We studied the relationship between coronary stenosis and midband, which was observed between pre- and β-lipoproteins, examined by 3% polyacrylamide gel electrophoresis in familial hypercholesterolemia (FH). Subjects were 95 patients with FH, in whom 28 patients were evaluated by coronary angiography. Stenosis score was expressed as the sum of stenosis points of each fifteen AHA segments of coronary artery. The stenosis score and the frequency of ischemic heart disease (IHD) in midband-positive group were higher than those in midband-negative group. There were no significant differences in the levels of serum total cholesterol, triglyceride, lipoproteinlipids, or apoproteins except apo E, between midband-positive group and midband-negative group. Only the level of apo E was higher in midband-positive group. The results suggest that the presence of midband is one of risk factors for coronary stenosis in familial hypercholesterolemia.

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Biosynthesis and secretion of HTGL were investigated by using human hepatoma cell line, Hep G2. The cells were labeled with ³⁵S-methionine and the labeled HTGL was specifically immunoprecipitated with monospecific anti-human HTGL antibody. The immunocomplexes were analized by SDS-PAGE and autofluolography. Hep G2 was cultured in the presence and absence of heparin. Two distinct labeled HTGL protein band having molecular size of 62kDa and 65kDa were detected in cells, but no HTGL protein band was observed from culture medium in the absence of heparin. The synthesized HTGL protein (65kDa) was released with heparin (10 units per ml) into the culture medium, while the HTGL protein (62kDa) was not released. These results suggested that HTGL was synthesized as a catalytically active form having a molecular size of 62kDa protein and posttranslationally processed to the 65kDa protein which is released by heparin.

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In this study, we investigated the effect of cumene hydroperoxide (CH), which initiates lipid peroxidation, on the adherence of cultured bovine vascular cells and the protective effects of antioxidants such as α-tocopherol (VE) or idebenone on adherence injury induced by CH.
1) CH induced the adherence injury to endothelial cells (EC) and smooth muscle cells (SMC) dose-dependently.
2) The concurrent addition of CH and either VE or idebenone to cell suspension showed that these antioxidants had an effect on the prevention of the adherence injury to EC but had little effect on SMC.
3) Either VE or idebenone had an effect on the prevention of the adherence injury to EC or SMC induced by CH after 24hrs preincubation, and VE also had still an effect on EC after 4hrs preincubation, but had no effect on SMC after only 4hrs preincubation.
These results suggest that oxidative stress induces vascular cell damage and may play a role in the pathogenesis of atherosclerosis, and that antioxidants may prevent the initiation and progression of atherosclerosis.

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Incubation of porcine aortic endothelial cell cultures with 4-methylumbelliferyl-β-D-xyloside resulted in a reduction of ¹²⁵I-antithrombin III binding to cells. When the amount of antithrombin III specifically bound was measured as a function of antithrombin III concentration, it was indicated that the maximum amount of antithrombin III binding was reduced by approximately 65% with little alteration in binding affinity. Reduction of ¹²⁵I-antithrombin III bound to the surface of endothelial cells after exposure to various concentrations of xyloside occurred in parallel with the decrease in biosynthesis of radiolabeled heparan sulfate on the cell surface. Characterization of heparan sulfate molecules derived from cell surface fractions revealed that a size of the molecule was not altered by β-D-xyloside treatment, although they appeared to have slightly less net negative charge and a significantly reduced proportion of the molecule with high affinity for antithrombin III in the presence of xyloside. On the other hand, free chondroitin sulfate polysaccharide chains were markedly increased in the medium from β-D-xyloside-treated endothelial cell cultures. These results suggest that β-D-xyloside treatment of endothelial cells caused a dose-dependent decrease in production of cell surface heparan sulfate, which could serve as antithrombin III binding sites on endothelial cells.

