In an attempt to obtain information regarding vascular elastase in children and young adults, under taken to elucidate the initial stage change in the arteries as regards atherosclerosis; we examined immunohistochemical localization of human pancreatic elastase and Apolipoprotein B on aorta in 21 patients (mean 20.9±14.8).
In order to obtain the objective parameter of atherosclerosis, these aortae were studied grossly by the point counting method employing a modified Gore's score, and histologically using Imagelyzer system for medial contents of elastin, collagen and smooth muscle cells.
The surface involvement and atherosclerotic index increased with age (p<0.01), and also their scores correlated to decrease of area % of elastin in media (p<0.05).
Elastase was also demonstrated in intimal background and SMC which increased with age (p<0.05), and medial SMC which showed no correlation with age.
Apolipoprotein B was already demonstrated in SMC of the intimal thickening of aortae which increased with age.
In conclusion, elastase seems to play an important role in the development of atherosclerosis even in children and young adults.

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Ring-like lipid deposits is the ring shaped Sudanophilic area in the lateral portion of the carotid sinus, usually observed in the young adults. These deposits were first described descriptively by Meyer and Noll (1974). In our present report, we study the atherosclerosis in the cervical bifurcation of the carotid artery, especially focusing in the ring-like lipid deposits, because the area of the deposits has recently been revealed to face on an interesting hemodynamic change. Three hundred eighty two carotid arteries from 318 autopsy cases were studied. They included 137 cases of young adults and children (less than 39-year-old). Sudan IV stain and gross measuring were tried in 59 cases under 39-year-old. Ring-like lipid deposits in the carotid sinus were suggested to appear and grow mainly influenced from the luminal side through endothelial layer by the factors created by blood flow and blood properties rather than influenced by the preformed intimal thickening and the characteristic medial structure. This suggestion was based on two facts that the foamy cell appearance which was the principle histological feature of the ring-like lipid deposits was usually observed in the shallow layer of the intima near the endothelial layer and that the ring-shaped hemodynamic change might possibly appear in the lateral portion of the carotid sinus, while there was no distinctive ring-shaped structure in the intima and media of the lateral portion of the carotid sinus. It is important to study the precise hemodynamics on the endothelial surface of the ring-shaped portion of the ring-like lipid deposits, because this characteristic hemodynamics might be those inducing localized lipid-deposits. Furthermore, we shall reveal a preatherosclerotic lesion, when the morphologic examination of the ring-shaped portion in the young cases without lipid deposits will be performed.

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We succeeded in producing cerebral atherosclerotic lesions in hypertensive rabbits fed with cholesterol. To examine the location and progression of atherosclerotic lesions, frontal dissection of cerebral arteries (vertebral arteries, basilar artery and posterior cerebral arteries) was performed and thus an overall view of these vascular luminal surface was acquired. Initial atherosclerotic lesions developed at the Y-bifurcation of arteries (from basilar artery to right and left posterior cerebral arteries) and confluent portion of arteries (from right and left vertebral arteries to basilar artery). Lesions observed by the scanning electron microscopy showed passing figures of macrophages and protrusion or distortion of endothelial cell configurations. These features are almost consistent with those described in aortic lesions. The location of lesion at the arterial Y-bifurcation made reminiscent of that in human cerebral atherosclerosis. In addition, it has been said that a peculiar form of eddies developes at Y-bifurcation of artery; observations on the normal rabbit cerebral artery disclosed that these vascular Y-bifurcation and confluent portions correspond to the turning and confluent points of endothelial arrangement of the corresponding arteries respectively. From these observations it was concluded that these specialities in blood stream and endothelial arrangement may relate to atherogenesis of the cerebral arteries.

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Abnormality in lipoproteins was studied in patients with cerebrovascular disease at the time when more than one month has elapsed after onset. All patients were classified into three groups, cerebral thrombosis, cerebral embolism, and cerebral bleeding, according to the symptoms, history, cerebral angiography and CT.
1) Serum apo A-I levels decreased and apo B levels increased in patient with cerebrovascular disease as compaired with control group. When apo B/A-I ratio was examined, it increased more remarkably in patients with cerebrovascular disease, and therefore is a good atherogenic marker in cerebrovascular disease.
2) Total cholesterol levels was not altered, but TG levels increased in patients with cerebrovascular disease compaired with control group.
3) In LDL fraction, cholesterol content did not change, but apo B increased in patients with cerebrovascular disease as compaired with control group. The chol/Apo B ratio in LDL fraction decreased in cerebrovascular disease, indicating apo B rich LDL being more atherogenic.
4) Serum oxidized lipoprotein levels increased in cerebral thrombosis and embolism, but not in cerebral bleeding. Further analysis has revealed that, in LDL fraction, oxidized LDL increased in all three groups.
These results suggest that qualitical abnormality in lipoproteins, especially apo B rich and oxidized LDL, have important roles in the outbreak and progression of cerebrovascular disease.

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The effects of prostaglandin E₂ (PGE₂) on the metabolism of β-migrating very low density lipoprotein (β-VLDL) in rat peritoneal macrophages were investigated. When cultured in vitro, macrophages apparently incorporated labeled β-VLDL time-dependently until 12h, when the incorporation appeared to reach a plateau. Labeled cholesterol ester in the macrophages increased rapidly until 2h of incubation, did not change from 2 to 6h, and then increased markedly until 28h. Labeled free cholesterol in the macrophages increased until 12h and then decreased until 28h. Exogenously added PGE₂ (10^-7-10^-5M) inhibited the accumulation of labeled cholesterol ester between 6h and 28h with or without increasing the level of labeled free cholesterol. Indomethacin stimulated cholesterol ester accumulation, which suggested that endogenous PGE₂ also had an inhibitory effect on cholesterol ester accumulation. PGE₂ affected neither uptake of β-VLDL into macrophages nor activities of enzymes hydrolyzing (cholesterol esterase) or synthesizing (acyl-CoA: cholesterol acyltransferase) cholesterol ester. On the other hand PGE₂ stimulated free cholesterol secretion into the medium.
The above results indicated that PGE₂ inhibited cholesterol ester accumulation by increasing the secretion of free cholesterol from macrophages into extracellular space.

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Low-density lipoprotein (LDL) metabolism was studied in human peritoneal macrophages isolated from continuous ambulant peritoneal dialysate (CAPD). The macrophages degraded ¹²⁵I-LDL as well as ¹²⁵I-Acetyl LDL specifically. Macrophagelike cell line U-937, lymphocyte cell line IM-9 could degrade ¹²⁵I-LDL but not ¹²⁵I-acetyl LDL. These cells also accumulated cholesteryl ¹⁴C oleate from ¹⁴C oleate in the presence of LDL.
The results indicate that human peritoneal macrophages possess the scavenger pathway of lipoproteins as reported in murine peritoneal macrophages, and that the cell lines U-937 and IM-9 can be used as cell models for studies of LDL metabolism.

