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T Nikkari

Publications and source records attributed to T Nikkari.

At least 55 records · Page 3Linked to original sources
PubMed1992

Multiple-modified desialylated low density lipoproteins that cause intracellular lipid accumulation. Isolation, fractionation and characterization.

BACKGROUND: The basic differences between sialylated (sialic acid rich) and desialylated (sialic acid poor) human low density lipoproteins (LDL) are not fully defined. It is not known whether there are any differences in the LDL composition of coronary atherosclerosis patients and healthy individuals. EXPERIMENTAL DESIGN: Sialylated (45 to 94% of total LDL) and desialylated (6 to 55%) LDL were separated by affinity chromatography on Ricinus communis agglutinin-agarose, and their chemical composition and physical properties were examined. RESULTS: Sialic acid contents in sialylated LDL fractions of healthy subjects and patients were the same and 1.5 to 3-fold higher than in desialylated LDL. Desialylated LDL had smaller sizes and greater electrophoretic mobility than sialylated ones. Desialylated, but not sialylated LDL, induced 1.5- to 4-fold accumulation of neutral lipids in human aortic smooth muscle cells and human blood monocytes. Subfractions of desialylated LDL containing lower amount of sialic acid revealed higher ability to accumulate lipids in cultured cells. Desialylated LDL contained lower amounts of cholesteryl esters, free cholesterol and triglycerides as compared with sialylated LDL. On the other hand, concentration of di-, monoglycerides and free fatty acids in desialylated LDL was 2 to 3-fold higher than in sialylated lipoproteins. Desialylated LDL fraction was characterized by lower levels of phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, but higher content of lysophosphatidylcholine. Freshly isolated sialylated and desialylated LDL contained equal amounts of thiobarbituric acid reactive substances, but oxidation of desialylated LDL was more pronounced in presence of Cu(2+)-ions. Desialylated LDL had higher level of oxysterols and lower amounts of vitamin A and E. Content of free amino groups of lysine in desialylated LDL of patients was 2-fold lower than in sialylated LDL. This difference was partially due to masking of amino groups caused by conformational change in the tertiary structure of apolipoprotein, partially to chemical modification of amino groups. When subfractionated by density gradient ultracentrifugation, desialylated LDL was represented by higher density particles than sialylated LDL. Sialic acid content in desialylated LDL subfractions decreased with rise of lipoprotein density. Higher density desialylated LDL and in less extent sialylated LDL contained smaller amounts of free and esterified cholesterol and phospholipids. Only the densest subfractions of desialylated LDL from healthy subjects caused intracellular lipid accumulation. Ability of patients' desialylated LDL to accumulate cholesterol in cells increased with particle density. CONCLUSIONS: Extensive biochemical and biophysical analysis performed in this study shows that desialylated LDL differ from these sialylated LDL in many respects. The LDL of coronary atherosclerosis patients differ from those in healthy individuals in several parameters.

Adult↗
PubMed1991

Serum micronutrients and risk of cancers of low incidence in Finland.

The associations between serum alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium levels and the subsequent occurrence of different cancers of low incidence were investigated in a nested case-control study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. During follow-up from the baseline in 1968-1972 to the end of 1977, a total of 115 cancers of the lip, oral cavity, pharynx, larynx, esophagus, liver, gallbladder, kidney, urinary bladder, brain, and skin were reported to the nationwide Finnish Cancer Registry. Alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium concentrations were determined from stored serum samples collected from these cancer cases and matched controls at baseline. Several sites indicated an elevated risk of cancer at low levels of the serum variables, although only a few of these associations were statistically significant. Only melanoma patients had significantly lower serum alpha-tocopherol and beta-carotene levels than corresponding controls. Since the numbers of cancer cases were small, no firm conclusions can be drawn from these results until they have been confirmed in studies based on larger cohorts or on pooled data from several small samples.

Adult↗
PubMed1991

Vitamin E and cancer prevention.

Some animal experiments and human studies suggest that vitamin E may protect against cancer. Serum alpha-tocopherol concentration was studied for its prediction of cancer in a cohort of 36,265 adults in Finland. During a mean follow-up of 8 y, cancer was diagnosed in 766 persons. The levels of serum alpha-tocopherol were determined from stored serum samples (at -20 degrees C) taken from these cancer patients and from 1419 matched control subjects. Individuals with a low level of alpha-tocopherol had about a 1.5-fold risk of cancer compared with those with a higher level. The strength of the association between serum alpha-tocopherol level and cancer risk varied for different cancer sites and was strongest for some gastrointestinal cancers and for the combined group of cancers unrelated to smoking. The association was strongest among nonsmoking men and among women with low levels of serum selenium. The findings agree with the hypothesis that dietary vitamin E in some circumstances protects against cancer.