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The proliferation of bovine aortic SMC was increased by hyperlipidemic LDL (HL-LDL) (44μg/ml as cholesterol) obtained from the Dextran Sulfate Cellulose Column (KNA-01) after plasmapheresis. The effects of heparin (HP) and glycosaminoglycans (GAGs) on the proliferation of bovine aortic SMC by HL-LDL were studied. Heparin suppressed the proliferation of both SMC cultured in DME with 5% FCS and with 5% FCS containing HL-LDL in a dose response manner. Although the suppression of increased proliferation of SMC by GAGs (except HA) was less marked than that of heparin, the effects of GAGs were more susceptible to the cells proliferated by HL-LDL in contrast to the results obtained by heparin. It is suggested from these results that GAGs might suppress the specifically the proliferation of SMC by HL-LDL, and that sulfated GAGs could be used as antiatherogenetic agents.

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Cholestyramine was given orally (4g twice or three times/day) to nineteen diabetic patients to clarify its efficacy on glycemic controls. In thirteen outpatients, fasting plasma glucose levels were decreased significantly from 185.0±7.9mg/dl (mean±SEM) to 154.5±9.4mg/dl after 3 months and its percent change was 16% (p<0.01). Glycated hemoglobin (HbA_1c) levels were decreased significantly from 7.8±0.4% to 6.8±0.4% after 3 months and its percent change was 13% (p<0.01). Serum cholesterol levels decreased significantly from 243.0±15.5mg/dl to 213.8±15.0mg/dl after 3 months (p<0.01). There was no correlation between percent changes of plasma glucose or HbA_1c and those of serum cholesterol. In six inpatients, daily glycemic profiles and the levels of 24 h-urinary glucose excretion were improved by cholestyramine administration for 2 weeks. Constipation was observed in 3 patients and mild increase in serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase or triglyceride levels were observed in 7 patients, but cholestyramine was well tolerated. Cholestyramine seems to be useful for the improvement of glycemic controls in diabetic patients.

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1) We developed a new technique for detecting lipid peroxide (LPO) in lipoprotein fractions. For LPO detection, MCDP method was used. For separation of lipoprotein fraction, high-performance liquid chromatography (HPLC) was used.
2) In this study, we investigated the effect of antioxidants upon the distributions of LPO in modified serum. To increase the content of LPO, we stored sera for 8 weeks at -40°C. For antioxidants, Vitamin C (10^-4M) and γ-oryzanol (500μg/ml) were selected.
3) By storage, total LPO content increased, whereas antioxidants reduced such increase.
4) By HPLC, in the stored serum, an additional peak of LPO was observed, which was thought to be located in LDL-fraction. Antioxidants reduced the height of the additional peak, but not that of the original peak.

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Evening primrose oil (EPO) contains of ca 9 of γ-linolenic acid which is an intermediate of linoleic acid to arachidonic acid. Recently, it has been reported that EPO decreases the level of plasma cholesterol in rats. In order to elucidate the effect of EPO on lipid metabolism, we administered orally EPO to patients with hyperlipidemia and compared the effect with that of safflower oil (SFO). Using cross-over method, we divided the 21 patients aged 42-63 years old into two groups. One group intook 3g of EPO/day for 8 weeks and then the same amount of SFO for following 8 weeks, and the other group intook the same kinds of test oil in reverse order. Lipid and fatty acid composition in the plasma and red blood cells were determined. We could not see much differences of the plasma cholesterol, but triglycerides and VLDL-cholesterol in plasma significantly increased and LDL-cholesterol decreased significantly by the administration of EPO. EPO increased the level of dihomo-γ-linolenic acid in plasma and red blood cells, but the content of arachidonic acid was not changed. These results suggested that EPO could decrease the atherogenic index and improve lipid metabolism in hyperlipidemia.

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The present study demonstrated that human promyeloleukemic cells, HL-60, expressed LDL receptor while differentiating into macrophages by phorbor myristate acetate or 1α, 25(OH)₂D₃. The extent of expression of the receptor on differentiated HL-60 cells was analysed by flow cytometry after stained with monoclonal antibodies to LDL receptor (C7) and FITC-conjugated goat anti-mouse IgG. Blocking of protein synthesis with cyclohexamide reduced the expression whereas inhibition of DNA synthesis with hydroxyurea did not.

