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C Funaki

Publications and source records attributed to C Funaki.

34 records · Page 2Linked to original sources
PubMed1990

Clinical and experimental approaches to the prevention of atherosclerosis by immunological regulations.

To evaluate the involvement of the complement system in atherogenesis, we investigated the effect of camostat mesilate (CM), C1r, and C1 esterase inhibitor on cholesterol-induced atherosclerosis in rabbits. We also examined the effect of sodium dextran sulfate (DS, molecular weight: 7000), which is reported to be effective in preventing arteriosclerotic diseases and in inhibiting cholesterol-induced atherosclerosis in experimental animals, on complement activation in vitro and in vivo. The administration of CM reduced the formation of atherosclerotic lesions in cholesterol-fed rabbits. DS inhibited complement pathway in vitro, and the administration of DS reduced the C3a level in subjects. These results suggest that complement activation may possibly be involved in the atherosclerotic process.

Aged↗
PubMed1990

Intimal thickening of jugular and femoral veins vs arteries in the rabbit following investment.

The authors induced intimal thickening in the jugular and femoral veins and in the common carotid and femoral arteries of rabbits by placement of a polyethylene tube cuff. The comparative effects on the intima were studied by light and electron microscopy. Even in the veins, thickening resulted from the migration of medial smooth muscle cells into the intima with subsequent proliferation. Thickening in the arteries consisted of tightly packed smooth muscle cells and a few elastic fibers, whereas that in the veins was characterized by an abundance of collagen fibers, layers of smooth muscle cells, and a few elastic fibers. Capillaries were often observed in the thickened intima of the veins but not of the arteries.

Animals↗
PubMed1990

Involvement of intracellular iron in the toxicity of oxidized low density lipoprotein to cultured endothelial cells.

We evaluated the role of iron in the toxicity of oxidized low density lipoprotein (Ox-LDL) to cultured vascular endothelial cells. Exposure of the endothelial cells to Ox-LDL led to cell lysis as judged by the release of lactate dehydrogenase into the medium. The presence of deferoxamine, an iron chelator, in the reaction medium containing Ox-LDL prevented the lysis of cells by Ox-LDL. Pretreatment of the cells with deferoxamine also reduced their susceptibility to the cytotoxicity of Ox-LDL. The formation of thiobarbituric acid-reacting substances (TBARS) was observed in the cells exposed to Ox-LDL. Pretreatment of cells with deferoxamine reduced the formation of TBARS which was induced by Ox-LDL. These observations suggest that the toxicity of Ox-LDL to cultured endothelial cells involves the lipid peroxidation of cellular membrane catalyzed by iron derived from the target (endothelial) cells.

Animals↗
PubMed1990

Delayed clearance of beta-very low density lipoprotein after feeding cholesterol to splenectomized rabbits.

The role of the spleen on the metabolism of lipids in cholesterol-fed rabbits was evaluated. Rabbits were divided into two groups: splenectomized and control (sham-operated) groups. After the operation, all rabbits were fed a 1% cholesterol diet for 12 weeks and the changes in serum lipids were observed. In a separate experiment, a study of the clearance of 125I-labeled lipoproteins, including beta-migrating very-low density lipoprotein (beta-VLDL), low density lipoprotein (LDL), and acetoacetylated-LDL, was carried out in both groups of rabbits. After cholesterol feeding, all rabbits showed marked hyperlipidemia; however, the splenectomized animals showed a significantly higher level of serum total cholesterol, triglycerides, and phospholipids together with a lower level of high-density lipoprotein cholesterol. A lipoprotein clearance study showed that beta-VLDL was cleared more slowly from the plasma of the splenectomized rabbits than of the controls fed a 1% cholesterol diet. Without cholesterol feeding, beta-VLDL was cleared more rapidly, and to a similar extent in both groups. The plasma clearance of either LDL or acetoacetylated-LDL did not differ between the two groups. These findings suggest that the spleen may play a role in catabolizing the excessive beta-VLDL in rabbits with dietary-induced hyperlipidemia.

Animals↗
PubMed1990

[Hyperlipidemia impairs vascular endothelium-dependent relaxation in pig coronary arteries].

