Kynurenine aminotransferase activity in human liver: identity with human hepatic C-S lyase activity and a physiological role for this enzyme

The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate.     

MR imaging of the brain in patients with hepatic form of Wilson''s disease

The aim of this study was to detect the sites and frequency of possible lesions by brain magnetic resonance imaging (MRI; 1,5T) in a group of 16 neurologically asymptomatic patients with hepatic form of Wilson's disease (WD; seven untreated and nine under treatment). Abnormal MR findings of the brain were found in 75% of patients. Lesions in brain parenchyma were detected in all untreated, drug-naive patients and in 44% of treated patients. Abnormal signal in globus pallidus, putamen, and caudate nucleus was revealed in 86, 71 and 71% of treated and in 33, 33 and 22% of untreated patients, respectively. In five of eight patients with putaminal pathology (62.5%) and in four of seven patients with caudate nuclei involvement (57%), only proton density 2-weighted sequence (PDW) exhibited sensitivity for lesion detection, with both T1W and long echo T2W sequences being insensitive. This superiority of PDW sequence was even more pronounced in the group of untreated patients in whom 80% of putaminal pathology was visible exclusively on this sequence. The lower frequency of lesions in the group of treated in comparison with untreated patients indicated that they might be reversible in the course of chronic chelating therapy.     

细菌内快速构建两种用于肝纤维化基因治疗的重组复制缺陷型腺病毒

目的 :在大肠杆菌内快速构建两种分别含有人肝细胞生长因子 (hepatic growth factor,HGF)和非分泌型人尿激酶型纤溶酶原激活剂 (urokinase- type plasm inogen activator,u PA) c DNA片段的重组复制缺陷型腺病毒。方法 :分别将人 HGF和 u PA c DNA片段与穿梭载体 p Track- CMV连接 ,线性化后与骨架载体 Ad Easy- 1在大肠杆菌 BJ5 183内同源重组获得腺病毒载体 p Ad HGF和 p Adu PA,经 2 93细胞包装后得到复制缺陷型重组腺病毒 Ad HGF和 Adu PA;将 Ad HGF和 Adu PA分别体外感染肝细胞株 L0 2 ,以 Northern印迹法和 Western印迹法检测两种病毒在肝细胞中的表达。 结果 :连接、重组后通过酶切和测序法筛选出病毒质粒 p Ad HGF和 p Adu PA;经 2 93细胞包装 ,3d后均观察到绿色荧光蛋白明显表达 ,Cs Cl梯度离心纯化最终分别获得 4× 10 1 0 efu/ m l滴度的重组病毒 Ad HGF和 6× 10 1 0 efu/ ml Adu PA;两种病毒体外感染肝细胞 3d后 ,HGF和u PA表达均明显增加。结论 :细菌内同源重组制备复制缺陷型腺病毒 ,纯化过程简单 ,重组腺病毒在肝细胞中均高效表达 ,为肝细胞移植基因治疗肝纤维化提供了新的手段     

提高抗肝癌药物的肝脏浓度并降低心脏,血液浓度的实验研究

实验研究结果表明：阿霉素（ＡＤＭ）在采用推进法注射时，经肝血管或外周静脉途径二者的肝、心与血液浓度均无显著差别．如采用控速缓慢输注法，则经肝血管较经外周静脉在提高肝脏浓度方面具有显著效果，心脏内浓度也有一定程度降低。如在肝血管内输注时与血液净化联合应用，则更能提高上述要求。以上结果将为临床抗癌药介入治疗应用方法的开展提供依据和参考价值。     

门静脉转流对肝硬化大鼠耐受入肝血流阻断时限的影响

目的：探讨门静脉转流对肝硬化大鼠耐受人肝血流阻断时限的影响。方法：观测门静脉转流与非门静脉转流条件下阻断入肝血流不同时程后动物存活率及肝脏能量代谢的变化，包括肝细胞线粒体呼吸控制率（RCR）、肝组织三磷酸腺苷（ATP）含量、动脉血酮体比值（AKBR）。结果：①术后两周存活率：肝硬化大鼠门静脉转流下入肝血流阻断（PBB）-30min组和PBB-45min组为100%，单纯入肝血流阻断（PTC）-30min组、PBB-60min组分别为65%和75％。②肝脏能量代谢：缺血后肝组织ATP、RCR及AKBR均明显下降。再灌注后上述指标逐渐恢复，但随缺血时间延长，升高幅度明显降低，甚至难以恢复。结论：门静脉转流能显著提高肝硬化大鼠常温下耐受入肝血流阻断的时限。     