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Recently Lipsky et al. developed a simplified method to detect LDL receptor defects by the measurement of lymphocytes proliferation depending on exogeneous LDL cholesterol under the condition that sterol biosynthesis was suppressed with mevinolin. We examined with CS-514, a HMG-CoA reductase inhibitor, instead of mevinolin, whether their method could be available for detection of LDL receptor defects in peripheral lymphocytes of familial hypercholesterolemia (FH) or not.
The mitogen stimulated proliferation of lymphocytes from a homozygous FH patient was significantly impaired comparing with those of normal controls and hyperlipidemic controls. But the difference of proliferation pattern of lymphocytes between heterozygous FH patients and normal controls was not significant.
This method has several merits, comparing with conventional radioreceptor assay, that it is easy to obtain peripheral lymphocytes, and ³H-thymidine is stable for long time and economical. Therefore further study is needed for application to detect heterozygous FH patients clearly.

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In order to clarify the effect of glomerulonephritis and hypercholesterolemia in atherogenesis, Masugi nephritis was induced in male Wistar rats fed a high cholesterol diet, containing 2% cholesterol and 0.5% cholic acid in a standard diet. Three groups of rats served as controls: (1) agematched, untreated normal rats, (2) Masugi nephritis-induced rats, (3) rats fed a high cholesterol diet. Experimental rats showed a high excretion of protein in the urine. Elevation of systolic blood pressure was slight, and moderate to marked increase in serum lipids and lipoproteins was observed. All experimental rats showed foam cells in the glomerular tufts. In electron microscopic study, foam cells were located in the mesangial matrix and subendothelium of the glomerular capillary. Aorta showed edematous intimal thickening. Experimental rats exhibited the greatest degree of edematous intimal thickening as well as the highest incidence of intimal lesions compared to control groups. Ultrastructural observation of aortic intima displayed a widening of the subendothelial space suggesting an early arteriosclerotic change.
These results suggest an additive effect of glomerulonephritis to hypercholesterolemia promotes the development of aortic intimal lesion in rats.

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The levels of serum apolipoproteins, lipoproteins and lipids in 36 patients undertaking coronary angiography were measured and their relations with the severity of coronary stenosis were evaluated.
Also, correlation between variables of stenosis (+) group and those of stenosis (-) group were evaluated.
There was a significant positive correlation between the severity of coronary stenosis and the serum level of apolipoprotein B (p<0.05).
The serum apolipoprotein B was significantly higher in the stenosis (+) group (p<0.05).
Apolipoprotein B/apolipoprotein A-II ratio in serum was also significantly higher in the stenosis (+) group (p<0.01).
The serum HDL₃ showed significantly lower level in the stenosis (+) group. From these findings apolipoprotein B may be an atherogenic factor and HDL₃ may be a antiatherogenic factor. Moreover, there were significant positive correlations both between the serum HDL₂ and apolipoprotein A-I and between the serum HDL₃ and apolipoprotein A-II, suggesting that they would have some relations one another.

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The relationship between risk factors such as hyperlipoproteinemia, diabetes mellitus (DM) or hypertension and the severity of atherosclerosis in coronary artery and abdominal aorta was investigated in 65 patients of coronary heart disease (CHD). The coronary stenosis index (CSI) was significantly correlated with the number of affected major coronary arteries (75% or more stenosis) and also with the wall thickening and stenosis index of the lower abdominal aorta assessed by the enhanced computed tomography (SI). All of 13 CHD patients with familial hypercholesterolemia (FH) were under 60 years of age, and SIs of them were not so high as CSIs. Hyperremnantemia defined as 200mg/dl or more of mid-band lipoprotein concentration became a risk factor of CHD such as single or double vessel disease occured in middle ages. Eleven of 19 patients of DM with low or intermediate insulin response on 75g oral glucose tolerance test reached CHD at 60 years or later, of whom 10 were suffered from double or triple vessel diseases with high score of SI. No correlation was seen between CSI and age in CHD group, but SI was significantly correlated with age (p<0.05).
In conclusion, hyperlipoproteinemia appeared from childhood was considered to make the progression of coronary atherosclerosis selectively, resulting in the occurence of CHD in comparative younger age, while DM, manifested mostly after 40 years of age, frequently got triple vessel disease as a result of general atherosclerosis with severe atherosclerotic change of abdominal aorta in 60 years or older.

