血管细胞粘附分子调控造血的研究进展

本文简述了血管细胞粘附分子 (Vascularcelladhesionmolecule 1,VCAM 1)的结构和生物学功能 ,总结了VCAM 1在恶性血液病骨髓基质中的表达和意义 ,探讨了VCAM 1在造血干细胞动员和归巢中的作用 ,指出VCAM 1作用机制的深入研究将对恶性血液病的治疗提供更为有效的方法。     

RNA干扰技术在以VEGF/VEGFR为靶点的膀胱癌治疗研究中的应用前景

RNA干扰（RNAi）是正常生物体内抑制特定基因表达的一种现象，它是指当细胞中导入与内源性mRNA编码区同源的双链RNA（dsRNA），该mRNA发生降解而导致基因沉默的现象。利用RNAi技术干涉VEGF表达，达到抑制肿瘤发展和转移的研究已较为广泛。膀胱癌生长、转移不仅有VEGF表达增多，同时发现VEGFR表达亦增高，成为RNAi的新靶点。现主要综述以VEGF/VEGFR为靶点的RNAi技术在膀胱癌治疗研究中的优势、发展前景以及存在问题与对策。     

反义AKT2 RNA抑制U251胶质瘤细胞生长的体内外研究

目的 研究反义AKT2RNA对U251人脑胶质瘤细胞在体内外的生长抑制效用。方法 将逆转录病毒pLXSN为载体的反义AKT2构建体转染U251人脑胶质瘤细胞系，应用蛋白印记确定基因转染前后AKT2的表达水平。流式细胞法与Matrigel基质生长实验评价肿瘤细胞转染前后的增殖活性。进一步应用裸鼠皮下荷瘤模型观察脂质体介导pLXSN、pLXSN-AS-AKT2基因治疗对U251细胞生长抑制作用。在28d的观察期内定期测量皮下肿瘤体积，对肿瘤标本应用免疫组化的方法进行AKT2和胶质纤维酸性蛋白（GFAP）表达比较。结果 脂质体介导pLXSN-AS-AKT2可显著抑制U251细胞AKT2表达。与对照组和pLXSN转染组比较，细胞周期分析结果表明AK—AKT2转染组进入S期的细胞数减少了8．5％～8．9％，而进入G0＋G1期细胞则增加了7．9％～8．6％。Matrigel基质生长实验显示对照组和pLXSN转染组细胞呈正常形态贴壁生长，而AS～AKT2转染组细胞不能贴壁生长，呈团块状簇集生长。裸鼠皮下荷瘤模型实验显示pLXSN-AS-AKT2显著抑制皮下肿瘤生长，组织病理学分析显示AS-AKT2转染组AKT2表达下降而GFAP表达上调。结论 体内外实验证明反义AKT2方法在抗胶质瘤增殖方面作用重要，AKT2可作为基因治疗胶质瘤的优选靶标。     

Cytochrome c mRNA levels decrease in senescent rat heart.

The concentration of mitochondria decrease in the heart as rodents age from maturity to senescence. The reason for this change is not known. One purpose of the present study was to determine if cytochrome c mRNA, representative of proteins of the inner mitochondrial membrane, decreased in the hearts of Fischer 344 rats as they aged from 12 to 24 months. Twenty-two percent less cytochrome c mRNA existed per given quantity of extracted RNA from the heart in 24-month-old rats as compared with the 12-month-old group. No change in the quantities of cardiac -actin mRNA, Ca²⁺/calmodulin protein kinase II mRNA or 18S rRNA was noted between 12- und 24-month-old hearts. Thus, the decrease in cytochrome c mRNA suggests that decreased in mRNAs for proteins of the inner mitochondrial membrane could play some role in the diminished concentration of mitochondria that exists in the senescent heart.     

Oral administration of an edible-mushroom-derived protein inhibits the development of food-allergic reactions in mice

BACKGROUND: Food allergy is a common disease without effective treatment. Since strict elimination of food allergens may be difficult, strategies for effective intervention are urgently needed. OBJECTIVE: The aim was to investigate the prophylactic use of orally administrated FIP-fve, an immunomodulatory protein isolated from the edible mushroom Flammulina velutipes, in a murine model of food allergy. METHODS: BALB/c mice were immunized twice intraperitoneally with ovalbumin (OVA), at an interval of 2 weeks. Before and during each period of immunization, FIP-fve (200 microg per mouse) or phosphate-buffered saline was given orally every other day with a total of five doses. Then OVA-specific antibodies and cytokine profiles were determined. Subsequently, the mice were orally challenged with OVA. Symptoms of anaphylaxis, levels of plasma histamine, and histology of intestines were examined. RESULTS: Mice receiving oral FIP-fve treatment during sensitization to OVA had an impaired OVA-specific IgE response with a Th1-predominant cytokine profile. These mice were protected from systemic anaphylaxis-like symptoms induced by subsequent oral challenge with OVA. CONCLUSION: Oral administration of FIP-fve has a Th1-skewing effect on the development of the allergen-specific immune response, and may serve the purpose of immunoprophylaxis for food allergy and other allergic diseases.     

