Ellipticine and derivatives induce breakage of L1210 cells DNA in vitro.

Part of the radioactive DNA extracted from prelabelled L1210 cells exposed in vitro to ellipticine, 9-hvdroxyellipticine, 2-methyl-9-hydroxyellipticinium and 9-aminoellipticine, migrate more slowly into an alkaline sucrose gradient. These effects occur in less than one hr of exposure, and can be detected at drug concentrations which lie respectively around 1000, 20, 100 and 500 ng per ml whereas the drug concentrations which inhibit by 50 per cent the rate of the in vitro cell growth are 242, 3.9, 13 and 53 ng per ml. The DNA breaks become rapidly undetectable when the cells' exposure to the drugs is discontinued.     

Interactions between the serotoninergic and noradrenergic systems of the brain and their role in the regulation of animal behavior

Studies were carried out using DBA/2 mice on the relationship between the behavioral effects of antagonists of different types of 5-HT receptors and the level of activity of α₂-adrenoceptors. The 5-HT_1c receptor antagonists mianserin (2 mg/kg) and cyproheptadine (2 mg/kg) and the 5-HT₂ receptor antagonist ketanserin (3 mg/kg) had no effect on movement activity, while the 5-HT₃ and 5-HT₄ receptor antagonists zacopride (1 mg/kg) and ICS 205-930 (1 mg/kg) reduced movement behavior in intact animals. On a background of treatment with the α₂-adrenoceptors blocker yohimbine (0.5 mg/kg), mianserin, cyproheptadine, and ketanserin inhibited movement activity and significantly reduced the sensitivity of animals to audiogenic convulsions. These data indicate that administration of α₂-adrenoceptors antagonists increases the efficiency with which serotonin receptors regulate behavior. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia; Department of Pharmacology, Scientific Health Center, University of Texas, San Antonio, USA. Translated from Fiziologicheskii Zhurnal im.I. M. Sechenova, Vol. 81, No. 8, pp. 101–103, August, 1995.     

Description of a Simple,Specific, and Sensitive Test for the Detection of Detergent-Solubilized C3b Receptor

The C3b receptor was isolated from detergent-solubilized human erythrocyte membranes by a previously described technique (1). The receptor glycoprotein was shown to enhance EAC14^oxy23b rosette formation with Raji lymphoblastoid cells. This provided a specific and sensitive test to detect the solubilized C3b receptor either in crude or highly purified form. The property of the C3b receptor tested by this assay appears to be analogous to properties of β1H.     

瑞芬太尼对人结肠癌COLO205细胞增殖及凋亡的影响

目的 探讨瑞芬太尼对人结肠癌COLO205细胞增殖及凋亡的影响.方法 体外培养人结肠癌细胞COLO205,按完全随机法分为两组:正常对照组和瑞芬太尼干预组.四甲基偶氮唑盐(monotetrazolium,MTT)法检测瑞芬太尼在相同浓度的条件下不同时间点对结肠癌COLO205细胞增殖的影响,测得抑制率并计算半数抑制浓度值,应用凋亡试剂盒结合流式细胞仪检测瑞芬太尼对人结肠癌COLO205细胞凋亡的影响.结果 MTT结果显示,相同浓度的瑞芬太尼干预结肠癌COLO205细胞,分别在24、48、72 h测算半数抑制浓度结果为(50.6±4.0)、(43.6±3.7)、(36.0±1.1)nmol/L;瑞芬太尼干预组凋亡率为(59±9)%,对照组凋亡率为(71±15)%.结论 瑞芬太尼能抑制结肠癌COLO205细胞增殖,促进其凋亡.     

