Biomedical subjects

H Sakane

Publications and source records attributed to H Sakane.

8 recordsLinked to original sources

PubMed1997

Specific reduction of plasma large, light low-density lipoprotein by a bile acid sequestering resin, cholebine (MCI-196) in type II hyperlipoproteinemia.

The effect of a bile acid sequestrant, cholebine (3 g/day), on plasma lipoprotein subfractions was investigated in 16 patients with type II hyperlipoproteinemia. Activities of low density lipoprotein (LDL)-receptor and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were assayed to address the mechanism of cholebine-induced changes in plasma lipoprotein subfractions. Twelve weeks of treatment with cholebine reduced plasma levels of total cholesterol (TC) and LDL-cholesterol (C) by 8.3 +/- 8.1% (mean +/- S.D.) and 14.4 +/- 11.9%, respectively (P < 0.001), but did not affect plasma levels of high density lipoprotein (HDL)-C. Cholebine significantly reduced plasma levels of LDL1-C (1.019 < d < 1.045) by 22.9 +/- 18.9% (P < 0.001) but did not affect plasma levels of very low density lipoprotein (VLDL)-C, intermediate density lipoprotein (IDL)-C, LDL2-C (1.045 < d < 1.063), HDL2-C, and HDL3-C (d > 1.125). Gradient polyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduced large LDL in plasma but had almost no effects on small LDL and HDL subfractions. Cholebine did not alter the activities of LCAT and CETP. LDL-receptor activities of cultured lymphocytes negatively correlated with the reduction in plasma levels of LDL-C (r = -0.500, P < 0.05), IDL-C (r = -0.581, P < 0.02), and LDL1-C (r = -0.610, P < 0.01), respectively. Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activities. We conclude that cholebine only reduces plasma levels of large, light LDL. This may be due to the stimulation of hepatic LDL-receptor activity.

Anticholesteremic Agents↗

PubMed1996

A case of moderate hypertriglyceridemia with apolipoprotein E phenotype E4/3.

Hyperlipoproteinemic subjects with apo(lipoprotein)E4 are usually hypercholesterolemic and those with apoE2 are hypertriglyceridemic. We report a case of moderate hypertriglyceridemia with apoE phenotype E4/3. Plasma levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL)-C, apoAI, apoB, apoCII, apoCIII, and apoE were 200mg/dL, 451 mg/dL, 31 mg/dL, 115 mg/dL, 99 mg/dL, 10.0 mg/dL, 22.2 mg/dL, and 12.0 mg/dL, respectively. Plasma levels of very low density lipoprotein (VLDL)-C and intermediate density lipoprotein (IDL)-C were high, and those of low density lipoprotein (LDL)-C and HDL2-C were low. All lipoprotein subfractions except VLDL were TG-rich. These findings are common in moderate hypertriglyceridemia. The plasma level of remnant-like particle (RLP, equivalent to chylomicron remnant)-C, was high. The lipoprotein lipase which removes TG from chylomicron and VLDL was normal. The activity of LDL receptor which removes remnants of chylomicron and VLDL as well as LDL was high. ApoE4 actively binds to receptors of remnant and LDL. Thus, the removal of TG-rich lipoproteins should not be impaired in this patient. Plasma levels of insulin during oral glucose tolerance test were high. Hyperinsulinism stimulates VLDL synthesis in the liver. Subjects with apoE4 show active synthesis of chyromicron. Thus, we concluded that the moderate hypertriglyceridemia in this E4/3 patient was due to the overproduction of chylomicron and VLDL.

Adult↗

PubMed1995

Effects of simvastatin on plasma lipoprotein subfractions, cholesterol esterification rate, and cholesteryl ester transfer protein in type II hyperlipoproteinemia.

