Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases

Composite lymphoma is a well‐known diagnostic entity exhibiting the synchronous occurrence of two or more distinct types of lymphomas in the same specimen. Here we report two patients, a 14‐year‐old female (Case 1) and a 45‐year‐old male (Case 2), with mediastinal composite lymphoma, comprising nodular sclerosis classic Hodgkin lymphoma (NSCHL) and primary mediastinal large B‐cell lymphoma (PMBL). Both patients had a mediastinal mass, and manifested two different histologic components in the same biopsy, one characteristic of NSCHL and the other PMBL. The NSCHL areas included Hodgkin and Reed–Sternberg (HRS) cells with typical immunophenotypic features (CD30‐positive and CD20‐negative), whereas the sheets of large tumor cells characteristic of PMBL were strongly and uniformly CD20‐positive. Interestingly, although both cases showed neoplastic PD‐L1 (nPD‐L1) positivity on the HRS cells of NSCHL, they differed regarding nPD‐L1 expression on the PMBL tumor cells. In Case 1, the nPD‐L1‐negative PMBL component was anatomically situated outside the NSCHL lesion. On the other hand, in Case 2, the nPD‐L1‐positive PMBL component was characterized by transitional or continuous areas with the NSCHL component. These findings suggested that nPD‐L1 expression may define two subtypes of PMBL that are more similar to or distinct from classic Hodgkin lymphoma.     

Quantification of Intracellular Accumulation and Retention of Lysosomotropic Macrocyclic Compounds by High-Throughput Imaging of Lysosomal Changes

Many marketed pharmaceuticals reach extremely high tissue concentrations due to accumulation in lysosomes (lysosomotropism). Quantitative prediction of intracellular concentrations of accumulating drugs is challenging, especially for macrocyclic compounds that mainly do not fit in current in silico models. We tested a unique library of 47 compounds (containing 39 macrocycles) specifically designed to cover the entire range of accumulation intensities observed with pharmaceuticals so far. For the first time, we show that intracellular concentration of compounds measured by liquid chromatography with tandem mass spectrometry correlates with the induction of phospholipidosis and inhibition of autophagy, but the highest correlation was observed with the increase of lysosomal volume (R = 0.95), all measured by high-throughput imaging assays. Based only on imaging data, we developed a 5-class in vitro model for the prediction of compound accumulation with the accuracy of 81%. The measured change of total lysosomal volume can thus be used in high-throughput screening for determination of the actual intensity of intracellular accumulation of new macrocyclic compounds. The models are largely based on macrocycles, greatly improving the screening and prediction of intracellular accumulation of this challenging class. However, all tested nonmacrocyclic compounds fitted well in the models, indicating potential use of the models in broader chemical space.     

肝脏切除术治疗肝脏海绵状血管瘤

从１９８３年至１９９３年共对２２例肝脏海绵状血管瘤进行了手术切除治疗。根据肿瘤的不同情况（如大小、位置以及与肝脏大血管的关系等）我们采用了不同的手术方式．包括肿瘤的膜外剥除、肝段切除、肝叶切除以及无血切肝术。我们体会到．有症状的或巨大的肝脏海绵状血管瘤应考虑积极的外科治疗．应根据肿瘤的具体情况，选择相应的手术方式。     

人参皂苷Rd对中国仓鼠肺细胞染色体畸变作用

目的研究人参皂苷Rd致中国仓鼠肺细胞（Chinese hamster lung cells,CHL）染色体畸变的作用。方法细胞计数法测定人参皂苷Rd对CHL细胞的半数抑制浓度（IC50）,根据IC50设立不同剂量组,进行染色体畸变试验,分别观察人参皂苷Rd染毒6、24h及加S9后染毒6hCHL细胞染色体的数目及结构变化,进行染色体畸变分析。结果人参皂苷Rd染毒6、24h及加S9后染毒6hCHL细胞染色体畸变为阴性。结论在本试验条件下,人参皂苷Rd不能引起CHL细胞染色体产生畸变。     

In vitro and in vivo assessment of the genotoxic activity of aloesin

Aloesin is a chromone that is a component of Aloe spp. It may have potential as a functional food ingredient as it has been shown to likely have beneficial effects in persons in a pre-diabetic state or who have metabolic syndrome. In this study the safety of aloesin has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell cytogenetic, and mouse micronucleus tests. Aloesin did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at any of the tested dose levels up to 10,000 μg/plate. Similarly, aloesin did not increase the incidence of chromosome aberrations when incubated with Chinese hamster lung cells at any of the tested concentrations up to 10,000 μg/mL. In vivo, there was no effect of aloesin on the incidence of micronucleated erythrocytes following oral administration on two consecutive days at doses up to 5000 mg/kg body weight. There was no evidence of toxicity to bone marrow. The results of these studies demonstrate that aloesin is without genotoxic potential.     

