The kidney is an organ that plays an important role in the cardiovascular system through circulation, metabolism and endocrine function, and it is a matter of course that any abnormality in renal function greatly affects the onset of vascular lesions. However, systemic studies on the mechanism of such influence have been scarce and consequently much remains to be educidated.
Concerning the participation of the kidney in the pathogenesis and development of arteriosclerosis, the authors have made the following speculations.
1) Since hypertension is considered to participate greatly in the pathogenesis and development of arteriosclerosis, various types of renal hypertension must be important factors of arteriosclerosis.
2) Interarenal small arteries and arterioles are susceptible to hypertensive lesions, probably resulting in consequent peripheral circulatory disturbance in the kidney. This is another renal factor in the pathogenesis of arteriosclerosis.
3) Arteriosclerosis is milder in dialyzed cases than in non-dialyzed cases among autopsy cases of chronic gromerulonephritis. This reveals that various renal dysfunctions cause abnormalities of blood and electrolytes and thus participate in the development of arteriosclerosis.
4) It is demonstrated that some arteriosclerotic changes could be induced by non-pressor vascular necrotizing fraction of the renal cortical extracts in our series of experiments using rats.

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There are some differences in the mechanisms of the initiation and progression of atherosclerosis in the various organ arteries. It seems important, in the cerebral atherosclerosis, to consider the morphological characteristics and permeability pattern of the cerebral arteries. In this paper, to elucidate the characteristics and atherogenesis of the cerebral arteries, the influence of renovascular hypertension and hypercholesteremia on the rabbit cerebral arteries, and localization of fibrinogen in the rabbit cerebral arteries were studied. Furthermore, vascular lesions and changes of permeability pattern of coronary and cerebral arteries induced by renal lysosomal contents were also studied.
1. Foam cell lesions were found in cholesterol-fed rabbits with induced hypertension, particularly in intimal cushions at branching sites, where permeability to peroxidase was enhanced. No foam cell lesions were observed in the intima of the cerebral arteries distant from branching sites.
2. Reaction product of anti-rabbit fibrinogen goat Fab′ conjugated with peroxidase (HRP-Fab′ conjugate) was identified both on the luminal surface and in the caveolae of the endothelial lining of the cerebral arteries of the untreated rabbits. Reaction product of HRP-Fab′ conjugate was occasionally observed in the subendothelial space and also both on the luminal surface and in the caveloae of the endothelial lining of the hypertensive and hypercholesteremic rabbits. In the foam cell lesions at the branching sites, reaction product of HRP-Fab′ conjugate was present in the subendothelial space and around the lipid droplets deposited in the subendothelial space. Reaction product of HRP-Fab′ conjugate was absent in the intercellular space of the endothelial lining. These findings suggest that fibrinogen insudates into the intima by vesicular transport and that in the state of hypertension and hypercholesteremia vesicular transport is enhanced.
3. The effect of the lysosomal contents of hog kidney cortex, especially of the fraction not bound by concanavalin A, on the permeability of the coronary and cerebral arteries of rats, were studied. This fraction was devoid of renin activity by bioassay. The coronary arteries of the bilaterally nephrectomized rats displayed fibrinoid degeneration and a large amount of the reaction product of peroxidase was present in the subendothelial space and media where fibrinoid degeneration was evident. Occasionally increased permeability of the intima was noted in the coronary arteries without medial damage. By contrast, neither fibrinoid degeneration nor increased permeability was noted in the cerebral arteries. This difference in the response of the two arteries seems attributable to the barrier effect of cerebral arterial intima.

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In order to study relationship between development of arteriosclerosis and renal diseases, arteriosclerotic changes of renal arteries, superior mesenteric arteries and small arteries of small intestine were examined in 250 autopsy cases including 78 vascular nephrosclerosis cases and 172 non-vascular nephrosclerosis cases. Histometrical method was applied to estimate degree of arteriosclerosis and the following results were obtained;
1) Weight of both kidneys gradually decreased with aging after the age of 20 years, and after the age of 40 years in nephrosclerosis group it decreased more than in non-nephrosclerosis group.
2) In non-nephrosclerosis group, decrease of kidney weight related to severity of sclerosis of medium-sized renal arteries and vascular nephrosclerotic process showed parallel correlation to severity of arteriosclerosis of small arteries of kidney.
3) Physiological arteriosclerosis of superior mesenteric arteries well developed at the proximal portion and degree of arteriosclerosis gradually decreased at the peripheral mesenteric arteries and small intestinal arteries.
4) In vascular nephrosclerosis group with cardiomegaly-index greater than or equal to 2, arteriosclerosis of peripheral portion of superior mesenteric arteries and intestinal arteries were mostly intensified. Even in vascular nephrosclerosis group with cardiomegaly-index less than 2, degree of arteriosclerosis of intestinal arteries showed higher level than in non-vascular nephrosclerosis group during the age of 50 to 60 years.
5) It was suggested that some other factors in addition to hypertension and aging may participate in development of extrarenal arterio-arteriolosclerosis in vascular nephrosclerosis.

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Atheromatous lesions were removed from 7 cases of ischemic cerebrovascular disease at the atherosclerotic carotid bifurcation during carotid endarterectomy. The intimal lesions of these specimens were observed with a scanning electron microscope (SEM) and areas of the lesions were further subjected to a study with a transmission electron microscope (TEM) after the specimen was re-immersed in a phosphate buffer solution and subsequently embedded in Epon.
The intimal lesions were devided in two groups according to degree and nature of covering of the lesion. In a group of “healed” lesion (3 cases) with a full coverage of the lesion by regenerated intimal cells, no thrombus was seen in and around the lesion.
However, intimal cells in the lesion were arranged in an irregular fashion and in one case, the arrangement of the intimal cells appeared to indicate regeneration of the intimal cells had originally occured in a cord-like fashion and subsequently in a sheet-like fashion.
In a group of “non-healed” lesion (4 cases) without full coverage of the lesion by regenerated intimal cells, red thrombi of various sizes were present except in one case in which the lesion was covered with “amorphous material” or packed white thrombus. Intimal cells in this group around the thrombi looked more irregular in shape, size and arrangement than they did in the “healed group”. Many of these intimal cells were identified as the “piggy-back cells” and protruded prominently in the vessel lumen on SEM observations. These protrusions were associated with separation and elevation of these cells from underlying cells on which the protruded cells had situated on TEM observations.
Subintimal layer of the former group was characterized by a cellular fibrous proliferation while in the latter group, areas of infiltration of blood cells and plasma components were seen in the severely fibrous subintimal layer. Clinical data were compared in these two groups. In the “healed” group, patients were younger, normotensive and were not lipidemic.
The authors discussed these findings with a control findings obtained from a reparative process of the cat carotid artery and concluded that the delayed and abnormal healing process of these lesions was mainly due to an abnormal hemodynamic effect at the atheromatous plaque rather than to an atheromatous nature of the intimal cells or the subintimal tissue, although there is a possible influence of patient's clinical condition in aggravating the abnormal and delayed healing of the lesions.

