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Biomedical subjects

T Nikkari

Publications and source records attributed to T Nikkari.

At least 37 records · Page 2Linked to original sources

Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer's disease.

The apoE phenotype of 83 patients with probable Alzheimer's disease (AD) and of 164 non-demented controls was determined by isoelectric focusing and Western blotting. The proportion of the epsilon 4 allele was 0.548 in AD and 0.202 in controls (P < 0.0001). The effect was seen in both early-onset and late-onset AD patients. The risk of AD in epsilon 4 homozygotes was 18-fold greater than in individuals without the epsilon 4 allele. ApoE concentrations were measured in serum and cerebrospinal fluid (CSF) from a subgroup of patients with AD (n = 72) and controls (n = 84) by a sandwich enzyme-linked immunosorbent assay. Although serum apoE concentrations were lower in individuals with the epsilon 4 allele than in those without the epsilon 4 allele, CSF apoE concentrations did not vary in different phenotype groups. However, CSF apoE levels were lower in AD patients than in controls. We conclude that the inheritance of the epsilon 4 allele of apoE is a risk factor for AD in the Finnish population.

Age of Onset↗

The fatty acid composition of banked human milk and infant formulas: the choices of milk for feeding preterm infants.

The fatty acid composition of 48 samples of banked human milk for preterm infants and four standard infants formulas available in Finland were analysed by capillary gas liquid chromatography. The banked milk was collected from mothers who had given birth 0-8 weeks previously. Saturated fatty acids accounted for approximately 50% of the fatty acids in both human milk and the formulas, while the relative content of monoenoic fatty acids tended to be higher in human milk than in the formulas. The relative content of 18:2n-6 was higher in the formulas (range 14.7%-23.2%) than in human milk (median 9.1%, range 6.3%-13.4%). Fat of banked human milk contained 0.9% and 0.7% polyunsaturated fatty acids with 20 and 22 carbon atoms (LCP), respectively, which is comparable to that of fresh mature human milk. In contrast, LCP could not be detected in any of the formulas. Conclusion. Banked human milk is a good source of LCP and offers a good alternative to LCP containing formulas.

Arachidonic Acid↗

Fatty acid composition of plasma and red blood cell phospholipids in preterm infants from 2 weeks to 6 months postpartum.

The purpose of this study was to follow the long-chain polyunsaturated fatty acid (LCP) status in initially human milk-fed preterm infants from 2 weeks to 6 months postpartum. Twenty-two infants aged 27-33 weeks of gestation at birth who had a birthweight of 710-2525 g were fed human milk for > or = 4 weeks. After discharge from the hospital, they were either human milk-fed or formula-fed according to their mothers' decision: 10 were fully breast-fed for 6 months and 12 were formula-fed after discharge at 1-2 months. The formula fat contained 20% 18:2n-6 and 3% 18:3n-3 but was devoid of long-chain polyunsaturated fatty acids (LCP). Blood samples were taken at 2 weeks, 3 months, and 6 months postpartum. Percentage fatty acid compositions in red blood cell (RBC) and plasma total phospholipids were analyzed by capillary gas liquid chromatography. In formula-fed infants, the change from human milk to formula resulted in a significant rise in plasma and RBC 18:2n-6 and 18:3n-3 and a decrease in plasma 20:4n-6. Interestingly, RBC 20:4n-6 remained constant in both groups, even after 4-5 months of formula feeding. In the formula-fed group, RBC 22:5n-6 showed an increasing trend. The largest changes were seen in 22:6n-3; in the formula-fed group, it decreased in both plasma and RBC, whereas in the human milk-fed group, it showed an increasing trend.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transfer of 15-lipoxygenase gene into rabbit iliac arteries results in the appearance of oxidation-specific lipid-protein adducts characteristic of oxidized low density lipoprotein.

