Biomedical subjects

K Saku

Publications and source records attributed to K Saku.

At least 73 records · Page 4Linked to original sources

PubMed1996

Short-term effects of a high-sucrose diet on plasma lipid, lipoprotein cholesterol, tissue lipoprotein lipase and hepatic triglyceride lipase in rats.

Short-term (2 weeks) effects of a high-sucrose diet on plasma lipids, lipoproteins, tissue lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were investigated in rats. Three days of sucrose feeding significantly increased plasma TG (42 +/- 3 mg/dl vs. 56 +/- 2 mg/dl, p = 0.032), while TC increased significantly after 10 days of the diet (50 +/- 2 mg/dl vs. 62 +/- 2 mg/dl, p = 0.0001). HDL-C increased significantly after 3 days of sucrose feeding (36.2 +/- 0.9 mg/dl vs. 42.4 +/- 2.7 mg/dl, p = 0.011). Although LDL-C tended to decrease on days 3, 7 and 10, these changes were not significant. The plasma glucose level did not change during the study. Increased LPL activity in adipose tissue and decreased enzyme activities in skeletal and heart muscles were observed. Adipose tissue LPL returned to the baseline value after 14 days of the diet treatment, while LPL in skeletal and heart muscles remained at the decreased level. HTGL and HTGL/total liver lipase activities were significantly increased after 14 days of the diet. The different responses of lipase activities in various tissues may help to regulate serum lipid and lipoprotein levels in sucrose-fed rats.

Adipose Tissue↗

PubMed1996

Analysis of a new polymorphism in the human apolipoprotein A-I gene: association with serum lipoprotein levels and coronary heart disease.

Systematic sequencing of the coding and exon flanking regions of the apolipoprotein (apo) A-I gene has identified a new polymorphic Msp I site (C C/T-GG). This polymorphism is situated between the transcriptional starting site and the signal peptide start coding site (intron 1), so may influence the efficiency of surrounding splicing, thereby interfering with the expression of the apo A-I gene product, or serve as a linkage marker with a hitherto unidentified mutation defect responsible for hyperlipidemia and/or premature coronary heart disease. However, there was no significant difference in the allele frequencies between control and coronary heart disease subjects in a Japanese population. The -78 G-->A promoter polymorphism of apo A-I, previously reported in Western populations, has also been analyzed. The results show that neither mutation is likely to be the etiology for predisposition to a change of high-density lipoprotein cholesterol and/or variation in lipid and lipoprotein levels, or for the occurrence of coronary heart disease in Japanese populations.

Aged↗

PubMed1995

High-density lipoprotein and apolipoprotein A-I deficiency induced by combination therapy with probucol and bezafibrate.

The effects of the administration of slow-release bezafibrate to hypercholesterolaemic patients who were already receiving long-term probucol treatment (mean 865 days, 500-1000 mg.day-1) were investigated. Bezafibrate was administered at either 200 mg.day-1 (13 males, 13 females, mean age 55.2 years) or 400 mg.day-1 (11 males, 14 females, mean age 57.2 years), and blood was taken at 0, 3, 6 and 12 months after the beginning of combination therapy. Overall, serum total cholesterol (TC), triglyceride (TG), very low density lipoprotein (VLDL)-TC, high-density lipoprotein (HDL)-TG, VLDL-TG, VLDL-phospholipid (PL), lipoprotein (a) [Lp(a)], apolipoprotein (apo) C-III, apo E levels and LCAT activity decreased significantly with this combination therapy, while HDL cholesterol (C), HDL3-C, HDL-PL, apo A-I and apo A-II levels significantly increased, as assessed by analysis of variance (ANOVA). Five patients (one receiving 200 mg.day-1, four receiving 400 mg.day-1 bezafibrate) showed drastic reductions in HDL-C (HDL-C levels were reduced by a mean of 46.2%, 59.3% and 61.6% at 3, 6 and 12 months, respectively) after beginning combination therapy. These HDL-C reductions were maintained for the 1 year of combination therapy, but then returned to pre-combination treatment levels 1 month after discontinuation of bezafibrate. Serum probucol concentrations and cholesteryl ester transfer protein (CETP) mass were assayed at 6 months, and the probucol concentration was higher in the HDL-deficient group (56.2 vs 26.5 micrograms/ml). In contrast, CETP mass was significantly lower in HDL-deficient patients than in non-HDL-deficient patients (2.08 vs 2.87 mg.1-1)(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Association between coronary heart disease and the apolipoprotein A-I/C-III/A-IV complex in a Japanese population.

