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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
1989 Volume 17 Issue 5 Pages
639-658
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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Progress in the study on lipoprotein (a) (Lp (a)) during last 25 years are reviewed. Lp (a) represents a class of plasma lipoprotein particles that have overall characteristics similar to LDL but distinct from them by having apo B-100 linked to apo (a) by disulfide bridge (s). This protein has recently been shown to have a striking amino acid sequence homology with plasminogen. The high incidence of Lp (a) in the plasma of patients with atherosclerotic diseases has been noted by many investigators. The new knowledge being rapidly aquired on the structure and physiological roles of Lp (a) should facilitate the understanding of the mechanism of its atherogenicity and perhaps shed light on its possible pathological roles and treatments.
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[in Japanese]
1989 Volume 17 Issue 5 Pages
659-660
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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Teruhiko MATSUSHIMA, Tamio TERAMOTO, Tsuyoshi WATANABE, Yukio HORIE, H ...
1989 Volume 17 Issue 5 Pages
661-663
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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The cDNA of guinea pig apolipoprotein E was cloned and sequenced. On the comparison of the amino acid sequence of guinea pig apo E to those of other species, possible pi helical conformation was found on the most highly conserved region. Analysis of the synthetic peptide of this region supported the conformation of pi helix and its amphiphilicity.
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[in Japanese], [in Japanese], [in Japanese]
1989 Volume 17 Issue 5 Pages
665-667
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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[in Japanese], [in Japanese], [in Japanese], [in Japanese]
1989 Volume 17 Issue 5 Pages
669-670
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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[in Japanese]
1989 Volume 17 Issue 5 Pages
671-674
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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Kouji KAJINAMI, Hiroshi MABUCHI
1989 Volume 17 Issue 5 Pages
675-678
Published: October 01, 1989
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The LDL receptor gene mutations of FH patients from 190 unrelated Japanese families were screened and the following results were obtained:
1. Four types of new variants were identified through Southern blotting.
i) FH-Tonami-1 with 6 kb deletion (exon 15) was found in 6 families. Neonatal diagnosis of FH in three fetuses from one family was possible through the analysis of their LDL receptor genes.
ii) FH-Okayama with 13kb deletion (exon 7-13) was found in 2 families.
iii) FH-Kanazawa with 12 kb deletion (exon 2 and 3) was found in 1 family.
iv) FH-Tonami-2 with 10kb deletion (exon 2 and 3) was found in 9 families. Abnormal LDL receptors produced by this mutant gene possessed half the activity of normal receptors. Both homozygous and heterozygous patients with this gene mutation showed mild clinical manifestations and longevity influences in comparison with “classical” FH patients.
2. A majority (90%) of Japanese FH patients had small gene mutations in their LDL receptor genes.
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Takanari GOTODA, Nobuhiro YAMADA, Fumimaro TAKAKU, Mototaka SENDA, Yas ...
1989 Volume 17 Issue 5 Pages
679-682
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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Human lipoprotein lipase (LPL) cDNA was cloned from a placental cDNA library using bovine LPL cDNA as a probe. To investigate the genetic basis of familial LPL deficiency, we analyzed profiles of restriction fragment length polymorphism (RFLP) with the 1.6kb cDNA fragment containing a full length of the coding region.
Digestion with restriction enzyme PvuII can identify a two allele polymorphism (A1: 7.9kb, A2: 5.1 and 2.8kb) as reported in Caucasians previously. The distributions of genotypes were, however, very unique and informative for this disease in Japanese. In 50 unrelated controls, 28 showed the A2A2 genotype (A2 homozygote), 22 had the A1A2 genotype (A1A2 heterozygote), but no A1A1 genotype was found.
In contrast, 4 of 8 familial LPL-deficient patients were found to be A1 homozygotes and the rest were A2 homozygotes. No A1A2 heterozygotes were found among the patients. Moreover, all parents of the 4 A1 homozygous patients were A1A2 heterozygotes and co-dominant inheritance was observed in all families. In addition, Southern blot analysis with the segments of cDNA probe located the PvuII polymorphic site between the 5'-2.8kb and 3'-5.1kb fragments.
These results indicate that the PvuII RFLP is a useful marker to analyze genetic defects in the patient families, particularly in Japanese.
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Takayoshi TODA, Masaru NAGAMINE, Hiroshi TAKEI
1989 Volume 17 Issue 5 Pages
683-690
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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Coronary arteriosclerotic lesions were studied with the aid of light microscopy, electron microscopy, immunohistochemistry, and in situ hybridization.
