It is well known that cerebrovascular disorders are the major causes of death among Japanese and the incidence of myocardial infarction is relatively low. In Hisayama survey, cerebrovascular disorders were present in 111 cases among 377 autopsy cases, and the incidence of cerebral infarction was one and a half times as many as that of cerebral hemorrhage. Atherosclerotic index (A. I.) of cerebral arteries increased markedly after the 6th decade, but the severity was less than that of aorta and coronary artery. In hypertensive cases statistically higher. A. I. was found in cerebral arteries after the 6th decade as compared with that of normotensive cases.
The endothelium of the basilar artery of rabbits was closely applied to the internal elastic lamina and endothelial cells showed a small number of caveolae and vesicles and the presence of tight junction in all the intercellular spaces. These observations suggested that insudation of plasma proteins was markedly restricted in the cerebral arteries, leading to less severe atherosclerosis than in the extracranial arteries. Postmortem angiography revealed a less number of vasa vasorum in the adventitia and media of cerebral arteries, compared with those of aorta and coronary artery.
Fibrinogen was detected in the highest frequency in the intima of branching portion of middle cerebral artery and lowest in the basilar artery.Fibrinogen was found in the subendothelial region even in microscopically normal cerebral artery and it was observed more frequently than β-lipoprotein in the thickened intima. It might be concluded that deposition of fibrinogen in the intima played a more important role in the evolution of cerebral atherosclerosis than that of β-lipoprotein, especially in its early stage of development and that the barrier function of the endothelium was disturbed at first in the branching portion, probably due to haemodynamic effects.
Hypertensive rabbits with constriction of bilateral renal arteries and long-term cholesterol feeding showed small foci of foam cell accumulation at the sites of branching of cerebral artery.Increased permeability to H. R. peroxidase was observed not only in the foam cell lesions but also in the other arterial segments without intimal thickening.
Intramural hemorrhage from newly formed intramural capillaries was the most conspicuous findings which might precede thrombus precipitation in 39 arterial segments with fresh occlusive thrombi in the cerebral arteries. Persistent hypertension was present in 75.9% of these cases.
It might be reasonable to assume that hypertension played a most important role in the development of cerebral atherosclerosis and also in the cerebral thrombosis.

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Based upon results of the group study organized by the Welfare Ministry, the present status of Buerger's disease (TAO) in Japan were described.
1. There may be about 4, 000-5, 000 patients with TAO at present in Japan. Results obtained from 3, 034 patients of TAO revealed that male vs female was 30:1 in incidence and 92.4% of the patients were smoking.
2. Although symptoms mainly appeared in the lower extremities, intermittent claudication was less observed than in Arteriosclerosis obliterans (ASO). Thrombophlebitis migrans was emphasized as a special sign of TAO.
3. Dangerous complications were far less found in TAO than in ASO.
4. In the histopathological study of the vessels in TAO, granulomatous changes with epitheloid cells and fibrous proliferation of intima were occasionally found in the acute stage of the disease. The pathogenesis of TAO, i. e., immunological factor or mechanical injury, were discussed in relation to those findings.
5. Angiographies in 809 cases with represented the characteristic findings of the disease as follows: The arterial occlusion may mainly be limited below the inguinal ligament or at the forearm and was most frequently observed near the foot or hand joint. It was confirmed that no changes is found in the arteries which are not occluded. However, irregularity of the wall or stenosis, which were distinctly differ from those frequently seen in ASO, were occasionally found. Other special findings to be emphasized were tapering-type occlusion, cork screw or tree root configuration, smooth diffuse narrowing and thread-like changes of the arteries.
6. By the haematological examinations, abnormalities in the blood coagulability and/or the platelett function may be supposed in the patients of TAO.
7. The immunogenetical examinations revealed that the special types (BJW22.2, J-1) of HLA-typing should be noticed in the patients of TAO and AVA in the serum was significantly higher in TAO (68.8%) than in ASO (12.5%).
8. The lipid metabolism may not be concerned in the genesis of TAO, because triglyceride, lipoprotein, NEFA, phospholipid, and total cholesterol were not significantly increased in the serum of patients.

