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排序方式: 共有1362条查询结果,搜索用时 15 毫秒
61.
62.
Joana R. Chora Michael A. Iacocca Lukáš Tichý Hannah Wand C. Lisa Kurtz Heather Zimmermann Annette Leon Maggie Williams Steve E. Humphries Amanda J. Hooper Mark Trinder Liam R. Brunham Alexandre Costa Pereira Cinthia E. Jannes Margaret Chen Jessica Chonis Jian Wang Serra Kim Mafalda Bourbon 《Genetics in medicine》2022,24(2):293-306
PurposeIn 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified.MethodsThe multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached.ResultsThe consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others.ConclusionEstablishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH. 相似文献
63.
Lankin VZ Ivanova MV Konovalova GG Tikhaze AK Kaminnyi AI Kukharchuk VV 《Bulletin of experimental biology and medicine》2007,143(4):414-417
We studied the effects of two inhibitors of β-hydroxy-β-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on
the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly
increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The
lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats.
In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving
simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time,
in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the
period of induction of oxidation increased by 3.3 times. Our results indicate that β-hydroxy-β-methylglutaryl coenzyme A reductase
inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.
__________
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 4, pp. 390–393, April, 2007 相似文献
64.
Intravenous infusion of nerve growth factor‐secreting monocytes supports the survival of cholinergic neurons in the nucleus basalis of meynert in hypercholesterolemia brown‐norway rats 下载免费PDF全文
Lindsay A. Hohsfield Daniela Ehrlich Christian Humpel 《Journal of neuroscience research》2014,92(3):298-306
The recruitment of monocytes into the brain has been implicated in Alzheimer's disease and recent studies have indicated that monocytes can reduce amyloid plaque burden. Our previous investigations have shown that hypercholesterolemic rats develop cognitive, cholinergic, and blood–brain barrier dysfunction, but do not develop amyloid plaques. This study was designed to evaluate the effects of repeated intravenous (i.v.) infusion (via the dorsal penile vein) of primary monocytes on cognition, the cholinergic system, and cortical cytokine levels in hypercholesterolemia Brown‐Norway rats. In addition, we also transduced the monocytes with nerve growth factor (NGF) to evaluate whether these cells could be used to deliver a neuroprotective agent to the brain. Our results indicate that repeated i.v. infused monocytes migrate into the brains of hypercholesterolemic rats; however, this migration does not translate into marked effects on learning. Animals receiving NGF‐loaded monocytes demonstrate slightly improved learning and significantly elevated cholinergic neuron staining compared to treatment with monocytes alone. Furthermore, our data indicate that repeated infusion of monocytes does not lead to elevated cytokine secretion, indicating that no inflammatory response is induced. This study provides an experimental attempt to evaluate the effects of blood‐derived primary monocytes in hypercholesterolemia rats. © 2013 Wiley Periodicals, Inc. 相似文献
65.
Anders Hovland Randolf Hardersen Joe Sexton Tom Eirik Mollnes Knut Tore Lappegård 《Journal of clinical apheresis》2009,24(6):247-253
Low‐density lipoprotein (LDL) apheresis is well‐established in selected patients with uncontrolled LDL levels. As such treatment affects biomarkers important in atherosclerosis and acute coronary syndromes, we systematically compared the inflammatory response induced by three LDL apheresis columns. Three patients with heterozygous familial hypercholesterolemia participated in a cross‐over study with six consecutive treatments with three different LDL apheresis columns: DL‐75 (whole blood adsorption), LA‐15 (plasma adsorption), and EC‐50W (plasma filtration). Biochemical parameters and inflammatory biomarkers, including complement activation products and 27 cytokines, chemokines, and growth factors were measured before and after treatment. Complement was activated through the alternative pathway. The final end product sC5b‐9 increased significantly (P < 0.01) and equally with all devices, whereas the anaphylatoxins C3a and C5a were lower by use of the adsorption columns. Hs‐CRP was reduced by 77% (DL‐75), 72% (LA‐15), and 43% (EC‐50W). The cytokines were consistently either increased (IL‐1ra, IP‐10, MCP‐1), decreased (IFN‐γ, TNF‐α, RANTES, PDGF, VEGF), or hardly changed (including IL‐6, IL8, MIP‐1αβ) during treatment. The changes were in general less pronounced with the adsorption columns. All columns reduced LDL significantly and to the same extent. In conclusion, three LDL‐apheresis devices with equal cholesterol‐lowering effect differed significantly with respect to the inflammatory response. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
66.
