Reduced expression of tissue inhibitor of metalloproteinase (TIMP)-2 in gestational trophoblastic diseases

To elucidate the involvement of type IV collagenases [matrix metalloproteinase (MMP)-2 and MMP-9] and their tissue inhibitors (TIMP-1 and TIMP-2) in the development of gestational trophoblastic disease (GTD), we quantified their levels in hydatidiform mole and choriocarcinoma tissues using specific enzyme-linked immunosorbent assays, and the results were compared with those from normal first trimester placenta. Levels of pro-MMP-2 were increased in hydatidiform mole, and they were further elevated in choriocarcinoma. Levels of pro-MMP-9 in choriocarcinoma and those of TIMP-1 in both hydatidiform mole and choriocarcinoma were also increased. In contrast, TIMP-2 levels were markedly decreased in both hydatidiform mole and choriocarcinoma. Similar results were obtained by the tissue culture of first trimester placenta and hydatidiform mole. Gelatin zymography indicated that the levels of both pro- and activated forms of MMP-2 and MMP-9 were higher in hydatidiform mole and choriocarcinoma. The decreased expression of TIMP-2 in hydatidiform mole and choriocarcinoma was confirmed by Western blot, Northern blot and immunohistochemistry, with the decrease being more pronounced in choriocarcinoma. Taken together, the present study shows that both TIMP-2 mRNA and protein levels are markedly decreased in GTD and the imbalance of MMP-TIMP production, shifted toward greater MMP activity, may be involved in the pathogenesis of GTD.     

Operation Everest II: Alterations in the immune system at high altitudes

We investigated the effects on immune function after progressive hypobaric hypoxia simulating an ascent to 25,000 ft (7620 m) over 4 weeks. Multiple simultaneousin vitro andin vivo immunologic variables were obtained from subjects at sea level, 7500 ft (2286 m), and 25,000 ft during a decompression chamber exposure. Phytohemag-glutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells were reduced at extreme altitudes. Mononuclear-cell subset analysis by flow cytometry disclosed an increase in monocytes without changes in B cells or T-cell subsets. Plasma IgM and IgA but not IgG levels were increased at altitudes, whereas pokeweed mitogen-stimulatedin vitro IgG, IgA, and IgM secretion was unchanged. During exposure to 25,000 ft,in vitro phytohemagglutinin-stimulated interferon production and natural killer-cell cytotoxicity did not change statistically, but larger intersubject differences occurred. IgA and lysozyme levels (nasal wash) and serum antibodies to nuclear antigens were not influenced by altitude exposure. These results suggest that T-cell activation is blunted during exposure to severe hypoxemia, whereas B-cell function and mucosal immunity are not. Although the mechanism of alteredin vitro immune responsiveness after exposure to various environmental stressors has not been elucidated in humans, hypoxia may induce alterations in immune regulation as suggested byin vitro immune assays of effector-cell function.Some of this study's results were presented as an abstract at the FASEB meeting in St. Louis, Missouri, 1986.     

甲襞、球结膜微循环的应急观测方法

甲襞、球结膜微循环的应急观测方法是在甲襞、球结膜微循环加权积分综合定量评价方法的基础上，保留权值为４、３的指标，同时观察血管清晰度和红细胞聚集二项指标而形成。同时提供其应急观测积分表、异常分度积分值、诊断标准，并与常规方法进行比较，证明其可以反映绝大部分流态类指标和大部分形态类指标及重要的袢周改变，没有丢失微循环重度异常的信息，保证了重度异常诊断的正确。但在大致正常、轻度异常和中度异常的诊断中应急方法部有判重的倾向，说明应急方法漏掉了一些信息，不能全面地了解微循环的改变，造成了判重的倾向。因此应急方法不能代替常规方法，只能在特定条件下应用。     

PBX1基因剪切体表达与SLE的相关研究

了解PBX1基因各种剪切体的表达在SLE患者和正常人中是否存在差异 ,探讨PBX1的表达与SLE发病的相关性。通过PCR扩增及毛细管芯片电泳 ,确证剪切体h、k、l存在于人体 ;通过实时荧光定量PCR技术 ,对剪切体h、k、l分别进行SLE患者组和正常组的mRNA表达定量比较。结果发现这 3种剪切体在患者组中的表达较正常人明显降低 ,正常人的表达是SLE的 9～ 12倍。重度患者的k、l剪切体与轻中度的病人相比表达明显降低 ,并发狼疮性肾炎的病人k剪切体的表达较无肾累及的病人显著降低。说明PBX1基因剪切体h、k、l在SLE患者中mRNA表达水平下降 ,并与SLE活动度及肾累及有关。提示机体通过PBX1的表达量的调节可能参与SLE的发病     

