Effects of fixed-interval duration on the development of tolerance to decreased responding byl-nantradol

The effects of several types of antidepressants in a recently developed behavioural despair model, the tail-suspension test, are described. Drug effects on the automatically recorded duration of immobility and power of movements were measured in three strains of mice. Only in one strain (NMRI) did almost all antidepressants tested showed the expected reduction in duration of immobility. Tranquillizing drugs, but not stimulants, could be distinguished from antidepressants. The power of movements could not definitively be related to the pharmacological profile of the drugs tested. The use of the tail-suspension test as a rapid and highly predictive behavioural primary screen for antidepressant drugs is suggested.     

Effects of ethanol on murine aggression assessed by biting of an inanimate target

The effects of acutely administered ethanol (0, 0.5, 1.0 and 2.0 g/kg, IP) were studied in a tube-restraint/target biting model of aggressive responding using naive group-and individually-housed male Swiss mice. Behavioural measures were the latency to the first bite and the biting frequency. In saline-injected control animals, the levels of responding were significantly higher in group-housed than isolated mice. Animals given alcohol exhibited a dose-dependent suppression of biting frequency, and an increase in biting latency. Mice experienced in the tube-testing situation showed reduced baseline levels of biting, but alcohol produced similar effects to those in naive mice. There was no evidence of a biphasic action of alcohol.     

The impact of DNA damage, genetic mutation and cellular responses on cancer prevention, longevity and aging: observations in humans and mice

Over the past 5 years, data collected from the mouse suggest that pathways important for either preventing or resolving DNA damage are longevity assurance mechanisms whose critical overall function is somatic cell maintenance, a necessary part of cancer prevention. These pathways include those that reduce DNA damage levels caused by exogenous sources, replication errors and by-products of cellular respiration. Unresolved DNA damage leads to permanent mutations in the genetic code that may be oncogenic. Therefore, pathways that resolve DNA damage are important anti-cancer mechanisms. As an important line of defense, there are a variety of pathways that repair DNA damage. In addition, there are anti-cancer pathways that respond to DNA damage by either preventing cellular replication or inducing cell death. Genes in these pathways, termed longevity assurance genes (LAG), code for proteins that reduce cancer incidence and as a result assures a sufficiently long health span needed for reproduction. Data from mouse models, many that were originally designed to study cancer, are showing that a potential consequence of DNA damage and responses to DNA damage is aging; these models support the hypothesis that at least some aspects of normal aging are the consequence of anticancer mechanisms designed to deal with damaged DNA.     

心脏直视手术患儿补体4基因多态性对体外循环中补体激活程度的影响

目的：研究补体4基因多态性与体外循环中补体系统激活程度和肺功能障碍之间的关系。方法：选择武汉市及周边地区在体外循环（CPB）下进行心脏直视手术的患儿156例,于术前抽血用交叉免疫电泳法进行补体4基因型分析。分别于CPB开始前,CPB结束时以及鱼精蛋白中和肝素后10min抽取动脉血样,以放免法对补体3和4活化产物C3a和C4a进行测定。同时记录肺顺应性。结果：补体4基因型AABB,AOBB,OOBB,AABO及AAOO出现频率分别为51．28%,17.95%,4.49%,19.87%及6．41％,CPB结束时C4a水平无明显升高,C3a水平显著升高。鱼精蛋白中和肝素后10min时C4a和C3a水平显著升高,以OOBB组升高最显著,其次为AOBB组;同时OOBB组肺顺应性下降最显著,其次为AOBB组,结论：体外循环由替代途径激活补体系统,鱼精蛋白－肝素复合物由经典途径激活补体系统,国人补体4基因型中,OOBB型出现的频率较白种人高,该基因型在体外循环中补体系统被激活及肺功能受损程度最严重。     

新工艺制备的β—TCP陶瓷小鼠肌肉内种植后的变化

目的：检测新工艺制备的β－磷酸三钙（β－TCP）的生物相容性,方法：将自制β－TCP植入小鼠股后肌袋。术后24,72h,1,2,4,8周分别取材做组织学检查,2,4周取材部分标本做扫描电镜（SEM）观察。结果：随着时间推移,β－TCP逐渐被纤维组织分割包围,但是无软骨,骨和坏死组织形成,结论：新工艺制备的β-TCP具有良好的组织相容性。     

重组人钙调素对白芷细胞增殖及结核杆菌生长的影响

目的 :探讨重组人钙调素 ( rh Ca M)对白芷悬浮细胞及结核杆菌增殖作用的影响。　方法 :用基因重组技术获得人钙调素基因 ( h Ca M c DNA)重组表达质粒 h Ca M / p BV2 2 0 ,将其转化大肠杆菌 DH5α。用 Phenyl-Sepharose CL -4 B疏水亲和层析法纯化重组菌超声上清表达产物。将纯化 rh Ca M加入悬浮培养的白芷细胞及结核杆菌培养基中 ,观察 rh Ca M对其增殖作用的影响。　结果 :含 h Ca M / p BV2 2 0的重组菌经温度诱导可高效表达Ca M蛋白 ,经 15 % SDS-PAGE分析 ,可观察到一相对分子质量为 170 0 0的表达条带 ,Western blot结果证实 ,此表达条带可与标准鼠抗 Ca M Mc Ab起特异反应。每 1L菌液经 Phenyl-Sepharose CL -4 B疏水亲和层析法纯化可获Ca M纯品 3～ 4mg。rh Ca M对白芷细胞增殖作用影响的研究结果表明 ,rh Ca M在低细胞密度培养条件下对白芷细胞有促进增殖作用 ,效果高于标准植物 Ca M。本研究同时还发现一定浓度的纯化 rh Ca M( 1、10μg/ ml)可促进牛型结核杆菌的生长。　结论 :rh Ca M对植物细胞和细菌均有细胞外促增殖作用     

