著者

佐野 隆一 阿部 隆三 平川 秀紀 金沢 義彦 小泉 勝 豊田 隆謙 後藤 由夫 及川 真一

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.11, no.3, pp.671-676, 1983

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In the present study, the effect of probucol (500mg×2, daily) on serum lipids and lipoproteirs level were studied in 9 patients with familial hypercholesterolemia (FH) during 3-4 months. The diagnosis of FH was established according to the criteria both of Fredrickson et al and of Makuchi et al. Thickness of Achilles tendon was over 9mm in all patients and the xanthomas were observed in 4 of 9 patients.<br>Before and 3-4 months after treatment of probucol the measurement of serum triglyceride (TG), total cholesterol (TC) and apolipoprotein (Apo) A-I and A-II were made. At the same time, serum VLDL, LDL, HDL₂ and HDL₃ were separated by successive ultracentrifugation. Thereafter, TG, TC and protein of each lipoprotein fraction were measured.<br>TG and TC were determined by enzymatic method, Apo A-I and A-II were done by single immunodiffusion assay, and protein was done by dye-binding method.<br>All data were expressed as mean ±S.E. and statistically analized by Student's t-test.<br>The results were as follows:<br>1) VLDL-TG levels were slightly increased, although no significance was found between VLDL-TG level before and after treatment.<br>2) The levels of serum TC were 388±37mg/dl and 308±28mg/dl (-21%, p<0.05) before and after probucol administration, respectively. LDL-cholesterol (LDL-C) levels decreased from 325±37mg/dl before treatment to 262±32mg/dl (-19%, p<0.05) after treatment. HDL-C values significantly decreased from 42±5mg/dl to 26±4mg/dl (-38%, p<0.01), and especially HDL₂-C showed significant fall (-48%, p<0.01).<br>3) Serum Lecithin: Cholesterol Acyltransferase (LCAT) activities were not changed.<br>4) The concentrations of Apo LDL decreased from 139±18mg/dl to 106±17mg/dl (-29%), but it was not significant statistically. Apo A-I levels decreased significantly from 92±10mg/dl to 66±10mg/dl (-28%, p<0.01). On the other hand, Apo A-II levels were unchanged.<br>These observations suggested that probucol would be a useful drug to improve serum and LDL cholesterol levels in FH. However, we should take care to use this drug because of its effect on HDL metabolism.

著者

及川 眞一 阿部 隆三 後藤 由夫

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.9, no.6, pp.1035-1039, 1982

被引用文献数

2

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It is thought that multi-factors may relate to the occurence and exaggeration of arterial sclerosis in diabetes mellitus. We pointed out the calcification of peripheral arteries in the legs on X-ray photographs as a sign of arteriosclerosis, and studied its prevalence in diabetics and nondiabetics. Furthermore, in order to clarify what correlates with the arteriosclerosis, we analysed the laboratory data and studied the differences between the diabetics with or without the peripheral arterial calcification.<br>We concluded that the incidence of the peripheral arterial calcification in diabetics (32%) was twofold higher than that in non-diabetics (16%).<br>It was clarified that the incidence of the calcification increased significantly in diabetics who had insulin treatment as compared with those who had oral agents or only diet therapy. Similarly, it was significantly higher in diabetics who were complicated with proliferative retinopathy than those who had simple or no retinopathy. And also, diabetics with longer duration of illness had significantly high incidence of the calcification as compared with those with shorter duration.<br>It was relatively higher frequency in diabetics who had hypertention and were controled poorly than those who had normotention and were controled well, respectively, but there was no significance between them.<br>There were no relationships between the peripheral arterial calcification and obesity, serum concentration of lipids, ischemic changes on ECG and aortic arch-calcification in diabetics.<br>These results suggested that the peripheral arterial calcification might relate to the metabolic derangement in diabetes mellitus.

