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Biomedical subjects

K Saku

Publications and source records attributed to K Saku.

At least 91 records · Page 5Linked to original sources
PubMed1993

In vivo kinetics of oxidatively modified HDL.

The kinetics of oxidatively modified high-density lipoprotein (HDL) in vivo were investigated. 125I-labeled oxidized (Ox) HDL and 131I-labeled native (N) HDL were injected simultaneously into control and WHHL rabbits. The fractional catabolic rates of 125I-labeled Ox-HDL were significantly greater than those of 131I-labeled N-HDL in both control (2.52 +/- 0.36/day vs 0.94 +/- 0.02/day) and WHHL rabbits (4.07/day vs 1.32/day). Oxidized HDL was catabolized faster than native HDL and was taken up primarily by the liver, spleen, and kidney.

Animals↗
PubMed1993

Two novel frameshift mutations associated with the presence of direct repeats of the LDL receptor gene in familial hypercholesterolemia.

Two novel frameshift mutations were detected in the mutant LDL receptor genes responsible for familial hypercholesterolemia. One was a 5-bp insertion at codon 395 in exon 9, and the other was a one nucleotide deletion at codon 531 in exon 11. Both mutations alter the reading frame and consequently produce a premature stop codon in the region of the mature LDL receptor homologous to the epidermal growth factor (EGF) precursor. With regard to the mechanism responsible for the generation of these frameshift mutations, strand slipped mispairing mediated by short direct repeats is considered to be the most likely. The findings seem to support the hypothesis that a short direct repeat in DNA sequence can have a profound influence on the stability of a given gene and promote human gene mutations.

Adolescent↗
PubMed1993

Combined therapy with probucol and pravastatin in hypercholesterolaemia. One year follow-up study.

The effect of co-administration of low doses of pravastatin to hypercholesterolaemic patients already receiving long-term probucol treatment (mean 500-1,000 mg/day for 350 days) were investigated. Pravastatin 5 mg/day (Group 1; 12 m, 13 f; mean age 59.1 y) or 10 mg/day (Group 2; 8 m, 11 f; mean age 60.8 y) was administered, and blood was taken after 0, 3, 6, and 12 months. Both groups showed a significant reduction in serum total cholesterol (TC), phospholipid (PL), low density lipoprotein-cholesterol (LDL-C), LDL-triglyceride (TG), LDL-PL, apolipoprotein (apo) B, and apo E after the combined therapy. These levels were reduced more in Group 2 than in Group 1 subjects. In Group 2, significant falls in serum TG and apo CII were also observed. The changes in TC, PL, LDL-C, apo B, apo CII and apo E were dependent upon the dose of pravastatin, as assessed by two-way analysis of variance. Serum high density lipoprotein (HDL)3-C, apo AI and apo AII were slightly but significantly increased in both groups after 12 months of combined therapy, but the increase was not sufficient to reverse the probucol-induced lowering of the HDL level. We conclude that combined therapy resulted in a significant reduction in atherogenic lipoproteins and apolipoproteins, and an increasing dose of pravastatin (5 mg to 10 mg daily) made the lipid lowering effect more prominent. The reduction in serum HDL-C due to long-term probucol administration was not reversed by the addition of pravastatin.

Adult↗
PubMed1993

Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus.

We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients (123 males, 29 females) undergoing maintenance hemodialysis (HD) with or without diabetes mellitus (DM), in 101 patients with diabetes mellitus without hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88 females). Serum Lp(a) levels were significantly (P < 0.01) higher in patients than in controls (26.2 +/- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD without DM, 27.1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in controls, respectively). Apo(a) phenotyping was performed by a sensitive, high resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In normal controls, the molecular weights of apo(a) isoforms were inversely correlated with plasma Lp(a) levels, and the same tendency was found in patients who were undergoing hemodialysis and/or who had diabetes mellitus. We assumed the differences in apo(a) phenotypes detectable with our method reflected consecutive differences in molecular weights of apo(a). The results of an analysis of covariance and a least square means comparison indicated that the regression lines between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in patient groups were significantly (P < 0.01) elevated for every apo(a) phenotype, as compared to the regression line of the control group. Even after the low molecular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was observed. However, no differences were observed between the patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

In vivo kinetics of lipoprotein(a) in homozygous Watanabe heritable hyperlipidaemic rabbits.

