Biomedical subjects

T Kuusi

Publications and source records attributed to T Kuusi.

At least 37 records · Page 2Linked to original sources

PubMed1990

Effect of fish oil treatment on plasma lipoproteins in type III hyperlipoproteinaemia.

Nine patients with type III hyperlipoproteinaemia and homozygosity for the apolipoprotein E2 isoform were treated with 15 g daily of MaxEPA, a fish oil preparation rich in eicosapentaenoic acid (2.7 g daily) and docosahexaenoic acid (1.8 g daily) for 16 weeks. Plasma lipoprotein and apolipoprotein concentrations were compared with those obtained during treatment with an olive oil preparation. MaxEPA treatment decreased plasma median total cholesterol, triglyceride and apolipoprotein B concentrations by 16, 53 and 19%, respectively. Plasma median very low density lipoprotein (VLDL)-cholesterol, triglyceride and apolipoprotein B concentrations were reduced by 45, 62 and 75% respectively, while the abnormal VLDL-cholesterol/triglyceride ratio remained unchanged. Individual reductions of VLDL concentrations varied considerably, for VLDL-cholesterol between 10 and 75%. In the majority of cases the abnormal late pre beta-bands on agarose electrophoresis, typical for type III hyperlipoproteinaemia normalized to pre beta-mobility on MaxEPA treatment. LDL-cholesterol and apolipoprotein B tended to increase after 8 weeks on MaxEPA but decreased again after 16 weeks. Median plasma high density lipoprotein cholesterol and apolipoprotein A-I did not change during MaxEPA treatment. It is concluded that MaxEPA have decreasing effects on plasma VLDL lipid and apolipoprotein concentrations in apolipoprotein E2 homozygous type III hyperlipoproteinaemia but that this effect is variable and unpredictable.

Adult↗

PubMed1990

Phospholipase A2 activity and concentration in several body fluids in patients with acute pancreatitis.

According to recent studies, phospholipase A2 (PLA2) may be an important factor in the pathogenesis and pathophysiology of acute pancreatitis. Increased serum PLA2 activities and concentrations have been measured in patients with acute pancreatitis. Serum PLA2 activities have been shown to correlate with the severity and prognosis of the disease. To study the different methods of PLA2 determination, we measured the PLA2 activity by means of an isotopic assay method and the concentration by a radioimmunologic method in several body fluids of 52 consecutive patients with acute pancreatitis. PLA2 activity and concentration were detected in all of the patient body fluids. The serum PLA2 activities were 2.5-fold higher (mean +/- SD, 7.6 +/- 6.0) than normal activities, and the concentrations were 9.6-fold higher (mean +/- SD, 41 +/- 88). The enzyme activities and concentrations correlated well in ascites, fluids from the pleural cavity, and peritoneal lavation and poorly in serum, urine, and fluid from pancreatic pseudocyst.

Acute Disease↗

PubMed1990

Apolipoprotein E polymorphism determined by restriction enzyme analysis of DNA amplified by polymerase chain reaction: convenient alternative to phenotyping by isoelectric focusing.

Three common alleles determine six apolipoprotein E (apo E) phenotypes that are associated with variations in serum cholesterol in the population. This genetic variation results from single nucleotide alterations at two DNA loci encoding the amino acid residues 112 and 158 of apo E. We compared results of apo E phenotyping carried out by isoelectric focusing with those of apo E genotyping accomplished by direct DNA analysis. In the latter, the target DNA was amplified by the polymerase chain reaction (PCR) and subsequently analyzed by digestion with the restriction enzyme Hha I, followed by polyacrylamide gel electrophoresis of the cleavage products. With one exception, these two techniques yielded similar results from all 40 samples tested. In addition, a rare variant form of apo E (phenotype E1) was analyzed separately and incorrectly diagnosed as E2 by the Hha I digestion method; the anticipated mutation in the codon 127 was, however, confirmed by demonstration of a new Taq I restriction site in this variant gene. These data confirm that the common isoforms of apo E usually arise from genetic variation of the codons 112 and 158 and demonstrate the feasibility of the PCR technique in apo E genotyping.