We examined the effects of a low pathophysiological level of hyperlipidemia and atherogenic lipoprotein (LDL) on the vascular responsiveness of isolated pig coronary arteries. Firstly, we studied the change of vascular responsiveness after feeding a cholesterol-rich diet to pigs for 4 or 9 weeks. Serum cholesterol level in pigs fed with the cholesterol-rich diet reached 218.5 +/- 32.9 mg/dl compared with 85.5 +/- 8.4 mg/dl in controls. Segments of the arteries were mounted in organ chambers for isometric tension recording. Contraction caused by KCl or prostaglandin F2 alpha was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered. Endothelium-dependent relaxation evoked by high but not low concentrations of bradykinin and substance P were reduced in pigs fed with the cholesterol-rich diet for 4 weeks as compared with those in normal pigs. Those evoked by bradykinin, substance P, and serotonin were significantly reduced in pigs fed with the cholesterol-rich diet for 9 weeks. Histologically, the fatty changes or intimal thickening were not so evident in coronary arteries of pigs fed for 4 weeks with the cholesterol-rich diet, but only minimal changes were observed in those fed with the diet for 9 weeks by light or electron microscopy. Secondly, the direct effects of LDL on the vascular responsiveness were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Protective role of intracellular glutathione against oxidized low density lipoprotein in cultured endothelial cells.

We examined the role of intracellular glutathione (GSH) in the defense of endothelial cells against oxidized low density lipoprotein (OX-LDL). Incubation of cultured bovine endothelial cells with OX-LDL produced a loss of intracellular GSH, followed by lysis. A decrease in the cellular stores of GSH by treating the endothelial cells with buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, increased the susceptibility of endothelial cells to lysis by OX-LDL. In contrast, an increase in cellular GSH level by treatment with L-2-oxothiazolidine-4-caboxylate, an effective intracellular cysteine delivery agent, reduced the toxicity of OX-LDL. These findings suggest that intracellular GSH plays an important role in the defense of endothelial cells against OX-LDL, and that the mechanism of OX-LDL toxicity is related to the depletion of intracellular GSH.

Animals↗
PubMed1989

Fibrinogen is chemotactic for vascular smooth muscle cells.

We studied the effect of fibrinogen on the migration of bovine aortic smooth muscle cells in culture, using a Neuro Probe 48-well micro chemotaxis chamber. Fibrinogen stimulated the migration of the cells dose-dependently at concentrations from 30 to 1000 micrograms/ml. A modified checkerboard analysis of the response demonstrated that the effect was largely chemotactic in nature. The present results suggest that fibrinogen may play an important role in the pathogenesis of arterial intimal thickening and atherosclerosis.

Animals↗
PubMed1989

Beta-migrating very low density lipoprotein attenuates endothelium-dependent relaxation in rabbit atherosclerotic aortas.

We studied the effects of beta-migrating very low density lipoprotein (beta-VLDL) on the vascular responses of isolated thoracic aortic preparations taken from normal and hypercholesterolemic rabbits. The endothelium-dependent relaxation induced by acetylcholine or adenosine triphosphate (ATP) was attenuated in the arteries from hypercholesterolemic rabbits that were fed a cholesterol-rich diet for 12 weeks. In these aortas, the lesional circumference of the atherosclerotic plaques (fatty streaks) was only 12.18 +/- 1.98%. The relaxation induced by the Ca2+ ionophore A23187 or nitroglycerin was not altered. Preincubation with beta-VLDL significantly inhibited the relaxation due to acetylcholine, ATP, or A23187, especially in the aortas of hypercholesterolemic rabbits. However, beta-VLDL did not alter the response to nitroglycerin. Preincubation with high density lipoprotein had no significant effect on vessel relaxation. These results indicated that endothelium-dependent relaxation was already inhibited in the early stages of atherosclerosis, and that the atherogenic lipoprotein, beta-VLDL, further inhibited endothelium-dependent relaxation in atherosclerotic aortas. It may be that beta-VLDL also plays a role in determining the level of vascular tonus in atherosclerosis.

Acetylcholine↗
PubMed1989

Vascular endothelial cell migration in vitro roles of cyclic nucleotides, calcium ion and cytoskeletal system.