著者

山田 憲一 阿部 隆三 鈴木 進 及川 真一 後藤 由夫

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.10, no.3, pp.489-495, 1982

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Diabetic autopsy cases were collected from the Annual Report of Pathological Autopsy Cases published by Japanese of Pathology for the year 1976-1978. 2089 primary diabetic cases were collected and the cause of death and pathoanatomical findings in various organs were analysed in these primary diabetic cases, and following results were obtained.<br>1) The main causes of death were cardiovascular diseases (43.1%), malignant neoplasma (22.6%), infections (16.2%), diabetic coma (1.9%) and hypoglycemia (0.3%).<br>2) In cardiovascular diseases, the leading cause was diabetic nephropathy (15.6%), followed by cerebral (14.6%) and coronary (10.5%) artery disease.<br>3) The frequency of arteriosclerotic cardiovascular diseases and malignant neoplasmas as cause of death increased with age. Diabetic nephropathy appeared as a cause of death in 3rd decade and the leading cause of death was diabetic nephropathy in 3rd decade (52%) and 4th decade (32%), and over 5th decade decreased with age. Cerebral vascular and coronary artery diseases increased with age and cerebral vascular disease was the leading cause of death over 6th decade.<br>4) In pathoanatomical findings, the frequencies of glomerulosclerosis, myocardial infarction, cerebral infarction and homorrhage were 40.9%. 17.2%, 15.6% and 7.0%, respectively. Myocrdial infarction and cerebral infarction were found in 4th decade and increased with age, while cerebral hemorrhage decreased over 6th decade with age. Diabetic glomerulosclerosis was found in the cases of 2nd decade and high frequencies of glomerulosclerosis were found in all decade and it was higher than those of other vascular lesions.<br>These results showed the characteristics in the causes of death of diabetics in Japan are a lower incidence of coronary artery disease and a high incidence of diabetic nephropathy.

著者

佐野 隆一 阿部 隆三 及川 真一 藤井 豊 後藤 由夫 高瀬 貞夫

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.15, no.4, pp.1005-1008, 1987

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

著者

松田 保 山之内 博

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.9, no.4, pp.543-549, 1981

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Hypothesis, firstly proposed by Rokitansky in 1852 and revived by Duguid in 1946, that atherosclerotic plaques result, at least partly, from organization of fibrin thrombi, is fascinating from view point of blood coagulation, although direct evidences have been lacking. Authors have demonstrated that levels of β-thromboglobulin and platelet factor 4 decreased following administration of antiplatelet agents and that concentration of antithrombin III in plasma lowered following decrease in levels of vitamin K dependent procoagulants by administration of warfarin. These results support Astrup's hypothesis that minimal fibrin deposition and its lysis continuously occurrs on vascular intima in normal subjects. Assuming that these hypotheses are true, hypercoagulability of blood in a broad sence may accelerate deposition of fibrin on vascular wall and may lead to progression of atherosclerosis.<br>Purpose of this study is to elucidate this problem from investigation of blood constituents which affect removal of activated clotting factors which are most important in formation of fibrin. Two major parameters which affect blood viscosity, namely hematocrit values and fibrinogen content, and two most important inhibitors of activated procoagulants, namely antithrombin III and α₂-macroglobulin, were compared to grade of atherosclerosis of coronary and cerebral arteries classified grossly with naked eyes in serial 537 autopsied cases without cancer or DIC.<br>Following results were obtained: Hematocrit values were significantly higher in patients with marked atherosclerosis of cerebral artery. There were no statistically significant correlations between levels of inhibitors or fibrinogen and the grade of atherosclerosis, although total antithrombin levels, which were generally lower in males because of higher content of α₂-macroglobulin in females, decreased in females with severe atherosclerosis. However, a 54-years old male with congenital dysfibrinogenemia, in whom delayed convertion rate of fibrinogen into fibrin and impaired platelet aggregability induced thrombin and angiographically marked sclerosis of cerebral artery were demonstrated, had repeated attack of cerebral infarction, although risk factor of arteriosclerosis was lacking but hypertension.<br>From these results, it is concluded that evidences in favor of the thrombogenic theory of atherosclerosis is insufficient and that mild suppression of blood clotting system is not enough to protect one from arteriosclerosis.

