Waardenburg syndrome, Hirschsprung megacolon, and Marcus Gunn ptosis

A patient with Waardenburg syndrome type II associated with Hirschsprung megacolon and Marcus Gunn ptosis is presented. It is suggested that these different anomalies are manifestations of the same neurocrestopathy.     

Human malignant mesothelial cells: Variability of ultrastructural features in established and nude mice transplanted cell lines

The aim of this study was to determine, by transmission electron microscopy, the differentiation features of 21 human malignant mesothelioma cell lines (HMCLs) established from 13 specimens of 12 confirmed human malignant mesotheliomas, and of tumours induced in nude mice injected with 16 HMCLs. Fifty per cent of HMCLs showed typical mesothelial differentiation (long and slender microvilli, desmosomes, perinuclear intermediate filaments); 29 per cent did not show differentiation; and the remainder were poorly differentiated. Three human tumour specimens gave several different HMCLs; the cell lines obtained from a given tumour exhibited variable mesothelial differentiation. Eleven HMCLs were compared with the native tumour. Four were similar to the tumour and seven were less well differentiated, in most cases in relation to their microvilli. With six HMCLs, tumours induced in nude mice were less well differentiated than the corresponding cell lines, whereas with four HMCLs, tumours were equally or better differentiated. However, in most nude mice tumours, typical mesothelial microvilli were present. These results show that cell lines established from malignant mesothelioma may exhibit dedifferentiated features. However, while the variability in ultrastructural differentiation may result from the culture microenvironment, it could also be related to the state of differentiation, of the native tumour sample and to tumour cell heterogeneity.     

Correlation of AIB1 overexpression with advanced clinical stage of human colorectal carcinoma

AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on 20q12 and is a candidate oncogene in human breast cancer. It is commonly amplified and overexpressed in several types of human cancers. In this study, we examined the expression of AIB1, as related to clinicopathologic features, in 85 human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53 expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In addition, the overexpression of AIB1 was observed more frequently in CRCs in later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage (P < .05). These results suggest that overexpression of AIB1 might provide a selective advantage for the developmental growth and/or progression of subsets of CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1 with p53 overexpression as well as with aneuploid DNA content was observed in these CRCs. The overexpression of p53 was also correlated significantly with CRC DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA content; most of these were in the later clinical stage. These findings suggest a possible convergence of AIB1 with a pathway involving p53, which might induce chromosomal instability and affect the clinical phenotype of a subset of CRCs.     

Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine or stavudine,each in combination with lamivudine and indinavir

The authors studied the effect of zidovudine (ZDV) resistance mutation on virologic response to treatment with ZDV or stavudine (d4T) each in combination with lamivudine and indinavir. Viral genotyping was performed on plasma HIV-1 RNA at study entry and concerned 155 patients previously treated with ZDV, didanosine, or zalcitabine and enrolled in the NOVAVIR (Agence National de Recherche sur le SIDA [ANRS] 073) trial. Three virologic responses were investigated: early response (<50 copies/mL at week 24), late response (<500 copies/mL at week 80), and virologic failure (two HIV-1 RNA >5000 copies/mL). Patients were classified as resistant or susceptible to ZDV according to the ANRS algorithm. Plasma viral RNA from 123 of 155 patients had two or more ZDV resistance mutations. The number of ZDV resistance mutations was positively correlated with the duration of prior antiviral therapy (p <.001). At week 24, 74% and 77% of patients with virus classified as resistant were responders in the d4T and ZDV arm, respectively. Similar results were found at week 80. Virologic failure was reached in 7 of 24 patients with virus classified as susceptible and in 26 of 131 patients with resistant virus (p =.29). In the ZDV arm, patients classified as resistant had longer times to virologic failure than those classified as susceptible (p =.003). In conclusion, sustained virologic response despite presence of ZDV resistance mutations implies that these mutations do not preclude an early and durable response to treatment with a potent three-drug regimen in these patients. Patients susceptible to ZDV had lower median mean corpuscular volumes and lower random indinavir levels, suggesting that adherence was the main reason for failure.     