According to the response to injury hypothesis, endothelial migration and repair may play an important role in the initiation and progression of atherosclerosis. In this study, we examined the regulatory mechanisms of endothelial cell migration in vitro, using cultured endothelial cells from fetal bovine aortas. Dibutyryl cyclic AMP, 8-bromo cyclic GMP, and theophylline (each at concentrations of 10(-4) to 10(-3) M) inhibited the migration of endothelial cells. Migration was not significantly affected by the Ca2+ channel blockers diltiazem (10(-6) to 10(-4) M) and nicardipine (10(-6) to 10(-5) M) or by La3+ (10(-4) to 10(-3) M), an inorganic Ca2+-antagonist, TMB-8 (10(-6) to 5 x 10(-5) M), an intracellular Ca2+ blocker, or the calmodulin inhibitors W-7 (10(-6) to 5 x 10(-5) M) and trifluoperazine (10(-7) to 10(-5) M). At the extracellular Ca2+ concentrations of less than 0.2 mEq/l, the migration was inhibited significantly. In addition, migration was markedly suppressed by colchicine (10(-8) to 10(-5) M), an inhibitor of tubulin polymerization, and by cytochalasin B (10(-7) to 10(-5) M), an inhibitor of actin polymerization. These results suggest that cyclic nucleotides, such as cyclic AMP and GMP, may regulate the migration of vascular endothelial cells. Although a low concentration of extracellular Ca2+ is essential to their migration, participation of the intracellular Ca2+-calmodulin system was not evident in this study. It appears that the cytoskeletal system, including microtubules and microfilaments, is involved in the mechanisms of migration.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Role of platelet secretory products in modified lipoprotein metabolism in macrophages.

Macrophage-derived foam cells and platelets are found in many lesions of atherosclerosis. Macrophages possess scavenger receptors that take up modified low density lipoproteins (LDL) like acetylated or acetoacetylated LDL (aLDL, aaLDL) resulting in accumulation of esterified cholesterol (EC) and acquisition of the characteristics of foam cells. We obtained a certain platelet secretory product from washed platelet-rich plasma which had been frozen and thawed three times (PSP alpha). We studied the effect of PSP alpha in modified lipoprotein metabolism in macrophages. When mouse or human macrophages were incubated with aaLDL and PSP alpha, much more EC was accumulated than with aaLDL only. Though the increase in EC of macrophages was dependent on the concentration of PSP alpha, it declined in high concentrations of PSP alpha. PSP alpha moderately increased 125I-aaLDL binding and cellular metabolism. PSP alpha also affected 125I-oxidized LDL binding and cellular metabolism, but it did not affect the metabolism of 125I beta-migrating very low density lipoprotein (beta VLDL). These results suggest that substances shed by activated platelets play a role in atherosclerosis as potent mediators of EC accumulation in macrophages and by affecting the receptor-mediated endocytosis of modified lipoproteins.

Animals↗
PubMed1988

Chemotactic response of vascular smooth muscle cells to acetoacetylated low-density lipoprotein.

We studied the effect of acetoacetylated low-density lipoprotein (LDL), which is recognized by the scavenger receptor, on the migration of fetal bovine aortic smooth muscle cells in culture, using a Neuro Probe 48-well microchemotaxis chamber. Acetoacetylated LDL is chemotactic and chemokinetic for the smooth muscle cells, and the effect is maximal with 50 micrograms/ml of protein, while native LDL has no significant chemotactic activity. These results suggest that denatured LDL might play an important role in the recruitment of smooth muscle cells from the media into the intima in atherosclerosis.

Animals↗
PubMed1988

Effects of splenectomy on serum lipids and experimental atherosclerosis.

The authors examined the effects of splenectomy on serum lipids in patients with hematologic disease, in rabbits, and also in cholesterol-fed rabbits with experimental atherosclerosis. Serum cholesterol was determined in patients with hypersplenism before and after splenectomy. Meanwhile serum lipids were determined in two groups of rabbits: splenectomy group (Spx group, n = 19), and sham operation group (Sham group, n = 14) before and after the operation. Then the rabbits were divided into four subgroups: cholesterol-fed groups--Spx-C (n = 12) and Sham-C (n = (9), and normal-chow-fed groups--Spx-N (n = 7) and Sham-N (n = 5). The Spx-C and the Sham-C rabbits were fed 1% cholesterol diet and the Spx-N and Sham-N rabbits were fed normal chow for twelve weeks. In patients preoperative serum cholesterol levels were low, and significant increase in serum cholesterol was observed following splenectomy. In rabbits, the Spx-C group showed significantly higher levels of serum cholesterol, triglycerides, and phospholipids in contrast to lower levels of high density lipoprotein cholesterol, as compared with the Sham-C group. The percentage of aortic plaque area in the Spx-C group tended to be higher than that in the Sham-C group. On the other hand, the Spx-N and the Sham-N group showed no difference in serum lipids during twelve weeks. The worsening of atherosclerosis in the Spx-C group was considered to be mainly due to an enhanced hyperlipidemia. Their results suggest a possible role of the spleen in lipid metabolism, in particular the existence of a splenic factor that can cause hypocholesterolemia in hyperplenism and can suppress hyperlipidemia.