著者

松田 保 村上 元孝

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.3, no.4, pp.447-455, 1976

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Coagulability of blood was measured in 80 cases of acute myocardial infarction, 98 cases of acute cerebral infarction and 33 cases of acute cerebral hemorrhage. Platelet counts, activated partial thromboplastin times, prothrombin times, plasma fibrinogen content, levels of plasma antithrombin III, α₂-macroglobulin and fibrin degradation products (FDP) determined within 1 month before the attack of myocardial infarction or stroke, and those measured within 48 hours or 3 to 7 days following the onset of these diseases were compared with data obtained from 370 healthy subjects over age sixty.<br>Concentrations of plasma antithrombin III were apparently decreased before and after the development of myocardial infarction. In ten autopsied patients with acute myocardial infarction, three cases with extremely low levels of plasma antithrombin III (less than 2 mg/d<i>l</i>) were complicated with disseminated intravascular coagulation (DIC), acute cerebral infarction and/or thromboembolism of lower extremities, while no thromboembolic episodes following myocardial infarction were observed in the other seven cases in whom plasma antithrombin III concentrations were more than 20mg/d<i>l</i>. Levels of the other thrombin inhibitor in plasma than antithrombin III, i. e. α₂-macroglobulin, were increased immediately after the occurrence of cerebral hemorrhage. Plasma fibrinogen content was markedly increased after the development of myocardial infarction or cerebrovascular diseases. Activated partial thromboplastin times, prothrombin times and FDP did not significantly change before and after the development of these diseases. These data suggest that there may be a relation between development of myocardial infarction and the low levels of plasma antithrombin III. Increased levels of plasma fibrinogen, as a result of myocardial infarction or stroke, may not accelerate coagulation mechanism but act disadvantageously by elevating blood viscosity.<br>Relationship between activated partial thromboplastin times, prothrombin times, plasma fibrinogen content, levels of plasma antithrombin III, α₂-niacroglobulin or FDP, determined within 1 month before death, and grade of atherosclerosis of aorta, cerebral, coronary or femoral artery, classified grossly with the naked eye, was investigated in 186 autopsied cases without cancer or DIC, retrospectively. There were no correlations between these parameters and the grade of atherosclerosis, except that levels of FDP were significantly increased in cases with severe atherosclerosis of femoral artery. From these results, direct evidences supporting thrombogenic hypothesis of atherosclerosis suggested by Duguid were not obtained. However, atherosclerotic lesion of peripheral artery may activate clotting processes and increase FDP.

著者

室田 誠逸 森田 育男

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.16, no.7, pp.925-928, 1988-12-01 (Released:2011-09-21)

参考文献数

2

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For the simple examination of the change in vascular permeability response of endothelial cells to various stimuli, we attempted to establish an in vitro experimental model using Boyden's chamber. This chamber has both upper and lower compartments with a partition filter between them. We succeeded in obtaining a monolayer of vascular endothelial cells on the surface of the filter by using a gelatin coated nucleopore filter. Both upper and lower compartments were filled with culture medium. When bovine serum albumin was added only to the upper compartment, the albumin was time-dependently leaked from the upper compartment to the lower compartment though the pores of the filter. The leakage was inhibited greatly when the surface of the filter was covered with entothelial cells.By monitoring the amount of albumin leaked into the lower compartment after the addition of various stimuli, such as histamine, serotonin, bradykinin, PAF (Platelet activating factor) etc., to the upper compartment, we could judge which stimulus could better influence vascular permeability. PAF was found to be the most active stimulus in increasing vascular permeability.During the course of the investigation, we found that such substances as having cytotoxic activity, i.e., lipid peroxides, antiserum in the presence of the complement etc., could also increase vascular permeability. Therefore, by measuring cell viability at the same time, this model can be used as an in vitro assay system for measuring vascular endothelial cell injury. This model may also be a useful in vitro assay system for the evaluation of cytoprotective drugs. By using this system we found that 15-HPETE (15-hydroxyeicosatetraenoic acid), one of the lipoxygenase metabolites of arachidonic acid, has a strong cytolitic activity on vascular endothelial cells and that MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) could prevent the cells from such injury.

