脂蛋白（a）和载脂蛋白（a）多态性与女性冠心病的相关性研究

冠心病（ＣＨＤ）在病因、发病年龄等诸多方面存在性别差异。载脂蛋白（ａ）［ａｐｏ（ａ）］多态性与脂蛋白（ａ）［Ｌｐ（ａ）］血浆水平对女性ＣＨＤ影响的资料甚少。我们通过检测３５例女性ＣＨＤ患者和４５例女性正常对照者的ａｐｏ（ａ）多态表型及Ｌｐ（ａ）水平，并与相应的男性组对比分析，发现含有等位基因Ｓ１、Ｓ２、Ｂ的ａｐｏ（ａ）低分子量表型的ＣＨＤ患者，女性占３７．１４％，显著高于对照组，而男性仅占２５．７１％，与对照组比较差异无显著性。在女性中低分子量表型发生ＣＨＤ危险度为对照组的４．７倍，在男性中仅为１．４倍。提示：低分子量表型对女性ＣＨＤ的影响大于男性。Ｌｐ（ａ）水平在两性ＣＨＤ组均明显高于对照组，而两性之间则差异无显著性。     

Outcomes comparing a pancreaticogastrostomy (PG) and a pancreaticojejunostomy (PJ) after a pancreaticoduodenectomy (PD)

BackgroundThe advantage of a pancreaticogastrostomy (PG) over a pancreaticojejunostomy (PJ) after a pancreaticoduodenectomy (PD) is not clear.AimThe aim of the present study was to compare the pancreatic fistula (PF, defined according to the International Study Group for Pancreatic Fistula classification) rate and other complications between both methods.MethodsRetrospective analysis of prospectively collected data of 424 [median: 65 years (17–83)] patients who underwent PG (239, 56.4%) and PJ (185, 43.6%) reconstruction between January 2005 and December 2009.ResultsPF occurred in 55 (23.5%) in the PG and 30 (16.2%, P= 0.067) patients in the PJ group. Grade A PF occurred in 19 (7.9%), B in 22 (9.2%) and C in 14 (5.8%) in the PG compared with 5 (2.7%), 12 (6.5%) and in 13 (7.0%), respectively, in the PJ group. The median hospital was 10 days in both groups. The morbidity was higher in the PG group (108, 45.2 vs. 62, 33.5%, P= 0.015). However, there was no significant difference in the 90-day mortality between both groups (PG-17, 7.0% vs. PJ-16, 8.6%, P= 0.558).ConclusionThere was no difference in the overall PF rate, hospital stay and overall mortality between PG and PJ reconstruction methods. However, the grade A PF rate was higher in the PG group.     

Lipoprotein (a) reduces platelet aggregation via apo(a)-mediated decreases in thromboxane A(2)production

Agonist (collagen- or ADP-)-stimulated platelet aggregation and thromboxane B(2) (T X B(2) ) production was reduced in human whole blood (WB) and washed platelets (WP) that were co-incubated with lipoprotein (a)[Lp(a)] at levels of 25, 50 and 100 mg % but not at 5 mg % relative to a baseline concentration of 1 mg %. Significant decreases in agonist-stimulated aggregation and T X B(2) levels were seen with 5, 25, 50 and 100 mg %purified apo (a) that was co-incubated with WB and WP relative to a baseline concentration of 1 mg %. Purified Lp(a) that was free of apo(a) [Lp(a)(-)], at concentrations of 5, 25, 50 and 100 mg %, that were co-incubated with WB and WP, had no impact on agonist-induced platelet aggregation and T X B(2) production relative to a baseline level of 1 mg %. A monoclonal antibody (Mab) (3B1) against apo(a) blocked Lp(a)-mediated reduction in platelet aggregation and T X B(2) concentrations in WB and WP that were stimulated by either agonist. Various Mabs against apoB failed to affect an Lp(a)-induced reduction in WB and WP aggregation or T X B(2) levels in response to either agonist. These results strongly suggest that Lp(a)-induced decreases in collagen or ADP stimulated platelet aggregation and T X B(2) production are mediated by apo(a).     

Lipoprotein (a)

The lipids are transported by lipoproteins in the blood system. Lipoprotein (a) [Lp (a)] is a unique lipoprotein of the human plasma discovered by professor Berg in 1963. Lp (a) consists of apolipoprotein (a) and LDL particles (apolipoprotein B100). The level and size of Lp (a) are highly variable and largely determined heredity. Clinical studies on animal models have shown that elevated Lp (a) levels are linked with a higher risk of atherosclerosis, even though not all of the conclusions based on the studies that have been carried are convincing. Concentration over 35 mg/dl is considered to be a risk level. Surprisingly high Lp (a) levels in old age are associated with longevity. This may be explained by the physiological role of Lp (a) in tissue reparation, wound healing and anti-cancer effect.     

