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11.
中国汉族人群APOE等位基因频率的初步研究 总被引:21,自引:2,他引:21
载脂蛋白E(apolipoproteinE,APOE)基因是一个多功能基因,除调节脂类及脂蛋白代谢之外,近年来还发现它与Alzheimer病及Ⅲ型高血脂症等病之间有密切关系。为对上述疾病进行病因学研究,作者采用一步法PCR技术对438名无亲缘关系的中国汉族健康受试者的APOE基因进行分型,并计算其基因频率分布,结果表明,中国治疗人群APOE3种等位基因的频率分别为:E2=0.0400,E3=0.8 相似文献
12.
Research into Alzheimer’s disease (AD) has been guided by the view that deposits of fibrillar amyloid-β peptide (Aβ) are neurotoxic and are largely responsible for the neurodegeneration that accompanies the disease. This ‘amyloid hypothesis’ has claimed support from a wide range of molecular, genetic and animal studies. We critically review these observations and highlight inconsistencies between the predictions of the amyloid hypothesis and the published data. We show that the data provide equal support for a ‘bioflocculant hypothesis’, which posits that Aβ is normally produced to bind neurotoxic solutes (such as metal ions), while the precipitation of Aβ into plaques may be an efficient means of presenting these toxins to phagocytes. We conclude that if the deposition of Aβ represents a physiological response to injury then therapeutic treatments aimed at reducing the availability of Aβ may hasten the disease process and associated cognitive decline in AD. 相似文献
13.
Shigemura K Shirakawa T Okada H Tanaka K Kamidono S Arakawa S Gotoh A 《Clinical and experimental medicine》2005,4(4):196-201
Abstract Familial hypercholesterolaemia is a genetic disorder characterised by high low-density lipoprotein (LDL) cholesterol concentrations,
which frequently gives rise to premature coronary artery disease (CAD). The clinical expression of familial hypercholesterolaemia
is highly variable even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental
and other genetic factors. Apolipoprotein E (Apo-E) has been extensively studied for its effects on the phenotype of familial
hypercholesterolaemia. In this study we examined the influence of Apo-E genotype on lipid parameters and the incidence of
CAD in 93 Greek patients with familial hypercholesterolaemia. Apo-E E2, E3 and E4 allele frequencies were 0.06, 0.86 and 0.09
respectively. The levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B and
lipoprotein α did not differ significantly among carriers and non-carriers of the E4 allele. The prevalence of CAD and hypertension
did not differ either. Our results suggest that the E4 allele is not associated with lipid levels or with the prevalence of
CAD among familial hypercholesterolaemia patients of the Greek population.
*The two authors were equally involved in the work 相似文献
14.
G. Feussner M. Eichinger R. Ziegler 《Journal of molecular medicine (Berlin, Germany)》1992,70(11):1027-1035
Summary Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study. With the 20-mg dose (n = 19) the mean plasma cholesterol level decreased from 13.24±8.04 8.04 at baseline to 8.04±4.19 mmol/l (mean reduction 39.3%; P<0.05), and the mean plasma triglyceride level decreased from 13.47±19.22 to 7.84±7.71 mmol/l (–41.8%; NS); this was due to a decrease in very low density lipoprotein (VLDL) cholesterol from 8.95±8.64 to 4.94±4.24mmo1/l (–44.8%; NS), a decrease in low density lipoprotein (LDL) cholesterol from 3.54±0.93to 2.25 ± 0.59 mmol/l (–36.5%; P<0.01), and an increase in high density lipoprotein (HDL) cholesterol from 0.72±0.28 to 0.85±0.34 (+18.1%; NS). Thirteen patients were treated with 40 mg simvastatin per day. Under this regimen there was a further significant decrease in LDL cholesterol from 2.33±0.62 to 1.81±0.49 mmol/l (–22.3%; P<0.01). In six patients who remained hyperlipidemic on monotherapy combination drug therapy with simvastatin (40 mg per day) and gemfibrozil (450 mg per day) was given. Compared to simvastatin alone the addition of gemfibrozil further lowered plasma concentrations of total cholesterol by 14.9%, VLDL cholesterol by 23.5%, and triglycerides by 17.1%, although this was not statistically significant. No patient was discontinued from single or combination drug therapy, and no severe clinical or biochemical side effects were observed. The results of this study demonstrate the usefulness of simvastatin in the therapy of type III HLP and indicate that in individual patients who remain hyperlipidemic on monotherapy combination drug therapy with both of these drugs is effective in further reducing plasma concentrations of total cholesterol, VLDL cholesterol, and triglycerides. Although no patient in this investigation developed myopathy or rhabdomyolysis, combined fibrate-HMG CoA reductase inhibitor treatment should be considered only for severe forms of hyperlipidemia and for patients who do not respond sufficiently to mon-therapy of any of these drugs.Abbreviations Apo
Apolipoprotein
- CPK
creatine phosphokinase
- GGT
gamma-glutamyl transpeptidase
- HDL
high density lipoproteins
- HLP
hyperlipoproteinemia
- HMG CoA
3-hydroxy-3-methyl glutaryl coenzyme A
- IDL
intermediate density lipoproteins
- LDL
low density lipoproteins
- TG
triglycerides
- VLDL
very low density lipoproteins 相似文献
15.
