老年2型糖尿病患者尿微量白蛋白与C反应蛋白及胰岛素抵抗关系的临床观察

目的了解老年2型糖尿病患者尿白蛋白排泄率(UAER)与C反映蛋白(CRP)及胰岛素抵抗(ISI)的关系.方法对血压正常的42例老年2型糖尿病合并微量白蛋白尿(MAU)患者与36例未合并MAU患者的C反应蛋白、胰岛素敏感指数(ISI)及血糖进行比较分析.并对所有病例的UAER与有关因素进行多因素逐步回归分析.结果老年2型糖尿病合并MAU时,其ISI显著降低(P＜0.01).UAER与.ISI呈独立的相关性[偏回归系数(β)=0.39,P＜0.01],而与CRP呈正相关.CRP与ISI呈显著负相关(P＜0.01).结论血压正常的老年2型糖尿病的胰岛素抵抗是MAU的独立危险因素,CRP也是MAU的危险因素.     

微量白蛋白尿与老年患者血管性认知功能障碍、颈动脉硬化的关系

目的 探讨微量白蛋白尿与血管性认知功能障碍（vascular congnitive impairment,VCI）、颈动脉硬化的关系,为早期发现和预防血管性认知功能障碍提供临床参考.方法 采集98例缺血性脑卒中老年患者一般资料,依据卒中后3个月的认知评定结果及相应的诊断标准分为VCI组和认知正常组（对照组）,所有病例均进行颈动脉超声检测和神经心理检查,采用免疫透射比浊法测尿微量白蛋白（MAU）,对两组数据进行比较分析.结果 VCI组患者年龄较对照组偏高,受教育年限较对照组偏低,差异有统计学意义（P＜0.05）;VCI组患者MMSE评分较对照组明显降低,差异有统计学意义（P＜0.01）.VCI组患者尿MAU水平较对照组明显增高,差异有统计学意义（P＜0.01）;根据IMT程度将VCI患者分为两组,IMT＞ 1.0 mm组与IMT＜ 1.0 mm组相比MAU水平明显增高,差异有统计学意义（P＜0.05）.结论 MAU水平升高是VCI患者认知功能损害、颈动脉粥样硬化的危险因素.     

原发性高血压早期肾损伤尿微量白蛋白检测的临床意义

目的探讨尿微量蛋白对原发性高血压早期肾损伤检测的临床意义。方法选取正常对照组50例及原发性高血压1、2级患者97例,采用免疫透射比浊的方法进行尿微量白蛋白(MA)、尿免疫球蛋白(IgG)、尿转铁蛋白(TRF)及尿α1-微球蛋白(α1-MG)检测。结果原发性高血压患者尿微量白蛋白的阳性率均高于正常对照组,且原发性高血压2级患者尿微量白蛋白的阳性率高于原发性高血压1级患者,差异具有显著性(P<0.05)。结论原发性高血压患者早期肾功能损伤的程度和部位在尿四项微量白蛋白检测中可较早反映,其中以α1-MG和MA最敏感,为临床早期诊断及治疗提供依据。     

MPU方案和MAU方案治疗原发性肝癌疗效对照分析

1987年元月～1990年8月共收治原发性肝癌45例,采取MPU方案治疗23例,有效率为43.48％,白细胞降到4.0×10~9/L以下者3例。MAU方案治疗22例,有效率为40.91％,白细胞降到4.0×10~9L以下者18例。两组治疗后右上腹疼痛均有不同程度的减轻,消化道反应多为轻度。两组从临床表现、分期、分型基本一致,有可比性,统计学处理后见右上腹疼痛缓解率、有效率,胃肠道反应、生存时间均无明显差别(P>0.05)骨髓抑制程度MPU方案明显轻于MAU方案(P<0.01),经分析见两方案均为治疗原发性肝癌较好的方案,临床价值MPU方案优于MAU方案。     

亚临床甲状腺功能减退对冠状动脉粥样硬化性心脏病患者C反应蛋白及尿微量白蛋白的影响

目的 探究亚临床甲状腺功能减退对冠状动脉粥样硬化性心脏病对于C反应蛋白(C-Reactive Protein,CRP)以及尿微量蛋白(microalbuminuria,MAU)的影响,并通过上述影响分析亚临床甲状腺功能减退与冠状动脉粥样硬化之间所存在的相关性进行讨论.方法 入住我院的32例冠心病患者,分为A、B两组,即A组为冠心病合并亚临床甲状腺功能减退患者组,B组为冠心病无亚临床甲状腺功能减退患者组,每组为16例.对上述两组患者的如下几个方面的指标进行检测,即同型半胱氨酸(Hcy)、甘油三酯、总胆固醇、MAU以及CRP.结果 A组的指标值比B组均大,经计算,P<0.05,具有统计学差异.结论 冠心病合并亚临床甲状腺功能减退在较大程度上影响患者的C反应蛋白以及尿微量蛋白的含量.     

