凉山彝族男性血管紧张素转换酶基因多态性与高血压的关系

目的　探讨血管紧张素转换酶（ＡＣＥ） 基因多态性与高血压的关系。方法　应用横断面调查方法和ＰＣＲ 技术。结果　正常血压人群ＡＣＥ 基因ＤＤ、ＩＤ 和ＩＩ基因型分别占１３ ．０ ％ 、５０ ．９ ％ 和３６ ．１ ％ 。Ｉ和Ｄ等位基因频率分别是为６１ ．６ ％ 和３８ ．４ ％ 。高血压人群ＡＣＥ 基因ＤＤ、ＩＤ 和ＩＩ基因型分别占９ ．７ ％ 、４８ ．４ ％ 和４１ ．９ ％ 。Ｉ和Ｄ 等位基因频率分别是６６ ．１ ％ 和３３ ．９ ％ 。彝族男性高血压和正常血压人群的ＡＣＥ基因型分布及Ｉ／Ｄ 等位基因频率差异无显著性。结论　彝族男性ＡＣＥ 基因多态性与高血压的关联尚不能确定。     

妊娠高血压综合征亚甲基四氢叶酸还原酶基因和血管紧张素转换酶基因多态性研究

目的　探讨N5,N10 亚甲基四氢叶酸还原酶 (methyenetetrahydrofolatereductase ,MTH FR)基因和血管紧张素转换酶 (angiotensin convertionenzyme,ACE)基因多态性与妊娠高血压综合征的关系。　方法　应用多聚酶链反应 限制性内切酶片段长度多态性 (PCR RFLP)技术检测 6 2例妊娠高血压综合征 (妊高征组 )患者及 12 0例正常妊娠 (对照组 )的ACE和MTHFR基因多态性。　结果　妊高征组MTHFR基因T/T基因型频率 ( 2 7% )显著高于对照组 ( 15 % ) (P <0 .0 5 ) ,T等位基因频率 ( 5 2 % )也显著高于对照组 ( 39% ) (P <0 .0 1) ,妊高征组ACE基因缺失型纯合子 (DD)频率( 4 0 % )显著高于对照组的 ( 10 % ) (P <0 .0 1) ,缺失型 (D型 )等位基因频率 ( 6 0 % )显著高于对照组的( 2 9% ) (P <0 .0 1)。MTHFR基因T等位基因与ACE基因D等位基因之间存在协同作用。　结论　MTHFR基因和ACE基因多态与妊高征的发病有关 ,ACE基因与MTHFR基因之间可能有协同作用     

环氧酮肽类蛋白酶体抑制剂的研究进展

随着硼替佐米和卡非佐米被FDA批准用于多发性骨髓瘤患者的治疗,蛋白酶体已成为一种越来越热门的抗肿瘤药物的靶点。环氧酮肽类化合物由于其良好的选择性和较低的不良反应已成为蛋白酶体抑制剂的研究热点。本文主要综述蛋白酶体的结构和功能、环氧酮肽类蛋白酶体抑制剂的作用机制及发展现状。     

Association of the angiotensin-converting enzyme gene polymorphism with chronic heart failure in Chinese Han patients

BACKGROUND: An insertion/deletion (I/D) polymorphism is present in the 16th intron of the angiotensin-converting enzyme (ACE) gene and is associated with serum and tissue ACE level. Some studies have shown that the DD genotype is associated with some cardiovascular diseases; while ACE polymorphism's effect on chronic heart failure (CHF) remains uncertain. AIM: To investigate the association of the ACE gene I/D polymorphism with CHF in the Chinese Han population. METHODS: The genotype was determined by polymerase chain reaction in 102 normal controls and in 79 patients with CHF. Plasma angiotensin (Ang) levels were assessed by radio-immunity assay. Left ventricular end-diastolic diameters (LVDD) and left ventricular ejection fractions were assessed by echocardiography. RESULTS: The ACE gene polymorphism distribution was similar in patients and control subjects. However, ACE gene DD polymorphism was associated with a more severe condition, greater LVDD [mm: DD: 71+/-7, ID: 62+/-5, II: 60+/-5, P<0.001 DD vs. ID, P<0.001 DD vs. II] and higher plasma Ang II level [pg/ml DD: 92+/-19, ID: 79+/-21, II: 65+/-17 P<0.05 DD vs. ID, P<0.001 DD vs. II]. CONCLUSION: In Chinese Han patients with CHF, ACE gene DD polymorphism might be a marker of a more severe condition, and a higher level of activation of the renin-angiotensin system.     

