This lecture is composed of clinical and pathological findings of the subjects aged 60 years or more, selected at random, concerning on atherosclerosis of the major cervical and intracranial arteries.
(1) The cross sectional study of the carotid and vertebral arteries revealed a stenosis of more than 50% in 15 to 25% of the patients examined. Complete occlusion was found in 2% in the internal carotid and in 6% of the vertebral arteries. In more than half of the cases, the degree of stenosis of the internal carotid was almost the same to the external carotid. Right internal carotid was more stenotic than the left.
The incidence of severe atherosclerosis of the cervical arteries did not differ by decades.
(2) In the cerebral arteries, incidence of atherosclerosis was well paralleled to the advance of age, based on the autopsy materials collected through Japan.
Sclerosis of the middle cerebral became more prominent with advancing age, while this tendency was not seen in the basilar system. We named the middle cerebral as “Life Artery” for its influence on human daily activity and basilar as “Living Artery” for its importance of maintaining life. Man cannot survive longer when the grade of the “Living Artery” surpasses a critical level. We also regard the coronary artery as another example of “Living Artery”.
(3) In our materials, grades of atherosclerosis are more advanced in the intracranial than in the extracranial arteries, which is a marked difference from the western countries.
(4) In general, cervical and cerebral atherosclerosis is clinically silent, although the following rare cases are known; hydrocephalus owing to mechanical disturbances of the elongated basilar artery; blindness or hemianopsia by chiasmal compression of the dilated anterior cerebral or internal carotid arteries. Tortuous vertebral and basilar artery may cause hemifacial spasm or numbness.
Advanced cerebral atherosclerosis is almost always known by an abrupt onset of brain ischemia. Some phenomena which suggest cerebral atherosclerosis are clinically important. According to our results, the subjects with carotid bruit were found to have significantly severe cerebral atherosclerosis and more frequently show cerebral infarction than in the no-bruit patients.
Vertigo was occasionally found in the cases with severe atherosclerosis on the vertebro-basilar system.
Aortic-arch calcification visible on the chest X-ray films was significantly more frequent in the patients with severe cerebral atherosclerosis.
(5) The risk factors of cerebral infarction differed by its location, i. e., cortical or perforating arterial system. Important risk of the cortical type infarction was severe sclerosis of the cerebral arteries. In the perforating arterial system, high hematocrit value, hypertension and angionecrosis are important. In massive cerebral hemorrhage, both hypertension and angionecrosis are main risk factors. Old subjects with high blood hematocrit values are prone to cerebral infarction when they have severe cerebral atherosclerosis, while this tendency was not recognized in the cases with none or slight sclerotic changes.
Platelet aggregability is occasionally accelerated in the perforator system infarction.
(6) Dementia is not a specific clinical picture of the elderly with severe cerebral atherosclerosis if they don't have multiple vascular lesions in the brain. Some neruotransmitters were significantly decreased in the patients with multi-infarct dementia, although the grades of which were not so severe as in senile dementia of Alzheimer type.
(7) A significant correlation between the low HDL-cholesterol (HDL-C) and cerebral infarction, especially of cortical type, was found. In liver chirrosis, HDL-C is also low because of a decrease of HDL₃-C; whereas, in cerebral infarction, the decrease was principally due to HDL₂-C. In some diseases of the nervo

抄録全体を表示

It is already reported that glucocorticoids increase the plasma level of cholesterol by promoting the synthesis of cholesterol in the liver and by decreasing its excresion to faces. To clarify the relationships of glucocorticoids with the formation of atherosclerosis, lipoprotein patterns of steroidinduced hypercholesterolemia were analyzed, and their possible role were discussed relating to its atherogenicity. Clinically, the changes of lipoproteins in collagen disease patients who were administered glucocoriticoids were studied. Increases in serum total cholesterol, triglyceride and phospholipid level of steroid-administered patients were obseved comparing to the control people. Increased cholesterol, triglyceride and phospholipid were observed mainly in very low density lipoproteins and in high density lipoproteins, but not in low density lipoproteins.
Next, the effect of glucocorticoids administration (20mg of hydrocortisone for 14 days) on lipoprotein pattern of rabbits were examined. Serum triglyceride and phospholipid levels were significantly increased. These increases were chiefly observed in VLDL but not in LDL or HDL. Acid cholesterol esterase and acid lipase activities of steroid-administered aorta were increased, but acylcoA cholesterol acyl-transferase activity (ACAT) was not changed. These results suggested that hyperlipidemia observed in steroid-administration might not be so atherogenic from the lipoprotein profiles. The production of intermediate lipoproteins and its role were still unclear. An increase in lysosomal cholesterol esterase and unchanged ACAT activity might be against cholesterol ester accumulation in the arterial wall. Relative decrease in LDL comparing to an increase in VLDL by steroid-administration to patients, suggests that degradation system of VLDL might be impaired by glucocorticoid.