2型糖尿病患者的脂蛋白(a)浓度和载脂蛋白(a)分型

目的 研究２型糖尿病患者的脂蛋白（ａ）〔Ｌｐ（ａ）〕浓度和载脂蛋白（ａ）〔ａｐｏ（ａ）〕的多态性以及与糖尿病慢性并发症的关系。方法 本研究用改良的Ｕｔｅｒｍａｎｎ和Ｇｕｏ方法对４０名非糖尿病对照和１７６名２型糖尿病患者进行ａｐｏ（ａ）分型检测,观察其与Ｌｐ（ａ）浓度以及微血管和大血管并发症之间的关系,包括肾脏病变、视网膜病变、神经病变、高血压、冠心病、脑梗塞。结果 ４０名非糖尿病对照之ａｐｏ（ａ）     

Lipoprotein(a) in nonhuman primates. Presence and characteristics of Lp(a) immunoreactive materials using anti-human Lp(a) serum

Lipoprotein(a) (Lp(a] immunoreactive materials were examined in serum samples from 77 nonhuman primates of 24 species by Ouchterlony's double diffusion procedure and an enzyme-linked immunosorbent assay (ELISA) using rabbit antisera to human Lp(a). The precipitates obtained with sera from orang-utan and chimpanzee formed reactions of complete identity with the Lp(a) precipitate with human serum. When sera from Old World monkeys and human subjects were tested in wells next to each other, spurs developed between the 2 precipitates, indicating that Lp(a)-like lipoproteins in Old World monkeys have partial identity with human Lp(a). Lp(a) immunoreactive materials were identified in association with lipids by means of fat staining of the precipitates. On the other hand, reactants which could be precipitated with anti-human Lp(a) sera were not detectable in prosimians and New World monkeys. These results suggest that serum Lp(a)-like lipoprotein is phylogenetically acquired in Old World monkeys. However, the possibility that the structures of serum Lp(a)-like lipoproteins in prosimians and New World monkeys are too different to react with anti-human Lp(a) sera cannot be ruled out.     

Living donor liver transplantation in a recipient with anti-Fy(a) and Jk(a) antibodies

We report a case of a living donor liver transplantation using right lobe graft to a recipient having anti-Fy(a) and Jk(a) antibodies. The red blood cell (RBC) antigens of the donor were Fy (a+) and Jk (a-). We attempted to eliminate donor RBCs remaining in the graft by perfusing histidine-tryptophan-ketoglutarate. Further, Fy (a-)/Jk (a-) RBC concentrates were transfused during the operation. However, the anti-Fy(a) titer increased approximately 8-fold on the seventh postoperative day. On the same day, serum levels of transaminase and total bilirubin increased presumably due to acute cellular rejection. Steroid administration immediately reduced levels of transaminase, total bilirubin and anti-Fy(a) titer. The increase of anti-Fy(a) titer may be due to a secondary immune response to the donor's Fy(a) antigen on RBCs remaining in the graft.     

L-carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a)

BACKGROUND AND AIMS: Elevated Lp(a) levels are a significant cardiovascular risk factor, particularly for young individuals and for subjects with concomitant high LDL cholesterol. Increased Lp(a) is believed to be linked to an enhanced production of the lipoprotein, controlled by genetic factors; it can be reduced by agents such as nicotinic acid, lowering free fatty acid inflow to the liver. METHODS AND RESULTS: L-carnitine, a natural compound stimulating fatty acid oxidation at the mitochondrial level, was tested in a double blind study in 36 subjects with Lp(a) levels ranging between 40-80 mg/dL, in most with concomitant LDL cholesterol and triglyceride elevations. L-carnitine (2 g/day) significantly reduced Lp(a) levels (-7.7% vs baseline and -11.7% vs placebo treatment), the reduction being more dramatic in the subjects with the more marked elevations. In particular, in the L-carnitine group, 14 out of 18 subjects (77.8%) had a significant reduction of Lp(a) vs only 7 out of 18 (38.9%) in the placebo group (chi 2 = 4.11, p = 0.0452). In a significant number of subjects the reduction of Lp(a) resulted in a return of this major cardiovascular risk parameter to the normal range. CONCLUSIONS: L-carnitine offers a potentially useful therapeutic agent for atherogenic conditions characterized by high Lp(a) levels, also in view of the excellent tolerability and essential lack of major side effects.     