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Transformation of macrophages into foam cells after the uptake of cholesterol oleate anisotropic liquid crystals was studied. A new technique to enhance the uptake of the liquid crystals by macrophages using an inverted petri dish was developed. Uptake of lipid droplets was found to increase in parallel with the amount of liquid crystals in the medium. A lysosomal enzyme was shown with lysosomotropic chloroquine to be involved in the hydrolysis of the liquid crystals. The 50% clearance time of the liquid crystals by the macrophages was about 24h, which was longer than that of denatured lipoprotein. The present model is useful for study of cholesterol ester accumulation and hydrolysis in macrophages.

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Probucol causes a rapid and marked regression of cutaneous and tendon xanthomas in spite of the decrease in plasma HDL-cholesterol levels. To elucidate the mechanism of such effect of probucol, we studied the in vitro effect of probucol on the intracellular accumulation of cholesterol using cells of a macrophage-like cell line (EU-12) which had been established from a human histiocytic lymphoma cell line.
Both morphologically and chemically, formation of these cells into foam cells in the presence of acetyl-LDL was markedly prevented by the addition of probucol into the medium.
Degradation of [¹²⁵-I]-acetyl-LDL by the cells was estimated before and after the cells were preincubated with probucol. Degradation activity was inhibited after the cells were preincubated with probucol, but it was not inhibited without preincubation, in spite of the presence of probucol in the medium.
We concluded that one of the mechanisms of regression of xanthomas by probucol was the decreased incorporation of denatured lipoprotein.

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Perforating arteries were examined electronmicroscopically in 60 stroke-prone spontaneously hypertensive rats (SHRSP), which were sequentially killed at 4-52 weeks of age before showing symptoms of stroke. Further 24 SHRSP were killed just after they became symptomatic by cerebral infarction. The initial vascular lesions observed in the asymptomatic group were focal cytoplasmic necrosis in the outer layers of the media. Focal cytoplasmic necrosis progressed into widespread medial necrosis with the passage of time. In the infarction group we discovered that numerous monocytes adhered to the endothelium of the arteries with advanced medial damage. Following the adherence of the monocytes enormous amounts of plasma components entered and accumulated in the arterial wall. Accumulation of the plasma components, especially fibrin, thickened the wall, narrowed the lumen and resulted in occlusion. These results suggest that monocyte may work on the endothelium and disturb the barrier function, the so-called blood-brain barrier. In other words the monocytes are closely related to the arterial occlusions, and then the cerebral infarction.

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Remnant lipoprotein levels elevate in plasma of diabetic patients, which is thought to be related to the occurrence and the development of atherosclerosis in diabetes. Our earlier report indicated streptozotocin-induced diabetic rats showed a marked hyperlipoproteinemia with the accumulation of chylomicron remnants after an exogenous cholesterol load. In order to clarify the mechanism of remnant accumulation in diabetes, we investigated post heparin lipolytic activity and hepatic lipoprotein receptors. However, elevated levels of remnant lipoproteins in diabetes could not be explained only by the impairments of either lipolysis or lipoprotein catabolism mediated through hepatic receptors. Then we investigated acyl CoA: cholesterol acyltransferase (ACAT) activity of absorptive epithelium in small intestine, which was reported to be one of regulating enzymes of intestinal cholesterol absorption. Streptozotocininduced diabetic rats were all given an equal amount of feed (20g/day) for 3 weeks. After a 24 hour fasting absorptive epithelium in small intestine of each rats was prepared and microsomal ACAT activity was measured in three groups; control group, diabetes mellitus (DM) group and cholesterol (chol)-fed DM group. ACAT activity in DM group was 4 times higher than that in control group (non-diabetic rats). There was no significant difference in ACAT activities between DM and chol-fed DM group. No significant difference was observed among 3 groups in microsomal levels of free cholesterol, which was used as substrate in measuring ACAT activity. Furthermore, in order to study the effect of melinamide, an inhibitor of ACAT, plasma lipoprotein levels after a 24 hour fasting were investigated in 3 groups; DM group, chol-fed DM group and melinamide-treated group. Cholesterol levels in melinamide treated group were lower than those in chol-fed DM group (p<0.01), and were higher than those in DM group (p<0.01). Triglyceride levels showed no significant difference among 3 groups. Lipoprotein analysis indicated that cholesterol levels in VLDL and IDL in melinamide-treated group were markedly lower than those in chol-fed DM group (p<0.05). In conclusion diabetic rats have elevated activity of intestinal ACAT and it may be a cause of remnant accumulation in cholesterol fed diabetic rats. Besides, it was confirmed that melinamide, an inhibitor of cholesterol absorption, is a effective drug for hyperlipidemia in diabetes mellitus.

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Activities of LDL and acetyl-LDL pathway by isolated rat parenchymal and non-parenchymal (endothelial) liver cells have been studied.
¹²⁵I-LDL & ¹²⁵I-acetyl-LDL association and degradation to rat parenchymal cells were measured at 37°C for 2 hours. About 50% of the associated ¹²⁵I-LDL & 60% of the associated ¹²⁵I-acetyl-LDL were degraded in isolated rat parenchymal cells, respectively. Specific binding of ¹²⁵I-LDL & ¹²⁵I-acetyl-LDL were measured at 4°C for 5 hours, and non-specific binding of ¹²⁵I-LDL & ¹²⁵I-acetyl-LDL accounted for about 30% & 40% of specific binding, respectively.
Acetyl-LDL replaced the binding of ¹²⁵I-LDL by rat liver parenchymal cells, but less efficiently than LDL. LDL did not affect the ¹²⁵I-acetyl-LDL binding to rat parenchymal cells. Acetyl-LDL competed ¹²⁵I-LDL binding to endothelial cells more efficiently than LDL.
Association and binding of ¹²⁵I-LDL by non-parenchymal cells amounted to 15-20% and degradation activity shared about 40°C compared with parenchymal cells. Association and binding of ¹²⁵I-acetyl-LDL by non-parenchymal cells showed high affinity, and the degradation in non-paren-chymal cells was twice higher than parenchymal cells.
In total liver, parenchymal cells showed LDL & acetyl-LDL association 50 & 10-fold greater than with endothelial cells, respectively. Therefore, parenchymal cells play a main role in LDL metabolism in rat liver. In endothelial cells, association of acetyl-LDL per cell corresponded to 10-fold higher than with LDL.