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We have studied the heart lesions in cerebral apoplexy for elucidating the pathogenesis of cardiocerebral apoplexy. We have already repoted that ther are pathological state in heart such as ischemic cardioencephalopaty in cases of cerebral infarction at the bases of cardiocerebral appolexy, which state is remarkably different in cases of cerebral hemorrhage and subarachnoid hemorrage. For one more step, we have studied possibility of multiorganic ischemic lesions as the base of cardiocerebral apoplexy.
We have studied pancreatic lesions in cases of cerebral apoplexy, 32 cases of cerebral infarction and 25 cases of cerebral hemorrhage. We observed parenchimal, ductal and arterial lesions. We have strongly suggested the presence of ischemic pancreatic fibrosis which is apperently prominent in cases of cerebral infraction particulary in fiftie's and sixtie's. But, incidence of ischemic lesions in pancreas is remarkably low than that of in heart in cases of cerebral infarction. Coreration of ischemic lesions in pancreas and heart is not evident, but 84% in cases of cerebral infarction there are ischemic lesion in any one organ, heart or pancreas.
Based on these results, we should be accept the base of cardiocerebral apoplexy at multiorganic ischemic lesion. Father more we must study other organs in the same stand point.

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Cardiocerebral apoplexy is nowadays applied to a paticular case of myocardial infarction with cerebrovascular accident. For clarifing the pathogenesis of this syndrome, it is mandatory to investigate cardiac lesions in cases of cerebrovascular diseases and also cerebral lesions in cases of cardiovascural diseases. In our previous paper related to cardiac lesions, it was shown that there is marked complication of myocardial infarction or marked myocardial fibrosis in cases of cerebral infarction. This result suggest the morphological evidence for the existence of “Ischemic Cardioencephalopathy”. And it also suggests the existence of multi-foci ischemic lesions which are wide spread various visceral organs.
With regard to this problem we observed renal lesions in 32 cases of cerebral infarction and 26 cases of cerebral hemorrhage. The results obtained were as follows.
1) ischemic changes such as micro-subcortical infarctions and sclerotic changes of arcuate artery are more marked in cases of cerebral infarction than in that of cerebral hemorrhage.
2) There are marked micro-subcortical infarction in all cases of cerebral infarction with myocardial infarction, and in 70% of cases of cerebral infarction with marked myocardial fibrosis.
The correlation of ischemic lesions in kidney and heart is noteworthy.

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Cardicerebral apoplexy is known as acute myocardial infarction with apoplexylike symptome. In spite of the symptome, some cases have no macroscopical findings in cerebrum and cerebellum. Others have encephalomalacia. We thought that it was needed to investigate macroscopically and microscopically cerebrum which accompanied myocaldialinfarction. We studied cerebrums of 27 cases.
1) 9 cases had macroscopical small encephalomalacia Another cases had no macroscopical finding. (No subarachnoidal and no cerebral hemorrhage, no large encephalomalacia).
2) Almost of all no macroscopical finding cases had microscopical encephalomalacia. At this investigation, there were two cases of cardioce-rebral apoplexy. One case belonged to small macroencephalomalacia group. The other case belongd to no macroencephalomalacia group. Both of them, showed diffuse microscopical encephlomalacia in basal ganglia. Macroscopical finding of cardiocerebralapoplexy, reported by Fujii and others consisted of multiple large encephlomalacias or hemorragic encephalomalacia. Our report was different from this Fujii's opinion. To investigate pathologically cardiocerebral apoplexy, we are studying another lesions of cerebrum in additional cases with consideration of this point.

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Pathway of the conduction system in the case of Ventricular Septal Defect (VSD) and Tetralogy of Fallot (TOF) has been well known, however correlation between conduction disturbances and its supplying arteries is not yet known. In 48 cases of VSD and 17 cases of TOF examined the past 5 years at the Department of Thoracic Surgery, 22% of the former and 11% of the latter cases showed more or less conduction disturbances in ECG before the surgical procedure.
Recently, although many studies concerning the myocardial and coronary lesions in infants, children, and young adult were performed, the authors also histopathologically examined the supplying arteries to the conduction system of the heart, by the method of serial sectioning, obtained by autopsy in 6 cases of VSD (age 2 months to 27 years) and 5 cases of TOF (age 8 months to 6 years), to know the effect of the ventricular septal defect upon the conduction system and its supplying arteries. As a result, the following findings of unusual vascular lesions were obtained: in the first place, adventitial fibrous proliferation associated with perivascular fibrosis of arteriole and small arteries, the second, initimal thickening with collection of insudative fluid and medial thickening due to proliferation of musculoelastic layers in small arteries, and finally those lesions were more severe in it. coronary branchies than rt. coronaries.
Conduction disturbances predominantly depend on fibrosis, degeneration and atrophic changes of conducting fibers, especially in His bundle to bifurcation, associated with perivascular fibrosis, and furthermore more than 50% of lesions of conducting fibers usually revealed clinical conduction disturbances appears in ECG.
These vascular lesions which are relatively prominent in VSD must be derived from peripheral circulatory disturbances. The reason for predominance of vascular changes in VSD compared to TOF is proposed as follows: in the case of VSD, vortical hemodynamic current may always exist in the direction left to right ventricle through the defect at just beneath the aortic valvular region, resulting the irregular coronary intravascular pressure.

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50 coronary arteries obtained from cases of accidental sudden death were studied. The intimal surface of coronary vessels was carefully sketched. For further refinement, the weight ratio of the sclerotic portion to total was calculated.
On the other hand, the atherosclerotic change of the left coronary artery was observed microscopically at the turning point between the anterior descending and circumflexous branches. The relative area of the lumen and the enlargement rate of the cross section area were determined by means of photographs of microscopic sections on enlarging paper. On the basis of the weight ratio of the sclerosis, the extent of coronary atherosclerosis was classified into 4 groups: normal, 0-10%; slightly sclerotic, 10-30%; moderately sclerotic, 30-60%; and severely sclerotic groups, above 60%. The lumen of normal group occupied 47% of the total cross section area of the artery. Slightly, moderately and severely sclerotic groups revealed 38%, 30% and 21%, respectively. About 10% decrements in the luminal area were found among these four groups in this order. The enlargement of cross section area was observed with the progress of atherosclerosis. The cross section area of slightly sclerotic group showed 3.3 times of that of normal arteries. Moderately and severely affected groups revealed 2.6 and 3.7 times, respectively.
On the peripheral portion of the coronary artery, perivascular changes were occured earlier than narrowing of the lumen. The constriction of the lumen in the peripheral portion was started when the area of the lumen revealed 20-30% of the total area in the central portion. Thus, the present classification of the extent of coronary atherosclerosis by the weight ratio of the sclerotic portion to total was supported by the microscopic observation.

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To study mural vascularization in coronary arteries and its role in progression of coronary sclerosis, three major approaches have been attempted, as one of the most impressive morphological characteristics of coronary atherosclerosis is a localized eccentric intimal thickening, and such characteristic may not be explained by generalized factors such as plasma constituent insudations. Circulatory disturbances within certain points of the arteries may be one of local factors partly responsible for such characteristic.
Firstly, 56 coronary arteries from child and adolescent autopsy cases, 10 from adults without significant cardiac diseases, and 35 arteries from cases with myocardial infarction were histologically studied on multiple step sections and serial section for selected occasions. Secondly, silicone perfusion to the arteries obtained from autopsy cases was tried to analyse a morphology of vasa vasorum. Thirdly, ferritin-used tracer electronmicroscopic investigation was carried out in the rabbit coronary arteries to study intramural circulation of arterial walls.
Vasa vasorum in the media were often found in the adults even in the non-atheromatous segments of the arteries, and occasionally in the childhood and adolescence. Vasa vasorum were more prominent in the segments of the arteries with intimal thickening, and seemed to have a communication to the adventitial side.
In the atherosclerotic areas, mural vessels were often seen also in the thickened intima. These intimal vessels might be produced from the endothelium or as a result of organization of thrombi. However, it was occasionally proven histologically on serial sections that intimal vessels had a direct communication with vessels entering from the adventitia. This presumably meant a possibility that intimal vessels might produce anastomoses with vasa vasorum from the adventitia.
In addition, it could be often found that there were focal edema, concentric lamellar fibrosis, small foci of macrophage accumulation, microhemorrhage and hemosiderin deposition around mural vessels, all of which might be a result following local circulatroy distrubances within the arterial walls.
Tracer-used EM study revealed a deposition of ferritin particles in the spaces just beneath the internal elastic lamina in the media and also even in the intercellular spaces in the most outer layer of the media close to the adventitia. This result has led to an idea that intramural intercellular fluid circulation may exist in the arterial walls, and there may be venous channels in mural vasculature system, which may play in part a role in progression of coronary sclerosis.