Lipoprotein(a) levels in centenarians

In elderly subjects (above 65 years), cardio- and cerebrovascular diseases are known to contribute to the death rate. Serum lipoprotein(a) = Lp(a), a low density lipoprotein, is involved in the atherogenic processes, as confirmed by several clinical trials. We evaluated serum Lp(a) levels in a group of centenarians (15 females and 7 males, mean age 102.81 +/- 2.5 years) compared to 25 healthy control subjects (10 males and 15 females, mean age 51.12 +/- 15.34 years). In all subjects Lp(a) serum levels were determined by ELISA method (EIA mod. 2550 reader). Statistical analysis of the results was performed by using the Student's t test. In centenarians the mean Lp(a) level increased (39.6 +/- 23.53 mg/dl) compared to that of the control group (16.78 +/- 16.24 mg/dl) (p < 0.005). The elevated Lp(a) values observed in centenarians may be attributed to the presence of low molecular weight lipoprotein isoforms which are known to be associated with cardio-cerebrovascular risk. Therefore, it seems that elevated Lp(a) levels alone are not risk factors for the onset of acute acute vascular accidents and do not influence longevity.     

Apolipoprotein (a) phenotypes and lipoprotein (a) concentrations in patients with type III hyperlipoproteinaemia

Abstract. Objectives . The familial lipoprotein disorder type III hyperlipoproteinaemia (HLP) carries a marked increase in the risk of accelerated and premature atherosclerosis, but there is considerable variation amongst affected individuals in their susceptibility to cardiovascular disease (CVD). Therefore, it was the aim of our study to investigate the possible influence of lipoprotein (a) [Lp(a)] in the pathogenesis of type III HLP. Design . Apolipoprotein (a) [apo(a)] phenotypes and Lp(a) concentrations were determined in patients with the disease and in an appropriate control group. Setting . University out-patient lipid disorder clinic. Subjects . Seventy-six apoE-2 homozygous patients with type III HLP and 76 normolipidaemic and healthy age- and sex-matched controls. Main outcome measures . The frequencies of different apo(a) phenotypes and their correlations with Lp(a) serum concentrations were determined in patients and controls. Results . Lp(a) concentrations were not significantly different in type III HLP patients (14.1±19.1 mg dl^-1) as compared with the controls (13.3±16.2 mg dl^-1; P = 0.549, NS). In addition, there was no significant difference in apo(a) phenotype frequencies amongst both groups (0.2 > P > 0.1). Conclusions . We conclude that the apo(a) polymorphism does not participate (to a significant extent) in the phenotypical expression of type III HLP.     

Relationship between 'sinking pre-beta-lipoprotein' (Lp(a) lipoprotein) and age in a family kindred

Serum Lp(a) levels have been measured in a family kindred of three generations by Laurell electrophoresis. It was found that individuals with Lp(a) levels exceeding 30 mg/dl exhibited an extra pre-beta-band in agarose gel electrophoresis (sinking pre-beta positive), and a significant positive correlation existed between serum Lp(a) levels and age. A positive correlation between Lp(a) and total serum cholesterol was observed only in sinking pre-beta-positive individuals, but not in sinking pre-beta-negative individuals with Lp(a) levels of less than 30 mg/dl. These findings are not contradictory to the assumption that Lp(a) might be an independent rise factor for atherosclerosis.     

Serum apolipoprotein(a) concentrations and apo(a) phenotypes in patients with liver cirrhosis

Objective: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline.
Methods: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function.
Results: Apo(a) serum levels were significantly lower ( p < 0.01 ) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations ( p = 0.0313 ). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration.
Conclusion: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apoliprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.     

Determination of lipoprotein(a) concentrations and apolipoprotein(a) molecular weights in diabetic patients

Lipoprotein(a) (Lp(a)) with atherogenic and thrombotic properties has been frequently studied in diabetes, because a high cardiovascular risk has been reported both in type 1 and type 2 diabetes. Few studies have considered genetic factors, especially the isoforms of apolipoprotein(a). The aim of this work is to determine the distribution of apo(a) phenotypes in the serum of 148 diabetic patients (59 type 1, 89 type 2) with or without vascular complications. Apo(a) phenotypes are determined using 4-15% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting (PhastSystem - Pharmacia). An inverse relationship is observed between Lp(a) serum concentration and the apparent molecular mass of apo(a) isoforms: type 1 r=- 0.61, p<0.01; type 2 r=- 0.55, p<0.01. The frequency of apo(a) isoforms is significantly different between type 1 and type 2 diabetes mellitus. A higher prevalence of isoforms of low molecular weight was observed in the type 2 diabetic population.