Adolescent↗
PubMed1987

Separation and characterization of macrophages and smooth muscle cells in rabbit atherosclerotic lesions.

Atherosclerotic aortic intimas of cholesterol-fed rabbits were enzymatically dispersed into single cells by collagenase and elastase. And monocyte-macrophages (M phi) were separated from smooth muscle cells (SMC), using the ability of M phi to adhere to a plastic dish firmly even in the enzyme solutions. Round or oval, heavily lipid-laden cells, so-called foam cells (FC), belonged to the M phi fraction. M phi-FC showed very strong activity for non-specific esterase using alpha-naphthyl butyrate, while SMC showed little or no activity. Some of the FC were large and multinucleated (multinucleated giant foam cells). They also showed positive non-specific esterase staining and are thought to be derived from M phi. M phi-FC synthesized various proliferate in the medium and the number decreased gradually within several days. Some SMC were heavily lipid-laden; however, they retained their original spindle shape. SMC lost lipid droplets gradually as they proliferated to confluence. SMC from atherosclerotic lesions showed higher proliferative activity than those from normal-appearing medias of atherosclerotic aortas or control aortas. Almost no M phi-FC were obtained from the intima-medias of grossly normal portions of atherosclerotic aortas and control aortas. The present method will be useful for studying the role of these cells in the pathogenesis of atherosclerosis.

Animals↗
PubMed1985

A new unstable, high oxygen affinity hemoglobin: Hb Nagoya or beta 97 (FG4) His----Pro.

An unstable hemoglobin was detected by isopropanol and heat precipitation tests in a 49-year-old Japanese man suffering from acute exacerbation of a chronic hemolytic disorder which was apparently triggered by infection of cholelithiasis. One of his two sons carried the same abnormal hemoglobin, and was jaundiced, but otherwise healthy, without anemia. The abnormal hemoglobin focused at a slightly more anodic position than Hb A in thin layer polyacrylamide gel electrofocusing. The abnormal beta chain emerged after normal beta chain in reverse phase high performance liquid chromatography of the hemolysate. It comprised 16.7% and 25.5% of the total beta chain in the propositus and his son, respectively. The partially heme-depleted abnormal beta subunit was precipitated with p-chloromercuribenzoic acid, and the abnormal beta chain was isolated by urea CM-cellulose column chromatography. Structural analysis demonstrated substitution of proline for histidine at position 97 (FG4) in the beta chain. The abnormal hemoglobin was purified by ion-exchange column chromatography. It showed a hyperbolic oxygen equilibrium curve indicating a high oxygen affinity and the absence of cooperative intersubunit interaction. Subunit dissociation seemed to be slightly enhanced. The variant was markedly susceptible to oxidation and rapidly lost heme upon oxidation.

Amino Acid Sequence↗
PubMedDate not supplied

[Three cases of Chilaiditi's syndrome--hepatodiaphragmatic interposition of the colon].

Three cases of Chilaiditi's syndrome are reported. Case 1: A 56-year-old woman was admitted with dysphagia. She had been suffering from progressive systemic sclerosis for 16 years. Three years before the admission, dysphagia developed and dilatation and hypomotility of the esophagus were observed. Chest and abdominal x-ray films on admission showed severe dilatation of the intestine, pneumatosis cystoides intestinalis, abdominal free air, and Chilaiditi's syndrome. Chilaiditi's syndrome and other signs disappeared after conservative treatment. She died four months later due to cor pulmonale. Case 2: An 87-year-old man was admitted with constipation and left lower abdominal pain. Physical examination showed ascites. Chest and abdominal x-ray examination showed Chilaiditi's syndrome. Cytological examination of ascites revealed adenocarcinoma cells. Diagnosis of peritonitis carcinomatosa due to cancer of pancreatic tail was made. Chilaiditi's syndrome disappeared after removal of ascites. Case 3: A 71-year-old bedridden man who had urinary incontinence developed meterorism. Repeated chest x-ray examinations constantly showed Chilaiditi's syndrome. He died of pneumonia two years later. The pathogenesis of Chilaiditi's syndrome was discussed and the literature was reviewed.

Abdominal Pain↗