ATF6对骨肉瘤MCA205细胞免疫原性的调控作用及其机制的初步探索

目的：探讨活化转录因子6(ATF6)对骨肉瘤细胞MCA205免疫原性的影响,初步解析其调控机制。方法：利用CRISPR-Cas9技术敲除MCA205细胞的Atf6基因,借助CCK-8实验、细胞能量代谢检测、流式细胞术、ATP检测试剂盒、干扰素刺激响应元件(ISRE)-荧光素酶报告细胞实验和qPCR法分别检测野生型(WT)和Atf6^-/-MCA205细胞在PBS或衣霉素(Tm)处理后的活力、线粒体耗氧速率(OCR)和胞外酸化速率(ECAR)、磷脂酰丝氨酸外翻和细胞膜通透性、胞内钙离子动员、胞内外ATP浓度、IFN-a/β分泌和干扰素刺激基因(ISG)的表达水平。在免疫系统健全的小鼠皮下接种WT或Atf6^-/-MCA205细胞,比较两者的成瘤速度、肿瘤组织基因转录图谱、局部抗肿瘤效应T细胞活化有无差异。将WT和Atf6^-/-MCA205细胞分别接种于nu/nu小鼠背部两侧皮下,或将Atf6^-/-MCA205细胞分别接种于免疫系统健全小鼠和Ifnar^-/-小鼠皮下,记录肿瘤生长曲线。...     

Multi-disciplinary clinical protocol for the diagnosis of bulbar amyotrophic lateral sclerosis

Introduction and objectives

The objective of this study was to examine the role of different specialists in the diagnosis of amyotrophic lateral sclerosis (ALS), to understand changes in verbal expression and phonation, respiratory dynamics and swallowing that occurred rapidly over a short period of time.

In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination

The prevention and treatment of prevalent infectious diseases and tumors should benefit from improvements in the induction of antigen-specific T cell immunity. To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues. Simultaneously, we injected agonistic alpha-CD40 antibody to mature the dendritic cells. We found that a single low dose of antibody-conjugated ovalbumin initiated immunity from the naive CD4+ and CD8+ T cell repertoire. Unexpectedly, the alphaDEC-205 antigen conjugates, given s.c., targeted to dendritic cells systemically and for long periods, and ovalbumin peptide was presented on MHC class I for 2 weeks. This was associated with stronger CD8+ T cell-mediated immunity relative to other forms of antigen delivery, even when the latter was given at a thousand times higher doses. In parallel, the mice showed enhanced resistance to an established rapidly growing tumor and to viral infection at a mucosal site. By better harnessing the immunizing functions of maturing dendritic cells, antibody-mediated antigen targeting via the DEC-205 receptor increases the efficiency of vaccination for T cell immunity, including systemic and mucosal resistance in disease models.     

5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae

Summary The present study was designed to characterize an atypical 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the rat oesophageal tunica muscularis mucosae. All experiments were performed under equilibrium conditions, using pargyline to inhibit the oxidative deamination of indoleamines, and cocaine and corticosterone to inhibit neuronal and extraneuronal uptake. Under these conditions 5-HT (0.3–1000 nmol/l) produced a concentration-dependent relaxation of carbachol-induced tension. The concentration-effect curve to 5-HT was unaffected by potent antagonists for 5-HT₁, 5-HT₂, 5-HT₃ and so called 5-HT_1P receptors (metergoline, methysergide, ketanserin, ondansetron, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide), but was antagonized competitively by ICS 205–930 (pA₂ = 6.7). Responses to 5-HT were mimicked by other indoleamines and substituted benzamides with the following order of potency: 5-HT 5-methoxytryptamine > cisapride = -methyl-5-HT = (S)-zacopride = renzapride > (RS)-zacopride > 5-carboxamido-tryptamine = metoclopramide = (R)-zacopride > tryptamine > 2-methyl-5-HT. ICS 205–930 afforded similar pA₂ values (6.0–6.7) against each agonist, indicating a common site of action. Concentration-effect curves to 5-HT were not affected by tetrodotoxin or indomethacin, sugesting that 5-HT-induced relaxation of the tunica muscularis mucosae was mediated via a postjunctional receptor, independent of endogenous prostanoids. The pharmacological profile of the 5-HT receptor in the rat oesophageal tunica muscularis mucosae correlates well with the 5-HT₄ receptor characterized recently in both the CNS and gastro-intestinal tract. Send offprint requests to D. E. Clarke at the above address