The insudation of blood plasma components into the intima is one of the most important atherogenic factors. But, the accumulation of blood components would not occur when the intimal fluid transportation (“clearance”) is satisfactory enough to carry them away.
We examine microscopically the declining of intimal clearance with aging about non-sclerotic areas of human aortic wall by Berlin-blue production after infusion of ferric citrate solution.
The infusion of fluid was much easier and more uniform in the younger aortas than in older cases, and it was washed away by perfusing of saline solution. But in older cases, blue dye remained distinctly in the intima.
It was noted that the clearance mechanism of human aortic wall declined steadily with aging even in the non-sclerotic “normal” areas.

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In connection with a symposium of the main subject “Role of Hemorheological Factors in Atherogenesis” some problems are discussed concerning the permeability of artery walls to clarify the role of hemorheological factors.
Recent experimental results of the permeability of artery walls by Fry and Nerem et al. are summarized. The pathways of macromolecules through endothelial cells are classified into two categories: passage along junctions between endothelial cells, and transport by vesicles through pinocytosis.
From the peculiar rheological properties of protoplasm, such as non-Newtonian viscosity, viscoelasticity and thixotropy, a molecular picture of protoplasm in endothelial cells is drawn. Based on such a molecular picture, a theoretical interpretation of the increase in the permeability of artery walls with increase in hemorheological factors is given.
Theoretical considerations are given about the mechanism of endothelial injury caused by hemorheological factors. Scanning electron micrographs of injured endothelium show complete falling away of endothelial cells. However, it seems difficult to consider sudden falling away of endothelial cells due to shear stress or turbulence.
Since the junctions are rather weak portions within the endothelium, those portions of endothelial cells which are quite close to the junctions are liable to be “peeled off” a bit at the initial stage of hemorheological effects. Such a local peeling of cells will then develop into a complete falling away of endothelial cells in a long period of time.

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The pathways of material transport across the endothelium at the ultrastructural level were examined in different kinds of blood vessels by using tannic acid or horseradish peroxidase as a tracer. Freeze-fracture replicas from the endothelial cells of the aorta and basilar artery of the rat were also made and examined by electron microscopy.
Tracer materials could be transported through the cytoplasm of the endothelial cells by means of vesicles linked with pinocytotic activity, transient transendothelial channels formed by serial fusion of vesicles, and fenestrae. The intercelluar gaps of the hepatic sinusoid endothelium could also be a pathway for tracer materials. In the aorta the intercellular junction between adjacent endothelial cells could be a passageway for both tannic acid and horseradish peroxidase, whereas in the basilar artery, these materials could not pass through that junction beyond the tight junction area. Freeze-fracture replicas showed that the strands of intramembrane particles at the tight junction constitute continuous complex networks in the basilar artery whereas those in the aorta were simple in organization, consisting of a few discontinuous strands accompanied with sporadic gap junctions. The observation in freeze-fracture replicas may well explain the fact that tannic acid and peroxidase cannot be transported through the intercellular clefts beyond the tight juction in the basilar artery.

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Atherosclerotic plaques occur predominantly at specific regions in the neighborhood of bends or junctions. These findings prompted many investigators to speculate that local hemodynamic forces are closely related to the pathogenesis and proliferation of atherosclerosis. The formation mechanism of thrombi in the cardiovascular system has also been considered in connection with changes in hemodynamic circumstance. Up to the present, however, no definite conclusion has been obtained in regard to the mode of participation of blood flow in the devlopment of atherosclerosis. The reason is that detailed information about the fluid dynamic features of blood flow has not been acquired owing to the difficulties in measuring the spatial and temporal distributions of velocities and pressures in the three-dimensional flow field inside the narrow blood vessel lumen. By means of the flow visualization technique, we have investigated flow patterns in various blood vessel models made of glass or metacrylate resin and reached a conclusion that complicated flow patterns seen in tubes with a stenosis, bifurcation, or branchings can be understood in terms of the occurrence of a secondary flow, named the horseshoe vortex.
The generation of the horseshoe vortex in a flow through the tube with a bluff protuberance into the boundary layer can be explained as follows. A radial pressure gradient toward the tube wall is produced along the upstream surface of the protuberance because of the interaction between the viscous sheared flow and the wall of the tube. This pressure gradient makes fluid particles turn round downward directly before the obstacle. Then they curled round on themselves and formed a bound vortex tube, the horseshoe vortex, which in turn passes round the front of the protuberance in both directions. In a tube with a Y-shaped bifurcation or a rectangular side branch, the flow divider at the branching site acts in place of the protuberance to produce a vortex tube similar in pattern to the horseshoe vortex. The vortex tube extends from the high pressure region, i. e. the apex of the flow divider, to the low pressure, i. e. the lateral margin of the branch orifice and generates swirling secondary flows in the main and branched tubes. From the results of the present model experiments, it will be suggested that the following mechanical factors may initiate or facilitate the atherogenesis and thrombogenesis: collision of blood vessel walls and the blood cells captured by the horseshoe vortex, the interaction of the walls and blood cells due to turbulence, and localized high wall shear stresses.

