Takayoshi Toda

The Role of 25-Hydroxy-Vitamin D3 in the Induction of Atherosclerosis in Swine and Rabbit by Hypervitaminosis D

Fibromuscular intimal thickening was seen in the ascending and thoracic aorta of the swine fed 62,500 IU of vitamin D3/kg of diet for three months duration; and after 3 months of vitamin D3 withdrawal, atherosclerotic lesions were found. In rabbits, pronounced aortic smooth muscle cell necrosis developed with the forced feeding of 10,000 IU vitamin D3 dissolved in corn oil/kg body weight/day for 14 days. Serum analyses indicated that blood calcium did not differ from that of animals fed corn oil alone, but that the level of serum 25‐hydroxy‐ vitamin D3 measured by HPLC was 30 times that in the control animals. These data suggest that choleclaciferol (the oxidized sterol with vitamin D3 activity) has a very destructive influence on the integrity of arterial wall, and that smooth muscle cell necrosis could be caused by enhanced membrane permeability to Ca2+ following 25‐hydroxy‐vitamin D3 incorporation into smooth muscle cell membranes.

Ultrastructural changes in the comb and aorta of chicks fed excess testosterone

The mode of cellular response to testosterone was monitored in the combs and aortas of chicks with the aid of an electron microscope. A 7-week treatment of 30 mg of testosterone per day had little effect on plasma lipid metabolism. However, this treatment resulted in the activation of fibroblasts in the comb, activation of fibroblast-like and smooth muscle cells in the aorta, and degeneration of smooth muscle cells in the aorta. A treatment of 150 mg of testosterone per day for 7 weeks induced hyperlipidemia and lipid-rich aortic lesions. The abdominal aorta had more activated and degenerated smooth muscle cells, with or without stainable lipid droplets, than the ascending aorta.

Coronary arterial lesions in sexually mature non-layers, layers, and roosters.

The effects of hereditary hyperlipidemia on coronary artery atherosclerosis were studied in 77 White Leghorn (DeKalb strain) chickens ranging from 4 to 13 months in age. After pubescence, the plasma levels of triglyceride and cholesterol in non-laying hens ranged 2- to 3-fold and 2- to 7-fold higher compared to layers. Serial sectioning revealed that most lesions were found in the proximal portions of both the left and right coronary arteries. Ultrastructurally, lesions in the roosters contained no foam cells, whereas some foam cells and small amounts of stainable lipid were observed in the thickened intima of layers. Half of the non-layers had stenotic lesions characterized by many foam cells, necrotic foci, and heavy stromal lipid deposits. Continuous permeation of excess plasma lipids into the arterial wall appeared to be an important factor in the development of coronary lesions.

Plasma lipid peroxidation in hyperlipidemic chickens

Laying and genetically defective non-laying hens were evaluated for plasma lipid and plasma peroxidation levels. The non-layers developed extreme hyperlipidemia as well as greatly increased levels of lipid peroxidation. It was concluded that the concurrent presence of lipid peroxidation products must be considered when evaluating hyperlipidemic causes of atherosclerosis in the chicken.

Antiatherosclerotic function of Kokuto, Okinawan noncentrifugal cane sugar.

In the present study, we investigated the effect of phenolic compounds (PCs) and policosanol of Kokuto, Okinawan noncentrifugal cane sugar, on the development of atherosclerosis. A total of 67 male Japanese quail were divided into eight dietary groups in trial 1. The dietary groups were fed the atherosclerotic diet (AD) containing 5% corn oil, 2% cholesterol, and 30% sucrose or seven different types of Kokuto. Dietary intakes of Kokuto notably prevented the development of atherosclerosis. Furthermore, there was a significant negative correlation between the serum radical scavenging activity and the degree of atherosclerosis in the dietary groups. In trial 2, a total of 63 Japanese quail were fed AD with sucrose, Kokuto, PC extracts from Kokuto, wax extracts from sugar cane, octacosanol, vitamin C, and vitamin E. As a result, the supplementation of the diet with Kokuto and PCs significantly reduced the development of atherosclerosis as compared with the ingestion of AD with sucrose. In conclusion, these findings suggest that, among various components of Kokuto, PCs play a central role for the prevention of experimental atherosclerosis in Japanese quail.