Molecules affecting myelin stability: a novel hypothesis regarding the pathogenesis of multiple sclerosis

In this Mini-Review we present a new hypothesis in support of the neurodegenerative theory as a mechanism for the pathogenesis of multiple sclerosis (MS). The pathogenesis of MS results from changes in two distinct CNS compartments. These are the "myelin" and "nonmyelin" compartments. The myelin compartment is where primary demyelination, amidst attempts at remyelination, is superseded in the CNS by ongoing disease. Recent evidence obtained via magnetic resonance imaging and spectroscopy techniques supports the view that the normal-appearing white matter (NAWM) in the MS brain is altered. Several biochemical changes in NAWM have been determined. These include the cationicity of myelin basic protein (MBP) as a result of the action of peptidyl argininedeiminase (PAD) activity converting arginyl residues to citrulline. The accompanying loss of positive charge makes myelin susceptible to vesiculation and MBP more susceptible to proteolytic activity. An increase of MBP autocatalysis in the MS brain might also contribute to the generation of immunodominant epitopes. Accompanying the destruction of myelin in the myelin compartment is the activation of astrocytes and microglia. These contribute to the inflammatory response and T-cell activation leading to autoimmunity. The complex environment that exists in the demyelinating brain also affects the "nonmyelin" compartment. The inappropriate up-regulation of molecules, including those of the Jagged-1-Notch-1 signal transduction pathway, affects oligodendrocyte precursor cell (OPC) differentiation. Other effectors of oligodendrocyte maturation include stathmin, a microtubule-destabilizing protein, which prevents healing in the demyelinating brain. The hypothesis we present suggests a therapeutic strategy that should 1) target the effectors within the myelin compartment and 2) enable resident OPC maturation in the nonmyelin compartment, allowing for effective repair of myelin loss. The net effect of this new therapeutic strategy is the modification of the disease environment and the stimulation of healing and repair.     

The activities of alanine aminopeptidase,leucine aminopeptidase,proline dipeptidase and prolyl dipeptidase in the mucosa of the small intestine

Alanine aminopeptidase (EC 3.4.11.2), leucine aminopeptidase (EC 3.4.11.1), proline dipeptidase (EC 3.4.13.9), and prolyl dipeptidase (EC 3.4.13.8) have been investigated in small intestinal mucosa homogenates of normal children and children suffering from different degrees of villous damage. The activities of proline dipeptidase and prolyl dipeptidase could be shown to be significantly decreased in cases of subtotal and total villous atrophy, whereas the activities of alanine aminopeptidase and leucine aminopeptidase were not influenced. The results are discussed in view of the subcellular distribution of these enzymes.     

高血压合并脑梗死患者ACE基因I/D多态性分析

目的 探讨血管紧张素转换酶(ACE)基因插入／缺失(I／D)多态性与高血压合并脑梗死的关系。方法应用聚合酶链反应(PCR)方法检测54名正常人、40例高血压但无心脑血管合并症患和54例高血压合并脑梗死患的ACE基因型，同时检测血清ACE水平：结果 ACE基因I／D多态性与高血压无相关关系。与偶测血压、体重指数、血脂及载脂蛋白等临床、生化指标亦无相关关系，而与血清ACE活性显相关。高血压合并脑梗死组的ACED等位基因频率(66．7％)显高于高血压组(52．5％)和对照组(49．1％)：有高血压家族史的高血压合并脑梗死患的DD基因型频率(50．0％)及D等位基因频率(70．0％)显高于高血压组(23．1％，48．1％)和正常对照组(28．6％，51．2％)。结论 (1)ACED等位基因频率为高血压合并脑梗死的独立危险因素；(2)ACE基因缺失多态性与血清ACE活性有关，并增加高血压合并脑梗死的危险；(3)ACE基因缺失型可能为高血压合并脑梗死的遗传因素。     

Determination of prolinase activity in plasma. Application to liver disease and its relation with prolidase activity

We describe prolinase (EC 3.4.13.8) activity in human plasma for the first time. Optimum activity was obtained with prolylvaline as substrate and 0.02 mmol/L manganese concentration at pH 9.0. Moreover, preincubation with manganese was not required, contrary to prolidase (EC 3.4.13.9) activity. The mean value observed in 106 subjects without liver and renal disorders was 16 U/L +/- 14 (2 SD). We determined this plasma enzyme activity in patients with acute hepatitis and chronic liver disease. Plasma prolinase activity was strongly dependent upon cytolysis because of the high activity in liver and the low activity in plasma. Of 24 patients with chronic liver disease (4 chronic hepatitis and 20 cirrhosis) and without cytolysis, prolinase activity was slightly increased in only three patients, whereas prolidase activity was increased in 13. This could be due to a difference in the activation of these two enzymes in liver during the fibrotic process.