Polymorphisms in the glutathione S-transferase class mu and theta genes interact and increase susceptibility to lung cancer in minority populations (Texas, United States)

The genes coding for separate isoforms of both the human glutathioneS-transferase class mu and class theta enzymes (GSTM1and GSTT1) arepolymorphic with a variable ethnic distribution. These enzymes detoxifyreactive epoxides, including carcinogens produced by tobacco smoke. Becauseof this, the null polymorphism in the GSTM1 gene (coding for the glutathioneS-transferase class mu enzyme) has been studied widely as a possible sourceof inherited susceptibility to smoking-related lung cancer. The more recentlydescribed null polymorphism in the GSTT1 gene also could contribute to anincreased risk of smoking-related lung cancer. As the incidence of lungcancer is known to differ by ethnicity, we have conducted a case-controlstudy in the United States of 108 African-Americans (Blacks) and 60Mexican-Americans (Hispanics) with lung cancer and 132 African-American(Black) and 146 Mexican-American (Hispanic) controls to investigate theassociation of the GSTT1 and GSTM1 polymorphi sms with lung cancer inminority populations. In the unadjusted data, there was a borderlinesignificant association of the GSTM1 null polymorphism with lung cancer inMexican-Americans (odds ratio [OR] = 1.8, 95 percent confidence interval [CI]= 1.0-3.3 ) that was not observed in African-Americans. The GSTT1 nullpolymorphism also had a higher prevalence in cases than controls in bothracial/ethnic groups, but this increase was not statistically significant.When the data were analyzed using logistic regression controlling for age,gender, race, and smoking, no significant association of either trait withlung cancer was observed, with ORs for both traits of approximately 1.3.However, when the prevalence of individuals who were null for bothpolymorphisms was compared by case status, a significant interaction wasobserved. Logistic regression models showed the OR for the association oflung cancer and the presence of both null polymorphisms compared with one(either GSTT1 or GSTM1) or no null genotype to be 2.9 (P < 0.04). Theseresults suggest that there may be carcinogenic intermediates in cigarettesmoke that are substrates for both the GSTT1 and GSTM1 enzymes, and that lungcancer risk is increased more than additively for individuals who have bothGSTT1 and GSTM1 null polymorphisms.     

Azoxymethane-induced colon tumors and aberrant crypt foci in mice of different genetic susceptibility

Azoxymethane (AOM) is an organotropic colon carcinogen that is commonly used to induce colon tumors in rodents. Unlike its parent compound, 1,2-dimethylhydrazine (DMH), a tumor susceptibility phenotype in inbred mice with respect to AOM has not been established. Thus, this study was undertaken to determine whether genetic susceptibility extends to this carcinogen. SWR/J, A/J (both susceptible to DMH carcinogenesis) and AKR/J (resistant) mice were treated with 10 mg/kg AOM i.p. once a week for 8 weeks. Twenty-five weeks after the initial injection, tumor yield was determined. With a single exception, only SWR/J and A/J mice developed tumors, with a distribution that was limited to the distal colon (16.3±1.1 and 36.4±2.4, respectively). The formation of aberrant crypt foci (ACF), putative preneoplastic lesions, was also assessed in whole-mount colons using Methylene Blue staining. Consistent with tumor multiplicity, the total number of ACF was highest in A/J mice, followed by SWR/J mice. In addition, A/J mice had a significantly greater number of large ACF (five or more crypts per foci) than the other strains. Despite the absence of colon tumors, however, AKR/J mice did develop a significant number of ACF. This finding suggests that ACF in resistant mice are persistent but do not progress to tumors.     

肿瘤患者合并肺部念珠菌感染药敏测定研究

采用ＲＰＭＩ１６４０及ＦＤＡ抗生素３号两种培养基的微量稀释法对肿瘤患者合并肺感染分离出５１株念珠菌进行药敏对比测定。结果显示二性霉素Ｂ在两种培养基中均具有非常好的抗菌活性，敏感率均为９８．０％，其次酮康唑也显示出良好的抗菌活性，敏感率均为９４．１％。相比之下，在ＲＰＭＩ培养基中伊曲康唑和氟康唑的敏感性稍差，敏感率分别为９２．２％和９０．２％，但在ＦＤＡ抗生素３号培养基中，伊曲康唑和氟康唑敏感性明显下降，敏感率分别为７０．６％和６６．７％。为此我们建议抗真菌药敏试验，尤其是咪唑类药物应该选用ＮＣＣＬＳ推荐的ＲＰＭＩ１６４０培养基做药敏试验     