Several studies have reported that a variant allele (S2) of the apolipoprotein (apo) A-I/C-III/A-IV complex is associated with hyperlipoproteinemia in some populations and that the frequency of this allele is two- to fivefold higher in patients with premature coronary heart disease (CHD) than in healthy controls. In the present study in a Japanese population, we were unable to confirm the association of the S2 allele with either coronary heart disease or elevated serum apo C-III levels, as has been previously reported in Caucasians. No genotype difference was observed among the severity of coronary heart disease, as determined by the number of involved vessels (one, two and three vessel disease), compared to controls. In addition, the frequency of the S2 allele among Japanese, in both CHD (0.328) and controls (0.369), was quite different from that in many other populations.

Aged↗

PubMed1995

Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in the families of NIDDM patients.

We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA1c 7.1 +/- 1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3-6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) nondiabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8 +/- 33.3 vs 22.3 +/- 19.5 mg/dl, p < 0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p < 0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p < 0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.

Apolipoproteins↗

PubMed1995

Oxidized low density lipoprotein stimulates collagen production in cultured arterial smooth muscle cells.

We examined the interactive effect of oxidized low density lipoprotein (LDL) and ascorbic acid on collagen production in cultured smooth muscle cells (SMCs). Porcine aortic SMCs were incubated with 50-200 micrograms/ml of human LDL with/without 5 microM Cu2+ for 24 h. Collagen production was assayed by successive salt precipitation at acidic and neutral pH after pepsin digestion of 3H-proline-labeled collagenous protein. Oxidation of LDL was evaluated by electrophoresis and by the level of thiobarbituric acid reactive substances (TBARS). Ascorbic acid reduced the oxidation of LDL + Cu2+ (53% reduction). In the presence of ascorbic acid, no differences were noted in collagen production between LDL and LDL + Cu2+. Without ascorbic acid, collagen production with LDL + Cu2+ was increased dose-dependently up to 6-fold with 150 micrograms/ml LDL, while no such effects were observed at any doses of native LDL. The addition of butylated hydroxytoluene to LDL + Cu2+ strongly suppressed oxidation (88% reduction), and significantly reduced collagen production close to that seen with native LDL. These results indicate that oxidized LDL stimulates collagen production in SMCs, while native LDL does not. Therefore, oxidized LDL may play a direct role in stimulating collagen production in SMCs, which could lead to collagenosis in atherosclerosis.

Animals↗

PubMed1995

Candidemia in non-neutropenic patients with an intravenous hyperalimentation catheter: good prognosis of Candida parapsilosis infection.

Positive blood cultures reported between 1986 and 1993 at the Tokyo Metropolitan Komagome Hospital were evaluated and all patients with an intravenous hyperalimentation catheter who developed candidemia, a total of 94 patients, were analyzed further, while patients with neutropenia were excluded. The primary diagnosis was malignancy in 87.2% of the cases, and Candida albicans and C. parapsilosis were the main organisms detected. A total of 17 patients died from candidemia. The patients who were positive for C. parapsilosis, however, all survived in spite of the fact that their main treatment was only removal of the catheter (20/32 cases), while eight of 25 patients who developed fungemia due to C. albicans died from the fungemia (p = 0.001). There were no significant differences in their risk factors. Because of the better outcome for the patients who developed candidemia due to C. parapsilosis, we might be able to consider less aggressive treatment for such patients.

Adult↗

PubMed1995

A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I gene without evidence of coronary heart disease.

We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as data from members of his family. Corneal opacity and a stomatocyte were found but not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol, apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and 175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase activity was half of normal, while lipoprotein lipase and hepatic triglyceride lipase activities were within normal limits. ApoA-I deficiency was confirmed by combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of the patient and five of his family members by direct sequencing after amplification by polymerase chain reaction and found a codon 8 nonsense mutation (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a pedigree analysis by DNA sequencing and restricted fragment length polymorphism (Sty I) were consistent with an autosomal codominant trait. Coronary angiography was performed to evaluate coronary atherosclerosis, but no significant luminal narrowing was detected. An intracoronary ultrasound study showed mild intimal hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without evidence of coronary heart disease.

Adolescent↗

PubMed1995

Different effects of subclasses of HDL containing apoA-I but not apoA-II (LpA-I) on cholesterol esterification in plasma and net cholesterol efflux from foam cells.

