肾组织中葡萄糖转运蛋白与糖尿病肾病的关系

目的：了解葡萄糖转运蛋白－１（ＧＬＵＴ１）和葡萄糖转运蛋白－４（ＧＬＵＴ４）在糖尿病患者肾组织中的分布特点及其与糖尿病肾病（ＤＮ）发生及病情进展的关系。方法：应用免疫组化技术和特异性抗体，对１９例ＤＮ和４例糖尿病无肾病患者组织中ＧＬＵＴ１和ＧＬＵＴ４进行了观察，并结合肾脏病理，血糖水平和ＧＬＵＴ１基因型进行了分析。结果：肾组织中ＧＬＵＴ１和ＧＬＵＴ４主要分布在部分肾小球，肾小管和间质血管。肾小球内     

氧化修饰低密度脂蛋白及抗氧化剂在糖尿病血管病变中的作用

为探讨氧化修饰低密度脂蛋白（ＯＸＬＤＬ）及抗氧化剂在糖尿病血管病变中的作用，采用酶联免疫吸附双抗体夹心法（ＥＬＡＳＡ法），测定了６０例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人及３０例正常对照者血浆ＯＸＬＤＬ水平。结果显示：（１）ＮＩＤＤＭ组与正常对照组比较，血浆ＯＸＬＤＬ水平显著增高（Ｐ＜０．０１）。ＮＩＤＤＭ有血管病变组与无血管病变组比较，血浆ＯＸＬＤＬ水平显著增高（Ｐ＜０．０５）。（２）２０例ＮＩＤＤＭ病人用维生素Ｃ及维生素Ｅ治疗后，血浆ＯＸＬＤＬ水平显著下降（Ｐ＜０．０５）。（３）血浆ＯＸＬＤＬ水平与ＬＤＬ－Ｃ、ＨＤＬ、ＴＧ、ＴＣ、ＡｐｏＡ１及ＡｐｏＢ均无显著相关性。提示ＯＸＬＤＬ可能与糖尿病血管病变的发生和发展有关。抗氧化治疗可能对预防血管病变的发生有一定的作用。     

血管紧张素转换酶基因多态性与糖尿病和糖尿病肾病…

目的：研究血管紧张素转换酶（ＡＣＥ）基因多态性与Ⅱ型糖尿病（ＮＩＤＤＭ）发病及其与微血管合并症之间的关系。 方法：应用ＰＣＲ方法对１３１例ＮＩＤＤＭ患者ＡＣＥ基因多态性进行了观察，并结合患者眼底和肾脏病变进行了分析。 结果：ＮＩＤＤＭ患者ＤＤ型的发生频率明显高于正常人（Ｐ〈０．０１），ＤＤ型与ＮＩＤＤＭ的发生明显相关（ＯＲ＝４．２６，９５％可信限为１．９４８￣９．３１４），ＮＩＤＤＭ患者伴眼底病变     

血管紧张素转换酶基因多态性与糖尿病和糖尿病肾病的关系

目的：研究血管紧张素转换酶（ＡＣＥ）基因多态性与Ⅱ型糖尿病（ＮＩＤＤＭ）发病及其与微血管合并症之间的关系。方法：应用ＰＣＲ方法对１３１例ＮＩＤＤＭ患者ＡＣＥ基因多态性进行了观察，并结合患者眼底和肾脏病变进行了分析。结果：ＮＩＤＤＭ患者ＤＤ型的发生频率明显高于正常人（Ｐ＜０．０１），ＤＤ型与ＮＩＤＤＭ的发生明显相关（ＯＲ＝４．２６，９５％可信限为１．９４８～９．３１４），ＮＩＤＤＭ患者伴眼底病变者ＤＤ型的发生频率明显高于无眼底病变的患者（Ｐ＜０．０５）。ＤＤ型与ＮＩＤＤＭ患者眼底病变的发生明显相关（ＯＲ＝４．６６７，９５％可信限为１．４１４～１５．４０）。ＮＩＤＤＭ患者伴肾病者ＤＤ型的发生频率明显高于无肾病患者（Ｐ＜０．０５），ＤＤ型与糖尿病肾病的发生明显相关（ＯＲ＝３．６３６，９５％可信限为１．１６８～１１．３２３）。结论：ＡＣＥ基因ＤＤ型与ＮＩＤＤＭ易感性相关，ＮＩＤＤＭ患者携带ＤＤ型者易罹患糖尿病眼底病变和糖尿病肾病。     