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To evaluate accuracy of coronary cine angiogram in predicting the degree of stenosis of coronary arteries, 9 autopsy cases including 4 cases of ischemic heart disease and 5 cases of valvular disease were selected for macro-and microscopic studies. In 8 of the 9 cases, tine angiogram had been obtained within 3 months before death, and the rest 1 case within 4 months. Cine angiogram of coronary arteries was divided into 16 segments to compare with pathological findings. Findings of cine angiogram were in agreement with pathological findings in 103 (87.3 percent) of the 118 segments and were not with those (more than 25 percent difference in over 50 percent lesion with cross-sectional lumen) in the rest 15 segments (12.7 percent). All of discordant segments were underestimated in cine angiogram and which were explained as follows; lesion of proximal portion of diagonal branch which lesion had continuity from left anterior descending artery (3 segments), distal portion of total obstruction which was estimated by retrograde flow through collateral circulation (3 segments), eccentric and/or slitlike lesion (6 segments), long circumferantial proximal lesion (1 segment), stenosis in tortuous posterior descending artery (1 segment) and the unknown rest one.

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This study is base upon the autopsiedmaterials of 100 cases who died during for these three years in our hospital.
Myocardial fibrosis, coronary sclerosis, the diameter and atherosclerotic changes of the aorta at its origin were measured systematically.
The data were dealed with the multi-variate-statistical analysis in order to examine the relationships among these pathological changes.
The following results were obtained.
1. The diameter and pathological changes of the aorta at its origin were well related to the aging, the grade of myocardial fibrosis, and the grade of coronary sclerosis.
2. The results of this study would give the possibility of the anticipation of the pathological changes by clinical measurement of the diameter and the elastance of the aorta at its origin.

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As the alteration in an aortic root function or morphology may have influences on the coronary circulation, the pathological and clinical study of the aortic root plays a great role in evaluation of ischemic heart disease. So the blood pressures and the human aortic root diameters (Ro) were clinically measured by using the UCG technique in 85 cases, and then the elastances (Ep) were calculated. The mean Ep in 85 cases was 1.6×10⁶ dyn/cm². This value coincided with that reported by Peterson et al. (1960), which were obtained from any kinds of arteries in dogs.
The Ros and the Eps of both the patients with and without ischemic heart disease, which was diagnosed electrocardiographically, showed the same mean values.
In hypertensive patients, the Ros and the Eps were significantly larger than those in normotensive patients. There were seen some young hypertensive patients whose Ros were significant greater as expected their age, but had the normal Eps. The Ros and the Eps in patients with the aortic calcification seen in the chest X-ray film were relatively larger than in patients without the calcification. These results suggested that the Ros and the Eps were influenced by high blood pressure and the age. However, other facters, such as aortic sclerotic changes, myocardial fibrosis, myocardial ischemia and cardiac dysfunction would relate to the diameter and elastance of the aorta.

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Ten atheromatous rabbits (1% cholesterol feeding, for 12-14 weeks), weighting 3.2-3.8kg were used. All rabbits were injected intrarenously with 5ml/Kg of 50% carbon suspension. Aortic specimens of 5 rabbits were taken 24hrs. after the injection of carbon suspensions, but other 5 aortic specimens were taken 7 days after the injection.
The cytoplasm of endothelial cells contained numerous lipid inclusions and carbon particles. These lipid inclusions and carbon particles were partially surrounded by the single electrondense layers. There were no carbon particles in lipid inclusions.
Typical foam cells contained lipid particles, carbon particles, ceroid bodies and multilaminated membrane structures (myelin fogures). Ceroid bodies were composed of numerous lipid droplets, laminated vesicles and granules.
The carbon particles were frequently found in ceroid bodies or myelin figures, but there were no carbon particles in lipid inclusions.
The smooth muscle cell contained numerous lipid inclusions soursounded by electron-dense layers (deposits).
It was suggested that foam cells in the subendothelial layer varied according to their stage of development, especially a lipid inclusion (particle)/ceroid body ratio.
Multilayered vesicles, granules and lipid droplets which were derived from the destoroyed cytoplasm of foam cells were frequently observed in extracellular spaces.

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Smooth muscle cells from freshly excised tunica media of the thoracic aorta of 6 month old swine were maintained in continuous culture for 6 months in a moist atmosphere of 95% air and 5% CO₂ at 37°C. The modified Dulbecco-Vogt culture medium containing 10% newborn calf serum and 1% antibiotic-antimycotic solution was changed every third day. Growth characteristics of the cells and the extracellular ground substances in long-term cultures were examined ultrastructurally. Cells began to grow out from the explants in 10 to 14 days, adhered to the culture flask and became confluent in 4 to 6 weeks. The cells cultured for 3 weeks had few mitochondria, small amounts of rough endoplasmic reticulum, and a large complement of free ribosomes. When the cultured cells grew to confluency, phasecontrast microscopy revealed that they formed a characteristic pattern of “hills and valleys” in which the cells, having an interlacing or overlapped arrangement, were bridged by parallel starts of surrounding monolayer cells. Ultrastructurally, their cytoplasm contained more numerous numbers of mitochondira, rough endoplasmic reticulum and Golgi complex than those in cultured cells at earlier stages of growth. The cultured cells of 6 month old still had myofilaments, fusiform densities, pinocytotic vesicles and basement membrane characterized as smooth muscle cells, although they had prominent rough endoplasmic reticulum, sparse myofilaments, myelin figures or other lysosomal particles of varying densities and glycogen granules.
After cultured cells became confluent, they scattered to form small-sized atherosclerotic mound-like colonies. These cellular aggregates gradually became larger, measuring up to 200μ or occasionally 2mm in width after 3 months. Ultrastructurally, those cellular aggregates exhibited 1 to 4 superficial layers of cells and beneath the layers of cells there were extensive amounts of thin and thick fibrils, amorphous electron dense materials, cellular debris and degenerative cells. The thin fibrils, measuring approximately 110Å in width and similar appearance to “elastin microfibrils”, were present throughout the growth. The thick fibrils somewhat resembled to basement membrane with a width of approximately 300Å were also located thoughout the matrix of cell culture specimens. Those fibrils did not have the periodicity of collagen. Foam cells did not occur in long-term cultures of the aortic smooth muscle cells. The present in vitro culture system dealed secretion of extracellular material and cellular degeneration led to the formation of nodular protrusions which may be convenience for the study of the morphological features of atherosclerotic lesions.