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The structural change of endothelial cells is responsible for the increased transport of lipid proteins into the arterial wall, the formation of thrombus and then the development of atherosclerosis. The endothelial injury is discussed under the microfluid mechanical interaction of blood flow and arterial wall. Some microrheological factors affecting the structure of endothelial cells are elucidated from a stand-point of fine structures of blood flow near the wall with a sticking white cell and near the wavy (or protuberant) wall.

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The role of hemodynamic factors in the atherogenesis has been noticed since virchow's refesences. Atherosclerotic lesions have definite predilection about their sites with a tendency to arise around the curve, branching or narrowing of the artery. Hemodynamic energy strips off the arterial endotheliums physically. Though the relationship between the sites of lesions and arterial structures shows some genetic or anatomic differences in various animals, the predilection of atheromatous lesions due to anatomical structure of the artery is one of the most important factors for atherogenesis.
Endothelial injury mainly produced by wall shear stress gives rise to the insudation of blood plasma into subendothelial tissue and finally may lead to the atherosclerotic lesions. The second factor which injures arterial endothelium hemodynamically is the separation of blood flow caused by obstacles such as atheromatous plaques or stenosis. The third one is the endothelial lesion which is caused by the vibration of vessel wall or of blood stream.
The vibration arises from the collision of blood stream to the vessel wall or from the vortex stream. The shear stress produced by vibration is closely related to the “hardness” of vessel wall, and hard vessels are exposed to much stronger vibration energy than soft ones.
The fouth factor which induces endothelial damage is the rheological change of blood itself. Dr. Isogai has shown that the blood of diabetic patients who have macro- or micro-angiopathies revealed disorders about plasma fibrinogen, VIII factor-related antigen, elasticity of blood clot, plasma viscosity and so on. These local rheological factors would work as definite atherogenetic agents together with systemic risk factors such as hypertension and hypercholesterolemia.

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The lipid compositions of serum lipoprotein (Lp) were determined by agarose gel electro phoresis and simple enzymatic method, at least a month after a myocardial infarction (MI) in 98 Patient, and the values obtained were compared with those in 79 healthy control subjects.
In total serum lipid, only triglycerides (TG) concentration in MI patients was significantly increased, and in Lp fractions, only HDL was singficantly decreased. In the lipids of HDL, choresterol (Chol) and phospholipids (PL) were decreased in these concentrations, TG was increased and Chol was decreased in the distribution ratios.
In LDL and VLDL, all lipid concentrations were significantly increased, but in the distribution ratios, chol was decreased in LDL, PL was decreased in VLDL.
When compared these distribuation ratios in the limitation of normal lipid level, Chol and PL in female in HDL, TG and Chol in male in LDL and PL in male and TG in female in VLDL showed significant difference. In the high TG level, however, there were marked differences in TG in both male and female and in Chol in male.
These changes of the Lp composition in HDL had significant correlations with serum TG levels, and it suggeted that the disorder of serum TG metabolism had some relation with those changes.

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We posturated that lysosomes involved in the accumulation of cholesterol ester in atheromatous aorta. To elucidale the mechanism further, we have developed cell culture system of foam cells from atheromatous aorta. The cells were prepared by the digestion of enzymes such as elastase, hyaluronidase and collagenase. Cross image, which may correspond to cholesterol ester inclusion bodies, was observed in living foam cells.