抄録全体を表示

We have compared lipoprotein lipid changes in third trimester pregnant Japanese women and late gestation (day 21) rats and determined the effect of pregnancy on HDL apoprotein and cholesterol turnover. In agreement with previous studies in pregnant Caucasians, elevations are observed in pregnant Japanese subjects in plasma triglyceride, cholesterol and phospholipid concentrations of total plasma, VLDL, and LDL. In HDL, triglyceride and phospholipid concentrations are markedly increased but cholesterol increases to only a small and non-significant degree. The triglyceride increase in LDL and HDL is markedly greater than cholesterol or phospholipid, a pattern similar to that seen in oral contraceptive treatment. There is little change in VLDL composition. In late gestation rats, many similar changes are observed with increases in triglyceride, cholesterol, and phospholipid concentrations in total plasma and VLDL. In LDL, cholesterol and phospholipid concentrations are increased. Unlike human pregnancy, triglyceride concentrations are not increased in LDL and HDL. HDL cholesterol and phospholipid concentrations are also not significantly increased in the pregnant rat, but total HDL protein and individual HDL apoprotein (determined by SDS polyacrylamide gel electrophoresis) were increased 60% or more.
To test the possibility that the metabolism of HDL apoprotein and cholesterol are increased in late gestation despite the absence of a change in HDL cholesterol concentration per se, in vivo metabolism of HDL was studied in both nonpregnant and pregnant rats. Animals were injected with preparations of HDL which were obtained from non-pregnant rats and labeled with ¹²⁵I in the protein moiety or ³H in the esterified cholesterol moiety. No differences were observed in fractional catabolic rate (FCR) and half-life of HDL protein between non-pregnant and pregnant rats. However, the calculated synthetic rate of HDL-protein was increased three-fold on the basis of the marked increase in plasma volume in pregnancy. Similarly, FCR and half-life of esterified ³H-cholesterol in compartment of pregnant rats did not differ from those of non-pregnant rats, but calculated HDL cholesterol ester synthetic rate increased approximately two-fold in pregnancy. These changes in lipoprotein metabolism may be caused by increasing estrogen concentrations during the late stage of pregnancy.
The results indicate that HDL protein and esterified Cholesterol turnover are increased in late pregnancy despite the absence of an increase in HDL cholesterol concentration per se. The increased turnover could enhanced cholesterol delivery to steroid hormone secreting organs with a high cholesterol requirement, and particulary the placenta. Increased HDL turnover could also enhance recovery of tissue cholesterol from other maternal tissue and offset an otherwise potentially atherogenic shift in the HDL cholesterol to total cholesterol ratio in pregnancy.

抄録全体を表示

We have previously reported, based on the standardization of the turbidometric method for the measurement of platelet aggregation (PA), that PA in arteriosclerosis is enhanced in the chronic state. The aim of this report is to investigate the effects of eicosapentaenoic acid (EPA), precursor of prostaglandins of the 3-series, on PA, bleeding time and fatty acid composition of plasma and platelets in man. We administered two types of EPA to the same volunteers, one was free EPA which was administered in capsule form (purity 73%), the other was EPA ethyl ester in capsule form (purity 66%), and the former was administered in summer, the latter in winter. We measured PA, bleeding time and fatty acid composition in 12 volunteers (10 patients with arteriosclerosis and 2 normals, mean age 60.7 years) before administration of EPA 2g/day, 10 days after administration in the case of free EPA and 2 weeks after administration in the case of EPA ethyl ester. ADP-, collagen- and adrenalineinduced PA were studied by the turbidometric method. Fatty acids were analysed by gas-liquid chromatography. The bleeding time was measured by Duke's method. The following conclusions were drawn from this study.
1. In the case of administration of free EPA, ADP- and adrenaline-induced PA increased significantly after administration (ADP: p<0.01, adrenaline: P<0.05), but collagen-induced PA showed no significant change. In the case of administration of EPA ethyl ester, all of these types of induced PA decreased significantly after administration (ADP: p<0.02, bovine collagen: p<0.01, equine collagen: p<0.02, adrenaline: p<0.01).
2. There was no significant change of bleeding time after administration of free EPA or EPA ethyl ester.
3. Lipid analysis demonstrated that EPA levels in platelet phospholipid and in plasma increased significantly after administration in both cases of free EPA and EPA ethyl ester (p<0.001), and that the arachidonic acid (AA) level in plasma increased significantly after administration of free EPA (p<0.05), but in the case of EPA ethyl ester there was no significant change of AA in plasma and there was no significant change of AA in platelet phospholipid in both cases of free EPA and EPA ethyl ester.
These results show that different effects of EPA on PA may be produced by difference of season of administration, duration of administration and type of EPA (free or ethyl ester), and that PA decreases after administration of EPA ethyl ester in winter, and suggest that EPA ethyl ester may have beneficial actions in the treatment of patients with arteriosclerosis who show enhanced PA.