应用DHPLC技术分析错配修复基因(hMLH1)T1151A多态与胃肠道肿瘤的遗传易感性

目的了解中国人hMLH1基因T1151A多态与胃肠道肿瘤的遗传易感性.方法采用病例对照研究设计,提取233例大肠癌(结,直肠癌)患者,273例胃癌患者和268例健康人外周血细胞的基因组DNA.PCR扩增hMLH1基因T1151A多态所在第12外显子的部分DNA片段(217 bp),变性高效液相色谱(DHPLC)检测,DNA测序验证,比较分析T1151A基因型在胃肠道肿瘤的分布.结果正常人群中T1151A多态T/A基因型频率为6.34%,其等位基因A频率为3.28%,在大肠癌患者和胃癌患者中T/A基因型频率与正常人群相比存在显著性差异,分别为11.6%(P=0.039)和12.1%(P=0.021),尤其在＜45岁的大肠癌患者和＜50岁的胃癌患者中,等位基因A频率与正常人群相比差异更为显著,分别为10.66%(P=0.002)和11.27%(P=0.001).结论T1151A作为中国人hMLH1基因上的一个多态位点,可能是中国人大肠癌和胃癌遗传易感因素,可作为中国人胃及大肠肿瘤、尤其是低龄胃及大肠肿瘤高危人群筛选的侯选指标.     

支原体耐药性与抗菌药消耗量相关性研究

目的：了解支原体耐药性与抗生素消耗量之间的相关性。方法：对112份解脲支原体阳性标本进行9种抗菌药敏感性试验，统计2002～2003年有关药物的消耗量，分析解脲支原体耐药率与相应药品消耗量之间的关系。结果：多因素逐步回归分析表明上年度相关药物成人剂型的消耗量是有显著性意义的相关因素（r=0．858，F=16.778，P〈0．01）。结论：支原体的耐药率主要与上一年度的相关药物消耗量相关。     

医院内深部真菌感染的临床分布和药敏结果

目的对350株临床深部真菌感染的标本进行分离鉴定和药敏试验,了解患者真菌性医院感染现状,为临床感染性疾病提供病原学诊断和合理使用抗真菌药物的依据。方法按常规方法培养,采用念珠菌显色培养基进行鉴定,对于少见的念珠菌采用PCR技术鉴定;对真菌用棉蓝染色直接镜检和培养相结合的方法进行鉴定。采用纸片扩散法进行药敏试验。结果350株真菌标本中,念珠菌属329株,占94.00%;真菌(丝状菌)21株,占6.00%;分离菌株对药物的敏感性分别为氟康唑92.40%、两性霉素B 97.57%、伊曲康唑93.01%、5-氟胞嘧啶88.10%。结论院内真菌感染以念珠菌属最为多见,特别是白色念珠菌和热带念珠菌;药敏结果显示氟康唑、两性霉素B、伊曲康唑、氟胞嘧啶均有较高的抗菌活性,但氟康唑对克柔念珠菌和光滑念珠菌有较高的耐药性;对送检标本及时进行真菌培养和药敏实验,合理使用抗真菌药物,减少多重耐药和深部真菌感染的发生。     

新生儿败血症血培养检出菌10年变迁及耐药分析

目的了解湖南省湘南地区近10年新生儿败血症病原菌的变迁及药敏变化。方法对2001年1月至2005年12月本院收治的新生儿血培养检出菌、药敏试验结果及临床用药进行回顾性调查，并与1991年1月至1995年12月的调查结果进行对比分析。结果共检出病原菌14种，292株。10年前与10年后比较，金黄色葡萄球菌（简称为金萄菌）、凝固酶阴性葡萄球菌（CNS）检出率构成比下降，大肠埃希菌、肺炎克雷伯杆菌等革兰阴性菌检出率构成比明显增加（P〈0．10）。各检出菌对常用抗生紊的敏感率均呈下降趋势。金萄菌对青霉素族和头孢唑啉、头孢他定，CNS对阿米卡星、头孢呋新敏感率均显著下降（P〈0．05），大肠埃希菌、肺炎克雷伯杆菌对庆大霉素、阿米卡星的敏感率也在下降。结论金葡菌、CNS、大肠埃希菌、肺炎克雷伯杆菌是新生儿重症监护病房（NICU）中新生儿败血症最常见的几种病原菌，对常用抗生素的敏感性10年来显著下降。     

