Global gene expression profiling in Barrett's esophagus and esophageal cancer: a comparative analysis using cDNA microarrays

In order to identify and contrast global gene expression profiles defining the premalignant syndrome, Barrett's esophagus, as well as frank esophageal cancer, we utilized cDNA microarray technology in conjunction with bioinformatics tools. We hybridized microarrays, each containing 8000 cDNA clones, to RNAs extracted from 13 esophageal surgical or endoscopic biopsy specimens (seven Barrett's metaplasias and six esophageal carcinomas). Hierarchical cluster analysis was performed on these results and displayed using a color-coded graphic representation (Treeview). The esophageal samples clustered naturally into two principal groups, each possessing unique global gene expression profiles. After retrieving histologic reports for these tissues, we found that one main cluster contained all seven Barrett's samples, while the remaining principal cluster comprised the six esophageal cancers. The cancers also clustered according to histopathological subtype. Thus, squamous cell carcinomas (SCCAs) constituted one group, adenocarcinomas (ADCAs) clustered separately, and one signet-ring carcinoma was in its own cluster, distinct from the ADCA cluster. We conclude that cDNA microarrays and bioinformatics show promise in the classification of esophageal malignant and premalignant diseases, and that these methods can be applied to small biopsy samples.     

Restoration of transforming growth factor Beta signaling by functional expression of smad4 induces anoikis

Smad proteins transduce signals carried by the transforming growth factor beta (TGF-beta) cytokine superfamily from receptor serine/threonine kinases at the cell surface to the nucleus, thereby affecting cell proliferation, differentiation, as well as pattern formation during early vertebrate development. Smad4/DPC4, located at chromosome 18q21, was identified as a candidate tumor suppressor gene that is inactivated in nearly half of all pancreatic carcinomas. For functional characterization of Smad4, a recombinant adenovirus encoding Smad4 (Ad-Smad4) was generated. When Smad4 was expressed in Smad4-null breast carcinoma cell line MDA-MB-468 using the recombinant adenovirus, TGF-beta signaling was restored as determined by TGF-beta-dependent activity of plasminogen activator inhibitor 1 promoter and p21 expression. Infection with Ad-Smad4 in the presence of TGF-beta1 also resulted in an altered cell morphology that coincided with enhanced beta1 integrin expression and reduced efficiency of colony formation in soft agar. In agreement with increased p21 expression, Smad4-expressing cells showed modest reduction in S phase. However, Smad4 expression did not lead to induction of apoptosis under normal culture conditions. Interestingly, when Smad4-expressing cells were detached and incubated in suspension, they underwent rapid apoptosis in a TGF-beta-dependent manner. Induction of apoptosis caused by loss of anchorage is known as anoikis. Anoikis is believed to prevent colonization elsewhere of detached cells. Additional characterization revealed an increase in the level of focal adhesion kinase 2 (or Pyk2) and activation of caspases 2, 3, 6, and 8 during anoikis because of Smad4 expression and restoration of TGF-beta signaling. Because resistance to anoikis in tumor cells is thought to contribute to metastasis, our data suggest a functional basis for the strong correlation between defects in Smad4 and development of malignancy.     

Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated demyelinating disease of the central nervous system (CNS). Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catabolizes tryptophan, which can result in the death of T lymphocytes. This effect of IDO is inhibited by 1-methyl-tryptophan (1-MT). We used a murine model of EAE to demonstrate: (1) opposing patterns of spinal cord IDO and interferon-gamma (INF-gamma) mRNA expression through the preclinical, acute and remission I phases of EAE; (2) a change in the kynurenine-to-tryptophan (K/T) ratio during these same phases; and (3) 1-MT-induced exacerbation of clinical and histologic disease parameters during EAE. These results suggest that IDO may contribute to the regulation of T cell activity associated with the different phases of this animal model of multiple sclerosis (MS).     

The effects of sympathectomy on capsaicin-evoked fos expression of spinal dorsal horn GABAergic neurons

In various hypothalamic and adjacent brain regions we have previously found a remarkable increase in nuclear estrogen receptor staining in Alzheimer's disease (AD). In order to see whether this was a general phenomenon or rather specific for those areas that are affected by the AD process we investigated ERalpha and ERbeta expression in the arginine-vasopressin (AVP) neurons of the human dorsolateral suparoptic nucleus (dl-SON), that is the major source of plasma AVP. These neurons remain exceptionally intact in AD. Changes in ER expression were studied in relation to early Alzheimer changes (i.e. hyperphosphorylated tau) and neuronal metabolism in AD as determined by the size of the Golgi apparatus (GA) or cell size. No difference in neuronal metabolism (i.e. GA size or cell size) of AVP neurons was observed between AD and control patients and no early cytoskeletal AD alterations were found confirming the resistance of the dl-SON to AD. While no differences between AD and control patients were present for ERalpha and ERbeta staining except for a lower proportion of nuclear ERbeta AVP-positive neurons in AD subjects, complex sex differences not directly related to AD were observed within each group. The main finding of the present study is that in the dl-SON, that remains active and spared of AD changes, the increase in nuclear ERs seen in adjacent affected areas in AD patients does not occur. This indicates that a rise of nuclear ERs is not a generally occurring phenomenon but rather related to the pathogenetic alterations of the AD process.     