抄録全体を表示

Abnormaly milky plasma appeared in donated blood was analyzed. The prevalence of milky plasma in 7, 877 subjects was 4.6%, and was found to be higher for the plasma from male than that from female donors (male 5.9%, female 2.6%, p<0.01). For male, the prevalence of milky plasma from the donors aged 30-59 years was higher than that from those aged 16-29 (p<0.001). The samples of milky plasma from 51 subjects were determined for their lipid levels; cholesterol level was in normal range, triglyceride remarkably high, and phospholipid slightly higher than normal. Furthermore, the analysis of lipoprotein showed low HDL-cholesterol, normal LDL, and remarkably high VLDL and chylomicron levels. Triglyceride content positively correlated with the chylomicron level (r=0.93).
The lipid contents and postheparin lipolytic activities of 9 subjects (7 males and 2 females), who donated milky plasma, were re-examined after over-night fasting. Five of these subjects showed normal serum lipid levels, but lipoprotein lipase activities in postheparin plasma were significantly low. The other four subjects showed still high triglyceride levels, and appeared to be type IV (3 subjects) and type III (1 subject) hyperlipoproteinemia.
These results show that there are significantly high prevalence of hyperlipemia, especially after the meal, among the people without any symptom. It should be investigated whether or not those transient hyperchylomicronemia with decreased HDL-cholesterol level could be one of the risk factors of atheroscrelosis.

抄録全体を表示

Serum cholesterol (Ch), HDL-Ch and triglyceride (TG) levels were measured in 342 school boys and 358 girls aged 6-14 years in Shinjo City in Nara Prefecture near Osaka. The average Ch level for each class (age group) of the primary school ranged between 173-186mg/dl for boys and 168-183mg/dl for girls. These values are considerably higher than those reported by Princeton study and Bogalusa heart study in U. S. A. The average Ch level in junior high school boys (164mg/dl) was significantly lower than the levels in younger boys.
The average TG level ranged between 58-78mg/dl in boys and 64-78mg/dl in girls. The average HDL-Ch level was 66mg/dl in boys, 62mg/dl in girls in the primary school and 63mg/dl in boys and girls in junior high school.
The prevalence of hypercholesterolemia (Ch> 230mg/dl) was 3%, and the family study revealed an inheritance of hyperlipidemia in 10 out of 17 boys and girls investigated. Possible diagnosis of familial hypercholesterolemia was given for two families.

抄録全体を表示

Ascochlorin had been isolated by the present authors from the culture broth of a fungus, Ascochyta visiae. As reported previously, its derivative 4-0-methylascochlorin (MAC) treatment markedly reduced the saline intake and urine volume in deoxycorticosterone acetate-loaded uninephrectomized rats.
This report mainly deals with effect of 4-0-hydroxycarbonyl methyl ascochlorin (AS-6), an ascochlorin derivative, on blood and urinary glucose in genetically obese diabetic mice, C57BL/ksj dbm⁺(dbm mice). The earliest abnormalities of dbm mice are a tendency towards obesity, a high level of circulating insulin and hyperglycemia. As the disease progresses, dbm mice show such symptoms as hyperlipoproteinemia, polyuria, polydipsia and glucosuria similar to an early stage of human maturity-onset diabetes mellitus.
When AS-6 (0.1% and 0.2%) was given mixed in the commercial diet CE-2 (Nikon CLEA) for 6 days to dbm mice, the urine volume, drinking water and urinary excretion of electrolyte (NA⁺, K⁺) were remarkably reduced without affecting diet intake. But the diet intake was significantly decreased at the higher dose of AS-6. In addition, the agent decreased urinary excretion of glucose in amount and concentration in dbm mice. The experiment was performed as to whether the improvement of glucose metabolism in the kidney was attributable to the reduction of urinary glucose excretion or not. Kidney slices derived from AS-6 treated mice increased glucose uptake, lactate and CO₂ production above the dbm controls.
The dbm mice were fed ad libitum the CE-2 containing 0.1% AS-6 for 1 week and AS-6 treatment reduced serum glucose by 19% and triglyceride 52% as compared with the dbm control. The serum IRI was elevated 6.7 times above their thin littermates. However, serum IRI fell after AS-6 treatment to 80% of the dbm control.