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A simplified intravenous fat emulsion tolerance test (FETT) was established to evaluate a triglyceride rich lipoprotein metabolism.
In the present study, fractional removal rate (K₂) of FETT in normolipidemic subjects (n=18) and primary hyperlipidemic patients (type IIa, IIb and IV) (n=48) was estimated. Also, the relationship between K₂ value and serum lipoproteins was investigated.
FETT: After an overnight fast, the subjects were injected 0.25ml/kg body weight of 10% Intralipid®, and blood was sampled 8 times during the following 20 minutes. K₂-value was determined by nephelometry as preveously reported. Serum lipoproteins were obtained by preparative ultracentrifugation according to Havel's method. Lipids in lipoprotein fractions were estimated by enzymatic methods.
Significant negative correlations were found between K₂ and VLDL-TG (r=-0.50, p<0.01) as well as between K₂ and VLDL-Chol (r=-0.50, p<0.01). Also, significant negative correlations were found between Log K₂ and Log VLDL-TG (r=-0.62, p<0.001) as well as between Log K₂ and Log VLDL-Chol (r=-0.53, p<0.01). There is no difference between K₂ levels of normolipidemic subjects (11.1±3.9%/mm, nmean±SD) and K₂ of type ha patients (11.3±3.6%/mm). nK₂ of type IIb patients (7.6±2.3%/min) and K₂ of type IV patients (7.4±3.6%/min) showed significantly lower value as compared with K₂ of normolipidemic subjects and type ha patients (p<0.005). However, K₂ value of some individuals in type lib and IV were similar to K₂ value of normolipidemic subjects.
These results suggest that K₂ in FETT might be influenced by concentration of VLDL and the catabolic disorder of TG-rich lipoprotein might exist in type IIb and IV patients, but not in type IIa patients. The results also suggest that type IIb and IV patients could be further classified in detail by means of the difference of K₂ value.

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To simplify characterization of VLDL subfractions, a separation procedure by high performance liquid chromatography (HPLC) was developed. Very low density lipoproteins (VLDL, d<1.006), low density lipoproteins (LDL, d=1.006-1.063) and high density lipoproteins (HDL, 4=1.063-1.210) were analyzed on two gel filtration TSK G5000PW columns connected in series. LDL and HDL each eluted as single non-overlapping peaks. VLDL eluted as two subfractions. Zonal ultracentrifugal subfractions of VLDL isolated from normolipidemic and hypertriglyceridemic subjects were analyzed by HPLC. VLDL₁ (Sf>120) from hypertriglyceridemic subjects produced a prominent peak of Fraction I (retention time-43 min), whereas VLDL from normolipidemic subjects eluted primarily as Fraction II (retention time-55 min). Zonal VLDL₂ (Sf60-120) and VLDL₃ (Sf20-60) eluted as Fractions II, but the peak retention time of VLDL₂ was shorter than that of VLDL₃. Fraction I was richer in triglycerides and poorer in protein than Fraction II. /β-VLDL from cholesterol-fed rabbits also eluted as two subfractions. Thus, HPLC provides a rapid and sensitive technique for characterizing VLDL size heterogeneity.

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Mean peak flotation rate of LDL measured by analytical ultracentrifugation were 26.2±1.6, 27.0±3.0, 24.7±2.4, 21.7±2.8, 17.4 in controls, type IIa, type IIb, type IV, type V, respectively.
Mean peak flotation rate of LDL in hypertriglyceridemia demonstrated the unusually low peak flotation rate, which of type IV was significantly lower (and presumably smaller) than that of controls. The mean LDL peak flotation rate of hypercholesterolemia (IIa and IIb phenotype) did not significantly differ from that found for control subjects. Regression analysis demonstrated that the mean peak flotation rate of LDL decreases with decreasing HDL-C or HDL₂ concentrations, and with increasing TG rich lipoproteins concentration. However when limiting serum triglyceride concentration up to 120mg/dl the peak flotation rate of LDL demonstrated significant correlation with HDL-C concentration but not with VLDL-TG. Together these data suggest that the major determinant of the peak flotation rate of LDL appears to be not only genetic but modified by metabolic influences.
Each lipoproteins thus differ in physical nature which might also have different metabolic and atherogenic roles in hyperlipoproteinemia.

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The effects of diltiazem on the suppression and regression of atherosclerosis were studied. Thirty-one rabbits were fed a 1% cholesterol (atherogenic) diet with the injection of saline (n=22) or diltiazem (n=9). After 10 weeks of feeding, 7 rabbits on the atherogenic diet with saline (n=7) or diltiazem (n=9) were killed. The remaining fifteen rabbits fed the atherogenic diet with saline were put on a standard (regression) diet with the injection of saline (n=7) or diltiazem (n=8) for the next 15 weeks.
As a control, 16 rabbits on a standard diet were used, half of which were killed at 10 weeks and other half were fed for the next 15 weeks.
The plasma LDL cholesterol level in the rabbits on the atherogenic diet with diltiazem was significantly lower than in those on the atherogenic diet with saline at 5 and 10 weeks. The aortic total cholesterol, esterified cholesterol, and calcium in rabbits on the atherogenic diet with diltiazem were significantly lower than in the rabbits on the atherogenic diet with saline.
At the end of 25 weeks (15 weeks on regression diet), plasma concentration of total, VLDL, LDL and HDL cholesterol, and triglyceride showed no differences in three groups.
Differences in aortic total cholesterol and calcium between two groups of regression diet were also insignificant, but aortic esterified cholesterol in the group of regression diet with diltiazem was significantly lower than in the group of regression diet with saline and in the group of atherogenic diet with saline.
The results suggested that diltiazem had a favorable effects on regression as well as suppression of atherosclerosis.

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A simple and highly reproducible culture method of aortic endothelial cells from cadaver is herein reported. Major bacterial contamination could be prevented by administration of an antibiotic cocktail consisting of gentamicin, ampicillin and amphotericin B.
Endothelial cells from the thoracic aorta were alive up to 15 hr postmortem and successfully culturable from the aorta by dispase desquamation from the subendothelial substrate. The cultured cells varied in size and shape depending on the degree of individual atherosclerotic severity and could be divided into two major subtypes. The first type is a small and polygonal uniform cell (typical endothelial cell) and the second type is a mixture of spindle and giant bizarre cells often associated with multinuclei (variant endothelial cell). Both types of endothelial cells have characteristics specific for endothelium, such as factor VIII related surface antigen, Weibel-Palade body and high productivity of prostacyclin.

