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.     

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     

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.     

糖尿病肾病患者治疗前后AT-Ⅱ,VEGF,ET和ANP水平变化

目的 :检测糖尿病肾病 (DN)患者治疗前后血管紧张素Ⅱ (AT -Ⅱ )、血管内皮生长因子(VEGF)、内皮素 (ET)和心钠素 (ANP)含量变化 ,以比较不同药物的治疗效果。方法 :对象为DN患者分为 2组 :中药治疗观察组 35例 ;对照组 35例 ;正常对照组 35例。用放免法和ELISA法分别测定治疗前后血浆AT -Ⅱ、VEGF、ET和ANP水平。结果 :2组DN患者治疗前AT -Ⅱ、VEGF、ET和ANP含量均明显高于正常对照组 (p <0 0 5～ 0 0 1) ,治疗后较治疗前明显降低 (p<0 0 5～ 0 0 1)。观察组治疗后各含量下降较对照组明显。糖尿病肾病患者AT -Ⅱ含量与VEGF呈正相关 (r=0 4 6 5 ,p<0 0 5 ) ,血浆ET含量与ANP呈正相关 (r=0 6 1,p <0 0 5 ) ,观察组疗效稍好于对照组。结论 :AT -Ⅱ、VEGF、ET和ANP与DN的发生发展和病情的严重程度有关 ,它们之间可相互作用共同参与DN病变过程。以它们的指标作为疗效观察 ,中西药结合治疗糖尿病肾病患者效果较好。     

纤维蛋白原与吸附白蛋白、肝素的新型血管支架材料氧化钛的血液相容性

探索纤维蛋白原(Fibrinogen,FIG)与吸附白蛋白、肝素的新型血管支架材料氧化钛(Titanium Oxide,Ti-O)的血液相容性。(1)研制Ti-O,切割成薄膜;(2)Ti-O薄膜涂层白蛋白和肝素;(3)血小板(platelet,PL)吸附试验;(4)酶联免疫试验测FIG吸附量;(5)动物犬股动脉内植入涂层的Ti-O薄膜与对照试片Ti-O和不锈钢(Stainless steel,SS)薄膜。结果发现:Ti-O完全具有固定白蛋白和肝素的结构与性能,比未涂层的Ti-O能更一步减少PL和FIG的吸附,实验动物体内薄膜6个月后取出扫描电镜观察黏附的PL少,形态无改变,血管内无血栓,优于未涂层的Ti-O,更明显优于SS。Ti-O为N型半导体,不易接受FIG的电荷,并且与血细胞有相似的界面张力,决定生物材料Ti-O有较好的血液相容性。Ti-O对白蛋白、肝素有极好的亲和力是因以化学键相结合,在血中进一步减少FIG和PL被涂层的Ti-O吸附。实验证明涂层的Ti-O有持久和稳定的抗凝血性能。     

抗CD3单克隆抗体重、轻链可变区基因的克隆及序列分析

目的：抗CD3单克隆抗体（WuT3)可变区基因克隆及序列分析。方法；采用RT-PCR技术，从WuT3杂交瘤细胞总RNA中扩增VH，VL片段，经酶切后通过链接反应构建重组克隆载体，测序鉴定。结果：通过国际联机检索发现VH，VL基因与Ig同源，分别符合小鼠IgVH,Vк基因特征。VH基因属于鼠重链VH第ⅡB亚类，全长363bp，可编码121个氨基酸；VL基因属于鼠к轻链第Ⅲ亚类，全长330bp，可编码110个氨基酸，结论：成功获得WuT3单抗的重，轻链可变区基因。