抄録全体を表示

The purpose of the present study was to characterize by heparin-Sepharose affinity chromatography, very low density lipoprotein (VLDL) of insulin deficient diabetic rats induced by streptozotocin, in order to provide some insight into causes for increased atherosclerotic cardio-vascular diseases associated with diabetes mellitus. Diabetes was induced in rats by intravenous injection of streptozotocin (STZ), 65mg/kg body weight. Plasma VLDL was isolated by ultracentrifugation at density 1.006g/ml in a type 50.3 Ti rotor on the Beckman L5-50 ultracentrifuge. VLDL dialyzed against 2mM sodium phosphate buffer, pH 7.4 containing 0.05M NaCl, were applied to a heparin-Sepharose 4B column (2.5× 10.0cm) equilibrated with 2mM sodium phosphate buffer, pH 7.4 containing 0.05M NaCl and eluted stepwise at 0.05M, 0.15M and 1.0M NaCl in 2mM sodium phosphate buffer, pH 7.4. In order to characterize the fractions of heparin-Sepharose 4B affinity chromatography of VLDL, percent distribution of lipid and particle sizes of lipoproteins by electron microscopy were studied after concentration approximately 15 times by ultrafiltration utilizing Diaflo Ultrafiltration membrane, YM 10 (Amicon Co., Lexington, Mass.) at 4°C. Samples for sodium dodecyl sulfate polyacrylamide gel electrophoresis were concentrated by lyophilization. Cholesterol, free cholesterol, triglyceride and phospholipid concentrations were measured enzymatically. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) was performed by 10 percent polyacrylamide in the presence of SDS. Sizes of lipoproteins negatively stained with sodium phosphotungstate were studied by electron microscopy. Heparin-Sepharose affinity chromatography of VLDL from control rats showed two peaks of heparin-bound and-unbound lipoproteins. VLDL from STZ-induced diabetic rats resulted in the appearance of lipoprotein eluted by 0.15M NaCl. Twelve of 15 VLDL preparations (80%) from diabetic rats showed this elution pattern. The lipoproteins eluted at this position were not observed by analyzing 7 preparations of VLDL from control rats. In diabetic rats, bound fraction eluted by 1.0M NaCl was the major fraction. Composition of lipid in unbound (0.05M NaCl) fraction and bound (1.0M NaCl) fraction of VLDL from control rats was investigated. Percent distribution of triglyceride in bound fraction was lower than in unbound fraction. Percent distribution of cholesterol was higher in bound fraction than in unbound fraction. Either of free and esterified cholesterol was increased and free/ester cholesterol ratio also increased. Composition of lipids in the fractions of VLDL from diabetic rats disclosed that 1.0M NaCl fraction had lower percent disbribution of triglyceride and cholesterol than 0.15M NaCl fraction in 2 of 3 preparations. Percent of phospholipid to total lipid was higher in bound fraction than in unbound fraction in 2 of 3 perparations. Apolipoprotein (Apo) composition of fractions of VLDL from diabetic rats was studied by SDS PAGE. One molar NaCl fraction exhibited the dark band which corresponds to Apo E. Unbound fraction (0.05M NaCl) and bound fraction eluted by 0.15M NaCl showed the bands comparable each other, although the slower migrating and unidentified bands were observed. The results indicated that bound fraction eluted by 1.0M NaCl is composed of Apo E-rich lipoproteins. Size of lipoprotein particles in 1.0M NaCl fraction was significantly smaller than those in 0.05M NaCl fraction from control rat. Sizes of lipoprotein particles prepared from diabetic rats were much more heterogeneous than those from control rats. In diabetic rats, size of lipoprotein particles in 1.0M NaCl fraction was significantly smaller than those in 0.15M NaCl fraction. Furthermore, lipoprotein particles from diabetic rats were larger than those from control rats. These data indicated the heterogeneity of VLDL in terms of affinity to heparin. VLDL from diabetic rats showed the higher affinit

抄録全体を表示

Coenzyme Q₁₀ and cholesterol were measured respectively in VLDL, LDL and HDL fractions of fasting serum separated by ultracentrifuge in eleven healthy subjects, nine diabetics without complications, eight diabetics with nephropathy and eight diabetics with coronary sclerosis.
Coenzyme Q₁₀ level was correlated significantly with cholesterol level in each fractions.
In the diabetics with nephropathy or coronary sclerosis, coenzyme Q₁₀ level was more increased than that in diabetics without complications in VLDL fraction, but decreased than that in diabetics without complications in HDL fraction.
About the coenzyme Q₁₀/cholesterol ratio, there is no correlation in each fractions.
From these results it was suggested that the coenzyme Q₁₀ level in lipoprotein fraction possessed the correlation with its vascular complications.

抄録全体を表示

It is important to treat serum hyperlipidemia in patients with diabetes mellitus in order to prevent diabetic complications.
1. By reducing body weight (BW) more than 2kg for 20 months, fasting blood sugar (FBS), total cholesterol (T-C) and triglyceride (TG) levels decreased significantly in 23 patients with diabetes mellitus.
2. There were significant correlations between relative body weight ratio and serum HDL cholesterol (HDL-C) or T-C/HDL-C ratio in 140 cases with glucose intolerance.
3. In 92 cases with diabetes mellitus, the change of T-C (ΔT-C)/the change of body weight (ΔBW) ratio tended to increase, when T-C was more than 210mg/dl. The ratio of ΔTG/ΔBW also tended to increase, when TG was more than 120mg/dl.
4. There were observed significantly a negative correlation between serum HDL-C and relative body weight ratio, negative correlations between serum HDL-C level and TG or LDL Cholesterol levels, and positive correlations between FBS and T-C or TG in 97 cases with glucose intolerance.
5. By reducing BW more than 1kg for 1 to 19 months in 182 male cases with diabetes mellitus, serum HDL-C tended to increase, when HDL-C was lower, and serum T-C or TG tended to decrease, when TC or TG was more than 210mg/dl or 120mg/dl respectively.
6. By administration of glucomannan for 3 months in 19 cases with glucose intolerance, serum T-C or TG decreased in 63.2% or 42.1% respectively.
7. By administration of aluminium clofibrate for one month, serum HDL-C tended to increase, and TG tended to decrease in 23 cases with glucose intolerance.