Electron microscopic examination confirmed that smooth muscle cells were the main cellular component of fibrocellular intimal thickening of the coronary artery, and that macrophage and smooth muscle cell type foam cells were located in the superficial and deeper portions of the atherosclerotic lesions, respectively.
Intimal cells in early atherosclerotic lesions reacted more intensely with antibodies for alpha-1-antitrypsin, alpha-1-antichymotrypsin, S-100 protein, calmodulin, and ras and myc oncogene products than did those in coronary arteries with intimal fibrocellular thickening. Lipid-containing macrophages had the largest amount of oncogene products of the ras and myc oncogene.
The presence of m-RNA of the myc oncogene in the intimal cells of early atherosclerotic lesions was also demonstrated by in situ hybridization. These results reflect the dysplastic nature of atherosclerosis, which is based on transformed intimal smooth muscle cells and activated macrophages.
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Yasuhide INOUE, Masanori EZAKI, Takako TOMITA
1989 Volume 17 Issue 5 Pages
691-693
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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The effects of hemostatic substances on the vascular tone and the influence of low density lipoprotein on tension were investigated in porcine coronary arteries. Thrombin induced a marked concentration-dependent relaxation in the prostaglandin F
2α-precontracted strips with intact endothelium, whereas it produced only a modest constriction in endothelium denuded arteries. Methylene blue eliminated the relaxation, but the indomethacin did not affect it significantly. Exposure of the intact strips to low density lipoprotein resulted in a marked inhibition of the relaxation to thrombin, but did not interfere with vasodilation by sodium nitroprusside. Inhibition by low density lipoprotein was reversed completely by washing. In contrast, high density lipoprotein lacked any such inhibitory effects. Adenosine diphosphate, calcium ionophore A23187 and platelet activating factor also produced endothelium-dependent relaxation in the precontracted strips. An exposure of the strips to low density lipoprotein almost completely eliminated relaxation to these substances. The inhibition was also reversible. Heat treatment or acid treatment of the low density lipoprotein resulted in a complete loss of inhibitory effects, but a diisopropyl fluorophosphate treatment did not alter the effect. Therefore, it is concluded that low density lipoprotein may play a new pathological role in promoting coronary vasospasm through the rapid and reversible inhibition of endothelium-dependent relaxation to hemostatic substances.
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Hirokazu KASHIWAGI, Hisako FUSHIMI, Hiroaki HORIE, Bunichiro KISHINO, ...
1989 Volume 17 Issue 5 Pages
695-698
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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We investigated 435 cases of cerebral infarction and hemorrhage (108 were diabetics and 327 were nondiabetics) which were confirmed by computed tomography in the Sumitomo Hospital from 1976 to 1987. Among the 327 nondiabetics, there were 67 cases (20.5%) of hemorrhage and 260 cases (79.5%) of infarction. Among the 108 diabetic patients, there were fewer cases of cerebral hemorrhage, 12 cases (11.1%), and more infarctions, 96 cases (88.9%) than in the nondiabetic patients. Among diabetic patients microangiopathic and neuropathic complications, the ratio of infarctions to hemorrhages was 41 to 8. However in diabetics with neuropathy, the ratio decreased markedly to 24 to 1. These results indicate that the proportion of cerebral hemorrhages to infarctions particularly decreases in diabetic patients with neuropathy.
We have already reported that studies on diabetic rats and humans with autonomic neuropathy have shown impaired catecholamines secretion. We may therefore, conclude that impaired catecholamines secretion may play a role in the decrease of the incidence of cerebral hemorrhage compared to infarctions in diabetic cases.
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Tsunehito SHIRAISHI, Shigeto MORIMOTO, Toshio OGIHARA
1989 Volume 17 Issue 5 Pages
699-701
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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The effect of ticlopidine, an anti-coagulant drug, on the release of platelet-derived growth factor (PDGF) from circulating platelets was examined. Five hundred mg ticlopidine were administered to 5 healthy male volunteers (mean±SD age of 30.0±3.2 years old, range 26 to 34 years old) for seven days. Just before and after administration of the drug, platelet rich plasma (4×10
8 platelets/ml) was obtained and adenosine diphosphate (ADP) was used to stimulate the release of PDGF. The quantity of PDGF released from the platelets was measured by radioimmunoassay. The administration of the ticlopidine significantly (p<0.05) suppressed the release of PDGF induced by 4μM ADP from 4.0±1.3ng/4×10
8 platelets to 0.8±0.2ng/4×10
8 platelets. These results suggest that ticlopidine may suppress the development of atherosclerosis by inhibiting the release of PDGF from platelets.