Animals↗
PubMed1991

Regional differences in apolipoprotein E polymorphism in Finland.

Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease risk. We determined apoE phenotypes and plasma lipid levels in 1564 subjects aged three to 18 years, living in five geographical areas of Finland in 1980. ApoE phenotyping was performed directly from plasma by isoelectric focusing and immunoblotting. The serum concentrations of total cholesterol, low density lipoprotein cholesterol and apolipoprotein B varied with apoE phenotype, and there were increases in all three variables (all P less than 0.001) of the order of E2/2 less than E3/2 less than E4/2 less than E3/3 less than E4/3 less than E4/4. These differences were present in all five areas. The mean levels of high density lipoprotein cholesterol, apolipoprotein A-I and triglyceride in the subjects did not differ between the apoE phenotypes or between their areas of residence. The apoE phenotype dependency of serum total and LDL cholesterol remained significant in all five areas during the six year follow-up from 1980 to 1986, when the mean level of serum total cholesterol fell by 5.8% in east (P less than 0.05) and by 4.4% in west Finland (P less than 0.05); the fall was steeper (P less than 0.01) in the east than the west. In all subjects, particularly those in west Finland, the size of the falls of serum total and LDL cholesterol concentrations depended on the apoE phenotype in the order of E3/2 less than E3/3 less than E4/3, but this effect was not seen in the east.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Oxidized low-density lipoprotein is chemotactic for arterial smooth muscle cells in culture.

The effects of human native and Cu2(+)-oxidized low-density lipoprotein (LDL) were tested on the migration of cultured bovine aortic smooth muscle cells (SMCs) in blind-well chambers. LDL oxidation was controlled by measuring the formation of conjugated dienes and lipid hydroperoxides, and by agarose gel electrophoresis. Oxidized LDL stimulated SMC migration, and the effect was dose-dependent up to 200 microgram/ml. The stimulation was chemotactic in nature. Native LDL was without significant activity. The results suggest that oxidized LDL may contribute to the migration of medial SMCs into the intima during atherogenesis.

Animals↗
PubMed1990

Biochemical composition of human internal mammary artery and saphenous vein.

The long-term patency of the internal mammary artery graft is better than that of the saphenous vein graft in coronary bypass surgery because of a low incidence of atherosclerosis in the internal mammary artery. In search of a possible biochemical explanation of the low degree of atherosclerosis in the internal mammary artery we compared the chemical compositions of human internal mammary artery and saphenous vein obtained from 37 patients undergoing coronary bypass surgery. The levels of esterified cholesterol and free cholesterol were higher in the internal mammary artery than in the saphenous vein (p less than 0.001 and p less than 0.01, respectively), but lower than the levels reported in previous studies for coronary arteries. The amount of collagen was higher in the saphenous vein (p less than 0.001). Heparan sulfate was the major glycosaminoglycan fraction in the internal mammary artery, probably reflecting the higher cellularity and thicker media in the arterial rather than in the venous tissue. The level of dermatan sulfate was higher (p less than 0.001) in the saphenous vein than in the internal mammary artery. This difference is in a direction that could favor atherogenesis in the saphenous vein graft.

Cholesterol↗
PubMed1990

Lipoprotein metabolism of human and rabbit arterial cells in primary culture.

The early atherosclerotic lesion, the fatty streak, consists of cholesteryl ester-containing foam cells originating mainly from monocyte-macrophages and to a lesser extent from smooth muscle cells. In this study, we describe lipoprotein uptake and cholesterol accumulation into enzyme-dispersed primary cell cultures from cholesterol-fed rabbit aortas and human aortic fatty streaks. Uptake of fluorescently labelled acetylated low density lipoprotein (acetyl-LDL) was demonstrable in macrophage-derived foam cells and in many smooth muscle cells in early primary cultures. The uptake of acetyl-LDL led to significantly enhanced cellular esterification of cholesterol. Fluorescent beta-migrating very low density lipoprotein (beta-VLDL) was internalized by a considerable number of lesion macrophages and also by smooth muscle cells. Also beta-VLDL uptake stimulated cholesterol esterification, although the effect was milder than that of acetyl-LDL. These findings lend support to the assumption that, during atherogenesis, arterial macrophages are capable of accumulating cholesteryl esters by receptor-mediated uptake of beta-VLDL and modified LDL. The internalization of modified LDL by smooth muscle cells represents a mechanism potentially contributing to the formation of foam cells in the atherosclerotic lesion.