Cell cycle-specific cleavage of Scc2 regulates its cohesin deposition activity

Sister chromatid cohesion (SCC), efficient DNA repair, and the regulation of some metazoan genes require the association of cohesins with chromosomes. Cohesins are deposited by a conserved heterodimeric loading complex composed of the Scc2 and Scc4 proteins in Saccharomyces cerevisiae, but how the Scc2/Scc4 deposition complex regulates the spatiotemporal association of cohesin with chromosomes is not understood. We examined Scc2 chromatin association during the cell division cycle and found that the affinity of Scc2 for chromatin increases biphasically during the cell cycle, increasing first transiently in late G₁ phase and then again later in G₂/M. Inactivation of Scc2 following DNA replication reduces cellular viability, suggesting that this post S-phase increase in Scc2 chromatin binding affinity is biologically relevant. Interestingly, high and low Scc2 chromatin binding levels correlate strongly with the presence of full-length or amino-terminally cleaved forms of Scc2, respectively, and the appearance of the cleaved Scc2 species is promoted in vitro either by treatment with specific cell cycle-staged cellular extracts or by dephosphorylation. Importantly, Scc2 cleavage eliminates Scc2–Scc4 physical interactions, and an scc2 truncation mutant that mimics in vivo Scc2 cleavage is defective for cohesin deposition. These observations suggest a previously unidentified mechanism for the spatiotemporal regulation of cohesin association with chromosomes through cell cycle regulation of Scc2 cohesin deposition activity by Scc2 dephosphorylation and cleavage.Multisubunit, ring-shaped cohesin complexes play key roles in chromosome morphogenesis that are required for faithful chromosome transmission to daughter cells. Newly replicated sister chromatids become tethered together by cohesins during S phase, which promotes chromosome biorientation on mitotic spindles (1). Cohesins also mediate efficient DNA double-strand break repair by homologous recombination (2, 3) and the formation or stabilization of chromatin loops that affect various nuclear processes, such as gene expression and Ig gene rearrangements (reviewed in refs. 4 and 5). Altered gene expression resulting from defective cohesin-mediated chromatin looping is likely responsible for the pathogenesis of Cornelia de Lange Syndrome (CdLS), a dominantly inherited human developmental disorder (6).Sister chromatid cohesion (Scc) proteins form a heterodimeric cohesin deposition complex, but the complex''s activity in deposition is not understood (7). Cohesins copurify with Scc2/Scc4, suggesting that Scc2/Scc4 plays a direct role in deposition (8–11). In the absence of either loader complex subunit, cohesin rings assemble, but fail to be deposited (7, 12, 13). ATP hydrolysis by cohesin’s structural maintenance of chromosome (SMC) subunits is required for cohesin loading, and deposition is inhibited when SMC hinge domains, which mediate Smc1/3 interactions within cohesin, are artificially tethered (8, 14, 15). Thus, Scc2/Scc4 may activate cohesin’s ATPase activity or facilitate a conformational change in cohesin structure that promotes its loading, perhaps by permitting transient hinge opening to allow chromatin to enter cohesin rings or by promoting cohesin oligomerization (14, 16).Factors that regulate Scc2/Scc4 chromatin association are only beginning to be elucidated. Interactions of Scc2 and Scc4 orthologs from Xenopus and humans, and their stable association with chromatin, require the amino termini of both proteins (10, 13, 17, 18). In contrast, the fission yeast Scc2 ortholog alone binds nonchromatinized DNA, but does not exhibit an expected preference for sequences shown to associate with Scc2/Scc4 in vivo (19). Xenopus Scc2/Scc4 chromatin association requires prereplication complexes and Drf1-dependent kinase (DDK) activity (10, 12, 20), although this scenario is not the case in budding yeast (21). Scc2/Scc4 interactions with histone deacetylases and an ATP-dependent chromatin remodeler suggest that underlying chromatin structure also influences Scc2/Scc4 chromatin association (22–26). Whether Scc2/Scc4 plays a role in chromatin remodeling or merely deposits cohesins at remodeled sites is unknown, however.The chromatin association of Scc2/Scc4 and its orthologs is also regulated temporally during the cell cycle, although the specifics of association vary across species. Scc2/Scc4 associates with chromatin in late mitosis of the previous cell cycle in metazoans (12, 13) and in late G₁ in budding yeast, but in all cases, this association precedes DNA replication initiation so that cohesins are deposited in time to tether newly replicated sister chromatids together. Surprisingly, budding yeast Scc2/Scc4 chromatin association is more robust in mitotically arrested cells than in G₁-staged cells. Reduced G₁ Scc2/Scc4 chromatin association is not due to the absence of either loader subunit, because Scc2 and Scc4 protein levels vary little during the cell cycle, or by a lack of assembled cohesin complexes in G₁, because Scc2/Scc4 chromatin association occurs independently of cohesins (18, 27, 28). Scc2/Scc4 removal from chromatin is also regulated and occurs during mitosis in Xenopus and, more specifically, during prophase in humans (12, 13). Although factors responsible for regulating Scc2/Scc4 chromatin association/dissociation during the cell cycle remain enigmatic, evidence that multiple Scc2 orthologs are phosphorylated suggests the intriguing possibility that Scc2 posttranslational modifications regulate Scc2/Scc4 chromatin association (29–31).Here, we describe our efforts to understand how budding yeast Scc2/Scc4 chromatin binding is regulated during the cell cycle. Our results demonstrate the existence of multiple Scc2 protein species in vivo and that a specific cleaved form of Scc2 accumulates at cell cycle periods when Scc2 chromatin binding is weak. The appearance of this cleaved Scc2 species is strongly correlated with Scc2 dephosphorylation, suggesting that the phosphorylation state of Scc2 is critical for the regulation of its stability. Scc2 cleavage is also correlated with the loss of Scc2–Scc4 interactions, and an scc2 truncation mutant that mimics cleaved Scc2 is defective in cohesin deposition. These observations suggest that Scc2–Scc4 interactions and, therefore, the function of the complex in cohesin deposition, may be influenced by dephosphorylation-induced Scc2 cleavage.     