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The relationship between the duration of obesity and atherosclerosis was examined in the aged. The subjects were 369 men and women over 60 years old who were autopsied in the Yokufukai Geriatric Hospital. The results showed that: 1. The mean age of death was independent of the duration of obesity. 2. A great number of cases with diabetes mellitus were observed in the group of obesity in old life, and the incidence of hypercholesterolemia was significantly higher in the group of obesity since adult life. On the other hand, there was no difference in the number of cases with hypertension among each group. The high frequency of cigarette smokers were observed in the lean groups. 3. The incidence of marked cerebral atherosclerosis was higher in the group of obesity since adult life than that of either lean in old life or normal weight in old life. There were no differences in the incidence of atherosclerosis of aorta, coronary artery, femoral artery or renal artery among any groups. There were no differences in the incidence of fatal cerebral vascular disease or myocardial infarction among any groups. The results may indicate that the long duration of obesity is a risk factor for cerebral atherosclerosis in the aged.

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Mononuclear phagocytes are recognized as important cells in antigen handling, immune regulation and effector functions against microorganisms and atherosclerosis. Various in vitro assays are available for evaluation of blood monocyte function in patients. Many investigators have studied various aspects of the macrophage function. However there is a poorly defined relationship between the macrophage function and agings concerning the host defense mechanism. It is well known that aging is one of the most important risk factor for developing and progressing atherosclerosis. In this paper we have tried to clarify the relationship between the macrophage function of the human peripheral monocyte and the scavenger for atherosclerosis.
Monocytes were separated from peripheral venous blood (10ml) of healthy young adults (20-40 years) and elderly persons (60-93 years).
Phagocytic assay of monocytes was performed by using fluorescence latex beads. Monocytes were incubated for 1 hour at 37°C with fluorescence latex beads (0.51μm). 0.2ml of incubation mixture dropped onto the object glass was dried. The glass was washed by propylen oxide to remove extracellular latex beads. The clean macrophages without contamination of non phagocytized beads were digested with 0.3% trypsin solution. The latex beads were quantitatively extracted with propylen oxide after trypsin digestion. The fluorescence of extracted solvent was determined by fluorescence spectrophotometry (the wave length of excitation 440nm, emission 510nm). The phagocytic activity was calculated by the standard curve of fluorescence latex beads. The phagocytic activity tested with fluorescence latex beads was powerful in the young but weak in elderly (p<0.005).
A new attempt to produce a cell with lipidsinclusion in vitro was carried out. Monocytes were incubated for 12 hours at 37°C with hypercholesterolemic (total cholesterol 400mg/dl) sera, and the macrophage samples were embedded in eppon after incubation. The electron micrograph of incubated monocytes with hypercholesterolemic sera showed the appearance of cells with lipid inclusion bodies only in samples from the young. These results suggested that human monocytes from young persons act as scavengers in vitro, and are similar to the macrophage in subendothelial space within human arteries. There is a decrease in the activity of scavengers, paralleling the phagocytic function of the human monocyte with aging.

