汉防己甲素对兔视网膜色素上皮细胞Bax、Bcl-2表达的影响

目的：评价汉防己甲素（Tet）对兔视网膜色素上皮（RPE）细胞增殖的抑制作用及对凋亡蛋白Bax、Bcl-2表达的影响。方法：MTT法检测Tet对体外培养兔RPE细胞增生的影响,流式细胞仪检测Tet对兔RPE细胞增殖周期、凋亡率及Bax、Bcl-2蛋白表达的影响。结果：Tet对兔RPE细胞的抑制率均随作用时间的延长而增高,各时间点之间差异均有统计学意义（P〈0.05）;抑制率均随药物质量浓度的增高而增高,除Tet10μg/ml、15μg/ml外,各质量浓度之间差异有统计学意义（P〈0.05）;Tet10μg/ml作用72 h后,出现G0/G1期细胞明显增多,S期与G2/M期细胞降低,Bax蛋白表达增加,Bcl-2蛋白表达下降,Bcl-2/Bax比值下降,以上与对照组相比均有显著性差异（P〈0.05）。结论：Tet可能通过干预RPE细胞Bax与Bcl-2蛋白的表达而对其增殖产生抑制作用。     

硅油眼前房水白细胞介素-6和血管内皮生长因子表达的研究

目的 检测白介素6(Interleukin-6,IL-6)和血管内皮生长因子(Vascular endothelial growth factor,VEGF)在硅油眼的前房水表达水平,并探讨其与硅油眼复发性视网膜前膜的关系.方法 研究纳入39例(40只眼)行玻璃体切除患者并采用前房穿刺方法获取前房水,其中14例(15只眼)硅油眼,15例(15只眼)增殖性玻璃体视网膜病变(Proliferative vitreoretinopathy,PVR),10例(10只眼)黄斑前膜/裂孔.硅油眼中合并复发性视网膜前/视网膜下增殖膜者共6只眼(亚组1),未合并者共9只眼(亚组2).采用ELISA方法检测前房水IL-6及VEGF浓度.结果 硅油眼前房水IL-6水平(307.33±152.68)pg/ml高于PVR组(235.35±98.41)pg/ml和黄斑前膜/裂孔组(30.18±14.3)pg/ml,差异有统计学意义.硅油眼亚组1的前房IL-6浓度(408.57±151.21)pg/ml显著高于亚组2及PVR组.硅油眼和PVR组的前房水VEGF浓度(294.94±121.81)pg/ml,(297.43±134.06)pg/ml差异无统计学意义,但均明显高于黄斑前膜/裂孔组水平(32.78±12.9)pg/ml.结论 硅油眼前房水VEGF和IL-6均高于PVR组.增生相关性因子在硅油跟的积聚可能刺激增殖膜生长从而导致视网膜复位失败.     

Familial retinal detachment associated with COL2A1 exon 2 and FZD4 mutations

Background: To characterize the clinical and genetic abnormalities within two Australian pedigrees with high incidences of retinal detachment and visual disability. Design: Prospective review of two extended Australian pedigrees with high rates of retinal detachment. Participants: Twenty‐two family members from two extended Australian pedigrees with high rates of retinal detachment were examined. Methods: A full ophthalmic history and examination were performed, and DNA was analysed by linkage analysis and mutation screening. Main Outcome Measures: Characterization of a causative hereditary gene mutation in each family. Results: All affected family members of one pedigree carried a C192A COL2A1 exon 2 mutation. None of the affected family members had early‐onset arthritis, hearing abnormalities, abnormal clefting or facial features characteristic of classical Stickler syndrome. All affected members of the familial exudative vitreoretinopathy pedigree carried a 957delG FZD4 mutation. Conclusions: Patients with retinal detachment and a positive family history should be investigated for heritable conditions associated with retinal detachment such as Stickler syndrome and familial exudative vitreoretinopathy. The absence of non‐ocular features of Stickler syndrome should raise the possibility of mutations in exon 2 of COL2A1. Similarly, late‐onset familial exudative vitreoretinopathy may appear more like a rhegmatogenous detachment and not be correctly diagnosed. When a causative gene mutation is identified, cascade genetic screening of the family will facilitate genetic counselling and screening of high‐risk relatives, allowing targeted management of the pre‐detachment changes in affected patients.     

