Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

Comparison of Marker Intervals and Number of Sib Pairs Used for Linkage Analysis on Simulated Nuclear Family Data

Using a two‐stage global scan design, we analyzed general population replicates 1 and 42 of the Genetic Analysis Workshop (GAW) 12 simulated data set using three methods: revisited Haseman‐Elston (HER), maximum likelihood variance estimation (ML), and variance components (VC). Three marker densities, 5‐, 10‐, and 15‐cM intervals, were examined in the first‐stage scan. We found that the 10‐cM interval appears to be the most cost‐effective approach in genotyping without sacrificing power when using a first stage significance level of 0.01. Subsequently, we performed the second‐stage scan at 1‐cM intervals for those putative positive regions identified in the first‐stage scan at a significance level of 0.01. We also compared the power to detect linkage using different numbers of sib pairs for a genome‐wide scan at a 10‐cM interval and found that power decreases nonlinearly as the number of sib pairs decreases. © 2001 Wiley‐Liss, Inc.     

Development of specificity in corticospinal connections by axon collaterals branching selectively into appropriate spinal targets

Corticospinal projections in adult rodents arise exlusively from layer V neurons in the sensorimotor cortex. These neurons are topographically organized in their connections to spinal cord targets. Previous studies in rodents have shown that the mature distribution pattern of corticospinal neurons develops during the first 2 weeks postnatal from an initial widespread pattern that includes the visual cortex to a distribution restricted to the sensorimotor cortex. To determine whether specificity in corticospinal connections also emerges from an intially diffuse set of projections, we have studied the outgrowth of corticospinal axons and the formation of terminal arbors in developing hamsters. The sensitive fluorescent tracer 1, 1′, dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine perchlorat (DiI) was used to label corticospinal axons from the visual cortex or from small regions of the forelimb or hindlimb sensorimotor cortex in living animals at 4–17 days postnatal. Initially axon outgrowth was imprecise. Some visual cortical axons extended transiently beyond their permanent targets in the pontine nuclei, by growing through the pyramidal decussation and in some cases extending as far caudally as the lumbar enlargement. Forelimb sensorimotor axons also extended past their targets in the cervical enlargement, in many cases growing in the corticospinal tract to lumbar levels of the cord. By about 17 days postnatal these misdirected axons or axon segments were withdrawn from the tract. Despite these errors in axon trajectories within the corticospinal tract, terminal arbors branching into targets in the spinal gray matter were topographically appropriate from the earliest stages of innervation. Thus visula cortical axons never formed connections in the spinal cord, forelimb sensorimotor axons arborized only in the cervical enlargement, and hindlimb cortical axons terminated only in the lumbar cord at all stages of development examined. Corticospinal arbors formed from collaterals that extended at right angles from the shafts of primary axons, most likely by the process of interstitial branching after the primary growth cone had extended past the target. Once collaterals extended into the spinal gray matter, highly branched terminal arbors formed within 2–4 days, beginning at about 4 and 8 days postnatal for the cervical and lumbar enlargements, respectively. These results show that specificity in connectivity is achieved by selectivty growth of axon collaterals in to appropriate spinal targets from the beginning and not by the later remodeling of intially diffuse connections. In contrast, errors occur in the initial outgrowth of axons in the corticospinal tract, which are subsequently corrected. Copyright © 1994 Wiley-Liss, Inc.     

医院感染及漏报率统计分析

目的　了解我院医院感染发生及漏报率。方法　将我院 2 0 0 3年 1～ 12月出院的所有病例进行回顾性调查。结果　医院感染率 7.3 2 %、漏报率 14 .93 %,均符合国家卫生部要求。结论　做好医院感染监测工作 ,严格执行各项工作制度 ,掌握医院感染与手术并发症的鉴别诊断 ,提高医院感染诊断的准确率     