老年高血压人群血HCY、尿MAU测定及其临床意义

目的探讨老年高血压人群血同型半胱氨酸(HCY)水平与微量白蛋白尿(MAU)的关系.方法将90例老年高血压患者分为尿MAU正常组(n=46)及尿MAU异常组(n=44),两组患者分别测定血压,进行血HCY、内皮素(ET)、一氧化氮(NO)、尿MAU检测,血HCY采用荧光偏振法测定,ET应用SN-682γ计数器测定,NO采用酶法测定,尿MAU应用速率散射法检测.结果 MAU正常组血HCY、ET、NO测定值分别为(12.3250±1.2324)μmol/L、(59.9986±6.2335)pg/ml、(82.6832±3.5103)μmol/L;MAU异常组分别为(13.5248±2.2821)μmol/L、(65.2089±9.0628)pg/ml、(80.8139±3.1720)μmol/L.两组患者尿MAU比较差别有非常显著性意义(P＜0.01),血HCY及血ET、NO水平比较差别均有非常显著性意义(均P＜0.01).结论 HCY引起的内皮功能失调是产生MAU的因素.     

2型糖尿病合并血脂异常患者尿微量白蛋白发生率观察

目的 通过观察2型糖尿病(Type 2 diabetes mellitus,T2DM)合并血脂异常患者尿微量白蛋白的患病率,探讨脂代谢异常与T2DM患者尿中微量白蛋白(Microalbunm inuria,MAU)之间的关系.方法 选择T2DM合并血脂异常患者133例,尿微量白蛋白测试条半定量测定MAU,根据检测结果分为阴性、微量及大量白蛋白尿组,测定各组患者体重指数、腰围、血压、空腹血糖、血脂.结果 在133例T2DM合并血脂异常患者中MAU及大量白蛋白尿的发生率分别为27%和22.6%,微量及大量组较阴性组TG显著增加(P＜0.01).结论 T2DM合并血脂异常惠者中有约50%的患者存在肾损害,推测从尿白蛋白阴性发展为MAU的过程中,高TG加强了高血糖引起的肾损害.