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A core lipid transfer protein (LTP) from human plasma was purified 16, 000 fold by acid-dextran sulfate precipitation in the presence of 17% ethanol, Phenyl-Sepharose, DEAF-Sephadex, Succinylated LDL-Sepharose, and Hydroxyl Apatite column chromatographies. The purified LTP showed a single band with an apparent molecular weight of 65, 000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Anti human LTP IgG was prepared from rabbit anti-serum. There was a single precipitation line between purified LTP and anti human LTP IgG by the Ouchterlony double-diffusion method. No visible precipitation line was seen between anti LTP IgG and apo D, apo A-I, apo A-II, human serum albumin, or lecithin-cholesterol acyltransferase. Addition of anti LTP IgG to the assay mixture containing purified LTP or plasma as a LTP source resulted in 100% inhibition of lipid exchange activity.
These results suggest that core lipid transfer protein in human plasma may be a single protein.

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The purpose of the present study is to elucidate the influences of an artificial fat emulsion (Intralipid®) on serum lipoproteins, particularly the HDL subfractions, in vivo.
Six healthy men participated in this study. After a 14-hour overnight fast, 300ml of a 10% fat emulsion was infused into an antebrachial vein for 4 hours. Blood was obtained before (0hr) and at 4 hours (4hr) and 6 hours (6hr) after the start of the Intralipid® infusion. Serum lipoproteins were separated by sequential ultracentrifugation. Lipid concentrations in serum and lipoprotein fractions were measured enzymatically. Proteins were determined by the method of Hartree and apolipoproteins (A-I, A-II, C-II and C-III) were measured by the SRID method. HDL particle size was determined by gradient gel electrophoresis. Statistical analysis was accomplished by the paired t-test.
Triglyceride (TG) in serum, chylomicron (chylo), VLDL and HDL increased significantly by 4hr but decreased significantly by 6hr. Similarly, Phospholipids (PL) in serum, chylo, VLDL, LDL and HDL showed a significant increase at 4hr and a decrease by 6hr especially in the serum and chylo. Free cholesterol (FC) in serum, chylo and VLDL was elevated at 4hr and then decreased by 6hr. Esterified cholesterol (EC) in chylo and VLDL was increased at 4hr (Table 1).
TG, FC, PL, Protein and total mass (TG+FC+EC+PL+Protein) of HDL₂ were increased significantly at 4hr and decreases were observed at 6hr. In HDL₃, TG increased and PL remained unchanged while FC and EC decreased significantly at 4hr (Table 2). Apo A-I and A-II levels in HDL₂ increased, but those in HDL₃ decreased by 4hr. Contrarily, apo A-I and A-II in HDL₂ decreased and those in HDL₃ increased by 6hr (Table 3). Decrease of apo C-II, C-III in HDL₂ and HDL₃ and elevations of those in chylo and VLDL were observed at 4hr. However, these changes were reversed at 6hr (Table 4). The particle size of HDL₂ and HDL₃ had increased at 4hr but had decreased by 6hr (Figs. 1, 2). From these results, it was suggested that exchanges of polar and non polar lipids, and the circulation of apo C-II and C-III between the fat emulsion and HDL might occur. Furthermore, changes of constituents, especially apo A-I, A-II and particle size in HDL subfractions might reflect the conversion of HDL₃ to HDL₂ and the reverse conversion of HDL₂ to HDL₃.

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Metabolism of acetyl low density lipoprotein (Ac-LDL) and β-very low density lipoprotein (β-VLDL) was studied in macrophage cell lines; U-937, J774.1, and P388D₁ to establish a system to detect atherogenic lipoproteins in disease states. J774 cell line degraded ¹²⁵I Ac-LDL and incorporated ¹⁴C oleate into cholesterol ester in the presence of Ac-LDL, but other two cell lines and cultured human fibroblasts did not. All three cell lines and fibroblasts degraded ¹²⁵I β-VLDL. ¹²⁵I β-VLDL degradation was completely replaced with 160μg/ml native LDL in P388 and fibroblasts, but not in J774 and U-937 cell lines by even 500μg/ml LDL. ¹⁴C oleate was incorporated into cholesterol ester in all three macrophage cell lines and fibrobalsts in the presence of β-VLDL. J774 cells incorporated ¹⁴C oleate more than 10 folds in the presence of β-VLDL compared with in the presence of the same concentration of LDL, while P388 and fibroblasts incorporated oleate 4-5 folds. No cell line incorporated oleate in the presence of glycated LDL.
These results indicate that J774 may be an useful cell line to detect abnormal lipoproteins appearing in various disease states, and also suggest the presence of functionally specific receptor for β-VLDL in J774 cell lines.

