally stable fusion partners for use in controlling protein stability. 相似文献
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FK506-binding protein mutational analysis: defining the active-site residue contributions to catalysis and the stability of ligand complexes 总被引:2,自引:0,他引:2
DeCenzo Maureen T.; Park Steven T.; Jarrett Beth P.; Aldape Robert A.; Futer Olga; Murcko Mark A.; Livingston David J. 《Protein engineering, design & selection : PEDS》1996,9(2):173-180
The 12 kDa FK506-binding protein FKBP12 is a cis-trans peptidyl-prolylisomerase that binds the macrolides FK506 and rapamycin. Wehave examined the role of the binding pocket residues of FKBP12in proteinligand interactions by making conservativesubstitutions of 12 of these residues by site-directed mutagenesis.For each mutant FKBP12, we measured the affinity for FK506 andrapamycin and the catalytic efficiency in the cistranspeptidyl-prolyl isomerase reaction. The mutation of Trp59 orPhe99 generates an FKBP12 with a significantly lower affinityfor FK506 than wild-type protein. Tyr26 and Tyr82 mutants areenzymatically active, demonstrating that hydrogen bonding bythese residues is not required for catalysis of the cistranspeptidyl-prolyl isomerase reaction, although these mutationsalter the substrate specificity of the enzyme. We conclude thathydrophobic interactions in the active site dominate in thestabilization of FKBP12 binding to macrolide ligands and tothe twisted-amide peptidyl-prolyl substrate intermediate. 相似文献
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Gertrude J. Nieuwenhuijs-Moeke Dirk J. Bosch Henri G.D. Leuvenink 《International journal of molecular sciences》2021,22(5)
Ischemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively impacts graft and patient outcome. Reperfusion takes place in the recipient and most of the injury following ischemia and reperfusion occurs during this reperfusion phase; therefore, the intra-operative period seems an attractive window of opportunity to modulate IRI and improve short- and potentially long-term graft outcome. Commonly used volatile anesthetics such as sevoflurane and isoflurane have been shown to interfere with many of the pathophysiological processes involved in the injurious cascade of IRI. Therefore, volatile anesthetic (VA) agents might be the preferred anesthetics used during the transplantation procedure. This review highlights the molecular and cellular protective points of engagement of VA shown in in vitro studies and in vivo animal experiments, and the potential translation of these results to the clinical setting of kidney transplantation. 相似文献
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Dr. Martijn D. P. Risseeuw Dries J. H. De Clercq Dr. Sam Lievens Dr. Ulrik Hillaert Dr. Davy Sinnaeve Freya Van den Broeck Prof. Dr. José C. Martins Prof. Dr. Jan Tavernier Prof. Dr. Serge Van Calenbergh 《ChemMedChem》2013,8(3):521-526
We present a scalable synthesis of a versatile MTX reagent with an azide ligation handle that allows rapid γ‐selective conjugation to yield MTX fusion compounds (MFCs) appropriate for MASPIT, a three‐hybrid system that enables the identification of mammalian cytosolic proteins that interact with a small molecule of interest. We selected three structurally diverse pharmacologically active compounds (tamoxifen, reversine, and FK506) as model baits. After acetylene functionalization of these baits, MFCs were synthesized via a CuAAC reaction, demonstrating the general applicability of the MTX reagent. In analytical mode, MASPIT was able to give concentration‐dependent reporter signals for the established target proteins. Furthermore, we demonstrate that the sensitivity obtained with the new MTX reagent was significantly stronger than that of a previously used non‐regiomeric conjugate mixture. Finally, the FK506 MFC was explored in a cellular array screen for targets of FK506. Out of a pilot collection of nearly 2000 full‐length human ORF preys, FKBP12, the established target of FK506, emerged as the prey protein that gave the highest increase in luciferase activity. This indicates that our newly developed synthetic strategy for the straightforward generation of MFCs is a promising asset to uncover new intracellular targets using MASPIT cellular array screening. 相似文献
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Holger Jahr Anna E. van der Windt Ufuk Tan Timur Esther B. Baart Wei-Shiung Lian Bernd Rolauffs Feng-Sheng Wang Thomas Pufe 《International journal of molecular sciences》2022,23(9)
Increasing extracellular osmolarity 100 mOsm/kg above plasma level to the physiological levels for cartilage induces chondrogenic marker expression and the differentiation of chondroprogenitor cells. The calcineurin inhibitor FK506 has been reported to modulate the hypertrophic differentiation of primary chondrocytes under such conditions, but the molecular mechanism has remained unclear. We aimed at clarifying its role. Chondrocyte cell lines and primary cells were cultured under plasma osmolarity and chondrocyte-specific in situ osmolarity (+100 mOsm, physosmolarity) was increased to compare the activation of nuclear factor of activated T-cells 5 (NFAT5). The effects of osmolarity and FK506 on calcineurin activity, cell proliferation, extracellular matrix quality, and BMP- and TGF-β signaling were analyzed using biochemical, gene, and protein expression, as well as reporter and bio-assays. NFAT5 translocation was similar in chondrocyte cell lines and primary cells. High supraphysiological osmolarity compromised cell proliferation, while physosmolarity or FK506 did not, but in combination increased proteoglycan and collagen expression in chondrocytes in vitro and in situ. The expression of the TGF-β-inducible protein TGFBI, as well as chondrogenic (SOX9, Col2) and terminal differentiation markers (e.g., Col10) were affected by osmolarity. Particularly, the expression of minor collagens (e.g., Col9, Col11) was affected. The inhibition of the FK506-binding protein suggests modulation at the TGF-β receptor level, rather than calcineurin-mediated signaling, as a cause. Physiological osmolarity promotes terminal chondrogenic differentiation of progenitor cells through the sensitization of the TGF-β superfamily signaling at the type I receptor. While hyperosmolarity alone facilitates TGF-β superfamily signaling, FK506 further enhances signaling by releasing the FKBP12 break from the type I receptor to improve collagenous marker expression. Our results help explain earlier findings and potentially benefit future cell-based cartilage repair strategies. 相似文献