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1. The ultrastructural and histochemical analyses of renal small arteries in forty hypertensive patients (ages ranged from 20 to 63 years) and forty normotensive ones (from 18 to 60 years) were performed.
Lysosomes containing lipid droplets and electron-dense structures were demonstrated in the center of smooth muscle cells. Around lysosomes Golgi complexes were well-developed, also numerous mitochondria and ribosomes were accumulated. These lysosomes were noted in all cases studied without regard to the presence or abscence of hypertension.
The basic pattern of the electron-dense structures within lysosomes appeared to be a series of three layers with a total thickness of 60-80Å like a unit membrane. These three-layered structures were parallelly arranged with the fundamental spacing of 40-50Å. The present authors call this pattern “the lamellar structure” within lysosomes. The examination in high magnification revealed that the lamellar structures showed several patterns such as the lamellar phase, the latticed phase, the hexagonal phase and the amorphous phase. These various patterns probably arose from a different orientation of the three-dimentional structure with respect to the direction of view. But there remained many obscure points about the lamellar structure. Further detailed studies will be required.
2. Male SHRSP of 10 weeks, 16 weeks and 20 weeks old were killed by perfusion fixation method with Karnovsky solusion. After the perfusion fixation cerebral arteries were dissected up to the periphery as much far as possible. The present authors observed various morphological changes in the cerebral arteries and analyzed the developmental mechanisms at work in these changes. In the main portion of cerebral arteries, both of endothelial and medial cells were almost always well-preserved. In a smaller number were observed degenerative or necrotic changes of smooth muscle cells especially next to the adventitia. Regressive changes were not found in endothelial cells at all.
Cerebrovascular changes were more prominent in the branches, especially surrounded by 1-2 layers of medial smooth muscle cells. In the cerebral arteries of SHRSP the medial damage appeared to precede the intimal degeneration. The hypertensive medial damages, characterized by degeneration, necrosis and disappearance of smooth muscle cells, were initially observed in cell bodies adjacent to the adventitia. In these lesions the present authors found two types of necrotic changes of smooth muscle cells. The first type was the Focal Cytoplasmic Necrosis (FCN), which fundamentally consisted of dense-granular substances. FCN also contained spindle-like structures, abundant cell debris and degenerated mitochondria. FCN appeared to have a close relation to giant vacuole formation in the cytoplasm.
The second type was characterized by reduction and disarrangement of myofilaments, and disappearance of cristae in mitochondria. These two types of necrotic changes were primarily associated with the disappearance of smooth muscle cells. In contrast endothelial cells were almost intact in the branches which had advanced medial damages. However in the area where the branches completely lost medial smooth muscle cells, various regressive changes, such as degeneration of cell organellae and giant vacuole formation, were noted. It was a point of importance that interendothelial junctions were well-preserved even in endothelial cells with advanced medial damages. Lysosomes were constantly small in size and were scarcely found in medial muscle cells. It was noteworthy that lysosomes did not appear to have a relation to the necrotic change of cell bodies.

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Biochemical, ultrastructural and immunohistochemical studies on collagen of the human aortic media and vena cava were performed. Biochemical analysis revealed that the aortic media consisted of 55% type I and 45% type III collagen. On the other hand, the collagen composition of the vena cava was further distinguishable form that of the aortic media by a high content of type I collagen (75%). In an ultrastructural study of collagen fibrils, the aortic media contained two distinct groups of collagen fibrils; small and large fibrils measuring 260±20Å and 440±40Å in diameter respectively. The vena cava also exhibited small (360±40Å) and large (560±40Å) groups of collagen fibrils, and the latter predominated in amount. However, the diameter of each groups of the fibrils of the vena cava was always larger than that of the aortic media. These findings presumably ensued the following results; the small collagen fibril, which was fairly less in amount in the vena cava, was made up of type III collagen molecules, and the large one was of type I collagen molecules. The difference of the diameter of collagen fibrils between the aortic media and the vena cava indicated that the diameter of collagen fibrils should be related to the circumstances in which collagen was synthesized. Immunohistochemically, the predominance of type III collagen in the intima and media of the aorta was, at this time, a matter of speculation.

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Platelet aggregation induced by two concentrations of ADP, fibrinogen, plasminogen and protease inhibitors were examined in 40 acute myocardial infarctions Patients with myocardial infarction were devided into two groups. One group is with past history of atherosclerotic vascular disease such as diabetes mellitus, hypertention and cerebrovascular disease and the other is without past history, of atherosclerotic vascular disease. And these two groups were matched with same age, sex and prognosis. Platelet aggregation and blood factors were compared with two groups, with history of vascular disease and no past history of atherosclerotic vascular disease.
1) Platelet aggregation patterns were classified into four types which were type I and II (normal pattern) and type III and IV (hyper aggregability pattern). The platé aggregation of acute myocardial infarction showed normal pattern (type I or II) immediately after attake in both groups but they began to increase 2nd or 3rd day after onset and lasting for ten days. The mean level of platelet aggregation in both groups still remained higher level than healthy persons. This platelet hyper aggregability never return to normal level within one month after attack. Furthermore, platelet aggregation in with past history of atherosclerotic vascular disorder group showed platelet hyperaggregability than in without complication. Fibrinogen and α₂-macroglobulin in with complication group were clearly elevated more than non-complicated group. α₁-antitrypsin and plasminogen showed no difference between two groups and any increase and decrease was not found in comparison with normal matched controle. Antithrombin III was shown in lower level than normal controle in both groups. And the lowest value of antithrombin III was observed in the group which has past history of atherosclerotic disorders. It is suggested that the decreese of antithrombin III in group which has complication was shown to have more risk to thrombolic complications after attack than in without complication group.

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Rabbits were subjected to direct denudation of aortic endothelium by a vinyl tube inserted from the femoral artery. Thrombus formation at the injured areas induced proliferation and migration of endothelial cells of the adjoing areas, proliferation of subendothelial cells, organization of the thrombi by the subendothelial cells and proliferation and migration of muscle cells in the inner media. Four weeks after the extraction of the inserted tube, the thrombi were almost covered by typical endothelial cells. It was suggested that the origin of the endothelial cells might be the adjacent endothelial cells, medial smooth muscle cells and cells from circulating blood. Organization of the thrombi left cellulofibrous intimal thickening. The origin of the intimal muscle cells suggested to be medial smooth muscle cells, endothelial cells, and cells from circulating blood.
Scanning electron microscopy showed that newly formed endothelial cells were polygonal in shape and arranged with their axes oblique to the long axes of the vessel. The junctions between the cells were fairly wide even 4 weeks after the extraction of the tube.
Transmission electron microscopy revealed that new lining cells and subendothelial cells which appeared first on and in the thrombi were bloodderived cells with a few myofilaments and many ribosomes. At 7-14 days after the tube extraction, luminal lining cells were typical endothelial cells and luminal smooth muscle cells. At 4 weeks after the extraction, all of the luminal lining cells were typical endothelial cells. Permeability of the new endothelial cells to Evans blue increased even 4 weeks after the extraction, but after 3-6 months, Evans blue had not permeated into the intima except for the areas of the thrombi.

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The effects of plasma lipoproteins on platelet aggregation were examined after incubation of platelet rich plasma (PRP) and different concentrations of plasma lipoproteins for 30-60min at room temperature.
Platelet aggregation was measured after addition of adenosine diphosphate (ADP) by Aggregation Meter of SIENCO company. Final concentration of ADP was 2μM.
PRP were prepared from normal subjects and patients with cerebral thrombosis and plasma lipoproteins were concentrated and divided into three fraction of very low density (VLDL d<1.006), low density (LDL 1.006<d<1.63) and high density (HDL 1.063<d<1.21) lipoproteins by the ultracentrifugation of Havel's method.
No significant changes of platelet aggregation were observed in both groups by the incubation of PRP with VLDL, LDL and HDL.
We conclude that plasma lipoproteins have no effects on platelet aggregation in short time incubation.