Recurrent genetic alterations in 26 colorectal carcinomas and 21 adenomas from Chinese patients

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The incidence of CRC in the Chinese population has increased dramatically during the last two decades; however, nonrandom chromosomal alterations in Chinese patients have not been described. In the present study, comparative genomic hybridization (CGH) was applied to detect recurrent chromosome alterations in 26 primary colorectal carcinomas and 21 colorectal adenomas from Chinese patients. In CRC, several recurrent chromosomal changes were found, including gains of 8q (14/26 cases, 54%), 20q (54%), 3q (50%), 13q (50%), 5p (46%), 7p (42%), 7q (42%), and 12p (38%) and losses of 18q (65%) and 17p (42%). From comparison with previous CGH studies, the frequent gains of 3q and 12p might be distinctive occurrences in Chinese patients. The distribution of frequently found chromosomal alterations in different locations was studied. The gain of 20q was more frequently found in colon cancer (P<0.01) and the gain of 12p was more frequently found in rectal cancer. Chromosomal alterations were found in 19/21 of adenomas; the most frequent chromosomal alteration was the loss of 18q (9/21 cases, 43%). These recurrent alterations provide several starting points for the isolation of candidate oncogenes and tumor suppressor genes.     

构建7q32区域鼻咽癌和正常鼻咽上皮细胞部分基因的表达图谱

目的构建７ｑ３２区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞的部分基因表达图谱。方法通过差异ＲＴ－ＰＣＲ和Ｎｏｒｔｈｅｒｎ杂交的方法检测定位于７ｑ３２区域的２０个ＥＳＴ在鼻咽癌细胞和鼻咽癌组织及原代培养人正常鼻咽上皮细胞ｍＲＮＡ的表达水平。结果８个ＥＳＴ在鼻咽癌细胞ＨＮＥ１和原代培养人正常鼻咽上皮细胞中表达量较一致，７个ＥＳＴ在两种细胞中均无表达，３个ＥＳＴ（Ｗ７２６８８、Ｈ１９８３０、ＡＡ１３０６３０）在鼻咽癌细胞株中表达上调，而２个ＥＳＴ（ＡＡ０７０４３７、Ｈ９０８８２）在原代培养人鼻咽上皮细胞中表达上调。在１３例鼻咽癌活检组织中３０．７％（４／１３）的ＡＡ０７０４３７表达下调，７７％（１０／１３）的Ｗ７２６８８和７７％（１０／１３）的Ｈ１９８３０表达上升。结论构建了７ｑ３２区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞部分基因表达图谱，并初步认为Ａ０７０４３７的表达下调和Ｗ７２６８８、Ｈ１９８３０的过表达与鼻咽癌的发生有关。     

Folic acid reduces chemokine MCP-1 release and expression in rats with hyperhomocystinemia.

OBJECTIVE: This study aimed to investigate the effects of folate on the monocyte chemoattractant protein-1 (MCP-1) expression and release in rats with hyperhomocystinemia induced by ingestion of excess methionine. METHODS AND RESULTS: Thirty male Sprague-Dawley rats (200+/-20 g) were randomly divided into three groups (n=10 for each group): control group (Control), high-homocystinemia (Hhcy) group, and folate treatment (FA) group. They were fed with a normal regular diet, enriched by 1.7% methionine plus 1.7% methionine and 0.006% folate for 45 days. Our study showed the following: (a) A high methionine diet for 45 days is sufficient to induce hyperhomocystinemia; folate supplementation to the rats fed the high-methionine diet prevented an elevation homocysteine (Hcy) levels in the blood (P<.01). (b) Compared with the Control group, the Hhcy group had elevated plasma levels of MCP-1, and Hcy was significantly correlated with MCP-1 (P<.05). (c) The protein and mRNA expression of MCP-1 in the aorta was higher in rats from the Hhcy group than in rats from the Control group. (d) Most important, after folic acid supplementation, the lowering of Hcy levels was accompanied by a marked reduction of MCP-1 expressed in aortae and released from plasma and peripheral blood mononuclear cells (PBMCs) stimulated by oxidized low-density lipoprotein (P<.05, P<.01). CONCLUSION: Folic acid supplementation not only can blunt the rise in Hcy and reduce MCP-1 released from both plasma and PBMCs of rats with hyperhomocystinemia but also can downgrade MCP-1 expression in the aorta of rats with hyperhomocystinemia.     