目的:研究P选择素在高胆固醇血症小鼠肾脏的表达,探讨脂质肾毒性损伤的机制。方法:24只雌性C57/BL小鼠分为2组,普通膳食组(A组)和高胆固醇膳食组(B组),喂养15周,用生化酶法检测血脂;用PAS和HE染色观察肾脏组织学改变;免疫组化SABC法检测P选择素的表达。结果:B组血清总胆固醇(Tch)和低密度脂蛋白胆固醇(LDL-C)浓度显著高于A组(P<0.05,P<0.01);肾小球细胞数及系膜区占肾小球面积比显著高于A组(P<0.05,P<0.01);P选择素表达明显增加(P<0.01)。结论:P选择素的明显表达可能与脂质引起的肾小管间质损害有关。 相似文献
67.
Berthold Koletzko Ingeborg Kupke Udo Wendel 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(9):682-685
In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
68.
目的比较中药血脂康、辛伐他汀(舒降之)治疗原发性高脂血症的调脂作用和安全性。方法80例原发性高脂血症患者随机分为血脂康组和舒降之组,各服药8周为1个疗程,治疗期间患者保持治疗前的饮食习惯,不用其他干扰血脂代谢的药物。8周后观察两组调脂效果和不良反应。结果血脂康组:TC降低25.15%,TG降低21.22%,DL-C降低38.08%,TC-HDL-C/HDL-C降低44.03%。舒降之组:TC降低26.02%,TG降低22.62%,LDL-C降低38.50%,TC-HDL-C/HDL-C降低44.22%,两组各项指标治疗后的组内相比,均有统计学意义(P<0.001),两组间各项指标治疗后对应比较均无统计学意义(P>0.05),两组间不良反应轻微,不影响继续治疗,不良反应总发生率血脂康组较低(P<0.05)。结论血脂康和辛伐他汀均有强大的降低TC、TG、LDL-C和TC-HDL-C/HDL-C的作用,均为治疗原发性高脂血症有效和安全的药物,血脂康不良反应更低,提示中药血脂康具有更好的耐受性。 相似文献
69.
de Bont N Netea MG Demacker PN Kullberg BJ van der Meer JW Stalenhoef AF 《European journal of clinical investigation》2000,30(9):818-822
BACKGROUND: All lipoproteins are able to bind to bacterial lipopolysaccharide (LPS), thereby neutralizing its deleterious effects. However, we demonstrated, recently, that in the absence of apolipoprotein E (apoE), eight-fold increased very-low-density lipoprotein levels were not sufficient to protect apoE-deficient (apoE-/-) mice against LPS. During a live Gram-negative infection, mechanisms other than LPS-neutralization may play a role in the pathogenesis of the disease. In the present study we further examined the role of apoE in Gram-negative sepsis. METHODS: Survival, bacterial outgrowth in liver, spleen, kidneys and blood, and tumour necrosis factor-alpha (TNF-alpha) production were measured in apoE-/- mice and control C57BL/6J mice, after an intravenous infection with Klebsiella pneumoniae. RESULTS: Mice that lack apoE showed higher mortality in response to K. pneumoniae than control mice (90% vs. 23% respectively after 2 weeks). ApoE-/- mice had 10-100 times more outgrowth of the bacteria in their organs than controls. Furthermore, circulating TNF-alpha concentrations 90 min after a challenge, were almost twice as high in the apoE-/- mice compared to controls (13.0 +/- 2.9 ng mL-1 vs. 7.6 +/- 3.8 ng mL-1). When apoE-/- and control mice were rendered neutropenic, the discrepancy in survival and outgrowth of K. pneumoniae disappeared. CONCLUSIONS: The apoE-/- mice were more susceptible than control C57BL/6 mice to a K. pneumoniae infection. The absence of apoE may render these mice more susceptible, since this protein is of importance in the detoxification of lipopolysaccharide of Gram-negative bacteria. On the other hand, the phagocytic capacity of granulocytes seems to be decreased in apoE-/- mice, resulting in increased outgrowth and mortality. 相似文献
70.