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9 male rabbits were exposed to short periods of systemic hypoxia for 2 weeks with nitrogen gas. They were classified into three groups by the contents of diet.
Group A: commercial diet
Group B: 2% cholesterol diet with low vita min E contents
Group C: 2% cholesterol diet with 500 I.U./kg of vitamin E
Atherosclerotic lesions in aortic wall were observed in all three groups. Microscopic examination of aortas showed thickened, calcified intima and marked degeneration media which were observed with human atherosclerosis in the early stage commonly. Concerning to the analysis of homogenized aortas, increase in total-cholesterol/free-cholesterol ratio, triglyceride and calcium concentration level were noticeably observed in group B. A model of experimental atherosclerosis with rabbits designed from hypoxic state with nitrogen gas will be useful to clear the mechanism of atherosclerosis.

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We have reported that the renal vasotoxic substance is included in the microsomal fraction of renal cortical extracts, and that the fraction has no-pressor effect.
In this experiment, Ouchterlony method and immuno-electrophoretic analysis are used in order to identify the renal vasotoxic substance in serum immunologically. Antigen-antibody reactions are performed using the rat serum which is treated with transient renal ischemia, and using anti-rat renal microsomal fraction rabbit serum. Ouchterlony method points out specific antigen antibody reaction lines clearly. Immuno-electrophoretic analysis also points out five bands corresponding with α₁, α₂, β, γ-globulin levels.
This results suggest a possibility that the injured kidney releases the renal vasotoxic substance which results in various vascular lesions.

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The innervation of the perforating and cortical branches of cerebral arteries of humans was examined by electron microscopy, formaldehyde histofluorescence and cholinesterase technique. When viewed by transmission electron microscopy, the perivascular automonic nerve fiber consisted of myelinated superficial nerve plexus and non-myelinated deep nerve plexus. Within the non-myelinated axon of deep nerve plexus, granular and non-granular synaptic vesicles were often seen. Histochemically, the perforating arteries were better supplied by adrenergic and cholinergic nerves than the cortical branches of cerebral arteries. Although the degree of innervation in the large cerebral arteries was always higher than that in the small arteries, there was a certain degree of regional variability.
Our results may represent the importance of dense innervation of perforating arteries concerning with the morphogenesis of “exhaustive degeneration” of medial smooth muscle cells of perforating arteries observed in hypertensive patients.

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We performed lightmicroscopic and electron-microscopic observation on pulmonary arterial walls in thrombosis of pulmonary arterial stem. In the arterial wall attached with thrombus, marked arteriosclerotic changes could be seen, that is, we could observe the prolifiration of elastic and collagen fibers in the intimal layer, fragmentation and destruction of internal elastic lamina and degeneration and atrophy of smooth muscle cells in tunica media. In pulmonary arterial tree the mechanical destruction of intimal layer and insudation of blood elements were confirmed throughout the peripheral small arteries and arterioles. It was difficult to observe these changes because of associated early organization of thrombus in the arterial stem, but in some cases we could confirm these changes and prove that these changes were greatest in pulmonary arterial tree. In conclusion totality of hemodynamic load due to pulmonary circulatory derangement in the periphery rebounded to the pulmonary arterial stem, and it caused destruction and insudation in the intima at the arterial stem. Consequently these arterial changes induced the thrombus formation in the pulmonary arterial stem.

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Arterial changes observed in the grafted kidney were studied from view point of the endothelial injury theory of atherosclerosis. Specimens were obtained by needle or open biopsy of transplanted kidneys from 15 patients with irreversible acute rejection, 6 from reversible acute rejection and 11 from chronic rejection.
Endothelial cells of the interlobular arteries were swollen, rounded and rather prominent, and desquamated at the early phase of the acute rejection as shown in Fig. 1. Denudation of the intima caused intraarterial coagulation and cortical necrosis in the patients with irreversible rejection. Fibrinolytic activities of the endothelium of the arteries and glomeruli examined with Todd's method were completely diminished in acute phase of rejection. These findings may indicate that the initial events of the arterial changes in the grafted kidney are endothelial injury by immunological processes.
Following changes after endothelial injury were appearance of foam cells in the intima (see Fig. 2). These foam cells were observed also in the capillary tuft of glomeruls as shown in Fig. 3. Electron microscopic observations revealed lipid droplets and cholesterol crystals in the cytoplasma of the cells as shown in Fig. 4. The foam cells were substituted with intimal and medial fibrosis. Fibrosis narrowed the lumina of the arteries in chronic phase of rejection (see Fig. 5).
Since several studies have reported that atherosclerosis is common cause of morbidity and mortality, and prevalence of hyperlipidemia in renal transplant patients, serum lipid alterations during the course of reversible rejection were studied. HDL cholesterol was significantly decreased at acute rejection as. compared that of prerejection or recovery phase. A tendency of hyperlipidemia was also observed in chronic phase of rejection (see Fig. 6).
From findings of the arterial lesion in the transplanted kidney, it may conclude that immunological injury of the endothelium induces enhanced permeability of the vascular wall with accumulation of foam cells and subsequently causes intimal and medial fibrosis. To resolve influences of hyperlipidemia on arterial lesions, further studies are required. Anyway, the arterial lesions in the transplanted kidney serves important informations in respect of immunological genesis of atherosclerosis.