Animals↗
PubMed1990

Intimal thickening in the coronary arteries of infants and children as an indicator of risk factors for coronary heart disease.

Narrowings of the coronary arteries were measured in 94 infants aged less than 1 year who died in hospital and 102 1- to 16-year-old children who died accidentally. The arteries were transformed mathematically to circles. The degree of narrowing caused by intimal thickening was determined as the ratio of intimal area to the original luminal area. This ratio was further transformed to percentage. The degree of narrowing varied between 0 and 58% (mean 20%). The mean degree of narrowing in the left coronary artery during the first year of life was 17% and, between 12 and 15 years, 34%. Narrowing was greater in males (P = 0.02), when all the 333 coronary samples were included in the analysis. The birthplaces of the subjects' grandparents were traced from population registers and it was found that narrowing in the left coronary artery of infants was greater in those descended from grandparents from eastern Finland, an area of high mortality from coronary heart disease (CHD). Intimal thickening in infants and children seems to be a morphological manifestation of hereditary predisposition to CHD.

Adolescent↗
PubMed1990

Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey.

From 1968 to 1977, the association between the level of vitamin A in serum and the subsequent incidence of cancer was examined in a longitudinal study of 36,265 persons initially aged 15-99 years in 25 population groups in Finland. During a mean follow-up of 8 years, 766 cancers were diagnosed. Serum retinol, retinol-binding protein, and beta-carotene levels were measured from frozen serum samples (stored at -20 degrees C) drawn from these persons before the start of follow-up and from 1,419 controls matched for sex, age, and place of residence who did not develop cancer during follow-up. The mean level of serum retinol among the cancer cases was 645 micrograms/liter for men and 587 micrograms/liter for women. The corresponding levels in the controls were 3.3% and 2.8% higher. There was an inverse gradient between serum retinol level and the occurrence of cancer among men. This association was, however, mainly concentrated in the first 2 years of follow-up. The mean level of serum beta-carotene was 72.3 micrograms/liter among male cases and 119.5 micrograms/liter among female cases. The corresponding levels of the controls were 14.0% and 5.5% higher. The differences were particularly clear with regard to lung cancer. These findings suggest that the association between retinol and cancer may be due to preclinical cancer and that there may be an association between beta-carotene and cancer.

Adolescent↗
PubMed1990

Metabolism of progesterone and testosterone by Bacillus cereus strain Socransky 67 and Streptococcus mutans strain Ingbritt.

Bacillus cereus strain Socransky 67 and Streptococcus mutans strain Ingbritt were grown overnight in complex medium and then in fresh medium flasks for 5 h. The bacterial cells in the medium were centrifuged and resuspended; 4-14C-progesterone or 4-14C-testosterone was added, and the samples were incubated for 2 h at 37 degrees C in a shaking water bath. The metabolites were analyzed with column and thin layer chromatography and radioautography and quantified by liquid scintillation counting. On the basis of the metabolites found it was concluded that B. cereus strain Socransky 67 contains 5 alpha-steroid hydrogenase, and 3 beta-, 17 beta- and 20 alpha-hydroxysteroid dehydrogenases and probably also steroid hydroxylases, and that S. mutans strain Ingbritt contains 5 alpha- and 5 beta-steroid hydrogenases, and 3 alpha-, 17 beta- and 20 alpha-hydroxysteroid dehydrogenases. The metabolic activity of B. cereus is several times higher than that of S. mutans. We suggest that the greater ability of B. cereus to metabolize progesterone and testosterone is probably due to its growth milieu in the gingival sulcus, where it is nearer to the gingival tissue.

Bacillus cereus↗
PubMed1990

Histological and histochemical studies on local coronary wall thickenings (cushions) in Finnish children who died violently. Cardiovascular risk in young Finns?

