Vitamin D receptor gene polymorphism in postmenopausal women of the Han and Uygur nationalities in China

Ｔｈｅｒｉｓｋｏｆｏｓｔｅｏｐｏｒｏｓｉｓｉｓｃｌｏｓｅｌｙｒｅｌａｔｅｄｔｏｂｏｎｅｍｉｎｅｒａｌｄｅｎｓｉｔｙ (ＢＭＤ ) ,ｗｈｉｃｈｉｓｕｎｄｅｒｓｔｒｏｎｇｇｅｎｅｔｉｃｃｏｎｔｒｏｌ Ｍｏｒｒｉｓｏｎｅｔａｌ1　ｈａｖｅｓｈｏｗｎａｓｔｒｏｎｇｒｅｌａｔｉｏｎｓｈｉｐｂｅｔｗｅｅｎｐｏｌｙｍｏｒｐｈｉｓｍａｔｔｈｅｖｉｔａｍｉｎＤｒｅｃｅｐｔｏｒ (ＶＤＲ)ｇｅｎｅａｎｄＢＭＤ ＩｎａｄｄｉｔｉｏｎｔｏＢｓｍⅠ ,ｒｅｓｔｒｉｃｔｉｏｎｆｒａｇｍｅｎｔｌｅｎｇｔｈｐｏｌｙｍｏｒｐｈｉｓｍａｔｔｈ…     

The mutation of insulin receptor substrate-1 gene in Chines e patients with non-insulin-dependent diabetes mellitus

Objective To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. Methods Samples were obtained from 68 Chinese patients with NIDDM and 68 control subjects. The +1700～+4437 bp fragment of the IRS-1 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. All SSCP variations were submitted to DNA sequence analysis. Results Two amino acid variations ［GGG →AGG(G(971) R) and CCT→TCT(P(1079) S)］ and 3 silent mutations ［GAT→GAC(D(422) D), CCA→CCC(P(737) P) and GCA→GCG(A(804) A)］ were identified, among which the CCA→CCC(P(737) P) and CCT→TCT(P(1079) S) have not been previously reported. All five variations were found in Chinese patients with NIDDM, while GCA→GCG(A(804) A) was the only one found in control subjects. The overall incidence of the five variations in Chinese patients with NIDDM were much higher than that in control subjects (38.2% vs 7.4%, χ(2)=18.42,P<0.01). The most common polymorphism in the Chinese population was GCA→GCG(A(804) A), and its frequency was significantly higher in Chinese patients with NIDDM than in controls (26.5% vs 7.4%, χ(2)=8.84,P<0.01). The homozygotes of the variation in patients with NIDDM and control subjects were 8.8% and 1.5%, respectively (χ(2)=2.41,P>0.05). Conclusion These results indicate that there may be a relation between these nucleotide variations of IRS-1 gene and Chinese patients with NIDDM     

流式细胞术三色分析循环活化血小板及其在缺血怀脑血管病中的 …

目的 探讨流式细胞术（ＦＣＭ）三色分析血液中循环活化血小板（ＣＡＰ）在缺血性脑血管病中的临床意义。方法 以纤维蛋白原受体（ＦＩＢ－Ｒ０、Ｐ－选择素（ＣＤ６２Ｐ）作为分子标志物,ＦＣＭ三色免疫荧光分析ＣＡＰ。结果 正常人静止血小板膜表面ＦＩＢ－Ｒ和ＣＤ６２Ｐ表达极低（阳性百分离的中位数分别为１．４％和０．７％）。０．１μｍｏｌ／Ｌ ＡＤＰ可使血小板明显活化,１０μｍｏｌ／Ｌ ＡＤＰ使活化血小板膜表面     

Expression of the human multidrug resistance gene mdr1 in leukemic cells and its application in studying P-glycoprotein antagonists

Objective To explore the role of endothelin (ET) in the pathogenesis of exercise-induced asthma (EIA), we investigated the effects of ET(B) receptor antagonists, ET-1 (11-21)fragment and N-cis-2,6-dimethylpi-peridinocardonyl-L-γ-methylleucyl-D-1-methoxycarbonyl tryptophanyl-D-norleucine (BQ788) on broncho-constriction elicited by isocapnic hyperpnea in guinea pigs. Methods Eighteen pathogen-free Hartley guinea pigs were randomly divided into three groups. A: normal saline (NS) inhalation control group (n=6), B: BQ788 group (n=6), and C: ET-1(11-21) fragment group (n=6). Guinea pigs were anesthetized with pentobarbital sodium. After measuring the basal value of lung resistance (R[L]) and dynamic compliance of the respiratory system (Cdyn), NS (0.96 ml), BQ788 (9 nmol) and ET-1(11-21)fragment (9 nmol) were inhaled. A rodent respirator with a dry 5%CO(2)-95%O(2) mixture at room temperature provided mechanical ventilation (V[T] 8 ml/animal, 100 breaths/min) for 5 min. R[L] and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge. Results In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in R[L] and decrease in Cdyn. R[L] and Cdyn of the guinea pigs from BQ788 group and ET-1(11-21)fragment group did not change significantly. Conclusion It was demonstrated that selective ET(B) receptor antagonists, ET-1(11-21) fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs. The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors. It was suggested that ET receptor antagonists, especially ET(B) receptor antagonist, might be beneficial in preventing EIA.     

