P-glycoprotein,multidrug resistance and tumor progression

P-glycoprotein (Pgp) is a plasma membrane protein that was first characterised in multidrug resistant cell lines. The occurrence of Pgp in clinical tumors has been widely studied. Recent investigations have begun to focus on the relationship between Pgp detection in tumors and treatment outcome. In several types of tumors, detection of Pgp correlates with poor response to chemotherapy and shorter survival. P-glycoprotein overexpression often occurs upon relapse from chemotherapy but may also occur at the time of diagnosis. Studies of experimental rat liver carcinogenesis have shown that Pgp expression increases in late stages of carcinogenesis, suggesting that Pgp may be involved in tumor progression. While some of the Pgp isoforms are known to transport hydrophobic chemotherapeutic drugs out of tumor cells, the biologic effects of Pgp overexpression in tumor cells are not fully understood, because the spectrum of substrates for Pgp-mediated transport has not been determined. In the rat liver carcinoma model, strong expression of Pgp is associated with a highly vascular stroma, suggesting that Pgp in tumor cells may affect the connective tissue stroma. The regulation of Pgp appears to be complex, and little is known about how it is up-regulated during carcinogenesis. Further studies of the role of Pgp in malignancy may contribute to our understanding of molecular mechanisms which underlie tumor progression.     

Extracellular signal regulated kinases 1/2 signal pathway and responses of astrocytes after diffuse brain injury

BACKGROUND: The treatment of diffuse brain injury during an acute period is focused on relieving degrees of secondary brain injury. Generation and development of pathological changes of secondary brain injury depend on signal conduction, so down-regulating over response of astrocyte through interfering a key link of signal conduction pathway may bring a new thinking for the treatment of diffuse brain injury. OBJECTIVE: To observe the effect of over activity of extracellular signal regulated kinases 1/2 (ERK1/2) signal pathway on the response of astrocyte during an acute period of diffuse brain injury. DESIGN: Completely randomized grouping and controlled animal study. SETTINGS: Department of Neurosurgery, the Third Affiliated Hospital, Nanchang University; Department of Neurosurgery, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: A total of 158 healthy male SD rats, of 11 weeks old, weighing 320–370 g, were provided by Experimental Animal Faulty, Tongji Medical College, Huazhong University of Science and Technology. Rabbit-anti-phosphorylated ERK1/2 (pERK1/2) polyclonal antibody was provided by R&D Company; rabbit-anti-glial fibrillary acidic protein (GFAP) polyclonal antibody, SP immunohistochemical kit and horseradish peroxidase (HRP)-labeled goat-anti-rabbit IgG by Santa Cruz Company; specific inhibitor U0126 of ERK1/2 signal pathway by Alexis Company. METHODS: The experiment was carried out in the Laboratory of Neurosurgery, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from September 2004 to March 2006. ① Detection of pERK1/2 expression: A total of 110 rats were randomly divided into sham operation group (n =5), model group (n =35), high-dosage U0126 group (n =35) and low-dosage U0126 group (n =35). Rats in the sham operation group were only treated with incision of epicranium and fixation of backup plate, but not hit. Rats in the model group were used to establish diffuse brain injury models based on Marmarou free falling body without drug intervention. Rats in the high- and low-dosage U0126 groups were injected into caudal vein with 0.1 and 0.05 mg/kg U0126, respectively, and then, rats were hit to establish injured models. Every 5 rats were collected from model, high- and low-dosage U0126 groups at 5, 30 minutes, 3, 12, 24, 72 hours and 7 days after diffuse brain injury to detect pERK1/2 expression in cortex of parietal lobe based on Western blot technique. ② Distribution of pERK1/2 and positive GFAP cells in brain tissue: Another 48 rats were randomly divided into sham operation group (n =3), model group (n =15), high-dosage U0126 group (n =15) and low-dosage U0126 group (n =15). The intervention and administration were dealt as the same as those mentioned above. Every 3 rats were collected from model, high- and low-dosage U0126 groups at 30 minutes, 3, 12, 24 and 72 hours after model establishment to observe the distribution of pERK1/2 and postive GFAP cells in brain tissue which was cut from coronal section at Bregma –4.8 mm layer with immunohistochemical staining. MAIN OUTCOME MEASURES: pERK1/2 expression in cortex of parietal lobe and distribution of pERK1/2 and positive GFAP cells in brain tissues. RESULTS: ① pERK1/2 expression: After diffuse brain injury, pERK1/2 expression in cortex of parietal lobe was rapidly increased in the model group, reached at peak at 5 minutes and then decreased gradually. But the expression was still in a high level until the 72nd hour and fallen to the basic level on the 7th day. pERK1/2 level was lower in high- and low-dosage U0126 groups than that in model group at various time points (P < 0.01); meanwhile, pERK1/2 level was lower in high-dosage U0126 group than that in low-dosage U0126 group. The results showed that there was a certain dosage dependence on pERK1/2 expression. ② Distribution of pERK1/2 and positive GFAP cells in brain tissue: Positive expression of pERK1/2 lasted in brain tissue from 30 minutes to 72 hours after diffuse brain injury (P < 0.05). In addition, from 30 minutes to 3 hours, brown-yellow stained cells were mainly distributed in plasma, but rarely in nucleus. A lot of positive cells had tree-like apophysis, which was similar to neurons. With the time passing by, more and more nuclei manifested positive stains; moreover, nuclei mainly manifested positive staining until 24 hours after diffuse brain injury. Immune-positive pERK1/2 cells were widely distributed in brain tissue, especially mainly in binding site between deep cortex and cerebral white matter, and then in hippocampus. In addition, ependymal cell and vascular endothelial cells of choroids plexus also manifested strongly positive staining. As compared with model group, positive cells were decreased gradually in high- and low-dosage U0126 groups. However, number of positive cells was less in high-dosage U0126 group than that in low-dosage U0126 group. CONCLUSION: Diffuse brain injury strongly induces the activity of ERK1/2 signal pathway and response of astrocyte; in addition, U0126 can inhibit response of glial cells during an acute period, and the effect manifests dosage dependence.     