Coronary arteries of 93 clinically healthy Finnish children of both sexes were collected from successive, medicolegal autopsies of victims of violent death. In the histological and histochemical study, local, cushion-type thickenings of the coronary walls were demonstrable in 47, i.e. 50 per cent, of the children, the occurrence increasing with age. The most prominent change was the splitting of the internal elastic membrane and the accumulation of smooth muscle cells, forming a new, musculo-elastic layer. Glycosaminoglycans appeared in the luminal parts of the thickenings. There was an average decrease in the succinate dehydrogenase reaction in the cushion area, implying a degenerative process. The increase in the reaction of "injury markers", acid phosphatase and esterase based on the increase of cells rich in these enzymes, indicated pathologic process. It was concluded that change of this kind, demonstrable early in childhood, may dispose coronary arteries to atherosclerosis.

Acid Phosphatase↗
PubMed1990

Lipoprotein degradation and cholesterol esterification in primary cell cultures of rabbit atherosclerotic lesions.

Lipoprotein metabolism and cholesterol accumulation in atherosclerotic lesions was studied using enzymatically isolated primary cell cultures from aortas of rabbits made atherosclerotic by cholesterol feeding. The cultures consisted of macrophages and smooth muscle cells, thus resembling, in composition, fatty streak lesions. The mean (+/- SD) cholesteryl ester content of the dispersed cells was 1059 +/- 445 micrograms/mg cell protein, but it declined steeply during 1 week in primary culture. The uptake of low-density lipoprotein (LDL), beta-migrating very low-density lipoprotein (beta-VLDL), and acetylated LDL (acetyl-LDL), labeled with 125I or with the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine (DiI), was studied in 2-day-old primary cultures. DiI-acetyl-LDL was avidly taken up by the macrophages and, to a lesser extent, by some smooth muscle cells. The uptake of DiI-beta-VLDL by the macrophages was weaker and less homogeneous than that of DiI-acetyl-LDL. The degradation rates of 125I-labeled beta-VLDL, LDL and acetyl-LDL were 135 +/- 54, 195 +/- 20, and 697 +/- 14 ng/mg cell protein/8 hours, respectively. Incubation with unlabeled acetyl-LDL enhanced the incorporation of [3H]oleate into cholesteryl esters and increased the cellular cholesteryl ester content. These results suggest that arterial macrophages and, to some extent, smooth muscle cells from cholesterol-fed rabbits actively metabolize acetyl-LDL and are thus capable of accumulating cholesteryl esters by uptake of modified forms of LDL.

Animals↗
PubMed1990

Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study.

Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was performed directly from plasma by isoelectric focusing and immunoblotting. The apoE allele frequencies in the population sample were epsilon 2 = 0.039, epsilon 3 = 0.767, and epsilon 4 = 0.194. There were no differences in the apoE phenotype distribution between East and West Finland or between sexes. The concentrations of serum total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B increased with apoE phenotype in the order of E2/2, E3/2, E4/2, E3/3, E4/3, and E4/4. This increase was already seen in 3-year-old children; it was observed in both sexes, but was clearer in males than in females. The mean levels of high density lipoprotein (HDL) cholesterol, apolipoprotein A-I, triglyceride, Lp[a] lipoprotein, and the activity of lecithin:cholesterol acyltransferase did not differ between the apoE phenotypes. The observed differences in serum cholesterol remained fairly stable during the 6-year follow-up from 1980 to 1986, while the mean serum cholesterol concentration in the whole study population decreased by 6.3%. This study confirms the reported higher frequency of the epsilon 4 allele in Finns as compared to most other populations; this may contribute to the high rates of CHD in Finland as compared to most other populations. The results do not, however, explain the higher rate of CHD in East Finland in comparison to the western part of the country.

Adolescent↗
PubMed1989

Receptor-mediated binding and degradation of subfractions of human plasma low-density lipoprotein by cultured fibroblasts.

The receptor-mediated metabolism of human plasma low-density lipoprotein (LDL) subfractions was studied. LDL was isolated from healthy donors and further fractionated by density gradient ultracentrifugation into three subfractions: (I) d = 1.031-1.037, (II) d = 1.037-1.041 and (III) d = 1.041-1.047 g/ml, comprising 24 +/- 7%, 46 +/- 8% and 30 +/- 9% of the total LDL protein, respectively. As assessed by electron microscopy and gradient gel electrophoresis, the LDL particle size decreased and the relative protein content increased from fraction I towards fraction III. Fraction II had the highest (Kd 2.6 micrograms/ml) and fraction I the lowest (Kd 5.8 micrograms/ml) binding affinity to LDL receptors of human fibroblasts at 4 degrees C. The rate of receptor-mediated degradation of fraction II was also higher than that of the other two fractions at 37 degrees C. These results suggest that LDL subfractions have different rates of receptor-mediated catabolism depending on particle size or composition, and therefore their metabolic fate and atherogenic properties may also differ.