不同年龄人脑视皮质毛细血管密度的计量分析

本文应用碱性磷酸酶染色,按立体学方法观测了不同年龄(14岁以下儿童4例,成年人2例,60岁以上老人2例)共8例人脑视皮质有纹区各层毛细血管的密度(各层均取40个数据).结果:成年组视皮质第三层血管网3c亚层(位于皮质第Ⅳc层)毛细血管密度平均为1580.79±47.73mm/mm~3;儿童组为1087.19±44.90mm/mm~3;老年组为619.95±21.39mm/mm~3.经方差分析检验,P<0.01,说明在第三层血管网3c亚层三个年龄组之间具有非常显著性差异.讨论了各年龄组之间视皮质有纹区毛细血管密度差异与机能的关系.     

远端蒂腓肠神经营养血管皮瓣与肌皮瓣的临床应用与改进

目的:报道应用远端蒂腓肠神经营养血管皮瓣,肌皮瓣修复小腿下段及足踝部软组织缺损的可行性安全性和临床效果。方法:对42例以远端蒂腓肠神经营养血管(肌)皮瓣修复小腿下段及足踝部不同原因所致软组织缺损病例进行总结分析。本组男36例,女6例;年龄最大75岁、最小6岁;皮瓣最大面积17.0cm×15.0cm,最小6.0cm×5.0cm,其中12例皮瓣面积在10.0cm×10.0cm以上;6例设计为肌皮瓣(腓肠肌外侧头),肌瓣最大为10.0cm×7.0cm×2.0cm,最小为6.0cm×5.0cm×1.0cm。结果:所有病例术后皆出现不同程度的皮瓣肿胀,暗道较明道者明显。2例大皮瓣经行小隐静脉远端结扎仍出现肿胀、色暗,皮瓣近侧1/3坏死。皮瓣边缘坏死3例,换药治愈。部分坏死需行植皮者3例。36例术后伤口I期愈合,骨外露软件组织缺损覆盖修复满意,6例II期愈合,其中糖尿病,地中海贫血各一例。结论:(1)远端蒂腓肠神经营养血管皮瓣转位修复小腿下1/3及足踝部缺损创面,极有临床实用价值;(2)设计切取腓肠神经营养血管肌皮瓣修复小腿及足踝填充感染创腔是可行的;(3)但对其皮瓣及所携带的肌瓣究竟切取多大面积是安全的、肌瓣的血运机理以及远端蒂筋膜皮瓣中小隐静脉干是否结扎,何处结扎等问题仍有待进一步研究。     

葡萄糖和胆固醇对人肝细胞ANGPTL3基因和蛋白质表达的影响

目的 观察葡萄糖和胆固醇对人肝细胞株(L02)血管生成素样蛋白3(angiopoietin-like pro-tein3,ANGPTL3)表达的影响,探讨其与糖尿病和高胆固醇血症的关系.方法 以L02细胞为研究对象,将其分为葡萄糖组(G)和胆固醇组(CH).分别在葡萄糖浓度为5.6 mmol/L(G1)、7.0 mmol/L(G2)、11.1 mmol/L(G3)、28.0 mmol/L(G4)、33.0 mmol/L(G5)的培养液和含胆固醇10 μmol/L、25 μmol/L、50 μmol/L、100 μmol/L的培养液中培养.采用RT-PCR方法检测各组细胞ANGPTL3 mRNA表达量,用Western印迹方法检测其蛋白质表达水平.结果 G3～G5组葡萄糖可剂量依赖性地增加ANGPTL3的mRNA表达(P<0.05);在蛋白质表达水平,G2～G5组与G1组比较差异均有统计学意义(P<0.05);G1～G5组各组间两两比较,除G4组与G5组呈现表达量虽升高,但差异无统计学意义(P>0.05)外,其它各组间差异均有统计学意义(P<0.05).4种胆固醇浓度均可促进L02细胞ANGPTL3的mRNA和蛋白质表达(P<0.05).结论 在一定浓度范围内葡萄糖可剂量依赖性地促进ANGPTL3 mRNA和蛋白质表达;AN-GPTL3的mRNA和蛋白质表达量还受环境胆固醇浓度影响.ANGPTL3的表达可能与糖尿病、高胆固醇血症密切相关.