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On our previous study of experimental atherosclerotic rabbits aortic prostacyclin production was significantly decreased and plasma lipoperoxide levels were elevated.
In the present study, the experimental atherosclerotic rabbits were produced by the feeding of 0.5% cholesterol containing diet. On these models platelet functions, i. e., ADP sensitivity, prostacyclin sensitivity and platelet malondialdehyde (MDA) formation were investigated.
Tissue (liver and aorta) lipoperoxide levels were also studied.
Following results were obtained.
(1) Platelets from rabbits fed with cholesterol rich diet had decreased sensitivity to prostacyclin.
The amount of prostacyclin required for 50% inhibition of platelet aggregation induced by 2.5μM ADP were 0.730±0.050ng/ml (mean±SD) in control rabbit platelets 1.157±0.087ng/ml in rabbits had with 0.5% cholesterol containing diet for 1 month, 1.247±0.145ng/ml in rabbit platelets had with 0.5% cholesterol containing diet for 2 months.
(2) The tendency of increased sensitivity of platelets to ADP aggregation was seen though statistically not significant.
From the magnitude of platelet aggregation induced by various concentration of ADP (0.3-4.0μM), the concentration of ADP required for the half maximum aggregation were 1.12±0.21μM in control rabbit platelets and 0.74±0.17μM in rabbit platelets fed with 0.5% cholesterol diet for 2 months.
(3) MDA formation of platelets were 0.17±0.049nmol/3×10⁸ plt. in control and 0.168±0.036 nmol/3×10⁸ plt. in cholesterol fed rabbits.
These results suggest the decreased aortic prostacyclin production and the dereased platelet sensitivity to prostacyclin may contribute the development and progression of atherosclerotis.

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Experimental nephrotic syndrome was raisedin rat by intravenous injection of 6mg/kg BW of Daunomycin.
Lipoprotein analysis, lipid synthesis in liver and lipid metabolism in arterial wall were examined and the effect of KCD-232 (4-(4′-cholrobenzyloxy) benzyl nicotinate) which was compound to have lipid lowering effct was examined. Total cholesterol and triglyceride were remarkably increased in nephrotic syndrome and KCD-232 decreased those to almost the same extent as the control. Under nephrotic conditions, LDL-cholesterol, LDL-triglyceride and VLDL-triglyceride was increased.
Those lipoprotein disorders were improved by administration of KCD-232. Lipid synthesis from acetate or palmitate in liver was increased in nephrotic syndrome. Lipid synthesis, those are PL, TG and FFA from palmitate and lipid synthesis from acetate, was inhibited by administ ration of KDC-232.
Acid cholesterol esterase and lipase activity were increased in nephrotic syndrome and remained unchaged by administration of KCD-232.

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HDL-Cholesterol (HDL-C) level was measured in relatively large number of subjects, and it was compared with other factors which were supposed to be related to serum HDL-C levels. In the present studies, the following results were obtained.
(1) HDL-C level was negatively corelated with atherogenic Index, pre-β+β/α ratio, plasma triglyceride levels and obesity Index for both sexes, and positively co-related with plasma PL levels for both sexes, and plasma T. C. and FFA levels for women.
(2) While the subjects with both obesity and hypertriglyceridemia demonstrated marked decrease of HDL-C levels, the subjects with only hypertriglyceridemia (not obese) demonstrated relative decrease of HDL-C levels compared with normal subjects. On the contrary, subjects with only obesity (not with hypertriglyceridemia) did not show decrease of HDL-C levels.
(3) While mean HDL-C level was significantly higher in the alcoholic subjects and the more the alcoholic intake, the higher the HDL-C level.
(4) While mean HDL-C level was significantly lower in the subjects with heavy cigarette smoking, mean triglyceride level was higher in the smoking subjects.
(5) The subjects with abnormal electrocardiography (non specific ST, T Change) did not demonstrate decrease of HDL-C level compared with normal subjects.