Adolescent↗

PubMed1989

Apolipoprotein E phenotype and cholesterol metabolism in familial hypercholesterolemia.

Serum lipids, lipoproteins, cholesterol absorption and parameters of cholesterol metabolism were related to apolipoprotein E phenotypes in 38 patients with familial xanthomatous hypercholesterolemia. Serum lipids and lipoproteins were similar in 2 most frequent apo E phenotypes E 3/3 and E 4/3. Coronary artery disease was not related to the apo E phenotypes. Cholesterol absorption efficiency was significantly lower in the apo E 3/3 patients than in the apo E 4/3 group. A high serum level of cholesterol precursor lathosterol, a high lathosterol/sitosterol ratio and sterol balance data suggest that cholesterol synthesis may be slightly higher in the apo E 3/3 than E 4/3 group. The findings indicate that the genetically determined apo E polymorphism contributes to cholesterol absorption efficiency in FH patients, but serum total and lipoprotein cholesterol levels are poorly related to apo E isoforms.

Apolipoproteins E↗

PubMed1989

Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia.

To study the role of the two postheparin plasma lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) in high density lipoprotein (HDL) metabolism at a population level, we determined serum lipoproteins, apoproteins A-I, A-II, B, and E, and postheparin plasma LPL and HL activities in 65 subjects with a mean HDL-cholesterol of 34 mg/dl and in 62 subjects with a mean HDL-cholesterol of 87 mg/dl. These two groups represented the highest and lowest 1.4 percentile of a random sample consisting 4,970 subjects. The variation in HDL level was due to a 4.1-fold difference in the HDL2 cholesterol (P less than 0.001) whereas the HDL3 cholesterol level was increased only by 32% (P less than 0.001) in the group with high HDL-cholesterol. Serum apoA-levels were 128 +/- 2.2 mg/dl and 210 +/- 2.8 mg/dl (mean +/- SEM) in hypo- and hyper-HDL cholesterolemia, respectively. Serum apoA-II concentration was elevated by 28% (P less than 0.001) in hyperalphalipoproteinemia. The apoA-I/A-II ratio was elevated only in women with high HDL-cholesterol but not in men, suggesting that elevation of apoA-I is involved in hyperalphalipoproteinemia in females, whereas both apoA proteins are elevated in men with high HDL cholesterol. Serum concentration of apoE and its phenotype distribution were similar in the two groups. The HL activity was reduced in the high HDL-cholesterol group (21.2 +/- 1.5 vs. 38.5 +/- 1.8 mumol/h/ml, P less than 0.001), whereas the LPL activity was elevated in the group with high HDL-cholesterol compared to subjects with low HDL-cholesterol (27.8 +/- 1.3 vs. 19.9 +/- 0.8 mumol/h/ml, P less than 0.001). The HL and LPL activities correlated in opposing ways with the HDL2 cholesterol (r = 0.57, P less than 0.001 and r = 0.51, P less than 0.001, respectively), and this appeared to be independent of the relative ponderosity by multiple correlation analysis. The results demonstrate major influence of both HL and LPL on serum HDL cholesterol concentration at a population level.

Adult↗

PubMed1988

Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal males.

We studied the effects of testosterone substitution on serum concentrations of lipids, lipoproteins, apoproteins and on the activity of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma and on the activity of LPL in adipose tissue (AT-LPL) in 13 male hypopituitary patients. The activities of LPL and HL in postheparin plasma were markedly increased by 1 week after a testosterone enanthate injection (P less than 0.001). The HL activity remained elevated (P less than 0.05) after 1 month's treatment, but the LPL activity declined to presubstitution levels. The prolonged substitution decreased serum apoproteins A-I and A-II (P less than 0.05). The changes of apo A-I and A-II correlated inversely with those of the free testosterone index (FTI) (r = -0.74, r = -0.67, P less than 0.05). Serum HDL-cholesterol level decreased slightly by 1 week and it correlated inversely with the increase in testosterone and the FTI (r = -0.67, r = -0.85, P less than 0.05). The results suggest that testosterone increases the activity of both lipolytic enzymes in postheparin plasma. The effect on HL appears to be more persistent than that on LPL. The data support a role for androgens in the regulation of serum lipoprotein and HDL-cholesterol levels.

