肌苷对大鼠脑缺血再灌注后GAP-43 mRNA表达影响

目的探讨肌苷对脑缺血再灌注后中枢神经再生的作用。方法线栓法建立大脑中动脉缺血再灌注模型,随机分为治疗组和对照组,每组再随机分为缺血1.5 h再灌注2 h、12 h、1 d、2 d、3 d、7 d1、4 d组(n=4),另取4只作假手术组。应用BEDERSON等神经功能评分法评定神经功能,原位杂交技术检测脑缺血再灌注后各时间点脑组织生长相关蛋白基因(GAP-43 mRNA)的表达。结果对照组于再灌注2 h~7 d、治疗组于再灌注12 h~7 d,GAP-43 mRNA表达与假手术组比较明显增多(t=2.70~29.84,P<0.05),治疗组与对照组比较GAP-43mRNA表达于再灌注2 h一过性下降,12 h和7 d明显增高(t=1.97~7.41,P<0.05);治疗组与对照组比较神经功能恢复于再灌注7 d有显著性差异(t=2.31,P<0.05)。结论肌苷可促进大鼠脑缺血再灌注后神经功能恢复,其作用机制可能是通过调节与神经轴突再生有关的GAP-43 mRNA表达而实现的。     

不同分化胃癌细胞系中间隙连接蛋白的表达

目的探讨间隙连接蛋白（Cx）Cx26、Cx32、Cx43、Cx45在转化的人胃细胞系（GES-1）、胃高分化腺癌细胞系（N87）和胃低分化腺癌细胞系（BGC-823）中的表达及其与胃癌发生、发展的关系。方法采用间接免疫荧光方法检测Cx26、Cx32、Cx43、Cx45在不同分化程度胃癌细胞株中的表达，并分析该蛋白表达与胃癌发生、发展的关系。结果在不同分化胃癌细胞株中。Cx26、Cx32、Cx43、Cx45表达呈现1个由高水平到低水平表达直至无表达的梯度分布，既Cx26、cx32、Cx43、Cx45在GES-1中高水平表达，在N87表达减少，在BGC-823中无表达，并且表达部位有差异。结论Cx26、Cx32、Cx43、Cx45的表达与胃癌细胞的分化关系密切，在胃癌的发生、发展中有一定作用。     

Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors.

BACKGROUND: BAY 43--9006, an oral multi-kinase inhibitor, targets serine-threonine kinases and receptor tyrosine kinases, and affects the tumor and vasculature in preclinical models. Based on its pharmacologic effect, it may be a useful cancer treatment. This study determined the maximum tolerated dose (MTD) of BAY 43-9006 in 42 patients with advanced, refractory metastatic or recurrent solid tumors. Dose-limiting toxicities (DLTs), safety, pharmacokinetics and tumor response were also evaluated. PATIENTS AND METHODS: In this open-label, phase I, dose-escalation study, BAY 43--9,006 was administered orally in repeated cycles of 35 days (28 days on/7 days off). Eight doses were investigated: from 50 mg every fourth day to 600 mg twice daily. Treatment continued until unacceptable toxicity, tumor progression or death. RESULTS: The MTD was 400 mg twice daily. BAY 43-9006 was well tolerated, with mild to moderate toxicities; only six patients discontinued study therapy due to adverse events. DLTs consisted of hand-foot skin reaction in three of seven patients receiving 600 mg twice daily. Stable disease was achieved in 22% of patients; median duration of stable disease was 7.2 months. Consistent with its observed half-life of approximately 27 h, BAY 43-9, 006 accumulated on multiple dosing. Increases in exposure were less than proportional to the increases in dose. CONCLUSIONS: Results indicate that further clinical investigation of BAY 43--9006 is warranted, and suggest it could be a promising future therapy for patients with cancer.     

大鼠视神经挫伤后生长相关蛋白的变化及重组人促红细胞生成素的作用

目的 研究大鼠视神经挫伤后视神经生长相关蛋白( GAP-43)的变化及重组人促红细胞生成素(rhEPO)的作用.方法 建立外伤性视神经损伤的动物模型,随机分为正常对照组、损伤组(视神经钳夹+生理盐水)及rhEPO组(视神经钳夹+rhEPO),于损伤后1d、4d、7d、14 d和28 d对各组视网膜及视神经进行形态学观察,免疫组化染色法测定视神经GAP-43的活性.结果 rhEPO组较损伤组视网膜及视神经病变明显减轻；在损伤后4d和7d趼组间损伤远端GAP-43表达差异无统计学意义(P＞0.05)；14 d和28 d rhEPO组损伤远端GAP-43表达较损伤组明显升高(P＜0.05).结论 rhEPO对视神经不完全损伤可促进视网膜神经节细胞存活与视神经纤维再生修复.     

The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists.     

First Report of an Acute,Obstructive Thrombosis of a Melody Valve Used for Transcatheter Pulmonary Replacement

Transcatheter pulmonary valve (TPV) replacement is an effective therapy of right ventricular outflow tract conduit dysfunction. Acute complications after TPV implantation include infective endocarditis, stent fracture, and device dislocation. We present a novel, life-threatening complication: an acute, noninfectious TPV thrombosis. Within 24 hours after implantation of a Melody system (Medtronic, Inc, Minneapolis, MN), the patient developed an acute TPV thrombosis characterized by severe TPV stenosis on echocardiography and contrast filling defects on computed tomography pulmonary angiography images. Genetic testing revealed heterozygous prothrombin G20210A polymorphism and homozygous 4G/4G polymorphism of the plasminogen-activator-inhibitor. The patient recovered after surgical valve replacement with a pulmonary homograft.     

Subcellular and regional location of “brain” proteins BASP1 and MARCKS in kidney and testis

Proteins BASP1 and MARCKS are abundant in axonal endings of neurons. Similarly to brain-specific protein GAP-43, BASP1 and MARCKS are reversibly bound to the plasma membrane. These proteins control both actin polymerization and actin cytoskeleton binding to the membrane. Performing these functions, BASP1 and MARCKS take part in growth cone guidance during development and in neurotransmitter secretion in adults. These activities predetermine the pivotal role of BASP1 and MARCKS in learning and memory. BASP1 and MARCKS were also found in non-nerve tissues, in particular, in the kidney and testis. Evidently, the physiological roles of these proteins differ in different tissues. Correspondingly, their intracellular location and activities may not be similar to those in neurons. In this paper, we analyze subcellular fractions (cytoplasm and nuclei) of rat kidney and testis with the purpose of determining the intracellular location of BASP1 and MARCKS. Western blots demonstrated that in these tissues, as in the brain, both proteins are present in the cytoplasm of the cell. According to our immunohistochemical study, BASP1 and MARCKS are specifically distributed in the tissues studied. In kidney, both proteins are present in cells located in glomeruli. In the testicular tubules, BASP1 is mainly expressed at the late stage of spermatogenesis (in spermatids) and is preserved in mature spermatozoa, while MARCKS appears equally during all stages of spermatogenesis. MARCKS is not found in mature spermatozoa. The results indicate that study of functions of BASP1 and MARCKS in the kidney and in the reproduction system holds much promise.