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Apolipoprotein C (apo C) percipitates great roles on lipid metabolism, especially on the catabolism of TG-rich lipoproteins. In vitro experiments, apo C II was recvealed to be an activator of lipoprotein lipase (LPL) and apo C III to be a inhibitor of LPL.
In present study, the percentage composition of apo C subgroup, apo C II, C III₀ C III₁ and C III₂ in VLDL was obtained by scanning the gel after loading the apo-VLDL on isoelectric focusing gel.
The relationship between plasma lipids and percent composition of apo C subgroups was as follows, positive correlation existed in triglycerides (TG) vs. C III₂, HDL-cholesterol (HDL-C) vs. C III₀, TG vs. C II/C III₀ ratio and HDL-C vs. C II/CII₂ ratio and negative correlation in TG vs. C III₀, HDL-C vs. C III₂ and HDL-C C II/CIII₀ ratio.
Pantethine (600mg/day) was prescribed to subjects, resulting the significant increase of plasma apo AI level, degrease of plasma TG and the increase of fractional removal rate of TG rich lipoprotein which was calculated from the decay curve of TG in Sf>400 fraction of plasma after intra-venous injection of Intralipid to the subjects (n=10). This drug also increased C II/C III₀ ratio in VLDL significantly.

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Plasma apo E levels are increased in type III hyperlipoproteinemia. Plasma apo E has been shown to have isoprotein forms, and it was re cently suggested that a deficiency of apo E-III isoprotein is associated with type III hyperlipoproteinemia.
To understand better apo E metabolism, we studied plasma apo E isoproteins using high resolution, two-dimensional polyacrylamide gel electrophoresis. Apo VLDL obtained from 10 normal subjects and 2 patients with type III hyperlipoproteinemia were analysed.
1 The patterns of VLDL apo E isoproteins from different normal subjects were of two major types, designated class α and class β according to Zannis et al. Class α consists of two major isoproteins, while class β consists of one major isoprotein.
2 Mixing experiments of apo VLDL obtained from different normal subjects with an α or a β pattern revealed that the α or β patterns were not always superimposable. It seemed that class α or class β is subdivided into several subclasses.
3 Two patients with type III hyperlipoproteinemia had a β pattern of VLDL apo E without any missing apo E isoproteins.
4 Mixing experiments of apo VLDL obtained from normal subject and patient with type III hyperlipoproteinemia indicated that the entire pattern of apo E isoproteins in patients with type III hyperlipoproteinemia was shifted to more acidic isoelectric points. This unique subclass of apo E isoproteins is seemed to be β IV pattern according to Zannis et al.

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Recently, presence of urinary HDL, LDL, apolipoproteins and hypoalphalipoproteinemia has been indicated in nephrotic syndrome of both human and experimental rats. In order to study the mechanism of abnormal lipid metabolism in patients with nephrotic syndrome, serum concentration of HDL cholesterol, apolipoprotein AI and urinary excretion of cholesterol, apolipoprotein AI were measured in 19 patients with chronic proteinuria of 0.7-20g/24hr. for more than two years. Indirect immunofluorescence of the renal biopsy specimens was also examined.
It was found that (1) serum concentration of HDL cholesterol and apoAI were lower significantly in patient with chronic proteinuria than in normal male controls (n=15, age 25-50), (2) positive correlations were found between urinary cholesterol, apolipoprotein AI excretion and proteinuria (g/24hr.), (3) electrophoresis of urinary lipoproteins in 8 subjects with urinary cholesterol of over 5mg/24hr. revealed an existence of HDL in all eight cases, and negative correlations were found between the serum concentration of apolipoprotein AI, HDL cholesterol and urinary excretion of apolipoprotein AI. Existence of LDL was shown in 3 of them. In prolonged nephrotic patients with urinary excretion of lipoproteins, apolipoprotein AI, CIII, B were localized in lysosomes of the tubular epithelium by fluorescent microscopy. These results suggest that HDL and LDL filtrated through damaged glomerular basement membrane were partly reabsorbed into the lysosomes of proximal tubular epithelium. Apolipoprotein deposits were not seen in the specimens from mild nephrotic patients or from non-nephrotic, chronic glomerulonephritis, suggestting that hyperpermeability and hyposelectivity due to severe damages of glomerular basement membrane have occured in prolonged nephrotic state.