著者

張 念中 河合 祥雄 岡田 了三

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.15, no.5, pp.1185-1191, 1987-10-01 (Released:2011-09-21)

参考文献数

25

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Mental stress from one's occupational circumstances is considered an important risk factor in the occurrence of myocardial infarction. However, because of difficulty in quantitative evaluation of such stress, this issue has not been fully studied. In the present work, we investigated the relationship between deaths from acute myocardial infarction (AMI) and occupation using data from the series of the Annual of the Pathological Autopsy Cases in Japan, in which autopsy cases throughout Japan are described. With regard to the 56, 268 persons who died at the age of 15 or older in 1973, 1974 and 1975, i. e., the year of economic depression due to the first oil shock and the years before and after the oil shock, we compared (I) the mortalities from AMI and frequencies of such deaths among all autopsy cases in Japan in relation to the occupational group in the three years and (II) the mortalities from AMI according to the occupation among 3, 241 randomly selected deaths in the three years. The mortality from AMI for 1973, 1974 and 1975 was 2.6%, 3.7% and 3.0%, respectively, showing a significantly higher value for 1974 (p<0.001). Among persons who died from AMI, the proportion of mental workers, particularly executives and managers, and unemployed/retired individuals was significantly higher (p<0.05) in 1974. As for randomly selected autopsy cases, the mortalities from AMI among mental workers in 1973, 1974 and 1975 were 7.8%, 17.0% and 6.2%, respectively, and the corresponding rates among physical workers were 2.0 %, 1.8% and 2.6%. Thus, the mortality among mental workers was significantly increased in 1974 (p<0.05), whereas there were no such variations among physical workers. In addition to the corroboration with the previous experience that deaths from AMI are more frequent among mental workers, particularly executives and managers, than among physical workers, we noted an increase in moratlity from AMI in the period of economic depression. It seems that stress derived from occupational circumstances rather than limited physical activities is involved in the occurrence of AMI.

著者

吉川 昌江 佐久間 長彦 日比 野剛 池内 玲子 佐藤 貴昭 米山 明彦 岩田 誠司 川口 正展 神谷 吉宣 伊藤 純子 藤浪 隆夫

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.22, no.2-3, pp.203-207, 1994-08-01 (Released:2011-09-21)

参考文献数

25

被引用文献数

1 1

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The Oxidative modification of low-density lipoprotein (LDL) could contribute to atherosclerosis as a result of its cytotoxic effect, uptake by the scavenger receptor, and its influence on monocyte and macrophage migration. Ascorbate is an important watersoluble, chain-breaking antioxidant in humans.In this study, we examined the effect of ascorbate on the Cu2+-induced oxidative modification of LDL. LDL was incubated for 24 hours with 2.5μM copper (Cu2+) in phosphate-buffered saline (PBS) in both the presence and absence of ascorbic acid (20μg/ml, 25μg/ml, 30μg/ml, and 35μg/ml). Ascorbate significantly inhibited the oxidative modification of LDL, as indicated by both the decreased electrophoretic mobility and the linoleic acid content. Oxidative modification was prevented in a concentration-dependent manner by the addition of ascorbate.Our data suggests that ascorbate may play an important physiological role in protection against the oxidative modification of LDL.

著者

佐藤 敬 高松 滋 逸見 一穂 作田 茂 水野 成徳 目時 弘文 高松 むつ

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.7, no.2, pp.271-277, 1979-07-01 (Released:2011-09-21)