We investigated the effects of subclasses of plasma LpA-I (HDL containing apoA-I but not apoA-II) on cholesterol esterification in plasma and net cholesterol efflux from foam cells. LpA-I was composed of particles of three diameters: large (11.1 nm; Lg-LpA-I), medium (8.8 nm; Md-LpA-I), and small (7.7 nm; Sm-LpA-I). Plasma concentrations of LpA-I were positively correlated only with the level of Lg-LpA-I. Plasma concentrations of Lg-LpA-I were inversely correlated with the rate of cholesterol esterification in plasma and VLDL- and LDL-depleted plasma. Plasma concentrations of Md-LpA-I and Sm-LpA-I did not correlate with the rate of cholesterol esterification in plasma or VLDL- and LDL-depleted plasma. When macrophage foam cells were incubated with Md- and Sm-LpA-I, cellular cholesterol mass was reduced by approximately 70%. In contrast, the cellular cholesterol-reducing capacity of Lg-LpA-I was negligible. Lg-LpA-I inhibited net cholesterol removal from foam cells that was mediated by Md- and Sm-LpA-I and cholesteryl ester production with these particles. These results suggest that Md- and Sm-LpA-I may actively participate in cellular cholesterol removal and cholesterol esterification in plasma and HDL, while Lg-LpA-I may regulate these functions of Md- and Sm-LpA-I.

Adolescent↗

PubMed1995

Combined effects of pravastatin and probucol on high-density lipoprotein apolipoprotein A-I kinetics in cholesterol-fed rabbits.

The combined effects of pravastatin and probucol on high- density lipoprotein (HDL) apolipoprotein (apo) A-I kinetics in cholesterol (Ch)-fed rabbits were investigated. Japanese White rabbits were treated with 0.15% pravastatin and 0.5% Ch (group 1) or 0.15% pravastatin plus 1% probucol and 0.5% Ch (group 2) for 2 months. After treatment, the serum total cholesterol levels in groups 1 and 2 had significantly (p < 0.01) increased (37.4 +/- 6.7 mg/dl vs 117.1 +/- 46.4 mg/dl, and 31.4 +/- 4.9 mg/dl vs 143.0 +/- 84.5 mg /dl, respectively). The serum HDL-cholesterol levels in both groups decreased (18.2 +/- 2.8 mg/dl, vs 16.2 +/- 3.7 mg/dl p < 0.01 for group 1; 18.2 +/- 1.9 mg/dl vs 15.5 +/- 4.5 mg/dl, ns for group 2). Apo A-I kinetics were assessed by injecting (125)I-labeled HDL intravenously into both groups of rabbits, and taking blood samples periodically for 6 days. Kinetic parameters calculated from apo A-I specific radioactivity decay curves showed that the apo A-I fractional catabolic rates in rabbits fed pravastatin and Ch (group 1) were significantly less than those in rabbits fed pravastatin plus probucol and Ch (group 2) (0.546 +/- 0.017 /day vs 0.730 +/- 0.126 /day, p < 0.05), while the synthetic rate of apo A-I was lower in group 2 than in group 1 (14.76 +/- 1.71 mg/kg per day vs 11.21 +/- 2.38 mg/kg per day, respectively, p < 0.01). These data indicate that pravastatin and probucol have different effects on HDL-apo A-I kinetics in a diet which includes cholesterol.

Animals↗

PubMed1995

Reduced coronary vasodilation in patients with familial hypercholesterolemia following intracoronary injection of isosorbide dinitrate.

To clarify the relationship between the dilatation of angiographically non-stenotic coronary artery segments in response to isosorbide dinitrate (ISDN), and serum lipids, 5 coronary segments in 7 patients with familial hypercholesterolemia (FH) and 43 patients with non-familial hypercholesterolemia (non-FH), who had either 1- or 2-vessel coronary heart disease, were investigated. The serum total cholesterol level was significantly greater in FH than in non-FH. Before and after the direct intracoronary injection of ISDN, coronary diameter was measured by a computer-assisted coronary angiography analysis system. The order of the dilative responses in coronary segments in non-FH patients (segments: #5 > #11 > #6 > #13 > #7) was exactly the same as the order of their original diameters, while the ratio of the increase in diameter (after/before ISDN injection) did not differ among any of the segments (mean: 1.08-fold increase). In the non-FH group, no correlation was found between the serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol, or high-density lipoprotein-cholesterol, and the ratio of the coronary diameter after and before injection of ISDN. Moreover, hypercholesterolemia in non-FH did not affect the coronary dilative response to ISDN injection. In the FH group, although the original diameter of each segment did not differ from that in the non-FH group, the ratio of the diameter after and before injection of ISDN was significantly smaller in FH than in non-FH (p < 0.01). These results suggest that a non-stenotic coronary artery in FH has a lower capacity for vasodilation in response to ISDN. Although hypercholesterolemia was excluded as a factor which may suppress the capacity for coronary dilation in non-FH, spontaneous hypercholesterolemia in FH may affect medial smooth muscle functions of the coronary artery.