Adipose Tissue↗

PubMed1988

Elevated adipose tissue lipoprotein lipase activity in craniopharyngioma patients.

The activity of lipoprotein lipase (LPL) was measured in adipose tissue (AT-LPL) and postheparin plasma (PH-LPL) of 13 obese patients (aged 11 to 31 years) who had surgery for craniopharyngioma 1 to 13 years earlier. AT-LPL activity (mean +/- SEM) was higher in them than in subjects matched with respect to age, sex, and relative body weight (4.6 +/- 1.1 v 2.1 +/- 0.4 mumol free fatty acids (FFA).h-1.g-1, P less than .05). The activity was also higher when expressed per fat cell.

Adipose Tissue↗

PubMed1988

Comparison of the effects of two different doses of alcohol on serum lipoproteins, HDL-subfractions and apolipoproteins A-I and A-II: a controlled study.

Our earlier studies have shown that heavy alcohol intake increases the serum concentration of HDL2. The present study aimed to test which HDL subfraction is affected by moderate alcohol intake, and to examine the time- and dose-dependency of alcohol-induced changes in serum lipoproteins. Therefore, 30 or 60 g day-1 of alcohol were given to 10 healthy male volunteers during two 3-week periods separated by an abstinence period of 3 weeks. Lipoproteins were fractioned by sequential flotation. On both doses the total HDL3 concentrations rose progressively, the maximum increases being 10 and 25% at the end of respective drinking periods. In contrast, the HDL2 increased slightly only on the dose of 60 g day-1. The serum concentrations of apoprotein A-I and A-II increased on both doses but significantly only on the dose of 60 g day-1; the increments being 22 and 35%, respectively. On the basis of these and our earlier findings we conclude that (i) the effects of heavy and moderate alcohol intake on serum HDL-subfractions are different: the former preferentially increases the HDL2 whereas the latter augments the HDL3; (ii) alcohol-induced changes in serum lipoproteins are both time- and dose-dependent.

Adult↗

PubMed1988

Lipoproteins, lipolytic enzymes, and hormonal status in hypothyroid women at different levels of substitution.

Serum lipoproteins and postheparin plasma lipoprotein lipase and hepatic lipase (HL) activities were determined in 23 hypothyroid women treated with graded doses of thyroxine (T4) (50, 100, and 150 micrograms/day), each given for 3 weeks. Since the sex hormone-binding globulin (SHBG) and thereby serum sex steroid concentrations are sensitive to thyroid status, we also measured serum testosterone, estradiol, and SHBG at each time. Stepwise T4 treatment resulted in gradual improvement in thyroid status. Concomitantly, serum low density lipoprotein (LDL) cholesterol decreased in a linear fashion from a mean of 4.72 +/- 0.31 (+/- SEM) to 3.21 +/- 0.18 mmol/L (P less than 0.001) after the largest dose. In contrast, serum high density lipoprotein (HDL) cholesterol decreased, although not in a dose-dependent fashion, from 1.61 +/- 0.07 to 1.44 +/- 0.05 mmol/L (P less than 0.001) after the largest dose. Serum SHBG increased along with improvement of thyroid function, but this increase did not have major impact on the changes in LDL during T4 treatment, as judged by multiple regression analysis. Thus, serum LDL correlated independently only with T4 (r = -0.38; P less than 0.001). The serum HDL changes were almost exclusively due to those in the HDL2 subfraction, and these were related to HL activity, which increased from 13.4 +/- 1.76 to 18.9 +/- 2.08 U/L after the largest dose. We conclude that thyroid hormones regulated serum HDL (HDL2) cholesterol mainly through their effect on HL.

Adult↗

PubMed1988

Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes.