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。     

Further evidence for excitability changes in human primary motor cortex during ipsilateral voluntary contractions

The present study aimed to further investigate whether the intracortical neural circuits within the primary motor cortex (M1) are modulated during ipsilateral voluntary finger movements. Single- and paired-pulse (interstimulus intervals, ISIs; 3 ms and 12 ms) transcranial magnetic stimulations of the left M1 were applied to elicit motor evoked potential (MEP) in the right first dorsal interosseous (Rt-FDI) muscle during voluntary contractions (10% and 30% maximum voluntary contraction) of the left FDI (Lt-FDI) muscle. F-waves of Rt-FDI muscle were recorded under these left index-finger conditions for ensuring that the excitability changes occur at the supraspinal level. MEPs were also recorded during motor imagery of the left index-finger abduction instead of overt movement. The results showed that, in single-pulse transcranial magnetic stimulation (TMS) paradigm, MEPs in Rt-FDI muscle were markedly enhanced during voluntary contractions of Lt-FDI muscle compared with the complete resting state. In paired-pulse TMS paradigm, the short intracortical inhibition was significantly reduced in proportion to increments of the ipsilateral muscle contraction, whereas the intracortical facilitation had no change. F-wave of Rt-FDI muscle was unchanged under these conditions, while MEP in Rt-FDI muscle was also enhanced during motor imagery of the left index-finger abduction. Based on the present results, it is suggested that the intracortical inhibitory neural circuits may be modulated in the transition from rest to activity of the ipsilateral homonymous muscle. The excitability changes in M1 might be induced by overflows of voluntary drive given to the ipsilateral limb, probably via the transcallosal pathway.     

Ganglioglial Differentiation in Medulloblastoma

A case of cerebellar medulloblastoma with clusters of mature ganglion cells and glial cells is described. The patient, a 15 -year -old girl, underwent three operations followed each time by radiation and chemotherapy during the four-year clinical course. Histologically, the ganglion cells were clearly identifiable by their abundant eosino-philic cytoplasm, round nuclei with prominent nucleoli, tigroid granules, and argyrophilic fibrils and axons. Im-munohistochemically, the cells were NSE- and NF positive, and ultrastructurally they contained abundant tubules and filaments, neurosecretory granules and well developed rough endoplasmic reticulum. There were many cells transitional in appearance between primitive cells and mature ganglion cells. The tumor also had many mature yet atypical astrocytes and oligodendrocytes. The exact mechanism of the extensive neuronal and glial maturation of medulloblastoma cells is unclear, but the repetitive surgical interventions, radiation and chemotherapy might have had certain cytostatic effects on rapidly dividing medulloblastoma cells, giving them a chance to mature into postmitotic cells with potential for neuronal and glial differentiation. Acta Pathol Jpn 40: 50–56, 1990.     

晶状体膜蛋白MIP基因C末端一个新的错义突变导致双眼多形性先天性白内障

目的 定位一个双眼多形性先天性白内障家系的致病位点,寻找疾病家系的致病基因.方法 应用ABI-MD10试剂盒中的常染色体382个微卫星位点,对一个常染色体显性、双眼具有不同白内障形态的先天性白内障家系进行全基因组扫描.MLINK软件进行两点连锁分析.直接测序候选基因外显子.结果 在D12S83处获得最大LOD值Zmax=5.44(θ=0),该家系致病位点被定位到12p11.2-q15之间的区域上,在该区域的白内障候选基因晶状体膜蛋白基因(major intrinsic protein,MIP)的第4外显子中发现单个碱基错义突变,702ntG→A,导致p.R233K.结论 该先天性白内障由MIP基因702ntG→A突变所致,导致MIP蛋白质的C-末端中p.R233K,从而可能减少了氢键的形成,影响了该蛋白C-末端的稳定性,推测影响了MIP对水的调节及由该蛋白质形成的细胞之间的连接.这一新突变为目前世界上首次报道.