Fat suppression by section-select gradient reversal on spin-echo MR imaging. Work in progress

A method to decrease the intensity of fat by reversal of the section-select gradient is demonstrated. This technique takes advantage of the chemical shift in section location.     

Mortality figures in a rural hospital

The causes of death in a rural hospital in Bophuthatswana were recorded in 1983, 1984 and 1985. Several preventable conditions were found to be the most common causes of death in adults and in children.     

参三七皂甙Rg1对实验性血栓形成的影响及其机制探讨

用大鼠动静脉血栓形成模型，研究参三七皂甙Ｒｇ１抗血栓作用。结果表明，参三七皂甙Ｒｇ１可明显降低实验性血栓形成，对大鼠血浆纤溶系统亦有明显作用，可升高血浆中组织纤溶酶原激活物（ｔＰＡ）活性和活性型ｔＰＡ百分比，降低组织纤溶酶原激活物抑制剂（ＰＡＩ）活性。同时利用培养大鼠血管内皮细胞实验，发现Ｒｇ１可以剂量依赖性提高血管内皮细胞一氧化氮（ＮＯ）释放。提示Ｒｇ１抗血栓作用与增强纤溶系统活性，促进血管内皮ＮＯ释放有关     

4-间氨基酚-4去甲表鬼臼醚诱导K562细胞凋亡

目的:鬼臼毒素具有抗炎作用,为限制其对机体产生不良反应,探讨经过结构改造的4-间氨基酚-4去甲表鬼臼醚对K562细胞生长抑制及诱导凋亡情况。方法:实验于2004-03/2005-01在兰州医学院完成。①实验材料:4-间氨基酚-4去甲表鬼臼酯由兰州大学应用有机化学国家重点实验室田暄教授惠赠,纯度98%。依托铂甙(连云港恒瑞药业产品,批号04060121,20g/L)临用前以5%二甲亚砜稀释至5g/L。K562细胞由兰州大学中药新药临窗前研究重点实验室传代保种。②细胞生长抑制率检测:取K562细胞,离心后调整浓度为1×108L-1,以100μL等量接种于96孔培养板。4-间氨基酚-4去甲表鬼臼醚组分别加入0.313,0.625,1.25,2.5,5,10,20,40mg/L的4-间氨基酚-4去甲表鬼臼醚药液10μL;依托铂甙组分别加入以上8种终浓度的依托铂甙药液10μL;正常对照组加入等量的溶媒;空白对照组不加细胞和任何药物,只加入等量的完全培养液。采用噻唑蓝法检测药物与细胞作用24,48,72h时K562细胞的生长抑制率。③细胞超微结构观察:取K562细胞,离心后调整浓度为1×109L-1,以2mL等量接种于24孔培养板。4-间氨基酚-4去甲表鬼臼醚组加入2.5mg/L的4-间氨基酚-4去甲表鬼臼醚药液200μL,正常对照组加入等量的溶媒。制作超薄切片,用醋酸双氧铀、柠檬酸铅染色,透射电镜观察细胞形态及细胞质、细胞核的变化。④细胞周期及凋亡检测:取K562细胞,离心后调整浓度为1×108L-1,以2mL等量接种于24孔培养板。4-间氨基酚-4去甲表鬼臼醚组分别加入1.25,2.5,5,10,20mg/L的4-间氨基酚-4去甲表鬼臼醚药液200μL,正常对照组加入等量的溶媒。在流式细胞仪上检测细胞周期,用Multicycle软件计算凋亡细胞百分率。结果:①4-间氨基酚-4去甲表鬼臼醚抑制K562细胞生长情况:在0.313～20mg/L范围内,其对K562细胞的抑制作用随浓度升高而增强,具有量效关系,同时抑制率随着作用时间的延长而升高,具有时效关系;超过20mg/L时抑制作用逐渐下降。依托铂甙对K562细胞的抑制情况与4-间氨基酚-4去甲表鬼臼醚类似。②细胞超微结构:正常对照组K562细胞核形状规则,核膜清晰可见,内质网丰富,内含大量线粒体,细胞表面微绒毛多,染色体分布于核中央。4-间氨基酚-4去甲表鬼臼醚组K562细胞出现明显的凋亡特征,微绒毛消失,细胞浆固缩,染色体凝集为团块状分布于核膜边缘,细胞内出现大量空泡,线粒体和内质网减少,细胞周围出现凋亡小体。③细胞周期及凋亡情况:1.25,2.5,5,10,20mg/L4-间氨基酚-4去甲表鬼臼醚作用24h,分别有19.4%,34.8%,34.0%,6.9%,4.5%的K562细胞发生凋亡,G0/G1期和S期K562细胞减少,于G2/M期明显增多。正常对照组凋亡率仅为0.3%。结论:①4-间氨基酚-4去甲表鬼臼醚能够抑制K562细胞的生长,呈时效、量效关系。②4-间氨基酚-4去甲表鬼臼醚可诱导K562细胞凋亡。     