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The endothelial lining of blood vessels is directly exposed to the effectors of immune and inflammatory reactions. But binding sites for complement and immunoglobulin G have not been observed by normal endothelial cells. Recently it was reported that receptors for third component of complement (C₃) and the Fc portion of immunoglobulin G (Fc) were expressed by virally infected endothelial cells and that deposition of C₃ and IgG was observed in atherosclerotic lesion.
We examined the localization of IgG and C₃ in cultured bovine endothelial cells with the use of immunofluorescence technique. It was observed that IgG and C₃ existed in injured cells which were visualized by a dye exclusion test, and no in uninjured cells.
These findings suggest that an accumulation of components of immune system in injured endothelial cells may be of importance for the destruction of endothelial cells and for the adhesion of white blood cells with regard to atherogenesis.

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There have been many reports about homocysteine (Hct)-induced endothelial cells (EC) injury. Then, we studied the inhibitory effects on fetal calf aortic EC injury by diltiazem, catalase or pyridoxal phosphate (Pal-P). Cell injury was determined by measuring of LDH level in the medium.
None of them had any effect on the cell injury in our experimental system. These results suggest that Hct-induced EC injury is not mediated by Ca²⁺ or H₂O₂ and is not inhibited by Pal-P. However, there are unresolved problems regarding to methods in researchs for interactions between Pal-P and Hct.

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Abnormal low density lipoprotein receptor (LDL-R) causes familial hypercholesterolemia (FH).
Some abnormalities of the LDL-R gene were revealed in FH patients, and common polymorphism in the LDL-R gene was reported. In order to analyze the gene abnormalities of FH, we compare the PvuII RFLP in the LDL-R gene of the FH patients with that of normolipidemic controls.
The results as follows:
1) There was no difference of the genotype distribution between 13 normolipidemic controls and 26 unrelated patients with heterozygous familial hypercholesterolemia.
2) The frequencies of two alleles were not significantly different from those reported by Humphries et al. and Hobbs et al.
3) Three patients with heterozygous FH (patient S. O. and her two daughters) had abnormal fragment of approximately 11.5kb length. This fragment may represent the abnormal LDL-R gene in this family.

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Previously we found a case of homozygous familial hypercholesterolemia with a defect in internalization of low density lipoprotein (LDL). Her LDL receptors were able to bind LDL normally but failed to cluster in coated pits. Hence transport of LDL into the cell could not occur in this case.
In the present study were analyzed the biosynthesis of LDL receptor in fibroblasts of this patient by labeling with ³⁵S-methionine followed by immunoprecipitation with anti-LDL receptor antibody.
The patient's cells synthesized LDL receptor with a molecular weight slightly smaller than normal in SDS polyacrylamide gel electrophoresis. Strikingly, a large portion of the synthesized receptors were secreted into the medium. It is supposed that the secretion was caused by the deletion of a part of the peptide chain near carboxy terminal which is necessary to anchor the receptor protein in the cytoplasmic membrane.

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Using anti-LDL receptor monoclonal antibody (IgG-C7), we analyzed biosynthetic process and cellular location of the LDL receptor in 10 kindreds with receptor-negative type familial hypercholesterolemia (FH).
1) From the analysis of cell surface binding to anti-LDL receptor antibody, we could devide the patients into two groups. Cells from 9 kindreds could not bind the antibody against the LDL receptor (CRM (-) type) and cells from one kindred could bind the antibody (CRM (+) type).
2) From the analysis of biosynthesis and processing, we could further divided the kindreds with receptor-negative/CRM (-) type into three different groups. Five kindreds produced no immunodetectable receptors (A). Two kindreds synthesized the receptors with markedly low level (B). Two kindreds synthesized precursor normally but the intracellular transport of the receptors was impared and little amount of the mature receptor existed on their cell surface (C). One kindred with CRM (+) type synthesized a unique receptor. The receptor of this kindred had an apparent molecular weight smaller than normal. The mature receptor once appeared on the cell surface but it was degraded rapidly. Thus the LDL receptor of this kindred had defects both in the ligand binding and in the stability of the receptor.
These data suggested that mutations occurred in various processes including synthesis, processing and ligand binding in our patients with receptor-negative type FH.

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In this study, we examined whether ¹²⁵I-VLDL was taken up by new human monocytoid leukemia cell line JOSK-I and the effects of competitors (LDL, HDL), Ca ion and pH in incubation media on its uptake. The following results were obtained.
1. VLDL was taken up by JOSK-I cells in manner of time and dose dependence and reached a plateau after saturable uptake. After the plateu of uptake, degradation of VLDL was remarkably increased.
2. Uptake of ¹²⁵I-VLDL was inhibited specificically by unlabeled VLDL, but not by LDL and HDL.
3. Uptake of VLDL was Ca ion dependent and remarkably increased in acidic pH.
4. Above characteristics of JOSK-I cells were similar to those of human peripheral blood monocytes.
5. Uptake of ¹²⁵I-VLDL was inhibited by hypertriglyceridemic VLDL as well as normal VLDL.
The results suggest that cell line JOSK-I has the mechanism of receptor-mediated uptake and degradation of VLDL and it is applicable to the investigation of VLDL receptor as the model of human monocyte/macrophages. The abnormal VLDL is also taken up via the same receptor as normal VLDL on these cells.

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To investigate the mechanism of hypercholesterolemia of STZ-diabetic rats caused by cholesterol feeding, we studied the receptor activity of liver membrane from the diabetic and normal rats. The metabolism of chylomicron in vivo was also studied. Following results were obtained.
1. The rate of removal of rat chylomicron from blood plasma was not different between normal chow fed diabetic rats and control, but delayed in cholesterol fed diabetic rats.
2. The binding of chylomicron to liver membranes was not different between normal fed diabetic rats and control and also was not affected by cholesterol feeding in both diabetic and normal rats.
3. The receptor activities were increased in estrogen-treated rats.
These findings suggest that the hypercholesterolemia in cholesterol-fed rats is not the result of impaired hepatic removal of chylomicron.

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To elucidate the role of apolipoprotein D in the lipid transfer reaction between lipoproteins, we purified apo D with our new method and examined the effect of apo D and anti apo D IgG on lipid transfer protein (LTP) assay system using apo A-I containing proteoliposomes as the lipid donor and LDL as the acceptor.
1) When purified apo D was added to the LTP assay system as LTP source, apo D showed no lipid transfer activity.
2) Apo D inhibited purified LTP activity dosedependently.
3) Anti apo D IgG had not a significant effect on the lipid transfer reaction in which we used purified LTP or plasma as LTP sample.
4) Anti LTP IgG showed 100% inhibition on purified LTP activity and plasma LTP activity.
These results indicate that apo D is not identical with cholesteryl ester transfer protein, but has some inhibitory effects on lipid transfer protein.