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During the past 14 years, 62 of 109 patients with the aortitis syndrome were operated on for some of the lesions. Ages of the majority of the patients were between 20 and 40 years with prevalence in females.
Eighteen patients with brachiocephalic occlusive lesions underwent reconstructive surgery to relieve their sumptoms comprising visual disturbance (8 cases), syncopal attack (7 cases), dizziness (6 cases) etc. Operative mortality was 16.7%. The most frequent cause of death was acute cerebral hemorrhage and edema. Follow-up study revealed improvement in 71% of the survivors. There was no late death.
Patients with earlier than stage III (Uyama's classification) of occular fundi, and less than 30mmHg retinal artery pressure are best indicated for surgery with promising result.
Nine patients with isolated atypical coarctation were operated upon by aortic bypass. Follow-up showed 89% improvement.
Results of 14 patients with renal artery stenoses combined with atypical coarctation were poor, imposing the most difficult problem.
Twelve patients with isolated renal artery stenoses (renovascular hypertension) were operated on and late results showed 83% cure and improvement in blood pressure.
Ten patients with aneurysms were operated on by resection, with 2 operative death. Late results showed 3 suture aneurysms, 2 of which ruptured.

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Pathophysiological view of the arteriosclerosis obliterance (ASO) of mostly lower extremity which we experienced in last 21 years were reviewed comparing with Buerger's Disease (TAO) of same period. The mean age of the ASO is 60.4 year-old, and the occluded lesions are seen mostly in above inguinal bands. The complications and symptoms of ASO are mainly intermittent claudication. ASO of our country has tendency of less serious complication than the western countries. However the motality rate of the ASO in 21 years is 34.3% mostly caused by cardiovascular disturbance, so that we have to consider that the ASO is one of the phenomenons of arteriosclerosis of general body, therefore we have to pay attension to careful controle on general body, especially on the cardiovascular system in the post operative period.

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Indication and result of surgical treatment for the peripheral arterial occlusive lesion of the lower extremity were discussed on the cases performed in 31 institutions in Japan within past three years from January 1973 to December 1975.
1. For atherosclerotic aorto-iliac occlusive lesion, 215 synthetic prostheses, 108 endarterectomies and 17 axillo-femoral bypass prostheses were performed. Long-term patency rates in each procedure were 79.1, 75 and 76.5 per cent respectively.
Delayed rupture of the suture line as a postoperative complication of the synthetic prosthesis appeared in about 10 per cent of the anastomoses. These complications were considered to be prevented by wrapping technique using synthetic mesh or felt.
2. For atherosclerotic femoro-popliteal occlusive lesion, 122 autogenous vein grafts, 61 endarterectomies and 20 synthetic prostheses were carried out. Long-term results in each procedure were fairly good with 70.5, 75.4 and 80 per cent in patency rate respectively. On the contrary, for the lesion natured by Berger's disease 67 autogenous vein grafts, 21 endarterectomies and 10 synthetic prostheses were performed having inferior results to that of reconstructions for atherosclerotic lesions.
In the vascular reconstruction for the peripheral arterial occlusive lesion in this level, it was considered to be very important to prevent early failure. On this regards, flow wave pattern recorded by an electromagnetic flowmeter at the end of operation was considered to be very useful as a sufficient indicator to assess the outcome of the reconstruction.
3. For infrapopliteal or extensive lesion, lumbar sympathectomy has been conventionally carried out. However, tibial arterial bypass technique using an autogenous vein graft, free transplantation of the omentum or so called A-V shunt procedure were recently deviced by some authors as an active reconstructive surgery for these intractable lesions. Long-term results of them were fairly good under the proper indication in each procedure respectively. Moreover, in some cases with ischemic ulcer at the foot and toes, continuous infusion of some vasoactive agents, that is Prostagrandin-E, various vasodilators, dextran sulfate or 0.15 per cent hyrogen peroxide solution, through a small teflon tube inserted into the regional artery was used showing considerable improvement of the ischemic ulcer in about 70 per cent of them.