Oxidized low density lipoprotein (LDL) possesses several atherogenic properties. The mechanisms by which LDL becomes oxidized in vivo remain unknown, but previous studies have suggested that 15-lipoxygenase may be one of the factors involved in the initiation of LDL oxidation in the arterial wall. 3 wk after a retrovirus-mediated 15-lipoxygenase gene transfer into iliac arteries of normocholesterolemic rabbits there was a threefold increase in 15-lipoxygenase activity but no signs of LDL oxidation. However, when animals were made moderately hypercholesterolemic by feeding a 0.13% cholesterol diet for 2-3 wk starting from day 4 after the gene transfer, oxidation-specific lipid-protein adducts characteristic of oxidized LDL were detected in 15-lipoxygenase-transduced arteries. Control experiments in which contralateral iliac arteries were transduced with beta-galactosidase-containing retroviruses showed only occasional signs of the presence of oxidation-specific adducts. The results support the hypothesis that products derived from the 15-lipoxygenase activity are involved in the induction of LDL oxidation within the arterial wall, provided that sufficient concentrations of lipoproteins are present in the artery.

Animals↗

Fatty acid composition of serum lipid fractions in relation to gender and quality of dietary fat.

UNLABELLED: The fatty acid compositions of serum lipid fractions are believed to reflect the quality of dietary fat, but only a few cross-sectional studies have examined these relationships in a representative free-living population. We related the composition of dietary fat obtained by 7-day food records from 84 free-living middle-aged married couples, on their habitual diets, to gas chromatographic analyses of the percentage compositions of fatty acids in three lipid fractions of fasting sera. Dietary polyunsaturated fat had Pearson's correlation coefficients of 0.63, 0.73 and 0.44 with n-6 polyunsaturated fatty acids in serum cholesteryl esters, triglycerides and phospholipids, respectively. Intake of fish showed correlations of 0.60, 0.36 and 0.52 with the percentage of eicosapentaenoate in the respective fractions. Dietary saturated fat had correlations of 0.57 and 0.54 with saturated fatty acids in serum cholesteryl esters and triglycerides, respectively. Dietary monounsaturated fat did not correlate positively with monounsaturated fatty acids in any serum lipid fraction. There were some small but significant gender differences in the serum fatty acid compositions. CONCLUSIONS: of the three serum lipid fractions, triglycerides appear to be the best reflectors of dietary polyunsaturated and saturated fat, but the intake of monounsaturated fat is poorly reflected in all serum lipid fractions. Intake of fish is mirrored in all serum lipid fractions, best in cholesteryl esters and phospholipids.

Adult↗

Association between serum lipids and apolipoprotein E phenotype is influenced by diet in a population-based sample of free-living children and young adults: the Cardiovascular Risk in Young Finns Study.

Apolipoprotein E (apoE) is a genetic determinant of coronary heart disease and lipid levels in several populations. We studied whether the association of apoE alleles with serum lipids varies with diet in a population of free-living young Finns. One thousand twelve subjects, aged 9-24 years, were studied as a part of the Cardiovascular Risk in Young Finns Study in 1986. Serum lipid concentrations and apoE phenotypes were determined, and the composition of the diet was assessed by the 48-h recall method. The subjects were divided into three groups according to the intake of dietary saturated fatty acids (SAFA, g/1000 kcal) and cholesterol (mg/1000 kcal). Group one (high SAFA-cholesterol group) was formed from subjects belonging to the highest tertiles of both cholesterol and SAFA intakes (n = 175); group two (middle SAFA-cholesterol group) consisted of subjects belonging to the middle respective tertiles (n = 119); and group three (low SAFA-cholesterol group) consisted of subjects belonging to the lowest respective tertiles (n = 192). The statistical significance of the association of serum total cholesterol and low density lipoprotein (LDL) concentration with apoE phenotype increased from the low SAFA-cholesterol group (P = 0.024 for total cholesterol and P = 0.015 for LDL-cholesterol, respectively) to the high SAFA-cholesterol group (P = 0.0022 and P = 0.00073, respectively). The middle SAFA-cholesterol group fell between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Monitoring of lipoprotein oxidation by gas chromatographic analysis of hydroxy fatty acids.

