Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways

Background  

Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes. However, Tat by itself or HHV8-genes alone cannot induce angiogenesis in vivo unless specific proteins/enzymes are produced synchronously by different cell-types. We therefore tested a hypothesis that chronic HIV-replication in non-endothelial cells may produce novel factors that provoke angiogenic pathways.     

Effect of hyperthermia and anoxia on glucocorticoid and mineralocorticoid receptor expression in neonatal rat hippocampus

Brief periods of neonatal asphyxia are frequently observed. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia. The hippocampus contains the highest concentration of both mineralocorticoid (MR) and glucocorticoid (GR) receptors and the balance between MR/GR activation influences cell birth and death. MR occupation appears to promote prosurvival actions, while GR overactivation favours neurodegeneration. It has been widely recognized that core body temperature is a critical determinant of the severity of hypoxic–ischemic brain injury; indeed, hyperthermia exacerbates the degree of damage. Therefore, the aim of the present investigation was to study the effect of elevated body temperature in newborn rats under control conditions or during neonatal exposure to a critical anoxia, on changes of MR and GR mRNA expression in the rat hippocampus. 2-day-old rats were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33 °C (typical for the rat neonates), or elevated to a level typical for febrile (39 °C) adults. Control rats were exposed to atmospheric air under the respective thermal conditions. The changes in MR and GR mRNA expression in hippocampus were examined 24 h after exposure. Our data show that hyperthermia with or without added anoxia, causes induction of MR mRNA expression in neonatal rat hippocampus without any effect on GR mRNA expression. We suggest this elevation of MR plays an important role in modulating the survival of neurons in the injured hippocampus.     

广东地区变应性结膜炎变应原筛选及预防

目的 观察广东地区变应性结膜炎患者气源性变应原的分布情况,为预防方案提供科学依据.方法 采用17种吸入性变应原对广东地区138例患有变应性结膜炎的患者进行皮内试验.结果 138例符合条件的变应性结膜炎患者的变应原皮肤实验阳性率以螨(122/138,88.41%)最高,其次为屋尘(88/138,63.71%)、刺苋菜(87/138,63.04%)、蟑螂(79/138,57.24%)、秋季花粉(75/138,54.35%)、垫料(75/138,54.35%)、蚕蛹(74/138,53.62%)、蜜蜂(65/138,47.10%)等.结论 螨、屋尘是广东地区变应性结膜炎的最常见变应原,临床上应重视环境对其预防的重要意义.     

乌梅丸的组方配伍特点与慢性肝病的治疗

通过分析《伤寒论》厥阴病篇的条文，得出厥阴病的病机是寒热夹杂、上热下寒；厥阴病主方是乌梅丸；乌梅丸的组方配伍特点是：辛酸温为主，佐以苦甘，寒温并用，辛开苦降，刚柔共济，有收有发，攻补兼施，体用同调，和水火而顺阴阳。比较慢性肝病与厥阴病的临床表现及病机，二者有相通之处，认为乌梅丸可以用于指导慢性肝病的治疗。     

中药药效/药动学(PK/PD)研究进展

综述了中药药效/药动学(PK/PD)近十几年来的研究进展,包括其研究目的和内容、研究方法等,以及所面临的问题。     

Classification based on the combination of molecular and pathologic predictors is superior to molecular classification on prognosis in colorectal carcinoma.

PURPOSE: Classification based on a combination of molecular and pathologic predictors had never been done using hierarchical cluster analysis. For this purpose, we identified prognostic classification based on molecular predictors, pathologic and molecular predictors, and compared their respective prognostic efficacy together with that of tumor-node-metastasis (TNM) stage. Moreover, we investigated the prognostic significance of molecular classification in different TNM stage. EXPERIMENTAL DESIGN: Six pathologic predictors (p) and 13 immunohistochemical predictors (m) were investigated in 221 colorectal carcinomas. Unsupervised hierarchical clustering analysis was done to group the data. Survival analysis was done by Kaplan-Meier method and log-rank test, and by multivariate COX proportional hazard model. RESULTS: Six pathologic predictors and four molecular predictors were of significant prognostic value (P 相似文献   

颜面部皮肤肿瘤的切除与整形修复

目的探讨面部肿瘤的手术治疗和相关整形修复问题。方法综合分析2002年1月至2004年12月收治的217例面部皮肤肿瘤患者的临床资料。结果面部良性肿物在年轻人以皮脂腺囊肿多见,老年人则以色素痣和脂溢性角化为主。恶性肿瘤多见于老年人,以基底细胞癌和鳞状细胞癌为主。治疗以直接切除缝合、转移皮瓣和植皮修复,术区外形和功能良好。结论将整形治疗原则应用于面部肿物的治疗,根据患者具体情况制定个体化的治疗方案,可以取得良好的治疗效果。     

Abrogation of MAPK and Akt signaling by AEE788 synergistically potentiates histone deacetylase inhibitor-induced apoptosis through reactive oxygen species generation.

PURPOSE: To evaluate the effects of combining the multiple receptor tyrosine kinase inhibitor AEE788 and histone deacetylase (HDAC) inhibitors on cytotoxicity in a broad spectrum of cancer cell lines, including cisplatin-resistant ovarian adenocarcinoma cells. EXPERIMENTAL DESIGN: Multiple cancer cell lines were treated in vitro using AEE788 and HDAC inhibitors (LBH589, LAQ824, and trichostatin A), either alone or in combination. Effects on cytotoxicity were determined by growth and morphologic assays. Effects of the combination on cell signaling pathways were determined by Western blotting, and the results were confirmed using pathway-specific inhibitors and transfection of constitutively active proteins. RESULTS: Cell treatment with AEE788 and HDAC inhibitors (LBH589, LAQ824, and trichostatin A) in combination resulted in synergistic induction of apoptosis in non-small cell lung cancer (MV522, A549), ovarian cancer (SKOV-3), and leukemia (K562, Jurkat, and ML-1) cells and in OV202hp cisplatin-resistant human ovarian cancer cells. AEE788 alone or in combination with LBH589 inactivated mitogen-activated protein kinase (MAPK) and Akt cascades. Inhibition of either MAPK and/or Akt enhanced LBH589-induced apoptosis. In contrast, constitutively active MAPK or Akt attenuated LBH589 or LBH589 + AEE788-induced apoptosis. Increased apoptosis was correlated with enhanced reactive oxygen species (ROS) generation. The free radical scavenger N-acetyl-l-cysteine not only substantially suppressed the ROS accumulation but also blocked the induction of apoptosis mediated by cotreatment with AEE788 and LBH589. CONCLUSION: Collectively, these results show that MAPK and Akt inactivation along with ROS generation contribute to the synergistic cytotoxicity of the combination of AEE788 and HDAC inhibitors in a variety of human cancer cell types. This combination regimen warrants further preclinical and possible clinical study for a broad spectrum of cancers.