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The present study was designed to evaluate the effect of polyenephosphatidylcholine (PC) on plasma lipid metabolism and lipid content in the liver of monosodium glutamate (MSG)-induced obese rats. Three groups (control group, MSG group and MSG-PC group) of male and female rats of Wistar strain were studied. MSG group and MSG-PC group were injected subcutaneously with a daily dose of MSG 4mg/g body weight for 5 days, beginning on the first day after birth. MSG-PC group was administered orally with a daily dose of PC 0.25mg/g body weight from 8th to 20th week after birth. MSG group and MSG-PC group revealed a marked increase of plasma triglyceride concentration and a slight but significant increase of total cholesterol and phospholipids concentrations in both male and female rats. There was no significant difference in plasma lipid concentrations between MSG group and MSG-PC group. Triglyceride content in the liver was significantly increased in MSG group than in control group in both male and female rats. Furthermore, triglyceride content in the liver was significantly decreased in MSG-PC group than in MSG group in male. There was no remarkable change in total cholesterol and phospholipids content in the liver among three groups. These results suggest that PC suppresses fatty liver in male MSG rats.

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The activities of phosphatase have been reported to increase with the development of atherosclerosis. This increase in phosphatase activity during atherogenesis suggests that phosphatases may be associated with the development of atherosclerosis. For this reason, phosphatases of the cultured rat aortic smooth muscle cells have been investigated. The alkaline phosphatase activity in cultured smooth muscle cells decreased drastically within primary culture and decreased gradually with subculture, whereas the acid phosphatase activity increased. In the arterial wall several alkaline phosphatases may change their activities with the development of atherosclerosis. Therefore, in order to know the type of alkaline phosphatase of the aorta, properties of that of the aorta were compared with those of the liver and intestine. Unlike human alkaline phosphatases, rat alkaline phosphatases of the aorta, liver and intestine showed no distinct differences in property. Acid phosphatase activities of smooth muscle cells cultured in the medium with various concentrations of Mg were virtually the same at any concentration of Mg. However, those in the medium with the physiological concentration of P and without P were high and enzyme activities were increased by 10% of the physiological concentration of Ca, Ca antagonists and chelating agents. Enzyme activities were also increased by the addition of chloroquine and sucrose to the medium, suggesting that these enzymes may be associated with lysosomes. These results suggest that low concentrations of extracellular Ca may enhance lysosomal function.

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We determined the correlation between the status of coronary atherosclerotic heart disease (CAHD) risk factors and aerobic power, and provided the threshold level of aerobic power to keep the CAHD risk factors to lower level. We measured the aerobic power (predicted maximal oxygen uptake per kilogram of body weight: VO₂ max/wt), percent body fat (%Fat), blood pressure (SBP/DBP), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and TC/HDL-C ratio in 123 healthy male aged 22 to 70 years.
Significant correlations were observed between VO₂ max/wt and CAHD risk factors except TC (p<0.001). The partial correlations adjusted for age and %Fat between VO₂ max/wt and TG (p<0.001), HDL-C (p<0.01) and TC/HDL-C ratio showed significant correlations (p<0.05). VO₂ max/wt corresponding to border line values of CAHD risk factors were similar values. The highest VO₂ max/wt (36.6ml/kg·min) was adopted as the lowest aerobic power level (critical point: CP) which is necessary to keep CAHD risk factors at low level. Then, the subjects were divided into good group (above CP) and poor group (below CP) by using CP. Good group showed significant lower %Fat, SBP, DBP, TG and TC/HDL-C ratio than those of poor group (p<0.001), while HDL-C was higher in good group than in poor group (p<0.001). Good group had one or two CAHD risk factors, whereas poor group had more than three CAHD risk factors. The subjects with ischemic change on ECG were mainly observed in poor group. These results suggest that predicted VO₂ max/wt (36.6ml/kg·min) corresponding to the borderline values of CAHD risk factors is a useful parameter of CAHD risk factors.

