The morphogenesis and healing process of arterial lesions in hypertensive rats with bilaterally constricted renal arteries were studied morphologically.
1. Arterial fibrinoid degeneration was seen in almost all organs, with special predirection in the mesentery, pancreas, right ventricle of the heart, and pretty often in the brain causing intracerebral massive hemorrhage. The lesion closely resembled to the so-called angionecrosis which is the direct cause of hypertensive intracerebral massive hemorrhage in human beings.
2. In the early stage, intimal edema, medial edema together with degeneration of smooth muscle cells, and adventitial cellular reaction were observed. Fibrinoid substance subsequently appeared in the intima. These lesions were considered to be ascribed to increased vascular permeability resulting from hypertension and other causal factors.
3. Rats survived for long period often revealed cellulofibrous intimal thickening as well as fibrinoid degeneration.
4. Constricting clamps were removed from the renal arteries after 517 weeks, at which time the fibrinoid degeneration was proven by biopsy of the mesenteric arteries.Then the blood pressure fell rapidly to normal level, increase of vascular permeability ceased, and no further cerebral hemorrhage occurred.
Histological study revealed two healing processes : a) complete disappearance of previously deposited fibrinoid substance with minimum intimal cell proliferation, and b) the healing process with remarkable cellulofibrous intimal thickening.
The morohogenesis of the cellulofibrous intimal thickening was further studied by means of electronmicroscopical and autoradiographical methods. These revealed that the endothelial cells of arteries play an outstanding role in the developement of the intimal cell proliferation.
The experimental results suggested that if the causes of angionecrosis are removed, it will be healed without residual change or healed with a kind of arteriosclerotic lesion.

View full abstract

In order to elucidate the role of the nutritional disturban e of the arterial wall and induced hypercholesteremia in the development and advancemet of arteriosclerosis, the following experiments were performed.
1) The left common carotid artery of the rabbit was stripped and invested with rubber dam or acrylic resin. With necrosis of the outer media, there appeared a fibrocelluler intimal thickening. It was camposed of proliferated fibroblasts and smooth muscle cells, increased acid mucopolysaccharides in the ground substance, and newly formed reticular and elastic fibers, and then it progressed to intimal fibrosis. Such a fibrocellular intimal thickening was also seen in the jugular vein invested with a crylic resin and in the carotid artery freed from the surrounding tissues.
2) When fed with a cholesterol diet, atherosclerotic lesions closely resembling the human atherosclerosis were formed at the invested segments of the carotid arteries. The most atherogenetic condition was the existence of hypercholestermia prior to the investment. When the hypercholestermia was preceded by the investment and intimal fibrosis was established, lipid deposition was scarce and no atherosclrosis was observed in the intima.
3) When rabbits were fed with a cholesterol diet for a long period, atherosclerotic lesions were formed in the intima of the aorta.When rabbits were fed with a cholesterol diet for a while and then fed with a stock diet, the fibrocellular tissue was developed in the aorta over the outer intima composed of foam cells, and in some animals of this group, atherosclerotic lesions closely resembled the human atherosclerosis were occurred in the intima.
4) These results suggested that arteriosclerosis and atherosclerosis preferably occurred in the arterial wall with disturbed nutrition and were resulted from insudation and proliferation. The endothelial cells, the intimal fibroblasts and smooth muscle cells both of which were developed from the endothelial cells played an important role in the development of the arterial lesions. The morphogenesis of the arterial lesions mentioned above were resulted from the combination of (1) insudation, (2) regenerative proliferation of the endothelial cells (3) proliferation of the endothelial cells and intimal cells caused by the insudation. With or without hypercholesteremia, atherosclerosis or fibrocellular intimal thickening was resulted.