参考文献数

12

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The HDL-cholesterol (HDL-Ch) concentration of 153 cerebrocascular patients within 1 year from onset and 257 controls were determined in the supernatant of serum in heparin-Ca++ precipitation method. In some patients, serum HDL-phospholipid (HDL-PL) concentrations were also determined. Liver function tests (GOT, GPT, TTT, ZST) were normal in all of these subjects, and control subjects had no adnormalities in physical findings, blood pressure, ECG, urinalysis etc.The average values in male and female controls were 65±20.9mg/dl and 65±22.3mg/dl, respectively. The value of female subjects over 55 years of age was lower than those of age-matched male and female under 54. There was no significant change by age in values of male control. In male patients with cerebral infarction, average HDL-Ch value was 55±18.6mg/dl and it was significantly lower than the control value. The value of female patients was 62±15.0mg/dl. In female, there was no significant difference between patients and control. Among the patients with cerebral infarction, the cases with angiographically demonstrated obstruction of internal carotid or middle cerebral arteries showed lower value as compared to those without such findings. In male and female patients with cerebral hemorrhage, average HDL-Ch concentrations were 55±13.3mg/dl and 60±16.8mg/dl respectively. Again only the value of male patients was significantly lower than that of control.Considering the importance of balance between atherogenic and anti-atherogenic properties of cholesterol in various lipoprotein fractions, HDL-cholesterol/total cholesterol (HDL-Ch/TC) ratio was calculated in each subjects. The average values of this ratio in healthy men and women were 0.37±0.13 and 0.37±0.14, respectively. The value of male patients with cerebral infarction was 0.30±0.10, it was significantly lower than the control value. The values of female patients with cerebral infarction, male and female patients with cerebral hemorrhage were 0.33±0.09, 0.35±0.10 and 0.35±0.11, respectively. These values exhibited no significant difference when compared with each controls. From these results, it was recognized that at a given concentration of serum total cholesterol, male patients with cerebral infarction had relatively less cholesterol in their HDL fraction as compared to healthy subjects.Serum HDL-PL concentrations in male patients either with cerebral infarction or cerebral hemorrhage, were significantly lower than the control value. The difference between female patients and control was insignificant.These results may suggest the importance of HDL-Ch for the development of cerebral atherosclerosis and subsequent cerebral infarction at least in man.

著者

森 聖二郎

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.26, no.2, pp.81-86, 1998-10-10 (Released:2011-09-21)

参考文献数

19

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Glucocorticoid-induced alterations of blood lipoprotein metabolism were analyzed in patients with various collagen diseases. Serum triglyceride concentration was rapidly and transiently increased by prednisolone treatment; it reached the maximal level after 2 weeks, and then gradually decreased to the initial level. On the other hand, serum total cholesterol concentration was slowly increased to the maximal level by 8 weeks and, thereafter, remained constant. Mathematical analysis has revealed that the average prednisolone-induced increase was about 2.5mg/dl/mg prednisolone for both serum total cholesterol and triglyceride levels. Ultracentrifugation analysis showed that not only low density but also very low density and high density lipoproteins were increased by prednisolone treatment. In a female patient with angina pectoris and xanthelasma, probucol treatment effectively normalyzed her glucocorticoid-induced hypercholesterolemia and, furthermore, the effective lowering of serum cholesterol level was also followed by successful cessation of angina attack and healing of xanthelasma. The data suggest the possible importance of glucocorticoid-induced hyperlipidemia in the development of atherosclerosis.

著者

張 念中 河合 祥雄 岡田 了三

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.15, no.5, pp.1185-1191, 1987

---

Mental stress from one's occupational circumstances is considered an important risk factor in the occurrence of myocardial infarction. However, because of difficulty in quantitative evaluation of such stress, this issue has not been fully studied. In the present work, we investigated the relationship between deaths from acute myocardial infarction (AMI) and occupation using data from the series of the Annual of the Pathological Autopsy Cases in Japan, in which autopsy cases throughout Japan are described. With regard to the 56, 268 persons who died at the age of 15 or older in 1973, 1974 and 1975, i. e., the year of economic depression due to the first oil shock and the years before and after the oil shock, we compared (I) the mortalities from AMI and frequencies of such deaths among all autopsy cases in Japan in relation to the occupational group in the three years and (II) the mortalities from AMI according to the occupation among 3, 241 randomly selected deaths in the three years. The mortality from AMI for 1973, 1974 and 1975 was 2.6%, 3.7% and 3.0%, respectively, showing a significantly higher value for 1974 (p<0.001). Among persons who died from AMI, the proportion of mental workers, particularly executives and managers, and unemployed/retired individuals was significantly higher (p<0.05) in 1974. As for randomly selected autopsy cases, the mortalities from AMI among mental workers in 1973, 1974 and 1975 were 7.8%, 17.0% and 6.2%, respectively, and the corresponding rates among physical workers were 2.0 %, 1.8% and 2.6%. Thus, the mortality among mental workers was significantly increased in 1974 (p<0.05), whereas there were no such variations among physical workers. In addition to the corroboration with the previous experience that deaths from AMI are more frequent among mental workers, particularly executives and managers, than among physical workers, we noted an increase in moratlity from AMI in the period of economic depression. It seems that stress derived from occupational circumstances rather than limited physical activities is involved in the occurrence of AMI.