乙烷硒啉致突变试验研究

目的观察乙烷硒啉是否存在遗传毒性。方法应用Ames试验、中国仓鼠肺细胞体外培养染色体畸变试验和小鼠骨髓嗜多染红细胞微核试验,研究乙烷硒啉的致突变作用。结果Ames试验在〈400μg/皿浓度下未见回复突变菌落数显著增加;中国仓鼠肺细胞体外培养染色体畸变试验在〈3.3μg/ml浓度下未出现细胞染色体畸变率显著增高;小鼠骨髓嗜多染红细胞微核试验在〈20.0g/kg剂量下未诱发微核细胞率的增高。结论乙烷硒啉在试验剂量范围内无致突变作用。     

"冻干江浙蛇毒"的致突变作用研究

目的:检测"冻干江浙蛇毒"的致突变性,以提供有关致突变的遗传毒性安全评价数据.方法:采用小数骨髓微核试验、微生物回复突变试验(Ames)、仓鼠肺成纤维细胞染色体畸变试验(CHL),研究"冻干江浙蛇毒"的致突变作用.结果:小鼠骨髓微核试验表明,"冻干江浙蛇毒"三个剂量组(1.0、0.5、0.25mg/kg腹腔注射)的微核出现率与阴性对照组(0.9%NaCl)比较无显著性(P＞0.05),与阳性对照组比较有显著性(P＜0.01);Ames试验表明,"冻干江浙蛇毒"采用5000、2500、1250、625和312.5ug/皿剂量时,在加和不加S9条件下,对TA97、TA98、TA100和TA102菌株回复突变菌落数结果为阴性;CHL试验也表明,"冻干江浙蛇毒"4.0、2.0、1.0和0.5ug/ml剂量对中国仓鼠肺成纤维细胞(CHL)体外培养染色体无畸变作用.结论:"冻干江浙蛇毒"无致突变性,有良好的应用前景.     

乌头类中药对CHL细胞的DNA损伤作用

[目的]观察乌头类中药盐附子和乌头碱对CHL细胞(中国仓鼠肺成纤维细胞)的DNA损伤作用。[方法]采用单细胞凝胶电泳法检测盐附子、乌头碱对CHL细胞DNA即刻损伤的影响。在加和不加S9时,盐附子均设5个剂量组(终浓度分别为5、2.5、1.25、0.625、0.313 mg生药∕ml)、乌头碱设4个剂量组(终浓度分别为100、50、25、5μg/ml),试验同时设PBS阴性对照组和阳性对照组,阳性对照在不加S9时为0.1 mmol/ml重铬酸钾,加S9时为80μg/ml环磷酰胺。[结果]在加和不加S9时,盐附子各浓度组拖尾细胞率和拖尾细胞尾长与阴性对照比较差异无统计学意义(P﹥0.05),乌头碱100μg/ml和50μg/ml组拖尾细胞率和拖尾细胞尾长与阴性对照之间差异有统计学意义(P﹤0.05),乌头碱各浓度组拖尾细胞率和拖尾细胞尾长存在剂量反应关系。[结论]在本试验条件下,加与不加S9时,乌头碱浓度为100μg/ml和50μg/ml时对CHL细胞有DNA损伤作用;盐附子5、2.5、1.25、0.625、0.313 mg生药/ml时未观察到对CHL细胞有DNA损伤作用。     

阿比哚致突变作用的研究

目的研究阿比哚的致突变作用。方法应用微生物回复突变试验、小鼠微核试验、哺乳动物培养细胞染色体试验 ,观察阿比哚对细胞的诱变性。结果阿比哚的Ames实验、小鼠体内微核试验、CHL细胞染色体畸变试验均呈阴性结果 ,阿比哚无诱变性。结论阿比哚无致突变作用。