抄録全体を表示

Hyperlipidemia can be often seen in Type 2 diabetic and IGT subjects in whom hyperinsulinemia are frequently observed. We studied the effect of insulin on hepatic fatty acid (FA) oxidation and lipid synthesis from palmitate, glucose and acetate.
1) As an early effect, insulin alone dose not affect fatty acid metabolism but insulin inhibits FA oxidation stimulated by submaximal dose of glucagon.
2) After 6 hours, insulin exhibits inhibition of FA oxidation and stimulation of TG formation from palmitate.
3) After 24 hours, insulin enhances lipid synthesis mainly TG formation from glucose.
4) As a delayed effect, insulin stimulates cholesterol and TG synthesis mainly in LDL and VLDL fraction from acetate.
In summary, insulin is necessary for the hepatic esterification of fatty acid (VLDL). Hyperinsulinemia seems to induce hypertriglyceridemia (VLDL) and hypercholesterolemia (LDL), although the former is more common product from dietary carbohydrate.

抄録全体を表示

The degradation of ¹²⁵I-labeled low density lipoprotein (¹²⁵I-LDL) was examined in both lymphocytes and monocyte-derived macrophages which were obtained from the same blood samples. As for lymphocytes, after the separation from the blood and the 3-days' culture with 10% lipoprotein deficient serum (LPDS), 10μg/ml of ¹²⁵I-LDL were added to the medium in the presence or the absence of 250μg/ml nonlabeled LDL, and then the lymphocytes were incubated for 5 hours. The radioactivity of the trichloroacetic acid-soluble fraction of the medium was measured and the degradation per cell protein was calculated according to the well-known methods.
The receptor-mediated degradation of LDL by lymphocytes was from 0.8% to 15.8% in homozygotes of familial hypercholesterolemia (FH) as compared with that of normal controls, and in heterozygotes the degradation was intermediate between homozygotes and controls. These data coincide well with those of Goldstein et al.
The 4-5 days' culture with 20% human serum altered monocytes to macrophage-like figures and the assay of the degradation was made on day 10. The degradation of LDL by monocyte-macrophages from normal subjects showed the saturable course when the concentration of LDL in the medium was increased, suggesting that those cells metabolised LDL with the high affinity process, namely the LDL receptor-mediated pathway.
The macrophages from a female homozygote of FH, in which the capacity of her lymphocytes to degrade LDL by the receptor-mediated pathway was only 0.8% of that of the normal control, degraded two and a half times more LDL than the macrophages from controls and the competitive study revealed that most of the LDL had been degraded by the receptor-independent pathway.
The importance of the interaction between the denatured or altered LDL and macrophages has been pointed out in terms of atherogenecity, but our data suggest that there may be some differences in macrophages themselves between normal subjects and the atherosclerotic patients as well as FH and that these difference may contribute to the development of atherosclerosis.

抄録全体を表示

Three cases of familiar hypercholesterolemia were found to represent the phenotype similar to Type III hyperlipoproteinemia, having broad β band in PAG-disc electrophoresis of lipoproteins and high ratio of cholesterol against triglyceride in very low density lipoprotein (VLDL) with increased intermediate density lipoprotein (IDL). The analysis of apo E in VLDL by means of isoelectric phocusing revealed decreased apo E in one case of them and normal level of apo E₃ in the rest two cases.
The two cases without apo E₃ deficiency showed impaired Post Heparin Lipolytic Activity (PHLA), especially Hepatic Triglyceride Lipase, suggesting impaired degradation of IDL. In all of the cases, clofibrate treatment coverted the lipoprotein pattern from Type III to Type IIa and decreased serum triglyceride, while serum cholesterol did not change substantially and even increased in one case by this drug treatment. The data above suggest that familial hypercholesterolem is may represents not only Type IIa or IIb but also Type III as phenotype caused by coexisting disorders of lipoprotein metabolism.

抄録全体を表示

We report a case of familial lipoprotein lipase deficiency. The patient was a 41-days-old female infant. The parents are second cousins. At about 25 days of age, she was noted eruptive xanthoma over the face and the trunk. At 41 days of age, she was noted poor sucking ability and was taken to a hospital. Hepatosplenomegaly, lipemia retinalis and foam cells in bone marrow were noted. The plasma was separated to a thick creamy layer and a clear infranatant after 48 hours in a refrigerator. Chemical analysis disclosed markedly elevated hypertriglyceride level. Lipoprotein electrophoresis showed a pattern of type I hyperlipoproteinemia. PHLA of the patient was within normal limit, but LPL was selectively deficient. Moderate deficiency of PHLA, LPL, and H-TGL was noted in her mother. The patient was diagnosed as familial LPL deficiency and her mother as heterozygote. After the administration of the MCT formula, the turbidity of the plasma was resolved and marked reduction of the serum triglyceride concentration was observed.