Lack of effect of cimetidine on cigarette smoking

Summary The efficacy of cimetidine as a treatment that could reduce smoking in heavily dependent smokers has been determined. In a randomised, double-blind, double-crossover experiment, 43 heavy smokers were divided into two groups, one receiving cimetidine 400 mg orally three times a day, and the other receiving placebo for two weeks followed by the alternative treatment (placebo or cimetidine).No significant difference in the mean alveolar carbon monoxide, nicotine or cotinine levels was found between the two treatment groups compared to baseline. Since the alveolar carbon monoxide level reflects the intensity of smoking behaviour, the results suggest that no change in smoking behaviour occurred in the subjects.Contrary to our previous findings that cimetidine decreased the total body clearance of nicotine by 30% in a population of non-smokers, in the heavily dependent smokers, cimetidine did not appear to alter nicotine elimination. One possible explanation for the discrepancy is that tobacco smoking is known to induce nicotine metabolism and the induction might have offset any effect of cimetidine on nicotine elimination.Cimetidine does not appear to be a useful treatment leading to a reduction or cessation of cigarette smoking.     

白细胞介素-10诱导的大鼠树突状细胞体外免疫功能的研究

目的　研究白细胞介素 10 (IL 10 )诱导的大鼠未成熟树突状细胞 (imDCs)体外诱导免疫耐受的可行性。方法　在经典诱导方案的基础上 ,应用IL 10 ( 10 μg/L)抑制大鼠骨髓来源DCs的成熟 (IL 10组 ,10例 ) ,并设对照组 (IL 4组 ,10例 )。培养期间观察DCs形态 ,检测DCs表型、摄取抗原能力、体外免疫功能及培养上清细胞因子水平。结果　与IL 4组比较 ,IL 10组DCs细胞表面CD80 、CD86及OX6低度表达 ( 2 5 .3 %、42 .4%、3 2 .3 % ) ,吞噬能力较强 ( 81.9) ,刺激同种异体淋巴细胞增殖能力下降 ,该淋巴细胞具有抗原特异性低反应性 ;培养上清中IL 12水平 ( 4 0 6.5pg/L)及初次MLR培养上清IL 2水平 ( 2 45 .4ng/L)均较低 ,差异有非常显著性 (P <0 .0 1)。 结论　IL 10作用的大鼠imDCs具有诱导免疫耐受的应用价值。     

Hemorrhagic fever with renal syndrome virus infection in livers studied by in situ hybridization and immunohistochemistry

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Acetylcholinesterase Adaptation to Voluntary Wheel Running is Proportional to the Volume of Activity in Fast, but not Slow, Rat Hindlimb Muscles

Chronic enhancement of neuromuscular activity by forced exercise training programmes results in selective adaptation of the G₄ acetylcholinesterase (AChE) molecular form in hindlimb fast muscles of the rat, with only minor and non-selective AChE changes in the soleus. In order to shed further light on the physiological significance of this G₄ adaptation to training, we turned to a voluntary exercise model. The impact of 5 days and 4 weeks of voluntary wheel cage running on AChE molecular forms was examined in four hindlimb fast muscles and the slow-twitch soleus from two rat strains. Inbred Fisher and Sprague– Dawley rats, placed in live-in wheel cages, exercised spontaneously for distances which progressively increased up to an average of ∼3 and 18 km/day, respectively, by the end of week 4. Fast muscles responded to this voluntary activity by massive G₄ increases (up to 420%) with almost no changes in A₁₂, so that by week 4 the tetramer became the main AChE component of these muscles. The additional G₄ was composed primarily of amphiphilic molecules, suggesting a membrane-bound state. The G₄ content of fast muscles was highly correlated with the distance covered by the rats during the 5 days before they were killed ( r = 0.850-0.879, P < 0.001 in three muscles). The soleus muscle, in turn, responded to wheel cage activity by a marked selective reduction of its asymmetric forms—up to 45% for A₁₂. This A₁₂ decline, already maximal by day 5 of wheel cage running, showed no relationship with the distance covered. The present results constitute strong new evidence suggesting that the role of AChE in neuromuscular transmission is not limited solely to the rapid inactivation of just-released acetylcholine.