Takada D Emi M Ezura Y Nobe Y Kawamura K Iino Y Katayama Y Xin Y Wu LL Larringa-Shum S Stephenson SH Hunt SC Hopkins PN 《Journal of human genetics》2002,47(12):0656-0664
16.
Reciprocal effects of apolipoprotein E alleles (ε2 AND ε4) on plasma lipid levels in normolipidemic subjects 总被引:2,自引:0,他引:2
A significantly lower frequency of the epsilon 2 allele and a significantly higher frequency of the epsilon 3 allele were found in the normolipidemic Japanese population than those in the normolipidemic Caucasian populations. We have compared plasma lipid variables among the apolipoprotein (apo) E phenotype groups and estimated the average effects of the three common alleles (epsilon 2, epsilon 3 and epsilon 4) on plasma lipid levels in normolipidemic subjects. Plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG, VLDL-cholesterol (C) and apo E levels were high in the apo E3/2 group, intermediate in the apo E3/3 group and low in the apo E4/3 group, whereas plasma total cholesterol (TC), low density lipoprotein (LDL)-C and high density lipoprotein (HDL)-C levels were low in the apo E3/2 group, intermediate in the apo E3/3 group and high in the apo E4/3 group. Furthermore, the epsilon 2 allele had an effect to increase the TG, VLDL-TG, VLDL-C and apo E levels and decrease the TC, LDL-C and HDL-C levels, whereas the epsilon 4 allele had an effect opposite to the epsilon 2 allele. These results indicate that the epsilon 2 and epsilon 4 alleles have the reciprocal effects on plasma lipid, lipoprotein and apo E levels. 相似文献
17.
Hunter S Weiss S Ou CY Jaye D Young A Wilcox J Arbiser JL Monson D Goldblum J Nolen JD Varma V 《Human pathology》2005,36(9):987-993
Apolipoprotein D (apoD) expression was studied in nonneoplastic peripheral nerve, neurofibromas (NFs), and malignant peripheral nerve sheath tumors (MPNSTs) by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. Multiplex quantitative polymerase chain reaction for messenger RNA was performed on a series of formalin-fixed and paraffin-embedded specimens that included 9 MPNSTs, 12 NFs, and 4 normal peripheral nerves. The average apoD expression was 108-fold decreased (DeltaCt = -7.3) in the MPNSTs compared with the NFs (P < .05). ApoD expression levels were 3.0-fold elevated (DeltaCt = 1.7) in the NFs compared with nonneoplastic peripheral nerve (P < .05). In situ hybridization for apoD RNA was performed on a separate series of 10 cases in which each microscopic section included both MPNST and the NF from which it arose. These studies confirmed elevated apoD expression in NFs compared with MPNSTs and demonstrated that this expression was variable among individual cells within the NFs. Differential expression by immunohistochemistry could only be demonstrated in selected areas, most likely because apoD protein is a small molecule that is secreted out of the cell into the extracellular space and plasma. ApoD expression initially increases a small amount with the formation of NFs from nonneoplastic peripheral nerve and subsequently decreases markedly as NFs transform into MPNSTs. This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis. 相似文献
18.