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Three hundred and eighty patients with various peripheral arterial occlusive diseases have been encountered at our department during the last 15 years. The most frequent clinical entity among them were thromboangitis obliterans (TAO), 145 cases and arteriosclerosis obliterans (ASO), 125 cases. Arterial occlusion in TAO occurs usually at the peripheral level of the limb artery where the conventional reconstructive surgery is hardly applied. On the contrarily, reconstructive surgery was able to apply to the most cases of ASO. Thus it was applied to 38 cases, or 26 per cent in TAO and 78 cases, or 64 per cent in ASO.
Results of reconstructive surgery (38 cases, 43 limbs and 52 operations in TAO, and 78 cases, 91 limbs and 100 operations in ASO) were analysed with special reference to operative procedures and complications. Results in TAO were not so favorable. Early patency rates of thromboendarterectomy (TEA), prosthetic graft bypass and autogenous vein bypass in TAO were 41 per cent, 33 per cent and 65 per cent, respectively, Late patency rates were 23 per cent, 0 per cent and 48 per cent, respectively. Those figures are well contrasted with the figures in ASO groups where early patency rate was 85 per cent and late patency rate was 69 per cent. Difference of results among the procedures is not so apparent, TEA and prosthetic graft bypass procedures proved to be unfavorable in TAO. Vein bypass was the single procedure applicable to obtain resonable results.
Most frequent complications were early thrombosis which occured 14 per cent in ASO and 46 per cent in TAO. Late occlusions were observed 16 per cent in ASO and 20 per cent in TAO. Infection was complicated in 3.3 per cent. Anastomotic aneurysm was observed in 2.6 per cent.

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The ultrastructure at the branching points of rat basilar arteries was studied. The endotherium of the intimal pad contained numerous bundles of microfilaments like those ofthe smooth muscle cell. The blebs containing small vesicles and electron lucent materials were seen on the surface of the endothelium. Just beneath the endothelium, degenerated cells were often observed. The internal elastic lamina in this area thinned on bifurcated at the margin of pads.
The extracellular space of this area was widened over other areas and contained a few collagen fivers and fragmented elastic fibers. Numerous cellular debris and degenerated cells derived from the smooth muscle cells or the endothelial cells also were observed in this area. Several junctional types were seen between smooth muscle cells.
The intimal pad seems to be the sites of enhanced degeneration of endothelia, smooth muscle cells and elastic fibers. These alterations may have resulted from the hypoxic condition induced by hemodynamic changes.

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Endotheliums of blood vessels are significantly important in every vascular diseases, especially in arteriosclerosis. However, detailes of the character and the function have not sufficiently proved. This paper represents the demonstration of contractile protein “actomyosin” as same as the smooth muscle and the reaction to the clot of blood in the cultured endothelial cells.
The smooth muscle actomyosin is extracted from canine intestinal smooth muscle by Becker's method, and the antiserum to the actomyosin is obtained by immunization to rabbits. The cultured endotheliums are brilliantly immunofluorescent in the cytoplasmas and gradually decrescent in the periphery, but not immunofiuorescent in the nuclei. As this, the cultured endotheliums even over twenty generations prove to have myofilaments electron microscopically and contractibility.
It is recently said that proliferation of endotheliums is stimulated by platelet rich serum. The cultured endotheliums promptly envelope around the dissociated platelet-fibrin clot three days after adding the blood coagulation. On the 9th day, the endotheliums penetrate into the platelet-fibrin clot and separate it to more small portions in which the nuclei are larger and hypercheomatic and make a tufting or budding architecture as seen in intravascular papillary endothelial hyperplasia. However, there does'nt participate in the growth of endotheliums only with blood or fibrin.
It is proved the platelet factor is very important to stimulate proliferation of endotheliums in vitro.