抄録全体を表示

Lipid composition and microviscosity of lymphocytes were examined in five healthy subjects, two patients with IIa type and five with IV type hyperlipoproteinemia.
The lymphocytes from IIa type patients showed significant higher levels of cholesterylester (26.0μg), free cholesterol (16.3μg) and phospholipid (62.1μg) per 106 cells accompanied with higher microviscosity (poise 1.960) in comparison with cholesterylester (5.1μg), free cholesterol (8.6μg), phospholipid (43.8μg) per 10⁶ cells and microviscosity (poise 1.750) in healthy controls, respectively.
The lymphocytes from IV type hyperlipoproteinemia significantly decreased to 4.9μg per 10⁶ cells in free cholesterol and to 1.400 in microviscosity than healthy controls.
It was concluded that there is a characteristic difference between lymphocytes obtained from patients with IIa and IV type hyperlipoproteinemia.

抄録全体を表示

Twenty two patients with familial Hypercholesterolemia (FH), five female and seventeen male, underwent clinical and coronary angiographic assessment to define the characterization of coronary artery disease (CAD) and the extent of coronary sclerosis. Eight patients had myocardial infarction, 11 patients had angina pectoris and 2 patients had asymptomatic CAD.
Angiography showed several characteristic findings;
1. A high incidence of left main disease (45%)
2. The incidence of stenotic lesions was higher in the proximal lesion such as segment (1), (2) for right coronary artery and (6), (7) for left anterior descending artery.
3. The occerence of triple vessel disease was as high as 55%, whereas that of single vessel disease was only 10%.
4. Half of cases showed calcifications in coronary arteries.
5. Most of cases showed high CAD-Extent score.
6. The development of collaterals was fairly good in 75% of total CAD cases.
These findings indicate that the coronary sclerosis of FH patients is diffuse and severe but the development of collaterals is not impaired.
There exists a good correlations between Age/HDL-cholesterol ratio and the extent of coronary artery disease.
Nine patients underwent aortocoronary bypass and their clinical course were fairly good, whereas 10 patients were inoperable due to diffuse coronary sclerosis and/or lowered cardiac function, and three inoperable patients died suddenly during following period.
These findings confirm that it is important for the FH patients to be managed intensively by phisicians, especially for their cardiovascular state, e.g. clinical symptoms, ECG abnormalities, age and serum lipids values, especially HDL-cholesterol values. Besides, they should be underwent coronary angiography in order to evaluate the indication of aortocoronary bypass surgery.

抄録全体を表示

Familial hypercholesterolemia (FH) is inherited disorder of autosomal dominant trait. Because of LDL-receptor or internalization defect, hypercholesterolemia and then premature atherosclerosis take place. Owing to properties of inherited disease, reports as to effect of diet-therapy on FH has been few. Moreover, almost these studies are concerned with constitution of nutrients and the study for total calory intake has scarcely been described. Then we tried the study of effect of low calory diet on hospitalized patients with FH. One of 7 subjects was diagnosed as homozygous and 6 of them were heterozygous for FH. The patients consumed daily formula diet (1000-1500kcal. containing 52-57% CHO, 18-20% fat (P/S=1.0) 25-28% protein) for 4 weeks. Effects of the low calory diet on serum lipids were shown that cholesterol was decreased in 18.4±6.9%, phospholipid in 16.6±8.0% and HDL cholesterol in 10.1±8.0% respectively.
Atherogenic index
(total cholesterol-HDL cholesterol/HDL cholesterol)
was prone to decrease, but not significant. These patients were diagnosed as FH before the study and fat or cholesterol intake seemed to be restricted to the same level of the diet. So it is likely that effects of the diet on serum lipids was due mainly to its low caloricity.

抄録全体を表示

To evaluate the progressive changes in the viscoelastic properties of the arterial system in such an animal model of the experimental atherosclerosis as produced by feeding cholesterol-rich food to rabbits, we developed a nontraumatic technique to measure the in-vivo pressure-volume relationship in the forearm arterial tree with the photoelectric plethysmography, employing the explicit relationship between the infrared light absorption through the tissue and blood volume contained in it as the principle. The system designed for this purpose was consisted of a light source, a photodetector, a compressing cuff driven by a micro-roller pump and the amplifirers for the phototransistor output and for the cuff compression pressure. The light source and detector tips were directly fixed on the rabbit forearm skin in the mutually opposing positions and the compression cuff was placed around the forearm so as to cover the tips at the middle portion. As the compression pressure of the cuff was gradually increased, the transmural pressure of the vessels under the cuff was reduced and the associated decrease in blood volume according to the overall vascular compliance was detected by the change in the transmitted light intensity proportional to the transistor output. The relative pressure-volume relationship normalized with the unstressed vascular volume was obtained for the arterial system, as well as the volume elastic modulus Ev for various as well as the volume elastic modulus Ev for various level of the transmural pressure.
The measurement of the pressure-volume relationship was repeated for each cholesterol loaded rabbit every two weeks. The results showed a distinct tendency of sclerotic changes of the arterial system ever decreasing the elasticity during the period of 6 months followed up. A similar but much faster change in the vascular elastic modulus was observed in the model of atherosclerosis experimentally induced by X-ray irradiation of the rabbit forearm.