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Epidemiologic evidences have been accumulated that lipid metabolism becomes abnormal not only in atherosclerosis but also arterio-/arteriolosclerosis. However, lipid metabolism in Hypertension has not so far been attracted much attention. This report deals with lipid metabolism in hypertensive rats induced by deoxycorticosterone acetate (DOCA) and 1% NaCl, together with the effect of a fungal prenylphenol, 4-o-methyl ascochlorin (MAc), an experimental hypolipidemic agent.
Unilateral nephrectomized rats, when treated with DOCA and NaCl for 7 weeks, became hyperlipidemia accompaning with hypertension without loading dietary lipid. The most striking correlation existed between the serum cholesterol and renal weight (r=0.9148). Therefore, we consider that renal abnormality in electrolyte metabolism is capable of inducing hyperlipidemia.
Ring like fat deposition were observed at mesenteric arteries in DOCA-hypertensive rats. Pathological change of mesenteric arteries was increased associated with elevating blood pressure. When hypercholesterolemia was induced, more fat deposited.
Fibrous thickening and fibrinoid degeneration were observed at renal arteries in DOCA-hypertensive rats. Degree of arterial injury in the rats fed on lipid rich diet was more seveare than in rats fed on normal diet.
Cholesterol content in aortas is not usually affected by serum cholesterol level alone in rats. Although when lipid rich diet was loaded, it was not increased. But in DOCA-hypertension, cholesterol in aortas was increased upto as twice high as that of the normal without any supply of excess dietary fat. These experimental evidences suggest that increased aortic cholesterol content related to hypertention, hyperlipidemia and aortic hypertrophy. Among these factors, aortic hypertrophy showed the highest correration (normal diet r=0.9514, lipid rich diet r=0.9426).
In DOCA-hypertensive rats either fed on normal or lipid rich diet, triglyceride content in aortas significantly reduced as compared with the corresponding normal. An alternative possibility that DOCA-hypertension causes altered energy metabolism leading to preferential utilization of fatty acids, thus resulting in decrease of triglyceride storage.
These alteration was prevented by treating with MAc, an experimenal hypolipidemic agent.

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Acid mucopolysaccharides (AMPS) contents in aorta of rats with experimental hypertension (two-kidney and one-kidney types of Goldblatt hypertension and DOCA-salt hypertension) were increased significantly with blood pressure elevation.
AMPS contents were decreased with blood pressure fall by the antihypertensive treatment (hydrochlorothiazide, reserpine and hydralazine), while plasma renin activity and plasma noradrenaline levels were rather increased by the antihypertensive treatment.
Changes in composition of AMPS were mainly induced by sulfated AMPS (mono-and highlysulfated AMPS).
These results suggest that blood pressure affects on AMPS contents in the blood vessels in hypertension and this mechanism might play a role in the progression of atherosclerosis in hypertension.

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Effects of hypovitamin C on chemical composition in serum lipoprotein and contents of lipids in the aorta were studied.
Guinea pigs were made hypovitamin C by scorbutogenic diet (group 1) or cholesterol and coconut oil added scortogenic diet (group 3) for two weeks. The controls for the experimental animals were fed on a similar diet and supplemented with 25mg of vitamin C daily (group 2 and 4). Lipoproteins were isolated with ultracentrifuge according to Hatch's method. Lipids contents in isolated lipoprotein fractions were estimated with conventional methods described elsewhere. Protein contents in the lipoproteins were estimated by Hartree's method. Amounts of chylmicron, very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) classes were significantly elevated as compared with the control, group 2. Concentration of triglyceride in VLDL, cholesterol ester in LDL were also increased in group 1. Increased amount of LDL, lower cholesterol and higher apoprotein levels in HDL of group 3 were observed as compared with the control, group 4. Eight bands of apoprotein were separated with triton containing polyacrylamide gel disc electorophoresis. The first band of group 1 was stained strongly dark and the others were faint as compared with those of group 2. First band of group 3 was also stained very dark as group 1. The staining intensity of other bands of group 3 were decreased relatively as compared with those of the control, group 4.
Total cholesterol, phospholipid and triglyceride tontents in the aorta of group 1 were increased significantly than those of group 2. There was a tendency of elevation of total cholesterol and phospholipid contents in the aorta of group 3, but no statistical difference were found against group 4.
From these results, impaired clearance of chylomiron remnants and accumulation of cholesterol ester rich chylomicron and LDL by hypovitamin C were assumed. Altered apoprotein constituents in HDL also may concern with changes of lipoprotein metabolism in hypovitamin C. Thus, hypovitamin C is pathogenic to atherosclerosis not only by decreased integrity of the vascular wall as previously reported, but also by altered lipid metabolism as observed in the present study.

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As it was reported already, the Ly-C from the hog renal cortex produced fibrinoid necrosis of the small arteries and arteriols in the bilaterally nephrectomized rats. The vasotoxic substances in the Ly-C were partially purified and both the affinity positive, rich in renin and glycoproteins, and negative fractions for concanavalin A were shown to have vasotoxic activities, the details of the latter were reported previously. The present study was carried out to answer the question whether fibrinoid necrosis produced by the affinity positive fraction of Ly-C was due to the elevated pressure by renin or the direct biochemical effect of renin on blood vessels or some other factors other than renin.
METHODS The Ly-C obtained from the hog renal cortex by differential centrifugation and osmotic shock treatment as reported previously. A further purification of the Ly-C was performed by the concanavalin A-Sepharose 4B column.
In order to determine whether fibrinoid necrosis produced by renin is due to elevated blood pressure or its direct biochemical effect, some of the conscious bilaterally nephrectomized rats were treated with SQ14225 to prevented an elevation of the blood pressure prior to the administration of the samples. Blood pressure of the rats was monitored continuously by the cannulation of carotid artery.
RESULTS Fractionation and Concanavalin A Affinity Column Chromatography of Lysosomal Contents: A contamination of Ly-C by the microsomal and mitochondrial fractions appeared to be approximately 1% in terms of specific activity of marker enzymes. The renin activity was detected mainly in Ly-C. When Ly-C were applied to concanavalin A affinity column, glycoprotein fractions containing renin were absorbed completely by Sepharose 4B-concanavalin A and eluted with methyl-α-D-glucoside.
Blood Pressure and Vascular Lesions: The affinity fraction containing renin (fraction B) as well as no affinity fraction (fraction A) of Ly-C produced similar angionecrosis of a fibrinoid type. When the fraction B was injected into the rats, the mean blood pressure was elevated. The microscopic studies of these rats revealed consistently fibrinoid type angionecrosis in the smaller arteries and arteriols of the pancreas, mesenterium and heart. In order to prevent an elevation of blood pressure by the fraction B SQ14225 was administrated orally one hour before the injection of the fraction B. An elevation of the mean blood pressure was mild and transient and angionecrosis was not produced.

