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.     

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.     

Cardiovascular regulation and lipoprotein profile during administration of co-dergocrine in essential hypertension

Summary Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by −7% and the upright plasma NE level by −24%. Supine plasma NE also fell (−24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by −6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL − cholesterol fraction.     

肝癌术后监测血清AFP的临床意义(附70例报告)

为探讨肝癌术后监测血清甲胎蛋白(AFP)的临床意义，回顾性分析1996年2月至2002年3月间肝癌根治切除术后定期监测发现血清AFP阳性的70例患者AFP升高与肿瘤残留、复发或转移的关系。肝癌术后血清AFP升高可见于肝癌的残留或早期转移、肝癌的复发或转移、肝癌的再发以及晚期肝硬变4种情况。对肝癌患者术后定期作AFP检查，有助于检出AFP阳性肝癌患者的肿瘤残留及亚临床期复发转移，不仅适用于术前AFP阳性，而且适用于术前AFP阴性的肝癌患者。肝癌患者术后AFP下降，但不能降至正常，可能与晚期肝硬变肝脏内干细胞-卵圆形细胞代偿性增生有关。     

Association of a genetic polymorphism in human apolipoprotein B-100 with intermediate density lipoprotein concentrations

Immunochemical techniques have been used to identify five antigenic (Ag) sites on apolipoprotein B-100 (apoB), the major protein constituent of very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL). Each Ag site results from allelic variation at a specific locus of the apoB gene. In the present study, we assessed whether variations in the five Ag loci were associated with concentrations of plasma lipids or lipoprotein fractions measured by analytical ultracentrifugation in a group of 44 healthy men. Pair-wise analyses of the Ag markers revealed that Ag(a1/d), in association with either Ag(x/y) or Ag(t/z), is significantly related to plasma IDL-mass concentrations. In this cohort we detected no significant associations of the Ag alleles (singly or in combination) with plasma total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, or mass of total VLDL or LDL. These results suggest that genetic variations in the apoB molecule may predispose to variations in concentrations of IDL that could have consequences for atherosclerotic risk.     

冠心病病人氧化修饰低密度脂蛋白的测定及临床意义

目的 :探讨氧化修饰低密度脂蛋白 (Ox LDL)对冠心病 (CHD)形成和发展的影响。方法 :CHD组 6 0例 ,对照组 5 3例。用酶标多克隆抗体夹心的方法检测血清Ox LDL含量。结果 :CHD组血清Ox LDL含量为 ( 48.6± 32 .8) μg dl。对照组( 2 5 .9± 2 2 .5 ) μg dl,两组之间Ox LDL含量存在显著性差异 (P <0 .0 0 1)。 结论 :Ox LDL和CHD有密切的关系 ,故可作为CHD病人特异性的辅助诊断指标。     

Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism

Abstract. The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of cholesteryl ester towards apolipoprotein B-containing lipoproteins. Phospholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipoproteins, insulin and C-peptide in fasting plasma from eight healthy obese men (body mass index >27 kg m^-2) and 24 non-obese subjects. The obese men had lower levels of HDL cholesterol (P<0·05) and higher levels of plasma triglycerides (P<0·05), insulin (P<0·05) and C-peptide (P<0·01), as compared to the quartile of subjects with the lowest body mass index (BMI <22·4 kg m^-2). CETP and PLTP activities were elevated in the obese men by 35% (P<0·01) and by 15% (P<0·05), respectively. LCAT activity was comparable among the quartiles. Linear regression analysis showed that CETP activity was positively correlated with body mass index (P<0·02), fasting blood glucose (P7lt;0·05) and plasma C-peptide (P<0·05). PLTP activity was positively related to body mass index (P<0·01), waist to hip circumference ratio (P<0·001), as well as to fasting blood glucose (P<0·05) and plasma C-peptide (P<0·05) It is concluded that the activities of CETP and PLTP are influenced by adiposity and possibly by insulin resistance. Elevated lipid transfer protein activities may provide a mechanism that contributes to alterations in HDL in insulin resistant states.     

Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats

Wilke , W. Lee & Person , A. E. G. 1992. Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats. Acta Physiol Scand 144 , 253–261. Received 26 June 1991, accepted 8 October 1991. ISSN 0001–6772. Department of Physiology, Colorado State University, Fort Collins, Colorado, USA and Department of Physiology and Biophysics, University of Lund, Sweden. Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg^-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 ± 2 mmHg vs. 38 ± 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 ± 0.03 vs. 0.31± 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 ± 2 to 44 ± 2 mmHg, P= 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 ± 0.02–0.42 ±0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post-surgery nephrectomized rats and their respective controls when combined (r = 0.89, P= 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r= 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups. We conclude that stop-flow pressure in remnant kidneys of pre-hypertensive rats is primarily determined by the post- to pre-glomerular resistance ratio, and increases in stop-flow pressure and post- to pre-glomerular resistance ratios in remnant kidneys are transient in the absence of systemic hypertension. The role of the renin-angiotensin system in determining the ratio and stop-flow pressure is dependent on time post-nephrectomy. Captopril-induced increases in stop-flow pressure and post- to pre-glomerular resistance ratio at 8 weeks, suggests that its primary effect at that time is not a preferential post-gIomerular vasodilation subsequent to reductions in intrarenal angiotensin II.