抄録全体を表示

Fatty acid composition of phospholipids of low-density lysosomal membranes prepared from rabbit atheromatous aorta was analysed. Percentage of polyunsaturated fatty acids of glycerophospholipids was small in the membranes if one compared with that in normal lysosomal membranes from rat liver.
The activity of acid cholesterol esterase was measured in the presence of various kinds of lecithin, such as dilinoleoyl, dioleoyl, distearoyl, dipalmitoyl and egg yolk lecithin. The activity was higher with the degree of unsaturation.
The alteration of fatty acid composition of phospholipids of lysosomal membranes may involve in the reduction of acid cholesterol esterase activity in arterial smooth muscle cells.

抄録全体を表示

Substances contained in human uninvolved aortic intimas and plaque aortic intimas were extracted with 0.15M NaCl at 4°C for 24 hours by gentle shaking.
5ml of these extracts as well as serum were passed through a column of agarose gel (Bio-Gel A-50m) and three fractions (Fr-I, Fr-II and Fr-III) were obtained from this intimal protein. The molecular weight decreased from Fr-I to Fr-II to Fr-III.
Cellulose acetate electrophoresis was performed on extracts, eluates and serum.
Results obtained are as follow:
1) Protein, cholesterol and phospholipids of Fr-I were more predominant in extract from plaque intimas than in uninvolved intimas. None of them were found in serum Fr-I.
2) Cellulose acetate electrophoretic patterns of protein and glycoprotein in intimal extracts were different from those of serum pattern. Patterns of Fr-I and Fr-II were quite different from those of serum but Fr-III was similar to those of serum.
3) Electrophoretically, plaque Fr-I remained at the origin and was stained with Ponceau 3R, PAS and Ozonaization-Schiff method. Lipoprotein was found at the origin and pre-β position in plaque Fr-II, and at the origin, pre β-β and α in plaque Fr-III.

抄録全体を表示

The effect of ethanol on cholesterol ester metabolism in rat arterial wall was studied. In rats kept on water containing in 0.5%, 2% and 10% ethanol (0.5%, 2% and 10% EtOH group), cholesterol esterase activity was estimated in homogenate of arterial wall by the method of Brecher, and fatty acid composition in arterial wall was also determined. Each value of EtOH group was statistically compared with the data of control rats kept on plain water (control group).
Acid (pH 4.5) cholesterol esterase activity in 10% EtOH group was higher than that in control group. Neutral (pH 7.4) cholesterol esterase activity in all EtOH groups was higher than that in control group. There was no significant difference in fatty acid composition between EtOH group and control group.
These results suggest that the change of cholesterol esterase activity in EtOH group might reduce cholesterol ester deposition in arterial wall.

抄録全体を表示

In order to elucidate the metabolism of coenzyme Q and vitamin E as the antioxidative agents in the acute vascular accidents, experimental myocardial necrosis induced by isoproterenol injection to rats, was made by the method of Rona. Coenzyme Q₉ (Co Q₉) and vitamin E (α-tocopherol) in the serum and the lipoprotein fraction were measured. In ordinary state, most of Co Q₉ was distributed in VLDL and LDL, and α-tocopherol was in HDL. Co Q₉ in VLDL decreased at 6 and 12 hours, most significantly at 12 hours, and in LDL significantly elevated at 12 hours after isoproterenol injection, α-tocopherol in the serum and VLDL showed a rapid decrease, reaching its minimum at 6 hours, and in LDL increased at 12 hours. These results suggest that Co Q₉ may locate in the core of VLDL and LDL, and α-tocopherol may predominantly exist in the surface area of the lipoprotein structure.

抄録全体を表示

Lysosomal cholesterol esterase from rabbit liver was solubilized with digitonin and purified 21, 000-fold to homogeneity by Bio-Gel A-1.5m, DEAE-Bio-Gel A, Phenyl-Sepharose column chromatography, preparative slab gel electrophoresis and finally Sephacryl S-200 column chromatography. The molecular weight of the purified enzyme, calculated by SDS-polyacrylamide gel electropholesis, was about 42, 000. The enzyme hydrolyzed both cholesterol oleate and triolein. It was activated by phospholipids (phosphatidylcholine, phosphatidylethanolamine) and lysosomal membrane. The enzyme was adsorbed on Phenyl-Sepharose and Concanavalin A-Sepharose anddissociated from them by ethylene glycol and a-methylmannoside, respectively, suggesting that it was a hydrophobic glycoprotein. We also discuss the implication of the enzyme for the accumulation of cholesterol ester in atheromatous aorta.