BRCA1蛋白在原发性上皮性卵巢癌中的表达

目的探讨卵巢癌乳腺癌易感基因1(BRCA1)蛋白在原发性上皮性卵巢癌中的表达。方法取本院妇产病理研究室1996年1月~2003年8月的原发性上皮性卵巢癌存档蜡块,共81例。用鼠抗人BRCA1蛋白C端单克隆抗体检测原发性上皮性卵巢癌BRCA1蛋白的表达,以同侧或对侧卵巢的正常生发上皮、同期12例良性上皮性卵巢肿瘤标本的BRCA1蛋白的表达作为对照。结果81例原发性上皮性卵巢癌中,仅44例(54.3%)BRCA1蛋白在细胞核中正常表达,34例(42.0%)在细胞浆中错位表达,3例(3.7%)表达完全缺失。13例原发性上皮性卵巢癌患者找到正常卵巢生发上皮,有2例BRCA1蛋白表达异常,异常表达率为15.4%。BRCA1蛋白在12例良性上皮性卵巢肿瘤的上皮细胞中未见异常表达。结论原发性上皮性卵巢癌中BRCA1蛋白异常表达率高,表达异常包括细胞核中表达下降甚至缺失,以及细胞浆中错位表达,这可能与卵巢癌的发生发展密切相关。     

MTHFR基因C677T和A1298C多肽与直肠癌的遗传易感性

目的探讨叶酸代谢中的亚甲基四氢叶酸还原酶(MTHFR)基因单核苷酸多肽与直肠癌风险的关系。方法以聚合酶链反应和限制性片段长度多态方法,对56例直肠癌患者和143例正常人对照的MTHFR基因C677T和A1298C基因型进行检测分析其对直肠癌风险的相关性。结果在正常对照组中,MTHFRC677TCC、CT、TT基因型频率分别为62·90%、35·08%和2·12%,而在直肠癌病人中分别为58·93%、26·77%和14·26%。A1298C与A1298C基因型在病例和对照中的分布差异无显著性意义。MTHFRA1298C基因型在病例和对照中的分布差异无显著性意义,1298变异基因型与677变异基因型之间无协同作用。结论MTHFR单核苷酸多肽不是中国人直肠癌的遗传易感性因素。     

1990-2004年上海地区临床分离大肠埃希菌耐药性变迁

目的 了解临床分离大肠埃希菌对抗菌药耐药性变迁情况。方法 对1990至2004年上海地区11所医院的细菌耐药监测资料中大肠埃希菌临床分离株的耐药性变迁情况进行分析，细菌药敏采用Kirby-Bauer法。结果 临床分离大肠埃希菌33495株对21种抗菌药药敏试验结果显示，该菌对大多常用抗菌药的耐药性在15年间呈上升趋势。对氨苄西林、哌拉西林的耐药率自69．0％和30．0％分别增至85．0％和71．4％。对头孢菌素类中的头孢唑啉（24．0％-48．3％）、头孢呋辛（18．0％-45．7％）、头孢克洛（33．3％-46．8％）的耐药率均增长，尤其是头孢噻肟的耐药率自1990年的6.0％增至2004年的35．2％。对氟喹诺酮类的耐药性15年间明显增高，且各品种间呈交叉耐药，自1990年的11．0％增至2004年的55．4％。对庆大霉素的耐药率缓慢上升（44．0％-54．0％）。大肠埃希菌对四环素、氯霉素、磺胺甲晤唑／甲氧苄啶（SMZ／TMP）耐药率始终较高。头孢他啶、头孢吡肟、亚胺培南、阿米卡星、β内酰胺类／β内酰胺酶抑制剂复方、呋喃妥因则保持了对大肠埃希菌的良好抗菌活性。产超广谱B内酰胺酶（ESBL）大肠埃希菌所占比例在2000-2004年间逐渐上升，自14．7％增至36．5％，产ESBL菌株耐药性均明显高于非产ESBL者。结论 临床分离的大肠埃希菌对常用抗菌药的耐药性在1990-2004年的15年间普遍呈明显增高趋势。 床分离的大肠埃希菌对常用抗菌药的耐药性在1990--2004年的15年间普遍呈明显增高趋势。