前哨淋巴结活检术应用于外阴癌的初步研究

目的 探讨前哨淋巴结活检术(SLNB)应用于外阴癌的可行性.方法 选择2004年10月-2008年4月间于中国医学科学院肿瘤医院接受手术治疗、术中采用SLNB的外阴癌患者21例,其中处于研究前期(即2005年5月前)的11例患者采用染料法识别前哨淋巴结(SLN)、处于研究后期的10例患者采用核素-染料联合法识别SLN,术后行常规病理检查.以病理检查结果为金标准,观察SLNB的检测效果;并观察与SLNB相关的并发症的发生情况.结果 21例患者中,20例(95%)检出SLN,其中8例为单侧腹股沟、12例为双侧腹股沟.20例SLN阳性患者共检出83枚SLN,每例患者平均检出4.2枚(1～9枚),每侧腹股沟平均2.6枚(1～6枚).其中,染料法每例患者平均检出4.4枚、每侧腹股沟平均2.5枚,核素-染料联合法每例患者平均检出3.9枚、每侧腹股沟平均2.7枚,分别比较,差异均无统计学意义(t=0.459,P=0.652;t=-0.421,P=0.717).20例SLN阳性患者腹股沟浅组淋巴结中均检出SLN,其中1例双侧腹股沟深组淋巴结中也检出SLN.20例SLN阳性的患者中,8例(10侧腹股沟)术后病理检查显示腹股沟淋巴结转移,其中7例患者(9侧腹股沟)的转移淋巴结中均包括有SLN、1例(1侧腹股沟)出现假阴性.以SLN识别预测同侧腹股沟淋巴结转移的假阴性率为10%(1/10),阴性预测值为96%(22/23).未发现与SLNB相关的损伤及不良反应.结论 SLNB应用于外阴癌安全、可行,以SLN预测同侧腹股沟淋巴结转移具有较高准确性.     

视盘血管炎——关于混合型的研讨

对６０例（６３眼）视盘血管炎的临床分型进行了探讨，结果表明，除分为Ⅰ、Ⅱ两型外，尚存在混合型，当视盘睫状血管炎性病变波及中央静脉，或两个血管系统同时受炎症侵犯时，即可再现混合型的临床表现，视盘明显水肿，视网膜静脉迂张，散在渗出，出血，动脉狭细。眼底荧光血管造影可见视盘荧光早期充盈明显迟缓，后期渗漏面积〉２．０ＰＤ，视网膜循环时间延长，混合型兼有Ⅰ，Ⅱ两型的临床特征，应作为一个独立类型存在，同时观察     

UVB radiation induces phosphorylation of the epidermal growth factor receptor, decreases EGF binding and blocks EGF induction of ornithine decarboxylase gene expression in SV40-transformed human keratinocytes

Abstract We previously demonstrated that epidermal growth factor (EGF) induces a several-fold increase in ornithine decarboxylase (ODC) activity and the steady-state level of ODC mRNA in cultured SV40-transformed human keratinocytes (1). Pretreatment of cell cultures with ultraviolet B (UVB) radiation resulted in a reduction of EGF-induced ODC activity. To determine whether UVB inhibits the accumulation of ODC mRNA by EGF, cells were pretreated with 20 mJ/cm² UVB or sham-irradiated and then incubated with 100 ng/ml EGF. Northern blot analysis revealed that UVB irradiation entirely blocked the EGF induction of ODC mRNA. Since the binding of EGF to its plasma membrane receptor is the first step in initiating a biological response, the effect of UVB on EGF binding was evaluated. UVB treatment of cultured keratinocytes resulted in an immediate and dose-dependent reduction of EGF binding. Scatchard analysis revealed thai the reduction of EGF binding was due to a 52% decrease in the number of available receptors, from 6.2 × 10⁴/cell to 3.0 × 10⁴/cell. However, UVB decreased the EGF-binding affinity very little (Kd = 0.60 nM in control and Kd=0.75 nM in UVB-treated Z114 cells). In addition, UVB did not alter the rate of EGF internalization. These data suggest that UVB blocks the signal transduction pathway of EGF that is involved in regulation of ODC gene expression. Immunoblot analysis of extracts from irradiated cells showed that UVB induced tyro-sine phosphorylation of EGFR and that the quantity of EGFR protein was unaffected by UVB treatment. Phosphorylation of EGFR may be responsible for decreased binding of EGF to its receptor.     

A framework for automatic analysis of the dynamic behaviour of coronary angiograms

A framework for coronary vessels analysis in digital subtracted angiograms is described. This method combines the motion estimation with the frame-to-frame structure detection in a natural way such that they act interactively. The first step consists of the extraction of the vessel centrelines in one image and their organization into meaningful constituents or branches of the coronary arterial tree. The motion is then estimated along the centrelines through a gradient based method. These motion estimates supply an initial positioning of an active contour model (or snake) in the next image. This model adapts itself by changing its shape to accurately fit onto the new centrelines. This process is then reiterated on the subsequent images to depict the dynamic behaviour of all the relevant branches. The main interests of this scheme are: (1) the active models operate locally so a fast detection of the vessels can be performed; (2) the centrelines extraction is fully guided by the confluence of the motion estimation and the contour model; (3) both morphological and kinetic features are provided on a quantitative basis.     

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.