米非司酮终止中期妊娠时胎盘循环与超微结构的变化

观察３０例妊娠１６～２４周需终止妊娠者服用米非司酮前后子宫动脉和脐动脉血流速度波型的变化，并用电镜观察了５例胎盘微血管的改变。结果：服用米非司酮后，子宫动脉阻力指数（ＲＩ）和Ｓ／Ｄ比值及脐动脉的Ｓ／Ｄ比值较用药前明显增高，胎盘微血管壁有损伤性表现。提示：子宫胎盘循环动力学的变化及胎盘微血管的损伤可能是米非司酮终止妊娠的重要环节。     

实验性自身免疫性甲状腺炎小鼠细胞免疫状态研究

作者检测了实验性自身免疫性甲状腺炎(EAT)小鼠的细胞免疫状态,结果表明:EAT小鼠脾细胞Thy-1.2和Lyt-2阳性T细胞数显著下降并伴随L3T4/Lyt-2阳性T细胞数比值升高;甲状腺球蛋白刺激的淋巴细胞增殖明显增强,但NK细胞活性无显著变化;脾细胞产生TNF和IL-1的水平明显高于正常小鼠。提示T细胞免疫功能紊乱和细胞因子的大量释放可能是引起此病的重要因素。     

Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage- derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage- derived cell line was sensitive to the growth inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.      

Cholera toxin induces synthesis of phospholipase A2-activating protein.

The mechanism of cholera toxin (CT)-stimulated arachidonate metabolism was evaluated. CT caused rapid in vitro synthesis of prostaglandin E2 (PGE2) in murine smooth muscle-like cells (BC3H1), reaching maximal levels within 3 to 4 min. In comparison, cyclic AMP (cAMP) levels were unchanged, and addition of dibutyryl cAMP did not affect PGE2 synthesis. CT-induced PGE2 synthesis was prevented by actinomycin D or cycloheximide, indicating a need for de novo protein synthesis. Northern blot analysis of total RNA from BC3H1 cells revealed that exposure to CT resulted in an increase in abundance of mRNA encoding phospholipase A2 (PLA2)-activating protein (PLAP). PLAP is a regulatory protein that increases the enzymatic activity of cellular PLA(2), which in turn causes increased hydrolysis of arachidonate from membrane phospholipids. Furthermore, CT evoked the accumulation of PLAP mRNA in J774 (murine monocyte/macrophage) and Caco-2 (human intestinal epithelial) cells in vitro, but the responses were more delayed than that of BC3H1 cells. A protein band of approximately 35 kDa, which corresponded to the size of PLAP, was observed in sodium dodecyl sulfate extracts of Caco-2 cells by Western blot (immunoblot) analysis using affinity-purified antibodies to PLAP synthetic peptides. Synthesis of PLAP protein was increased after 2 h of exposure to CT. Exposure of mouse intestinal loops to either CT or live Salmonella typhimurium for 3 h increased mucosal PLAP mRNA levels. The role of PLAP in CT-induced PGE2 synthesis provides an attractive explanation for the reported suppression of CT-induced intestinal secretion by inhibitors of protein synthesis.     

Primary structure of human amphiphysin, the dominant autoantigen of paraneoplastic Stiff--Man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14

Amphiphysin is a protein peripherally associated with synapticvesicles. It is expressed in many neurons, certain endocrinecell types, and spermatocytes. Autoantibodies against amphiphysinoccur in patients afflicted with a rare neurologic autoimmunedisease, paraneoplastic Stiff—Man syndrome. To providea basis for the understanding of antl-amphiphysin autolmmunity,we have cloned cDNAs and determined the primary structure ofhuman amphiphysin. Comparison with chicken amphiphysin definesdomains of low and high amino acid sequence conservation. Asa candidate for heritable disorders of the nervous system, endocrinetissues or male fertility, the human amphiphysin gene was mappedto chromosome 7, region p13–p14.     