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The purpose of this study is to establish an assay system for the determination of phospholipid transfer activities in human sera, using pyrene labeled phospholipid that is 1-myristoyl-2[9(1-pyrenyl)nonanoyl] phosphatidylcholine (MPNPC). The principle of this assay system is based on the inherent properties of MPNPC which either occur in the form of dimer when concentrated, or in the form of monomer when diluted. The former emits a fluorescence of 475nm, whereas the latter emits a fluorescence of 396nm. Hence the amounts of transferred MPNPC can be determined without the prior separation of donor and acceptor vesicles, if both the fluorescence intensities at 396 and 475nm are measured.
Five mol percent mixture of MPNPC and egg phosphatidyl-choline (PC) was dissolved in ethanol (1%) and injected into a buffer, PC vesicles thus obtained were concentrated and fractionated on a Sepharose CL-4B column (donor). PC vesicles were prepared in the same way without MPNPC (acceptor). Transfer reaction continued in the buffer containing donor (0.01mg/ml) and acceptor (0.12-0.25mg/ml) at 37°C in the dark. After a 30 minute incubation, transfer reaction was stopped by placing the test tube on ice and then the fluorescence intensities at 396nm (M) and 475nm (E) were determined.
PC transfer rate remained unchanged in the wide range of acceptor concentration (Fig. 1). When human sera was added directly into the reaction mixture, transfer rate (log E/M) was increased in proportion to the amount of sera (2-20μl)(Fig. 2). Transfer activities of sera were determined in healthy controls and patients. No significant correlations were found between the transfer activities and the level of total cholesterol or HDL-cholesterol (Figs. 5, 6). No significant differences in transfer activities were observed between healthy controls and patients with ischemic heart disease, cerebrovascular disease or hyperlipoproteinemia (Fig. 7).

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The obese children were selected from approximately 10, 000 elementary school students and 4, 700 junior high school students. The incidences of obesity were 2.16%, 1.69%, 2.41% and 1.45% in male and female elementary school students and male and female junior high school students, respectively. Hypercholesterolemia was observed in approximately 30% of moderately to severely obese children (obesity index>130%). Incidence of hypertriglyceridemia in the obese children was around 10%. Plasma triglyceride levels were significantly increased in moderately (126.2±11.1mg/dl) and severely (163.3±29.6mg/dl) obese male junior high school children and severely obese female junior high school children (206.5±121.5mg/dl) than control (male; 78±4.4mg/dl, female; 78±4.0mg/dl). HDL-cholesterol measured by precipitation method using dextran sulfate and magnesium chloride, were decreased in moderately (50.7±1.5mg/dl) and severely (51.1±12.9mg/dl) obese male junior high school students and moderately obese female junior high school students (51.1±12.9mg/dl) than control (male; 61±3.0mg/dl, female; 63±2.7mg/dl). Plasma apolipoproteins (apo) A-I, B, C-II and E were measured by single radial immunodiffusion method. Significant differences were observed in plasma concentrations of apo A-I and apo B between the obese and non-obese children. Plasma apo A-I concentrations were significantly higher in moderately (164.0±3.5mg/dl) and severely (166.5±6.7mg/dl) obese male elementary school students, moderately obese male junior high school students (158.2±2.2mg/dl) and moderately obese female primary school students (149.4±12.1mg/dl) than control (130±6.2mg/dl). Hyper apo A-I lipoproteinemia observed in the obese children is in contrast to the decreased apo A-I levels in the obese adults, reported by Avogaro P. et al (Prog. Biochem. Pharmacol. 19: 141, 1983). Plasma apo B concentration showed significantly higher levels in the obese children (95.8±4.6mg/dl) than control (68±2.9mg/dl). Plasma apo C-II and apo E concentrations showed tendency to increase in the obese children. The present study clarified the characteristics of metabolic abnormalities of plasma lipids, lipoproteins and apolipoproteins in the obese Japanese children.

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The present study examined the relationship between obesity and atherosclerosis in the aged. The subjects were 531 cases over 60 years old who had undergone a 50g oral glucose tolerance test and were necropsied at Yokufukai Geriatric Hospital.
There were no differences in the numbers of cases with hypertension, hypercholesterolemia or diabetes mellitus between the obese and non-obese subjects.
The incidences of marked cerebral and coronary arteriosclerosis were significantly higher in the obese subjects than in the non-obese subjects.
On the other hand, there were no differences in the incidences of arteriosclerosis of the aorta, femoral artery or renal artery between the obese and non-obese subjects.
In the elderly, the total insulin levels in the obese and non-obese subjects were not statistically different from the normal and borderline type of 50g oral glucose tolerance test.
There were no differences in the incidences of fetal cerebral vascular disease or myocardial infarction between the obese and non-obese subjects. These results suggest that adiposity may not play an important role in the development of atherosclerosis in the elderly.

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We studied serum lipids and lipoproteins of healthy lean subjects. Those are total cholesterol (T. Chol), triglycerides (T-G), high density lipoprotein cholesterol (HDL-C), low density lipoproteins (LDL) and very low density lipoproteins (VLDL).
The data from 7, 952 were reviewed who had had medical check-up between April 1980 and April 1986. Of them, chosen were those who were in good health and weighed less than 80% of desirable weight for Japanese. They included 61 men and 53 women. Almost all of the men had habits of daily smoking and drinking, while all of the women did not. Healthy controls were also chosen from the same population, who weighed 95 to 105% of the desirable weight. They included 61 men matched with the lean male subjects for age, and daily consumption of cigarette and alcohol, and 141 women who did not smoke nor drink. The range of age was 30 to 69 years for men and 20 to 69 years for women.
Healthy lean subjects of both sexes were found to have significantly lower values of T-G and VLDL (p<0.01), and significantly higher ones of HDL-C (p<0.001). LDL levels tended to be lower than those of controls. No significant differences were noted in the levels of T. Chol. The data from subjects divided into groups of each 10 years of age showed the same tendency as the above-noted results. LDL levels were shown to have a weak linear correlation with age (r=0.48 in lean, and r=0.41 in controls).
The results of lipids and lipoproteins in our study of lean subjects would be considered to be in a mirror-image of those obtained from obese subjects by other investigators.