We investigated the effects of simvastatin on plasma levels of lipoprotein subfractions, cholesterol esterification rates and activities of cholesteryl ester transfer protein in 28 patients with type II hyperlipoproteinemia (i.e., nonfamilial hyperlipoproteinemia type IIa and type IIb, and heterozygous familial hypercholesterolemia (FH)). Plasma levels of VLDL-cholesterol (C) and VLDL-triglyceride (TG) were significantly reduced overall by 12.9 +/- 58.0% (mean +/- S.D.; P < 0.05) and 4.2 +/- 54.2% (P < 0.05) respectively, but not in FH. Plasma levels of IDL-C and IDLT-G were decreased overall by 23.2 +/- 47.5% (P < 0.001) and 12.3 +/- 49.7% (P < 0.05), respectively, again mainly due to decreases seen in nonfamilial type II hyperlipoproteinemia. Plasma levels of LDL1 (1.019 < d < 1.045)-C and LDL1-TG were significantly reduced by 33.1 +/- 12.9% (P < 0.001) and 23.3 +/- 24.7% (P < 0.001), respectively. Plasma levels of LDL2 (1.045 < d < 1.063)-C were significantly reduced by 22.9 +/- 18.1% (P < 0.001) overall but not in FH. Gradient PAGE showed no consistent changes in the distribution of LDL particles. Thus, plasma levels of all apo B-containing lipoprotein subfractions were reduced by simvastatin, but its effects varied among the three subgroups. Cholesterol esterification rates were suppressed by 9.3 +/- 19.7% (P < 0.01) and activities of cholesteryl ester transfer protein were reduced by 30.6 +/- 21.5% (P < 0.001). Changes in CETP activity and in plasma levels of cholesterol in lipoprotein subfractions were not correlated. Thus, the changes in distribution of lipoprotein subfractions were not due mainly to CETP suppression.

Adult↗

PubMed1994

Effects of bezafibrate therapy on subfractions of plasma low-density lipoprotein and high-density lipoprotein, and on activities of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in patients with hyperlipoproteinemia.

We investigated the effects of 12 weeks of bezafibrate treatment on plasma lipoprotein subfraction levels and on activities of LCAT and CETP in 25 patients with hyperlipoproteinemia. Bezafibrate reduced plasma levels of VLDL-TC and VLDL-TG by 69% and 66% (P < 0.001) and plasma levels of IDL-TC and IDL-TG were decreased by 37% and 31% (P < 0.01). Bezafibrate had no significant effects on plasma levels of LDL1 (1.019 < d < 1.045)-TC and LDL1-TG in the study population as a whole but significantly increased the plasma level of LDL1-TC in the subgroup of 9 patients with type IV hyperlipoproteinemia. Bezafibrate reduced plasma levels of LDL2 (1.045 < d < 1.063)-TC, LDL2-TG by 48% and 44% (P < 0.001) in both type II and type IV hyperlipoproteinemic patients. Gradient polyacrylamide gel electrophoresis revealed a decrease in small LDL particles. Bezafibrate did not affect the plasma level of HDL2-TC but reduced the HDL2-TG concentration significantly (P < 0.001). Bezafibrate increased the plasma level of HDL3-TC by 37% and reduced the HDL3-TG level significantly by 20% (P < 0.001). Gradient polyacrylamide gel electrophoresis revealed an increase in HDL3a and a decrease in HDL2a. Bezafibrate suppressed the activities of LCAT and CETP by 21% (P < 0.001) and 17% (P < 0.01), respectively. The bezafibrate-induced decrease in plasma levels of small, heavy LDL might be related to its inhibition of LCAT and CETP activities which resulted in suppression of heteroexchange of HDL-EC with triglyceride in large, light LDL. The bezafibrate-induced increase in large HDL3 (HDL3a) could not be explained solely by its suppression of LCAT and CETP activities. The decrease of plasma small, heavy LDL as well as TG-rich lipoproteins by bezafibrate seems to be beneficial for prevention of atherosclerotic diseases.

Adult↗

PubMed1993

Antithrombotic effect of an anti-glycoprotein IIB/IIIA antibody in primate lethal thrombosis.

We investigated the antithrombotic effect of anti-glycoprotein (GP) IIb/IIIa antibody in a primate model of lethal thrombosis. Eight monkeys were injected intravenously with an anti-CD9 antibody (MALL13). They died within 5 min and displayed severe thrombocytopenia. Histological examination showed multiple platelet thrombi in the pulmonary microvasculature, but no thrombi in the liver, kidneys, or spleen. In contrast, monkeys pretreated with an anti-GPIIb/IIIa antibody (NNKY1-32) at 30 min before MALL13 administration did not die, and the thrombocytopenia in these animals did not develop as rapidly or become as severe. These results suggest that the antiCD9 antibody caused lethal pulmonary thrombosis in vivo, and that pretreatment with the anti-GPIIb/IIIa antibody was able to prevent this thrombosis.

Animals↗

PubMed1993

Decrease of plasma large, light LDL (LDL1), HDL2 and HDL3 levels with concomitant increase of cholesteryl ester transfer protein (CETP) activity by probucol in type II hyperlipoproteinemia.

