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991.
Introduction
Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether 99mTc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis.Methods
The RRL peptide was designed and radiosynthesized with 99mTc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. 99mTc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of 99mTc-RRL was also explored.Results
The labeling efficiencies of 99mTc-RRL reached 76.9%±4.5% (n = 6) within 30–60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that 99mTc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of 99mTc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2–6 h after injection of 99mTc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with 99mTc-RRL was comparable with that of 18F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of 99mTc-RRL with R2 = 0.821.Conclusion
99mTc-RRL can be used as a potential candidate for visualization of tumor angiogenesis in malignant carcinomas. 相似文献992.
A capillary electrophoresis method was developed to separate the enantiomers of cefoperazone. Different cyclodextrins, including alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), gamma-cyclodextrin (gamma-CD), 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and methyl-beta-cyclodextrin (Me-beta-CD), were tested as chiral additives in the running buffer. The effect of various parameters on enantioseparation such as concentration of NaH(2)PO(4), buffer pH, and CD concentration was also studied. The cefoperazone enantiomers were baseline separated under conditions of 0.04 mmol/L beta-CD, 75 mmol/L NaH(2)PO(4) buffer at pH 4.0. A fused silica capillary (40 cm effective length x 75 microm ID) was used. The applied voltage and capillary temperature were 20 kV and 25 degrees C, respectively. Under these conditions, linear calibration curves were obtained in the 5-500 microg/ml range using UV detection at 280 nm. The limit of detection for both isomers was 0.1 microg/ml. The method was used for the analysis of different pharmaceutical preparations (dose) and biological samples containing cefoperazone. 相似文献
993.
994.
利用体视显微镜观察、测量、记录菜粉蝶不同虫态雌雄个体间的形态特征差异。雌雄菜粉蝶幼虫、蛹和成虫均存在显著的雌雄二型特征,3龄之后雄性幼虫的第6腹节有一对肾型黑斑,雌性幼虫无此斑。雄蛹第9腹节有生殖孔和一条短纵裂缝,裂缝两侧有凹凸不平的半圆形瘤状突起;雌蛹腹部第8、9腹节分别有生殖孔和产卵孔,且两孔之间亦有一条纵裂缝。雌蝶前翅背面有一对上下排列的黑圆斑,其腹部末端外生殖器为圆筒型;雄蝶前翅背面一对黑斑相对较小,颜色较浅,尤其下斑为浅灰色,腹部末端具钳状外生殖器。本研究揭示了菜粉蝶幼虫、蛹及成虫不同虫态的雌雄二型差异,比较研究并提出了便于快速鉴别雌雄个体的典型特征和识别方法。 相似文献
995.
996.
Jiaxiang Hu Xiaoxue Wang Yanling Xing Enguang Rong Mengfei Ning Jacqueline Smith Yinhua Huang 《BMC evolutionary biology》2018,18(1):201
Background
Oligoadenylate synthetases (OASs) are widely distributed in Metazoa including sponges, fish, reptiles, birds and mammals and show large variation, with one to twelve members in any given species. Upon double-stranded RNA (dsRNA) binding, avian and mammalian OASs generate the second messenger 2'-5'-linked oligoadenylate (2-5A), which activates ribonuclease L (RNaseL) and blocks viral replication. However, how Metazoa shape their OAS repertoires to keep evolutionary balance to virus infection is largely unknown. We performed comprehensive phylogenetic and functional analyses of OAS genes from evolutionarily lower to higher Metazoa to demonstrate how the OAS repertoires have developed anti-viral activity and diversified their functions.Results
Ancient Metazoa harbor OAS genes, but lack both upstream and downstream genes of the OAS-related pathways, indicating that ancient OASs are not interferon-induced genes involved in the innate immune system. Compared to OASs of ancient Metazoa (i.e. sponge), the corresponding ones of higher Metazoa present an increasing number of basic residues on the OAS/dsRNA interaction interface. Such an increase of basic residues might improve their binding affinity to dsRNA. Moreover, mutations of functional residues in the active pocket might lead to the fact that higher Metazoan OASs lose the ability to produce 3'-5'-linked oligoadenylate (3-5A) and turn into specific 2-5A synthetases. In addition, we found that multiple rounds of gene duplication and domain coupling events occurred in the OAS family and mutations at functionally critical sites were observed in most new OAS members.Conclusions
We propose a model for the expansion of OAS members and provide comprehensive evidence of subsequent neo-functionalization and sub-functionalization. Our observations lay the foundation for interrogating the evolutionary transition of ancient OAS genes to host defense genes and provide important information for exploring the unknown function of the OAS gene family.997.