View full abstract

1. Clinicopathological Studies
Histological observations were made on adrenals which were removed 91 hypertensive and 39 non-hypertensive patients or autopsies, and simultaneously histochemical observation were also done on those from 7 hypertensive and 7 non-hypertensive cases with the purpose of elucidating, the relationship between hypertension and the adrenal, and further more presuming the activity of the adrenal by assaying 17 OHCS and catecholamine.
1) The weights of the adrenal and thickenings of the medulla increased in cases of hyphertension more than those in non-hypertension, and they were especially remarkable in cases of essential hypertension.
2) Histological changes which were found in adrenal cortex were as follows : cortical nodule 50.6%, cortical hyperplasia 23.8%, cortical adenoma 14.3%, in cases of hypertension, while cortical nodule in cases of non-hypertension 38.5%, cortical adenoma 5.1% and cortical hyperplasia 3.2%.
3) Medullary hyperplasia were fond in 12 cases of essential hypertension and 2 cases of renal hypertension while they were not observed in non-hypertensive cases. Clinical implication of medullary hyperplasia was also studies.
4) High activities of catecholamine, especially of noradrenaline were proved hystochemically in adrenal gland of hypertensive cases. Both alkaline and acid phosphatase activities was also found elevated.
5) The content of catecholamine, and noradrenaline in urine increased in some case of essetial hypertension.
6) The content of urinary 17 OHCS in cases of hypertension was not increased more than that in cases of non-hypertension.
2. Experimental Studies
Experimental renal hypertension were induced in dogs by unilateral stricture of renal artery, and histochemical observation made on their adrenals. Furthermore, blood concentrations of 17 OHCS were assayed to estimate adrenal activites.
1) By using my angiosurgical technique, unilateral stricture of renal artery was made in dogs, and at length renal hypertension which continued during more than 3 months wete induced successfully without contralateral nephrectomy.
2) The induction of hypertension was related to the degree of stricture.
3) Blood concentration of 17-OHCS was remarkably increased in animals surviving more than one month after surgical operation.
4) Zona glomerulosa of the adrenal was found enlarged histologically, and activity of catecholamine, especially of noradrenaline was significantly elevated histochemically.
5) Effect of unilateral renal disorder on the contralatetal kidney was sought enzymologically, and alkaline phosphatase and ATPase activity wete found lowered.

View full abstract

1) Mice were infected with a virulent strain of S. euteritidis and treated with kanamycin.
2) The growth of infected bacteria in the organs of mouse was suppressed to the levels at 10² to 10³ /g by with adequate amount of kanamycin.
3) Thesemice survived during the infection with a virulent strain of S. enteritidis and kan amycin treatment and also acquired high resistance against further infection of the same microorganisms.
4) Serum agglutinin (anti-O) was found in all animals 4 weeks after immunization.
5) Histological changes of liver and spleen of mice which were given infection of a virulent strains 116-54 and also treated with kanamycin were described.

View full abstract

The mouse super-immunized with live vaccine of Salmonella enteritidis acquired high antilethal resistance and survived intravenous injection with 1000 MLD of a fully virulent strain 116-54 of the same organism. In vitro studies demonstrated that the mononuclear phagocytes obtained from the abdominal cavity, liver or subcutaneous tissue of mouse superimmunized with live vaccine of S. enterjtidis inhibited the intracellular multiplication of the same organism regardless of the presence c f antibody in the cell culture medium, wherease the cell of mouse immunized with dead vaccine did not.
In this paper in vitro transfer of cellular immunity of mouse super-immunized with live vaccine of S. enteritidis and some properties of transfer agent are described.
1) Transfer of cellular immunity :
The supernatant fluid of monocytes culture (SEC) was obtained 24 hrs after phagocytosis of heat killed bacteria from the cell culture of normal or immune monocytes.
When the normal monocytes were incubated for 3 days in cell culture medium containing 50% of SFC obtained from the monocytes of mouse immunized with live vaccine, the cells acquired the ability to inhibit the intracellular multiplication of virulent strain and resisted the cellular degeneration caused by intracellular existence of bacteria. But the normal monocytes treated with SFC obtained from normal monocytes or from mouse immunized with dead vaccine were unable to inhibit the intracellular multiplication of bacteria, and the cells were destroyed.
2) Serial transfer :
The supernatant fluid of monocytes culture obtained from the mouse immunized with live. vaccine was designcd as the original TA (transfer agent). The first TA was obtained by the same way of the original TA from the 1st recipient monocytes treated for 3 days with the original TA. As well as the 1st TA, 2nd TA was obtained from the 2nd recipient monocytes treated with the 1st TA. When the 1st, 2nd and 3rd recipient monocytes treated for 3 days with the original, 1st and 2nd TA respectively, in all cases the recipient acquired the ability to inhibit the intracellular multiplication of bacteria.
3) Treatment of nuclease :
Transfer Agent was treated with ribo- and deoxy-ribonuclease in the concentration of 50μg and 100μg/ml.
By treatment with RNese, TA decreased its ability to transfer the cellular immunity and the cells were destroyed by intracellular multiplication of bacteria, but by treatment with DNase, TA still retained the activity to transfer the cellular immunity.

View full abstract