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Regarding to the pathological genesis of renal arteriolar hyalinosis in diabetic nephropathy, neumerous literature of the morphological studies have been documented. Recently have been emphasized by YAJIMA the importance of renal circuratoly disturbance for pathogenesis of renal arteriolar lesion from observation on various disease.
Based on this viewpoint, observation were made in 65 autopsy kidneys of clinical diabetic patients by light microscopy and 10 cases of them by electron microscopy.
Result: In diabetic nephropathy, arteriolar hyalinosis is usually very remarkable and could be frequently found not only in WK-lesion but also in other forms. The nodular and exudative lesions were closely related to the grade of arteriolar hyalinosis. The morphological character and localization of hyalinosis were that its hyalinosis appeared in the afferent arterioles and its adjacent proximal portion of the intralobular artery, but in some advanced cases it could be found in an intraglomerular branches of afferent arterioles. By electron microscopy, initial lesion that no findings by light microscopy were observed at the part of entrance of glomerulus. Its lesion were subendothelial serum deposition with degeneration of endothelial and smooth muscle cells.
The morphological character and localization of arteriolar hyalinosis is caused by its hemodynamic alteration due to circulatory disturbances which is considered to be brought about by spasm of the peripheral portion of afferent branches.

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It is the purpose of present report to analyze whether kidney influences development of arteriosclerosis.
Of the total 73 autopsy cases examined, 25 were grouped as dialyzed chronic glomerulonephritis, 20 non-dialyzed chronic glomerulonephritis, 28 controle cases.
The results obtained were summarized as follows;
1) The arteriosclerotic severity of proximal portion of superior mesenteric arteries showed parallel correlation to age and cardiomegaly-index in renal failure groups.
2) Arteriosclerosis of small arteries and Arterioles in the small intestine were higher in degree in non-dialyzed chronic glomerulonephritis group than these in the other two groups.
3) Non hypertensive renal factor as well as aging and hypertension may be closely related to the pathogenesis of arteriosclerotic changes in middle-sized and small arteries, and arterioles examined.

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In order to confirm rather unexpected declining trends in age-sex-specific death rates from ischemic heart disease (IHD) in the Japanese population, mode of death certification, particularly of the diagnosis of IHD was studied by an inquiry to a certifying doctor about used diagnostic methods. A sample of 516 was drawn from 744 deaths which occurred in the Itabashi-east area, northern Tokyo in 1975. The sample consisted of all cardiovascular deaths, all deaths from unidentified causes and randomly selected half of the remainder, excluding violent deaths and deaths of children below the age of 1 year. Answers were obtained on 398 cases (response rate 77%).
Around 80% of each of IHD, symptomatic heart disease, stroke and ill-defined conditions were certified by private practitioners and in private hospitals. Frequency of used diagnostic examinations by private practitioners were 37% for electrocardiogram (ECG) and also 37% for serum enzyme determination, and no autopsy was made. Corresponding figures were higher in hospitals. These observations imply that the only way of improving diagnostic accuracy and medical care of patients with IHD at the community level is upgrading services of private physicians.
The above mentioned diseases were main sources of undiagnosed or misdiagnosed IHD, and were checked whether or not objective diagnostic methods such as electrocardiography or autopsy was undertaken.
Death certificates used to be signed before autopsy in Japan. Of 48 diagnosis of IHD as a cause of death, 13 underwent autopsy, of which 3 were proved to have died from other causes, and 32 including 9 with autopsy confirmation as well, had an ECG examination. These were regarded as definite cases, but remaining 12 had none of these examinations and were considered as possible cases. Three out of 27 autopsied cases from 41 cases of ill-defined conditions and 2 more from other diseases were added to definite IHD according to autopsy findings. Nine cases with cardiac insufficiency without mentioning underlying causes were also considered as possible cases of IHD, under the assumption that frequency of IHD be same as that among cases with cardiac insufficiency of known causes. Thus instead of 48 certificates which listed IHD as a cause of death, 38 cases with definite IHD and 21 cases with possible IHD came up as a more closer-to-real estimate in this community.
The way in which IHD was diagnosed was not uniform and accuracy of the diagnosis of IHD was not high at a community level. Mortality statistics of IHD may therefore be used for a crude estimate but cannot be used for sophisticated analysis.