单克隆抗体(Monoclonal antibody, mAb)在癌症以及自身免疫等疾病的诊断与治疗中得到广泛应用, 并且取得了重大进展。当今应用于临床的单克隆抗体是在免疫球蛋白的基础上进行改造研发而得。然而近期发现的无颌类脊椎动物的特异性抗原受体-可变淋巴细胞受体(Variable lymphocyte receptor, VLR), 为抗体类试剂或药物的研发提供了新的视角。与免疫球蛋白(Immunoglobulins, Ig)相比, VLR与抗原结合的特异性、亲和力及稳定性都优于Ig类抗体, 并且抗原特异性单克隆VLR的制备技术日趋成熟。因此, VLR在临床诊断和治疗中具有更高的应用价值, 并可能成为新一代的抗体药物。文章就VLR的基本特征、制备方法及其应用前景进行综述, 为实现VLR在临床诊断与治疗等领域中的应用提供有益参考。 相似文献
998.
Li R Wang WQ Zhang H Yang X Fan Q Christopher TA Lopez BL Tao L Goldstein BJ Gao F Ma XL 《American journal of physiology. Endocrinology and metabolism》2007,293(6):E1703-E1708
Plasma adiponectin level is significantly reduced in patients with metabolic syndrome, and vascular dysfunction is an important pathological event in these patients. However, whether adiponectin may protect endothelial cells and attenuate endothelial dysfunction caused by metabolic disorders remains largely unknown. Adult rats were fed with a regular or a high-fat diet for 14 wk. The aorta was isolated, and vascular segments were incubated with vehicle or the globular domain of adiponectin (gAd; 2 mug/ml) for 4 h. The effect of gAd on endothelial function, nitric oxide (NO) and superoxide production, nitrotyrosine formation, gp91(phox) expression, and endothelial nitric oxide synthase (eNOS)/inducible NOS (iNOS) activity/expression was determined. Severe endothelial dysfunction (maximal vasorelaxation in response to ACh: 70.3 +/- 3.3 vs. 95.2 +/- 2.5% in control, P < 0.01) was observed in hyperlipidemic aortic segments, and treatment with gAd significantly improved endothelial function (P < 0.01). Paradoxically, total NO production was significantly increased in hyperlipidemic vessels, and treatment with gAd slightly reduced, rather than increased, total NO production in these vessels. Treatment with gAd reduced (-78%, P < 0.01) superoxide production and peroxynitrite formation in hyperlipidemic vascular segments. Moreover, a moderate attenuation (-30%, P < 0.05) in gp91(phox) and iNOS overexpression in hyperlipidemic vessels was observed after gAd incubation. Treatment with gAd had no effect on eNOS expression but significantly increased eNOS phosphorylation (P < 0.01). Most noticeably, treatment with gAd significantly enhanced eNOS (+83%) but reduced iNOS (-70%, P < 0.01) activity in hyperlipidemic vessels. Collectively, these results demonstrated that adiponectin protects the endothelium against hyperlipidemic injury by multiple mechanisms, including promoting eNOS activity, inhibiting iNOS activity, preserving bioactive NO, and attenuating oxidative/nitrative stress. 相似文献
999.
1000.
免疫缺陷动物是研究免疫相关疾病的良好动物模型。Beige-Nude小鼠是T淋巴细胞和NK细胞同时缺陷的小鼠,其T细胞和NK细胞活性很低,最初为肿瘤的研究而培育。从上世纪七十年代起,学者们对其免疫学特性进行了广泛而深入的研究,为其在其他领域的应用奠定了免疫学基础。 相似文献