髓母细胞瘤比较基因组杂交分析及ERBB-2异常表达的意义

目的研究髓母细胞瘤全基因组的遗传学异常,探讨癌基因的异常表达在髓母细胞瘤发病机制中的作用以及与预后的关系。方法应用比较基因组杂交（comparative genomic hybridization,CGH）技术检测14例髓母细胞瘤全基因组的遗传学改变;同时,在扩大系列的29例髓母细胞瘤中,应用荧光原位杂交（fluorescence in situ hybridization,FISH）和免疫组化染色分别检测ERBB-2在基因水平和蛋白水平的表达。结果（1）CGH结果显示,在所有14例髓母细胞瘤标本中,每一条染色体臂上都检测到了染色体的失衡（获得或丢失）,最常见的染色体异常为17q（85．7％）和7q（35．7％）的获得,以及8p（50％）、16q（28．6％）和17p（35．7％）的丢失;（2）FISH检测中,44．5％（13／29例）的肿瘤细胞有ERBB-2基因的异常表达;（3）免疫组化结果显示,37．9％（11／29例）的病例有抗体c-erbB-2的阳性表达;（4）在预后较差的16例患者中,56％（9／16例）的病例有ERBB-2的过度表达。结论CGH研究发现了髓母细胞瘤全基因组的染色体失衡。在染色体17q特异性位点上ERBB-2基因的异常改变很可能在髓母细胞瘤的发病机制中起着重要的作用,其过度表达与患者的预后密切相关。     

免疫组织化学和电镜在腹膜间皮瘤和浆液性癌鉴别诊断中的价值

上皮样间皮瘤，特别是那些呈乳头状和管状乳头状生长的间皮瘤，与原发性或转移性浆液性乳头状癌弥漫累及腹膜者很难鉴别。1998年一个研究报道有16种标记在间皮瘤的诊断中有一定的价值，该项研究认为，calretinin、thrombomodulin和CK5／6是间皮瘤最好的诊断指标，MOC-31、B72．3、Ber—EP4、CA19—9和Leu—M1（CD15）在间皮瘤中表达阴性，可用于区分腹膜上皮样恶性间皮瘤和乳头状浆液性癌弥漫累及腹膜。D2-40和podoplanin是2个最近认识的淋巴管内皮细胞标记物，它们也表达于正常间皮细胞和间皮瘤。为了比较这两种新的间皮细胞标记和以前其他用于间皮瘤和浆液性癌鉴别诊断的标记的特异性，     

软骨组织工程中力学因素的影响及应用

力学因素是软骨组织工程中的重要影响因素之一。近年来的研究表明，力学作用可以刺激细胞因子及激素的分泌，改变三维支架上培养的软骨细胞的新陈代谢，从而促进软骨组织的生长与重建。目前已经有诸多关于体外构建软骨组织的报道，但对于其中的力学因素的影响（包括力学因素对软骨细胞增殖的促进及力学刺激的传导机制等）还没有完全认识。就以上几方面做一综述，并简单介绍生物反应器在软骨组织工程中的应用。     

透皮给药研究的新进展

透皮给药安全可控，是无创给药的新途径，有着广阔的市场前景。现有的透皮药物限于小分子和低浓度，角质层屏障使大多数药物难以通过或难以达到有效浓度和有效速率。透皮给药的关键在于促进药物渗透，使药物透皮吸收进毛细血管。促渗手段有：使用化学促渗剂；对药物进行化学修饰制成前体药物；使用物理方法；将药物载入载体。这些方法的原理大致分为三种：改变角质层结构；外力驱动药物；将药物进行修饰或包裹。简要地介绍了增强药物透皮的物理方法和载体方法研究的新进展。     

Ki67 LABELLING INDEX: AN INDEPENDENT PREDICTOR OF PROGRESSION IN PROSTATE CANCER TREATED BY RADICAL PROSTATECTOMY

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. Both tumour cell proliferation and neuroendocrine differentiation have been suggested as additional prognostic parameters, neuroendocrine differentiation being considered to enhance tumour cell proliferation. This study investigated the prognostic value of tumour cell proliferation [Ki67 labelling index (LI), MIB 1] and neuroendocrine differentiation and their relationship to each other. One hundred and thirty-seven paraffin-embedded radical prostatectomy specimens were examined. Neuroendocrine differentiation was found in 58 per cent of cases, but was not associated with pTN stage, Gleason score, Ki67 LI, or tumour progression. Ki67 LI was not significantly associated with pTN stage or with Gleason score. High grade ( P =0·0005), advanced local stage ( P =0·0004), positive lymph nodes ( P =0·02), and high Ki67 LI ( P =0·0203) were predictors of tumour progression if univariate analysis was performed, but Cox stepwise regression showed that only advanced local stage ( P =0·0025) and Ki67 LI ( P =0·0105) were independent predictors of tumour progression, the relative risk being 3·6 and 2·5, respectively. It is concluded that Ki67 is an important prognostic marker in prostate cancer with a potential for routine application.     