The effects of 12 week probucol treatment on plasma lipoprotein subfraction levels and on lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities in type II hyperlipoproteinemia were investigated. Plasma VLDL-TG, VLDL-apoB, VLDL-apoCII and VLDL-apoCIII concentrations were not changed by probucol, but VLDL-TC and VLDL-PL levels were slightly reduced. Probucol slightly reduced plasma IDL-TC, but not IDL-TG, IDL-PL and IDL-apoB levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL, LDL1-apoB levels were decreased significantly by 28.5 +/- 20.1% (p < 0.001), 18.1 +/- 18.8% (p < 0.01) and 23.3 +/- 19.1% (p < 0.001) by probucol treatment while LDL1-TG concentration was unchanged. Absolute amounts of plasma small, heavy LDL(LDL2)-TC, LDL2-TG, LDL2-PL and LDL2-apoB levels remained unchanged but percent increases of LDL2-TC and LDL2-apoB were statistically significant (p < 0.05). 2-16% gradient polyacrylamide gel electrophoresis demonstrated the diminution of LDL of large size by probucol treatment. Probucol markedly reduced plasma high density lipoprotein levels. The reductions of HDL2-TC, HDL2-TG, HDL2-PL and HDL2-apoAI concentrations were 36.2 +/- 25.4% (p < 0.001), 25.8 +/- 36.9% (p < 0.01), 34.4 +/- 23.8% (p < 0.001) and 35.6 +/- 28.4% (p < 0.001). Probucol significantly decreased plasma HDL3-TC, HDL3-PL and HDL3-apoAI amounts by 17.4 +/- 22.9% (p < 0.01), 18.3 +/- 20.8% (p < 0.01) and 19.8 +/- 27.9% (p < 0.01) without change of HDL3-TG level. The decrease of HDL2 level was more marked than that of HDL3 level. Probucol did not change LCAT activities. Probucol significantly stimulated CETP activities from 126.6 +/- 50.6 units to 172.8 +/- 40.2 units by 12 week treatment (p < 0.001). We concluded that probucol decreased plasma LDL1, HDL2 and HDL3 amounts and made them triglyceride-rich with the concomitant increase of CETP activities.

Carrier Proteins↗

PubMed1991

Effects of probucol on plasma lipoprotein subfractions and activities of lipoprotein lipase and hepatic triglyceride lipase.

The effects of 12 weeks treatment with probucol on plasma lipoprotein subfraction levels and on LPL and HTGL activities were investigated. Plasma VLDL-C, VLDL-TG, VLDL-apo B levels were not changed. Probucol significantly reduced plasma IDL-C and IDL-apo B levels by 26.7% and 23.8%, respectively. Plasma cholesterol and apo B levels of large light LDL (LDL1) were decreased significantly by 27.8% and 23.2% by probucol treatment. Plasma cholesterol and apo B levels of small heavy LDL (LDL2) remained unchanged. Probucol markedly reduced plasma HDL2 levels. The reduction rates of plasma TC, TG and apo A-I levels of HDL2 were 43.0%, 43.6% and 47.0%. Probucol significantly decreased HDL3-C and HDL3-apo A-I levels by 18.0% and 19.2%. LPL activities in the post-heparin plasma were decreased significantly from 2.53 +/- 0.71 mumol free fatty acids (FFA)/ml/h to 1.71 +/- 0.71 mumol FFA/ml/h by probucol while HTGL activities remained unchanged. We conclude that probucol suppresses LPL activity and decreases plasma IDL, LDL1 and HDL2 levels due to disturbances of VLDL conversion to LDL1 via IDL and of HDL3 conversion to HDL2.

Aged↗

PubMed1991

Inhibition of platelet aggregation by low concentrations of sodium fluoride. Significance of the intracellular calcium ion concentration.

Sodium fluoride activates platelets but its mechanism of action has not yet been completely identified. We examined the effect of a low concentration of sodium fluoride (which could not cause aggregation) on thrombin-induced changes in the intracellular calcium ion concentration ([Ca2+]i). In the presence of 1 mM extracellular Ca2+, preincubation with a low concentration of sodium fluoride decreased the peak of the thrombin-induced elevation of [Ca2+]i, when measured with aequorin. When [Ca2+] was measured using fura-2, preincubation caused no marked changes in its peak, but the later changes that were thought to mainly reflect extracellular Ca2+ influx were inhibited. The inhibitory mechanism of sodium fluoride appears to depend on reducing extracellular Ca2+ influx. Aequorin appears to reflect [Ca2+]i near the cell membrane and is thus easily affected by the extracellular Ca2+ influx.

Blood Platelets↗