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Korean Red Ginseng (KRG) has been known to have hypolipidemic effect or insulin like effects on blood sugar and lipid metabolism. Effect of KRG on lipoprotein metabolism were examined in 6 healthy volunteers, who were administerd 1400Cal of diet (fat: 101.8g, carbohydrate: 106.9g, protein: 34.6g) with KRG (3.0g) or placebo after 12hrs fasting.
Lipoproteins were analysed by ultracentrifugation method. Total triglyceride concentration in blood was almost linearily increased for 3hrs up to 200% comparing with the values before diet load. Triglyceride levels in KRG administered groups were slightly less than that of control diet administered groups. Triglyceride in chylomicron and VLDL, and FFA in blood was less in KRG administered group than that of control. Furthermore, HDL cholesterol concentration was not changed. These results suggest that lipid lowering effect of KRG might not be due to the increase in catabolism of triglyceride but to the inhibition of absorption in intestine.

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This study was performed to investigate the effects of Lipoclin, a new lipid-lowering drug, on serum lipoproteins, apoproteins (A-I, A-II) and LCAT activity in 14 hyperlipidemic patients (Type IIa, IIb). The patients were administered 600mg Lipoclin daily for twelve weeks and the following results were obtained.
(1) Lipoclin produced a significant redution of total cholesterol, VLDL-cholesterol, LDL-cholesterol and triglicerides (VLDL-TG LDL-TG), but increased in HDL-cholesterol significantly (p<0.01).
(2) In high density lipoprotein subfractions (HDL₂ and HDL₃), Lipoclin increased HDL2-cholesterol significantly (p<0.001) whereas the HDL₃-cholesterol remained unchanged.
(3) Lipoclin treatment also caused significant increases in both of the plasma apoprotein A-I (p<0.01) and LCAT activity (p<0.01) but did not influence the level of apoprotein A-II.

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Effect of pantethine on high density lipoprotein (HDL) cholesterol levels was studied with normolipemic rabbits. When rabbits were treated with pantethine at 1% in diet for 32 days, a significant increase in HDL-cholesterol and apolipoprotein A₁ antigen levels in serum was observed without any changes in (V) LDL-cholesterol and apolipoprotein B antigen levels. The increase in HDL-cholesterol was accompanied by a significant increase in triglyceride clearance of injected intralipid or chyromicron/VLDL from the circulating blood. Pantethine also caused a considerable increase in the heparin-releasable lipoprotein lipase activity in the epididymal adipose tissue and LCAT activity in serum. These effects of pantethine strongly suggest a stimulation of “VLDL-HDL Pathway” to produce HDL and to increase HDL-cholesterol values. This was further evidenced by the kinetic study of injected ¹²⁵I-labeled VLDL in these rabbits. Patethinetreated rabbits showed significantly higher fractional catabolic rates for ¹²⁵I-labeled apolipoproteins in both VLDL and HDL fractions than control rabbits.
On the other hand, the liver perfusion study indicated that a greater amount of apolipoprotein A₁ was produced in the liver from pantethine-treated rabbits than in control livers and that incorporation of ³H-labeled leucine into apolipoprotein A₁ was increased in the livers from the treated rabbits. No difference was observed in production of apolipoprotein B and albumin in the livers between the 2 groups. A mechanism of the selective or preferential action of Pantethine towards apolipoprotein A₁ is not clear yet.
In conclusion, pantethine caused an increase in the adipose tissue LPL and serum LCAT activities and in hepatic apolipoprotein A₁ synthesis in normal rabbits. These effects may lead to the elevation of HDL levels through acceleration of the “VLDL-HDL Pathway”.

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Rets were fed on a moderate high cholesterol diet which didn't result in hypercholesterolemia. Effect of γ-oryzanol on lipid metabolism involving serum lipoproteins, liver cholesterol content, cholesterol esterase (CEase) and acyl-CoA cholesterol acyltransferase (ACAT) activities in the arterial wall, was evaluated. Rats were divided into 3 groups. Group I fed on normal diet (ND), group II fed on high cholesterol diet (HCD: 0.7% cholesterol plus 0.5% cholisc acid).
Group III fed on HCD plus γ-oryzanol (250mg/kg weight). Each rat was fed 20g a day for 16 weeks. There were no significant differnce in body weight, liver weight and serum total cholesterol level among 3 groups. VLDL-cholesterol was high and HDL-cholesterol was low in group II and group III compared to group I. LDL-cholesterol remained unchanaged. The liver cholesterol contensts in group I, II or III were 4, 14 or 10mg/g liver wet weight, respectively. There were no significant difference in CEase activities among 3 groups. But activities were slightly low in group II compared to group I and slightly high in group III comparted to group II. ACAT activity was the lowest in group III. When serum cholesterol level reamins within normal limits, moderate HCD resulted in changes in lipoprotein-cholesterol content and elevation of liver cholesterol content. And these changes are considered to be atherogenic. γ-oryzanol improved these changes, so it may have protective effect against atherogenic changes.