糖尿病家系及群体胰岛素受体基因变异的对照研究

目的　进一步了解 2型糖尿病胰岛素抵抗的发生机理。方法　运用聚合酶链反应及单链构型多态性 (PCR- SS-CP)技术 ,分析 4个 2型糖尿病家系、5 2例 2型糖尿病患者及 5 4例正常对照者的胰岛素受体基因第 17及 2 0外显子的变异。结果　 17外显子 10 0 8位甘氨基 (Gly)的 GGC→ GGT多态性频率在 2型糖尿病家系及群体分别为 18%和 2 9.4% ,而正常对照组为 9.3% (χ2 =12 .7133,P<0 .0 0 0 5 )。与正常对照组比较 ,2型糖尿病家系、群体的相对危险性分别为 RR=1.944 ,RR=3.738。家系连锁分析显示 L OD最大值为 0 .46 5 736 (θ=0 .0 0 0 0 )。 2 0外显子 Gly的 116 9位 GGT→ GGC多态性频率在 2型糖尿病家系、群体及正常对照组分别为 10 .0 %、15 .4%和 3.7% (χ2 =3.2 36 ,P>0 .0 5 ) ,该位点在 2型糖尿病家系、群体的相对危险性分别为 RR=2 .70 0 ,RR=3.92 7。家系连锁分析显示 L OD最大值为 1.80 334 (θ=0 .0 0 0 0 )。结论　 Gly1 0 0 8和 Gly1 1 6 9位点多态性可能是 2型糖尿病的遗传标志。     

胸部肿瘤患者手术前后血清STNFRI含量变化的分析

目的 研究胸部肿瘤患者手术前后STNFRI在血清中的变化。方法 采用ELISA方法测定了46例食管癌,32例贲门癌,80例肺癌,14例非肿瘤患者,61例志愿健康成年人。结果 胸部肿瘤患者中可溶性肿瘤坏死因子（STNFRI）的平均水平明显高于健康对照组和非肿瘤组。按肿瘤的TNM分期,STNFRI手术前后的值和升高幅度与疾病分期明显相关,与病理类型无关（P＜0．01）。结论 在排除自身免疫疾病和感染,STNFRI的测定对肿瘤的诊断、筛选、预后有辅助意义。     

应用动态血压观察氯沙坦钾治疗难治性高血压的临床疗效

目的 :观察氯沙坦钾治疗高血压的临床疗效。方法 :选择 3 2例其他降压药物疗效不佳的高血压患者 ,年龄 4 1～ 67( 55.6± 6.5)岁 ,服用氯沙坦钾 50 mg～ 1 0 0 mg/d,总疗程为 6w。全部病人在服用氯沙坦钾前和服用氯沙坦钾 6w后均行动态血压监测 ( ABPM)、偶测血压及肝肾功能、血脂和血糖检查。结果 :1 .用药后 2 4 h平均血压、日昼和夜间平均血压比用药前下降 ( P<0 .0 1 ) ,用药后收缩压及舒张压负荷均较用药前明显下降 ( P<0 .0 1 )。 2 .偶测血压疗效　服氯沙坦钾降压有效率为 1 0 0 % ,其中 2例需 1 0 0 mg/d,1例加用了双氢克尿噻 1 2 .5mg/d。 3 .降压作用的谷 /峰比值　氯沙坦钾降低收缩压和舒张压的谷 /峰比值分别为 71 .6%和 68.1 %。结论 :Ang II受体拮抗剂是继 ACEI之后的新一类抗高血压药物 ,与 ACEI相比 ,此类药物直接作用于AT1受体 ,降压作用安全可靠 ,副作用少 ,对于其他降压药物疗效不佳的高压患者也有良好效果     

哮喘急性发病与IL-5、sIL-2R及NO关系的研究

目的;探讨白介素－５（ＩＬ－５）、可溶性白介素－２受体（ｓＩＬ－２Ｒ）、一氧化氮（ＮＯ）及嗜酸粒细胞（ＥＯＳ）计数在哮喘急性发病中的意义。方法：对急性发作期哮喘患者及正常对照者血清ＩＬ－５,ｓＩＬ－２Ｒ和ＮＯ水平及ＥＯＳ计数进行了研究。使用ＩＬＩＳＡ法检测血清ＩＬ－５、ｓＩＬ－２Ｒ水平,硝酸还原酶法检测ＮＯ,伊红粉法计数ＥＯＳ。结果：哮喘急性发作组血清ＩＬ－５,ｓＩＬ－２Ｒ,ＮＯ及ＥＯＳ水平均明显     

Single-cell fate mapping reveals widespread clonal ignorance of low-affinity T cells exposed to systemic infection

T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen-specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self-antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen-specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single-cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high-affinity antigen-specific CD8⁺ T cells are efficiently recruited upon systemic infection. In contrast, most low-affinity antigen-specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high-affinity ligand. These data establish the widespread clonal ignorance of low-affinity T cells as a major factor shaping the composition of antigen-specific CD8⁺ T cell responses to systemic infection.     

非NMDA受体拮抗剂对大鼠牙髓伤害性刺激诱导的延髓Fos表达

目的 研究兴奋性氨基酸非ＮＭＤＡ受体在牙髓伤害性信息传递中的作用,为揭示牙痛的产生机制打下基础。方法 将实验动物随机分为４组。第１组单纯给予机械穿髓刺激;第２组预先侧脑室注射非ＮＭＤＡ受体拮抗剂ＣＮＱＸ,再给予相同的穿髓刺激;第３组只行ＣＮＱＸ侧脑室注射,不予穿髓刺激;第４组为正常对照组。动物存活相同时间后取延髓做Ｆｏｓ蛋白免疫组化反应。观察３组动物Ｆｏｓ免疫反应阳性细胞的数量与第１组比较没有显著