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Yitao Luo Chengqiang Zhang Li Ma Yuxiao Zhang Zhengyuan Liu Li Chen Rui Wang Yujing Luan Yulan Rao 《Journal of lipid research》2022,63(6):100228
7-dehydrocholesterol (7-DHC) and cholesterol (CHOL) are biomarkers of Smith-Lemli-Opitz Syndrome (SLOS), a congenital autosomal recessive disorder characterized by elevated 7-DHC level in patients. Hair samples have been shown to have great diagnostic and research value, which has long been neglected in the SLOS field. In this study, we sought to investigate the feasibility of using hair for SLOS diagnosis. In the presence of antioxidants (2,6-ditert-butyl-4-methylphenol and triphenylphosphine), hair samples were completely pulverized and extracted by micro-pulverized extraction in alkaline solution or in n-hexane. After microwave-assisted derivatization with N,O-Bis(trimethylsilyl)trifluoroacetamide, the analytes were measured by GC-MS. We found that the limits of determination for 7-DHC and CHOL were 10 ng/mg and 8 ng/mg, respectively. In addition, good linearity was obtained in the range of 50–4000 ng/mg and 30–6000 ng/mg for 7-DHC and CHOL, respectively, which fully meets the requirement for SLOS diagnosis and related research. Finally, by applying the proposed method to real hair samples collected from 14 healthy infants and two suspected SLOS patients, we confirmed the feasibility of hair analysis as a diagnostic tool for SLOS. In conclusion, we present an optimized and validated analytical method for the simultaneous determination of two SLOS biomarkers using human hair. 相似文献
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Chiara Pavanello Alice Ossoli Arianna Strazzella Patrizia Risè Fabrizio Veglia Marie Lhomme Paolo Parini Laura Calabresi 《Journal of lipid research》2022,63(7):100232
Mutations in the LCAT gene cause familial LCAT deficiency (Online Mendelian Inheritance in Man ID: #245900), a very rare metabolic disorder. LCAT is the only enzyme able to esterify cholesterol in plasma, whereas sterol O-acyltransferases 1 and 2 are the enzymes esterifying cellular cholesterol in cells. Despite the complete lack of LCAT activity, patients with familial LCAT deficiency exhibit circulating cholesteryl esters (CEs) in apoB-containing lipoproteins. To analyze the origin of these CEs, we investigated 24 carriers of LCAT deficiency in this observational study. We found that CE plasma levels were significantly reduced and highly variable among carriers of two mutant LCAT alleles (22.5 [4.0–37.8] mg/dl) and slightly reduced in heterozygotes (218 [153–234] mg/dl). FA distribution in CE (CEFA) was evaluated in whole plasma and VLDL in a subgroup of the enrolled subjects. We found enrichment of C16:0, C18:0, and C18:1 species and a depletion in C18:2 and C20:4 species in the plasma of carriers of two mutant LCAT alleles. No changes were observed in heterozygotes. Furthermore, plasma triglyceride-FA distribution was remarkably similar between carriers of LCAT deficiency and controls. CEFA distribution in VLDL essentially recapitulated that of plasma, being mainly enriched in C16:0 and C18:1, while depleted in C18:2 and C20:4. Finally, after fat loading, chylomicrons of carriers of two mutant LCAT alleles showed CEs containing mainly saturated FAs. This study of CEFA composition in a large cohort of carriers of LCAT deficiency shows that in the absence of LCAT-derived CEs, CEs present in apoB-containing lipoproteins are derived from hepatic and intestinal sterol O-acyltransferase 2. 相似文献
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Genetic analysis of murine strains C57BL/6J and C3H/HeJ to confirm the map position ofAth-1, a gene determining atherosclerosis susceptibility 总被引:4,自引:0,他引:4
Beverly Paigen Deborah Albee Patricia A. Holmes Diane Mitchell 《Biochemical genetics》1987,25(7-8):501-511
Previous results suggested that strains C57BL/6J and C3H/HeJ differed in a single gene for atherosclerosis susceptibility, calledAth-1. Based on data from recombinant inbred strainsAth-1 was tentatively assigned to chromosome 1 linked toAlp-2. In this report, a cross between C57BL/6 and C3H/HeJ was carried out in order to test whether the tentative map position was correct. Parental strains and F1 and F2 progeny were examined. Susceptible alleles ofAth-1, found in C57BL/6, are associated with relatively low levels of high-density lipoprotein (HDL)-cholesterol in animals fed an atherogenic diet; resistant alleles ofAth-1 are associated with relatively high levels of HDL-cholesterol. F1 progeny have HDL levels that are intermediate between these of the two parental strains. Among the F2 progeny,Alp-2 andAth-1 cosegregated, providing confirmatory evidence thatAth-1 is linked toAlp-2 on chromosome 1. Three mice recombinant forAlp-2 andAth-1 were found among the 60 chromosomes tested, giving an estimated map distance between these two genes of 5.0±2.8 (SE) cM. The phenotypic characteristics ofAth-1 resemble a genetic trait in humans, hyperalphalipoproteinemia, which is characterized by elevated levels of HDL-cholesterol, reduced risk of heart disease, and increased longevity.This work was supported by Grant HL-32087 from the Heart, Lung, and Blood Institute, National Institutes of Health, Grant 1858 from the Council for Tobacco Research, Grant 86-1387 from the American Heart Association with funds contributed in part by the Alameda, Orange, and Santa Barbara County Chapters, and Grants 85-N132A and 85-N136A from the California Affiliate of the American Heart Association. 相似文献
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Summary Light-microscopic immunohistochemistry was used to localize insulin- and somatostatin-immunoreactive cells within developing endocrine pancreatic tissue of metamorphosing lampreys, Petromyzon marinus. The extrahepatic common bile duct and a portion of the intrahepatic bile duct develop into the caudal portion of the endocrine pancreas. The cranial pancreas is composed of follicles originating in the intestinal and diverticular epithelia, thus following the method of formation of pancreatic follicles from gut epithelium in larvae. In both the cranial and caudal portions, and in an intermediate cord of isolated follicles which connect these two major masses, insulin-immunoreactive cells appear first and are followed by cells showing somatostatin-immunoreactivity. In all stages of metamorphosis individual endocrine cells demonstrate immunoreactivity to a single hormone. Biliary atresia in lamprey may have some adaptive significance in providing cells that produce a caudal endocrine pancreas.Supported by NSERC of Canada grant No. A5945 and MRC of Canada grant No. MA8629 to JHY 相似文献
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Cholesterol binding reserve of hyperlipemic rat serum lipoproteins in chronic ethanol administration
Chronic administration of ethanol in rats caused the reduction of serum cholesterol binding reserve. The very low density
and high density lipoproteins, main serum cholesterol binding reserves, were slightly increased with corresponding increases
in their lipid and protein components during initial stage of alcohol consumption. However, these capacities get deminished
during reversal of hyperlipemia induced by prolonged action of ethanol. This situation may be an early indicator for the initiation
of hepatic damage and a variety of secondary effects of ethanol. 相似文献