牛磺酸结合氧透射载体疗法治疗糖尿病的临床研究

采用牛磺酸及氧透射载体疗法（ＯＴＩＵ）治疗４９例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、２２例胰岛素依赖型糖尿病（ＩＤＤＭ）及４１例糖耐量降低（ＩＧＴ）患者。结果：急性降糖试验显示，本方法有显著的降糖作用，并可降低口服葡萄糖耐量试验（ＯＧＴＴ）曲线的峰值水平，使糖耐量曲线睛面积明显减少，但对血胰素释放影响不大。慢性降糖试验显示。患者血糖、尿糖均有下降，但ＮＩＤＤＭ组较ＩＤＤＭ组下降更明显，ＩＧＴ组血糖     

线粒体基因突变与糖尿病

线粒体ｔＲＮＡ（ＬＥＵ（ＵＵＲ））的保留位置３２４３核苷酸的基因发生突变（Ａ→Ｇ）可致糖尿病，该类糖尿病主要发生在ＮＩＤＤＭ患者中，为母系遗传方式。线粒体糖尿病具有一系列的临床特征。     

家族性非胰岛素依赖型糖尿病家系中一级亲属的脂质代谢紊乱

非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者最常见的脂质代谢异常是极低密度脂蛋白（ＶＬＤＬ）、血浆甘油三酯（ＴＧ）及血浆总胆固醇（ＴＣ）升高，高密度脂蛋白胆固醇（ＨＤＬＣ）降低［１］。我们在对家族性ＮＩＤＤＭ患者家系调查中［２］，研究家系各类成员的脂质代...     

非胰岛素依赖型糖尿病患者血管紧张素转换酶与慢性并发症的关系

目的探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者血清血管紧张素转换酶（ＳＡＣＥ）水平及其与各种慢性并发症的关系。方法６７例ＮＩＤＤＭ患者用紫外法测定ＳＡＣＥ水平。结果ＮＩＤＤＭ全组ＳＡＣＥ为（３３９±１２４）Ｕ／Ｌ，明显高于正常人［（２８．１±５．７）Ｕ／Ｌ］，Ｐ＞００１。其中超出正常范围（３９５Ｕ／Ｌ）者１８例，占２７％；糖尿病肾病（ＤＮ）者（３０例）ＳＡＣＥ更高［（４２６±１０．６）Ｕ／Ｌ］，而无ＤＮ者［３７例，（２６９±５．７）Ｕ／Ｌ］与正常人无异。结论ＮＩＤＤＭ患者ＳＡＣＥ升高与病程、ＤＮ、视网膜病变（ＤＲ）、神经病变、心血管病变等慢性并发症有关。为临床应用ＡＣＥ抑制剂防治糖尿病慢性并发症提供部分依据。     

空腹血糖水平对非胰岛素依赖型糖尿病发病的预测价值——638例非糖尿病人群六年前瞻性观察

为了解空腹血糖（ＦＢＧ）水平对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）发病的预测价值，对１９８６年６３８例非糖尿病人群（糖耐量正常３４１例，糖耐量低减２９７例）于１９９２年进行血糖复查。结果发现，随着初访时ＦＢＧ水平增高，６年后ＮＩＤＤＭ发病率逐步增加。ＣＯＸ成比例风险模型分析，在调整了年龄、性别和体重指数的影响后，在糖耐量低减组ＦＢＧ仍与ＮＩＤＤＭ发病显著正相关（Ｐ＝０．０００１），ＦＢＧ均值为５．１９ｍｍｏｌ／Ｌ亚组与均值４．６１ｍｍｏｌ／Ｌ亚组相比，ＮＩＤＤＭ发病危险已有显著差异（ＲＲ２．１，９５％可信区间１．１９～３．７４，Ｐ＝０．０１）。ＦＢＧ均值为６．５０ｍｍｏｌ／Ｌ组，ＮＩＤＤＭ发病危险更高（ＲＲ２．９，９５％可信区间１．７９～４．５９，Ｐ＝０．０００１）。认为ＦＢＧ水平为ＮＩＤＤＭ发病的独立危险因素     