Adult↗

PubMed1994

Plasma HDL levels are regulated by the catabolic rate of large particles of lipoprotein containing apo-A-I.

Lp-A-I was isolated by immunoaffinity chromatography and then separated into two fractions of large and small Lp-A-I particles by conventional ultracentrifugation with a cut-off density of 1.125 g/ml. The large and small particle-rich fractions were then radiolabeled with [125I]-Na and [131I]-Na, respectively. Both of the labeled lipoproteins were injected (20 microCi, i.v.) simultaneously into normolipidemic rabbits. The FCR of the large Lp-A-I particles was much less than that of the small Lp-A-I particles (0.801 +/- 0.026/day vs. 2.227 +/- 0.067/day, P < 0.0001). These data indicate that the two particles have distinctly different metabolic pathways and that the lower FCR of larger Lp-A-I particles can effectively raise plasma HDL levels.

Animals↗

PubMed1994

In vitro conversion of recombinant human proapolipoprotein A-I to apolipoprotein A-I.

We recently investigated the in vivo conversion of recombinant human proapolipoprotein A-I (rh-Met-proapo A-I) from E. coli to apolipoprotein (apo) A-I in rabbits. In vitro incubation of rh-Met-proapo A-I with rabbit serum produced mature apo A-I3 isoproteins, as determined by the immunoblotting method. However, at the time we were unable to chemically confirm a newly produced protein band which appeared at the position of human apo A-I3. Since then, we have confirmed the amino acid sequence of the protein using a membrane protein sequence technique, and have concluded that it corresponds to human apo A-I3.

Amino Acid Sequence↗

PubMed1994

Quantitative characterization of insulin-glucose response in Watanabe heritable hyperlipidemic and cholesterol-fed rabbits and the effect of cilazapril.

A great deal of evidence suggests that insulin resistance, via hyperinsulinemia, contributes to hyperlipoproteinemia and coronary atherosclerosis. When Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia (FH), are compared with normolipidemic Japanese White (JW) rabbits, an elevated fasting plasma insulin level and a heightened plasma insulin response to an intravenous (i.v.) glucose challenge are found. To elucidate the mechanism behind this phenomenon, a two-compartment model of the glucose/insulin system was fitted to empirical time courses of glucose and insulin concentrations during an i.v. glucose tolerance test (IVGTT) by nonlinear least-square regression, and the model parameters such as the glucose utilization rate constant, insulin degradation rate constant, and pancreas sensitivity were determined. WHHL rabbits showed decreased values of glucose utilization and insulin degradation rate constants and slightly higher values of pancreas sensitivity. This suggests that insulin resistance occurs in extrapancreatic tissues, and that this may be attributable to insulin receptor and/or post-insulin receptor abnormalities. Cholesterol feeding did not significantly change glucose tolerance or insulin action in JW rabbits. The effects of an angiotensin-converting enzyme (ACE) inhibitor, cilazapril, on insulin resistance were also examined in WHHL and JW rabbits. A decreased insulin response to an i.v. glucose challenge and increased glucose utilization and insulin degradation rate constants were observed in WHHL rabbits that had been treated with cilazapril, indicating that cilazapril improved insulin resistance in WHHL rabbits, possibly by increasing the number of insulin receptors. No significant differences were found in glucose tolerance and insulin action in JW rabbits before and after cilazapril administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[Tangier disease].

