Interleukin-12 enhances the sensitivity of human osteosarcoma cells to 4-hydroperoxycyclophosphamide by a mechanism involving the Fas/Fas-ligand pathway.

Cyclophosphamide (CY) and its derivative ifosfamide are alkylating agents used to treat osteosarcoma (OS). The purpose of these studies was to determine whether alkylating agents affect the expression of Fas ligand (FasL) and whether interleukin 12 enhances the sensitivity of human OS cells to alkylating agents. 4-Hydroperoxycyclophosphamide (4-HC), the preactivated CY compound, and 4-hydroperoxydidechlorocloclophosphamide (4-HDC), its nonalkylating analogue, human OS LM6 cells, and a clone of cells derived by transfection with the interleukin 12 gene (LM6-#6) were used for these studies. Incubation of LM6 and LM6-#6 with 10 micro M 4-HC increased the expression of FasL mRNA (2.5- and 3.0-fold, respectively). By contrast, 4-HDC, Adriamycin (ADR), cisplatin (CDP), and methotrexate (MTX) had no effect on FasL mRNA expression. Increased FasL expression after treatment with 4-HC was also demonstrated by immunohistochemistry and flow cytometry. Drug-induced FasL was functional and mediated cell death. We examined the effect of FasL up-regulation by 4-HC on LM6 and LM6-#6 cells. Flow cytometry showed that LM6-#6 cells expressed 2.2-fold more Fas than LM6 cells. Cytotoxicity of 4-HC, 4-HDC, ADR, CDP, and MTX on LM6, LM6-neo, and LM6-#6 were quantified. Colony-forming assay revealed an IC(50) of 2.10 micro M for 4-HC in LM6-neo cells compared with 0.41 micro M in LM6-#6 cells. The IC(50) for 4-HDC, ADR, CDP, and MTX were not significantly different between the two cell lines. We concluded that the increased expression of Fas enhanced LM6-#6 sensitivity to 4-HC. These data indicate that Fas/FasL may be involved in the cytotoxic pathway of CY. Combining biological agents with chemotherapeutic agents that have complementary Fas/FasL pathway actions may offer new therapeutic alternatives.     

Increased Fas expression reduces the metastatic potential of human osteosarcoma cells.

PURPOSE: The process of metastasis requires the single tumor cell that seeds the metastatic clone to complete a complex series of steps. Identifying factors responsible for these steps is essential in developing and improving targeted therapy for metastasis. Resistance to receptor-mediated cell death, such as the Fas/Fas ligand pathway, is one mechanism commonly exploited by metastatic cell populations. EXPERIMENTAL DESIGN AND RESULTS: LM7, a subline of the SAOS human osteosarcoma cell line with low Fas expression, was selected for its high metastatic potential in an experimental nude mouse model. When transfected with the full-length Fas gene (LM7-Fas), these cells expressed higher levels of Fas than the parental LM7 cells or LM7-neo control-transfected cells. These cells were also more sensitive to Fas-induced cell death than controls. When injected intravenously into nude mice, the LM7-Fas cell line produced a significantly lower incidence of tumor nodules than control cell lines. Lung weight and tumor nodule size were also decreased in those mice injected with LM7-Fas. Levels of Fas were quantified in osteosarcoma lung nodules from 17 patients. Eight samples were Fas negative, whereas the remaining 9 were only weakly positive compared with normal human liver (positive control). CONCLUSIONS: Our results demonstrate that altering Fas expression can impact the metastatic potential of osteosarcoma cells. We conclude that the increase of Fas on the surface of the LM7 osteosarcoma cells increased their sensitivity to Fas-induced cell death in the microenvironment of the lung, where Fas ligand is constitutively expressed. Thus, loss of Fas expression is one mechanism by which osteosarcoma cells may evade host resistance mechanisms in the lung, increasing metastatic potential. Fas may therefore be a new therapeutic target for osteosarcoma.     

扁桃体周脓肿感染途径的探讨

为探讨扁桃体周脓肿的真正发病机理、感染途径，对连续诊治的１３１例扁周脓肿患者进行研究。其中８３例患侧的扁桃体被切除，切除之扁桃体外侧面均平整。通过８３例组织学观察，扁桃体上极表面既无扁桃溃破亦无脓瘘，邻接扁桃体上方之软腭粘膜下发现有感染及／或纤维化的小唾液腺（Ｗｅｂｅｒ腺），这些与扁桃体相邻的腺体在其他非扁周脓肿患者则显示正常形态与结构。从而认为扁桃体周围的化脓性感染可能与Ｗｅｂｅｒ腺有关，而非急性扁桃体炎。主张早期扁桃体切除术治疗扁周脓肿，目的在于获得充分引流。     

加入WTO后我国健康相关产品管理的挑战与机遇

2001年我国加入世界贸易组织(WTO)，作为WTO成员国按照国际贸易规则建立一个完整的、更具活力和长久性的多边产品贸易体制，促进和规范产品贸易良好发展是我们面临的任务之一。WTO成员国通过降低关税和其他贸易壁垒，在国际贸易中消除歧视性待遇，达到互惠互利的目的。WTO诸     