Sex steroids influence serum high density cholesterol (HDL) concentrations through their effects on postheparin plasma hepatic lipase activity. This enzyme is remarkably sex steroid sensitive; its activity is increased by treatment with androgens and androgenic progestins but decreased by estrogens. Hepatic lipase also is regulated by endogenous estradiol, but less is known about its regulation by endogenous androgens. We measured serum lipoproteins and postheparin plasma hepatic lipase and lipoprotein lipase activities in relation to sex steroids in 13 boys in whom testicular sex steroid production was stimulated by 4 injections of hCG given at 3-day intervals. Serum testosterone, but not estradiol, concentrations increased in 8 boys (group I, prepubertal and early pubertal boys), whereas in 5 boys both testosterone and estrogen concentrations increased concomitantly (group II, pubertal boys). Postheparin plasma hepatic lipase activity increased by 34% (P less than 0.001) in group I, but did not change in group II. Serum HDL cholesterol concentrations did not change during hCG stimulation. However, postheparin plasma hepatic lipase activity correlated inversely with serum HDL (r = -0.34; P less than 0.05) and HDL2 cholesterol levels (r = -0.51; P less than 0.001), and the changes in HDL2 levels and hepatic lipase activity were inversely related (r = -0.63; P less than 0.05). Postheparin plasma lipoprotein lipase activity decreased during hCG stimulation. Its activity was positively related to HDL (r = 0.47; P less than 0.05) and HDL2 cholesterol levels (r = 0.54; P less than 0.001). These results suggest that endogenous androgens and estrogens are involved in the regulation of postheparin plasma lipase activities and serum HDL cholesterol concentrations.

Adolescent↗

PubMed1988

Short-term effects of prednisone on serum lipids and high density lipoprotein subfractions in normolipidemic healthy men.

To study the effects of short term low dose prednisone administration on serum lipids and lipoproteins we measured the concentration and composition of serum lipoproteins; serum apoproteins (apo) A-I, A-II, and B; and plasma lipolytic enzymes before and during prednisone administration (30 mg/day for 7 days) in eight normal men. We also measured insulin binding to adipocytes. Serum high density lipoprotein (HDL) cholesterol increased significantly after 2 days of prednisone administration; the maximal increase was 27% (P less than 0.01 after 5 days). The rise of HDL cholesterol was accounted for by that of HDL2 cholesterol. There were marked changes in the distribution of HDL particles; HDL2 increased, whereas HDL3 decreased. These changes were also apparent after 2 days of prednisone administration and were maximal at 5 days [mean, 1.58 +/- 0.12 (+/- SE) vs. 2.00 +/- 0.14 g/L (P less than 0.001) for HDL2; 1.82 +/- 0.11 vs. 1.61 +/- 0.06 g/L (P less than 0.05) for HDL3], and they were due to opposing changes in cholesterol, phospholipids, and proteins in the HDL subfractions. The change in HDL2 protein correlated inversely with that in HDL3 protein (r = -0.73; P less than 0.05). Notably, prednisone did not change the apo A-I concentration, but that of apo A-II decreased (0.32 +/- 0.02 vs. 0.27 +/- 0.01 g/L; P less than 0.05). Consequently, the lipid to protein ratio of HDL increased. Prednisone induced no significant changes in very low density or low density (LDL) lipoproteins. Adipose tissue LPL activity did not increase until after 7 days of prednisone intake (1.10 +/- 0.28 vs. 3.43 +/- 1.02 mumol FFA/g.h; P less than 0.05), and the same was true for muscle LPL (0.49 +/- 0.14 vs. 0.82 +/- 0.11 mumol FFA/g.h; n = 4; P = 0.06). Specific insulin binding was normal, but both basal and maximal insulin-stimulated glucose transport decreased significantly. In summary, prednisone induces changes in serum HDL which are characterized by redistribution of particles within HDL density toward less dense particles and a quantitative rise of lipids in the HDL2 fraction.

Adipose Tissue↗

PubMed1988

Role of apolipoproteins E and C in type V hyperlipoproteinemia.