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It has been known that atherosclerosis suddenly develops after menopause in women, suggesting the presence of the interrelationship between atherosclerosis and estrogen deficiency. The purpose of this study is to investigate the interrelationship between arterial calcification and serum estradiol levels and bone mineral content in the aged. Seventy-seven postmenopausal women (age 47-82, mean 71 years old) and 59 mean (age 41-91, mean 70 years old) were subjected to the study. Presence or absence of the arterial calcification was examined macroscopically by X-ray films, serum estradiol was measured by radioimmunoassay, and radial mineral con tent was measured by Bone Mineral Analyzer.
The results were as follows; (1) Arterial calcification and serum estradiol; In women, the mean serum estradiol level (11.5±1.3pg/ml) in those with calcification of the abdominal aorta was significantly lower than that (15.7±2.5pg/ml) in those without it (p<0.01), and serum estradiol level (8.4±1.4pg/ml) in those with calcification of the iliac artery was sifnificantly lower than that (16.1±1.6pg/ml) in those without it (p<0.001). In men, the mean serum estradiol level (19.2±2.5pg/ml) in those with calcification of the iliac artery was significantly lower than that (29.7±2.4pg/ml) in those without it (p<0.01). (2) Arterial calcification and radial mineral content (RMC); In women, RMC (0.46±0.02g/cm²) in those with calcification of the abdominal aorta was significantly lower than that (0.52±0.02g/cm²) in those without it (p<0.02), and RMC (0.44±0.02g/cm²) in those with calcification of the iliac artery was significantly lower than that (0.52±0.01g/cm²) in those without it (p<0.001). In men, there was no relationship between arterial calcification and RMC. (3) Serum estradiol and RMC; In women, there was a positive correlation between serum estradiol level sand RMC (Y=0.0025X+0.4551, X=serum estradiol level, Y=RMC, p<0.02). In men, there was no correlation between serum estradiol and RMC.
These results suggest that in both women and men, decrease of endogenous estrogen might accelerate the arterial calcification, and that the estrogen might protect the artery from calcification through a direct action on the arterial wall. Only in case of women, increased bone resorption might partly contribute to the arterial calcification.

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Serum levels of α-tocopherol, lipoperoxide (TBARS), total cholesterol (TC) and free fatty acid (FFA) were studied before and after the administration of vitamin E (dl-α-tocopheryl acetate) for 4 weeks (400mg/d im for the first week, thereafter 600mg/d po) in the acute stage of cerebrovascular accident (stroke).
Serum α-tocopherol was significantly lower, but TBARS was higher than that of the control on the first day of outbreak. Then, vitamin E administration elevated serum α-tocopherol level in a few days, but did not affect on TC level. On the other hand, serum TBARS level did not arise and was in plateau during 4 weeks. These result led us to have a conclusion that administrated vitamin E must inhibit the elevation of TBARS, which otherwise, was observed in most cases in the first week. Lastly, there were three stroke patients whose serum α-tocopherol had been happenly measured 2 or 4 months prior to attack, and two of them had revealed low level of α-tocopherol (less than 0.5mg/dl) at that time. Soon after stroke developing, seum α-tocopherol was commonly proven to be lower, as others, in three patients.
These findings might roughly suggest that low level of serum α-tocopherol could be one of risk factors of cerebrovascular accident.

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A new antiatherosclerotic agent, Phthalazinol (EG 626), a thromboxane A₂ antagonist and a c-AMP phosphodiesterase inhibitor, has been shown to prevent atherosclerosis in the cholesterol fed rabbits. In an attempt to clarify the mechanism the effect of EG 626 on the lipolytic enzyme activities in the aorta and epididymal adipose tissue was investigated in vivo and in vitro with Pyridinol carbamate (Anginin) as a reference compound.
Administration of EG 626 (100-200mg/kg, per os, daily, 1-2 weeks) did not influence lysosomal cholesterylester hydrolase (CEH) and acid phosphatase (a marker enzyme of lysosome) activities of the aorta, but lipoprotein lipase (LPL) activity which was known to produce cholesterol rich remnants in the endothelium, significantly decreased by the treatment with EG 626 (100mg/kg, 6 days).
EG administration exerted marked effects on CEH activity and lipolysis, both c-AMP dependent, in the epididymal adipose tissue. CEH activity significantly increased (20-100%) by EG treatment, but not by Anginin treatment. In the experiment of adrenalin-induced lipolysis EG administration increased the basal lipolysis and greatly enhanced the lipolytic response to adrenalin at the low concentration (2.7×10^-4mM), but not at the high concentration (2.7×10^-2mM).
The stimulatory effects of EG 626 on CEH and lipolysis was also observed in vitro. Preincubation (30min, 37°) of the adipose tissue with EG (1mM) elevated CEH activity by 25%. Theophylline (1mM) and adrenalin (2.7×10^-4mM) activated the activity to the same degree. The ratio of stimulated lipolysis to basal lipolysis and the log concentration of EG (0-1mM) in the incubation medium was in a linear relationship. EG (0.229mM) and teophylline (0.603mM) were equivalent to adrenalin (2.7×10^-2mM) in lipolysis activation.
These results suggest that the enhancement of CEH activity and lipolysis in the epididymal adipose tissue is possibly mediated by an increase in c-AMP level induced by EG treatment. With regard to the absence of EG effect on arterial CEH, the presence of prostacyclin in arteries which antagonizes thromboxane A₂ and prostaglandin endoperoxides may obscure the EG effect. The preventive effect of EG 626 on arterial lipid accumulation may partly due to the decrease in arterial LPL activity.

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It is a well known fact that Pantethin is stable as one of the precursors of Coenzyme A, and indicates various effects.
In this paper the effect of Pantethin on experimental rabbit atherosclerosis caused by loading cholesterol was studied.
METHOD Twenty male rabbits weighing 2-3kg were used. They were fed with Oriental Yeast's chow containing 1% cholesterol. Separately, Pantethin was specially ordered to be contained in the said 1% cholesterol chow at a ratio of 5%.
For the first two weeks all of 20 rabbits were raised only with the chow containing 1% cholesterol, and after that serum cholesterol was measured using blood collected from auricle. According to the results of cholesterol values measured, the animals were divided to two groups to have nearly equal mean values of serum cholesterol, then a group of 10 rabbits was fed with only the chow containing 1% cholesterol and another group of 10 rabbits were fed with the chow containing 1% cholesterol and 5% Pantethin. They were raised for 10 weeks, and in either case amount of chow fed was 100g per head a day.
Serum cholesterol was measured by the enzyme method, neutral fat by Triglyceride Test Wako (acetyl acetone method), betalipoprotein by Walton-Scott's Method modified by Kuzuya and phospholipid by PL Kit N Method, and serum lipid peroxide by TBA method.
RESULTS Pantethin group showed lower serum cholesterol, neutral fat, phospholipid and beta-lipoprotein compared with the control. The substance with serum TBA reaction positive also showed a reducing trend. However, in either case no significant difference was observed statistically between the groups.
Upon autopsies carried 10 weeks later, even by gross observation, fatty streak in aortic wall, sclerotic intimal thickening and atheroma were found to be inhibited in the Pantethin group. CONCLUSION It was confirmed experimentally that Pantethin inhibits experimental atherosclerosis on rabbits raised with 1% cholesterol diet.

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Effects of stress, D-penicillamin (D-P) and chondroitin 4-sulfate (C-4S) on cell growth reaction were studied by using ³H-thymidine to 36 Wister rats. Six groups were divided as follows: 1) Stress, 2) C-4S, 3) D-P, 4) stress plus C-4S, 5) stress plus D-P and 6) control. C-4S was injected 50mg twice and D-P 95mg twice 24 hours before sacrifice. Stress was given as that rats were drawn from roof for 8 hours. ³H-thymidine (5μC/g body weight) was then injected intraperitoneally into the rats which were sacrified one hour after ³H-thymidine injection.
Stress and C-4S increased the number of ³H-thymidine incorporated cells in both rat heart and aorta, while D-P decreased the cell mitosis. The group 4 and 6 showed less incorporated ³H-thymidine. C-4S and D-P affected cell growth reaction by stress. The averaged number of ³H-thymidine incorporated cells in the aorta were as follows: stress 20, D-P 13, C-4S 22, stress plus D-P 10, stress plus C-4S 10 and control 4. ³H-thymidine increased in adventitia. The same tendency was shown in the heart: stress 149, D-P 53, C-4S 163, stress plus D-P 40, stress plus C-4S 54, control 27. Thus, C-4S seemed to suppress the effects of stress as a defence mechanism of vascular tissue.