We describe a method developed for the quantitative analysis of hydroxy fatty acids derived from fatty acid monohydroperoxides formed during lipoprotein oxidation. The procedure starts with catalytic hydrogenation of the lipid extract, whereby hydroperoxyl groups are converted to hydroxyl groups and double bonds are eliminated, and the risk for lipid oxidation during the rest of the procedure is eliminated. The fatty acids are converted to methyl esters, which are fractionated by gas chromatography on a nonpolar column. The major differences to existing methods are that a mass spectrometer is not required and that the specificity thus lost is replaced by gas chromatography before and after acetylation of the hydroxyl groups. This changes the retention times of the hydroxyacids with respect to the unsubstituted fatty acids moving them to positions usually occupied by trace components only. The method allows quantification of monohydroxy fatty acids derived from 18-, 20- and 22-carbon polyunsaturated fatty acids. Positional isomers are separated from each other to some extent. The method has been mainly used for analysis of hydroperoxides in human low density lipoprotein preparations and for following lipoprotein oxidation in vitro.

Acetylation↗

Nitric oxide donor GEA 3162 inhibits endothelial cell-mediated oxidation of low density lipoprotein.

The effect of a nitric oxide (NO) donor GEA 3162 on the endothelial cell (EC)-mediated oxidation of low density lipoprotein (LDL) was studied. In comparison to LDL incubated with EC without GEA 3162, the presence of GEA 3162 inhibited LDL oxidation by EC, as indicated by the following findings. (a) The degradation rate of LDL in macrophages was reduced to control levels. (b) The electrophoretic mobility of LDL decreased in a dose-dependent manner. (c) The concentrations of thiobarbituric acid-reactive substances and hydroperoxide-derived hydroxy fatty acids were lower. (d) The breakdown of apolipoprotein B was reduced. The results indicate that GEA 3162 prevents EC-mediated oxidation of LDL.

Animals↗

Changes in the fatty acid composition of preterm and term human milk from 1 week to 6 months of lactation.

Using capillary gas chromatography, we analyzed the fatty acid composition of human milk from 23 women who had delivered prematurely and 16 women who had delivered at term. Milk samples were obtained at 1, 2, 4, 12, and 26 weeks after delivery. The relative amounts of saturated and monounsaturated fatty acids in preterm and term milk remained stable throughout the 6 months of lactation. The proportions of linoleate (18:2n-6) and alpha-linolenate (18:3n-3) were similar in preterm and term milk and showed an increasing trend from transitional (8.7-9.9% and 0.9-1.1% of total fatty acids, respectively) to mature milk (9.9-11.8% and 1.2-1.5%, respectively). The proportions of the major long-chain polyunsaturated fatty acids (LCP), 20:3n-6, 20:4n-6, 22:5n-3 and 22:6n-3, were highest at 1 week and decreased thereafter in both types of milk. In term milk, the proportion of LCP continued to decrease from 1 month to 6 months, whereas in preterm milk it was fairly constant. Consequently, at 6 months of lactation, the relative content of arachidonate (20:4n-6) was 1.5 times (p < 0.05) and that of docosahexaenoate (22:6n-3) was two times higher (p < 0.01) in preterm than in term milk. We conclude that in long-term lactation, preterm human milk provides a significantly higher relative supply of LCP than term human milk. This higher LCP content may be of special benefit to the development of a preterm infant.

Analysis of Variance↗

Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and scavenger receptor in human atherosclerotic lesions.