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It is well recognized that a change of fatty acid composition of plasma lipoproteins and cellular membranes alters membrane fluidity, producing significant influences on the functions of membrane-bound enzymes or lipoprotein receptors. It is important, then, to know whether or to what extent dietary fat manipulation may influence the fatty acid composition of lipoproteins and cellular membranes. We studied fatty acid composition of lipoproteins and membranes of hepatocytes and erythrocytes in rats after feeding of different fats.
Wister male rats were divided into two groups which received a diet supplemented with either butter or margarine. After several feeding periods plasma levels of lipids and fatty acid composition of phospholipids in high density lipoprotein (HDL), hepatocyte membranes and erythrocyte membranes were examined. Extraction of total lipids from HDL and hepatocyte membranes was conducted by the method of Folch, and from erythrocytes by the method of Rose. Isolation of total phospholipids was done by thin layer chromatography and fatty acid composition was analyzed by gas liquid chromatography.
Plasma levels of triglyceride and phospholipid after two weeks of feeding were significantly higher in the butter-fed rats than in the margarine-fed rats. The difference of cholesterol level did not reach a statistical significance.
Fatty acid composition of phospholipids in HDL, hepatocyte and erythrocyte showed a characteristic response for each feeding. The level of linoleic acid in HDL, hepatocyte and erythrocyte was higher in the margarine-fed rats and the level of arachidonic in HDL and hepatocyte was also higher in the margarine-fed rats. The level of oleic acid in HDL and hepatocyte and the level of palmitic acid in hepatocyte were higher in the butter-fed rats. These results show that the fatty acid composition in lipoproteins and cellular membranes responds well to a change of dietary fats.

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Effects of dietary Ca and Mg on coronary atherosclerosis in swine fed various levels of vitamin D₃ (VD₃) were studied. Progression of intimal thickening and Ca deposition were observed in swine fed mildly or highly excessive VD₃ when treated with high Ca or lower Mg. Degenerated smooth muscle cells were frequently present in the swine fed excessive VD₃ irrespective of dietary Ca or Mg levels. Progression of arterial lesions was obtained only when a significantly high frequency of degenerated smooth muscle cells was present. These results suggest that even mildly excessive VD₃ can induce coronary atherosclerosis when high dietary Ca or low Mg is present. Also, the presence of degenerated smooth muscle cells might be important in eliciting high Ca and low Mg effects.

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A patient with lipoprotein lipase deficiency which became manifest in the third trimester of pregnancy was reported. A 28-year-old woman, gravida 2, para 2, with a pregnancy of 37 weeks gestational age was admitted to the hospital because of high fever, abdominal pain, nausea and vomiting. On admission, marked tenderness in the upper abdomen and ascites were noted. Serum amylase, elastase 1 and triglyceride were markedly elevated to 2, 240u, 3, 200ng/dl and 11, 360mg/dl, respectively. A diagnosis of acute pancreatitis secondary to hyperchylomicronemia was made. A cesarean section delivery resulted in the birth of a healthy female infant of 2, 990g on the second hospital day, when treatments with total parenteral nutrition, antibiotics and Gabexate (FOY) were begun. The patient followed a favorable course after the delivery. Pancreatitis and hyperchylomicronemia were subsided in one month. The serum level of triglyceride declined to a normal value in 45 days concomitant with a lowering of apolipoproteins B, C-II, C-III and E. On 75th hospital day the patient was discharged. Lipoprotein lipase activities in post heparin plasma measured one month and seven months after the onset were decreased to 25% of the normal value. A fat load test done one year later disclosed a slow clearance of triglyceride in vivo. However, even the patient had been taking 50g of fat per day, the fasting serum level of triglyceride remained normal for 12 months.
The transient hyperchylomicronemia may be attributable to a partial LPL deficiency which became manifest during a course of pregnancy.

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A case with glycogen storage disease type I (GSDI) associated with hepatic tumor and severe hypertriglyceridemia was reported. A high density area (1.5×1.9cm) in seg. 8 was revealed by liver CT scan and multiple small fillings with contrast medium appeared in the late phase of the hepatic angiography. Transcatheter hepatic artery embolization (TAE) was performed, since malignancy was highly possible. Following TAE, serum triglyceride (TG) levels decreased transiently and returned to the initial levels after 5 weeks. Depressed liver cell function by TAE might cause a marked depression of the synthesis of TG rich lipoproteins. Post heparin lipolytic activity showed lipoprotein lipase (LPL) activity was extremely low, while hepatic TG lipase was subnormal. These data indicates that the mechanism of hypertriglyceridemia in the patients are combination of the overproduction of TG rich lipoproteins and deficiency of LPL.

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One female inpatient, K. N., aged 57 years, suffered from liver cirrhosis, hypothyroidism, hypoadrenalism and bleeding tendency. After admission she received the administrations of diuretics such as furosemide and spironolactone to improve her anasarca, and also those of levothyroxine and prednisolone to fill up the deficient thyroid or adrenal functions.
Slight to moderate elevations of transaminase activities, alkaline phosphatase activity of total bilirubin and increased gamma globulin concentrations were observed in this case, while low levels of triiodothyronine, total thyroxine, cortisol or urinary 17-hydroxycorticoid.
Serum LCAT activity was extremely decreased, that was, 16nmol/ml/hr. She also had extremely low levels of serum lipids or apoproteins. For examples serum total cholesterol was 16mg/dl, triglyceride 18mg/dl, HDL-cholesterol 8mg/dl, phospholipid 27mg/dl, apoproteins A-I, C-II or C-III 0mg/dl, A-II 2.8mg/dl, B 10mg/dl and E 0.8mg/dl. VLDL-Chol, VLDL-TG, VLDL-PL and LDL-TG were smaller in the proportions of lipoprotein fractions, while HDL-TG, LDL-Chol and LDL-PL larger.
One rare cirrhotic case with extremely low levels of serum lipids, apoproteins or lipoprotein fractions were shown in this article.

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The lipid levels of serum and lipoproteins were examined in eleven patients with myotonic dystrophy (MD) and ten normal subjects. Hyperlipoproteinemia was seen in six patients, including type IIb of three patients, type IIa of two and type V of one. Total cholesterol (C) and triglyceride (TG) levels of serum and lipoproteins in MD were not significant. TG/C ratio of lipoproteins in MD were not so high compared with normals.
The mean age of the patients with hyperlipoproteinemia was significantly higher than that of normolipoproteinemia. The correlation coefficients between age and lipid levels of serum and lipoproteins were examined. The age was positively correlated to serum C and VLDL-TG levels. Further, in the MD patients except for case 1 with type V hyperlipoproteinemia, the age was positively correlated to LDL-TG and LDL-C levels, and negatively correlated to HDL-TG levels.
In conclusion, the LDL levels increased and the HDL levels decreased with age in MD. These results suggest that the abnormalities of serum lipid metabolism is one of the characteristic changes in MD.