原发性前列腺印戒细胞癌(1例报告并文献复习)

目的探讨原发性前列腺印戒细胞癌的临床特征。方法回顾性分析1例原发性前列腺印戒细胞癌患者的临床资料,并结合文献进行复习讨论。结果患者前列腺穿刺活检病理报告为前列腺印戒细胞癌,免疫组织化学检查示PSA( ),PAS、CEA、LCA、CKH(-),行双侧睾丸切除术和氟他胺治疗,术后1月死于肺部转移。结论原发性前列腺印戒细胞癌来自前列腺腺泡上皮,确诊依靠病理组织学和免疫组化检查。临床罕见,恶性程度高,预后较差。     

颅脑外伤后肢体痉挛状态的显微外科治疗

目的 探讨显微外科治疗颅脑外伤后肢体痉挛状态的疗效.方法 回顾分析2006年7月至2008年7月实施的21例显微外科治疗颅脑外伤后肢体痉挛状态,根据不同病例采用相应的选择性周围神经部分切断术,包括:胫神经、肌皮神经、正中神经、尺神经和腰骶段脊神经后根,共计50个肢体.结果 术后随访2～24个月,全部患者术后立即感相应肢体痉挛状态缓解,随访期间缓解率为98%(49/50).随访期间运动功能改善率为86%(18/21),生活质量提高率为95%(20/21).术后发生肢体麻木、疼痛等感觉异常26个(52%),肌力下降18个(36%),随访期间均见好转.术后痉挛状态复发1个(2%).结论 选择性周围神经部分切断术是治疗颅脑外伤后肢体痉挛状态安全有效的方法.选择适应证及手术时机和术后坚持康复训练是保证疗效的关键.     

微血管减压术治疗舌咽神经痛16例临床分析

目的　研究舌咽神经痛 (glossopharyngealneuralgia,GPN)手术治疗的最佳术式 ,评估微血管减压手术(microvasculardecompression ,MVD)的效果、并发症和随访结果 ,探讨可能的治疗机制。方法　 2 0 0 0年 12月到2 0 0 3年 10月间 ,16例GPN患者接受了MVD ,无一例行神经根切断术。患者全部进行了电话或信件随访。结果　15例患者术后疼痛消失 ,1例患者为不典型GPN ,术后疼痛减轻。 1例患者术后出现轻度声音嘶哑和吞咽困难 ,1例患者出现偶发干咳。本组患者平均随访时间为 14 .1± 6 .3月 ,随访期间无一例复发。结论　MVD是治疗舌咽神经痛的一种安全、有效的手术方式 ,尤其适用于典型的GPN患者。     

Protein ubiquitination in postsynaptic densities after transient cerebral ischemia.