Type V hyperlipoproteinemia is characterized by elevations of chylomicron (CM) and very low density lipoprotein (VLDL) triglycerides. The development of this lipid disorder involves a multitude of metabolic derangements including deficient clearance of triglycerides and/or their increased output aggravated by obesity, diabetes, alcohol intake, or use of some hormones. Some studies have suggested that the apolipoprotein E4 phenotype is involved in this dyslipoproteinemia but this concept is still a matter of controversy. Therefore, we determined the apoE phenotype in 21 patients with severe hypertriglyceridemia classified as type V. Their apoE4 gene frequency was 0.595 which is 2.6-fold higher (P less than 0.001) than that in the Finnish population. Correspondingly, their apoE3 gene frequency was lower than that in the normal population. No differences were noted in plasma lipoproteins of the apoE4 phenotypes and the other type V subjects. The apolipoprotein C-II and C-III distribution was similar to that in normolipidemic subjects. The results suggest that apoE4 may be involved in the development of type V hyperlipoproteinemia.

Adult↗

PubMed1988

Effects of long-term physical exercise on serum lipids, lipoproteins and lipid metabolizing enzymes in type 2 (non-insulin-dependent) diabetic patients.

The effects of four months' physical exercise on serum lipids, lipoproteins and lipid metabolizing enzymes were studied in 25 non-insulin-dependent diabetic patients divided randomly into exercise (n = 13) and control (n = 12) groups. Exercise induced a significant decrease in serum LDL-cholesterol and an increase in serum HDL-cholesterol and HDL2-cholesterol. Triglycerides showed a temporary decrease. Apoproteins A1 and B were virtually unchanged. Postheparin plasma lipoprotein lipase increased markedly during the exercise period while no change occurred in adipose tissue lipoprotein lipase, hepatic lipase or lecithin:cholesterol acyltransferase. In the control group no significant changes occurred in any of the lipid variables. In the light of the knowledge of LDL-cholesterol as a causative and HDL-cholesterol as a protective factor in atherogenesis in non-diabetics the changes caused by exercise in non-insulin-dependent diabetics can be considered favourable.

Adipose Tissue↗

PubMed1987

Alcohol-induced changes in serum lipoproteins and in their metabolism.

The effects of alcohol intake on serum lipids and lipoproteins depend on the dose and mode of alcohol intake, individual susceptibility, genetic variables, and dietary factors. Therefore the changes of lipoprotein pattern are different among moderate and heavy drinkers. Moderate intake of alcohol increases the concentrations of apolipoproteins (apo) AI, apo AII, and high-density lipoprotein subfraction (HDL3) in plasma without any effects on other lipoproteins. If alcohol intake exceeds 60 to 80 gm per day, the synthesis of very low-density lipoprotein (VLDL) particles is stimulated. Even short-term use of alcohol stimulates lipoprotein lipase (LPL) activity in adipose tissue, and consequently the concentration of VLDL in plasma stays normal or is even subnormal. If alcohol intake continues in excessive amounts, the increased transport rate of VLDL particles as a result of high LPL activity results in the up regulation of HDL2. This is clearly evident in chronic alcoholics. Low or subnormal low-density lipoprotein (LDL) levels are another characteristic of the lipoprotein pattern in chronic alcoholics. The increase of HDL (HDL2) and reduction of LDL levels could well explain the reduced risk of coronary heart disease in chronic alcoholics, whereas the causal factors remain open among moderate drinkers.

Alcoholism↗

PubMed1987

High density lipoprotein, apoproteins A-I and A-II and postheparin plasma lipolytic enzymes after ileal bypass.

Apoproteins A-I and A-II, and the activities of lipoprotein lipase (LPL) and hepatic lipase (HL), were studied in 16 patients 3-12 years after ileal bypass operation and in 13 controls, all heterozygous for familial hypercholesterolemia, to investigate why the operated subjects had a higher HDL cholesterol level than the unoperated controls. HDL- and HDL2-cholesterol and apoprotein A-I were higher, HDL3-cholesterol was similar and apoprotein A-II tended to be lower in the operated than the control subjects. The activities of LPL and HL were similar in the 2 groups. HL was negatively correlated with HDL2-cholesterol, whereas LPL was not associated with any of the HDL components. The controls had gained in weight during the follow-up, but the HDL components were not correlated with relative body weight. It is concluded that in familial hypercholesterolemia ileal bypass results in higher HDL- and HDL2-cholesterol and apoprotein A-I level than conservative treatment and that postheparin plasma lipolytic enzymes do not explain the higher level of these HDL components in the operated subjects.