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Lipoprotein patterns and cholesteryl-ester transfer activity (CETA) were examined in the patient with familial hyperalphalipoproteinemia (FHALP). The proband was a 41-year-old Japanese male who was working as a plumber. He was found to have hypercholesterolemia, with serum total cholesterol level of 9.93mmol/l (382mg/dl) and HDL-cholesterol level of 4.60mmol/l (177mg/dl). HDL showed a high cholesterol/apo A-I ratio and appeared to have a larger-sized particle than normal HDL on agarose gel column chromatography. His father, two of the proband's siblings and one of the children showed higher HDL-cholesterol levels (91, 100, 75, 98mg/dl, respectively). Neither had cutaneous and tendinous xanthomas nor any clinical signs of atherosclerosis. Apo A-I isoforms of the proband was not different from that of controls.
Cholesteryl-ester transfer activity was studied by Dr. Albers et al. The proband appears to have only one-tenth the normal level of cholesteryl-ester transfer. However, the levels of lipid-transfer protein-I (LTP-I) activity were near normal. Thus this patient most likely has an exaggerated level of LTP-I inhibitor (s). The above mentioned data in the patient with FHALP presumably accounted for the increase in particle size and cholesterol enrichment of HDL.

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A case of HyperHDL-cholesterolemia woman was reported. Plasma HDL cholesterol level was 214mg/dl. Her mother, sister and 2 children were also HyperHDL-cholesterolemia: each HDL cholesterol level were 82mg/dl, 74mg/dl, 82mg/dl and 82mg/dl, respectively.
There were no clinical signs of atherosclerosis such as angina pectoris, calcification of aorta and atherosclerosis obliterance.
Zonal ultracentrifugation profiles of serum lipoproteins showed the marked increase level of HDL and the existence of HDLc like particles. Fat loading and heparin injection study suggested that there was no increase of HDL production from VLDL.
Patient's HDL and HDLG like particles were incorporated into rabbit hepatocytes samely as normal control HDL. The incorporation of normal HDL particles into patient's lymphocytes was lower than into lymphocytes from normal subjects.
These results suggest that marked HyperHDL-cholesterolemia in this case might be caused partly by the decreased incorporation of HDL into parenchymal cells due to disturbance of HDL-receptor function.

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We report here a case of amyloidosis associated with hyper-α-lipoproteinemia. An 80-year-old man admitted to our University Hospital because of foot edema and general malaise. Laboratory examination revealed slight increase in transaminase (GOT 149, GPT 146IU/l), remarkable elevation of alkaline phosphatase (ALP, 1, 241IU/l), and elevation of high density lipoprotein (HDL)-cholesterol (182mg/dl) as well as total-cholesterol (390mg/dl).
From the 29th admission day to the 34th day HDL-cholesterol was decreased to 19mg/dl. Totalcholesterol maintained an elevated level. ALP, which had already been at high level on admission increased to 2, 369IU/l at day 30. Total bilirubin was also increased and attained the level of 25mg/dl at day 47, when the patient died of hepatic failure. Liver tissue specimens taken immediately after death showed severe atrophy of hepatocytes secondary to dense amyloid infiltration.

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A case of 35-year-old women with an acute onset of diabetes mellitus followed by marked hyper-HDL-cholesterolemia was studied. Her diabetes was non-insulin-dependent, and the associated hyper-HDL-cholesterolemia was not related to insulin treatment.
Serum lipid analysis disclosed an increase in total cholesterol, cholesteryl ester, HDL-cholesterol, and phospholipids. Triglycerides were slightly decreased. Lipoprotein fractionation by preparative ultracentrifugation revealed both total cholesterol and phospholipids were markedly increased in the HDL₂ fraction, and were moderately increased in the LDL and HDL₃ fractions. However, they were markedly decreased in the VLDL fraction. Apo A-I, C-II, C-III, and E were also increased in the HDL₂ fraction. Thin-layer chromatography of phospholipids showed an increase in percentages of lecithin, but could not detect lysolecithin. There was a wide fluctuation in the HDL-cholesterol level, and this was accompanied by a parallel changes in the cholesteryl ester, phospholipids, apo C-II, C-III, and E levels. The apo A-I and A-II levels did not show such changes. The LDL-cholesterol calculated by Friedewald's equation were normal to moderately increased. However, they did not fluctuate concomitantly to HDL-cholesterol. When the fasting blood sugar level elevated, the HDL-cholesterol level was also markedly elevated. A positive correlation was noted between these two levels. In contrust, no correlation was found between the cholesterol and triglycerides levels. The determination of postheparin lypolytic activities and lecithin-cholesterol acyltransferase (LCAT) activity revealed that hepatic triglyceride lipase (HTGL) activity was decreased, and both lipoprotein lipase and LCAT activities were normal.
In summary, marked hyper-HDL-cholesterolemia seen after acute onset of diabetes mellitus was caused by an increase in the HDL which was enriched in cholesteryl ester and phospholipids, and differed from the ordinary HDL by containing apo E. A wide fluctuation in the HDL level, and the positive correlation of HDL-cholesterol to fasting blood sugar are peculiar findings to this case, and these are opposit to those found in most studies on non-insulin-dependent diabetes mellitus. The decreased HTGL activity and the limited availability of VLDL for the lipid transfer process between HDL and VLDL were probably impaired the HDL catabolism, and resulted in marked hyper-HDL-cholesterolemia of this case.

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Pulse wave velocity of aorta (PWV) was measured and chest X-ray was taken in 114 patients.
PWV is a method of examining the degree of atherosclerosis non-invasively. The first left arch of mediastinum in the frontal image of a chest X-ray represents a part of the aorta, and it changes depending on the degree of atherosclerosis.
PWV was studied comparatively with regard to the degrees of calcification and projection of the aortic arch, and the following conclusions were arrived at:
(1) The aortic arch calcification group in chest
X-ray showed a significantly higher PWV value than the non-calcification group (p<0.001).
(2) However, as a result of the comparison of PWV between the groups of calcification and noncalcification at the same age above the 40's, no significant difference was obtained except in the 50's.
(3) The group with prominent projection of the aortic arch towards the left shoulder joint showed a significantly higher PWV value than the group with a slight projection (p<0.05).
From the above, it is considered justified to suspect an atherosclerotic disease in cases showing the above changes of the aortic arch and to examine them thoroughly.