Tumor Necrosis Factor Gene Polymorphism in Chronic Sinusitis

Objectives It is likely that genetic factors play a role in the etiology of chronic sinusitis, and airway inflammation is an important pathological feature in chronic sinusitis. We hypothesized that individuals with greater inflammatory responses may be more likely to acquire the disease. Polymorphisms of the tumor necrosis factor (TNF) genes have been described, and certain inflammatory diseases are reportedly associated with certain alleles of TNF genes. The purpose of this study is to examine whether there is an association between some alleles of TNF genes and chronic sinusitis. Study Design Thirty‐eight Japanese patients with intractable chronic sinusitis were selected on the basis of the following criteria: 1) persistent mucous or mucopurulent nasal discharge and/or postnasal dripping for longer than 3 years and 2) opacification in bilateral maxillary sinuses and ethmoid cells on plain radiographic films. Methods Both tumor necrosis factor‐α (TNF‐α) and tumor necrosis factor‐β (TNF‐β) gene polymorphisms were analyzed by polymerase chain reaction (PCR) with restriction fragment length polymorphisms in these patients and 35 healthy control subjects. Results A significantly higher frequency (P < .05) of TNFB*2 allele of TNF‐β gene polymorphism was observed in patients with chronic sinusitis (74%) compared with control subjects (56%). There was no association between alleles of TNF‐α and chronic sinusitis. Conclusion We concluded that TNF‐β gene polymorphism may form a component of the genetic predisposition to chronic sinusitis in Japanese patients.     

Caffeine enhances the stimulant effect of methamphetamine,but may not affect induction of methamphetamine sensitization of ambulation in mice

Methamphetamine (MAP: 1 and 2 mg/kg SC) and caffeine (CAF: 1, 3, 10 and 30 mg/kg SC) dose-dependently increased ambulation in mice. Repeated administration (5 times at 3 to 4-day intervals) of MAP, but not CAF, induced sensitization to its effect. Furthermore, the mice repeatedly receiving CAF showed no significant change in the sensitivity to MAP. Combined administration of MAP with CAF increased the effect. In the combinations of MAP (1 mg/kg) with CAF (3, 10 and 30 mg/kg), and MAP (2 mg/kg) with CAF (1 and 3 mg/kg), the effect was enhanced by the repeated administration. However, MAP sensitization was not modified by the combination with CAF in the repeated administration schedule, except in the combination of MAP (1 mg/kg) with CAF (30 mg/kg). The ambulation-increasing effects of MAP (1 mg/kg), CAF (10 mg/kg) and combination of MAP with CAF were almost equivalently inhibited by SCH 23390 (0.01 and 0.1 mg/kg SC) and YM-09151-2 (0.01 and 0.1 mg/kg SC). However, the inhibitory effects of apomorphine (0.05 mg/kg SC) andN ⁶-(L-phenylisopropyl)-adenosine (0.1 and 0.2 mg/kg SC) were stronger for CAF than for MAP and the combination, and those of -methyl-p-tyrosine (200 mg/kg IP, 4 h before) and reserpine (1 mg/kg SC, 4 h before) were stronger for MAP and CAF alone than for the combination. The present results suggest that, although the combination of MAP and CAF enhances the ambulation-increasing effect through an interaction at dopaminergic system, CAF may not significantly modify the induction of MAP sensitization in mice.     

p16在肝细胞癌组织内变异的研究

应用分子杂交及免疫组化方法检测５６例ＨＣＣ组织内的抑癌基因ｐ１６。结果显示,ＨＣＣ标本中ｐ１６蛋白在癌细胞内表达的阳性率为３７５％（２１／５６）,而ｐ１６ＤＮＡ斑点杂交的阳性率为５５３６％（３１／５６）。Ｓｏｕｔｈｅｒｎ转膜杂交证实,１２５％（７／５６）ＨＣＣ标本存在ｐ１６的甲基化变异,４４６４％（２５／５６）ｐ１６基因缺失。提示ＨＣＣ发生、发展过程中存在ｐ１６基因的缺失和甲基化变异     

The function of presenilin-1 in amyloid β-peptide generation and brain development

Several mutations in genes that cause the familial form of Alzheimer’s Disease (FAD) have been identified. All mutations in the three FAD genes, i.e., amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2) cause an increased production of a longer, more amyloidogenic form of the amyloid peptide corroborating strongly the idea that abnormal processing of APP is central to the pathogenesis. In PS-1 deficient mice, 80% less amyloid peptide was produced. Instead, membrane associated carboxyterminal fragments generated by α- and β-secretase accumulated suggesting that PS-1 is involved in the gamma-secretase activity cleaving the transmembrane domain of APP after α- and β-secretase cleavage has occured. The clinical mutations in PS-1 which increase the production of βA4_1-42 therefore seem to cause a “selective” gain of its normal function. During cortical plate development in PS-1-deficient mice, neurons do not terminate their movement at the outer margin of the cortical plate, but enter the marginal zone and subarachnoid space. These focal heterotopias closely resemble those occuring, e.g., in human lissencephaly type II. The extracellular matrix of the cortical plate and marginal zone was altered as a consequence of a loss of Cajal-Retzius (CR) neurons from the marginal zone. The pathogenesis of this neuronal migration disorder is associated with a reduction and redistribution of notch-1 immunoreactivity in CR- and cortical plate neurons, a cell surface receptor operative in cell fate selection, which similar to APP is cleaved in its transmembrane domain during activation by a γ-secretase like protease.