Tangier disease, a familial HDL-deficiency syndrome, was first reported by Fredrickson et al. in 1961. Since then, a great deal research on the mechanism of HDL-deficiency in this disease has been done from the prospective of lipoprotein compositions, in vivo HDL kinetics, cell and receptor interactions and genomic DNA analysis. These studies have found a relatively increased fractional catabolic rate of apo HDL with essentially no change in the synthesis of apo HDL. As yet, no structural defect has been found in the apo A-I gene. However, there have been reports of irregular lipid metabolism and of disorders in the Golgi apparatus and lysosome processing. Interestingly, the frequency of coronary heart disease is low in patients with Tangier disease. In this report, we describe the clinical and biochemical characteristics of Tangier disease and suggest some possible mechanisms for preventing coronary heart disease.

Apolipoproteins↗

PubMed1993

Polymorphic site study at codon 347 of apolipoprotein A-IV in a Japanese population.

In a population of Japanese subjects, we surveyed codon 347 of the apolipoprotein (apo) A-IV gene and found that the frequency of a rare allele at this point was extremely low compared to that in western populations. Only one of 850 unrelated samples showed mutation at the enzyme recognition site by agarose gel electrophoresis. However, direct sequencing of the coding region revealed that it did not result from the ACT (Thr) to TCT (Ser) mutation which has been reported in western countries, but from an ACT to ACG (Thr) mutation, which does not affect the primary structure of apo A-IV. Two additional family members showed the same point mutation at codon 347.

Adult↗

PubMed1993

In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) to apolipoprotein AI in rabbits.

In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) from E. coli to apolipoprotein (apo) AI was investigated. rh-Met-proapo AI was labeled with 125I, and then administered intravenously to rabbits. Blood was sampled periodically for 6 days. The plasma decay curves of radioiodinated rt-Met-proapo AI were similar to those of human mature apo AI (fractional catabolic rate (FCR); 1.018 +/- 0.090/day vs. 0.976 1 0.031/day, respectively). In vivo conversion of rh-Met-proapo AI to mature apo AI was examined by autoradiography of the isoelectric focusing (IEF) slab gel, i.e., the HDL fraction from each sampling point was semiquantitatively applied to IEF. It was found that the radioactivity of rh-Met-proapo AI migrated to more acidic isoproteins, the conversion was complete within 24 h, and the FCR of rh-Met-proapo AI was 9.20 +/- 1.34/day. Although the plasma decay curves of both human pro (rh-Met-proapo AI) and mature apo AI were significantly steeper than those of rabbit mature apo AI4 and apo AI5 (FCR; 0.703 +/- 0.027/day and 0.795 +/- 0.031/day, respectively), the conversion rate of human rt-Met-proapo AI to mature apo AI in rabbit was assumed to be 1:1. In vitro incubation of rh-Met-proapo AI with rabbit serum produced mature apo AI isoproteins, as determined by the apo AI immunoblotting method. Prediction of the amino acid sequence at the NH2 terminus of rabbit proapo AI showed that the prosegment consisted of an alpha helix with a high probability of a beta turn at Pro9, which is close to that in humans. Thus, (1) the proteolytic cleavage of proapo AI is an extracellular event, (2) the converting enzyme in rabbits can also process human proapo AI, (3) this converting enzyme does not specifically and directly attack the Gln6-Asp7 bond which links the carboxyl-terminal residue of the hexapeptide to the amino-terminal residue of human mature apo AI. The conformation of proapo AI at the NH2 terminus (alpha helix of the prosegment and a beta turn at Pro9) may have a key role in this cleavage, and (4) the examination of rh-Met-proapo AI in rabbits helps to explain the early events of HDL biogenesis.

Amino Acid Sequence↗

PubMed1993

Characteristics of reactive electropermeable points on the auricles of coronary heart disease patients.

In oriental medicine there is a hypothesis related to acupuncture that the auricle is a projection of the functional anatomy of the whole human body. In this study reactive electropermeable points (REPP), that is, points on the skin with low electrical resistance, on the auricle were measured on patients with coronary heart disease using a neurometer LC-M. Our findings correlated positively with the particular points--heart I (shin) and heart II (shinzo)*--named by the Chinese group as being related to the functional anatomy of the heart. The incidence of positive REPP test results at the shin and shinzo points for subjects with acute myocardial infarction (AMI) were extremely high, and positive test results for patients with old myocardial infarction (OMI) and angina pectoris (AP) were also significant. There was no significant difference in the incidence rates of REPP at the shin and shinzo points between the OMI and AP groups. High incidence of positive REPP test results at the lung and heart III (shinyu) points occurred only in the AMI group, and this was significantly high when compared with the control group.

Acupuncture Points↗