Composition of Swine Arterial Tissue

The effects of trans‐fatty acid‐rich and saturated acid‐rich diets on the fatty acid composition and morphology of swine arterial tissues were studied. Three groups of two‐month‐old swine were fed either a basal diet or a basal diet containing 8.3% margarine or butter for 4 months. The most significant change observed in the fatty acid pattern was the accumulation of 18: 2ω6 and the supperssion of both 20:4ω6 and 22:4ω6 acids in the aortic tissues of swine fed either butter or margarine as compared to swine fed the basal diet. Also, ω6 metabolites were significantly decreased in swine fed diets containing butter or margarine, as compared to those fed a basal diet. The group of swine which were fed either butter or margarine containing diets suffered a significant increase in intimal thickening of the coronary artery compared to those fed the basal diet. These thickened intima were characterized by the presence of modified smooth muscle cells, lipid containing cells, and degenerated cells without stainable lipids. However, there was no significant difference in the incidence and extent of intimal thickening of the coronary arteries between swine fed either of the two fat containing diets.

Clinicopathologic features of resected primary adenosquamous carcinomas of the liver.

Four cases of resected adenosquamous carcinoma of the liver were clinicopathologically reviewed, together with immunohistochemical findings. Although no lymph node metastases were seen and a curative resection was achieved in all cases, two patients had recurrences in the peritoneum and distant organs such as the pericardium and pleura relatively soon after the operation. Of the remaining two cases, one patient died during the postoperative period and the other died of coexistent hilar cholangiocarcinoma. Together these findings suggest that this disease tends to spread locally and distantly in the early phase of tumor growth and shows aggressive biological behavior. In an immunohistochemical study, involucrin was a specific marker for the squamous component and CA19-9 was a marker for the adenomatous component.

The effect of elastase on chickens with endogenous hyperlipidemia

Elastase has been reported to have a multiplicity of activities which may be protective against atherosclerosis. The data reported here support those reports and show a clear antiatherosclerotic effect in hyperlipidemic chickens. We have shown here that a reduction in calcium and lipid accumulation in aortic tissue and possibly a plasma cholesterol lowering effect can be seen in the chicken when treated with elastase. The most important effect in this animal is probably to aid removal of lipid bound to elastin in the intima. This was achieved at a dose of only 600 U elastase while reductions in tissue calcium required 1800 U elastase.

EFFECT OF MAGNESIUM DEFICIENCY ON ULTRASTRUCTURAL CHANGES IN CORONARY ARTERIES OF SWINE

The effects of magnesium (Mg) deficiency on the coronary arteries of 27 Yorkshire swine were studied by light and electron microscopy. The experimental animals were divided into 4 groups which received the following supplements: Group I, basal ration with adequate Mg (540 mg/kg diet), Group II, basal ration with insufficient Mg (270 mg/kg diet) Group III, 10% milk powder with adequate Mg (540 mg/kg diet), Group IV, 10% milk powder with insufficient Mg (270 mg/kg diet). Serum analysis indicated that dietary low Mg supplementation decreased cholesterol levels and increased phospholipid concentrations significantly. The highest magnitude and incidence of intimal thickening were observed in the coronary arteries of Group IV (p < 0.003). No significant intimal thickening was detected in any of the other groups. Ultra‐structural studies revealed a greater frequency of degenerated cells in Group III and IV (p<0.01). Numerous calcifications were observed in only Group IV. These data suggest that moderate Mg deficiency can promote atherosclerosis in combination with some atherogenic diet, and that the presence of smooth muscle cell degeneration is important in order for a magnesium deficiency to exert an effect on the coronary artery of swine.

Plexiform leiomyoma of the esophagus: A peculiar gross variant simulating plexiform neurofibroma

A plexiform variant of leiomyoma of the esophagus in a 51-year-old woman is reported. The patient was diagnosed with a tumor of the esophagus in an X-ray mass survey of the upper gastrointestinal tract. She was referred to the Ryukyu University Hospital for further examination. She appeared healthy with no complaints. Upper gastrointestinal series revealed an oval, well-defined filling defect in the lower esophagus just above the esophagogastric junction. Endoscopy revealed an undulating bulge covered with normal esophageal mucosa. Endoscopic ultrasonography showed a sharply demarcated hypoechoic mural tumor with internal linear pattern, with no evidence of penetration into the surrounding tissue. These findings were evaluated as consistent with a leiomyoma. Removing the tumor by enucleation was easily accomplished. Unexpectedly, on gross inspection, the tumor was a plexiform type, mimicking a plexiform neurofibroma. Light and electron microscopic examination and immunohistochemistry of the tumor tissue confirmed leiomyoma. Since the enucleation of the tumor, the patient has been free of recurrence and symptoms for 1.5 years at the time of this report.