Macrophage- and smooth muscle cell (SMC)-derived foam cells are typical constituents of human atherosclerotic lesions. At least three receptor systems have been characterized that could be involved in the development of foam cells: alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP), scavenger receptor, and LDL receptor. We studied the expression of these receptors in human atherosclerotic lesions with in situ hybridization and immunocytochemistry. An abundant expression of alpha 2MR/LRP mRNA and protein was found in SMC and macrophages in both early and advanced lesions in human aortas. alpha 2MR/LRP was also present in SMC in normal aortas. Scavenger receptor mRNA and protein were expressed in lesion macrophages but no expression was found in lesion SMC. LDL receptor was absent from the lesion area but was expressed in some aortas in medial SMC located near the adventitial border. The results demonstrate that (a) alpha 2MR/LRP is, so far, the only lipoprotein receptor expressed in lesions SMC in vivo; (b) scavenger receptors are expressed only in lesion macrophages; and (c) both receptors may play important roles in the development of human atherosclerotic lesions.

Adult↗

Apolipoprotein E phenotypes and serum lipids in newborns and 3-year-old children: the Cardiovascular Risk in Young Finns Study.

BACKGROUND: Apolipoprotein E (apoE) phenotype is a genetic determinant of plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations, that are classical coronary heart disease risk factors. ApoE appears in three major isoforms E2, E3, and E4, coded by corresponding alleles epsilon 2, epsilon 3, and epsilon 4. These give rise to six different phenotypes. OBJECTIVE: To study the associations of apoE phenotype with cord serum lipids (during minimal enteral nutrition), and with serum lipids of 3-year-old children. SUBJECTS AND METHODS: We determined serum lipid levels and apoE phenotypes in 206 newborns and 259 3-year-old children in connection with a larger follow-up study of atherosclerosis precursors in children and young adults. ApoE phenotyping was done directly from plasma by isoelectric focusing followed by immunoblotting. RESULTS: The effect of apoE phenotype on serum total and LDL cholesterol was significantly different in newborns and 3-year-old children (two-way ANOVA, interaction between apoE phenotype and age group: P < .001 for both). In 3-year-old children, the concentrations of serum total cholesterol and LDL cholesterol increased with apoE phenotype in the order of E3/2, E3/3, E4/3, and E4/4, in both males and females (P < .0001). On the contrary, in neonates total cholesterol and LDL cholesterol concentrations were low and did not differ significantly between apoE phenotypes (P > .05) either in males or in females. The mean serum levels of triglycerides and high density lipoprotein cholesterol did not differ between apoE phenotypes either in 3-year-old children or newborns. CONCLUSIONS: The results show that the differences in serum total and LDL cholesterol levels between apoE phenotypes are formed after birth by the influence of environmental factors and suggest that both genetic and external factors influence the levels of serum cholesterol concentrations during the first years of life.

Adolescent↗

Characteristics of low-density lipoprotein subfractions from patients with coronary artery disease.

BACKGROUND: The low-density lipoprotein (LDL) of patients with coronary artery disease (CAD) has been reported to enhance cholesterol ester accumulation in aortic cells. The LDL of patients with CAD also has a higher mean density than the LDL of healthy subjects, indicating a different subspecies distribution. Because these density differences may be associated with altered metabolism and atherogenicity of LDL, we studied the properties and effects of isolated LDL subfractions on cell lipid metabolism and cholesterol accumulation. METHODS: Plasma pools of patients with angiographically proven CAD (A) and healthy controls (C) were used to isolate and fractionate LDL into five subfractions (1 to 5, from the lowest to the highest density) by gradient ultracentrifugation. Each of the LDL subfractions was analyzed for particle diameter, chemical composition, sialic acid content, and their effect on lipid content and cholesterol esterification in arterial cell and macrophage cultures, respectively. RESULTS: The chemical compositions of the respective subfractions revealed no differences between patients and controls, except that the sialic acid content was reduced in dense LDL subfractions, especially in the samples from patients with CAD (fractions A3, A4, A5, and C5). LDL subfractions with reduced sialic acid content also enhanced the incorporation of [14C]-oleate into cholesterol esters in mouse peritoneal macrophage cultures (fractions A4, A5, and C5) and increased the cholesterol ester content in primary cultures of human aortic intimal cells (fractions A3, A4, A5, and C5). CONCLUSIONS: The results suggest that the dense LDL subfractions of patients with CAD are atherogenic by promoting intracellular cholesterol ester accumulation. The results also suggest that the atherogenicity is associated with reduced sialic acid content of the LDL subspecies.