Adult↗

PubMed1987

Post-heparin plasma hepatic lipase activity as predictor of high-density lipoprotein response to progestogen therapy: studies with cyproterone acetate.

Cyproterone acetate (CPA) was administered to 13 menstruating women from day 14 to day 27 of the cycle at a dose of 5 mg/day. Serum lipoprotein lipid levels and postheparin plasma lipase activity were determined on day 27 of the cycle before treatment and during two treatment cycles. No significant changes were observed in hepatic lipase activity or in very-low-density (VLDL) or low density lipoprotein (LDL) concentrations. However, analysis of high-density-lipoprotein (HDL) subfractions by precipitation demonstrated a significant reduction in HDL2 cholesterol (-24%, P less than 0.05) during cyproterone acetate treatment. It is suggested that this change is related to oestrogen deficiency induced by inhibition of luteinizing hormone (LH) secretion.

Adult↗

PubMed1987

Enzymes involved in triglyceride hydrolysis.

The lipolytic enzymes LPL and HL play important roles in the metabolism of lipoproteins and participate in lipoprotein interconversions. LPL was originally recognized to be the key enzyme in the hydrolysis of chylomicrons and triglyceride, but it also turned out to be one determinant of HDL concentration in plasma. When LPL activity is high, chylomicrons and VLDL are rapidly removed from circulation and a concomitant rise of the HDL2 occurs. In contrast, low LPL activity impedes the removal of triglyceride-rich particles, resulting in the elevation of serum triglycerides and a decrease of HDL (HDL2). Concordant changes of this kind in LPL and HDL2 are induced by many physiological and pathological perturbations. Finally, the operation of LPL is also essential for the conversion of VLDL to LDL. This apparently clear-cut role of LPL in lipoprotein interconversions is contrasted with the enigmatic actions of HL. The enzyme was originally thought to participate in the catalyses of chylomicron and VLDL remnants generated in the LPL reaction. However, substantial in vitro and in vivo data indicate that HL is a key enzyme in the degradation of plasma HDL (HDL2) in a manner which opposes LPL. A scheme is presented for the complementary actions of the two enzymes in plasma HDL metabolism. In addition, recent studies have attributed a role to HL in the catabolism of triglyceride-rich lipoproteins, particularly those containing apo E. However, this function becomes clinically important only under conditions where the capacity of the LPL-mediated removal system is exceeded. Such a situation may arise when the input of triglyceride-rich particles (chylomicrons and/or VLDL) is excessive or LPL activity is decreased or absent.

Animals↗

PubMed1987

A simple isotopic assay method for human serum phospholipase A2 activity.

An assay using 2-(1-14C)palmitoyl-labelled dipalmitoyl phosphatidylcholine substrate for the determination of serum phospholipase A2 (PLA2) activity is described and validated. The rapid determination of the enzyme activity is enabled by a simple liquid-liquid partition system to replace the laborious thin-layer chromatography used in earlier studies. The PLA2 activity of human pancreatic juice was used for the optimization of the assay. Interference by serum phospholipids can be avoided by using 10 microliter aliquots of serum in the assay, whereas larger amounts caused a progressive inhibition of the enzyme activity. Virtually no enzyme activity is determined in serum from normal healthy subjects (range from 1.2 to 3.0 IU/l). In acute haemorrhagic pancreatitis the PLA2 activity is markedly elevated (range from 10.7 to 42.0 IU/l). Due to the simple extraction of the reaction products the results can be obtained the same day. Therefore, the assay can conveniently be used for the rapid clinical identification of subjects with acute haemorrhagic pancreatitis.

1,2-Dipalmitoylphosphatidylcholine↗