抄録全体を表示

In order to test the hypothesis that estrogen protect coronary arteriosclerosis, a systemic ultrastructural survey was conducted on arterial lesions in chicks fed various combination of cholesterol and estradiol. The combination of cholesterol and estradiol induced more hyperlipidemia than cholesterol alone. Lipid vacuoles were observed more frequently in the interlameller connective tissue cells than in the smooth muscle cells of the thoracic aorta of 1% cholesterol fed chicks. Estradiol supplementation with or without cholesterol caused lipid deposition in medial smooth muscle cells as well as in interlamellar connective tissue cells of the thoracic aorta. Moreover, both non-foam and foam cell type smooth muscle cell degeneration was observed in the abdominal aorta and coronary artery of chicks fed estradiol supplemented diets. These results suggested that estradiol has a potent angiotoxic effect.

抄録全体を表示

Triacylglycerol lipase activities in adrenals and testes of rats were measured and the properties of enzymes were characterized. The enzymes were extracted from acetone-ether dried powder of the tissues and the crude extracts were applied to a heparin-Sepharose affinity chromatography. The enzymes bound to the column were then eluted at different ionic strengths. Two lipases could be detected in rat adrenals: one was inactivated by the antiserum raised against hepatic triacylglycerol lipase and the other had the properties of lipoprotein lipase. In testes, only lipoprotein lipase could be detected. The results were discussed in connection with the possible functions of these two lipases in the organs utilizing lipoprotein-cholesterol for the steroid hormone synthesis.

抄録全体を表示

Lipoprotein Lipase, purified from bovine milk, lost 90% of its activity when incubated in Hanks' solution for 5min at 37°C. Bovine endothelial cells in culture markedly stabilized this enzyme. The stabilizing factor of endothelial cells was non-dialyzable, resistant to heating at 100°C and to changes in pH, and unaffected by treatments of cells with proteolytic enzymes or with heparinase. However, the stabilizing effect on lipoprotein lipase was reduced by 60-70% by the extraction of cells with the lipid solvent. The lipid extract of the cells stabilized the enzyme, suggesting that lipid component(s) of the cells account for their stabilizing effect. Since the endothelial cell is thought to be the site of action of lipoprotein lipase, stabilization of the enzyme by this cell may play a role in its preservation and function in vivo.

抄録全体を表示

The inhibitory effect of 15-hydroperoxy arachidonic acid (15-HPAA) on post-heparin lipolytic activity (PHLA) was studied. The procedures of PHLA was fundamentally that described by Boberg and Carlson. Human ³H-chylomicron was used as the substrate. 15-HPAA was added to the medium with a value of lipid peroxide up to 10 nmoles/ml (Yagi's method). As control, same moles of arachidonic acid was used. In saturated reaction ([S]>>Km), maximal hydrolysis rate was determined and in unsaturated reaction ([S]<<Km) half life time was measured. Km was obtained by Lineweaver-Burk plots. The obtained Km was 0.7mM in this experiments. Addition of 15-HPAA to the medium induced a decrease in approximately 20% of maximal hydrolysis rate (0.09) μmoles/ml/min to 0.072μmoles/ml/min in average), but did not change the half life time.
In conclusion, the data suggest that 15-HPAA damage at least a part of the solubilized lipoprotein lipase.

抄録全体を表示

Ductus arteriosus was used to monitor the alteration of vascular smooth muscle cells under hypoxia. Normally closing ductus arteriosus exhibited active intimal smooth muscle cell growth in early fetal life. These intimal smooth muscle cells apparently originated from medial smooth muscle cells. Intimal thickening became more obvious after delivery at which time functional closure occured. Active growth and degeneration of smooth muscle cells, production of collagen and intra- and extra cytoplasmic lipid vacuoles were observed in the completely closed lumen of ductus arteriosus. This process simulated the basic developmental process of atherosclerosis in which hypoxia is an important factor.

抄録全体を表示

Effects of simfibrate on serum lipids and lipoprotein metabolism were studied in 40 patients with hyperlipidemia. The patients received 1, 500mg of simfibrate everyday for 8 or 12 weeks. Serum lipids and apoprotein A-I and C-III were measured in every four week during the treatment. By simfibrate treatment, cholesterol levels decreased by 10 to 20% of the initial values and triglyceride decreased 40 to 50% of the initial values. Simfibrate increased HDL cholesterol levels by 20% of the initial values. Apoprotein A-I increased by 20% and C-III decreased by 30% of the initial values. These results indicated that simfibrate reduced the levels of very low and low density lipoprotein and increased the levels of high density lipoprotein.

抄録全体を表示