The mechanisms underlying neurologic deficits and delayed neuronal death after ischemia are not fully understood. In the present study, we report that transient cerebral ischemia induces accumulation of ubiquitinated proteins (ubi-proteins) in postsynaptic densities (PSDs). By immunoelectron microscopy, we demonstrated that ubi-proteins were highly accumulated in PSD structures after ischemia. On Western blots, ubi-proteins were markedly increased in purified PSDs at 30 minutes of reperfusion, and the increase persisted until cell death in the CA1 region after ischemia. In the resistant DG area, however, the changes were transient and significantly less pronounced. Deposition of ubi-proteins in PSDs after ischemia correlates well with PSD structural damage in the CA1 region as viewed by electron microscopy. These results suggest that the ubiquitin-proteasome system fails to repair and remove damaged proteins in PSDs. The changes may demolish synaptic neurotransmission, contribute to neurologic deficits, and eventually lead to delayed neuronal death after transient cerebral ischemia.     

彩色多普勒超声心动图与核磁共振诊断主动脉夹层动脉瘤的对比研究

目的　通过彩色多普勒超声心动图 (CDUCG)和核磁共振成像 (MRI)诊断主动脉夹层动脉瘤 (AD)的影像学特征 ,比较两种无创检查技术诊断AD的临床价值。方法　对临床疑诊AD的患者行CDUCG心脏各切面探查 ,重点扫查并测量主动脉各节段异常超声征象 (夹层发生部位、内膜片跨度、管径宽度等 ) ,对相同患者行MRI检查时在扫描图像上辨认并确定夹层发生的部位、撕裂范围等。结果　CDUCG诊断Ⅰ型AD 4例 ,Ⅱ型 2例 ,Ⅲ型AD 1例。MRI对Ⅰ、Ⅱ、Ⅲ型AD均可明确诊断。本文 3例Ⅲ型AD经MRI确诊并检出附壁血栓 2例 ,1例Ⅰ型AD可疑 ,余结果同CDUCG。结论　两种技术诊断AD各有优缺点 ,CDUCG偏重于诊断Ⅰ、Ⅱ型 ,MRI适合各型AD的诊断。前者更为迅速、直观 ,重复性强 ,可了解心血管病变的全部信息 ;危急重症患者不宜或难以接受MRI检查。     

超声心动图对62例房间隔缺损封堵术后心功能变化的评价

目的：应用超声心动图评价房间隔缺损(ASD)封堵术前后左、右心室功能的变化。方法：对62例成功施行经皮穿刺ASD封堵术的患者进行研究。所有患者在术前、术后1周及1个月分别进行超声心动图检查．观察心脏大小及功能的改变。结果：ASD封堵术后，左室舒张末期前后径、左室舒张末期容积、左室每搏量及左室射血分数增大，而左室收缩末期容积未见明显改变；右室舒张末期前后径、右室舒张末期容积、右室收缩末期容积、右室每搏量、右室射血分数及右室心肌工作指数均减小。结论：经皮穿刺ASD封堵治疗既可减轻右室容量负荷，改善右室功能，也可改善左室的收缩功能：超声心动图对ASD封堵前后心脏血流动力学评价及疗效的观察起了重要的作用。     

Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

斑点免疫金渗滤法的改进

目的 :改进斑点免疫金渗滤法的渗滤装置 ,降低成本 ,使之更适用于现场操作。方法 :用自制的圆形渗滤片替代塑料渗滤盒 ,并比较二者的效果。结果 :自制的渗滤片体积更小 ,成本更低 ,为一次性使用材料 ;检测抗体的效果与塑料渗滤盒法一致。结论 :自制的渗滤片优于常用的塑料渗滤盒