THE SIGNIFICANCE OF B-CELL CLONALITY IN GASTRIC LYMPHOID INFILTRATES

The significance of the demonstration of a clonal B-cell population in gastric lymphoid infiltrates was investigated by analysis of immunoglobulin heavy chain (IgH) gene rearrangements using sensitive polymerase chain reactions, employing fluorescently labelled primers to target the FR3 and FR1 regions. Tissue blocks were studied showing different histological features (high-grade lymphoma, low-grade lymphoma, and chronic gastritis) from 12 gastrectomies for primary gastric lymphoma, together with blocks showing chronic gastritis from 13 cases of gastric adenocarcinoma and biopsies from 33 patients with active Helicobacter -associated chronic gastritis. Clonal IgH gene rearrangements were detected in lymphoma samples from eight of the gastrectomies for lymphoma (67 per cent). In four of these eight specimens, clonal rearrangements were also detectable in the samples showing only chronic gastritis. Three of 28 (11 per cent) informative biopsies showing active Helicobacter -associated chronic gastritis had detectable clonal populations. Clonal rearrangements were also demonstrated in two of eight (25 per cent) informative blocks showing chronic gastritis from eight gastrectomies for adenocarcinoma. It is concluded that the detection of a clonal population in a suspicious lymphoid infiltrate does not confirm the diagnosis of lymphoma, nor does the absence of such a population imply benignity.     

Spontaneous Mucosal Lymphocyte Cytokine Profiles in Children with Autism and Gastrointestinal Symptoms: Mucosal Immune Activation and Reduced Counter Regulatory Interleukin-10

A lymphocytic enterocolitis has been reported in a cohort of children with autistic spectrum disorder (ASD) and gastrointestinal (GI) symptoms. This study tested the hypothesis that dysregulated intestinal mucosal immunity with enhanced pro-inflammatory cytokine production is present in these ASD children. Comparison was made with developmentally normal children with, and without, mucosal inflammation. Duodenal and colonic biopsies were obtained from 21 ASD children, and 65 developmentally normal paediatric controls, of which 38 had signs of histological inflammation. Detection of CD3⁺ lymphocyte staining for spontaneous intracellular TNF, IL-2, IL-4, IFN, and IL-10, was performed by multicolor flow cytometry. Duodenal and colonic mucosal CD3⁺ lymphocyte counts were elevated in ASD children compared with noninflamed controls (p<0.03). In the duodenum, the proportion of lamina propria (LP) and epithelial CD3⁺TNF⁺ cells in ASD children was significantly greater compared with noninflamed controls (p<0.002) but not coeliac disease controls. In addition, LP and epithelial CD3⁺IL-2⁺ and CD3⁺IFN⁺, and epithelial CD3⁺IL-4⁺ cells were more numerous in ASD children than in noninflamed controls (p<0.04). In contrast, CD3⁺IL-10⁺ cells were fewer in ASD children than in noninflamed controls (p<0.05). In the colon, LP CD3⁺TNF⁺ and CD3⁺IFN⁺ were more frequent in ASD children than in noninflamed controls (p<0.01). In contrast with Crohns disease and non-Crohns colitis, LP and epithelial CD3⁺IL-10⁺ cells were fewer in ASD children than in nondisease controls (p<0.01). There was a significantly greater proportion of CD3⁺TNF⁺ cells in colonic mucosa in those ASD children who had no dietary exclusion compared with those on a gluten and/or casein free diet (p<0.05). There is a consistent profile of CD3⁺ lymphocyte cytokines in the small and large intestinal mucosa of these ASD children, involving increased pro-inflammatory and decreased regulatory activities. The data provide further evidence of a diffuse mucosal immunopathology in some ASD children and the potential for benefit of dietary and immunomodulatory therapies.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

颅底外面枕骨基底部及周边骨性结构的测量和临床意义

目的为斜坡区肿瘤手术提供解剖资料。方法20例整颅,10例行水平切面,10例行正中矢状切面。测量切牙孔、前鼻棘、后鼻棘、枕骨大孔前端、枕髁前端、卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至咽结节的距离;测量卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至正中线的距离;测量枕骨基底部颅底外面的长径、枕骨大孔纵径(FML)、枕骨大孔前正中点与枕髁后缘连线垂直距离(AOCP)、枕髁轴径(OCA)、枕髁间距。结果切牙孔后缘、前鼻棘、后鼻棘、枕骨大孔前端、枕髁前端、卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至咽结节的距离分别为(mm):72.12±4.25、77.77±3.89、33.73±2.07、13.14±1.91、15.71±1.74、27.51±2.12、15.98±1.98、25.93±2.23、19.15±1.49。卵圆孔、破裂孔、颈动脉管及舌下神经管外口的内侧缘至中线的距离分别为:25.55±1.63、11.72±1.70、25.75±1.98、17.41±1.41。枕骨基底部颅底外面长径、FML、AOCP、OCA、枕髁间距分别为(mm):28.80±2.67、35.84±2.59、17.10±1.13、24.55±2.35、21.07±1.92。结论经口咽至斜坡区的手术入路中,开骨窗时安全范围是以咽结节为中心,以15mm为半径做斜坡磨除;也可以做矩形骨窗,即以咽结节为中心开一长(高)25mm×宽20mm的骨窗。