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Tsunehito SHIRAISHI, Shigeto MORIMOTO, Toshio ONISHI, Toshio OGIHARA
1989 Volume 17 Issue 5 Pages
703-707
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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A mouse monoclonal antibody toward a 73-97 fragment of human platelet-derived growth factor (hPDGF) B-chain was used to develop a radioimmunoassay (RIA) for serum hPDGF. In the single step procedure of the double antibody technique, the measurable range was 10-1, 000ng/ml. The coefficients of variation within and between the series were 10.2% and 12.1%, respectively, and satisfactory dilution curves were obtained for sera from normal subjects. The hPDGF levels in all the plasma samples from the 15 normal subjects examined were below the detection limit (10ng/ml). However, the mean hPDGF concentration (±SD) in serum samples of the 60 normal subjects was 31.9±20.4ng/ml. This value was significantly (p<0.01) higher than the mean for the 21 patients with idiopathic thrombocytopenic purpura (12.6±4.5ng/ml). There was a significant positive (r=0.481, p<0.01), but not strong (r
2=0.23) correlation between the peripheral blood platelet counts and serum hPDGF levels of all the subjects. This RIA system should prove useful for clinically measuring the serum hPDGF.
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Hirotada TAKAI, Toshitaka TAMAI, Ryuichi FUJIWARA, Tsuguhiko NAKAI, Su ...
1989 Volume 17 Issue 5 Pages
709-715
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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It has been reported that endurance-type exercise induces decreased atherogenic profiles of plasma lipids and lipoproteins. Previous studies have shown that the plasma triglycerides and VLDL concentrations are lower and that the HDL is higher in endurance-trained subjects than in sedentary subjects. The aim of the present study was the evaluation of the effect of endurance-type exercise on the metabolism of exogenous lipoproteins. This study uses apolipoprotein (apo) B-48 as a marker. This study compared the plasma lipids, lipoproteins and apolipoproteins and VLDL-apo B subspecies in 19 fasting female distance runners (R) and 23 similarly aged sedentary control women (S). Lipoproteins were fractionated by sequential ultracentrifugation. Apolipoproteins were measured by a single radial immunodiffusion. Apo B subspecies in VLDL (d<1.006g/ml) were analyzed by SDS-3.5% polyacrylamide gel electrophoresis. After staining, the protein bands were evaluated with a densitometer and the peak area was measured. The apo B-48 ratio (percentage of apo B-48 in the total apo B) was calculated. The fasting plasma concentrations of lipids and apolipoproteins were as follows (S vs. R, mg/dl, Mean±SE): triglyceride (TG); 78.5±7.1vs. 66.7±4.4, cholesterol (Ch); 164.4±5.9vs. 189.5±5.6 (p<0.005), HDL-Ch; 69.0±3.5vs. 83.8±3.9 (p<0.01), apo A-I; 160.9±5.0vs. 183.3±5.2 (p<0.005), apo B; 94.6±3.2vs. 101.5±2.7, apo C-II; 3.2±0.2vs. 3.3±0.2, apo C-III; 7.8±0.4vs. 8.6±0.4, apo E; 3.5±0.1vs. 4.6±0.3 (p<0.005). Plasma concentrations of Ch, HDL-Ch, apo A-I and apo E were significantly higher in runners than in the sedentary controls. In lipoprotein fractions, runners had lower VLDL concentrations and a higher HDL than sedentary controls primarily caused by an increase of HDL
2. The apo B-48 ratio in VLDL was significantly (p<0.05) lower in runners (2.86±0.39%) than in the sedentary controls (4.6±0.54). In the sedentary controls, an age-related rise in the apo B-48 ratio was observed. However, such a increase was not observed in runners. Runners showed a tendency toward a positive correlation between the apo B-48 ratio and concentrations of VLDL-TG. Additionally, a significant negative correlation was observed between the apo B-48 ratio and concentrations of HDL
2-Ch. These data indicate that endurance-type exercise decreases exogenous lipoproteins which are most likely mediated by the increase of LPL activities. Some studies have suggested that a chylomicron remnant may contribute to atherogenesis. We speculate that endurance-type exercise favorably affects exogenous lipoprotein metabolism.
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Mitsuaki TAKEDA, Ichiro MICHISHITA, Yoshihide UNO, Akihiro INAZU, Haji ...