Sarcoidosis and primary biliary cirrhosis

Summary An unusual case of a woman with primary biliary cirrhosis and cutaneous sarcoidosis is described. The factors that allow a specific diagnosis of each condition are presented and the literature pertaining to such complex and unusual cases is presented.This work was supported in part by a grant from the Gastroenterology Medical Research Foundation of Southwestern Pennsylvania.     

ERK信号传导通路调控乙醛刺激的肝星状细胞Na+/Ca2+泵mRNA表达的研究

目的 :探讨Erk信号传导通路调控乙醛刺激的肝星状细胞 (HSC)Na /Ca2 泵mRNA表达的影响。方法 :用链霉蛋白酶和胶原酶原位灌流 ,Metrizamide密度梯度离心分离大鼠肝星状细胞 ,采用RT PCR测定PD980 5 9阻断乙醛激活的肝星状细胞Erk活性后Na /Ca2 泵mRNA表达。结果 :乙醛刺激后 ,HSC后明显促进Na /Ca2 泵mRNA表达 (P<0 0 1) ,不同剂量PD980 5 9对肝星状细胞Na /Ca2 泵mRNA表达的影响无统计学意义。结论 :Erk信号传导通路可能对乙醛刺激的肝星状细胞激活状态的启动无明显影响     

枳鳖胶囊抗大鼠肝纤维化形态学及肝组织Ⅲ型胶原mRNA表达的实验研究

目的:观察枳鳖胶囊抗肝纤维化形态学和Ⅲ型胶原mRNA表达的变化。方法:选择66只健康清洁级SD大鼠,雌雄各半,随机分为:正常对照组,模型组,秋水仙碱组,枳鳖胶囊大、中、小剂量组。以40%四氯化碳花生油皮下注射结合高脂饲料、酒水饮料复合因素诱导大鼠肝纤维化模型。造模结束后,除正常组不予处理外,其他组分别以蒸馏水,秋水仙碱混悬液,高、中、低浓度枳鳖胶囊溶液灌胃,疗程36d。疗程结束后,观察大鼠新鲜肝脏的表面情况、色泽、质地等大体形态,测定肝组织Ⅲ型胶原mRNA的表达,光镜观察肝组织HE染色和网状纤维染色的病理形态学改变。结果:模型组大鼠肝细胞损害、肝脏脂肪变性和胶原纤维增生的程度最显著,Ⅲ型胶原mRNA的表达最强。枳鳖胶囊组上述改变明显减轻,且可抑制Ⅲ型胶原mRNA的表达,疗效优于秋水仙碱组。结论:枳鳖胶囊可较好地保护肝细胞,并能阻止肝纤维化进程甚或逆转肝纤维化病理改变,抑制胶原基因表达,抑制胶原基因表达可能是其抗肝纤维化的作用机理之一。     

软肝丸治疗慢性血吸虫肝纤维化200例临床观察

目的 观察软肝丸对慢性血吸虫肝纤维化的疗效。方法 用软肝丸治疗慢性血吸虫肝纤维化病人200例，观察治疗前后肝脏的B超影像学改变。结果 治疗24周后，软肝丸组肝脏影像学有明显改善或恢复正常，与对照组比较，差异具有显著性（P〈0．05）。结论 软肝丸可明显改善慢性血吸虫肝纤维化。     

Liver pathology associated with the use of anabolic-androgenic steroids

Abstract: This review examines the liver-damaging side effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved that AAS can cause development of hepatocellular carcinomas when used in the usual therapeutic doses. Tumours reported as hepatocellular carcinomas caused by AAS seem to be hyperplastic lesions of a benign nature able to regress with withdrawal of the putative agent. The effects of untraditional combinations and high-dose AAS are not yet known, leaving the possibility of a carcinogenic effect in those cases.