Adult↗

Tracking of serum fatty acid composition: a 6-year follow-up study in Finnish youths.

The composition of fatty acids in serum cholesteryl esters was analyzed with gas chromatography in 759 Finnish boys and girls aged 3-18 years in 1980 and again in the same subjects in 1983 and in 1986. The mean percentage of linoleate (18:2 n-6) increased from 50.85% in 1980 to 52.60% in 1986, while there was a decrease in myristate (14:0), palmitate (16:0), and eicosapentaenoate (20:5 n-3). The percentage of oleate (18:1) did not change. The stability (tracking) of cholesteryl ester fatty acid composition was examined by calculating linear correlation coefficients among the percentages of each fatty acid at the three study points. For linoleate, 3- and 6-year tracking correlations were 0.59-0.61 and 0.50, respectively; they were of about the same magnitude for arachidonate (20:4 n-6) and lower for the other fatty acids. Results indicate that the serum cholesteryl ester fatty acid composition has somewhat lower tracking than the total cholesterol concentration. The changes in the mean fatty acid composition of the study population obviously reflect a shift from saturated to unsaturated dietary fats.

Adolescent↗

Serum ceruloplasmin and the risk of cancer in Finland.

The relationship between serum ceruloplasmin level and cancer incidence was investigated in a case-control study nested within a longitudinal study of 39,268 Finns participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey carried out in 1968-1972. During a median follow-up of 8 years, 766 cancer cases were identified. Ceruloplasmin levels were determined from stored serum samples collected at the baseline from these cancer cases and from two matched controls per case. The overall incidence of cancer was positively associated with serum ceruloplasmin level. The association was strongest for lung cancer and other cancers related to smoking and, consequently, in males. The smoking-adjusted relative risk of lung cancer among men was 4.3 (95% confidence interval (CI) = 1.8-10.6) in the highest quintile of serum ceruloplasmin as compared with that in the lowest quintile. The corresponding relative risks for cancers related to smoking combined, and for cancers not related to smoking were 3.9 (CI = 1.9-8.4) and 0.9 (CI = 0.6-1.5), respectively. The elevated risk of lung cancer at high concentrations of serum ceruloplasmin persisted after further adjustment for several potential confounding factors such as serum levels of vitamins A and E and selenium. The risk was stronger during the first 6 years of follow-up than later, and strongest during the first 2 years. The most likely explanation of the present results thus is that high serum ceruloplasmin levels in lung cancer are mainly due to occult cancer.

Adolescent↗

Correlation of serum fatty acid composition with dietary intake data in children and young adults.

The percentage compositions of fatty acids in serum cholesteryl esters and phospholipids were analysed with gas chromatography in 759 nine- to 24-year-old Finns. The correlations of serum fatty acids with dietary fat intake data were calculated from a 48-h recall survey. The dietary P/S ratio had correlations of r = 0.50 and r = 0.40 with linoleate (18:2) in serum cholesteryl esters and phospholipids, respectively. The intake of fish and fish products correlated positively with the percentages of eicosapentaenoate (20:5 n-3) and docosahexaenoate (22:6 n-3) in both cholesteryl esters and phospholipids. Dietary intake of saturated fat correlated positively with the percentages of all saturated fatty acids in cholesteryl esters and with myristate (14:0) in phospholipids. The intake of monounsaturated fats did not correlate positively with serum monoenes. In conclusion, the dietary P/S ratio is well reflected in the fatty acid composition of serum cholesteryl esters and phospholipids, the intake of saturated fats less well, and the intake of monounsaturated fats not at all.

Adolescent↗