Effect of silicon carbide whisker-silica heat treatment on the reinforcement of dental resin composites

The strength and fracture resistance of dental resin composites need to be improved to extend their use to large stress-bearing crown and multiple-unit applications. Recent studies showed that the addition of ceramic whiskers significantly reinforced resin composites. The aim of the present study was to use a silicon carbide whisker-silica particle mixture to reinforce resin composites, and to investigate the effect of whisker-silica mixture heat-treatment on composite properties. The whiskers were blended with silica particles and were thermally fused in an attempt to roughen the whiskers for improved retention in the matrix. The mixtures were heat-treated at temperatures of 500, 650, 800, 950, and 1100 degrees C for 10 min, 30 min, and 3 h. The mixtures were then silanized, incorporated into a dental resin, and the paste was placed into 2 x 2 x 25 mm molds and heat-cured at 140 degrees C for 30 min. A 3-point flexural test was used to measure flexural strength and work-of-fracture. Two commercial indirect composites were tested as controls. Two-way ANOVA showed that there was no significant effect from temperature or time. Therefore, all the whisker-silica mixture samples were combined into one group (n = 96), and compared to composites filled with silica only or whisker only, and the two indirect control composites. The whisker-silica mixture group had a flexural strength (mean +/- SD) of (186 +/- 24) MPa, significantly higher than (99 +/- 29) MPa for silica only, (131 +/- 22) MPa for whisker only, and (109 +/- 23) MPa and (114 +/- 18) MPa for the two indirect composites (Tukey's multiple comparison test; family confidence coefficient = 0.95). Similar results were obtained on work-of-fracture. Scanning electron microscopy revealed rough fracture surfaces for the whisker-silica composites, indicating crack deflection and bridging by whiskers as toughening mechanisms. Whisker-silica mixture minimized whisker entanglement and enhanced whisker-resin bonding, resulting in substantially stronger and tougher dental resin composites.     

围产期母亲和胎儿心动周期信号分析

同时分析围产期胎儿和孕妇心动周期信号的数字特征(混沌和谱特征)以评价自主神经系统功能。用可视化程序设计的方法实现提取和分析围产期母亲和胎儿心动周期信号。受试者取仰卧位，心电信号从置于腹壁下部耻骨联合导联获得。胎儿心电信号用小波分解进行信号预处理。采用本实验室已经完成开发的技术实现心动周期信号数字特征的分析。该系统可以评价胎儿和孕妇的自主神经系统功能，特别是分别定量评价交感和副交感神经系统功能；该系统还可用以预测胎儿窘迫。胎儿和其它年龄段的心动周期信号数字特征随年龄的变化提示了自主神经系统的发育、成熟和衰老的生理过程，基于这一点我们可以寻找抗衰老的方法；胎儿的心动周期信号数字特征介于新生儿和成人之间，提示胎儿的自主神经系统的调节可能受母体神经内分泌系统的影响。     

Altered feeding responses in mice with targeted disruption of the dopamine-3 receptor gene

Dopamine signaling has been implicated in the control of food intake and body weight. In particular, dopamine is important in the control of meal size and number and is thought to mediate the response to metabolic deprivation states. In the present experiments, the authors assessed the role of the dopamine-3 receptor (D3R) in the feeding responses to 2-deoxy-D-glucose, mercaptoacetate, and peripheral insulin. All 3 compounds increased food intake in wild-type mice, but the hyperphagic responses were blunted in D3R-/- mice. In other experiments, D3R-/- mice were hyperresponsive to the administration of amylin and leptin relative to wild-type mice. These results support the hypothesis that D3Rs chronically inhibit the effects of adiposity hormones, thereby contributing to a net anabolic state.     

Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors

The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis. We therefore sought to determine whether ACTRII was involved in non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9 (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one (14.3%) of the seven LOH-positive primary tumors from which total RNA was available. We also performed DNA sequencing analysis of tumors showing LOH. One LOH-positive primary tumor exhibited a novel germline missense sequence alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23 additional normal individuals, implying that this alteration is not a frequent polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup.