Polymorphisms of DNA repair genes and risk of glioma

DNA repair genes play a major role in maintaining genomic stability through different repair pathways that are mediated by cell cycle control genes such as p53. We found previously that glioma patients were susceptible to gamma-ray-induced chromosomal breaks, which may be influenced by genetic variation in genes involved in DNA strand breaks, such as XRCC1 in single-strand break repair, XRCC3 and RAD51 in homologous recombination repair, and XRCC7 in nonhomologous end joining double-strand break repair. Therefore, we tested the hypothesis that genetic polymorphisms in XRCC1, XRCC3, RAD51, XRCC7, and p53 were associated with risk of glioma in 309 patients with newly diagnosed glioma and 342 cancer-free control participants frequency matched on age (+/- 5 years), sex, and self-reported ethnicity. We did not find any statistically significant differences in the distributions of XRCC1 Arg399Gln, XRCC3 Thr241Met, RAD51 G135C, and P53 Arg72Pro polymorphisms between the cases and the controls. However, the XRCC7 G6721T variant T allele and TT genotype were more common in the cases (0.668 and 43.4%, respectively) than in the controls (0.613 and 38.9%, respectively), and the differences were statistically significant (P = 0.045 and 0.040, respectively). The adjusted odds ratios were 1.78 (95% confidence interval, 1.08-2.94) and 1.86 (95% confidence interval, 1.12-3.09) for the GT heterozygotes and TT homozygotes, respectively. The combined T variant genotype (GT+TT) was associated with a 1.82-fold increased risk of glioma (95% confidence interval, 1.13-2.93). These results suggest that the T allele may be a risk allele, and this XRCC7 polymorphism may be a marker for the susceptibility to glioma. Larger studies are needed to confirm our findings and unravel the underlying mechanisms.     

假鹰爪根化学成分的研究

假鹰爪(Desmos cochinensis Lour.)根的石油醚提取物中分得三个黄酮类化合物。其中化合物Ⅰ和Ⅱ分别鉴定为5,7-二羟基-6-甲酰基-8-甲基双氢黄酮(lawinal)和5,7-二羟基-6-甲酰基-8-甲基黄酮(isounonal)。Ⅲ为一含醛基的新化合物。根据光谱分析(紫外、红外、质谱、氢谱、碳谱、二维核磁共振异核位移相关谱及X-单晶衍射)证明其结构为4,7-二羟基-5-甲氧基-6-甲基-8-甲酰基黄烷。化合物Ⅰ和Ⅱ均属首次从该植物中分得。     

骨髓间充质干细胞移植对心肌梗死大鼠血管新生和内皮功能的影响

目的:通过检测血特异的内皮细胞标记物管性假血友病因子,观察骨髓间充质干细胞移植治疗急性心肌梗死后大鼠局部新生血管情况,并探讨内皮血管功能指标E-选择素与新生血管的关系。方法:实验于2005-09/2006-06在唐山工人医院中心实验室完成。①选用清洁级健康近交系SD大鼠40只,随机数字表法分为假手术组、模型对照组、干细胞移植组、细胞培养基组,10只/组。②另取1只大鼠用于骨髓间充质干细胞的提取。大鼠处死后无菌条件下分离股骨和胫骨,应用密度梯度法分离培养骨髓间充质干细胞。待细胞80%贴满培养瓶底时,用乙二胺四乙酸和胰蛋白酶混合消化传代。将50mg/L4,6-二脒-2-苯基吲哚加入第3代细胞培养基中,制成细胞悬液备用。③术前各组大鼠均行气管插管,建立急性心肌梗死模型,以远端供血区心肌组织颜色苍白、心电图检测Ⅱ导联ST段持续抬高为模型建立成功的标志。假手术组仅开胸予以前降支穿线但不结扎。④造模成功后1～3h,干细胞移植组用微量注射器吸取4,6-二脒-2-苯基吲哚标记好的第3代骨髓间充质干细胞悬液50μL,直接注入梗死区边缘心肌组织。细胞培养基组按干细胞移植组的方法于相同部位注射等量无血清DMEM低糖培养基(pH值为6.9),模型对照组仅制作心肌梗死模型不作其他处理,假手术组亦不作其他处理。⑤造模后2,4周各组处死半数大鼠,切取心脏组织,于梗死边缘区心肌组织制作切片,荧光显微镜下观察4,6-二脒-2-苯基吲哚标记的供体细胞。链霉亲和素免疫组化法检测心肌细胞中血管性假血友病因子评估新生血管情况,酶联免疫吸附法测定血清E-选择素含量,评估内皮功能。结果:40只大鼠均进入结果分析。①各组大鼠心脏标本4,6-二脒-2-苯基吲哚标记移植细胞存活状况:骨髓干细胞移植治疗后,荧光显微镜下可见成团和散在的DAPI阳性细胞,其余3组大鼠心脏标本中均未见荧光细胞。②各组大鼠血清E-选择素的检测:心肌梗死后2,4周模型对照组及细胞培养基组E-选择素明显增高,与假手术组比较差异显著[2周:(36.04±4.47),(34.10±2.04),(13.37±3.01)μg/L;4周:(33.02±4.78),(33.96±5.18),(13.94±2.87)μg/L,P<0.01],干细胞组移植组E-选择素较模型对照组明显降低[2周:(24.29±3.51),(36.04±4.47)μg/L;4周:(17.45±3.22),(33.02±4.78)μg/L,P<0.05]。③各组大鼠心肌组织血管性假血友病因子表达情况:链霉亲和素免疫组化法显示,造模后2周干细胞移植组心肌细胞血管性假血友病因子呈强阳性表达,模型对照组和细胞培养基组血管性假血友病因子表达减弱。造模后4周干细胞移植组心肌细胞血管性假血友病因子表达仍呈强阳性,模型对照组和细胞培养基组血管性假血友病因子表达有减弱趋势。结论:①移入的骨髓间充质干细胞存活。②骨髓干细胞移植治疗实验性大鼠心肌梗死模型后,可提高心肌细胞血管性假血友病因子水平,促进局部血管新生。③移植后心肌梗死大鼠血清中E-选择素的降低,可能与其参与血管新生有关,同时也提示骨髓干细胞移植不会诱发E-选择素增高而加重动脉硬化。     

Exposure to Ethylene Glycol Monomethyl Ether: Clinical and Cytogenetic Findings

Glycol ethers are known reproductive and developmental toxins in laboratory animals, but little is known about their genotoxic effects in humans. In the current article, the authors tested the hypothesis that human in utero exposure to ethylene glycol monomethyl ether (EGME) is associated with the development of specific congenital anomalies and elevated levels of chromosome aberrations. The authors conducted a clinical and cytogenetic evaluation of 41 offspring of 28 females occupationally exposed to EGME for an average duration of 4.6 yr. Six offspring of 5 women who were occupationally exposed to EGME during pregnancy exhibited characteristic dysmorphic features that were not observed in 35 offspring of 23 women who worked in the same facility, but who were not pregnant at the time of exposure. Persistent cytogenetic damage was observed exclusively in all 6 in-utero-exposed offspring, but not in their 12 match non-in-utero-exposed controls. The study characterizes EGME as a human teratogen, as indicated by the prevalence of characteristic dysmorphic features and persistent cytogenetic damage in individuals exposed in utero to this chemical     

Pericardial Effusion in a Preterm Infant Resulting from Umbilical Venous Catheter Placement

Pericardial effusion in neonates is a rare occurrence associated with malpositioning of central venous catheters. This report describes a case of pericardial effusion in which echocardiographic determination of line position, typically considered one of the most reliable means of placement verification, was misleading. The infant ultimately did well after pericardiocentesis, with complete resolution of symptoms and no further complications.     

Genetic predisposition to chronic obstructive pulmonary disease and/or lung cancer: important considerations when evaluating risk

Chronic obstructive pulmonary disease (COPD) is defined as a disease causing an airflow limitation that is not fully reversible. COPD is phenotypically complex and characterized by small-airway disease and/or emphysema that result from the interaction between host genetic susceptibility and environmental exposures. As in lung cancer, smoking exposure is the most important risk factor for the development of COPD, accounting for 80% to 90% of all cases. COPD affects an estimated 8% to 10% of the general adult population, 15% to 20% of the smoking population, and 50% to 80% of lung cancer patients (with substantial smoking histories). In prospective studies, COPD has been found to be an independent risk factor for lung cancer, conferring a three- to 10-fold increased risk of lung cancer when compared with smokers without COPD. These findings suggest that smokers have a host susceptibility to COPD alone, COPD and lung cancer (i.e., overlap), and lung cancer in the absence of COPD. This minireview focuses on important points that need to be addressed when studying genetic susceptibility factors for COPD and its complex relationship with susceptibility to lung cancer.     

Parental alcohol consumption and childhood cancers: a review

The etiology of childhood cancers remains generally unknown. Given that the metabolites of alcohol are likely carcinogens and that leukemia, the most frequent childhood cancer, can arise in utero, the study of alcohol consumption as a potential risk factor for the development of childhood cancer is justified. This article summarizes the epidemiological evidence on the association between parental exposure to alcohol and the risk of childhood cancers. To do this, a thorough search of the literature from 1960 to 2003 using the PubMed database was carried out. It yielded 33 case-control studies published between 1982 and 2003, including 13 studies that considered paternal exposure in the preconceptional period. In 10 of the 33 studies at least 1 statistically significant risk increase was reported in relation with parental alcohol consumption; in 7 of these studies the increase was related to maternal consumption, whereas in 3 studies, it was related to paternal consumption. The cancers most often found associated with parental drinking were leukemia, brain tumors, and neuroblastoma. A few studies also reported a protective effect with maternal exposure at modest levels. Inconsistencies in the results and the low risks reported do not suggest an association between childhood cancer and parental consumption of alcohol. However, before reaching any definitive conclusions, methodological issues need to be addressed in future studies, as well as the role of genetic susceptibility. Moreover, subtypes of specific cancers need to be studied separately.     

Genetic polymorphism of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients

Polymorphic changes in the GSTM1, CYP2E1 and the CYP2D6 geneshave been reported to be individually associated with increasedsusceptibility to certain cancers. In the present study, therelationship between genetic polymorphism for these genes anddevelopment of urinary bladder cancer among Egyptian patientswas investigated. Our results indicate that the frequency ofbladder cancer patients with the GSTM1 null genotype is significantlyhigher than that of the normal controls (86.3 and 47.6%, respectively)with an odds ratio (OR) of 6.97 (95% CL = 1.59–30.57,Fisher's exact P = 0.008). In contrast, our investigation failedto demonstrate any difference in the distribution of CYP2E1polymorphism between bladder cancer patients and controls asdetected by PstI restriction fragment length polymorphism (RFLP)analysis. RFLP analysis of the CYP2D6 gene revealed a non-significantincrease in the number of extensive metabolizers (EM) amongthe patients compared to the controls (68 versus 48%). However,the EM genotypes enhances the risk further for individuals harboringthe GSTM1 null genotype as individuals harboring both the EMand the GSTM1 null genotypes have an odds ratio of 14.0 (95%CL = 1.3–151.4, Fisher's exact P = 0.02) compared to individualsharboring the EM and the GSTM1+/+ genotypes. In conclusion,our results indicate that genetic polymorphism, especially inGSTM1 and CYP2D6 could play an important role as host risk factorsfor development of urinary bladder cancer among Egyptians.