In vivo kinetics of lipoprotein(a) [Lp(a)] were investigated in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits (an animal model of familial hypercholesterolemia (FH)), and in normolipidemic Japanese White rabbits (controls). 125I-labelled Lp(a) and 131I-labelled LDL were simultaneously injected intravenously. Blood samples were then taken periodically. Kinetic parameters were calculated from the plasma radioactivity decay curves. The fractional catabolic rates (FCRs) of both Lp(a) and LDL (1.355 +/- 0.189 pools per day and 1.278 +/- 0.397 pools per day, respectively) in the WHHL rabbits were significantly (P < 0.005) smaller than those in the control rabbits (2.008 +/- 0.083 pools per day and 2.855 +/- 0.759 pools per day, respectively). In WHHL rabbits, the FCRs of Lp(a) and LDL were similar. However, in control rabbits, the FCR of Lp(a) was significantly (P < 0.01) smaller than that of LDL. In WHHL rabbit organs, the mean ratio of 125I-Lp(a): 131I-LDL, 48 h after injection, normalized to the corresponding isotope ratio in plasma, were 1.525, 1.020, 1.819 and 1.967, in liver, kidney, spleen and bile, respectively. These values were significantly higher than the corresponding values in control rabbits (0.590, 0.677, 0.862 and 0.766, respectively). Our data strongly suggest that Lp(a) clearance is not entirely dependent upon LDL receptors and may be mediated by some other mechanisms.

Animals↗
PubMed1993

Serum lipoprotein (a) levels in maintenance hemodialysis patients.

To further understand lipoprotein (a) [Lp(a)] and atherosclerosis, we measured serum Lp(a), lipoprotein, and apolipoprotein levels in 55 patients (males, 24-73 years old) on maintenance hemodialysis, and compared them with those of 82 controls (males, 21-81 years old). The serum Lp(a) levels in patients on maintenance hemodialysis were significantly higher than those of the normal controls, while serum total cholesterol (TC), high-density lipoprotein-cholesterol, (HDL-C), HDL2-C, HDL3-C, apolipoprotein (apo) Al, apo All levels, and lecithin-cholesterol acyltransferase (LCAT) activities were significantly (p < 0.05) reduced in the patient group. The frequency distribution of serum Lp(a) levels in the patients was different from that in the control group, and no prognostic tendency of serum Lp(a) levels was noted by the etiology of renal failure as histologically determined by the renal biopsies. In the patient group, we also found that serum Lp(a) levels negatively correlated with serum triglycerides (TG) and total protein (TP) concentrations (p < 0.05), but no correlation was found between the duration of hemodialysis therapy or patient age and the serum levels of TC, TG, apo B and Lp(a) levels when tested for simple regression. Significant (p < 0.05) positive correlations were also found between TP and serum TG, apo B, and LCAT activities. These opposing tendencies of Lp(a) and serum TG, apo B, when measured against TP concentrations, indicate that serum TP levels may not affect serum lipoprotein and Lp(a) levels in the same direction. These data suggest that hemodialysis or end-stage renal disease itself, rather than hypoproteinemia, may hold the key to high serum Lp(a) levels in hemodialysis patients.

Adult↗
PubMed1993

Long-term administration of probucol and QTc interval prolongation.

Electrocardiographic QTc intervals were measured in twenty-one hypercholesterolemic patients before and after long-term probucol (500-1,000 mg/day for 30 months) treatment. Probucol reduced serum total cholesterol (TC), triglyceride (TG), and high density lipoprotein-cholesterol (HDL-C). Mean QTc interval prolongation after probucol was 17 msec. A positive correlation was found between the change in QTc interval after probucol (delta QTc) and the total amount of probucol administered. delta QTc was negatively correlated to the pre-treatment QTc interval. No correlation was observed between serum probucol concentrations and delta QTc. Neither clinical evidence of cardiotoxicity nor critical arrhythmias were noted during the treatment period.

Aged↗
PubMed1992

Effects of lisinopril and low-dose trichlormethiazide on lipoprotein metabolism in patients with mild to moderate hypertension.

Fifty-six hypertensive patients were recruited to participate in a 12 week, randomised, multicentre trial to compare the effects of lisinopril (n = 31) and low-dose trichlormethiazide (n = 25) administration on blood pressure and lipoprotein metabolism. Both systolic and diastolic BPs decreased significantly after administration of lisinopril (5-40mg/day, mean dose 11 mg/day) and trichlormethiazide (2.0-4.0 mg/day, mean dose 2.2 mg/day). There were no significant changes in lipids, lipoproteins or apolipoproteins with either drug for 12 weeks and no significant differences between the two drugs for these parameters. It is concluded that lisinopril and low-dose trichlormethiazide administration are effective antihypertensive measures without any adverse effects after 12 weeks on lipoprotein metabolism in patients with mild to moderate essential hypertension.

Adult↗
PubMed1992

Effects of Chinese herbal drugs on serum lipids, lipoproteins and apolipoproteins in mild to moderate essential hypertensive patients.