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Cholestyramine, an antihypercholesterolemic agent having a basic anion exchange characteristic, was studied for its effects on serum lipids and for its safety when administered to Type II hyperlipidemic patients at dose levels of either 8Gm per day (4Gm bid) or 12Gm per day (4Gm tid) for 8 consecutive weeks. A total number of patients treated was 44 consisting of 9 Type IIa receiving 8Gm per day, 19 Type IIa receiving 12Gm per day, 7 Type IIb receiving 8Gm per day, 6 Type IIb receiving 12Gm per day, and 3 who were excluded from the data analysis due to low pretherapy values of serum total cholesteol showing less than 220mg/dl.
An average pretherapy value of serum total cholesterol was 333.1mg/dl among the 41 patients analyzed indicating no significant difference between each Type of patients and dose groups. Cholestyramine was remarkably effective for reducing serum total cholesterol as shown by the Percent Reduction Through Therapy which was 15.0% in Type IIa, 16.3% in Type IIb and 15.4% in overall patients. Cholestyramine also demonstrated an excellent dose-response in non-familial Type IIa and Type IIb while it did not show a clear-cut response in familial Type ha which displayed a less percent reduction than did non-familial Type IIa. Data on other serum lipids indicated that triglyceride was not significantly altered whereas HDL-cholesterol had a tendency to increase.
Adverse reactions included constipation in 5 patients (11.4%) and diarrhea in 1 patient (2.3%). Two patients recovered from severe constipation when cholestyramine was withdrawn while the others were able to continue the therapy without interruption. A transient increases in GOT, GPT, CPK and LDH was seen in some patients with the values reversed to normal as the therapy continued. There were no abnormal values found in urine, hematology and serum biochemistry tests concurrently performed.
These data demonstrate that cholestyramine is highly effective in the treatment of severe hypercholesterolemia including familial hypercholesterolemia and is relatively free from serious adverse reactions.

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The effect of low density lipoprotein (LDL) on the microviscosity of cells has been examined to elucidate whether LDL induces altered microviscosity of cell membrane immediately after binding with LDL receptors. Peripheral blood B lymphocytes from healthy adults were used as a model of cells with LDL receptors, and T lymphocytes as well as lymphocytes from patients with familial hyper cholesterolemia were used as control cells which have much less activity as LDL receptors than B lymphocytes. Microviscosity of cell membrane was determined by fluorescence polarization analysis of the fluorescent hydrocarbon probe, 1, 6-diphenyl-1, 3, 5-hexatriene. Elevation of microviscosity after incubation with LDL at 0°C for 30min was induced only in B lymphocytes, but not in T lymphocytes or familial hypercholesterolemic lymphocytes. In parallel studies, it was shown that the activity of LDL receptor was observed exclusively in B lymphocytes but not in T lymphocytes or familial hypercholesterolemic whole lymphocytes.
It is concluded that binding of LDL to LDL receptors increases the microviscosity of membrane without internalization of LDL into cells. It is suggested that this method can be applied for the evaluation of LDL receptor activity under vaious clinical conditions.

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Twenty-two patients with hyperlipidemia (total cholesterol ≥220mg/dl or triglyceride≥120mg/dl) were treated with elastase (10800 El. U./day) for 12 or 24 weeks, during which time changes in serum lipid levels were observed.
The serum level of total cholesterol was reduced significantly within 4 to 20 weeks following the administration of elastase, while that of HDL-cholesterol was increased. Therefore, the atherogenic index was lowered significantly.
Serum triglyceride, β-lipoprotein and phospholipid levels were also significantly reduced at 8 and 12 weeks, respectively, following medication. On the other hand, no change in the serum free fatty acid level was recognized.
Complications caused by this drug were not found in any of the patients given this medication.

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