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We screened abnormal alleles of the low density lipoprotein receptor (LDLR) gene in 35 unrelated Japanese patients with heterozygous familial hypercholesterolemia (FH), and obtained the results as follows;
1. A new variant of LDLR gene that had a 6kb deletion was found in two patients (S. O. and K. Y.).
2. We could make a neonatal diagnosis of FH in the two babies in the family of S. O. by checking this deletion in the LDLR gene.
3. S. O. and K. Y. might have a common ancestor despite no relation between their studied family pedigrees.
We designated the patient with this new mutant LDLR gene as “FH-Tonami” as both of their birthplaces were in Tonami district of Toyama prefecture in Japan.

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Hemorrheological studies were carried out on the blood sampled from the cubital veins (CV), the femoral veins in the occlusive limbs (FV), and the femoral arteries in the non-occlusive limbs (FA) of the patients with arteriosclerosis obliterans (ASO). The passage time through the Nuclepore membrane with the pore size of 5νm was measured on the whole blood, plasma, and 40% red blood cell (RBC) suspension. The viscosity was measured on the whole blood and plasma by Low Shear-30® (Contraves) at the shear rate of 94.5sec^-1.
The passage time of the whole blood sampled from CV, FV, and FA were significantly longer than that from CV of healthy subjects. The passage time of 40% RBC suspension was significantly longer only in FV. The whole blood viscosity in CV, FV, and FA was not significantly different from that in CV of healthy subjects. However, the whole blood viscosity and hematocrit were significantly longer in FV and FA than in CV of the patients of ASO. Good correlations were observed on each hemorrheological parameter among three sites in ASO patients.
These results show that hemorrheological changes are the greatest in FV, and the passage time of the whole blood changes most sensitive in the patients of ASO. The hemorrheological parameters in CV probably reflect the hemorrheological change in ASO patients.

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Aortic pulse wave velocity (PWV) is one of the non-invasive methods for diagnosis of atherosclerosis. We discussed the usefulness of this method in a few pathological conditions.
The subjects were 227 diabetic patients, 48 heterozygotes of familial hypercholesterolemia (FHC) and 185 patients undergoing chronic hemodialysis for chronic renal failure. PWV was measured by the method of Hasegawa et al.
In diabetic patients, the PWV showed statistically significant and positive correlation with age (r=0.288; p<0.01), suffering period (r=0.239; p<0.01), serum triglyceride (r=0.155; p<0.05) and Hb A₁ (r=0.142; p<0.05). As for serum cholesterol, the PWV showed a slight but not statistically significant increase according to its increment. The PWV in patients whose serum HDL cholesterol level were lower than 50mg/dl was significantly faster than that of patients whose levels were higher than 50mg/dl.
In FHC patients, the PWV showed statistically significant and positive correlation with age (r=0.601; p<0.01). But, the PWV was normal in FHC patients younger than sixty. The PWV of hypertensive FHC patients was significantly faster than that of normotensive FHC patients.
In chronic hemodialysis patients, the PWV showed statistically significant and positive correlation with diastolic blood pressure (r=0.228; p<0.05). We followed the PWV of each cases for three years. The PWV increased six times faster in chronic hemodialysis patients than in normal controls.