We investigated the effects of the traditional Chinese herbal drugs, Dai-saiko-to (D) and Saiko-ka-ryukotsuboreito (S) on blood pressure, pulse rates, serum lipids, lipoproteins and apolipoproteins in 30 patients with mild to moderate hypertension in an open, randomised trial. After the drug treatment, BP remained unchanged, but pulse rates declined significantly after 3 months in the S treated group. Serum total cholesterol and triglyceride values did not change, but high density lipoprotein-cholesterol increased significantly (P < 0.05) in both groups. Apo-AI (P < 0.1 in S group) and apo-AII (P < 0.05 in D group, P < 0.1 in S group) tended to increase 3 months after treatment. These data indicate that both of these traditional Chinese medicines have a preferential effect on lipid metabolism with little antihypertensive action.

Apolipoproteins↗
PubMed1991

HDL metabolism in HDL deficiency associated with familial hypertriglyceridemia: effect of treatment with gemfibrozil.

Plasma high density lipoproteins (HDL) and their major proteins--apolipoprotein (apo) AI and apo AII--are subnormal in most patients with familial hypertriglyceridemia. However, the pathophysiology of low plasma apo AI and apo AII is unclear. The kinetic parameters (turnover) of HDL apo AI and apo AII were studied in six lean patients with primary HDL deficiency associated with familial hypertriglyceridemia and normolipidemic healthy controls. The radioactivity decay curve of 125I labelled HDL was used for assessment of kinetics. Mean plasma apo AI and apo AII were significantly lower (p less than 0.001) in patients than normals (70.4 +/- 2.7 v 106.9 +/- 7.0; 24.2 +/- 1.6 v 39.2 +/- 0.9 mg/dl, respectively). The mean fractional catabolic rates (FCR) obtained from plasma 125I-HDL, apo AI, apo AII radioactivity decay curves and by Berson and Yalow's method (urine/plasma radioactivity ratios) were significantly greater (p less than 0.05) in patients than in controls (0.387 v 0.299; 0.391 v 0.309; 0.361 v 0.275; 0.272 v 0.207/d; respectively). The synthetic rates (SR of apo AI and apo AII were significantly lower in patients than in controls (11.12 v 14.17 mg/kg body weight/d. p less than 0.05; 3.53 v 4.68 mg/kg body weight/d, p less than 0.05, respectively). Each patient was also investigated for HDL and triglyceride metabolism immediately before and after 8 wk of gemfibrozil (1200 mg/d) treatment. Gemfibrozil significantly increased plasma HDL cholesterol, apolipoprotein (apo) AI, and apo AII by 36%, 29%, and 38% from baseline, respectively. Plasma TG decreased by 54%. Gemfibrozil increased synthetic rates of apo AI and apo AII by 27% and 34%, respectively, without changing the FCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗
PubMed1991

Family studies of the LDL receptor gene of relatively severe hereditary hypercholesterolemia associated with Achilles tendon xanthomas.

To assess the relationship between relatively severe hereditary hypercholesterolemia with Achilles tendon xanthomas and the defect of the low density lipoprotein (LDL) receptor gene, family studies were carried out in 17 hypercholesterolemic families. In 16 out of the 17 families, hypercholesterolemia co-segregated with four different gross rearrangements, six different restriction fragment length polymorphism (RFLP) haplotypes, or an abnormal TaqI band of the LDL receptor gene. These findings are compatible with the interpretation that hypercholesterolemia is caused by defective LDL receptor genes, and that the origin of the mutant LDL receptor genes in Japanese generally differs among different pedigrees. In the remaining family, the proband and his sibling, both having relatively severe hypercholesterolemia and Achilles tendon xanthomas, shared an RFLP haplotype, although the proband's other sibling with moderate hypercholesterolemia but without Achilles tendon xanthomas did not. The mutant gene for familial defective apolipoprotein B-100 was not detected in the 17 probands. These data suggest that most, if not all, of the relatively severe hereditary hypercholesterolemia associated with Achilles tendon xanthomas is caused by a defect of the LDL receptor gene.

Achilles Tendon↗
PubMed1991

Effects of Chinese herbal drug, dai-saiko-to on plasma lipids, lipoproteins and liver lipid contents in guinea pig.

Effects of Chinese herbal drug, Dai-saiko-to, on plasma lipids, lipoproteins and liver lipid contents were investigated in guinea pig with/without cholesterol feeding. Guinea pigs were divided into 4 groups (Group 1: normal chow (N) diet, Group 2: N + 1% Dai-saiko-to (D) diet, Group 3: 1% cholesterol (C) diet, Group 4: 1% C+ 1% D diet), and were treated for 5 weeks. Significant body weight reductions were observed in Groups 3 and 4 compared to Groups 1 and 2. Significant reductions of plasma triglyceride (TG) and very low and low density lipoproteins [(V) LDL]-TG were found in Group 3 compared to Groups 1, 2, and 4. (HDL)-TG significantly decreased in Groups 3 and 4 compared to Groups 1 and 2, but no significant difference was noted between Groups 1 and 2, and Groups 3 and 4. Liver lipid contents analysis showed no significant changes between Groups 1 and 2, and Groups 3 and 4, respectively, but the distribution of lipid droplets as pathologically determined using a computer program showed Group 4 had less lipid deposition compared to Group 3. These data suggest that Dai-saiko-to acts on triglyceride metabolism in hypercholesterolemic guinea pigs.

