Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.     

The insulin‐like growth factor system and sarcomas

Sarcomas are a diverse group of malignant mesenchymal tumours arising from bone and soft tissues. The identification of critical cellular signalling pathways in sarcomas is an important issue for the development of new targeted therapies. This review highlights the experimental and clinical evidence supporting the role of the insulin‐like growth factor (IGF) signalling system in the cellular transformation and progression of several types of sarcoma, including rhabdomyosarcoma, synovial sarcoma, leiomyosarcoma, Ewing's sarcoma and osteosarcoma. Preclinical data suggest that the IGF system could be a promising target for therapy in these sarcomas. Currently, therapies interrupting IGF signalling have been or are being developed. In recent phase 1 clinical studies with humanized monoclonal antibodies directed against IGF receptor type 1 (IGF‐1R), objective tumour responses were observed in several patients with Ewing's sarcoma, encouraging further clinical testing in Ewing's sarcoma and other sarcoma (sub)types. Moreover, the occasional occurrence of paraneoplastic hypoglycaemia as a result of the secretion of incompletely processed forms of pro‐IGF‐II by sarcomas is discussed. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

松质骨中两种纵波的传播特性分析

基于松质骨的层状模型，利用Schoenberg理论分析了松质骨中两种纵波(快纵波和慢纵波)的传播特性；并在理论和实验上详细分析了骨小梁方向与传播方向间的夹角对松质骨中快纵波和慢纵波传播特性的影响。分析结果表明，当超声波平行于骨小梁入射时，松质骨中两种纵波都传播，入射角度在60度附近时，松质骨中两种纵波的相速度曲线有一个转折点，入射角度在60度以上，角度越大时，骨髓和骨小梁耦合得越紧，因此阻止了慢纵波的传播，而只有快纵波传播。     

藏汉民族线粒体基因组全序列的比较研究

目的 以藏汉民族线粒体基因组全序列为基础,进行Haplogroup构建和系统发生分析,在全序列水平上比较核苷酸的变异,阐释可能的变异机制和蕴含的生物学意义.方法 采用Applied Biosystems 3730DNA自动测序仪分别对40名藏族和50名汉族的标本进行线粒体DNA序列测定,应用phredPhrap 16.0软件进行全序列拼接,并以rCRS(revised Cambridge Reference Sequence)为标准与测定序列进行比对分析;根据MTTO-MAP的标准,通过Network方法进行Haplogroup构建和系统发生的分析,并结合其它方法对产生的数据进行深入解读.结果 数据分析结果显示:在系统发生上,藏汉民族90个线粒体DNA序列归类到13个Haplogroups,除M9以外,其它各Haplogroup出现频率之间比较差异无统计学意义;通过两个民族的线粒体DNA全序列比对,发现21个分布频率有统计学意义的变异位点,其中的5个为新变异位点;另外,对D-Loop区的5个突变位点进行了单倍型构建,90个标本可分为2种Supertype,发现在藏汉民族之间Supertypel和Supertype 2的分布频率均有统计学意义.结论 藏汉民族在种族起源和系统发生上具有较近的母系遗传关系;在全序列有统计学意义的位点究竟是适应性或者中性选择,抑或是一种病理性突变尚需深入的探讨.     

An Analytic Model of Subminiature Auditory Sensation System for Sound Source Localization

It is reported that some types of insects have a remarkable ability to detect the direction of an incident sound even though its acoustic sensory organs are in very close proximity each other. Maybe the ears are jointed by a cuticular structure with which the separated motions can be coupled mechanically and thus be magnified. In this paper, a detailed model is setup to describe the principle of this type of localization using a mechanical coupled structure. The transfer functions and the responses of the model in terms of time and frequency are analyzed to describe the mechanism of its ability of directional hearing. This analytical model provides a method to design the experimental model for the predetermined incident sound pressure, and the analysis of this model shows that this structure have the ability to determine the direction of the incident stimulus.     