近视眼后极部视网膜厚度与眼轴长度的相关性研究

目的:探讨近视眼后极部不同区域的视网膜厚度与眼轴长度的关系。方法:采用视网膜厚度分析仪(retinalthicknessan-alyzer,RTA)测定45例(85眼)近视患者后极部视网膜厚度,并分析视网膜厚度与眼轴长度的相关性。结果:近视眼后极部视网膜平均厚度与性别、年龄无关,与眼轴长度明显相关,随着近视眼眼轴延长,近视屈光度明显增加,后极部视网膜厚度明显变薄,其中以黄斑周围区比黄斑区视网膜变薄更明显。结论:近视眼眼轴延长不仅会引起屈光度的近视化,还导致后极部视网膜厚度明显变薄。     

Construct Validity of the EQ-5D in Low-Income Chinese American Primary Care Patients

OBJECTIVES: Although the EQ-5D has been used with increasing frequency to measure health-related quality of life, to date, the measure's validity has not been examined in Chinese American immigrants. We evaluated the construct validity of the EQ-5D by testing its performance with respect to sociodemographic and clinical characteristics of the population and comparing responses on the EQ dimensions with the SF-36 subscales. METHODS: The study surveyed low-income Chinese patients attending a community health center in New York City's Chinatown. Participants received self-administered versions of the EQ-5D and SF-36 and additional questions regarding demographic and clinical information. RESULTS: 856 patients were approached and data were collected from 523 patients (61%). Analysis of the EQ-5D responses by sociodemographic and clinical variables found significant differences among categories of age, gender, marital status, number of medical problems, self-rated health, and specific medical problems. Correlations between similar dimensions and subscale scores were stronger between the two measures than dissimilar ones. Patients without impairments on a given EQ dimension tended to have higher SF-36 subscale scores than patients reporting 'any' impairment (i.e. some/moderate or severe). CONCLUSIONS: The results provide initial support for the construct validity of the EQ-5D in our sample. Further studies should compare the performance of the EQ-5D with other preference-based measures in Chinese persons and examine the valuations that both low-income and Chinese persons place on core aspects of health.     

益肾活血胶囊抗病毒性心肌炎的实验研究

目的　探讨益肾活血胶囊对病毒性心肌炎的治疗作用。方法　选用BALB/C小鼠 6 0只,随机分为正常对照组、模型组、益肾活血胶囊组、阳性药物组,每组分别给药后,测定LDH和AST含量,并进行组织病理学检测,各区测定值采用t检验进行组间比较。结果　益肾活血组小鼠LDH、AST水平较模型组明显降低,(p <0 0 0 1);组织病理学检测发现,心脏组织病理改变程度较模型组明显减轻。结论　益肾活血胶囊对于病毒性心肌炎模型小鼠有一定的治疗作用。     

Construction of a bioengineered cardiac graft

OBJECTIVES: Currently available graft materials for repair of congenital heart defects cause significant morbidity and mortality because of their lack of growth potential. An autologous cell-seeded graft may improve patient outcomes. We report our initial experience with the construction of a biodegradable graft seeded with cultured rat or human cells and identify their 3-dimensional growth characteristics. METHODS: Fetal rat ventricular cardiomyocytes, stomach smooth muscle cells, skin fibroblasts, and adult human atrial and ventricular cardiomyocytes were isolated and cultured in vitro. These cells were injected into or laid onto biodegradable gelatin meshes, and their rate of proliferation and spatial location within the mesh was evaluated by using a cell counter and histologic analysis. RESULTS: Rat cardiomyocytes, smooth muscle cells, and fibroblasts demonstrated steady proliferation over 3 to 4 weeks. The gelatin mesh was slowly degraded, but this process was most rapid after seeding with fibroblasts. Human atrial cardiomyocytes proliferated within the gelatin meshes but at a slower rate than that of fetal rat cardiomyocytes. Human ventricular cardiomyocytes survived within the gelatin mesh matrix but did not increase in number during the 2-week duration of evaluation. Grafts seeded with rat ventricular cells exhibited spontaneous rhythmic contractility. All cell types preferentially migrated to the uppermost surface of each graft and formed a 300- to 500-microm thick layer. CONCLUSIONS: Fetal rat ventricular cardiomyocytes, gastric smooth muscle cells, skin fibroblasts, and adult human atrial cardiomyocytes can grow in a 3-dimensional pattern within a biodegradable gelatin mesh. Similar autologous cell-seeded constructs may eventually be applied to repair congenital heart defects.     

解密抑郁症

来自美国、瑞典及法国的科学家发现，有一种蛋白可能在抑郁症的发病过程中起着极为重要的作用。他们希望这一发现将有助于明确抑郁症的病因，找到新的治疗方法（Svenningsson P et al．Sc／ence．2006：311：77—80）。     

DIAGNOSIS AND TREATMENT OF MEDIASTINAL ENTEROGENOUS CYSTS IN CHILDREN

MEDIASTINAL enterogenous cysts are congen-ital anomalies rarely seen in the pediatric agegroups.Most children are first admitted tohospital due to respiratory symptoms.Neonates and littleinfants often have the symptom of respiratory distress,while a few a…