Further identification of NSF* as an epilepsy related gene

Previous data proved that NSF* was an epilepsy related gene (ERG1). In this study, using phosphorothioate oligodeoxynucleotide (PS-ODN), an antisense of NSF to downregulate the function of NSF in vitro cultured hippocampus neurons and PC12, this treatment simultaneously induced enhancement of the neurite outgrowth of hippocampal neurons and PC12, a phenomenon similar to the structural changes following epilepsy. Immunocytochemistry analysis showed that the enhancement of neurite outgrowth was in a sequence-specific manner and Northern blot confirmed that the decrease of NSF mRNA levels in PC12 was in a dose-dependent manner. Moreover the expression of NSF was downregulated during differentiation of PC12 induced by NGF and high KCl. Therefore, providing more evidence to support the fact that NSF was an ERG1.     

法医学鉴定质量管理体系的初步研究

法医学鉴定是运用现代科学技术手段，对诉讼、仲裁等活动中所涉及的专门性问题进行检验、鉴别和判断的活动，具有遵循科学标准和法律规范的双重属性。通过对法医学鉴定管理体系的建立，使法医学鉴定活动全过程（组织、计划、协凋和控制）经常性地处于受控状态，明确法医学鉴定人的资格、资质，规范法医学鉴定的程序、标准，整合现有的法医学鉴定资源，实施法医学鉴定质量管理体系，提高法医学鉴定整体水平服务。     

大鼠脑挫裂伤后海马区神经细胞凋亡及血清NGF的变化

目的探讨大鼠脑挫裂伤后海马区神经细胞凋亡及血清神经生长因子(NGF)的变化及意义。方法按照改良Feeney自由落体脑损伤模型方式制作大鼠左顶叶脑挫裂伤模型,应用酶联免疫吸附法和原位细胞凋亡法,分别对脑挫裂伤后0.5,1,3,6,12,24,72,120,168,240h各时相点血清NGF含量及脑组织细胞凋亡进行检测。结果大鼠脑挫裂伤后24h海马区神经细胞开始出现凋亡阳性细胞(16.50±2.51),72,120h逐渐增多[分别为(17.83±2.04),(23.67±1.51)],168h达到高峰(27.33±1.86),240h开始下降(21.67±2.07);血清NGF含量于脑挫裂伤后3h开始增高[(6.31±1.93)pg/ml],12h达顶峰[(20.57±12.44)pg/ml],24h开始降低[(6.78±3.62)pg/ml],120h接近正常组水平[(3.25±0.81)pg/ml],168,240h回升[分别为(6.59±3.14)pg/ml、(5.92±3.40)pg/ml]。结论大鼠脑挫裂伤后海马区神经细胞凋亡与时间有关,血清NGF含量增高对脑创伤后神经细胞有一定的保护作用,适时使用抗凋亡药物可能对减轻脑创伤后神经细胞损伤有益。     

新生儿缺氧缺血性脑病CT动态表现(附80例分析)

目的提高对新生儿缺氧缺血性脑病CT影像表现的认识,探讨新生儿缺氧缺血性脑病在不同时间段内CT影像的变化。方法收集来我院进行检查的缺氧缺血性脑病患儿80例,最早于产后5小时扫描,最迟于1岁后复查,观察其不同时期CT表现的变化。结果早期(发病0~6天内)主要表现为脑内低密度灶、脑实质水肿以及颅内不同部位出血;中期(发病7~14天)前述病灶表现为部分低密度灶好转、出血吸收;15天后为后遗症表现,局部脑萎缩、软化灶形成,部分轻度病例可表现正常。结论新生儿缺氧缺血性脑病的CT表现随时间变化有其演变过程,正确认识影像表现对临床治疗及预后评估有很大意义。     

上腹部手术患者血清高敏C-反应蛋白和肿瘤坏死因子α水平的变化

目的　探讨上腹部手术患者术后血清高敏C -反应蛋白 (hs-CRP)和肿瘤坏死因子α(TNF -α)的变化及临床意义。方法　采用胶乳增强免疫透射比浊法和ELISA法对 2 0例上腹部手术患者术前、术中 1h、术后 2 4 ,72 ,1 2 0h分别进行hs -CRP和TNF -α含量测定。结果　术后 2 4hhs-CRP含量急剧升高 ,72h达到高峰 ,与各时间点比较 ,差异有统计学意义 (P <0 .0 1 ) ;1 2 0h后迅速下降回落。TNF -α与术前比较差异无统计学意义 (P >0 .0 5)。结论　监测术后hs-CRP含量变化有利于创伤预后判断。     

论孕期科学锻炼

许多西方发达国家常见的妊娠相关疾病或合并症如:妊娠期肥胖、妊娠期糖尿病、妊娠高血压综合症、妊娠期心理障碍等,在我国的发病率明显上升,难产率、病理产率急剧增加.目前,大中城市常规分娩率逐年降低,剖宫产率居高不下,均与孕期缺乏锻炼有关.健康孕妇的科学锻炼对母婴均有利,可以对以上疾病起到有效的防治作用.