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Elastin was extracted from normal and plaque intima of the human aortae with different methods, i.e.; (1) 0.1N NaOH at 100°C of Lansing with subsequent 0.5M EDTA treatment, (2) 5M guanidine-HCl and collagenase extraction of Ross with subsequent EDTA treatment, and (3) 10% NaCl and collagenase extraction of Tokita with subsequent EDTA treatment.
The lipid content of elastin preparations from normal intimae was 2 to 3%, whereas that from plaque intimae was up to 4 to 6%.
The lipid composition of elastin preparations varied significantly according to the extraction procedures and the phospholipid content was relatively lower in alkali-purified elastin preparations.
Elastin from plaque intimae contained significantly higher amount of cholesterol than that of elastin from normal intimae. However in all preparations the contents of free and esterified cholesterol fractions were quite comparable and sphingomyelin occupied approximately 40 to 80% of total phospholipids.
The polar aminoacids were not increased in elastin samples from plaque intimae obtained by alkali extraction as compared with those obtained by other extraction procedures, and it was found out that the polar aminoacid contents of elastin samples were slightly decreased after treatment with EDTA.

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Rats were fed in the following manner, 1) Normal diet for 16 weeks 2) High cholesterol diet for 8 weeks and then normal diet for 8 weeks 3) High cholesterol diet for 8 weeks and then normal diet plus pantethine for 8 weeks 4) High cholesterol diet for 16 weeks 5) High cholesterol duet for 8 weeks and then high cholesterol plus pantethine for 8 weeks 6) High cholesterol diet plus pantethine for 16 weeks. Serum cholesterol level in rats fed a high cholesterol diet for 16 weeks was considerably higher than in rats fed a normal diet for 16 weeks. The increased serum cholesterol was significantly lowered by administration of pantethine for 16 weeks or last 8 weeks. Acid cholesterol activity in rat arterial wall extract fed a high cholesterol diet was less than that in normal diet for 16 weeks. The activity in groups administered pantethine was increased more than that of controls. The ratio of cholesterol ester synthesizing activity to alkaline cholesterol esterase activity was increased in arterial wall extract from rats fed a high cholesterol diet for 16 weeks than in those from rats fed a normal diet for 16 weeks.
The ratio in arterial wall extract from rats fed a high cholesterol diet administered pantethine for 16 weeks was lower than in those from rats fed a high cholesterol diet for 16 weeks. These results suggest that the deposition of cholesterol ester might be increased in lysosome or microsome of arterial wall and pantethine might protect the deposition.

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Combining a quantitative histochemistry method with the Firefly luciferase method we found that adenosine-triphosphate (ATP) could be accurately measured in 100-200μg of aortic tissue. Trichloroacetic acid solution was used for extraction of ATP and by so doing, weighing at the freezing point or neutralization by (potassium hydroxide) KOH in case of perchloric acid could be eliminated. Simultaneous assay of cyclic nucleotides was thus feasible. Contents of ATP and ADP in intima and media of aortic wall of rabbits, cows and pigs were measured. The levels of these nucleotides in intima of aortic wall of these animals were low, as compared with those in media. Acquisition of these information in intima is vital for monitoring changes in levels of adenine nucleotides in relation to vascular injury and atherosclerosis.

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In order to elucidate the effects of serum HDL levels to the extent to increased LDL caused by the high cholesterol diet, six egg yolks were administered daily to twenty-six clinically healthy males (25-45 year old) for 7 days (approximately 1.5 gram of cholesterol/day). Serum lipid levels and various lipoproteins, and lipid compositions of the lipoproteins were determined before and after the administration.
Results and conclusion:
1) On the high cholesterol diet LDL concentration increased markedly and VLDL and HDL concentrations increased slightly. In the lipid compositions of the lipoproteins, increases of LDL-cholesterol and LDL-phospholipid were noticed.
2) From the aspects of major HDL and HDL-cholesterol concentrations, the subjects were classified into following subset groups; the first group with normal levels of HDL and HDL-cholesterol, the second with normal level of HDL and low level of HDL-cholesterol and the third with low level of HDL and normal level of HDL-cholesterol. The first group occupied 60% of total cases, the second 10% and the third 30%. It is of interest that influences of high cholesterol diet to the serum lipoprotein concentrations were obviously different among three subset groups.
3) In the first group, LDL increased markedly and major HDL, HDL₂ and HDL₃ were not affected by the high cholesterol diet.
4) In the second group, HDL-cholesterol increased and reached to the normal level. LDL, major HDL, HDL₂ and HDL₃ were not affected.
5) In the third group, although major HDL increased markedly, HDL-cholesterol was not affected. In this group, only HDL₃ increased significantly so that the observed increase of major HDL may be a reflect of that in HDL₃.
6) The quantitative cholesterol content in major HDL in the second group was observed to be significantly lower than that in the other groups. The quantitative phospholipid content in HDL in the third group was higher than that in the other groups. These abnormalities of HDL lipid content in the second and third groups were normalized by the high cholesterol diet.
7) From above mentioned results, it may be suggested that distribution of dietary cholesterol in the various lipoproteins is so regulated by the serum levels of HDL and HDL-cholesterol that effect of high cholesterol diet to the serum lipid levels should be considered in case by case according to individually different concentrations of HDL and HDL-cholesterol.

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In order to elucidate the role of VLDL-catabolism in cholesterol content of HDL, we have determined the composition of plasma lipoprotein, before and 10 minutes after heparin infusion (10U/kg body weight) in men aged under 65 years old.
The twenty two subjects were divided into two groups according to triglyceride concentration in VLDL. Each lipoprotein fraction was separated by ultracentrifugation and then TCh (total cholesterol), FCh (free cholesterol), TG (triglyceride), and protein were determined by standard methods.
There was not significant change in plasma TCh after heparin infusion in spite of extreme decrease in VLDL-TG in all subjects. These results were indicated that total mass of TCh in plasma was not affected by enhance of VLDL-TG catabolism during 10 minutes induced by heparininfusion.
There was conflicting result which the degree of reduction of VLDL-TCh seen in VLDL-TG over 180mg/dl was not related to change in VLDL-TG. On the other hand, the degree of VLDL-TCh reduction in VLDL-TG under 180mg/dl was in proportion to decrease in VLDL-TG. Therefore, it was estimated that two behaivors existed in VLDL-catabolism as follow; (1) TG-hydrolysis in VLDL accompanied with TCh-transport into HDL, (2) Over-hydrolysis in VLDL-TG upon TCh-transport.
In eleven of 14 subjects with VLDL-TG under 180mg/dl, HDL-TCh increased (p<0.01) and this was not accompanied in TCh/protein ratio in HDL. In seven of 8 subjects with VLDL-TG over 180mg/dl, HDL-TCh decreased. These results were discussed in the context of the possible role of VLDL-catabolism in plasma lipoprotein metabolism.
We concluded that excess hydrolysis of TG in VLDL made it possible to increase in LDL-TCh rather than in HDL-TCh and to cause in cholesterol-rich VLDL with low content of cholesterol in HDL.