非胰岛素依赖型糖尿病和糖耐量低减患病情况研究

我们于１９９４年７月－１９９５年３月对湖北省部分地区２５岁及以上的９４５０名居民进行了非胰岛素依赖型糖尿病与糖耐量低减患病率的抽样调查。结果表明：ＮＩＤＤＭ患病率为２．６２％，ＩＧＴ患病率４．４８％，男女性的ＮＩＤＤＭ与ＩＧＴ患病率差异无显著性，城乡ＮＩＤＤＭ，ＩＧＴ患病率差异有显著性，ＮＩＤＤＭ和ＩＧＴ的患病率均随着年龄升高而升高。     

Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase (NAT) 2 polymorphisms and susceptibility to urothelial cancer

Purpose Arylamines are suspected to be the primary causative agent of urothelial cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a cytochrome P450 (CYP)1A2-catalyzed reaction, which produces a substrate for O-esterification that can be catalyzed by N-acetyltransferases (NAT) or sulfotransferases (SULT). Recently, several polymorphisms of CYP1A2, SULT1A1, and NAT2 that affect their activities have been reported.Methods In this study, 306 Japanese patients with urothelial transitional cell carcinoma and 306 healthy controls were compared for frequencies of CYP1A2, SULT1A1, and NAT2 genotypes.Results The frequencies of NAT2 intermediate or slow acetylator genotype were significantly higher in the urothelial cancer patients than in the healthy control subjects [odds ratio (OR)=1.49, 95% confidence interval (95% CI) 1.06–2.09, OR=3.23, 95% CI 1.72–6.08, respectively]. Stratifying by amount of smoking, among subjects who consumed >33.5 pack-years and carried the SULT1A1 *1/*1 or NAT2 slow acetylator genotype, the OR was 1.73 (95% CI 1.01–2.97) whereas it was 7.31 (95% CI 1.90–28.05) in non-smokers who carried the homozygous wild genotype, respectively. The relationships between CYP1A2, SULT1A1, and NAT2 polymorphisms and clinical findings including tumor differentiation, stage, and recurrence rate were analyzed. Only associations between NAT2 genotype and pathological findings were admitted, and the higher OR of NAT2 intermediate and slow acetylator genotype was more likely to present to a low-grade tumor (G1) among heavy-smokers.Conclusions Our results suggest that SULT1A1 *1/*1 and NAT2 slow acetylator genotypes might modulate the effect of carcinogenic arylamines contained in tobacco smoke, and that the modulation of NAT2 intermediate and slow acetylator genotype has a tendency to present a higher risk for highly differentiated tumors among heavy-smokers.     

Cyclin-dependant kinase inhibitors CIP1 (p21) and KIP1 (p27) in ovarian cancer

Purpose: Deregulation of the cell cycle is one of the important prerequisites for cancer development. p21 and p27 are both universal inhibitors of cyclin-dependant kinases and can therefore influence cell cycle or tumor progression. The aim of this study was to determine the influence of p21 and p27 expression on survival and chemotherapy response. Methods: 165 patients with ovarian cancer have been examined for p21 and p27 expression by immunohistochemistry on formalin-fixed, paraffin-embedded tissue using the monoclonal primary antibody WAF1 (Oncogene Science) and KIP1 (Transduction Laboratories). Results: High p21 expression (>50%) correlates only with early tumor stage (P=0.04). There was no correlation found between p21 and p27 expression. Patients with high p27 expression (>25%) had a longer DFS (disease free survival) in both univariate and multivariate analysis (P=0.05 and P=0.043) than patients with low p27 expression. A longer overall survival (OS) could only be proven for the group of high p27 expression in univariate analysis (P=0.03). Conclusion: p27 is an independent prognostic factor for ovarian cancer for DFS though this was not true for OS.     