Alanine Transaminase↗
PubMed1990

Putative mechanisms of action of probucol on high-density lipoprotein apolipoprotein A-I and its isoproteins kinetics in rabbits.

Probucol is a widely prescribed lipid-lowering agent, the major effects of which are to lower cholesterol in both low- and high-density lipoproteins (LDL and HDL, respectively). The mechanism of action of probucol on HDL apolipoprotein (apo) A-I kinetics was investigated in rabbits, with or without cholesterol feeding. 125I-labeled HDL was injected intravenously, and blood samples were taken periodically for 6 days. Kinetic parameters were calculated from the apo A-I-specific radioactivity decay curves. Fractional catabolic rate (FCR) and synthetic rate (SR) of apo A-I in rabbits fed a normal chow and normal chow with 1% probucol were similar. Apo A-I FCR of the rabbits fed 0.5% cholesterol was significantly increased but there were no changes in SR, compared to findings in the normal chow-fed group. Apo A-I FCR of the rabbits fed 1% probucol with 0.5% cholesterol (both 1 month and 2 months) was significantly increased compared to findings in rabbits fed the normal chow as well as 0.5% cholesterol diet group, while SR of apo A-I was significantly reduced in the former groups. Kinetics at 1 month after discontinuation of 1% probucol (under cholesterol feeding) showed a similar FCR of HDL-apo A-I to that of the rabbits fed 0.5% cholesterol, but the SR of apo A-I remained lower. Apo A-I isoproteins kinetics assessed by autoradiography of isoelectric focusing slab gels showed that the synthesis of proapo A-I was significantly reduced in the 1% probucol with 0.5% cholesterol administered, compared to the 0.5% cholesterol group. Thus, the action of probucol on HDL apo A-I kinetics was only prominent in case of higher serum cholesterol levels. The decreased HDL or apo A-I seen with probucol was apparently the result of an increase in FCR and a decrease in SR of HDL-apo A-I. A decreased synthesis of apo A-I remained evident even 1 month after discontinuing probucol. The action of probucol on the intracellular synthetic processes of apo A-I was revealed by the reduced synthesis of proapo A-I.

Animals↗
PubMed1990

Alcohol consumption, serum lipids and severity of angiographically determined coronary artery disease.

The relation of alcohol consumption to serum lipids and the severity of coronary atherosclerosis was examined in 212 men undergoing coronary angiography. The severity of coronary atherosclerosis was assessed in terms of the presence of greater than or equal to 75% diameter stenosis and the Gensini severity score. Alcohol consumption was divided into 4 categories: none (0 ml alcohol/week), light (1 to 100 ml alcohol/week), moderate (101 to 300 ml alcohol/week) and heavy (greater than or equal to 301 ml alcohol/week). Alcohol consumption was positively related to high-density lipoprotein cholesterol and inversely related to total cholesterol, but was not associated with triglyceride. After adjustment for these serum lipids as well as for cigarette smoking and systemic hypertension, the risk of coronary stenosis was significantly decreased in the moderate drinkers. A decreased risk among moderate drinkers also was noted in terms of Gensini's severity score. These findings suggest that moderate alcohol consumption may protect against severe coronary atherosclerosis.

Alcohol Drinking↗
PubMed1990

[Production and characterization of a monoclonal antibody specific for Salmonella O19-antigen].

A monoclonal antibody, SBY1 (IgM, kappa), against the Salmonella O-antigen was generated by using the myeloma cell line Sp2/O-Ag14 as a fusion partner with spleen cells from BALB/c mice immunized with S. senftenberg 963 K. SBY1 was characterized by the slide agglutination and absorption test. SBY1 was believed to show the specificity to O1-, O3- or O19-antigens of Salmonella because S. Senftenberg 963 K (O1, 3, 19) was used as the antigen for immunization. The slide agglutination test with the Salmonella serovars indicated the responsiveness of SBY1. SBY1 was reactive only with strains that possessed O19-antigen. The agglutinating ability of SBY1 was absorbed completely with bacilli possessing O19-antigen. These finding indicates that SBY1 is specific for O19-antigen. Polyclonal factor sera for he serotyping of the O3, 10 group of Salmonella cross-reacted with Salmonella group O1, 3, 19 in the slide agglutination test. In contrast, SBY1 did not cross-react with serovars from several other Salmonella groups. These data suggest the usefulness of SBY1 as a serodiagnostic tool for serotyping of Salmonella.

Antibodies, Monoclonal↗