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50g. oral glucose tolerance test was performed on 18 subjects with moderate obesity to elucidate the significance of FFA response to caloryrestriction in human. The subject were divided into following three groups; (A) with normal glucose tolerance at four weeks during caloryrestriction therapy accompaning with (1) normal response of immunoreactive insulin (IRI) (n=8), (2) high response of IRI to glucose load (n=6). (B) with glucose intolerance (DM type with fasting glucose under 120mg/100ml) at four weeks (n=4).
Results; (1) Mean value of maxium decreased FFA (basal FFA) before the diet-therapy was higher in group (B) than in both group (A)-1 and (A)-2, but there was not significant difference in mean value of relative body weight (RBW) and plasma tryglyceride (TG) between groups before the diet therapy. (2) The significantly increased basal FFA and the significantly decreased TG after the diet-therapy was seen in group (A)-2 and in group (A)-1, respectively.
These results, especially the increase of basal FFA after calory-restriction seen in the subjects with high response of IRI, might be estimated the different action of insulin between glucose-utilization and inhibition of FFA-release in obese subjects.

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From the aspect of atherogenesis of lipid peroxide, studies on the antioxidative substance such as α-tocopherol should be important. The purpose of this study is to investigate the serum concentration and distribution within various serum lipoprotein fractions of α-tocopherol in the patients with ischemic heart and cerebral diseases.
Method: 21 cases of male patients with atherosclerotic disease and 30 cases of healthy matched control have been subjected. Then, serum total cholesterol (TC), triglycerides (TG), phospholipids (PL), various serum lipoproteins and α-tocophrol (VE) were determined.
Results: 1) In hyperlipidemics of both atherosclerotics and controls, distribution of VE within HDL decreased and within LDL increased as compaired with those in normo-or hypolipidemics.
2) In the atherosclerotics with or without hyperlipidemia, distribution of VE within HDL decreased and within LDL increased as comparied those in the controls.
3) In the hyperlipidemics of both atherosclerotics and controls, quantitative VE content in 1mg of HDL were higher than that in the controls without hyperlipidemia.
On the other hand, quantitative VE content in 1 mg of HDL in the hypolipidemic atherosclerotics significantly lower than that in the controls without hyperlipidemia.
4) Upper limit may be exist for the quantitative VE content of HDL. Determined limit value in this study is approximately 1.4±0.3μg/mg of HDL. Exess amount of VE seems to be distributed within the LDL.
5) Several discussions especially atherogenesis related to hypolipidemics have been made from the obtained results.

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In studying the role of phospholipids (PL) in progression and regresison of atherosclerosis, 50μCi of emulsified ¹⁴C-dilinoleoyl lecithin was injected into 26 fasting rabbits fed laboratory chow with an average body weight of 3120±250g.
¹⁴C-Lecithin was rapidly incorporated into lipoprotein PL and transfered by transesterification to cholesteryl esters (CE) in VLDL+LDL and HDL fractions. The half life gained from the specific activity curves was 26 hours for VLDL+LDL-PL and 34 hours for HDL-PL, while 34 hours both for VLDL+LDL and HDL-CE. The ratio of DPM of CE/PL were e. g., 0.60 in VLDL+LDL and 0.32 in HDL at 10 hours.
Labeled lipoprotein lipids were further incorporated into arterial tissue, whose uptake curve consisted of two phases; the first gradual rise in 3 hours, and the second almost stationary phase in 48 hours. In CE fraction of aortic tissue, no significant counts were gained, thus the DPM ratio of CE/PL in serum lipoproteins was not maintained in the arterial tissue. These results indicate that the uptake of lipids in normal arteries with an integrated endothelium occurred predominantly in the form of molecular flux, rather than a penetration of lipoproteins in the particulate form across the cell wall.

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Recently, erythrocyte deformability has been observed as one of many factors relating to microcirculation. We have improved on the Reid's filtration technique for the determination of erythrocyte deformability, and measured erythrocyte deformabilities in patients with cerebrovascular accidents (C. V. A.) by this method, as well as erythrocyte 2, 3-DPG and ATP concentrations.
Heparinized venous blood was immediately washed once with triethanolamine HCl buffer (pH 7.40, 294mOsm/1)at 0 to 4°C, and made into a hematocrit 40% red cell suspension in the same buffer. Then, erythrocyte deformability was measured after the 30 minutes incubation at 37°C.
With reference to aging, there was no significant difference in the deformability index (D. I.) among non-smoking normal subjects. D. I. levels in normal subjects (mean=67.9ys. o.), patients with cerebral thrombosis (m.=64.3ys. o.) and patients with cerebral hemorrhage (m.=69.4ys. o.) were 0.80±0.07, 0.57±0.06 and 0.48±0.06ml⋅RBC/min., respectively. There was statistically a definite difference between normal and C. V. A. groups. A marked reduction in D. I. was observed among patients who suffered from an attack of cerebral thrombosis within one month, but after that the reduced D. I. was improved gradually.
On the other hand, there was no difference in erythrocyte 2, 3-DPG levels among C. V. A., but there was a marked increment of erythrocyte ATP contents. Generally it is known that a reduction in erythrocyte ATP induced erythrocyte deformability. Therefore, as our results the mechanism of reduced D. I. in C. V. A. is obscure.
These above observations suggest that a reduction of D. I. might be one of the most important factors in the cause of C. V. A. and also develops tissue anoxia.

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Wistar-King Strain rats were divided into two feeding groups. The one was fed on tocopherol deficient diet containing 1% cholesterol and 0.5% cholic acid (HCD-Toc D) and the other was fed on tocopherol supplement diet (20mg/100g) containing the same dose of cholesterol and cholic acid (HCD-Toc S). A remarkable decrease in serum tocopherol concentration was observed in HCD-Toc D. And in this group, thiobarbituric acid reactive substance (TBA-RS) concentrations of the aorta, the liver, the lung and the brain were increased. In these conditions, enzyme activities of acid and neutral cholesterol esterase, acid and neutral lipase, acyl-CoA synthetase, triglyceride synthesizing activity and cholesterol ester synthesizing activity of HCD-TocD was significantl decreased. Choline phosphotransferase activity of HCD-Toc D was significantly increased. Decreased activity of acid cholesterol esterase might cause deposition of cholesterol ester in lysosome of the arterial wall of tocopherol deficient rats. No change of the ratio of cholesterol ester synthesizing activity to neutral cholesterol esterase was observed between both groups. This might suggest that deposition of cholesterol ester in microsome of the arterial wall of tocopherol deficient rats was not induced by these change of enzyme activities. The relationship between elevated TBA-RS and lipid deposition in the arterial wall was discussed.

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50g oral glucose tolerance test (50g OGTT) was performed on 61 hospitalized patients suffered from ischemic or hypertensive heart disease (without acute stage of myocardial infarction, congestive heart failure, renal or hepatic disorder, secondary hyperlipidemia, endocrine disorder, etc.) to elucidate the significance of plasma free fatty acids (FFA) in men fed 1, 000 calory formula diets. The subjects were divided into four groups according to basal FFA level (maximum decreased level of FFA during 50g OGTT) with or without glucose intolerance.
Results: In the groups with normal glucose tolerance the different level of basal FFA caused the characteristics as follow. Relatively high basal FFA (over 391μEq/l) accompanied with significantly high response of insulin to 50g oral glucose (123±57μU/ml to 37±21μU/ml for low basal FFA) in spite of low frequency of delayed maximum insulin and low insulinogenic index. This subgroup also had high relative body weight before the calory-restriction though there was not seen in different response of body weight to calory-restriction.
These results, especially the increase of basal FFA after calory-restriction seen in the subjects with high response of insulin, might be estimated the different action of insulin between glucose utilization and the inhibition of FFA release in obesity.
In the groups with abnormal glucose tolerance high basal FFA was not shown only hyperresponse of insulin to 50g oral glucose but also obesity.
These results are discussed on the content of the possible role of plasma FFA in obesity and glucose intolerance.

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