αE‐catenin is a candidate tumor suppressor for the development of E‐cadherin‐expressing lobular‐type breast cancer

Although mutational inactivation of E‐cadherin (CDH1) is the main driver of invasive lobular breast cancer (ILC), approximately 10–15% of all ILCs retain membrane‐localized E‐cadherin despite the presence of an apparent non‐cohesive and invasive lobular growth pattern. Given that ILC is dependent on constitutive actomyosin contraction for tumor development and progression, we used a combination of cell systems and in vivo experiments to investigate the consequences of α‐catenin (CTNNA1) loss in the regulation of anchorage independence of non‐invasive breast carcinoma. We found that inactivating somatic CTNNA1 mutations in human breast cancer correlated with lobular and mixed ducto‐lobular phenotypes. Further, inducible loss of α‐catenin in mouse and human E‐cadherin‐expressing breast cancer cells led to atypical localization of E‐cadherin, a rounded cell morphology, and anoikis resistance. Pharmacological inhibition experiments subsequently revealed that, similar to E‐cadherin‐mutant ILC, anoikis resistance induced by α‐catenin loss was dependent on Rho/Rock‐dependent actomyosin contractility. Finally, using a transplantation‐based conditional mouse model, we demonstrate that inducible inactivation of α‐catenin instigates acquisition of lobular features and invasive behavior. We therefore suggest that α‐catenin represents a bona fide tumor suppressor for the development of lobular‐type breast cancer and as such provides an alternative event to E‐cadherin inactivation, adherens junction (AJ) dysfunction, and subsequent constitutive actomyosin contraction. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

An accidental gallbladder schwannoma misdiagnosis as malignant cancer

<正>To the Editor: Schwannomas are mainly benign neurogenic tumors originating from the Schwann cells in peripheral nerves sheaths and occur in patients at any age and in every location [ 1, 2 ]. The most common occurring sites of schwannomas are the head, neck and extremities [3]. In the abdominal cavity, the most frequently involved sites are the retroperitoneum and stomach [4].     

Protein macromonomers containing reduction-sensitive linkers for covalent immobilization and glutathione triggered release from dextran hydrogels

We report an efficient strategy to conjugate methacrylamide moieties to the lysine units of lysozyme for co-polymerization and subsequent triggered release from hydrogels. Two novel linker molecules, containing an ester bond and/or a disulfide bond for temporary immobilization, were synthesized and conjugated to lysozyme. Lysozyme was successfully modified with on average 2.5 linker molecules per protein molecule, as evidenced by MALDI-TOF and by titration of the free amine groups, while spectral analysis verified the preservation of the protein structure. Next, methacrylated dextran (Dex-MA) was polymerized in presence of native or modified lysozyme to yield hydrogels. The release of native and modified lysozyme from Dex-MA hydrogels was studied in acetate buffer (pH 5, in absence of any trigger) and only a minor fraction (~ 15%) of the modified lysozyme was released, whereas ~ 74% of the native lysozyme was released. This indicates successful immobilization of the majority of the modified lysozyme in the hydrogel network. Upon hydrolysis of the ester bonds or incubation with glutathione to reduce disulfide bonds of the linker molecules that conjugate the lysozyme to the gel network, the modified lysozyme was mobilized and released from the hydrogel to the same extent as native lysozyme. These data were confirmed by fluorescence recovery after photobleaching experiments. This approach appeared to be highly interesting for temporary immobilization and subsequent glutathione triggered intracellular delivery of proteins from hydrogels.