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Serum cholesterol of 1, 789 private school students aged 12, 15, 18 and 19 years and 1, 953 civil servants aged 20-69 years of both sexes were measured in 1976. They were middleclass residents of Tokyo.
Mean serum cholesterol of students ranged 165-176mg/dl through these age groups, and was almost same as that of U. S. white students reported in the Bogalusa study.
Mean cholesterol of civil servants at any sexage specific (with 10-year intervals) subgroup was, however, lower than that of the U. S. whites reported in the Framingham study and a study by Dr C. J. Clueck et al. The older the civil servants, the wider the gaps in serum cholesterol between the Japanese and American counterparts.
Three crossovers in age-specific mean cholesterol in men and women were observed in this study. At the age of 12, serum cholesterol of boys and girls was 166±26, and 164±20mg/dl respectively and was almost identical. At the age of 15, nearly all girls had passed menarche and thereafter showed little growth in mean height and weight. Mean cholesterol rose steeply initially but the rising trend stopped afterwards. Mean cholesterol stayed lower in boy students, during which periods growth continued. A rapid rise up to 182±29mg/dl in men exceeding 178±23mg/dl in women occured in the third decade.
Thereafter mean cholesterol rose continuousely with age to reach the highest level of 198±28mg/dl at the fifth decade in men, and 200±24mg/dl in women at the sixth decade, exceeding men again.
Serum cholesterol of urban Japanese children thus no longer differs from their American counterparts. This was most likely caused by ample (or over-) nutrition provided, especially by westernstyle school lunch services. Serum cholesterol was much lower in the third decade and thereafter. These civil servants at the third and fourth decades also had had such school lunch services. The difference between the two population groups might stem from still continuing process of westernization of Japanese diets. A more plausible explanation, however, is that changes of their diets to a more traditional ones after leaving schools decelerates the rising trend in cholesterol with age.It therefore appears that focusing attention on teenagers or the early twenties rather than on children or babies may be an efficient and effective strategy for controlling hyperlipidemia, and consequently for preventing atherosclerosis. Follow-up of these cohorts, however, is necessary since this hypothesis is based on combined cross-sectional data from two different populations.

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Hourly changes of salivary total binding hexose (STBH) during 100g glucose tolerance test (GTT) were investigated in 129 cases with mild hypertension, diabetics and gastritis.
And also as control, hourly changes of STBH by water administration of 500ml were observed in 5 cases of the young and 13 cases of the aged.
Sephadex G-100 column chromatography of STBH was performed in 3 cases of the healthy young and 3 cases of the healthy aged.
1) Though the amounts of STBH were not changed hourly by oral water administration, the amounts of STBH were obviously increased 30 minutes and 6 minutes after 100g GTT.
2) The increased amounts of STBH by 100g GTT were in such relationships as “the young>the aged”, considering types of GTT.
3) The STBH was separated at least into two fractions (FrI, FrII) by sephadex G-100 column chromatography. The molecular weight is in such relationships as “FrI>FrII”.
The increased amounts of FrI and FrII by 100g GTT were in such relationships as “the healthy young>the healthy aged”. Therefore, there are close relationships between the both fractions and aging.
4) It was speculated that the dry feeling of oral cavity in the aged related to the decreased secretion of STBH.

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Aortas taken from 375 unselected autopsy cases in Japanese were morphologically studied, for measurement of perimeter at the initial portion of the thoracic aorta (PM) and percent area with various atherosclerotic lesions including fatty streaks, fibrous plaques, atheromas and complicated ones, to whole intimal surface. The PM increased with age (A), hypertension and advancing atherosclerosis. The PM increase in the normotensives (NT) showed a rapid upward gradient till the 3rd decade, then a slow one till the 5th decade, and again a rapid one thereafter. Hypercholesterolemia affected the PM with some increase in older age group and a decrease in younger age group in the NT. Hypertension made an increase in the PM after the 6th decade, and the existence of hypertension was important but not its grade. In the hypertensive group (HP), serum cholesterol level had no definite effect to the PM. The atherosclerotic areas were devided into 6 groups, that is, 0, 10, 25, 50, 75 and 100% to the entire intimal surface and were compared to the PM. The involved areas showed positive logarithmic correlation to the PM with a minor dent formation between 25 and 50% lesion in the NT group. The positive relation was also existed in the HP group, but difference between NT and HP was narrowed in the cases with advanced sclerotic lesions. After consideration of these factors, though its application was limited to cases after 6th decade, the following equations could be set; for 10% lesion group, PM (cm)=0.017 A (year-old)+4 (for men) or 3.8 (for women), for 25% lesion group, PM=0.032 A+3.5 (for men) or 3.3 (for women), and for 75% lesion group, PM=0.042 A+3.5 (for men) or 3.3 (for women). The existence of hypertension could affect the PM by 10% more than expected from these formulas.