Uruwan Yamborisut Pongtorn Sungpuag Wanphen Wimonpeerapattana 《Pediatrics international》2008,50(4):557-562
Background: There is evidence to show that atherosclerosis can occur in young children and that elevated total cholesterol and low density lipoprotein cholesterol concentrations are risk factors for atherosclerosis. The aim of the present cross-sectional study was to investigate the influence of maternal and nutritional factors on blood cholesterol in primary school children.
Methods: One hundred and ninety-five population-based mother–child pairs (obese child–overweight mother pairs, n = 60; obese child–normal-weight mother pairs, n = 48; wasted child–overweight mother pairs, n = 37; normal-weight child–normal-weight mother pairs, n = 50), were enrolled in the study. Various anthropometric parameters were measured and serum lipids of subjects were further determined. Biological data and children's eating behavior were obtained from the mothers through interviews.
Results: Hypercholesterolemia was found in 64.6–65% of obese children, 24.3% of wasted children and in 56% of the normal-weight children; whereas the proportion of children in all groups who had normal blood cholesterol levels was in the lower range. Multivariate logistic regression indicated that mother's serum cholesterol (odds ratio [OR], 2.41; 95% confidence interval [CI]: 1.12–4.78), child obesity defined by weight-for-height Z-score > +2SD (OR, 2.56; 95%CI: 1.33–4.98), and child's energy intake ≥75th percentile (OR, 2.59; 95%CI: 1.01–6.66) were the significant factors associated with hypercholesterolemia in children.
Conclusion: Hypercholesterolemia in school children is associated with familial factor, bodyweight and nutrient intake. Elevated blood cholesterol was also found in some of the normal-weight and wasted children. Effective family-based intervention programs are urgently needed to modify risk factors predisposing to coronary heart disease. 相似文献
Methods: One hundred and ninety-five population-based mother–child pairs (obese child–overweight mother pairs, n = 60; obese child–normal-weight mother pairs, n = 48; wasted child–overweight mother pairs, n = 37; normal-weight child–normal-weight mother pairs, n = 50), were enrolled in the study. Various anthropometric parameters were measured and serum lipids of subjects were further determined. Biological data and children's eating behavior were obtained from the mothers through interviews.
Results: Hypercholesterolemia was found in 64.6–65% of obese children, 24.3% of wasted children and in 56% of the normal-weight children; whereas the proportion of children in all groups who had normal blood cholesterol levels was in the lower range. Multivariate logistic regression indicated that mother's serum cholesterol (odds ratio [OR], 2.41; 95% confidence interval [CI]: 1.12–4.78), child obesity defined by weight-for-height Z-score > +2SD (OR, 2.56; 95%CI: 1.33–4.98), and child's energy intake ≥75th percentile (OR, 2.59; 95%CI: 1.01–6.66) were the significant factors associated with hypercholesterolemia in children.
Conclusion: Hypercholesterolemia in school children is associated with familial factor, bodyweight and nutrient intake. Elevated blood cholesterol was also found in some of the normal-weight and wasted children. Effective family-based intervention programs are urgently needed to modify risk factors predisposing to coronary heart disease. 相似文献