Presence of autoantibodies to apolipoprotein A-1 in patients with acute coronary syndrome further links autoimmunity to cardiovascular disease 总被引:2,自引:0,他引:2
Vuilleumier N Reber G James R Burger D de Moerloose P Dayer JM Roux-Lombard P 《Journal of autoimmunity》2004,23(4):227-360
Anti-apolipoprotein A-1 (Apo A-1) autoantibodies were described in autoimmune disorders such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and might be involved in the genesis of arterial and venous thrombotic events. To investigate the presence of these autoantibodies in patients with acute coronary syndrome (ACS) without other features of autoimmunity, we set up an enzyme-linked immunosorbent assay (ELISA) for anti-Apo A-1 antibodies. We used it to investigate their prevalence in ACS as compared to SLE and APS and correlated them to plasma Apo A-1 and serum amyloid A protein (SAA) concentrations. The prevalence of anti-Apo A-1 autoantibodies in the healthy control group was 1% (1/92), but was significantly higher in other groups: 21% (11/53) in ACS group (P=0.001), 13% (12/92) in SLE and/or APS group (P=0.005). Multiple linear regression revealed a significant correlation between plasma Apo A-1 (r=-0.72, P=0.013), plasma SAA concentration (r=0.76, P=0.0066) and anti-Apo A-1 IgG titre in ACS patients. The presence of anti-Apo A-1 autoantibodies in patients with ACS highlights an additional link between autoimmunity, inflammation and atherosclerosis. 相似文献
19.
人血清载脂蛋白H的纯化与鉴定 总被引:1,自引:0,他引:1
为了研究载脂蛋白H(apoH)与疾病的关系,分别用HClO4,(NH4)2SO4沉淀、DEAE-纤维素离子交换层析,从人血清中纯化了载脂蛋白Ho用测定分子量,分析氨基酸组成和N-端氨基酸测序三个方面进行鉴定。用SDS-PAGE测得其相对分子量对54000。用高效液相色谱测定其中15种氨基酸的相对含量(mol/10^3mol残基)如下:Asp119.8,Glu108,Thr94.8,Ser78.6,Phe64.9,Gly1008,Ala57.2,Val57.2,Met10.6,Ile50.3,Leu77.1,Tyr31.9,His15.2,L-ys81.4,Arg39.4;d PE-ABI公司生产的475A型气相蛋白质测序仪上测得其N端10个氨基酸残基顺序如下:NH2-Gly-Arg-Cys-Pro-Asp-Asp-Leu。纯化得到的apoH与肝素有高的亲和性,还能与乙肝表面抗原结合。纯化apoH的方法相对比较简单,能达到测序的要求。 相似文献
20.
Renata Boldrini Roberto Biselli Cesare Bosman 《Pathology, research and practice》2001,197(11):753-757
Three children with malabsorption presumably caused by celiac disease had undergone jejunal biopsy. While a histological examination revealed microvacuolization of enterocytes in the absence of celiac lesions, an ultrastructural investigation disclosed numerous chylomicrons and larger lipid vacuoles inside the cytoplasm of enterocytes, mostly in the supranuclear region. No chylomicrons were evident in the interstitium between adjacent enterocytes, as observed in normal subjects. These ultrastructural findings allowed for the diagnosis of "Chylomicron retention disease" (CRD). CRD was described for the first time by Anderson in 1961, and it is included in the group of disorders of biosynthesis and secretion of B apolipoproteins (apoB). This disease, in particular, appears to result from a specific defect involving the secretion of lipoproteins containing apoB-48 from the gut, with the complete absence of post prandial chylomicrons in the sera. CRD needs to be recognized early because of its adverse effects on growth and its potential for neurological and ocular complications, and the ultrastructural identification of chylomicron-size lipid droplets clustered in the enterocytes, with the absence of fat outside the cells, represents the gold standard to identify CRD. together with clinical aspects and laboratory measurements. In this study, we describe the histological and ultrastructural aspects observed in three pediatric cases of CRD. 相似文献