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A novel method for the estimation of fibrinolytic activity is proposed. In this method, a fibrin clot suspension is used as a substrate. With this method, we found that free fatty acids inhibited plasmine activity even in the presence of albumin. Then experiments were carried out to clarify details of free fatty acid-producing system in arterial walls. Pseudocholine esterase was purified from human serum and was demonstrated to be identical with the non-specific esterase. When the purified esterase was incubated with slices of rat aorta which was pretreated with heparin to remove lipase, remarkable elevation of lipase activity was observed. The recovery of lipase activity by addition of the esterase was also confirmed by histochemical method. These results suggested that plasma esterase might convert to lipoprotein lipase in aorta. Experiments were now in progress to certify this possibility.

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It has been revealed that human pancreatic tissue or juice contains two elastases, elastase-1 and elastase-2, which are distinct from each other with respect to their physicochemical and enzymological properties.
We have recently isolated two elastases from human pancreatic juice and investigated physicochemical, enzymological and immunological properties of these two human pancreatic elastases.
Elastase-1 was an anionic protein with a molecular weight of 30, 500 and elastase-2 a cationic protein with a molecular weight of 24, 500. Elastase-1 showed rather potent esterolytic activity but less elastinolytic activity in comparison with elastase-2. The kinetic parameter, Km toward suc-(Ala)₃-pNA, was 1.0mM for elastase-1 and 14mM for elastase-2. The aminoacid compositions of the two elastases were very similar although there was a little difference in the glutaminic acid, serine and proline contents. Different antigenicity of the two elastases were demonstrated in immunodiffusion and immunoelectrophoresis. Elastase-2 did not result in a precipitant with anti-elastase-1 antibody.
The results obtained in the present study indicated that our elastases were identical with elastases previously reported by other investigators. Our elastase-1 was identical with elastase-1 of Largman et al. and protease E of Mallory and Travis, and our elastase-2 with elastase-2 of Largman et al. and cationic elastase of Ohlsson and Olsson.
In summary, we have revealed that the two elastases are clearly distinct from each other in respect to their ionicity, molecular weight, enzymological property and antigenicity even though there is a close correlation with respect to their amino acid composition.
The possible role of these two pancreatic elastases on the development of atherosclerosis was also discussed.

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Cyclic GMP (cGMP) is an important key substance in cell function. As the content of this nucleotide in the cells is so minute an accurate estimation is difficult. We developed a microassay method for cGMP in 40-100μg dry weight (d. w.) of tissue samples by succinylation and succeeded in assaying the content of cGMP in separate intima and media tissues from rabbits, cows, pigs and sheep. Briefly, the protein was removed and the sample lyophilized. Such was then dissolved with 50μl of H₂O and 30μl of succinylation mixture (40mg succinic anhydride dissolved in 0.9ml dioxane:triethylamine=9:1) was added. After succinylation, the sample was loaded on an alumina column for chromatographic analysis. Succinyl cAMP was eluted from the column with 3ml of 0.4 formic acid and then cGMP was eluted with 4ml of 3M formic acid. After lyophilization, radioimmunoassay was carried out using Yamasa's kit. Recovery rates of cAMP and cGMP were 71.9±0.6 and 74.1±0.9%, respectively. Levels of cGMP in the intima and media of the aorta from cows, sheep, pigs and rabbits were, intima: 250±50, 126±8, 280±20 and 250±50 fmole/mg d.w., respectively. Levels in the media were, 173±3, 176±24, 146±14 and 173±50, respectively. It should be noted that the levels of cGMP in the intima of the aorta from cows, sheep and rabbits were statistically higher (p<0.05) than these levels in the media.

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