The HGAR1 familial hypercholesterolemia pedigree

Data on 232 members of a single pedigree, descended from two pairs of original parents, were made available to the participants of Genetic Analysis Workshop 8 (GAW8). In addition to information concerning age and sex, measurements for 10 quantitative traits and genotypes at 22 polymorphic marker loci were also provided for a subset of 193 of these family members. © 1993 Wiley-Liss, Inc.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

绝经后阴道出血852例临床分析

探讨经经后阴道出血的原因，相关因素来指导临床实践。方法；对我院收治的８５２例绝经后阴道出血的临床资料进行回顾性分析。结果；以阴道炎最多２６９例、慢性宫颈炎１８８例，功能失调性子宫出血１０２例，宫内节育器９８例，恶性肿瘤５９例，以内膜癌 ３３例，卵巢恶性肿瘤次之１６例。     

Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). Individuals with Type 1 and Type 2 diabetes are more susceptible to the effects of homocysteine than non-diabetic subjects. The interaction between homocysteine-thiolactone (Hcy-thiolactone), a reactive product of Hcy, and low-density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL) and it has been suggested that homocysteinylation could increase atherogenicity of lipoproteins. AIM: The aim of the study was to compare the effect of in vitro homocysteinylation of LDL isolated from healthy control subjects (C-LDL) and from Type 1 diabetic patients (DM-LDL) and to investigate the effect of homocysteinylated LDL (Hcy-C-LDL and Hcy-DM-LDL) on peroxynitrite production of endothelial cells. METHODS: The in vitro homocysteinylation of LDL isolated from control (n = 12) and DM subjects (n = 12) was carried out by incubating lipoproteins with Hcy-thiolactone. The reaction was verified by quantifying the increase in sulphydryl groups (-SH groups) in Hcy-LDL with respect to control LDL. Control and homocysteinylated LDL were incubated with human aortic endothelial cells (HAEC) in culture. Peroxynitrite production in cells treated in different experimental conditions was assayed by a fluorimetric method. RESULTS: The increase in -SH groups after incubation with homocysteine was greater in LDL from diabetic subjects compared with LDL from control subjects (P < 0.001). In addition, peroxynitrite production from HAEC incubated with Hcy-LDL from diabetic patients was greater than after incubation with Hcy-LDL from control subjects and untreated LDL from diabetic patients (P < 0.001). CONCLUSIONS: These results show that LDL from diabetic patients is more susceptible to in vitro homocysteinylation than LDL from non-diabetic individuals and demonstrate that the compositional changes in Hcy-LDL from diabetic subjects have cytotoxic effects on human endothelial cells.     

脑梗死患者血浆氧化低密度脂蛋白与一氧化氮、假性血友病因子及血浆颗粒膜蛋白的关系研究

目的探讨动脉粥样硬化性脑梗死患者血浆氧化低密度脂蛋白与血管内皮损伤及血小板活化程度的关系。方法用酶联免疫吸附测定（ELISA）的方法检测49例脑梗死患者和50例相匹配的对照组血浆氧化低密度脂蛋白（OX-LDL）、血管性假血友病因子（VWF）、血浆颗粒膜蛋白（GMP-140）水平，同时用硝酸还原酶比色法测定血清一氧化氮（NO）水平，并把、VWF、GMP-140、NO与OX-LDL作相关分析。结果脑梗死组血浆OX-LDL、、VWF、GMP-140明显高于对照组（t=2．91，P〈0．01；t=3．94，P〈0．001；t=2．08，P〈0．05），而脑梗死组血清NO水平明显低于对照组（t=4．02，P〈0．001）；相关分析表明血浆OX-LDL水平与血清NO水平呈负相关（r=-0．204，P〈0．05），与血浆懈呈正相关（r=0．60，P〈0．01），与血浆GMP-140呈正相关（r=0．430，P〈0．01）。结论脑梗死患者的血浆OX-LDL明显增高，而OX-LDL增高可能是脑梗死的危险因素。     

Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT

Objectives: To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. Methods: In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. Results: Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. Conclusions: The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE–MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE–MPA therapy, at the doses used here, promote fibroid growth.     

Diuretic treatment and serum lipoproteins: Effects of tienilic acid and indapamide

Summary Treatment with the commonly used diuretic, chlorthalidone, has previously been found to increase the serum low-density-lipoprotein cholesterol (LDL-C) fraction. Therefore, the effects of two new agents, tienilic acid (a combined diuretic-uricosuric) and indapamide on serum lipid and lipoprotein levels were assessed. Six weeks of treatment with tienilic acid, 250 mg/day, markedly decreased serum uric acid and significantly increased LDL-C and triglycerides in 16 men. In contrast, indapamide 2.5 mg/day, had no apparent influence on serum lipids or lipoproteins in 18 men.Supported in part by the Swiss National Science Foundation     

Effect of recent alcohol intake on acceptor properties of high-density lipoproteins and their interaction with liver cells

Institute of Therapy, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. All-Union Preventive Medicine Research Center, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. P. Nikitin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 12, pp. 611–613, December, 1990.