动态研究HBV和AFB1诱发树鼠句肝细胞癌过程中一些基因的表达

目的：探讨人乙肝病毒(HBV)和黄曲霉毒素B,(AFB1)致肝细胞癌(HCC)及协同致HCC作用的机制。方法：将树鼩分为4组：A组：感染HBV加摄入AFB,;B组：只感染HBV;C组：只摄入AFB1;D组：作空白对照。然后定期行肝活检,用免疫组化、分子生物学等技术动态观察一些癌基因(蛋白)和抑癌基因的表达。结果：①A组谷胱苷肽转移酶(GGT)阳性灶个数及面积明显多于、大于B、C组;②A组P21蛋白检出率明显高于B和C组,A组6只P21蛋白阳性的树鼩到120周时全部发生了HCC;③实验后期,A组HBxAg检出率及HBVDNA整合率明显高于B组;④在诱癌过程中,IGF-Ⅱ表达率呈波动形,带癌肝的表达率显著高于无癌肝;⑤105周时,A、B、C组P53蛋白表达率显著高于D组;在A,C组检出P53异常带;⑥第45及105周时,A组c-fos表达率分别为23．1％和20％;C组为38．5％和15．4％,B,D两组均未检出;⑦H-c-myc基因：直到120周,无癌肝组织均未见异常;在肝癌组织中,A组有4例扩增,c组无异常;@CDK4基因：只有A组在第75周有1例扩增,该树鼩在第106周时发生了HCC。在HCC中,A组有25％出现CDK。扩增,C组未见异常。结论：再次证实HBV和AFB。有协同致HCC作用;AFB、有利于HBxAg的表达和HBVDNA的整合;CDK4、Kiras和P53基因的变异参与了HCC的发生和演进;P21和c-fos蛋白的过表达与P^53蛋白的失活,促进了HCC的发生和演进;CDK4和c-myc基因的改变与HBV的感染有一定的关联。     

Tuberculous granuloma in haemangiomatous nasal polyp

Tuberculosis of upper respiratory tract is quite infrequent especially the nasal involvement. Isolated cases have been reported by certain authors. A ease of nasal tubercolosis is being presented for its rare site and its association with haemangioma.     

How many sputum smears are necessary for case finding in pulmonary tuberculosis?

We reviewed the laboratory registers of 42 tuberculosis (TB) diagnostic centres in the southern region of Ethiopia to determine the value of submitting serial sputum samples for the diagnosis of pulmonary TB (PTB) and estimate the proportion of suspects that are smear positive. A total of 15,821 TB suspects submitted three smears each (47,463 smears) in 2000 with a median of 228 per centre. The smear positivity rate (two or more positive smears) was 25%, with a range of 16.8-36.4% per zone. This exceeds the international recommendations of examining 10 suspects to identify one case. A total of 4099 (26%) of the suspects had at least one positive smear with 3753 (91.6%) of the first specimens being positive. A further 303 (7.4%) were negative in the first specimen but had a positive second specimen and 42 (1%) suspects had two negative specimens followed by a positive third smear. The value of the third sputum is negligible as 99% of the cases were identified from the first and second specimens. Reducing the number of specimens to two or even one would have multiple advantages in countries where laboratories are usually over-burdened and are not easily accessible to the population. Submission of two specimens on the same day could improve compliance in submitting samples and collecting results as the number of diagnostic visits would be reduced without significant loss of sensitivity.     

Chemoprevention of liver cancer by plant polyphenols

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.     

山萸肉饮片中黄曲霉毒素B1含量及限度的研究

目的测定山萸肉饮片中黄曲霉毒素B1(AFB1)的含量并建立限度标准。方法间接竞争酶联免疫吸附法(ELISA)。结果山萸肉饮片均有不同程度的污染黄曲霉毒素B1(AFB1),炮制后降低,但都在国家规定的食品类AFB1限度范围之内。结论山萸肉饮片中黄曲霉毒素B1的含量限度标准初步确定为≤5μg/kg,与国家食品类限度标准相同。     

Selective impairment of drug-metabolizing enzymes in pig liver during subchronic dietary exposure to aflatoxin B1.

Consequences of subchronic exposure to aflatoxin B1 (AFB1) on liver monooxygenase and transferase enzymes were compared in control pigs and pigs given 385, 867 or 1,807 microg AFB1/kg of feed for 4 weeks. Animals exposed to the highest dose of toxin developed clinical signs of aflatoxicosis, like liver fibrosis, hepatic dysfunction and decreased weight gain. This group had significantly lower levels of liver cytochrome P450, ethoxyresorufin O-deethylase (EROD) activity, testosterone metabolism, P450 1A and P450 3A protein expression. By comparison, mild degenerative hepatic changes, no hepatic dysfunction but a similar pattern of liver P450 enzymes activity without changes in P450 3A expression were observed in pigs exposed to 867 microg AFB1/kg of feed. Benzphetamine and aminopyrine N-demethylase activities were increased in pigs exposed to 867 or 1,807microg AFB1/kg of feed. Pigs exposed to 385 microg AFB1/kg of feed had low levels of EROD activity and all other biotransformation and clinical parameters remained at control levels. Aniline hydroxylase activity, P450 2C protein expression, UDP-glucuronosyl and glutathione S-transferase activities were unaffected at all doses of AFB1. In conclusion, P450 1A and P450 3A appear to be specific targets of AFB1 even if pig did not display clinical sign of liver toxicosis.     

黄曲霉毒素高危区肝细胞癌患者微粒体环氧化物水解酶基因检测

目的 :探讨微粒体环氧化物水解酶 (microsomalepoxidehydrolase ,mEH)低活性基因型与肝细胞癌 (hepatocellularcarcinoma ,HCC)的相关性。方法 :应用PCR RFLP和PCR方法检测 5 2例HCC患者和5 6例健康成人中微粒体环氧化物水解酶及谷胱甘肽硫转移酶M1和T1基因型频率的分布。结果 :发现mEH第 3外显子 113纯合组氨酸型和第 4外显子 139纯合组氨酸型都是低活性基因型 ,在HCC组和对照组分别占 5 7 1% (30 /5 2 )、4 8 2 % (2 7/5 6 ) ,82 7% (4 3/5 2 )、73 2 % (4 1/5 6 ) ,两组比较差异无显著意义 ,P >0 0 5。然而 ,mEH低活性型联合谷胱甘肽硫转移酶 (glutathiones transferase ,GST)M1和T1基因缺失型 ,差异有显著意义 ,P <0 0 5。结论 :mEH处于低活性基因型可能是地区性易感HCC的原因之一 ,但单一种解毒酶不起决定作用 ,多种解毒酶联合作用 ,可增加HCC危险性