Angiogenesis-related cytokines in serum of proliferative diabetic retinopathy patients before and after vitrectomy

AIM: To evaluate serum concentrations of angiogenesis-related cytokines in proliferative diabetic retinopathy (PDR) before and after vitrectomy. METHODS: Serum samples were collected from 30 PDR patients with varying severity before and after vitrectomy. Serum concentrations of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10) were determined by enzyme-linked immunosorbent assays (ELISA). RESULTS: Serum concentrations of VEGF, PEDF, IL-8 and IP-10 were significantly higher in PDR patients than that in controls, respectively (P<0.05). VEGF concentration decreased significantly in postoperative samples than that in preoperative samples (P<0.05). The concentrations of PEDF, IL-8 and IP-10 did not exhibit significant changes after vitrectomy. CONCLUSION: Elevated cytokines levels in serum may be diagnostically useful in PDR. Angiogenesis-related cytokines play important roles in the development of PDR, and would instruct the risk assessment of pathogenetic condition in PDR patients.     

Clinicopathologic features and histochemical analyses of proliferative activity and angiogenesis in small cell carcinoma of the esophagus

Background We investigated clinicopathologic features in patients with esophageal small cell carcinoma (SCEC), and its proliferative activity and angiogenesis. Methods Ten patients with SCEC from 335 esophageal carcinoma patients were analyzed clinicopathologically. For analyses of cell proliferation, apoptosis, and angiogenesis of SCEC, Ki-67 immunostaining, the TUNEL method, and CD31 and CD68 immunostaining were used. Results Esophagectomy was performed in nine patients, while one with extensive SCEC was treated by repeated chemotherapy and radiotherapy. Four patients received chemotherapy both before and after surgery, one only before surgery, and four only after surgery. Cisplatin and etoposide were given to five patients, while irinotecan and cisplatin were given to three. Five survived more than 18 months, and two more than 36 months. One of these two had limited SCEC treated by surgery and chemotherapy, whereas the other had extended SCEC treated by repeated chemotherapy and radiotherapy. The microvessel count and the Ki-67 labeling index of SCEC were higher than those of squamous cell carcinoma (P = 0.0033 and P = 0.0005, respectively). Between SCEC with and without preoperative chemotherapy, the Ki-67 labeling index was lower (P = 0.027) and the apoptotic index was higher in the treated SCEC (P = 0.014). Between SCEC patients who survived more or less than 18 months, the microvessel count was lower in those who survived more than 18 months (P = 0.049). Conclusions Esophagectomy may be indicated for limited SCEC combined with chemotherapy. SCEC has high proliferative activity and rich neovascularization, and its proliferative activity may be suppressed by chemotherapy.     

Parasites alter the pathological phenotype of lupus nephritis

Abstract

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis.     

Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry

ABSTRACT— To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.     

玻璃体血管生成素2浓度与糖尿病玻璃体出血的相关性

目的探讨血管生成素2（Ang-2）与糖尿病玻璃体出血的相关性。方法用ELISA法分别检测糖尿病玻璃体出血患者31例和非糖尿病视网膜脱离患者25例玻璃体和血浆Ang-2浓度。统计分析玻璃体Ang-2浓度、血浆Ang-2浓度、血压、血脂、FPG及HbA1c等指标与糖尿病玻璃体出血的关系。结果糖尿病玻璃体出血患者玻璃体Ang-2浓度（中位数：3765ng/L）较非糖尿病视网膜脱离组（274ng/L）显著升高（P〈0.05）,糖尿病组玻璃体Ang-2浓度（3765ng/L）高于同组患者血浆Ang-2浓度（2716ng/L）。以行玻璃体切除术患者为整体,是否糖尿病玻璃体出血为因变量进行logistic回归分析,玻璃体Ang-2浓度和HbA1c水平进入回归方程。结论玻璃体Ang-2浓度升高是糖尿病玻璃体出血的重要独立危险因素之一。     

DeltaA mRNA and protein distribution in the zebrafish nervous system

Physical interaction between the transmembrane proteins Delta and Notch allows only a subset of neural precursors to become neurons, as well as regulating other aspects of neural development. To examine the localization of Delta protein during neural development, we generated an antibody specific to zebrafish DeltaA (Dla). Here, we describe for the first time the subcellular localization of Dla protein in distinct puncta at cell cortex and/or membrane, supporting the function of Dla in direct cell–cell communication. In situ RNA hybridization and immunohistochemistry revealed dynamic, coordinated expression patterns of dla mRNA and Dla protein in the developing and adult zebrafish nervous system. Dla expression is mostly excluded from differentiated neurons and is maintained in putative precursor cells at least until larval stages. In the adult brain, dla mRNA and Dla protein are expressed in proliferative zones normally associated with stem cells. Developmental Dynamics 238:3226–3336, 2009. © 2009 Wiley‐Liss, Inc.