超声背散射系数评价松质骨状况的可行性研究

目的研究超声背散射信号及其背散射系数（backscatter coefficient,BSC）评价松质骨状况的可行性。方法首先建立了一种蜂窝状的松质骨理论模型,然后将BSC与频率的理论关系和牛胫骨松质骨实验结果进行了比较;最后实验分析了BSC与松质骨表观密度的关系。结果松质骨中超声BSC随入射频率的增加而非线性的增加,理论模型和实验结果是一致的。随松质骨表观密度的增大,BSC增大。结论在用超声评价松质骨状况时,背散射信号具有重要作用,其BSC可用于评价松质骨状况。     

基于反向滤波器的倒谱法估计平均骨小梁间距

目的 探讨用改进的倒谱方法估计平均骨小梁间距(mean trabecular bone spacing,MTBS)的可行性.方法 提出了一种基于反向滤波器的改进的倒谱分析方法用于估计MTBS,并将该方法应用于仿真及离体牛胫骨松质骨中的实验信号.结果 改进的倒谱方法能有效减少超声换能器脉冲响应和组织散射特性对倒谱的干扰,而且实现简单,计算量小.结论 相比于传统的倒谱方法,改进的倒谱方法在估计MTBS时, 对弥散散射和噪声有更强的鲁棒性,因此估计MTBS的精度更高.     

曲马多对母婴乳酸盐和新生儿神经行为的影响

目的　研究曲马多对母婴血乳酸盐和新生儿神经行为与适应能力评分 (NACS)的影响。方法　 6 0例足月妊娠剖宫产产妇随机分三组 :T0 组 ,2 0例 ,肌注 0 9%氯化钠 2ml;T1组 2 0例 ,肌注曲马多 1 5mg/kg ;T2 组 ,2 0例 ,肌注曲马多 2mg/kg。各组肌注后开始麻醉 ,三组均采用脊麻与硬膜外联合阻滞。观察指标 :新生儿生后 15min的Apgar评分及新生儿生后 15min的NACS ;胎儿娩出时采脐动、静脉血和母体动脉血各 2ml,行血乳酸值测定及血气分析。结果　三组新生儿Apgar评分无明显差异 ,T0 组NACS明显高于T1组 (P <0 0 5 )和T2 组 (P <0 0 1) ;T2 组脐动、静脉血乳酸值明显高于T1组 (P <0 0 5 )和T0 组 (P <0 0 1) ;母体乳酸值三组间无明显差异 ;T2 组母体和脐动、静脉血PaCO2 明显高于T0 组 (P <0 0 1) ,T2 组脐动、静脉血SaO2 明显低于T0 组 (P <0 0 5 )。结论　剖宫产术前肌注曲马多 1 5mg/kg对新生儿无明显不良影响。但 2mg/kg曲马多肌注具有呼吸抑制作用 ,使脐动、静脉血乳酸盐增加 ,对新生儿NACS有一过性影响     

Nonhuman primates express human leukemia-associated antigens

Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation.     

臂丛神经根性损伤膈神经移位术对青壮年患者早期呼吸功能的影响

目的研究臂丛神经损伤膈神经移位术对青壮年患者早期呼吸功能的影响.方法对16例接受膈神经移位治疗的患者,在术前、术后（10 d）进行肺功能指标的比较,同时定期进行门诊随访,观察呼吸系统自觉症状程度.结果13例术后出现了不同程度的供氧不足症状,16例全部出现一侧膈肌抬高,术后第10天肺活量（VC）、肺活量预计值百分数（VC%）分别比术前减少37.98%和26.88%,两者差异有统计学意义（tvc=11.532、tvc%=0,P＜0.01）.其它项目如残气量（RV）较术前轻度下降,肺总量（TLC）下降值达到术前肺总量的36.49%,残气量/肺总量比值（RV/TLC%）较术前上升了4.75%,上述各指标的差值均有统计学意义.1 s用力呼气量/用力肺活量比值（FEV1/FVC）和术前比基本无改变,但其差值有统计学意义.膈神经移位右侧（10例）与左侧（6例）术前、术后肺活量比较差异有统计学意义.术后随访8个月～2年,所有患者均无明显呼吸困难和胸闷等症状.结论膈神经移位术后对青壮年患者肺容量有较大的丧失,肺通气功能减弱和小气道阻力增加,但其丧失程度在机体自身代偿耐受范围内,不会导致急剧发生的严重呼吸功能障碍.建议对右侧臂丛神经根性损伤的患者,术前进行严格的肺、心功能检查,避免发生较为严重的并发症.