Cells, Cultured↗
PubMed1989

Down's syndrome and atherosclerosis.

Necropsy findings in patients with Down's syndrome have suggested an absence of atherosclerosis throughout the cardiovascular system, but there are also contradictory results. We compared the left coronary arteries of 15 institutionalised Down's syndrome patients (5 males, 10 females, mean age 51 years) with those of 6 other institutionalised mentally retarded patients (4 males, 2 females, mean age 49) and 20 normal, free-living subjects (10 males, 10 females, mean age 48) by macroscopic inspection of the opened coronary arteries and by biochemical analysis of their intima-media. The arteries of Down patients contained a lower percentage of raised lesions and less calcium than the arteries of the control groups. Thus, even though the coronary arteries of mongoloids were not completely free of atherosclerosis, it was milder than in other mental patients and free-living subjects of the same age.

Adult↗
PubMed1989

Ultrastructural, immunochemical and electrophoretic study of smooth muscle cells in internal mammary arteries of patients undergoing coronary bypass surgery.

The internal mammary artery (IMA) is used widely in bypass grafting for coronary artery disease because of its resistance to atherosclerotic obstruction. Since there are no data on the ultrastructure of IMA or the phenotype of its smooth muscle cells (SMC), we studied the distal parts of left IMA obtained at the time of surgery from 14 coronary bypass patients, aged 43-67 years. Eight IMA were examined by transmission electron microscopy. The distribution of the cytoskeletal proteins actin, vimentin, and desmin in the intima-media of 6 IMA was studied by immunofluorescence microscopy, polyacrylamide gel electrophoresis, and two-dimensional gel electrophoresis. The intimas were very thin, from 3 to 32 microns. The thinnest regions contained no cells. Most intimal cells had the ultrastructural features of SMC; no foam cells were found. The majority of both intimal and medial SMC had a myofilament-rich phenotype. Cells reacting to antibodies of vimentin, desmin and alpha-actin were found in both intima and media. alpha-Actin formed 67% of all actin isoforms in the intima-medial extracts. Our study confirms ultrastructurally the reported scarcity of atherosclerosis in the human IMA and shows that the majority of SMC in the IMA of even severely atherosclerotic coronary bypass patients are both ultrastructurally and biochemically in a differentiated state, which agrees with their resistance to atherosclerosis.

Actins↗
PubMed1989

Macrophage foam cells from human aortic fatty streaks take up beta-VLDL and acetylated LDL in primary culture.

Intimal cells from human aortic fatty streak lesions were isolated with collagenase-elastase digestion and the cellular uptake of lipoproteins fluorescently labeled with 3,3'-dioctadecylindocarbocyanine (DiI) was studied in primary culture. The majority of the cells in primary culture contained lipid droplets and the foam cells consisted of both macrophages and smooth muscle cells (SMC), identified with electron microscopy and the macrophages also using the monoclonal anti-Leu-M3 antibody. The lipid inclusions contained cholesteryl ester, as visualized with filipin staining. Arterial macrophages took up DiI-labeled acetylated low density lipoprotein (DiI-acetyl-LDL) in the same way as did monocyte-macrophages isolated from blood. DiI-labeled beta-very low density lipoprotein (DiI-beta-VLDL) isolated from cholesterol-fed rabbits, was taken up by both macrophages and SMCs. In macrophages DiI-beta-VLDL was internalized also in the presence of excess unlabeled low density lipoprotein (LDL), whereas in SMCs the uptake was partially prevented. DiI-LDL uptake was only seen in SMCs free of lipid inclusions and especially during cell growth. The present results show that, in human aortic fatty streaks, (a) both macrophages and SMCs accumulate cholesteryl ester, (b) macrophage foam cells possess active scavenger receptors capable of mediating the uptake of acetyl-LDL, and (c) macrophages are also capable of accumulating cholesteryl ester by receptor-mediated uptake of beta-VLDL.

Adult↗