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It is well known that the increase of serum cholesterol causes the accumulation of cholesterol ester (CE) in aortas and that lowering serum cholesterol level prevents atherosclerosis. But the precise relationship between serum cholesterol level and CE accumulation in the aortas is not clear. The purpose of this study is to clarify the relationship between serum cholesterol level and CE content of rabbit aortas, and to clarify whether CE content of aortas is lowered by some mechanisms other than lowering serum cholesterol level. When serum cholesterol level is increased linearly with feeding period, it is suggested that cholesterol exposure to aortas is expressed as (serum cholesterol)×(feeding period)×1/2 and so we named (serum cholesterol level)×(feeding period)×1/2 as accumulated cholesterol index. To clarify the relationship between accumulated cholesterol index and CE content of aortas and effects of EPL on lipid accumulation in the aortas, rabbits were fed on 0.5% cholesterol diet for 8-20 weeks with or without EPL. The relationship between accumulated cholesterol index and CE content of aortas on high cholesterol diet was not linear, but CE content was increased steeply when accumulated cholesterol index ranged from 500 to 3, 000 and CE content was increased slowly when the index was below 500 or over 3, 000. If the effect of EPL is only to the decreased serum cholesterol level, CE content of aortas with EPL will be estimated by the relationship between accumulated cholesterol index and CE content. But the relationship between accumulated cholesterol index and CE content of aortas with EPL was deviated and CE content with EPL was lower than CE content estimated by the relationship between accumulated cholesterol index and CE content. These results suggested that CE content of aortas is decreased by EPL not only by the mechanism of lowering serum cholesterol level but also by some mechanisms other than lowering serum cholesterol level.

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Cholestyramine, an anion exchange resin, is a hypolipidemic drug widely used as the bile acids sequestrant and Lipid Research Clinics Program reports showed its clinical benefit reducing the risk of coronary heart disease due to the decrease in total and LDL cholesterol in the serum (1984).
As MCI-196 a water insoluble anion exchange resin with an imidazolium base as a functional group on copolymer of epichlorohydrin and 2-methylimidazol, the hypolipidemic effects of MCI-196 were examined in both basal and 0.67% cholesterol diet fed rabbits (male New Zealand White strain) compared with cholestyramine. After cholesterol diet feeding for a week, the oral administrations of resins once a day were performed following 2 weeks at dosages of 125 and 500mg/kg, respectively.
The plasma cholesterol elevation by cholesterol diet feeding was markedly inhibited by MCI-196 treatment and statistical analysis showed MCI-196 was 4.3 fold more potent than cholestyramine. The plasma phospholipid levels elevated in cholesterol diet fed rabbits were also decreased by resin treatments, which was considered to be based on the reduction of VLDL and LDL lipids. The increases in the levels of liver cholesterol and the hepatic bile cholesterol and phospholipid by cholesterol diet feeding levels were also decreased by resin treatments, which revealed the reduction of the hepatic lipid pool. Their basal levels of plasma, liver and hepatic bile in basal diet fed rabbits were slightly decreased by resin treatments. No effects of resin on the levels of liver phospholipid and triglyceride, plasma triglyceride and biliary total bile acids were observed in both basal and cholesterol diet fed rabbits. On the other hand, the fecal sterol excretion (cholesterol and bile acids) were markedly increased by MCI-196 treatment in both basal and cholesterol diet fed rabbits. Cholestyramine stimulated fecal bile acid excretion but not cholesterol.
These results suggest that MCI-196 is a highly active bile acid sequestrant more than cholestyramine and inhibits the intestinal bile acid reabsorption and promotes cholesterol metabolism to bile acids and finally decreases plasma and liver cholesterol levels according to the same mechanism of cholestyramine.

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A case of apolipoprotein (apo) C-II deficiency was reported. The patient had high triglyceride levels ranging from 400-910mg/dl. Apo C-II deficiency was tested by immunochemistry, iso-electric focusing and enzyme assay.
In this patient plasma lipoproteins (Lps) were mainly chylomicrons, low density Lps (LDL) and high density Lps (HDL) being very low. The findings were compatible with low levels of plasma apo A-I, A-II, B and HDL-cholesterol (HDL-C).
In the relatives of the patient his mother and 4 siblings were diagnosed as heterozygotes who had apo C-II concentrations about 50% of normal values and had normal plasma triglyceride levels.
The results in this study were confirmed that the defect is inherited as an autosomal recessive trait.

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