1989 Volume 17 Issue 5 Pages
717-724
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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One homozygous and four heterozygous patients with familial hypercholesterolemia received. LDL-apheresis treatment from 1985 to 1987. In the homozygous patient, LDL-apheresis was carried out every 3 or 4 days with a treated plasma volume of 4 liters. In the other four heterozygous patients it was carried out every one or two weeks with 3-5 by dextran sulfate-cellulose-column. The long-term effects of LDL-apheresis on coronary artery stenosis was studied by coronary angiography. The angiographic measurement of coronary artery stenosis was scored on Coronary Atherosclerosis Index (CAI). Treatment by LDL-apheresis maintained mean plasma cholesterol levels between 130 and 180mg/dl, prevented the progression of coronary stenosis and caused the regression of skin xanthomas. All the patients have noted improvement in their angina pectoris after the LDL-apheresis treatment.
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Yukio KISHI, Takashi ASHIKAGA, Takahiro KOBAYASHI, Noriko FURUTA, Mich ...
1989 Volume 17 Issue 5 Pages
725-733
Published: October 01, 1989
Released on J-STAGE: September 21, 2011
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We investigated the erect of bifemelane hydrochloride on human platelet aggregation and platelet cyclic nucleotide metabolism in order to elucidate its mechanism. Bifemelane inhibited platelet aggregation induced by collagen and ADP with an IC
50 value of 6.6×10
-5M and 1.2×10
-4M, respectively. The inhibitive effects of the agent on platelet aggregation increased in the presence of 10
-9M PGI
2. Bifemelane significantly increased platelet adenylate cyclase activity in concentrations of 10
-5M and 10
-4M and inhibited cyclic AMP phosphodiesterase activity with an IC
50 value of 6.6×10
-4M. Cyclic AMP accumulation in intact platelets in response to bifemelane alone significantly increased only in high concentrations of 10
-3M. However, a synergistic effect on cyclic AMP accumulation was found between the bifemelane and PGI
2. Although a concentration of 10
-4M of bifemelane had no effect on guanylate cyclase activity it did attenuate activity at 10
-3M. Bifemelane inhibited cyclic GMP phosphodiesterase activity with an IC
50 value similar to cyclic AMP phosphodiesterase (4.5×10
-4M). Bifemelane up to a concentration of 10
-4M, did not alter cyclic GMP accumulation. However, bifemelane in a concentration 10
-4M did decrease activity.
We conclude that bifemelane hydrochloride inhibits human platelet aggregation by modulating the cyclic AMP metabolism. Synergism between bifemelane and prostacyclin may also contribute to the enhancement of the antiplatelet action of bifemelane in vivo.
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Hiroyuki HIRATA, Takao FUJINAMI, Yoshinori NOGUCHI, Takayoshi ICHIKAWA ...
1989 Volume 17 Issue 5 Pages
735-740
Published: October 01, 1989
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This study was designed to examine the erects of regression on contractile and relaxation responses to vasoactive agents in atherosclerotic rabbit aortas. Twenty-eight male rabbits were separated into four groups as follows: Group (G) I was fed a normal diet for 16 weeks, GII was fed a 1% cholesterol diet for 16 weeks, GIII was fed a 1% cholesterol diet for 16 weeks followed by a normal diet for 16 weeks, GIV was fed a normal diet containing 0.5% probucol for 16 weeks after induction of atherosclerosis as GII. Thoracic) aortas were cut into ring preparations and suspended in an organ bath containing Krebs-Ringer solution. Isometric tensions generated by KCl, histamine (His), norepinephrine (NE) were recorded and the relaxation response to acetylcholine (ACh) was also examined.
The percentile area of atheromatous plaque was 0.91±6, 51±10, 44±6 (mean±SE) respectively in the four groups. The maximum tension developed by KCl was approximately the same in all four groups. The maximum tension generated by His and NE was lower in GII and GIII than in GI, although the same tension was maintained in GIV as in GI.
The maximum relaxation response induced by ACh was 42±6, 14±3, 1.5±0.9, 2.3±1.5, respectively in the four groups when the tension generated by 10
-6 M PGF
2α was defined as 100%.
ED
50 under KCl was lower in GIII than in the other three groups. ED
50 under NE was greater in GII and GIII than in GI. ED
50 under His was the same for all four broups. T 1/2 was increased and dT/dt was reduced in atherosclerotic aortas (GII), and regression was not improved.
Regressed aortas caused by probucol showed recovery of contractile responses to His and NE, but not by a normal diet. The relaxation response to ACh, T 1/2 and dT/dt in regressed aortas-(GIII and IV) were not improved.
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