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鹿茸多肽对兔骨髓间质干细胞体外增殖的影响 总被引:7,自引:1,他引:6
目的探讨鹿茸多肽(PAP)对兔骨髓间质干细胞(MSCs)体外增殖的影响。方法分离MSCs,并用流式细胞术检测CD34、CD45、CD29、CD90表达;将MSCs分为对照组、PAP不同浓度组、转化生长因子β1(TGFβ1)组,培养48h后用四唑盐比色法测细胞活力、流式细胞术测细胞增殖指数(PI)、免疫组织化学Envision二步法测增殖细胞核抗原(PCNA)表达。结果CD34、CD45、CD29、CD90分别为0.81%、0.09%、95.90%、67.00%;PAP不同浓度组与TGFβ1组吸光度值与PI较大,免疫组织化学表达棕褐色颗粒较多,与对照组比较差异有统计学意义(P<0.0.1);PAP不同浓度组MSCs在体外连续培养中没有异倍体的产生。结论PAP对兔MSCs的增殖有促进作用,且能逆转MSCs体外连续培养中异行性的产生。 相似文献
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SMAD4 mutations found in unselected HHT patients 总被引:1,自引:0,他引:1
Gallione CJ Richards JA Letteboer TG Rushlow D Prigoda NL Leedom TP Ganguly A Castells A Ploos van Amstel JK Westermann CJ Pyeritz RE Marchuk DA 《Journal of medical genetics》2006,43(10):793-797
Background
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease exhibiting multifocal vascular telangiectases and arteriovenous malformations. The majority of cases are caused by mutations in either the endoglin (ENG) or activin receptor‐like kinase 1 (ALK1, ACVRL1) genes; both members of the transforming growth factor (TGF)‐β pathway. Mutations in SMAD4, another TGF‐β pathway member, are seen in patients with the combined syndrome of juvenile polyposis (JP) and HHT (JP‐HHT).Methods
We sought to determine if HHT patients without any apparent history of JP, who were undergoing routine diagnostic testing, would have mutations in SMAD4. We tested 30 unrelated HHT patients, all of whom had been referred for DNA based testing for HHT and were found to be negative for mutations in ENG and ALK1.Results
Three of these people harboured mutations in SMAD4, a rate of 10% (3/30). The SMAD4 mutations were similar to those found in other patients with the JP‐HHT syndrome.Conclusions
The identification of SMAD4 mutations in HHT patients without prior diagnosis of JP has significant and immediate clinical implications, as these people are likely to be at risk of having JP‐HHT with the associated increased risk of gastrointestinal cancer. We propose that routine DNA based testing for HHT should include SMAD4 for samples in which mutations in neither ENG nor ALK1 are identified. HHT patients with SMAD4 mutations should be screened for colonic and gastric polyps associated with JP. 相似文献7.
Juha-Matti Savola Michael Hill Mia Engstrom Hannele Merivuori Siegfried Wurster Steven G McGuire Susan H Fox Alan R Crossman Jonathan M Brotchie 《Movement disorders》2003,18(8):872-883
Previous studies in the MPTP-lesioned primate model of Parkinson's disease have demonstrated that alpha(2) adrenergic receptor antagonists such as idazoxan, rauwolscine, and yohimbine can alleviate L-dopa-induced dyskinesia and, in the case of idazoxan, enhance the duration of anti-parkinsonian action of L-dopa. Here we describe a novel alpha(2) antagonist, fipamezole (JP-1730), which has high affinity at human alpha(2A) (K(i), 9.2 nM), alpha(2B) (17 nM), and alpha(2C) (55 nM) receptors. In functional assays, the potent antagonist properties of JP-1730 were demonstrated by its ability to reduce adrenaline-induced (35)S-GTPgammaS binding with K(B) values of 8.4 nM, 16 nM, 4.7 nM at human alpha(2A), alpha(2B), and alpha(2C) receptors, respectively. Assessment of the ability of JP-1730 to bind to a range of 30 other binding sites showed that JP-1730 also had moderate affinity at histamine H1 and H3 receptors and the serotonin (5-HT) transporter (IC(50) 100 nM to 1 microM). In the MPTP-lesioned marmoset, JP-1730 (10 mg/kg) significantly reduced L-dopa-induced dyskinesia without compromising the anti-parkinsonian action of L-dopa. The duration of action of the combination of L-dopa and JP-1730 (10 mg/kg) was 66% greater than that of L-dopa alone. These data suggest that JP-1730 is a potent alpha(2) adrenergic receptor antagonist with potential as an anti-dyskinetic agent in the treatment of Parkinson's disease. 相似文献
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Familial Mediterranean Fever (FMF) is an inherited disease whose pathogenesis is obscure. We raise the possibility that the short episodes of fever, joint pains and the abdominal manifestations of this entity may be related to a genetic defect in the interferon system of these patients. 相似文献
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Mai Shimizu Tatsuki Fukami Hiroyuki Ogawa Toshio Taniguchi Yukihiro Nomura Miki Nakajima 《Journal of pharmaceutical sciences》2021,110(2):925-934
Prodrug development is a common approach in drug development. In a recent study, we established a systematic strategy for selecting prodrugs with improved membrane permeability or solubility based on log D value, solubility in artificial intestinal fluids, membrane permeability, and metabolic instability. The purpose of this study was to evaluate the utility of this strategy using oseltamivir and 23 kinds of oseltamivir analogues having various types of side chain as well as their active metabolite, oseltamivir acid. Log D values of oseltamivir and analogues (2.0 to 4.9) were higher than that of oseltamivir acid (0.7), supporting the previous development of oseltamivir to improve permeability of oseltamivir acid. Solubilities of analogues in artificial intestinal fluids were over 80%, except the compound with the highest lipophilicity. Positive correlation was observed between membrane permeability and log D values of analogues. In metabolic profiles, species differences in the hydrolysis efficiency were observed depending on analogues. Using our strategy, it was demonstrated that oseltamivir and some analogues are appropriate prodrugs that could be advanced to in vivo pharmacokinetic studies, with selection of suitable animals. This study confirmed the utility of our strategy for narrowing down of candidate compounds to proceed into in vivo study. 相似文献
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Both aortic dissection and tension pneumothorax are conditions that require urgent treatments. However, the diagnosis of these emergencies is sometimes challenging because of various symptoms and difficulty obtaining their medical history due to severe conditions. Here, we present the case of a patient with type A aortic dissection associated with tension pneumothorax. This is the second report of such a case worldwide. A 61-year-old man presented to the emergency department with sudden-onset chest and back pain. Upon presentation, his blood pressure was 97/58 mmHg, oxygen saturation on room air was 96%, and respiratory rate was 28 breaths/min. His physical examination revealed no jugular venous distention; however, breath sounds over the left lung were diminished. Bedside chest radiography revealed left tension pneumothorax with mediastinal shift to the right. Needle and chest tube thoracostomies were performed; however, the patient's vital signs did not improve and reexpansion pulmonary edema developed following tube thoracostomy. Contrast-enhanced computed tomography revealed type A thrombosed aortic dissection with bullae in the upper lobe of the left lung. Therefore, the patient was admitted to the intensive care unit, conservatively treated, and discharged without any complications. In conclusion, type A aortic dissection may be associated with tension pneumothorax and should be considered if the patient's vital signs do not improve even after decompression of the tension pneumothorax. 相似文献