Human NAD(P)H:quinone oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) polymorphisms and urothelial cancer risk in Taiwan

Purpose To investigate whether the NAD(P)H:quinone oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) polymorphisms are associated with urothelial cancer (UC) risk in Taiwan. Methods In this study, 600 study subjects (including 300 UC patients and 300 cancer-free controls) were recruited from September 1998 to December 2005. We analyzed the NQO1 and SULT1A1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A comprehensive interview was conducted to collect information, including baseline characteristics and cigarette smoking status. We used an unconditional multivariate logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). Results We found a significantly increased UC risk in study subjects with the NQO1 C/T and T/T genotypes (OR = 1.5; 95% CI: 1.03–2.1). A significantly increased UC risk was found in those with the SULT1A1 G/G genotype (OR = 2.0; 95% CI: 1.3–3.2). Subjects who had ever smoked with either the NQO1 C/T and T/T genotypes or the SULT1A1 G/G genotype had significantly increased UC risks, showing ORs of 3.0 and 5.3, respectively. Subjects carrying both the NQO1 C/T and T/T genotypes and the SULT1A1 G/G genotype had a significantly increased UC risk (OR = 3.7; 95% CI, 1.4–9.7). Moreover, those who had ever smoked with both the NQO1 C/T and T/T genotypes and the SULT1A1 G/G genotype had the highest UC risk (OR = 8.6; 95% CI: 2.5–29.7). Conclusions These findings suggest that NQO1 and SULT1A1 polymorphisms are associated with the risk of UC, particularly among those who have ever smoked.     

阿托伐他汀对氧化低密度脂蛋白诱导的内皮基质金属蛋白酶-1表达的影响

目的 探讨不同浓度的阿托伐他汀对氧化型低密度脂蛋白（OX-LDL）诱导的人脐静脉内皮细胞（HUVECs）基质金属蛋白酶-1（MMP-1）mRNA表达的影响。方法 体外培养人脐静脉内皮细胞，待细胞生长到融合状态时加入oxLDL（100μg／m1），作用24h后分别加入不同浓度的阿托伐他汀（1～30ixmol／L），采用逆转录一聚合酶链反应（RT-PCR）技术测定MMP-1 mRNA的表达。结果 OX-LDL可诱导HUVECs MMP-1 mRNA的表达；不同浓度的阿托伐他汀可抑制OX-LDL诱导的MMP-1 mRNA的表达，并呈浓度依赖性（1、10及30μmol／L）（均P〈0．05）。结论 阿托伐他汀可抑制OX-LDL诱导的HUVECs MMP-1 mRNA的表达，并呈浓度依赖性；具有抗炎作用，其机制可能与抑制MMP-l的表达有关。     

Circulating Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1): Relationship with carotid artery elasticity in patients with impaired glucose regulation (IGR)

Objective

To investigate the relations of circulating adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) with carotid artery elasticity in patients with impaired glucose regulation (IGR).

HIF-1α、iNoS在溃疡性结肠炎中的表达及临床意义

目的探讨低氧诱导因子-1α（（HIF-1α）、诱导型一氧化氮合酶（iNOS）在溃疡性结肠炎（UC）组织中的表达及与疾病活动性的关系。方法采用免疫组织化学方法检测51例UC患者（活动期38例、缓解期13例）和20例正常对照组中的HIF-1α、iNOS表达。结果UC患者活动期HIF-1α表达显著高于正常人，差异有显著性（153．29±15．26 vs 193．28±16．65，P〈0．01），缓解期HIF-1α表达与正常人差异无显著性（185．45±12．08 vs 193．28±16．65，P〉0．05），HIF-1α的表达与Walmsley评分标准呈正相关；iNOS在溃疡性结肠炎患者活动期的表达显著高于正常人，差异有显著性（151．32±14．62 vs 196．67±17．43，P〈0．01），缓解期的表达与正常人差异无显著性（189．93±15．20 vs 196．67±17．43，P〉0．05），iNOS的表达与Walmsley评分标准也呈正相关；HIF-1α和iNOS在溃疡性结肠炎中表达水平呈正相关（r=0．627，P〈0．05）。结论HIF-1α和iNOS均参与了溃疡性结肠炎的发病且与疾病的活动性有关，HIF-1α作为一种转录因子可能是iNOS基因表达中的一个重要调节者。     

Lipoprotein (a) and microvascular disease in type 1 (insulin-dependent) diabetes.

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.