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Eleven fetus rats and three rats at the 1, 5, 9, 17 days after birth were subjected for the study. ³H-thymidine (5μC/g body weight) was injected into the rat abdomen, one hour before sacrifice.
The aorta and heart were fixed with formalin and dehydrated by ethanol and xyrol. Hematoxylin eosin was used for the stain. The aorta was divided into three layers of the intima, media and adventitia.
The heart was divided into the left and right ventricles and the septum. These parts were counted for ³H-thymidine labelled cells on 33 blick fields totally 99 parts in each rat. The averaged ³H-thymidine labelled cells in the heart were 2, 829 in fetus and 2, 267, 3, 534, 3, 231 and 283 at 1, 5, 9 and 17 days after birth. In the aorta, the number of ³H-thymidine labelled cells were counted 599, 502, 732, 392 and 38 in fetus and at the time of 1, 5, 9 and 17 days after the birth, respectively.
These data suggested that a suppresive effect on DNA synthesis in vascular wall was observed during the period from 9 to 17 day after birth. The vascular wall and the left ventricle and seputum were remarkably thickened and the incorporation rates of the ³H-thymidine were increased.

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Nonenzymatic glycation is called a Maillard reaction, which is a nonspecific binding reaction between proteins and sugars, occurring not only with hemoglobin but also other tissue proteins. Nonenzymatic glycation increases with increasing age and in tissues in diabetic patients.
In order to investigate the relation between arteriosclerosis and nonenzymatic glycation, we determined the nonenzymatic glycation of aorta protein using furosine which is a specific degradation product of fructose-lysine upon acid-hydrolysis. The aorta specimen was collected at autopsy and the severity of arteriosclerosis of the aorta was graded according to the criteria established by Gore.
The furosine levels in the aorta with arterio-sclerosis were significantly higher than those in the aorta without arteriosclerosis. A significant positive correlation was found between the grade of arteriosclerosis and the furosine level in the aorta.
It is considered that an increase in nonenzymatic glycation in the human aorta may be an etiological factor of arteriosclerosis.

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The tunica media of aortas of control male rats in age from 1 to 12 months and estradiol-treated rats in age from 6 to 12 months were examined by light and electron microscopy. Light microscopically any changes of the aortas of control rats and estradiol-treated rats were not found, but collagen fibers were increased in the media of 6 and 12 months in control rats.
Electron microscopically the media of control rats showed atrophic changes of smooth muscle cells, increasing of collagen fibers and thinning or fragmentation of elastic fibers with age. The estradiol administration inhibited the aging changes of the aortic media.

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Physiological effects of pyridoxal 5'-phosphate (PLP) on enzymatic reactions of cross-linking formation in collagen and elastin were studied. In the previous report of authors, it was observed that PLP combined with β-aminopropionitrile (BAPN) and considerably inhibited the BAPN induced depression of activities of vitamin B₆ dependent enzymes in vitro. In this study, we performed an animal experiment using SD rats fed the lathyrogen (BAPN) and the effects of PLP on these animals were examined.
Thirty male SD rats were separated the following five groups: Group 1, three rats fed just a standard diet as control. Group 2, six rats receiving 250mg/kg/day of pyridoxine hydrochloride (PIN). Group 3, seven rats receiving 300mg/kg/day of BAPN. Group 4, seven rats receiving the same dose of BAPN as rats of group 3 and 125mg/kg/day of PIN. Group 5, seven rats receiving the same dose of BAPN as rats of group 3 and 250mg/kg/day of PIN. Authors observed the occurrence of death to be due to lethargic dissection of aorta for 189 days.
During the observation period, six rats of group 3 and six rats of group 4 died evidently on account of toxic effects of BAPN. But there were three survivors in group 5. It was generally observed that mean value of days required to occur lethargic dissection of aorta in group 5 was longer than those of groups 3 and 4.
From these results, it was concluded that the existence of sufficient dose of vitamin B₆ may be necessary for mainteining the activity of lysyl oxidase which is the key enzyme for cross-linking formation of collagen and elastin, and lethargic dissections of aorta in rats caused with BAPN were inhibited by the administration of vitamin B₆.

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Antigenic substance which was recognized by monoclonal antibody EMR1a/212D against extracellular matrix deposited with lipids was analyzed in this study. In WHHL rabbit serum the substance was detected. The antigenic substance was partially purified from serum by ammonium sulfate precipitation and DEAE-Sepharose CL-6B column chromatography. It was a glycoprotein containing sialic acid with a molecular weight of 66, 000.

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During the last four years, 415 patients were diagnosed as having ischemic heart disease at the Outpatient Clinic of the Second Department of Internal Medicine, Gunma University Hospital. Of these, 327 were males and 88 were females. The male to female ratio decreased with the advancing age, from 7.7 in the fourth decade to 1.6 in the eighth decade.
In the females, the incidences of diabetes mellitus and the history of hypertension were more frequent in the patients of is chemic heart disease than in the control group. The serum total cholesterol and the serum apoprotein A-I were significantly higher in the ischemic heart disease group, and there was a significant positive correlation between the serum total cholesterol and the severity of angiographically determined coronary atherosclerosis. As compared with the males, the relative impact of serum total cholesterol and diabetes mellitus in ischemic heart disease was substaintially great in the females. On the other hand, the correlation was not obvious between the serum triglycerides and apoproteins A-II and B, and the weverity of the coronary atherosclerosis.

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In a previous report from a epidemological study in Japan, it was clearly shown that the average of serum cholesterol level in the population has increased during the past 20 years, accompanying the increase in adipose tissue content noted by skinfold. It may be likely that the accumulation of body fat enhances the correlation between saturated fatty acid and hypercholesterolemia.
In this study, we set out to establish whether dietary calorie-restriction is feasible and effective in the treatment of hypercholesterolemia in general practice.
Twenty-six patients with type II hyperlipoproteinemia in out-patient clinic were allocated to 2 groups which one was the group (effective group) with 10% reduction of plasma LDL (low density lipoprotein) after 6 weeks of dietary instruction and other was the group without reduction of plasma LDL. These patients on non-medication for hyperlipidemia were randomly instructed on how reduce carbohydrate intake or animal fat intake by dietcian. Age, plasma cholesterol, triglyceride level, relative body weight, and the background of dietary habitude shown by interview method before the instruction were matched in the two groups.
The 11 of 26 patients with hypercholesterolemia were decreased in LDL after 6 weeks of dietary instruction. In these patients, the reduction of body weight was significantly high if compaired with the non effective group. It depends on decrease in intake of calorie due to reduce the intake of carbohydrate. But change of animal fat intake was variable in both groups.
The frequency of decreased carbohydrate/Energy ratio after dietary instruction was found in 9/11 (82%) on effective group and 4/15 (27%) in non effective group (x²=7.72, p<0.01).
In these results, we concluded the dietary factors for hypercholesterolemia was relatively high ratio in carbohydrate/Energy-intake, and animal fat was not yet major dietary factor for hypercholesterolemia in population of Japan.

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